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<div class="header">
<h1>Clinical Trial Matching Analysis:<br>Mavacamten & Aficamten vs. Your Data</h1>
<div class="subtitle">Cross-referencing 18 years of FHIR health records against pivotal HCM trial criteria</div>
<div class="disclaimer">This is an AI-generated analysis for informational and educational purposes only. It is not medical advice. Discuss any treatment decisions with your care team.</div>
</div>
<div class="container">
<!-- Patient Profile -->
<div class="profile-card">
<h2>Your Clinical Profile (Extracted from FHIR Data)</h2>
<div class="profile-grid">
<div class="profile-section">
<h3>Diagnoses</h3>
<div class="profile-item"><span class="label">Primary</span><span class="value">Obstructive HCM (I42.1)</span></div>
<div class="profile-item"><span class="label">AFib Status</span><span class="value caution">Persistent (I48.19)</span></div>
<div class="profile-item"><span class="label">VT History</span><span class="value">Yes (I47.2, since 2009)</span></div>
<div class="profile-item"><span class="label">Hypertension</span><span class="value">Yes (since 2022)</span></div>
<div class="profile-item"><span class="label">Prediabetes</span><span class="value">Yes (since 2024)</span></div>
<div class="profile-item"><span class="label">Sleep Apnea</span><span class="value">Yes (since 2022)</span></div>
</div>
<div class="profile-section">
<h3>Most Recent Echo (Jul 27, 2024)</h3>
<div class="profile-item"><span class="label">LVEF (biplane)</span><span class="value highlight">73%</span></div>
<div class="profile-item"><span class="label">LVEF (Teicholz)</span><span class="value highlight">75%</span></div>
<div class="profile-item"><span class="label">IVS Thickness (diastole)</span><span class="value alert">2.0 cm (20 mm)</span></div>
<div class="profile-item"><span class="label">LVOT Peak Gradient (rest)</span><span class="value caution">9 mmHg</span></div>
<div class="profile-item"><span class="label">LVOT Mean Gradient (rest)</span><span class="value">5 mmHg</span></div>
<div class="profile-item"><span class="label">LV Posterior Wall</span><span class="value">1.4 cm</span></div>
<div class="profile-item"><span class="label">LVOT Diameter</span><span class="value">1.9 cm</span></div>
<div class="profile-item"><span class="label">LVOT Peak Velocity</span><span class="value">1.53 m/s</span></div>
</div>
<div class="profile-section">
<h3>Prior Echo (Jun 2, 2023)</h3>
<div class="profile-item"><span class="label">LVEF (biplane)</span><span class="value">60%</span></div>
<div class="profile-item"><span class="label">IVS Thickness</span><span class="value alert">2.8 cm (28 mm)</span></div>
<div class="profile-item"><span class="label">MV Regurgitant Volume</span><span class="value">39.2 mL</span></div>
</div>
<div class="profile-section">
<h3>CPET Results (Mar 13, 2024)</h3>
<div class="profile-item"><span class="label">Peak VO₂</span><span class="value caution">24.6 mL/kg/min</span></div>
<div class="profile-item"><span class="label">% Predicted Peak VO₂</span><span class="value caution">77%</span></div>
<div class="profile-item"><span class="label">Max RER</span><span class="value">1.02</span></div>
<div class="profile-item"><span class="label">AT (VO₂)</span><span class="value">13.8 mL/kg/min</span></div>
<div class="profile-item"><span class="label">Max HR</span><span class="value">117 bpm</span></div>
<div class="profile-item"><span class="label">Exercise Duration</span><span class="value">10:30</span></div>
<div class="profile-item"><span class="label">HR Recovery (1 min)</span><span class="value">16 bpm</span></div>
</div>
