Amyloid fibrils clumps of misfolded proteins deposited into heart tissue cause Transthyretin amyloid cardiomyopathy (ATTR-CM). 

It is a rare condition that impacts on heart and brain functions caused due to TTR mutations, but also affect those without genetic variants. 

TTR is a tetrameric protein encoded with TTR gene on chromosome 18 and it is mainly produced in the liver with smaller amounts. 

Systemic ATTR disease causes extracardiac signs/symptoms due to amyloid deposition in tissues. 

Primary T4 carrier protein TTR regulates T4 distribution helps myoblast differentiation through MYL2 and thyroid hormone production.
There are two types of ATTR-CM as: 

Hereditary ATTR-CM (hATTR-CM) 

Wild ATTR-CM (wATTR-CM) 

There are differences in the incidence and prevalence of hATTR amyloidosis among various groups and geographical areas. Ethnic groups or geographical regions there is a higher occurrence of certain TTR gene variants.  

Age-related increases in the incidence of wtATTR indicate that the disease mostly affects the elderly with most cases being diagnosed in those over 60. 

The symptoms like heart failure and neuropathy are frequently mistaken for other common aging disorders, estimates imply that wtATTR amyloidosis may be underdiagnosed. 

For wtATTR estimated prevalence in men over 60 years is 10% to 25%. Males are more affected than females for wild-type ATTR. 

Mutations in the TTR gene cause the generation of mutant TTR proteins that are prone to misfolding which causes hereditary ATTR amyloidosis (hATTR). The cause of wild-type ATTR amyloidosis (wtATTR) is not a genetic mutation.  

People over 60 years old with normal TTR protein may misfold. Amyloid fibrils are prone to self-assembly from misfolded TTR monomers.  

The impacted tissues and organs suffer structural damage and functional impairment because of amyloid accumulation. 

Amyloid fibrils in myocardial interstitium cause thick walls in restrictive cardiomyopathy. 

ATTR-CM is caused due to misfolded TTR proteins that aggregate in heart muscles. 

TTR proteins with a tendency to misfold and aggregate into amyloid fibrils. Numerous TTR gene variants have been found, exhibiting differing levels of penetration and clinical presentations. 

The inheritance pattern for hATTR amyloidosis is autosomal dominant. To get the illness, a person must inherit one copy of the defective gene from each parent. 

Amyloid fibrils deposit disrupts heart function to cause restrictive cardiomyopathy, heart failure symptoms. 

The degree and course of hATTR amyloidosis can be affected by mutations in the transthyretin gene.  

The functional state of patient at the time of diagnosis may have an impact on its outcome. Those who have minor symptoms and preserved organ function might fare better than those who have severe impairments to their functional capacity and organ function. 

Symptomatic cardiac involvement in ATTR does not always indicate a bad prognosis, unlike light chain amyloidosis. 

wtATTR-CM occurs in men over the age of 60 years old. While hATTR-CM occurs between the age group of 30 to 50 years old. 

Cardiovascular Examination 

Respiratory Examination 

Abdomen Examination 

The specific genetic mutation underlying hATTR-CM may influence the age of onset and severity of symptoms. 

wtATTR-CM amyloidosis occurs later in life, usually after the age of 60, because of age-related misfolding of normal transthyretin protein. 

Sodium restriction and diuretics maintain hydration in ATTR-CM. Oral loop diuretics with high bioavailability used with aldosterone blockers. 

Poor tolerance to extreme heart rate changes due to LV size and dysfunction. 

Amiodarone preferred for antiarrhythmics due to safety profile in cardiomyopathy. 

Increase the lower pace rate in pacemaker-dependent patients with advanced disease to improve cardiac output in heart failure. 

Management of ATTR-CM amyloidosis focuses on controlling blood pressure, optimizing glycemic control, and address complications. 

Patisiran, vutrisiran, inotersen, and eplontersen these are FDA-approved drugs for adult hATTR polyneuropathy. 

Treatment of ATTR-CM should include early consideration of tafamidis to slow disease progression. 

Rheumatology

Ensure adequate and restful sleep it improve the overall health of patient. 

Avoid processed foods and use herbs and spices for seasoning instead of salt. Monitor daily fluid intake to avoid excessive drinking of fluids. 

Patient should take healthy diet such as whole grains, vegetables, fruits, and low saturated fats to maintain heart function. 

Proper education and awareness about ATTR-CM should be provided and its related causes with management strategies. 

Appointments with a physician and preventing recurrence of disorder is an ongoing life-long effort. 

Rheumatology

Tafamidis:  

It binds to the thyroxine binding site of TTR molecules to stabilize the tetrameric structure.  

Rheumatology

Inotersen: 

It causes degradation of mutant and wild-type transthyretin mRNA with the help of TTR mRNA.  

Rheumatology

Cardiac device implantation is performed to maintain an adequate heart rate and improve cardiac output. 

Cardiac transplantation is conducted to replace the diseased heart with a healthy donor heart. 

Rheumatology

In the initial diagnosis phase, evaluation of neurological and gastrointestinal symptoms to confirm diagnosis. 

Pharmacologic therapy is very effective in the treatment phase as it includes use of cardiovascular agent, antisense oligonucleotides and surgical intervention. 

In supportive care and management phase, patients should receive required attention such as lifestyle modification and rehabilitation. 

The regular follow-up visits with the physician are schedule to check the improvement of patients along with treatment response.