MolDx Cardio Genetic LCDs - June 2025 - Chat GPT Clarifies

 I asked Chat GPT to try a re write for clarity, while preserving each LCD's coverage criteria.

Here's the original blog June 12 on the two new LCDs.

https://www.discoveriesinhealthpolicy.com/2025/06/moldx-releases-two-cardiac-genetic-lcds.html

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🔹 LCD L39950 – Hereditary Transthyretin Amyloidosis (hATTR)

Rewritten Coverage Criteria:

Molecular genetic testing for hereditary transthyretin amyloidosis (hATTR) is covered when all the following criteria are met:

1. Patient Presentation
   The patient meets either of the following:

   • Has a clinical diagnosis of ATTR (wild-type or hereditary), or

   • Has cardiac signs or symptoms suggestive of ATTR cardiomyopathy (e.g., unexplained heart failure, arrhythmias),
     and at least one of the following:

     • African ancestry

     • A first-degree relative with a confirmed hATTR diagnosis

     • Clinical features aligned with published expert consensus (e.g., bilateral carpal tunnel syndrome, lumbar spinal stenosis)

2. Neuropathy Variant
   Alternatively, if the patient presents with progressive sensorimotor and/or autonomic neuropathy, then either of the following must also apply:

   • A first-degree relative with a confirmed hATTR diagnosis

   • Additional features consistent with hATTR per consensus guidelines

3. Test Utilization and Counseling

   • The patient has received pre-test counseling about the implications of the test.

   • The test results will be used to inform clinical management, such as therapy initiation.

4. Test Design and Validity

   • The test includes only the minimum validated gene content required for clinical decision-making (e.g., TTR) or a known familial variant.

   • The test does not include unvalidated or non-actionable genes that could mislead care.

   • The test must have passed MolDX Technical Assessment (TA) confirming its clinical validity and utility.

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🔹 LCD L39946 – Heritable Thoracic Aortic Disease (HTAD)

Rewritten Coverage Criteria:

Genetic testing for Heritable Thoracic Aortic Disease (HTAD) is covered when all the following criteria are satisfied:

1. Clinical Indication
   The patient has a diagnosis of aortic root or ascending aortic dilation, aneurysm, or dissection (per national guidelines),
   and at least one of the following applies:

   • Onset or presentation before age 60

   • Syndromic features suggestive of a connective tissue disorder (e.g., Marfan syndrome, Loeys-Dietz, vascular Ehlers-Danlos)

   • A first- or second-degree relative with:

     • Thoracic aortic disease, or

     • Aneurysms (peripheral or intracranial), or

     • Unexplained sudden death at a relatively young age

2. Test Design and Content

   • The patient has received genetic counseling on the risks and implications of testing.

   • The test includes only clinically validated genes with definitive or well-established evidence per ACC/AHA and ClinGen guidelines.

     • A single-variant test is permitted only if a known familial variant is being evaluated.

   • The panel must exclude genes of uncertain significance or poor validation that might lead to inappropriate clinical decisions.

3. Regulatory Requirements

   • The test has passed MolDX Technical Assessment (TA)

   • The test is compliant with related MolDX policies, such as restrictions on repeat germline testing (L38353)

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I then asked Chat GPT to provide constructive criticism for the LCD author.

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Yes — both LCDs (L39950 and L39946) are generally well-aligned with clinical guidelines and thoughtfully written, but they do suffer from some recurring issues that may hinder clarity, consistent application, and efficient use by labs, clinicians, and payers. Here's a structured critique:

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⚠️ Common Issues Across Both LCDs

1. Overly Verbose and Redundant Language

Both LCDs repeat ideas in multiple places, especially in the coverage sections. For example:

• The need for counseling, minimum gene content, and test utility appears multiple times, sometimes with slightly different phrasing.

• They mix clinical eligibility, test design requirements, and regulatory compliance into a single list, when they could be cleanly separated.

Impact: Slows comprehension and increases the risk that clinicians or test developers misinterpret which criteria are patient-facing vs lab-facing.

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2. Vague Terms Without Operational Definitions

Both LCDs use terms like:

• "Features consistent with expert consensus"

• "Genes with definitive or well-established evidence"

• "Properly validated" or "unclear clinical utility"

These phrases are not anchored to a specific source, leaving ambiguity:

• Which specific guidelines qualify as “expert consensus”? ACC/AHA? ESC?

• Which genes are deemed valid? The LCD references ClinGen in L39946 but does not give a list.

Impact: Creates interpretive flexibility that could lead to coverage disputes or inconsistent TA approvals.

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3. Lack of Clarity About Single-Gene Testing vs Panel Testing

While both LCDs permit single-variant testing when a familial mutation is known, they don’t:

• Clarify if this applies to duo/trio testing or reflex testing.

• Clarify if limited panels (e.g. just TTR, or just FBN1/ACTA2) are acceptable for patients without known familial variants.

Impact: Labs may be uncertain whether they can offer targeted panels unless a family mutation is already known, potentially discouraging cost-effective testing.

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4. Limited Guidance on Cascade or Family Testing

Both LCDs imply support for familial risk assessment, but do not clearly state:

• Whether testing in asymptomatic relatives is covered

• Whether cascade testing is included when the proband is Medicare-eligible

This is particularly relevant in L39946 (HTAD), where early detection in relatives can be life-saving.

Impact: May deter cascade testing or lead to unnecessary denials.

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5. Technical Assessment (TA) Language Is Ambiguous

Both LCDs require that a test:

“has successfully completed a technical assessment (TA)...”

However, they don’t:

• Define what the TA evaluates (analytical validity, clinical validity, or both?)

• Link to a checklist or reference document explaining TA criteria

• Distinguish between new and grandfathered tests

Impact: Adds friction for test developers seeking coverage, particularly new market entrants.

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🔍 LCD-Specific Observations

📄 L39950 (hATTR)

• The clinical phenotypes of hATTR-CM and hATTR-PN are mixed together in one long bulleted list. It would be clearer to break them into two distinct diagnostic pathways.

• There's an overemphasis on detailed drug mechanisms and trials (tafamidis, acoramidis, RNAi agents). This may be more appropriate in a background article, not an LCD.

📄 L39946 (HTAD)

• The LCD refers to ACC/AHA and ClinGen guidelines, but doesn’t specify a minimum list of genes (though it hints at 11 validated genes). A table of “required core genes” would enhance usability.

• While it’s based on high-quality data, the gene–phenotype correlations are buried in long paragraphs that make it hard to parse actionable coverage implications.

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✅ What They Do Well

• Align with current guidelines (especially 2022 ACC/AHA for aortopathies and hATTR diagnosis).

• Emphasize clinical utility, not just analytic validity — a good signal for payers and clinicians.

• Include appropriate flexibility for new evidence or guideline changes.

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🛠️ Suggested Fixes

• Help the reader - Streamline coverage criteria into 3 buckets: (1) Patient eligibility, (2) Test design, (3) Compliance.

• Provide an appendix or hyperlink to required gene lists (ClinGen, ACC/AHA)

• Clarify whether family member testing is covered when a proband has a known mutation

• Offer TA submission guidance in a separate MolDX companion article

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Would you like a suggested redraft of the coverage criteria section using these structural improvements?