By Van Selby, MD

Assistant Professor of Medicine, University of California, San Francisco Cardiology Division, Advanced Heart Failure Section

Dr. Selby reports no financial relationships relevant to this field of study.

SYNOPSIS: In a cohort of older patients undergoing carpal tunnel release surgery, an analysis of tenosynovial tissue revealed amyloid deposits in 10% of patients. This development may facilitate early diagnosis of cardiac amyloidosis.

SOURCE: Sperry BW, Reyes BA, Ikram A, et al. Tenosynovial and cardiac amyloidosis in patients undergoing carpal tunnel release. J Am Coll Cardiol 2018;72:2040-2050.

Amyloidosis encompasses a group of disorders caused by protein misfolding and subsequent aggregation, leading to organ dysfunction. Light chain (AL) and transthyretin (ATTR) amyloid are the two amyloid types that affect the heart most commonly. New therapies are improving outcomes for patients with both ATTR and AL cardiac amyloidosis. However, early diagnosis and prompt initiation of treatment are crucial. Amyloidosis is a systemic disease, often involving noncardiac sites, too. Previous studies have revealed that amyloid, particularly ATTR, frequently deposits in the tenosynovium and transverse carpal tunnel ligaments, leading to carpal tunnel syndrome (CTS). Patients often present with CTS five to 10 years before the diagnosis of cardiac amyloidosis. Patients undergoing carpal tunnel release surgery may present an opportunity to diagnose cardiac amyloidosis earlier in the disease course.

Sperry et al studied men ≥ 50 years of age and women ≥ 60 years of age who underwent carpal tunnel release surgery. Patients with known amyloidosis or CTS thought to be secondary to another condition were excluded. At the time of surgery, surgeons excised a small sample of the tenosynovium, which was evaluated for amyloid deposits using hematoxylin and eosin and Congo red staining. When amyloid was identified, mass spectrometry was used to determine the amyloid type (i.e., AL vs. ATTR). All patients with amyloid identified subsequently underwent thorough evaluation for cardiac involvement, including labs, echocardiography, and nuclear imaging.

Of the 98 patients enrolled, investigators found amyloid deposits in the tenosynovium in 10 patients. The authors found ATTR in seven patients and AL amyloid in two patients. Among the 10 patients with amyloid, two were diagnosed with cardiac amyloidosis and one with amyloid polyneuropathy, allowing early initiation of treatment. Patients with amyloid deposits were older (mean age, 72.5 years) and all had been diagnosed with bilateral CTS. The authors concluded that tenosynovial biopsy is a low-risk procedure that may lead to early diagnosis of amyloidosis in those with CTS.

COMMENTARY

Cardiac amyloidosis has been considered a rare disease with no effective treatments. Because of this, many clinicians do not routinely consider amyloidosis in their evaluation of patients presenting with heart failure. However, recent data suggest that cardiac amyloidosis, particularly ATTR amyloid, is much more prevalent than previously thought. With new treatments available for cardiac amyloidosis, identifying these patients has taken on new importance. Currently available treatments for cardiac amyloidosis work by suppressing the production of new amyloid fibrils or preventing those fibrils from depositing in tissues rather than addressing the amyloid that has deposited in the heart or other organs already. Therefore, earlier identification of amyloidosis and earlier initiation of therapy will prevent accumulation of amyloid fibrils in the first place and improve patient outcomes.

Sperry et al have built on previous studies that identified amyloid deposits in the soft tissues leading to CTS as well as spinal stenosis and biceps tendon rupture. They found that 10.2% of older patients with idiopathic CTS who are referred for surgery exhibit evidence of amyloid deposition, particularly ATTR. Given the frequency of CTS, this represents a large number of patients with potential cardiac amyloidosis. The authors also found that routine evaluation for amyloid led to early initiation of therapy in three patients.

This was a cross-sectional cohort study with important limitations. While the authors identified amyloid in the carpal tunnel specimens of many patients, their study design cannot determine how many of those patients will go on to develop clinically significant cardiac involvement. In the seven patients with amyloid identified on tenosynovial biopsy but without evidence of cardiac amyloid, the appropriate management is unclear. There are no data to support starting amyloid therapies in these patients. Perhaps serial monitoring for development of cardiac disease would be the best approach. Longer-term follow-up of this study cohort is planned and will clarify what proportion of these patients with amyloid will develop cardiac involvement.

Despite these limitations, the findings from Sperry et al carry implications for two different groups of providers: hand surgeons and cardiovascular providers. Hand surgeons should consider developing an algorithm to determine when to send carpal tunnel tissue for pathologic evaluation. Ideally, cardiology providers at larger institutions will work with hand surgeons to develop these protocols and follow the patients in whom amyloid is identified. The other crucial lesson for cardiologists is to remember the link between CTS and cardiac amyloidosis.

When evaluating a patient with heart failure (particularly heart failure with preserved ejection fraction), a history of bilateral CTS, particularly in the five to 10 years before onset of cardiac symptoms, should be a strong clue to screen for cardiac amyloidosis. Once providers start inquiring about CTS, they will be surprised how often CTS appears in many patients’ medical histories. A substantial proportion of these patients will, in fact, receive a cardiac amyloidosis diagnosis. With effective treatment for cardiac amyloidosis now available, the cardiovascular community should embrace this opportunity to facilitate early, rapid identification of patients with cardiac amyloidosis.