Clearing Up Misconceptions About Cardiac Amyloidosis to Promote Early Diagnosis and Treatment

Cardiac amyloidosis (CA) can be confused with other cardiac diseases and often goes unrecognized until the disease is advanced. To take advantage of disease-modifying therapies, earlier diagnosis is needed to initiate treatment and improve patient outcomes.

Several cardiologists recently outlined current evidence surrounding the misconceptions about CA to help providers better understand the disease.

Misconception: Cardiac amyloidosis is a rare disease.

Current evidence: Although the monoclonal light chain amyloid form of CA (AL-CA) is rare, with approximately 10,000 people living with the disease, an autopsy study revealed the presence of transthyretin amyloidosis (ATTR) fibrils in approximately 25% of individuals aged >80 years. Furthermore, evidence of ATTR-CA on 99mtechnetium pyrophosphate (99mTc-PYP) cardiac scintigraphy was found in 16% of patients evaluated for transcatheter aortic valve replacement for severe aortic stenosis. In addition, individuals of sub-Saharan African descent are more commonly found to have the V122I variant form of ATTR.

Misconception: Only one type of amyloidosis affects the heart.

Current evidence: Both AL-CA, a consequence of amyloid formation from monoclonal free light chains produced by plasma cells, and ATTR-CA, caused by transthyretin amyloid deposition, frequently affect the heart. Common to both forms of amyloidosis, cardiac manifestations are a result of extracellular accumulation of amyloid in the myocardium.

Misconception: Clinical manifestations of amyloidosis are usually late and signify end-stage disease.

Current evidence: The symptoms of amyloidosis can occur early and several years before cardiac manifestations. Bilateral carpal tunnel syndrome is a common symptom of patients with ATTR and often occurs ≥5 years before cardiac involvement. Similarly, transthyretin amyloid deposits are frequently found in patients with lumbar spinal stenosis and a history of biceps tendon rupture. Some variant forms of ATTR can also cause significant peripheral and autonomic neuropathies.

Misconception: Imaging and electrocardiographic manifestations are nondiagnostic.

Current evidence: Electrocardiography, echocardiography, cardiac magnetic resonance imaging, and bone scintigraphy imaging often show features that suggest CA even if the individual findings are nonspecific.

Misconception: Endomyocardial biopsy is highly sensitive and is required in all cases.

Current evidence: Patient history, physical exam, electrocardiography, and echocardiography should be used during the initial workup. A diagnosis of AL-CA requires a biopsy because elevated monoclonal protein in serum is not definitive. In the absence of monoclonal gammopathy on serum and urine evaluation, ATTR-CA can be diagnosed definitively with a positive 99mTc-PYP scan. When 99mTc-PYP scan is negative or indeterminant and suspicion for CA remains high, an endomyocardial biopsy should be performed.

Misconception: Beta blockers should be avoided in patients with CA.

Current evidence: Patients with CA can have hypotension, which may be aggravated with beta blockers. However, beta blockers may also be useful for controlling tachyarrhythmias in patients with CA.

Misconception: All CA subtypes should be treated in the same manner.

Current evidence: The management of ATTR-CA differs from that of AL-CA. Treatments targeting amyloid-producing cells are used for AL-CA, whereas ATTR-CA is treated by reducing transthyretin production and increasing transthyretin stability. Cardiac injury is not necessarily repaired by these therapies. Regardless of CA subtype, the management of heart failure and other cardiovascular comorbidities should be instituted with the appropriate use of diuretics.

Misconception: Patients with CA should not undergo heart transplantation because their outcomes are worse.

Current evidence: In recent years, survival rates for heart transplantation in patients with CA, regardless of the subtype, have improved. Two decades ago, patients with AL-CA who underwent transplantation had significantly worse 5-year survival compared with patients transplanted for other indications. However, more recently, good survival outcomes were seen in transplanted patients with AL-CA compared with those transplanted for nonamyloid indications, with a median survival of approximately 10 years in those also treated with chemotherapy or autologous hematopoietic stem-cell transplantation.

Misconception: Mechanical circulatory support should be avoided in patients with CA.

Current evidence: Mechanical circulatory support has been used successfully in some patients with CA but remains challenging due to high rates of mortality and postoperative complications compared with patients without CA.

Misconception: CA only affects left ventricular myocardium.

Current evidence: Many patients with CA have right ventricular involvement, and biventricular cardiomyopathy is common.

Misconception: Mechanical circulatory support should be avoided in patients with CA.

Current evidence: Mechanical circulatory support has been used successfully in some patients with CA but remains challenging due to high rates of mortality and postoperative complications compared with patients without CA.

Misconception: CA only affects left ventricular myocardium.

Current evidence: Many patients with CA have right ventricular involvement, and biventricular cardiomyopathy is common.

Misconception: The approach to atrial fibrillation in patients with CA should be similar to the approach used in those without CA.

Current evidence: Some clinicians recommend mandatory transesophageal echocardiography for patients with CA and atrial fibrillation before direct current cardioversion, no matter how long these patients have received anticoagulation therapy.

The researchers stated that the evidence for CA does not solely lie in techniques such as advanced imaging studies or biopsies but rather can be found in a patient’s history, physical exam, and electrocardiogram. They recommended that suspected cases of CA be referred to specialized centers so that patients can receive early treatment, which may prevent disease progression.

Source: Nguyen FD, Rodriguez M, Krittanawong C, et al. Misconceptions and facts about cardiac amyloidosis. Am J Cardiol. 2021;160:99-105.

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