99m Technetium-pyrophosphate scintigraphy: a practical guide for early diagnosis of transthyretin amyloid cardiomyopathy

Abstract

Transthyretin amyloid cardiomyopathy (ATTR-CM) is caused by the cardiac deposition of insoluble amyloid fibrils formed by misfolded transthyretin proteins and is associated with various cardiac symptoms, such as progressive heart failure, conduction disturbance, and arrhythmia. The implementation of ^99m technetium (^99m Tc)-labelled bone radiotracer scintigraphy for diagnosing ATTR-CM has enabled accurate diagnosis of the disease with high sensitivity and specificity and positioned this diagnostic modality as an integral part of disease diagnostic algorithms. In 2020, ^99m Tc-pyrophosphate scintigraphy received exceptional approval for Japanese national health insurance reimbursement as a diagnostic method of ATTR-CM. Nevertheless, the utility of ^99m Tc-labelled bone radiotracer scintigraphy and the importance of an early diagnosis of suspected ATTR-CM using this technique have yet to be internalized as common practice by general cardiologists, and guidance on daily clinical scenarios to consider this technique for a diagnosis of suspected ATTR-CM is warranted. In this review, we discuss the utility of ^99m Tc-labelled bone radiotracer scintigraphy for the early diagnosis of ATTR-CM based on published literature and the outcomes of an advisory board meeting. This review also discusses clinical scenarios that could support early diagnosis of suspected ATTR-CM as well as common pitfalls, correct implementation, and future perspectives of ^99m Tc-labelled bone radiotracer scintigraphy in daily clinical practice. The clinical scenarios to consider ^99m Tc-labelled bone radiotracer scintigraphy in daily practice may include, but are not limited to, patients with a family history of the hereditary type of disease; elderly patients (aged ≥60 years) with unexplained cardiac findings (e.g. cardiac hypertrophy associated with abnormalities on an electrocardiogram, heart failure with preserved ejection fraction associated with unexplained left ventricular hypertrophy, and heart failure with reduced ejection fraction associated with atrial fibrillation and left ventricular hypertrophy); and patients with cardiac hypertrophy associated with diastolic dysfunction, right ventricular/interatrial septum/valve thickness, left ventricular sparkling, or apical sparing. Cardiac hypertrophy and persistent elevation in cardiac troponin in elderly patients are also suggestive of ATTR-CM. ^99m Tc-labelled bone radiotracer scintigraphy is also recommended in patients with characteristic cardiac magnetic resonance findings (e.g. diffuse subendocardial late gadolinium enhancement patterns, native T1 increase, and increase in extracellular volume) or patients with cardiac hypertrophy and bilateral carpal tunnel syndrome.

Keywords: 99mTechnetium-pyrophosphate scintigraphy; Amyloidosis; Cardiomyopathy; Heart failure; Transthyretin.

Figure 1

Conceptual diagram for the pathophysiology of transthyretin amyloid cardiomyopathy (ATTR‐CM) and applicability of non‐invasive diagnostic techniques. CMR, cardiac magnetic resonance.

Figure 2

Typical indicators to suspect transthyretin amyloid cardiomyopathy (ATTR‐CM) and consider ^99mTc‐PYP scintigraphy in daily clinical practice. CMR, cardiac magnetic resonance; CTS, carpal tunnel syndrome; ECV, extracellular volume; ECG, electrocardiogram; LGE, late gadolinium enhancement; NT‐pro‐BNP, N‐terminal pro–B‐type natriuretic peptide; HFpEF, heart failure with preserved ejection fraction.

Figure 3

Representative images of patients with transthyretin amyloid cardiomyopathy (ATTR‐CM). (A) Heart failure with pulmonary congestion and pleural effusion, (B) carpal tunnel syndrome (CTS) with thenar muscle atrophy (red arrows) and numbness in the thumb to the thumb side of the ring finger (area served by the median nerve), (C) electrocardiogram with low voltage (red box) and pseudo‐infarct pattern (blue box), (D) cardiac hypertrophy [left ventricular hypertrophy (LVH) with granular sparkling] on echocardiography, (E) apical sparing on echocardiography, (F) cardiac magnetic resonance (CMR) with subendocardial late gadolinium enhancement (LGE). A ring‐shaped subendocardial contrast is observed, consistent with the endocardium. The septal site has transmural enhancement (arrow), and the right ventricle also shows contrast enhancement.

Figure 4

(A) Representative planar (top) and single‐photon emission computed tomography/computed tomography (SPECT/CT; bottom) images of patients with Grade 1 myocardial tracer uptake and negative monoclonal protein test. White and red arrows indicate cardiac blood pools and positive cardiac uptake, respectively. (B) Flow chart of transthyretin amyloid cardiomyopathy (ATTR‐CM) diagnosis in patients with planar ^99mTc‐PYP scintigraphy Grade 1 and a negative monoclonal protein detection test. Endomyocardial, abdominal fat pad, or upper gastrointestinal tract biopsy is recommended. For patients who test negative with a biopsy, it is advisable to schedule regular follow‐up with scintigraphy after 6 months–1 year. Grade 1 in ^99mTc‐PYP scintigraphy refers to mild uptake less than rib uptake.