Bilateral Biceps Tendon Ruptures in a Patient with Hypertrophic Cardiomyopathy (HCM)

I manage lipids in a 61 year-old man who was diagnosed with hypertrophic cardiomyopathy (HCM) before I met him. He tore his biceps tendon with minimal provocation about 12 years ago, and was told by the pharmacist that statins could cause tendon ruptures so he stopped his statin. I reassured him that statins causing tendon rupture was rare, if ever, restarted his statin, and he partially tore his other biceps tendon with minimal strain several weeks later. That got my attention. One of our former fellows, Dr. Raja Pullatt, researched the relationship of tendons and statins and noted that matrix metalloproteinases (MMP) 2 & 9 are required for tendon repair. MMPs degrade damaged collagen allowing its replacement with healthy collagen. Statins are known to reduce MMP 9. This MMP reduction is probably one of the reasons why statins reduce the rupture and erosion of atherosclerotic fibrous caps thereby reducing acute coronary syndromes. We reported the case, along with 247 other cases of tendon injury reported in the FDA’s adverse drug reaction database.1

I remembered this case when I recently heard two excellent lectures on cardiac amyloidosis. The first presentation was by Dr. Rodney Falk, an internationally known cardiac amyloidosis expert, at our annual cardiovascular symposium on October 2, 2019. The second was by Dr. Lane Duvall, our director of nuclear cardiology, at our weekly cardiology grand rounds on November 5, 2019. Both mentioned that transthyretin amyloidosis (TTR) is associated with orthopedic issues such as bilateral biceps tendon rupture or carpal tunnel syndrome 10–15 years before the presentation of cardiac symptoms.

I decided (with the private cardiologist’s permission) to perform a technesium pyrophosphate (TPP) scan. TTP is used for bone imaging, but binds to amyloid. To my surprise, this patient’s entire LV lit up with tracer. He may or may not have HCM, his diagnosis for years, but he does have cardiac amyloidosis.

Honestly, the recommended approach is to first do a serum lambda/kappa ratios plus serum and urine immunofixation studies to exclude AL amyloid. TPP binds less readily to AL so it is possible to have cardiac amyloidosis and a negative TPP scan with AL amyloid. Both Lane and Sabrina Arora have pointed this out to me. I wanted to do the TPP without other studies because my patient had myocardial cardiac hypertrophy and tendon issues. Both cardiac involvement and the tendon issues are more frequent in TTR.

This diagnosis comes at a good time because we now have some promising medications to remove amyloid fibrils (doxycycline — although this is controversial because the positive paper had not been reproduced), to stabilize the amyloid (diflusinal and tafamides), and to reduce amyloid production by blocking TTR mRNA (pitisiran and intersen) although these last drugs are approved only for the peripheral neuropathy of amyloidosis.

So, what are the clinical messages?

· Go to lectures and pay attention. I go in with the question of what can I learn to help my patients. Continuing medical education courses now require that we identify the “knowledge gaps” that will be addressed by the lecture. I find identifying my own gaps impossible because “I don’t know what I don’t know”. So, anything you learn may turn out to be useful.

· Remember the law of diagnostic parsimony, which means, make the fewest diagnoses possible. Rather than statin-induced tendon rupture and HCM, perhaps I should have thought what diagnosis links bilateral biceps tendon ruptures with cardiac hypertrophy. Granted he may have both HCM and cardiac amyloidosis, but I doubt it.

· Remember the importance of a past medical history and the review of systems. Both often give you just the clues you need in an unusual or difficult case.

· Remember that orthopedic issues can precede the cardiac symptoms of TTR amyloid by years, and that making an early diagnosis may be even more important if these promising drugs prove effective.

I guess this also makes me wonder if there is some possible interaction of statins and TTR. Statins have been examined for their effects on cerebral amyloid deposits in Alzheimer disease, but could statins hasten the TTR-related tendon issues? That sounds like a good topic for a literature review.

1. Pullatt RC, Gadarla MR, Karas RH, Alsheikh-Ali AA, Thompson PD. Tendon rupture associated with simvastatin/ezetimibe therapy. Am J Cardiol. 2007;100(1):152–153.