Cardiac Amyloidosis May Be Linked to Carpal Tunnel Syndrome

here’s a breakdown of the article, presented as a bulleted list:

Study Objective: To investigate if an early diagnosis of Carpal Tunnel syndrome (CTS) can predict an early diagnosis ofATTRwt (Transthyretin Amyloidosis with wild-type transthyretin), and how frequently enough orthopedic surgeons consult with cardiologists on these cases.

Data Source: 42 diagnosed ATTRwt cases at Juntendo University Faculty of Medicine, Tokyo, Japan (August 2019 – December 2024).

Patient Demographics:
Total cases: 42
Male: 34
Female: 8
Average age: 77.7 years

Exclusion Criteria:
No genetic testing performed.
Diagnosed with ATTRv (variant ATTR).
Died or dropped out before definitive diagnosis.
Incomplete data. Key Findings (CTS and ATTRwt):
History of CTS: 26 out of 42 cases (61.9%) had a history of CTS.
CTS Laterality (amongst those with CTS history):
Bilateral CTS: 15 cases (57.7%)
Unilateral CTS: 11 cases (42.3%)
Timing of Diagnosis (amongst those with CTS history):
CTS diagnosed before ATTRwt: 24 cases (92.3%)
CTS diagnosed after ATTRwt: 2 cases (7.7%)
Time Lag: Average of 6.7 years (range: 0-29 years) between CTS and ATTRwt diagnosis when CTS was diagnosed first.
Mortality: 4 out of the 26 participants with a CTS history died, with an average time of 17.5 months (range: 2-39 months) after ATTRwt diagnosis.

Inter-specialty Consultations:
Cardiologists consulted orthopedic surgeons on differential diagnosis of CTS in only 4 out of 42 ATTRwt cases.
No orthopedic surgeons consulted cardiologists.

Study Limitations:
Small Sample Size: Only 42 cases met the criteria.
CTS Diagnosis Method: Based on “history of CTS” in patient records, which may lead to false negatives due to varying symptom severity and latency.
Treatment Inclusion: Both surgical and conservative CTS treatments were included.
Increased Amyloidosis Risk: The risk of developing amyloidosis was higher in participants who underwent CTS surgery.

Comparison with Previous Studies:
Previous studies report 40%-50% of ATTRwt patients also had a history of CTS.
A meta-analysis showed 38% of Cardiac amyloidosis (CA) patients had a history of CTS, but only 13% of CTS patients developed CA, with an average time of 7.02 years from CTS diagnosis to CA development. Future Research Recommendations:
* Focus on larger-scale studies,meta-analyses,and prospective studies to further investigate the CTS and ATTRwt relationship.

Could the presence of carpal tunnel syndrome, particularly in the absence of typical risk factors, prompt inquiry for underlying cardiac amyloidosis?

Cardiac Amyloidosis might potentially be Linked to Carpal Tunnel Syndrome

Understanding the connection: Amyloidosis & Carpal Tunnel

For years, carpal tunnel syndrome (CTS) has been largely attributed to repetitive hand motions, genetics, and conditions like diabetes. Tho, emerging research suggests a surprising link: cardiac amyloidosis. This connection is gaining traction as clinicians observe a higher-than-expected incidence of CTS in patients later diagnosed with amyloidosis, particularly transthyretin amyloid cardiomyopathy (ATTR-CM). Understanding this relationship is crucial for earlier diagnosis and improved patient outcomes.

What is Cardiac Amyloidosis?

Cardiac amyloidosis occurs when abnormal proteins,called amyloid,build up in the heart muscle. This buildup stiffens the heart,hindering its ability to pump effectively. Ther are several types,with ATTR-CM being the most common.

ATTR-CM (Transthyretin Amyloid Cardiomyopathy): Caused by a misfolded transthyretin protein. This can be hereditary (hATTR) or wild-type (wtATTR), occurring without a known genetic cause.

Light-Chain Amyloidosis (AL amyloidosis): Associated with plasma cell disorders, like multiple myeloma.

Other Forms: Less common types exist, but ATTR-CM and AL are the most frequently encountered in clinical practice.

Symptoms of cardiac amyloidosis often mimic other heart conditions, including:

shortness of breath

Fatigue

Swelling in the legs and ankles

irregular heartbeat (arrhythmia)

Dizziness or lightheadedness

How Does Amyloidosis Relate to Carpal Tunnel Syndrome?

The link between amyloidosis and carpal tunnel syndrome isn’t promptly obvious. The connection lies in the way amyloid deposits affect peripheral nerves. Amyloid fibrils can infiltrate the median nerve at the wrist, causing compression – mirroring the pathology of classic CTS.

Here’s a breakdown of the proposed mechanisms:

1. Nerve Infiltration: Amyloid deposits directly within the carpal tunnel compress the median nerve. This is distinct from the typical causes of CTS, like swelling from tendonitis.
2. Systemic Nerve Involvement: Amyloidosis is a systemic disease, meaning it can affect multiple organs, including peripheral nerves throughout the body. this widespread nerve damage can manifest as CTS,alongside other neuropathies.
3. Increased risk in ATTR-CM: Studies indicate a significantly higher prevalence of CTS in individuals with ATTR-CM compared to the general population. This suggests a strong association, particularly with the transthyretin protein misfolding.

Recognizing Amyloid-Related Carpal Tunnel Syndrome

Distinguishing between typical CTS and amyloid-related carpal tunnel syndrome is vital. Several factors should raise suspicion:

Bilateral and Symmetrical Symptoms: While CTS can be bilateral, amyloid-related CTS frequently enough presents symmetrically in both hands.

Atypical Presentation: symptoms may not respond to conventional CTS treatments like splinting or steroid injections.

Presence of Other Systemic Symptoms: Look for signs of heart failure (shortness of breath, edema), unexplained fatigue, or other neurological symptoms.

Age of Onset: Amyloid-related CTS often appears later in life,typically after age 50.

Family History: A family history of heart disease or neuropathy should prompt further investigation.

Diagnostic Approaches: Beyond Standard CTS Testing

if amyloidosis is suspected,standard CTS diagnostic tests (nerve conduction studies,electromyography) may be helpful,but they are not definitive. Additional testing is crucial:

1. Echocardiogram: To assess heart structure and function, looking for signs of amyloid infiltration (thickened heart walls, diastolic dysfunction).
2. Cardiac MRI: Provides detailed images of the heart and can detect amyloid deposits. Gadolinium contrast agents are often used.
3. Technetium-99m Pyrophosphate (PYP) Scintigraphy: A nuclear imaging scan that can identify amyloid deposits in the heart. This is particularly useful for ATTR-CM.
4. Fat Pad Aspiration & Congo Red Staining: A biopsy of abdominal fat can reveal amyloid deposits. Congo red staining under polarized light shows characteristic apple-green birefringence.
5. Genetic Testing: For suspected hATTR amyloidosis, genetic testing can identify mutations in the TTR gene.
6. Serum Free Light Chain Assay: Helps detect AL amyloidosis by measuring levels of immunoglobulin light chains.

Treatment Implications & Management

Early diagnosis is paramount. Treatment for amyloidosis focuses on stabilizing the condition and managing symptoms.

ATTR-CM Specific Therapies: New medications, like tafamidis, are designed