Sudden cardiac death affects 220,000 U.S. adults annually, most of whom have no prior symptoms of a heart issue. By identifying rare DNA variants that substantially increase risk of sudden cardiac death, researchers led by investigators at Massachusetts General Hospital (MGH) and the Broad Institute of MIT and Harvard have laid the foundation for efforts to identify individuals who could benefit from prevention strategies prior to experiencing symptoms.
The scientists also determined that such variants are present in approximately 1 percent of asymptomatic adults—corresponding to 3 million people in the U.S.
The findings are presented at the Scientific Sessions of the American Heart Association and published in the Journal of the American College of Cardiology.
The authors performed gene sequencing in 600 adult-onset sudden cardiac death cases and 600 controls who remained healthy—the largest such study performed to date and first to use a control group. A clinical geneticist reviewed all of the DNA variants identified, classifying 15 as clinically important pathogenic variants.
"Strikingly, all 15 of these pathogenic variants were in sudden cardiac death cases, with none in controls," said lead author Amit V. Khera, MD, cardiologist and associate director of the Precision Medicine Unit at MGH's Center for Genomic Medicine and the Broad Institute's Cardiovascular Disease Initiative. The prevalence of a pathogenic variant was found to be 2.5 percent in cases and 0 percent in controls.
Next, the investigators studied the genes of 4,525 middle-aged adults without any signs of heart disease, finding that 41 (0.9 percent) carried a pathogenic variant. These individuals have been followed for over 14 years, and those who inherited a pathogenic variant had a more than three times higher risk of dying from cardiovascular causes.
Based on these results, Khera and colleagues plan to conduct genetic sequencing tests for thousands of adult patients at MGH and affiliated hospitals who volunteered for a research program designed to understand how genetic and environmental factors impact risk of important diseases. They aim to find the one percent of individuals with rare genetic variants linked to heart disease. They plan to offer tailored prevention programs in a Cardiovascular Genetics Program or a new MGH Preventive Genomics Clinic that Khera is co-leading and is embedded within primary care.
Biomarker predicts heart failure patients with a higher risk of dying
A UCLA-led study revealed a new way to predict which patients with "stable" heart failure—those who have heart injury but do not require hospitalization—have a higher risk of dying within one to three years. Although people with stable heart failure have similar characteristics, some have rapid disease progression while others remain stable. The research shows that patients who have higher levels of neuropeptide Y, a molecule released by the nervous system, are 10 times more likely to die within one to three years than those with lower levels of neuropeptides.
About half of people who develop heart failure die within five years of their diagnosis, according to an American Heart Association (AHA) report, but it hasn't been understood why some live longer than others despite receiving the same medications and medical device therapy. The researchers set out to determine whether a biomarker of the nervous system could help explain the difference. To date, no other biomarker has been identified that can so specifically predict the risk of death for people with stable heart failure.
The researchers analyzed blood from 105 patients with stable heart failure, searching for a distinct biomarker in the blood that could predict how likely a person would be to die within a few years. They found that neuropeptide Y levels were the clearest and most significant predictor.
The scientists also compared nerve tissue samples from patients with samples from healthy donors and determined that the neurons in the people who were at most at risk for dying from heart failure were likely releasing higher levels of neuropeptides.
The results could give scientists a way to distinguish very-high-risk patients with stable heart failure from others with the same condition, which could inform which patients might require more aggressive and targeted therapies.
REGULATORY HIGHLIGHTS—
CMS 2020 annual updates for clinical laboratory fee schedule and services
The Centers for Medicare and Medicaid Services updates their Common Procedural Technology (CPT) codes and guidelines by deleting codes, guidelines, or adding and revising codes to reflect current technologies, techniques, and services. Below is a summary from the current updates.
The annual update to the local clinical laboratory fees for CY 2020 is 0.90 percent. Beginning January 1, 2020, this update applies only to pap smear tests. For a pap smear test, Section 1833(h)(7) of the Act requires payment to be the lesser of the local fee or the National Limitation Amount, but not less than a national minimum payment amount. However, for pap smear tests, payment may also not exceed the actual charge. The CY 2020 national minimum payment amount is $15.12 (This value reflects the CY 2019 national minimum payment with a 0.9 percent increase or $14.99 times 1.0090).
The affected codes for the national minimum payment amount are: 88142, 88143, 88147, 88148, 88150, 88152, 88153, 88164, 88165, 88166, 88167, 88174, 88175, G0123, G0143, G0144, G0145, G0147, G0148, Q0111, Q0115, and P3000.
The annual update to payments made on a reasonable charge basis for all other laboratory services for CY 2020 is 1.6 percent (See 42 CFR 405.509(b)(1)).509(b)(1)). The Part B deductible and coinsurance do not apply for services paid under the CLFS.
