With effective therapies available, the findings suggest screening with nuclear imaging should be more frequent in this population.
Transthyretin cardiac amyloidosis (ATTR-CA) is a frequent cause of heart failure (HF) in older Black individuals, particularly in the oldest men, the prospective SCAN-MP study affirms.
The highest rate of ATTR-CA in a cohort of Black and Caribbean Hispanic patients older than 60 with HF was seen in Black men over the age of 75 (17.2%), researchers led by Frederick Ruberg, MD (Boston Medical Center, MA), report in a study published online this week in JAMA Cardiology.
Of note, more than half of ATTR-CA cases identified in the cohort (55.8%) involved a normal TTR genotype, with a minority related to the abnormal V142I variant, which means that genotyping alone cannot be used to reliably identify ATTR-CA in this population.
The high prevalence of ATTR-CA, especially in older Black men, “really speaks to the point that you have to look for this amyloidosis in a way that we haven’t done before,” Ruberg told TCTMD. “The guidelines for treating these diseases, and heart failure in general, are evolving based upon evidence such as this to really kind of suggest that clinicians think about amyloidosis and perform appropriate testing to identify patients who might have it because we can now get them on specific therapy.”
Only one therapy—tafamidis (Vyndaqel and Vyndamax; Pfizer)—was approved to treat ATTR-CA when this study began in 2019, but acoramidis (Attruby; BridgeBio) and vutrisiran (Amvuttra; Alnylam) have since been approved by the US Food and Drug Administration.
“Now that we have a treatment, we thought it was really important to try to identify the proportion of people who actually have heart failure that’s caused by amyloidosis, with the idea that then we could get them on therapy that would change the course of their illness,” Ruberg said.
The SCAN-MP Study
The SCAN-MP investigators focused on Black and Hispanic patients with HF because these groups tend to be understudied and more frequently have the abnormal V142I variant of the TTR gene that causes ATTR-CA, Ruberg said.
For the study, conducted at centers in Boston, New York, NY, and New Haven, CT, Ruberg and his colleagues enrolled Black and Caribbean Hispanic people who were older than 60 years and had HF with an echocardiographic left ventricular wall thickness of 12 mm or greater and an LVEF above 30%.
ATTR-CA was identified through radionuclide imaging—almost entirely Tc99m-pyrophosphate (PYP) imaging. Investigators also performed blood tests to exclude the presence of light-chain amyloidosis and genotyping to study the proportion of cases related to the V142I variant.
The analysis included 646 patients (median age 73 years; 50.6% women), with 85.1% identifying as Black and 28.8% as Caribbean Hispanic. Median LV wall thickness was 13 mm ,and median LVEF was 61%.
You have to look for this amyloidosis in a way that we haven’t done before. Frederick Ruberg
The overall prevalence of ATTR-CA was 6.7%, with a numerically higher rate in men versus women (8.2% vs 5.2%; P = 0.13). Historically, ATTR-CA was thought to be a disease exclusive to men, but newer data show that’s not the case, Ruberg indicated. Regarding women, he said, “you still need to look for amyloidosis in this population as well, because you’ll find it.”
Prevalence was significantly higher in Black versus Hispanic patients (7.8% vs 2.2%; P = 0.004). Among Black individuals, ATTR-CA was more common over age 75 than it was at younger ages (14.0% vs 3.4%; P < 0.001).
The V142I allele was found in 5.6% of the cohort overall. Slightly more than half of individuals with the genetic variant (52.8%) also had testing consistent with ATTR-CA.
Study ‘Needed to Be Done’
Commenting for TCTMD, Jeremy Slivnick, MD (University of Chicago, IL), said the study “really needed to be done” because much of the data in this space has come from retrospective analyses and has not focused on underrepresented groups like Black and Hispanic individuals.
The relatively high prevalence of ATTR-CA in this study “brings to light the need to consider this diagnosis, particularly in African Americans, and to have a low threshold to screen them if there’s increased thickening of the left ventricle,” Slivnick said. “I think based on this data that any patient with a wall thickness over 12 millimeters who’s got heart failure with preserved ejection fraction, who’s an African American patient—or, to a lesser extent, Hispanic—should be strongly considered for screening for cardiac amyloidosis.”
Cardiac amyloidosis is a treatable disease, with multiple therapies available that can improve survival, Slivnick said. “Even if we’re identifying 8% of patients, that 8% of patients stands to benefit a lot from this type of screening,” he said. Other signs and symptoms associated with ATTR-CA, like carpal tunnel syndrome or low back pain caused by lumbar spinal stenosis, can increase the pretest probability of finding amyloid.
Even if we’re identifying 8% of patients, that 8% of patients stands to benefit a lot from this type of screening. Jeremy Slivnick
Though PYP imaging used to detect ATTR-CA is widely available, there could be a challenge with scaling up this type of screening in communities where there’s less recognition of cardiac amyloidosis and perhaps less infrastructure to support it, Slivnick said.
Moreover, getting patients on the available therapies requires teams of pharmacists and physicians that are available at expert centers to obtain coverage for the medications and then guide management. “One other thing that would have to be dealt with in scaling up screening would be what to do with the positive cases,” Slivnick said. He highlighted, too, the high cost of these therapies, which would have to be considered.
But that shouldn’t be a reason to avoid identifying patients with ATTR-CA, he stressed. “These are lifesaving drugs. We need to figure out ways to make these drugs cheaper [and] not be worried about finding patients because of the cost.”
Ruberg said one of the goals of the current study “is to raise awareness of the disease, prompt clinicians to screen for it, and then take appropriate action.”
The cost of PYP imaging to screen for ATTR-CA is relatively low, he said, adding that the main risk of screening would be misdiagnosis. He added that his group recently received funding to perform research into a blood-based test for ATTR-CA, which would simplify screening and aid in scaling up such efforts.