Doctors are great at coming up with fancy words to make themselves appear cleverer than perhaps they are! I recall reading somewhere that completing a medical degree is the equivalent of learning a new language. The word phenocopy is a good example of this. In my world, it basically means a medical condition that looks like one thing, but in fact is caused by something else. The reason to mention it here is to describe two interesting patients I saw last week who had just such a condition.
When I see a patient with a thickened heart muscle on a scan, the most common cause is high blood pressure. As the heart has to squeeze harder to pump blood around the body, the muscle enlarges just as a bicep does in someone going to the gym regularly.
There are however many other causes of a thick heart muscle. Often the age of a patient can give you a clue as to what that cause is. For example, in a younger person, inherited causes such a hypertrophic cardiomyopathy would be more likely. In a person over the age of 80, there is another condition which previously was thought of as rare, but in actual fact we probably were simply not recognising it. As techniques such as MRI of the heart have become more widespread, we are realising that this particular condition is much more common that we thought. I estimate that I diagnose 1-2 new cases per month.
The first of my recent patients had been getting breathless for several months, with some swelling of their ankles. When I saw them in clinic, I noticed that their ECG (paper tracing of the heart) suggested there was a thin-walled heart, but the echocardiogram (ultrasound scan) showed a very thick-walled heart. What could the cause be? (This is something I test my junior doctors on when we see it!)
The answer is a condition called cardiac amyloid. Up to about 10% of patients previously thought to have heart failure with preserved ejection fraction (which I have discussed previously) are thought actually might have excess amyloid in their hearts.
Cardiac amyloid is a condition where a protein gets manufactured in the liver, but it gets altered by enzymes and then deposited in various sites in the body, the heart being one of them. It also has a prediliction for the carpel tunnel ligaments, so patients often get carpel tunnel syndrome on both sides long before they get heart symptoms. When I asked my patient about this, although they hadn’t seen their doctor, they had classical symptoms of carpel tunnel syndrome!
Typically the heart gets a bit thicker and stiffer, and the symptoms include breathlessness, swollen ankles, tiredness and often heart rhythm problems (many patients go on to need a pacemaker). The guts can be affected too, with patients experiencing an altered bowel habit. Lastly the peripheral nerves can be affected causing altered sensation, and unsteadiness.
You can usually spot signs of amyloid on an echo (ultrasound) scan of the heart and an ECG, but a MRI or special bone scan (called a DPD, no relation to the postal company) is used to confirm.
My second patient had had a bone scan for prostate cancer (which often can metastasise to the bones). Thankfully, the cancer had not spread, but interestingly the heart lit up like a christmas tree on the scan. There is only one thing that can cause this – amyloid.
There are a few forms of amyloid, and typically 2 affect the heart. The first is called AL amyloid, and is often associated with myeloma. It tends to be a more aggressive form of the condition. Treatment in selected cases is with chemotherapy and sometimes a bone marrow transplant.
TTR amyloid (which stands for transthyretin) on the other hand can take an awful long time to develop (years) and typically patients only get diagnosed well into their 70s or 80s. There are two forms, one of which is inherited. If patients are picked up sooner, then the options for treatment are better. There are some new novel therapies designed to alter either the amount of amyloid protein produced, or to affect the way it gets folded (and therefore stuck in the heart).
Some types of treatment involve RNA (a molecule similar to DNA) to interfere with the liver amyloid production, and can transform the lives of affected patients. It’s only been available for a year or two, and is testament to how translational medicine can take science from the bench to the bedside. Another treatment binds to the mis-folded protein to try and stop it being deposited in the heart.
The way in which these treatments has evolved also, from needing regular intravenous infusions every 2 weeks in hospital, to home-delivered injections under the skin every few months. I know which I would prefer! I have several patients on these drugs, and can say they have been nothing short of life-changing for them.
At the time of writing, these drugs are only prescribed via the National Amyloid Centre in London, with local consultants helping with shared care. The drugs are very expensive, and for new drugs for what is a niche condition there needs to be centralised oversight to begin with. However, this situation is likely to be changing, as we are now seeing more and more patients who might benefit, and depending on where you live, London can be a long way to travel.
In the meantime, there are other simpler drugs that can be used to manage fluid overload, and patient education regarding some lifestyle measures is really important.
I hope you found this description of a phenocopy interesting and informative, and if you ever meet someone who has had carpel tunnel syndrome on both left and right sides, you might just advise them to get their hearts checked!