CLFS data reporting delayed
• For Clinical Diagnostic Laboratory Tests (CDLTs) that are not Advanced Diagnostic Laboratory Tests (ADLTs), the data reporting is delayed by one year. CDLT data that was supposed to be reported between January 1, 2020, and March 31, 2020, must now be reported between January 1, 2021, and March 31, 2021. Labs must report data from the original data collection period of January 1, 2019, through June 30, 2019. Data reporting for these tests will then resume on a three-year cycle, beginning in 2024. (Section 105(a)(1) of the Further Consolidated Appropriations Act of 2020 (FCAA)).
• In addition, the statutory phase-in provisions are updated. For 2020, the rates for CDLTs that are not ADLTs or new CLDTs may not be reduced by more than 10 percent of the rates for 2019. There will be a 15 percent reduction cap for each of 2021, 2022 and 2023. (Section 105(a)(2) of FCAA).
Provider types affected
This MLN Matters Article is intended for clinical diagnostic laboratories that submit claims to Medicare Administrative Contractors (MACs) for laboratory services provided to Medicare beneficiaries.
Provider action needed
CR 11598 provides instructions for the Calendar Year (CY) 2020 Clinical Laboratory Fee Schedule (CLFS), mapping for new codes for clinical laboratory tests, and updates for laboratory costs subject to the reasonable charge payment. Make sure your billing staffs are aware of these updates.
The next data reporting period is January 1, 2020, through March 31, 2020, where laboratories report applicable information to CMS. CMS will use this data to calculate revised private payer rate-based CLFS rates effective January 1, 2021. Specific directions on data collection and data reporting are available at https:/www.cms.gov/Medicare/Medicare-Fee-for-ServicePayment/ClinicalLabFeeSched/PAMA-regulations.html.
Applicable laboratories
In 2019, CMS made two revisions to the regulatory definition of applicable laboratory:
1. Medicare Advantage plan revenues were excluded from total Medicare revenues (the denominator of the majority of Medicare revenues threshold).
2. Hospitals that bill for their non-patient laboratory services may use Medicare revenues from the Form CMS 1450 14x Type of Bill (TOB) to determine whether its hospital outreach laboratories meet the majority of Medicare revenues threshold and low expenditure threshold.
The regulatory definition of an applicable laboratory is summarized below.
1. Is a laboratory as defined under the Clinical Laboratory Improvement Amendments(CLIA) regulatory definition of a laboratory (42 CFR 493.2)
2. The laboratory bills Medicare under its own National Provider Identifier (NPI) or
a. For hospital outreach laboratories -- bills Medicare Part B on the Form CMS 1450 under TOB.
3. The laboratory must meet a “majority of Medicare revenues” threshold, where it receives more than 50 percent of its total Medicare revenues from one or a combination of the CLFS or the PFS in a data collection period. For purposes of determining whether a laboratory meets the “majority of Medicare revenues” threshold, total Medicare revenues includes: fee-for-service payments under Medicare Parts A and B, prescription drug payments under Medicare Part D, and any associated Medicare beneficiary deductible or coinsurance.
4. The laboratory must meet a “low expenditure” threshold, where it receives at least $12,500 of its Medicare revenues from the CLFS in a data collection period.
Hospital outreach laboratories that met the definition of an applicable laboratory will be required to report applicable information to CMS during the next data reporting period, which is January 1, 2020, through March 31, 2020.
Additional sub regulatory guidance will be made available on the CLFS website under the PAMA regulations tab at https:/www.cms.gov/Medicare/Medicare-Fee-forService-Payment/ClinicalLabFeeSched/PAMA-regulations.html.
Advanced Diagnostic Laboratory Tests (ADLTs) effective January 1, 2020.
1. The ADLT DecisionDx-Uveal Melanoma owned and furnished by Castle Bioscience was assigned Proprietary Laboratory Analyses (PLA) code 0081U effective January 1, 2019. This code is being deleted effective December 31, 2019, and replaced by CPT code 81552, effective January 1, 2020. Short Descriptor: ONC UVEAL MLNMA MRNA 15 GENE. Long Descriptor: Oncology (uveal melanoma), mRNA, gene expression profiling by real-time RT-PCR of 15 genes (12 content and 3 housekeeping), utilizing fine needle aspirate or formalin-fixed paraffin embedded tissue, algorithm reported as risk of metastasis
2. Existing code 81538 is an ADLT and is priced at its median private payer rate.
3. For additional information regarding other ADLTs, see https://www.cms.gov/Medicare/Medicare-Fee-for-ServicePayment/ClinicalLabFeeSched/PAMA-Regulations#ADLT_tests.
