Navigating Diagnostic Ambiguities in Cardiac Amyloidosis: Insights from a Case with Delayed Diagnosis of AL Amyloidosis

Abstract

BACKGROUND Cardiac amyloidosis is the accumulation of aberrant proteins in the heart, liver, brain, and several other organs. It presents both extracardiac and cardiac symptoms, making diagnosis difficult and early detection crucial in the prognosis of the patient. Diagnostic techniques for cardiac amyloidosis can present false-negative results, making diagnosis difficult in the early stage of the disease. CASE REPORT A 67-year-old man presented for worsening dyspnea of several months' duration and recent cough. Echocardiography study showed unexplained biventricular hypertrophy with preserved left ventricular systolic function, and a restrictive filling pattern suggesting an infiltrative heart disease like cardiac amyloidosis. Technetium pyrophosphate scan, light-chain assay, and serum and urine protein immunofixation were negative. The patient was treated as a case of advanced heart failure, with initial improvement. He started deteriorating progressively, and repeating the workup was considered. Six months later, a repeated echocardiogram showed severely impaired left ventricular systolic function and findings suggestive of advanced cardiac amyloidosis. Free light-chain assay was positive, in favor for AL amyloidosis, which was confirmed by a bone marrow biopsy and cardiac MRI. Chemotherapy was started, but the patient died due to stage D heart failure caused by advanced AL amyloidosis. CONCLUSIONS We aim at increasing awareness of the early diagnosis of cardiac amyloidosis and highlighting the importance of considering the disease even with an initial negative workup. We will also try to explain the reason for the false-negative initial workup and to implement the use of cardiac MRI in early stages if the clinical suspicion for the disease is high.

Figure 1

Echocardiographic findings showing restrictive filling pattern with E/E’: 19.88 and an E/A ratio >2 (arrow), a hallmark of cardiac amyloidosis.

Figure 2

Echocardiographic finding showing right ventricle hypertrophy (arrow) and spontaneous echo contrast in left atrium.

Figure 3

Echocardiographic finding showing left ventricular hypertrophy (arrow) with speckled myocardial appearance and pleural effusion.

Figure 4

Echocardiographic finding showing systolic flow reversal (arrow) in the hepatic vein indicative of severe tricuspid regurgitation.

Figure 5

Mild pericardial effusion and significant pleural effusion (arrow).

Figure 6

Very low septal E’ (arrow).

Figure 7

Diagnostic algorithmic approach for cardiac amyloidosis.

Figure 8

Algorithms that summarize the approach used in treatment of cardiac amyloidosis. Transthyretin amyloidosis (ATTR); Heart failure (HF); Direct oral anticoagulant (DOAC); Cardiac variant transthyretin amyloidosis ATTRwt-CM; Variant transthyretin amyloidosis (ATTRv); Permanent pacemaker (PPM); Implantable cardioverter-defibrillator (ICD); Cardiac resynchronization therapy (CRT); Ventricular tachycardia (VT); Sudden cardiac death (SCD).