<div class="profile-section">
<h3>Cardiac Biomarkers</h3>
<div class="profile-item"><span class="label">BNP (Apr 2024)</span><span class="value caution">128 pg/mL</span></div>
<div class="profile-item"><span class="label">BNP (Sep 2023)</span><span class="value">123 pg/mL</span></div>
<div class="profile-item"><span class="label">BNP (Mar 2023)</span><span class="value caution">166 pg/mL</span></div>
<div class="profile-item"><span class="label">BNP (Apr 2021)</span><span class="value alert">321 pg/mL</span></div>
<div class="profile-item"><span class="label">NT-proBNP (Oct 2007)</span><span class="value highlight">31 pg/mL</span></div>
</div>
<div class="profile-section">
<h3>Device & Medications</h3>
<div class="profile-item"><span class="label">ICD</span><span class="value">Dual-lead, DDDR mode</span></div>
<div class="profile-item"><span class="label">Battery</span><span class="value highlight">Beginning of Service</span></div>
<div class="profile-item"><span class="label">Metoprolol XL</span><span class="value">200 mg daily</span></div>
<div class="profile-item"><span class="label">Verapamil SR</span><span class="value">120 mg daily</span></div>
<div class="profile-item"><span class="label">Dabigatran</span><span class="value">150 mg BID</span></div>
<div class="profile-item"><span class="label">Chlorthalidone</span><span class="value">25 mg daily</span></div>
</div>
</div>
</div>
<!-- CPET Highlight -->
<div style="margin: 8px 0 24px;">
<div class="cpet-grid">
<div class="cpet-card">
<div class="cpet-label">Peak VO₂</div>
<div class="cpet-value">24.6</div>
<div class="cpet-note">mL/kg/min</div>
</div>
<div class="cpet-card">
<div class="cpet-label">% Predicted</div>
<div class="cpet-value" style="color: #fbbf24;">77%</div>
<div class="cpet-note">FRIEND reference (≤90% = impaired)</div>
</div>
<div class="cpet-card">
<div class="cpet-label">Resting LVOT Gradient</div>
<div class="cpet-value" style="color: #fbbf24;">9</div>
<div class="cpet-note">mmHg (low at rest)</div>
</div>
<div class="cpet-card">
<div class="cpet-label">IVS Thickness</div>
<div class="cpet-value" style="color: #f97066;">20</div>
<div class="cpet-note">mm (severe hypertrophy)</div>
</div>
<div class="cpet-card">
<div class="cpet-label">LVEF</div>
<div class="cpet-value" style="color: #64ffda;">73%</div>
<div class="cpet-note">well preserved</div>
</div>
</div>
</div>
<!-- TRIAL 1: EXPLORER-HCM -->
<div class="trial-card">
<div class="trial-header">
<div>
<div class="trial-name">EXPLORER-HCM</div>
<div class="trial-drug">Mavacamten (Camzyos) · Phase 3 · NCT03470545</div>
</div>
<div class="trial-verdict verdict-partial">LIKELY EXCLUDED</div>
</div>
<div class="trial-body">
<table class="criteria-table">
<tr>
<th>Criterion</th>
<th>Required</th>
<th>Your Data</th>
<th>Status</th>
</tr>
<tr>
<td class="col-criterion">Age ≥ 18</td>
<td class="col-required">≥ 18 years</td>
<td class="col-patient">Adult</td>
<td class="col-status"><span class="status-badge status-pass">✓ Pass</span></td>
</tr>
<tr>
<td class="col-criterion">Obstructive HCM diagnosis</td>
<td class="col-required">Confirmed oHCM</td>
<td class="col-patient">Obstructive HCM (I42.1)</td>
<td class="col-status"><span class="status-badge status-pass">✓ Pass</span></td>
</tr>
<tr>
<td class="col-criterion">LVOT gradient ≥ 50 mmHg</td>
<td class="col-required">≥ 50 mmHg (rest or provocation)</td>
<td class="col-patient">9 mmHg at rest (Jul 2024)</td>
<td class="col-status"><span class="status-badge status-uncertain">? Unknown</span></td>
</tr>
<tr>
<td class="col-criterion">LVEF ≥ 55%</td>
<td class="col-required">≥ 55%</td>
<td class="col-patient">73% (biplane, Jul 2024)</td>
