Inflammation or Small-Vessel Disease Could Be Responsible for a False-Positive Bone Scintigraphy Signal for Transthyretin Amyloidosis

For the purposes of diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM), a positive nuclear scintigraphy with hydroxy bisphosphonate bone tracer (99mTc-HPD) is thought to have high sensitivity (>99%) and specificity (91%). Chimenti and colleagues described a case report of an 85-year-old male. Due to systemic arterial hypertension, he had been hospitalized due to presyncope related to evidence of bradyarrhythmia (first-degree atrioventricular block) and tachyarrhythmia (nonsustained ventricular tachycardia).

Two years earlier, he had undergone surgery for bilateral carpal tunnel syndrome. At that time, cardiac examination was unremarkable. With the exception of high sensitivity elevated cardiac troponin (0.295 mcg/L; normal range, <0.014 mcg/L) and N-terminal pro-B-type natriuretic peptide (384.3 pg/mL; normal range, 0-254 pg/mL), routine laboratory tests were normal. Electrocardiographic findings showed sinus rhythm of 53 bpm, left anterior fascicular block, first-degree atrioventricular block, and normal left ventricular QRS voltages. Severe hypertrophy of the left ventricle was shown by a 2-dimensional echocardiography, and because of the suboptimal echocardiographic window, strain imaging was not detected. Left ventricular hypertrophy with maximal wall thickness of 20 mm in the middle-basal septum was confirmed by cardiac magnetic resonance imaging.

This presentation of increased thickness of ventricular walls and a positive bone scintigraphy highlights a clinical conundrum; unexpectedly, he was discovered to have sarcomeric hypertrophic cardiomyopathy via left ventricular endomyocardial biopsy. On 6 left ventricular samples, immunohistochemistry, Congo Red staining, and transmission electron microscopy scored negative for amyloidosis, yet they suggested sarcomeric hypertrophic cardiomyopathy. In hypertrophic cardiomyopathy cases, false-positive bone scintigraphy can be observed. Therefore, particularly in light of potential specific, sustained, and costly treatment, endomyocardial biopsy is recommended for diagnosing TTR cardiac amyloidosis.

The investigators concluded that TTR was not shown in the genetic study, and sarcomeric gene mutations were not generally involved. They hypothesized that inflammation or small-vessel disease could be responsible for a false-positive bone scintigraphy signal for transthyretin amyloidosis in hypertrophic cardiomyopathy focal cell necrosis related to the demand and supply of oxygen being mismatched. Due to these findings, it is highly recommended for the correct diagnosis of cardiomyopathies with hypertrophic phenotype to utilize endomyocardial biopsy. To scrutinize the incidence of false-positive TTR cardiac amyloidosis to bone scintigraphy and to more fully understand the associated molecular pathways, compared with endomyocardial biopsy, further studies are warranted.

Source: Chimenti C, Alfarano M, Maestrini V, et al. False-positive bone scintigraphy denoting transthyretin amyloid in elderly hypertrophic cardiomyopathy. ESC Heart Fail. 2021;8:3387-3391.

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