Dr Jamshed Dalal, Director, Cardiac Sciences, Kokilaben Dhirubhai Ambani Hospital, Mumbai explains about Transthyretin amyloid cardiomyopathy (ATTR-CM) and highlights that ATTR-CM leads to progressive heart failure and can be fatal. It is therefore important for doctors and cardiologists to be aware of this rare condition. With the advances in diagnostics and treatment today, we have no excuse to let patients go undiagnosed and suffer from the morbidity and mortality that result from ATTR-CM
Globally, heart failure is a major burden on healthcare with around 21 million adults worldwide living with heart failure. The estimated prevalence of heart failure in India according to the INDUS study is about 1 per cent of the population or about 8–10 million individuals[1]. The condition brings with it high mortality and till recently 50 per cent of heart failure patients died within five years from diagnosis. While heart failure commonly results from ischemic heart disease, hypertension, Rheumatic Heart Disease (RHD), endomyocardial fibrosis and anaemia, there is another cause that is under-recognised and under-diagnosed-Transthyretin Amyloid Cardiomyopathy (ATTR-CM). In many patients, ATTR-CM is often confused with and misdiagnosed as high blood pressure-related heart disease
What is ATTR-CM?
ATTR-CM is a condition that results from a protein called transthyretin (TTR) building up in the organs including the heart tissue. Clumps of the TTR protein called fibrils accumulate in the heart muscle. It leads to the thickening and stiffening of the heart muscle especially the left ventricle, the main pumping chamber of the heart. This prevents the heart from pumping blood to the body effectively. Patients with ATTR-CM suffer from fatigue, shortness of breath and swelling in the lower limbs. Other symptoms include bloating in the abdomen, mental confusion. They can also have arrhythmias (abnormal heart rhythms) such as atrial fibrillation or ventricular tachycardia that increase the risk of stroke or sudden death. Over time, the condition progresses to heart failure.
Types of ATTR-CM
The two types of ATTR-CM include hereditary ATTR-CM and wild-type ATTR-CM. In the first type, hereditary ATTR-CM, there is a mutation in the transthyretin gene that leads to amyloid deposits in the heart, nerves and other organs. This can run in families or can also occur in an individual without a family history. The symptoms may start early at 20 years of age or even as late as 80 years.
In wild-type ATTR-CM, there is no mutation in the transthyretin gene, and this variety may present with pain and numbness in the hands and feet due to carpal tunnel syndrome or peripheral neuropathy in addition to affecting the heart. The symptoms usually start after age 65 and the wild-type forms a majority of patients with ATTR-CM.
TTR protein abnormality
In both genetic and wild-type ATTR-CM, the problem is the same. The body produces abnormal TTR proteins that break apart, fold and form clumps called amyloid fibrils. These amyloid fibrils’ clumps are carried throughout the body in the blood and deposited in nerves, the heart, the kidneys and other organs. Over time, this leads to organ and/or nerve damage with accompanying symptoms.
An under-recognised, under-diagnosed condition
ATTR-CM is more common than previously recognised as patients may have no symptoms or the symptoms may be mild and remain undiagnosed. While the exact prevalence of ATTR-CM is not known, studies indicate that less than 1 per cent of people with the disease are diagnosed.
In its early stages, ATTR-CM may mimic the symptoms of conditions such as heart failure related to hypertension and hypertrophic cardiomyopathy. Amyloidosis is also sometimes accompanied by aortic stenosis or narrowing of the aortic valve. Outside the heart, the TTR protein accumulation can result in kidney dysfunction, digestive problems and can also cause the narrowing of the spinal canal in the lower back known as lumbar spinal stenosis.
The patient’s condition often worsens and progresses to end-stage heart failure. Recent studies have suggested that up to 10 per cent to 15 per cent of older adults with heart failure may be suffering from ATTR-CM that is not recognized.[2]
Cardiologists are well aware of Amyloid cardiomyopathy but are unaware of ATTR-CM in particular, the reason being there was no diagnostic test available for ATTR-CM. Routine heart testing is unlikely to diagnose cardiomyopathy caused by ATTR-CM. Specialised testing is required for a diagnosis.
Advances in diagnostic technology for ATTR-CM
Fortunately, advances in diagnostic capabilities now makes it possible to diagnose ATTR-CM at an early stage. Advances in nuclear medicine scan using radiotracer scintigraphy technology, a radiographic technique using radioactive tracers help to confirm this condition. Specialised imaging studies of the heart including a cardiac MRI and a tissue biopsy of an affected organ and genetic testing can help to further confirm the diagnosis. Especially, the advent of Pyrophosphate Nuclear Scan (PYP) has made ATTR-CM easy and simple to detect. The use of these advanced diagnostic techniques has led to the realisation that there is a higher prevalence of ATTR-CM in patients with heart failure than previously recognised.
Benefits of an early diagnosis
Considering that ATTR-CM is a deadly disease and if not treated, an affected individual can die within 2-6 years from diagnosis[3], it is important that ATTR-CM be diagnosed as early as possible. Early diagnosis is critical for efficacious treatment, and the earlier the diagnosis, the earlier the medication can be started to stop further deterioration of the patient’s condition. Now specific treatment for ATTR-CM is available that can reduce symptoms and halt the progression of the disease making early diagnosis mandatory.
This is important as while the ATTR-CM is not curable and the existing amyloid deposits cannot be reversed, medications can halt disease progression by slowing or stopping the build-up of new protein deposits in the heart and other organs. The medications target the TTR proteins, prevent the folding and formation of clumps to stabilise the condition. For the patient, there is a reduction in the symptoms with an improvement in the quality of life and an increase in the survival period.
No patient with ATTR-CM should go undiagnosed
In conclusion, ATTR-CM leads to progressive heart failure and can be fatal. It is therefore important for doctors and cardiologists to be aware of this rare condition. With the advances in diagnostics and treatment today, we have no excuse to let patients go undiagnosed and suffer from the morbidity and mortality that result from ATTR-CM. They must suspect and look for ATTR-CM in patients presenting with signs and symptoms of heart failure, and whose walls of the heart are thickened. This will enable early detection and initiation of treatment to manage the condition and ease the patient’s life.
References
[1] https://www.j-pcs.org/text.asp?2016/2/1/28/182988
[2] https://pubmed.ncbi.nlm.nih.gov/31171094/
[3] https://cdn.pfizer.com/pfizercom/news/ATTR-CM_Toolkit_Factsheet_D01_022619.pdf