<td class="col-status"><span class="status-badge status-pass">✓ Pass</span></td>
</tr>
<tr>
<td class="col-criterion">NYHA Class II–III</td>
<td class="col-required">Symptomatic, Class II or III</td>
<td class="col-patient">Not coded in FHIR data</td>
<td class="col-status"><span class="status-badge status-uncertain">? Unknown</span></td>
</tr>
<tr>
<td class="col-criterion">No AFib at screening</td>
<td class="col-required">No atrial fibrillation</td>
<td class="col-patient">Persistent AFib (I48.19)</td>
<td class="col-status"><span class="status-badge status-fail">✗ Excluded</span></td>
</tr>
<tr>
<td class="col-criterion">No sustained VT with exercise</td>
<td class="col-required">No syncope or sustained VT</td>
<td class="col-patient">VT history + ICD</td>
<td class="col-status"><span class="status-badge status-conditional">Conditional</span></td>
</tr>
</table>
<div class="trial-notes">
<h4>Analysis</h4>
<p><strong>The persistent AFib is the primary barrier.</strong> EXPLORER-HCM excluded patients with atrial fibrillation at screening. Your persistent AFib (documented since June 2021) would have been disqualifying.</p>
<p>The resting LVOT gradient of 9 mmHg is well below the 50 mmHg threshold. However, this was measured at rest on maximally-tolerated medical therapy (metoprolol 200mg + verapamil 120mg). Provoked gradients (with Valsalva or post-exercise) were not captured in the structured FHIR data and could potentially be significantly higher given the 20mm septal thickness.</p>
<p>Your LVEF of 73% comfortably exceeds the ≥55% requirement. Your CPET data showing 77% predicted pVO₂ suggests meaningful functional limitation consistent with NYHA Class II–III.</p>
</div>
</div>
</div>
<!-- TRIAL 2: VALOR-HCM -->
<div class="trial-card">
<div class="trial-header">
<div>
<div class="trial-name">VALOR-HCM</div>
<div class="trial-drug">Mavacamten (Camzyos) · Phase 3 · NCT04349072</div>
</div>
<div class="trial-verdict verdict-complex">COMPLEX FIT</div>
</div>
<div class="trial-body">
<table class="criteria-table">
<tr>
<th>Criterion</th>
<th>Required</th>
<th>Your Data</th>
<th>Status</th>
</tr>
<tr>
<td class="col-criterion">Age ≥ 18</td>
<td class="col-required">≥ 18 years</td>
<td class="col-patient">Adult</td>
<td class="col-status"><span class="status-badge status-pass">✓ Pass</span></td>
</tr>
<tr>
<td class="col-criterion">Obstructive HCM with wall thickness ≥ 15mm</td>
<td class="col-required">≥ 15mm (or ≥ 13mm with family Hx)</td>
<td class="col-patient">20 mm (Jul 2024)</td>
<td class="col-status"><span class="status-badge status-pass">✓ Pass</span></td>
</tr>
<tr>
<td class="col-criterion">LVOT gradient ≥ 50 mmHg</td>
<td class="col-required">≥ 50 mmHg (rest or provocation)</td>
<td class="col-patient">9 mmHg at rest</td>
<td class="col-status"><span class="status-badge status-uncertain">? Provoked unknown</span></td>
</tr>
<tr>
<td class="col-criterion">LVEF ≥ 60%</td>
<td class="col-required">≥ 60%</td>
<td class="col-patient">73%</td>
<td class="col-status"><span class="status-badge status-pass">✓ Pass</span></td>
</tr>
<tr>
<td class="col-criterion">NYHA Class III–IV (or II with syncope)</td>
<td class="col-required">Severe symptoms</td>
<td class="col-patient">Not coded; CPET suggests limitation</td>
<td class="col-status"><span class="status-badge status-uncertain">? Unknown</span></td>
</tr>
<tr>
<td class="col-criterion">Maximally-tolerated medical therapy</td>
<td class="col-required">Including combination therapy</td>
<td class="col-patient">Beta-blocker + CCB (no disopyramide)</td>
<td class="col-status"><span class="status-badge status-conditional">Partial</span></td>
