Utility and pitfalls of the electrocardiogram in the evaluation of cardiac amyloidosis

Abstract

Background: Cardiac amyloidosis is a protein misfolding disorder involving deposition of amyloid fibril proteins in the heart. The associated fibrosis of the conduction tissue results in conduction abnormalities and arrhythmias. "Classical" electrocardiogram (ECG) findings in cardiac amyloidosis include that of low voltage complexes with increased left ventricular wall thickness on echocardiography. However, this "classical" finding is neither sensitive nor specific. As cardiac amyloidosis is associated with a generally poor prognosis, the need for early recognition of this disease is important given the availability of new treatment options. In this review, we highlight 3 cases of patients with cardiac amyloidosis. Although presenting with typical clinical signs and symptoms, ECG for all 3 patients was not consistent with the classical findings described. They underwent further diagnostic tests which clinched the diagnosis of cardiac amyloidosis, allowing patients to receive targeted treatment. Through the review of the literature, we will highlight the different ECG patterns in patients with different types of cardiac amyloidosis and clinical scenarios, as well as the pitfalls of using ECG to identify the condition. Lastly, we also emphasize the current paradigms in diagnosing cardiac amyloidosis through the non-invasive methods of echocardiography, cardiac magnetic resonance imaging, and nuclear technetium-pyrophosphate imaging.

Conclusions: Electrocardiogram is often the first investigation used in evaluating many cardiac disorders, including cardiac amyloidosis. However, classical features of cardiac amyloidosis on ECG are often not present. A keen understanding on the ECG features of cardiac amyloidosis and knowledge of the diagnostic workflow is important to diagnose this condition.

Keywords: cardiac amyloidosis; electrocardiogram; light chain amyloidosis; transthyretin amyloidosis.

FIGURE 1

(a) Electrocardiogram of patient showing sinus rhythm with low voltage complexes in the chest leads and pseudoinfarction pattern in leads II and III. (b) Technetium‐pyrophosphate imaging of patient showing diffuse pattern of moderately intense radiotracer uptake seen in the left ventricular myocardium compared with the bony rib cage. Heart‐to‐contralateral lung ratio is 1.89 at 1 h. Semiquantitative interpretation in relation to rib uptake reveals increased myocardial uptake as compared to the rib tracer uptake, score 3. The scintigraphic features are strongly suggestive of transthyretin amyloid cardiomyopathy

FIGURE 2

(a) Electrocardiogram of patient showing sinus rhythm, left axis deviation, and incomplete left bundle branch block with large complexes in precordial leads. (b) Left ventricular strain imaging on transthoracic echocardiogram revealing a “cherry‐on‐top” appearance with relative apical sparing

FIGURE 3

(a) Electrocardiogram of patient showing sinus rhythm, borderline left ventricular hypertrophy, and P pulmonale. (b) Diffuse subendocardial and transmural late gadolinium enhancement (LGE) of the left ventricular myocardium is present. Extensive LGE of right ventricular myocardium, atrial walls, and atrial septum is also noted