Hip and Knee Replacements More Common In Patients With Transthryretin Cardiac Amyloidosis

MedicalResearch.com Interview with:

Dr. Mathew Maurer, Medical Director The Hypertrophic Cardiomyopathy Center NewYork-Presbyterian/Columbia University Medical Center.

Dr. Maurer

Dr. Mathew Maurer, Medical Director
The Hypertrophic Cardiomyopathy Center
NewYork-Presbyterian/Columbia University Medical Center.

MedicalResearch.com: What is the background for this study?

Response: Transthryretin cardiac amyloidosis (TTR-CA) is an underdiagnosed type of cardiomyopathy in which TTR (transthyretin, also known as prealbumin), a protein that forms amyloid fibrils, deposits in the heart. The deposits cause thickening of the ventricular wall and diastolic as well as systolic dysfunction. It is usually discovered around age 75 and presents more commonly in men than in women. With advances in non-invasive diagnostic modalities and growing awareness, TTR-CA is being diagnosed increasingly more frequently. Additionally, there are several emerging treatments that are under active investigation. Most of these therapies prevent disease progression and don’t address the amyloid already deposited in the heart. Accordingly, it is imperative that we diagnose TTR-CA before patients develop significant amyloid heart disease. However, this presents a great challenge since there are few known clinical predictors that might alert even the most astute physician that a patient is at such risk. With identification of predictors that may appropriately raise the index of clinical suspicion, clinicians may begin to pick up more subtle (and perhaps not yet clinically significant) forms of TTR-CA and initiate treatment before significant damage occurs.

The few known clinical predictors of TTR-CA include bilateral carpal tunnel syndrome and lumbar spinal stenosis, and numerous studies found TTR on biopsies and autopsies of other musculoskeletal sites, particularly in hip and knee joints. (Just last week, and also discussed here on MedicalResearch.com, biceps tendon rupture was also shown to occur more frequently in TTR-CA!) We suspected that patients who ultimately develop TTR-CA may first develop clinically significant hip and knee disease, enough to even warrant a hip (THA) or knee (TKA) replacement.

MedicalResearch.com: What are the main findings?

Response: In over 170 patients with Transthryretin cardiac amyloidosis, we found that patients were over 5 and 3 times more likely to undergo THA and TKA, respectively, compared to the general population. (The prevalence of THA and TKA in the general population was studied in a separate, large United States nationwide study.) On average for each patient, their first joint replacement occurred over 7 years before they were diagnosed with TTR-CA.

MedicalResearch.com: What should clinicians and patients take away from your report?

Response: Hip and knee replacements appear to be significantly more common among patients who ultimately develop TTR-CA. This introduces a new clinical predictor of TTR-CA which clinicians may use to increase their index of clinical suspicion for future development of TTR-CA in such patients. Additionally, this study contributes to a growing body of literature that TTR may be a key element of joint disease. Some have already suggested that TTR may be at the root of osteoarthritis – the leading indication for hip and knee replacements.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: To definitively confirm the association between joint replacements and TTR-CA, this should be studied prospectively by analyzing pathological specimens of removed hip and knee joints from all patients undergoing such joint replacement, testing them for amyloid. If amyloid is identified pathologically in the joints, then further evaluation for early amyloid heart disease using Tc99-PYP scanning may identify affected subjects early in the course of the disease. Even if testing for amyloid heart disease is not present at the time of joint replacement, longitudinal evaluation over the next 7 to 10 years will likely demonstrate the subsequent development of TTR-CA.

Additionally, we may investigate the mechanism by which amyloidosis leads to hip and knee replacements. Perhaps it is due to direct deposition, as in TTR-CA. Even if so, we must investigate where this deposition occurs. It could be in the ligaments, tendons, articular cartilage, the bone itself, or perhaps the synovial fluid. This also begs the question of why amyloid may preferentially deposit in the joints at all? Or perhaps the joint replacements are related to an inflammatory response to amyloid presence but not directly due to the deposition itself. Alternatively, amyloid presence may be a benign finding in the elderly and the joint replacements are caused by another mechanism entirely – perhaps from chronic repetitive joint trauma gone unnoticed by a patient suffering from peripheral neuropathy, another potential complication of amyloidosis.

MedicalResearch.com: Is there anything else you would like to add?

Response: For the sake of completion: There is another type of amyloid protein, called AL (or light chain amyloid) that also causes cardiac amyloidosis (AL-CA). In numerous studies, AL was not found to be significantly present in joints. (Why not? Add that to the list of future research!) In our study, we also analyzed rates of THA and TKA in over 140 patients with AL-CA and, as expected, their rates of THA and TKA did not differ from the general population

Disclosures: Dr. Maurer or his institution receives funding for research and serving on advisory boards and DSMBs from Pfizer Inc., Alnylam Pharmaceuticals Inc., GSK Inc., ISIS Pharmaceuticals and Prothena Inc.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.


Hip and Knee Arthroplasty are Common among Transthyretin Cardiac Amyloidosis Patients and Occur 7.6 Years before Cardiac Amyloid Diagnosis: Can We Identify Affected Patients Earlier?
Rubin, Jonah,   Mathew S. Maurer et al.
Journal of Cardiac Failure , Volume 23 , Issue 8 , S27

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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