</tr>
<tr>
<td class="col-criterion">Referred for septal reduction (SRT)</td>
<td class="col-required">Actively considering SRT</td>
<td class="col-patient">No SRT referral in records</td>
<td class="col-status"><span class="status-badge status-fail">Not referred</span></td>
</tr>
</table>
<div class="trial-notes">
<h4>Analysis</h4>
<p><strong>VALOR-HCM targeted the most severely symptomatic patients</strong> who were already being considered for surgical septal myectomy or alcohol septal ablation. The bar was higher: NYHA III–IV, on maximal medical therapy, and actively referred for SRT.</p>
<p>Your records don't show an SRT referral, and your 77% predicted pVO₂ while impaired may not reach the severity typically prompting SRT consideration. However, the 20mm septal thickness and documented progression of AFib burden could make SRT relevant in the future.</p>
<p>One important nuance: VALOR-HCM required LVEF ≥ 60% (stricter than EXPLORER's ≥ 55%). Your 73% easily qualifies, but the study's emphasis on maximally-tolerated therapy is notable. Your current beta-blocker + CCB combination represents a substantial regimen, but disopyramide (another option in HCM) hasn't been trialed.</p>
</div>
</div>
</div>
<!-- TRIAL 3: SEQUOIA-HCM -->
<div class="trial-card">
<div class="trial-header">
<div>
<div class="trial-name">SEQUOIA-HCM</div>
<div class="trial-drug">Aficamten (Myqorzo) · Phase 3 · NCT05186818 · FDA Approved 2025</div>
</div>
<div class="trial-verdict verdict-likely">CLOSEST MATCH</div>
</div>
<div class="trial-body">
<table class="criteria-table">
<tr>
<th>Criterion</th>
<th>Required</th>
<th>Your Data</th>
<th>Status</th>
</tr>
<tr>
<td class="col-criterion">Age 18–85</td>
<td class="col-required">18 – 85 years</td>
<td class="col-patient">Adult</td>
<td class="col-status"><span class="status-badge status-pass">✓ Pass</span></td>
</tr>
<tr>
<td class="col-criterion">Confirmed oHCM (wall ≥ 15mm)</td>
<td class="col-required">LV wall thickness ≥ 15 mm</td>
<td class="col-patient">20 mm</td>
<td class="col-status"><span class="status-badge status-pass">✓ Pass</span></td>
</tr>
<tr>
<td class="col-criterion">LVEF ≥ 60%</td>
<td class="col-required">≥ 60%</td>
<td class="col-patient">73%</td>
<td class="col-status"><span class="status-badge status-pass">✓ Pass</span></td>
</tr>
<tr>
<td class="col-criterion">Resting LVOT gradient ≥ 30 mmHg</td>
<td class="col-required">≥ 30 mmHg at rest</td>
<td class="col-patient">9 mmHg at rest</td>
<td class="col-status"><span class="status-badge status-fail">✗ Below threshold</span></td>
</tr>
<tr>
<td class="col-criterion">Valsalva LVOT gradient ≥ 50 mmHg</td>
<td class="col-required">≥ 50 mmHg (provoked)</td>
<td class="col-patient">Not in FHIR data</td>
<td class="col-status"><span class="status-badge status-uncertain">? Unknown</span></td>
</tr>
<tr>
<td class="col-criterion">Predicted pVO₂ ≤ 90%</td>
<td class="col-required">≤ 90% predicted</td>
<td class="col-patient">77% predicted</td>
<td class="col-status"><span class="status-badge status-pass">✓ Pass</span></td>
</tr>
<tr>
<td class="col-criterion">Max RER ≥ 1.05</td>
<td class="col-required">≥ 1.05 at baseline</td>
<td class="col-patient">1.02</td>
<td class="col-status"><span class="status-badge status-fail">✗ Slightly below</span></td>
</tr>
<tr>
<td class="col-criterion">NYHA Class II–III</td>
<td class="col-required">Symptomatic</td>
<td class="col-patient">Not coded; CPET consistent</td>
<td class="col-status"><span class="status-badge status-uncertain">? Likely II</span></td>
</tr>
<tr>
<td class="col-criterion">Stable background therapy > 6 weeks</td>
