A new study by researchers at Columbia University Medical Center (CUMC) and NewYork-Presbyterian has found that amyloid related heart disease can be detected by imaging techniques, thereby eliminating the need for a biopsy. The technique is known as technetium 99m pyrophosphate (Tc 99m PYP) cardiac imaging.
A retrospective cohort study was performed at three academic specialty centers for cardiac amyloidosis in the United States in which 229 participants were evaluated for cardiac amyloidosis — an abnormal disorder of the heart in which the amyloid protein is deposited in the heart. The patients also underwent Tc 99m PYP cardiac imaging. The date of analysis and final confirmation from the statistician was May 4, 2016.
The researchers investigated the diagnostic capabilities of the Tc 99m PYP test for ATTR-CA, with special focus on accuracy with respect to sensitivity and specificity. The study included 179 amyloidosis patients (58 patients were excluded since they hadn’t performed standard tests and those were not included for whom it was difficult to assess if they had cardiac amyloidosis), 121 patients had ATTR-CA while 50 had other types of amyloidosis who were evaluated at three leading amyloidosis centers (CUMC, the Mayo Clinic, and Boston University School of Medicine). The imaging scans were compared to tissue biopsy results, the gold standard for diagnosing ATTR.
The research team found that the imaging test was able to correctly identify ATTR in 91% of those diagnosed with the disease, and was able to rule out ATTR-CA in 92% of those with other forms of amyloidosis or patients who did not have amyloidosis. The results were published in JAMA.
Lead researcher Mathew S Maurer, MD, medical director of the HCM Center at NewYork-Presbyterian Hospital/Columbia University Medical Center, acknowledged that the technique could also detect the heart condition known as transthyretin-related cardiac amyloidosis (ATTR-CA) before it progressed to advanced heart failures and could cause further medical complications.
“This is a huge advancement for patients with ATTR-CA, which is under-recognized and often misdiagnosed,” said co-first author Adam Castano, MD, a cardiology fellow at CUMC. “This test will spare certain patients from having to undergo a biopsy in order to get a definitive diagnosis. Many people with ATTR-CA are frail and elderly, so being able to avoid a biopsy, even when it can be done with a less-invasive catheter-based procedure, is a significant step forward.”
ATTR-CA is one of many types of amyloidosis, a condition in which the transthyretin (TTR) protein breaks down and forms fibrils that deposit in organs and tissues. In the heart, the extracellular amyloid deposits lead to congestive heart failure. Since there are so many different types of amyloidosis, each requiring its own treatment, accurate diagnosis can be an arduous task.
ATTR-CA is most common in older adults, with the normal variant of the transthyretin (TTR) breakdown causing amyloidosis in 32% patients of age 75 who died of heart failure. TTR protein can, though, have a mutated form as well that can be passed genetically. This mutated TTR can also cause ATTR-CA in some individuals, though the prevalence of amyloidosis resulting from this inherited condition is unknown. The most common mutation in the United States, however, is present in 3% to 4% of individuals of African American ethnicity.
The diagnostic tool evaluated in the study known as Tc 99m PYP Planar Cardiac Scintigraphy was built upon bone scintigraphy, a form of single-photon emission computed tomography, or SPECT, that is conventionally used to detect bone cancer, and diagnose severity of a variety of other bone diseases and conditions using small amounts of radioactive material. In bone scintigraphy, patients are injected with a radioactive isotope which is attracted to bony materials that have remodeled due to bone cancer. During the initial stages, researchers observed that the isotope, technetium 99m pyrophosphate (Tc 99m PYP), also had an affinity to amyloid deposits in the heart, which is a highlighting factor of ATTR-CA.
Despite such positive results, the accuracy and effectiveness of this application in a multicenter and the association of Tc 99m PYP myocardial uptake with survival are unknown. But more importantly, though, this technique was able to correctly differentiate ATTR-CA from other type of amyloidosis conditions. What’s even more positive is the fact that the findings of this study have come at just the right time as a majority of TTR focused therapies are in phase 3 of clinical trials.
Currently the use of magnetic resonance imaging (MRI) to differentiate ATTR-CA from other amyloidosis conditions is flimsy, showing poor reproducibility. However, when MRI results combined with clinical tests point towards a susceptibility of amyloidosis, Tc 99m PYP can be used to confirm ATTR-CA. Therefore, the researchers’ findings can have many clinical implications, especially in performing non-invasive procedures to diagnose ATTR-CA, which in turn guarantees patient’s safety.