Cardiac Amyloidosis

Cardiac amyloidosis is caused by the buildup of clumps of abnormally folded protein (known as amyloid fibrils) in the heart muscle. This impairs its ability to function normally. It typically presents with rapidly progressive diastolic dysfunction in a non-dilated ventricle. It is one of the underdiagnosed disease entities. The diagnosis of cardiac amyloidosis requires a high degree of suspicion, with cardiovascular imaging being pivotal in reaching the diagnosis.  Cardiac amyloidosis may affect how electrical signals move through the heart (conduction system). This can lead to abnormal heartbeats (arrhythmias) and faulty heart signals (heart block).

Several types of amyloidosis are caused by different proteins that form amyloid fibrils.  Patients with amyloidosis may present with primary cardiac symptoms, or cardiac amyloidosis may be diagnosed incidentally in patients undergoing evaluation for other systemic involvements.

 

 

Cardiac amyloidosis can cause a range of symptoms, including:

Fatigue
Shortness of breath during exercise or other physical activities
Shortness of breath while lying down
Feeling faint or light-headed
Swelling in the legs
Abdominal distension or "swelling."

 

There are standard tests in the diagnostic journey of Cardiac amyloidosis

Electrocardiogram:

Echocardiography:

Cardiac MRI:

Nuclear SPECT:

Endomyocardial biopsy:

Genotyping:

 

 

 

While diagnosing cardiac amyloidosis may sound worrisome, various effective treatments are available.  Early diagnosis is the key to determining prognosis. A high degree of suspicion based on the clinical history and laboratory investigations can lead to earlier diagnosis and quicker initiation of therapy.  The prognosis of patients with AL amyloidosis has dramatically improved over time, with a four-year overall survival of approximately 90% for successfully treated patients with stem cell transplantation in the contemporary era.

Figure 2 - The parasternal long-axis view of a transthoracic echocardiogram shows a thickened bright myocardium, which is often the first clue towards the diagnosis of cardiac amyloidosis. This patient had a low voltage ECG despite thickened myocardium, as shown in Figure 1. Contributed by Pirbhat Shams, MBBS
Figure 2 - The parasternal long-axis view of a transthoracic echocardiogram shows a thickened bright myocardium, which is often the first clue towards the diagnosis of cardiac amyloidosis. This patient had a low voltage ECG despite thickened myocardium, as shown in Figure 1. Contributed by Pirbhat Shams, MBBS
AL: Light chain amyloid; ATTR: Transthyretin amyloid; Wt: wild type; Hr: Hereditary type (genetic). Contributed by Anubhav Jain, MD
AL: Light chain amyloid; ATTR: Transthyretin amyloid; Wt: wild type; Hr: Hereditary type (genetic). Contributed by Anubhav Jain, MD

Overall, cardiac amyloidosis is a rare disorder. The prevalence varies with the etiological type. About 10% of multiple myeloma cases may have AL amyloidosis, and 50 to 70% may have cardiac involvement. The annual incidence of AL amyloidosis is 1 per 100,000

In AL amyloidosis, amyloid protein is derived from immunoglobulin light chains, and most often involves the kidneys and the heart. ATTR amyloidosis is categorized as mutant or wild-type depending on the genetic sequence of the transthyretin (TTR) protein produced by the liver.

Wild-type ATTR amyloidosis mainly involves the heart, although the reported occurrence of bilateral carpal tunnel syndrome, spinal stenosis and biceps tendon rupture in these patients speaks to more generalized protein deposition.

Mutant TTR is marked by cardiac and/or peripheral nervous system involvement.

Cardiac involvement is associated with symptoms of heart failure and dictates the clinical course of the disease.

Siddiqi OK, Ruberg FL. Cardiac amyloidosis: An update on pathophysiology, diagnosis, and treatment. Trends Cardiovasc Med. 2018 Jan;28(1):10-21.

Shams P, Ahmed I. Cardiac Amyloidosis. [Updated 2022 Jul 1].

Muchtar E, Jevremovic D, Dispenzieri A, Dingli D, Buadi FK, Lacy MQ, et al. The prognostic value of multiparametric flow cytometry in AL amyloidosis at diagnosis and at the end of first-line treatment. Blood. 2017;129(1):82–7.