Thursday, June 12, 2025

MolDx Releases Two Cardiac Genetic LCDs - Final LCDs

MolDx releases two cardiac genetic LCDs, requested by Invitae in about February 2023 (about 2.5 years ago).   Both were issued as draft LCDs last year.

Note that Invitae writes it requested two genetic LCDs, one neurologic, one cardiologic, and what it has gotten, today, is two cardiologic LCDs.  The LCDs were proposed in mid-June 2025, so they appear as final about 52 weeks later.

The bottom line?

The bottom line is: The LCDs, in Medicare terminology, are close to recent professional society guidelines for cardio-genetics in adults.

##

L39946

Genetic Testing for Heritable Thoracic Aortic Disease

LCD here.

Billing and Coding A59870.

Q&A A60207     Request letter here.

The LCD is 8 pages with 24 references.  See original for the full rules. 

  • The patient has aortic abnormalities and meets ONE of the following.  Before age 60; OR syndromic features (e.g. Marfan); OR Family hisotry in 1st or 2nd degree; OR unexplained sudden death in 1st or 2nd degree relative.
  • The test must have ample recommended genetic content but not "unvalidated" content.

The billing article points to 81410/81411 or 81479, plus Z code.

The Q&A discussion includes a discussion of alignment to ACC guidelines for genetic testing and features that suggest a hereditary as opposed to inborn anatomic origin.

##

L39950  

Molecular Testing for Identification and Management of Hereditary Transthyretin Amyloidosis  ATTR

LCD here.  

Billing and Coding A59874.

Q&A A60202.  Request letter here.

The LCD is 9 pages and has 53 references.

In summary - see original for the full rules:

  • The patient has a clinical diagnosis of ATTR, OR, has features suggesting of ATTR cardiomyopathy AND African, OR first degree-relative, OR additional guideline suggested feature.
  • OR has progressive sensorimotor or autonomic neuropathy AND 1st degree relative with ATTR Dx OR one additional feature per guidelines.
  • The patient has had counseling and result will inform treatment decisions.  The test has minimum genetic content and does not included unvalidated genes.

The Billing Article simply says "use appropriate CPT code" (!!! thanks) and Z code.

The Q&A notes that a draft exclusion of "test that includes genetic content considered harmful" was revised to 'test does not include content that is not properly validated" etc.


###

AI Corner

I asked for re-write of the coverage criteria, for clarity.  At link.

https://brucedocumentblog.blogspot.com/2025/06/moldx-cardio-genetic-lcds-june-2025.html

###

AI CORNER

For your curiousity only, here are Chat GPT summarizes of the LCDs.  Do not make any decisions except by reference to the original LCD text, not this AI summary.

Here is a summary of the two complementary MolDX Local Coverage Determinations (LCDs), L39950 and L39946, both effective July 27, 2025, for Medicare beneficiaries with cardiac conditions requiring genetic testing. 

These LCDs mark a significant expansion in Medicare coverage for cardiogenetic diagnostics.

1. L39950: Molecular Testing for Hereditary Transthyretin Amyloidosis (hATTR)

LCD Title: MolDX: Molecular Testing for Identification and Management of Hereditary Transthyretin Amyloidosis
Jurisdiction: Noridian MAC J-F (13 states, incl. WA, AZ, UT)

Covered Indications

Genetic testing is covered when the patient:

  • Has a clinical diagnosis or cardiac features suggestive of ATTR-CM, and

    • Is of African ancestry, or

    • Has a first-degree relative with hATTR, or

    • Displays features consistent with expert consensus or guidelines (e.g., neuropathy, autonomic failure)

  • Has sensorimotor/autonomic neuropathy plus relevant family history or clinical indicators

  • Has been counseled on test implications

  • Will use the result to inform treatment decisions

  • Receives a test with validated genes (minimum content includes TTR and possibly others)

  • Uses a test that has passed MolDX Technical Assessment

Clinical Rationale

  • hATTR is a treatable, underdiagnosed cause of cardiomyopathy and polyneuropathy.

  • The most common U.S. pathogenic variant, TTR p.Val142Ile, is highly prevalent (~3.4%) in African ancestry populations and primarily cardiac in expression.

  • Gene sequencing improves diagnostic accuracy, especially as clinical features overlap with other conditions (e.g., diabetic neuropathy, hypertensive heart disease).

  • The test supports earlier diagnosis and therapy (e.g., tafamidis, RNAi drugs like patisiran and vutrisiran).

2. L39946: Genetic Testing for Heritable Thoracic Aortic Disease (HTAD)

LCD Title: MolDX: Genetic Testing for Heritable Thoracic Aortic Disease
Jurisdiction: Noridian MAC J-F (same 13 states)

Covered Indications

Genetic testing is covered when:

  • The patient has aortic root/ascending aorta dilation, aneurysm, or dissection, and

    • Presents before age 60, or

    • Has syndromic features (e.g., Marfan, Loeys-Dietz, vascular Ehlers-Danlos), or

    • Has a family history of thoracic aortic disease, aneurysms, or sudden death

  • Counseling is provided

  • The test:

    • Covers the minimum validated gene set, including FBN1, TGFBR1/2, SMAD3, COL3A1, ACTA2, etc.

    • Excludes non-validated or unclear variants

    • Has completed MolDX Technical Assessment

    • Does not violate repeat germline testing policies (L38353)

Clinical Rationale

  • HTAD accounts for ~20% of thoracic aortic aneurysms (TAA).

  • Guidelines from the ACC/AHA (2022) and ClinGen strongly recommend genetic evaluation for younger TAA cases or syndromic/familial presentations.

  • Identifying pathogenic variants informs timing of surgery, surveillance strategies, and cascade testing.

  • Recognized gene panels influence decisions well before aortic diameter reaches generic intervention thresholds.

Summary Implications

Together, these LCDs establish broad Medicare coverage for two distinct forms of inherited cardiovascular disease:

  • One focused on amyloidosis of cardiac and/or neurologic origin (hATTR),

  • The other on genetic aneurysmal disease of the thoracic aorta (HTAD).

Both policies:

  • Require pre-test counseling, use of validated gene panels, and MolDX TA approval

  • Emphasize early intervention and family risk stratification

  • Are anchored in strong guideline support and target diseases with overlapping but misdiagnosed phenotypes

These LCDs will likely drive:

  • Expansion of NGS panels in cardiovascular practice,

  • Increased testing in Black Medicare populations (esp. hATTR),

  • Coverage for multigene panels aligned with ACC/AHA guidelines, and

  • Pressure for national harmonization of cardiac genetics coverage.

Let me know if you'd like side-by-side tables, CPT implications, or billing summaries.

##

Disclaimer.  The AI summary is for curiousity only.  I haven't proofed it against every detail of the LCDs.

##

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

##

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:

⚠️ 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.

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.

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.

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.

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.

🔍 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.

✅ 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.

🛠️ 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

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