<td class="col-required">Stable meds for ≥ 6 weeks</td>
<td class="col-patient">Current regimen stable</td>
<td class="col-status"><span class="status-badge status-pass">✓ Pass</span></td>
</tr>
<tr>
<td class="col-criterion">Persistent AFib enrollment cap</td>
<td class="col-required">Capped at ~15% of enrollment</td>
<td class="col-patient">Persistent AFib (I48.19)</td>
<td class="col-status"><span class="status-badge status-conditional">Capped, not excluded</span></td>
</tr>
<tr>
<td class="col-criterion">No prior SRT</td>
<td class="col-required">No history of septal reduction</td>
<td class="col-patient">No SRT in records</td>
<td class="col-status"><span class="status-badge status-pass">✓ Pass</span></td>
</tr>
<tr>
<td class="col-criterion">No rhythm-restoring Rx within 6 months</td>
<td class="col-required">No AFib rhythm Rx ≤ 6 months</td>
<td class="col-patient">Amiodarone discontinued</td>
<td class="col-status"><span class="status-badge status-conditional">Depends on timing</span></td>
</tr>
</table>
<div class="trial-notes">
<h4>Analysis</h4>
<p><strong>SEQUOIA-HCM is the closest fit, and the most interesting comparison.</strong> Unlike EXPLORER-HCM, this trial did not categorically exclude persistent AFib. Instead, it capped enrollment at ~15%. This means patients with your AFib profile were specifically represented in the trial population.</p>
<p>The key obstacles are hemodynamic, not arrhythmic. Your <em>resting</em> LVOT gradient of 9 mmHg is well below the 30 mmHg resting threshold. However, your FHIR data only captures resting gradients. With 20mm septal thickness and known obstructive HCM, it's quite possible your provoked gradient (with Valsalva or post-exercise) could exceed 50 mmHg, which would satisfy the criterion. This is a common clinical scenario in medically-treated oHCM: medications suppress the resting gradient while significant latent obstruction remains.</p>
<p>Your max RER of 1.02 just misses the ≥ 1.05 requirement (a quality control measure to confirm adequate effort during CPET). This is borderline and could reflect chronotropic limitation from beta-blocker therapy rather than suboptimal effort. Your 77% predicted pVO₂ does meet the ≤ 90% threshold.</p>
<p>The amiodarone discontinuation timing matters: the trial excluded patients who had rhythm-restoring treatment within 6 months. If amiodarone was stopped more than 6 months before a hypothetical screening, this criterion would be met.</p>
</div>
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</div>
<!-- The Big Picture Insight -->
<div class="insight-section">
<h2>The Bigger Picture: What This Analysis Reveals</h2>
<p>This exercise exposes something important about the gap between clinical trials and real-world patients. Your profile represents a <strong>common but underrepresented phenotype in HCM trials</strong>: obstructive HCM with concomitant persistent atrial fibrillation, on dual AV nodal agents, with a low resting gradient but potentially significant provoked obstruction.</p>
<div class="callout callout-blue">
<strong>The LVOT Gradient Paradox:</strong> Your resting LVOT gradient is only 9 mmHg, well below trial thresholds. But you have 20mm septal thickness and a confirmed diagnosis of obstructive HCM. The low resting gradient likely reflects the suppressive effect of metoprolol 200mg + verapamil 120mg. If these medications were reduced or withdrawn, the gradient would almost certainly rise, possibly well above 50 mmHg. Ironically, the very medications controlling your obstruction may be masking the hemodynamic severity that would qualify you for a therapy targeting that same obstruction.
</div>
<div class="callout callout-amber">
<strong>The AFib Exclusion Problem:</strong> EXPLORER-HCM excluded AFib entirely. SEQUOIA-HCM capped persistent AFib at 15%. Yet AFib occurs in 20–25% of HCM patients over their lifetime, and it is one of the most clinically impactful arrhythmias in this population. This means the evidence base for cardiac myosin inhibitors in HCM + AFib is thinner than it should be. Patients with your combined profile, representing a substantial minority of real-world HCM patients, must rely on extrapolation from trial populations that were specifically designed to underrepresent them.
</div>
<div class="callout callout-green">
<strong>What the Data Suggests Despite the Gaps:</strong> Aficamten (Myqorzo) was FDA-approved in 2025 for symptomatic obstructive HCM. The approved indication does not exclude patients with AFib. The mechanism of action, reducing cardiac myosin hypercontractility and thereby lowering LVOT obstruction, addresses the underlying substrate of your disease regardless of rhythm status. With your preserved LVEF (73%), severe septal hypertrophy (20mm), and documented exercise limitation (77% predicted pVO₂), the pathophysiologic rationale for a cardiac myosin inhibitor is sound. The question is whether your resting obstruction is high enough, or could be demonstrated to be high enough under provocation, to warrant it.
</div>
<p style="margin-top: 20px;">Three questions worth discussing with your cardiologist:</p>
<p><strong>1.</strong> Has a provoked LVOT gradient (Valsalva or post-exercise) ever been formally measured? The resting gradient of 9 mmHg on maximal medical therapy doesn't tell the full story of the obstruction severity.</p>
<p><strong>2.</strong> Given that both sotalol and amiodarone have been tried and discontinued, and the current strategy is rate-control-only for persistent AFib, is there a role for a cardiac myosin inhibitor to address the HCM substrate directly, potentially reducing the hemodynamic consequences that contribute to AFib maintenance?</p>
<p><strong>3.</strong> Would a trial reduction of the beta-blocker or CCB, under supervision and with ICD backup, reveal the true resting LVOT gradient and clarify whether you meet the hemodynamic criteria for mavacamten or aficamten?</p>
</div>
<div class="source-list">
<h3>Sources & Trial References</h3>
<a href="https://clinicaltrials.gov/study/NCT03470545" target="_blank">EXPLORER-HCM (NCT03470545) – ClinicalTrials.gov</a>
<a href="https://www.ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.120.006853" target="_blank">EXPLORER-HCM Study Design – Circulation: Heart Failure</a>
<a href="https://www.jacc.org/doi/10.1016/j.jacc.2022.04.048" target="_blank">VALOR-HCM – JACC</a>
<a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC10463171/" target="_blank">VALOR-HCM Week 56 Results – PMC</a>
<a href="https://www.jacc.org/doi/10.1016/j.jchf.2023.10.004" target="_blank">SEQUOIA-HCM Baseline Characteristics and Study Design – JACC: Heart Failure</a>
<a href="https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2024/05/23/14/16/sequoia-hcm" target="_blank">SEQUOIA-HCM Results – ACC</a>
<a href="https://ir.cytokinetics.com/press-releases/press-release-details/2025/Cytokinetics-Announces-FDA-Approval-of-MYQORZO-aficamten-for-the-Treatment-of-Adults-with-Symptomatic-Obstructive-Hypertrophic-Cardiomyopathy-to-Improve-Functional-Capacity-and-Symptoms/default.aspx" target="_blank">Aficamten (Myqorzo) FDA Approval – Cytokinetics</a>
<a href="https://www.ahajournals.org/doi/10.1161/JAHA.124.038758" target="_blank">Safety and Efficacy of Mavacamten and Aficamten – JAHA</a>
<a href="https://www.ahajournals.org/doi/10.1161/CIR.0000000000001250" target="_blank">2024 AHA/ACC HCM Management Guidelines – Circulation</a>
<a href="https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219083s000lbl.pdf" target="_blank">Myqorzo (Aficamten) Prescribing Information – FDA</a>
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