99mTc Bone-Avid Tracer Cardiac Scintigraphy: Role in Noninvasive Diagnosis of Transthyretin Cardiac Amyloidosis.

Transthyretin cardiac amyloidosis (ATTR-CA) is an overlooked cause of heart failure, with substantial morbidity and mortality. The emergence of several novel therapies has fueled the interest in early and accurate diagnosis of ATTR-CA so that potentially life-saving pharmacologic therapy can be administered in a timely manner. The most promising imaging modality and biomarker is SPECT imaging with technetium 99m (99mTc)-radiolabeled bone-seeking tracers, which have high specificity in the diagnosis of ATTR-CA, potentially obviating biopsy. In this article, the authors provide a focused review on the use of 99mTc pyrophosphate (PYP), 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), and hydroxymethylene diphosphonate (HMDP) for diagnosis of ATTR-CA, present a systematic approach to interpretation of the scans, and highlight several common pitfalls to illustrate important diagnostic principles for accurate interpretation of these images. The authors indicate when to use endomyocardial biopsy for the diagnosis of cardiac amyloidosis and conclude with a section on quantitation of 99mTc-PYP/DPD/HMDP imaging.

Mechanism and management of leaks arising after left atrial appendage closure (LAAC).

This article reviews the latest available data in regard to the diagnosis, management, and intervention of both central and peri-device leaks that arise after left atrial appendage closure (LAAC). The aim of this article is to have a better understanding of both addressing leaks arising after LAAC, and which interventions and closure methods are best served for each type of residual leak based on etiology, size, and operator experience.

Echocardiographic indices of left ventricular function and filling pressure are not related to blood pool activity on pyrophosphate scintigraphy.

BACKGROUND: Pyrophosphate (PYP) imaging has a high diagnostic accuracy for transthyretin cardiac amyloidosis (ATTR-CA). Indeterminate findings are often reported due to persistent blood pool activity, presumed to be from low cardiac output. We evaluated the relationship between blood pool activity on PYP imaging and echocardiographic indices of cardiac function. METHODS: Clinical and imaging data of 189 patients referred for PYP scintigraphy were evaluated. All patients underwent planar imaging and SPECT (diagnostic standard). Among those with a negative PYP SPECT, persistent left ventricular blood pool activity on planar images was inferred by a visual score ≥2 or a heart-to-contralateral (HCL) ratio ≥ 1.5. Absence of blood pool activity was inferred when both visual score was < 2 and HCL was < 1.5. Left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), stroke volume index (SVi), and left atrial pressure (LAP) were calculated from standard transthoracic echocardiograms. RESULTS: ATTR-CA was present in 43 (23%) patients. Among those with a negative PYP SPECT, 11 patients had significant blood pool activity. Patients with ATTR-CA had a lower LVEF, SVi, and GLS, with a higher LAP, compared to those without ATTR-CA. Among those without ATTR-CA, there were no significant differences in these parameters. CONCLUSION: Approximately 8% of patients with a negative PYP SPECT have significant blood pool activity. Measures of cardiac function are not different among those with and without blood pool activity. PYP SPECT should be routinely performed in all patients to avoid false image interpretation.

Inter-observer reproducibility and intra-observer repeatability in 99mTc-pyrophosphate scan interpretation for diagnosis of transthyretin cardiac amyloidosis.

AIM: The purpose of this study was to determine the inter- and intra-observer variability in 99mtechnetium-pyrophosphate (99mTc-PYP) scan interpretation for diagnosis of transthyretin cardiac amyloidosis (ATTR). METHODS AND RESULTS: Our study cohort comprised 100 consecutive subjects referred for 99mTc-PYP imaging based on clinical suspicion of ATTR cardiac amyloidosis. Myocardial 99mTc-PYP uptake was assessed by both visual (comparison of myocardial to rib uptake) and semi-quantitative (heart-to-contralateral lung uptake ratio, H:CL) methods. Twenty scans were analyzed twice, at least 48 hours apart, by each of two independent observers. Patients with visual scores of ≥ 2 on planar imaging as well as myocardial uptake on SPECT/CT were classified as ATTR positive. Diagnosis of ATTR by visual 99mTc-PYP grade was perfectly reproducible [concordance: positive and negative scans 100% (53/53 and 47/47, respectively). Both inter- and intra-observer correlations for H:CL ratio (r2 = 0.90, 0.99 (Observer 1) and 0.98 (Observer 2), respectively) and repeatability values on Bland-Altman plots were excellent. The coefficient of variation (%) for Observers 1 and 2 was 3.21 (2.14 to 4.29) and 7.49 (4.95 to 10.09), respectively. In addition, there was 100% concordance in positive and negative scan interpretation by visual grading between novice CV imagers (< 3 years' experience) and an experienced CV imager (10 years' experience). CONCLUSIONS: This study showed excellent inter-observer reproducibility and intra-observer repeatability of 99mTc-PYP visual scan interpretation and H:CL ratio for diagnosis of cardiac ATTR amyloidosis. Cardiac ATTR amyloidosis can be diagnosed reliably using 99mTc-PYP SPECT/CT by novice and experienced CV imagers.

Comparison of planar with tomographic pyrophosphate scintigraphy for transthyretin cardiac amyloidosis: Perils and pitfalls.

BACKGROUND: Tc-99m pyrophosphate (PYP) SPECT is recommended for indeterminate findings on planar imaging. We aimed to compare the findings on planar PYP scintigraphy alone to that of routinely performed PYP SPECT. METHODS: PYP scintigraphy data of 133 patients (53% men; mean age 76 years) were evaluated. SPECT was routinely performed following 1-hour planar imaging, in all cases. Semiquantitative visual score and heart-to-contralateral (H/CL) ratio were determined in all patients as recommended. RESULTS: PYP images from 35 patients (26%) were considered to be positive based on SPECT myocardial uptake. Among them, 20 (57%) had a H/CL ratio ≥1.5 and 34 had a visual score ≥ 2. SPECT identified myocardial uptake in one patient with a visual score < 2 and refuted the presence of myocardial uptake in two patients with a visual score ≥ 2. Visual score correlated well with SPECT (r = 0.94; P < .0001) and had an accuracy of 98% for tomographic myocardial uptake. Addition of H/CL ratio reduced the diagnostic performance of visual score. CONCLUSIONS: Planar-derived visual score has an excellent accuracy for tomographic myocardial uptake, though it misclassifies a small proportion of patients. H/CL ratio decreases the diagnostic certainty of planar imaging. Tomographic imaging prevents misdiagnoses and should always be performed.

SPECT Versus PET Myocardial Perfusion Imaging in Patients with Equivocal CT.

PURPOSE OF REVIEW: The most pertinent clinical question in post-coronary computed tomography angiography (CCTA) patients is the assessment of the physiological significance of an anatomically identified stenosis. The clinical application of radionuclide MPI using single-photon emission computed tomography (SPECT) versus positron emission tomography (PET) in the evaluation and management of patients with an inconclusive CCTA is reviewed using a case-based approach. RECENT FINDINGS: Recent evidence suggests that CCTA is the most sensitive non-invasive test to exclude angiographic CAD and may be an effective first-line test especially among symptomatic low-intermediate risk patients. However, in the presence of angiographic atherosclerosis, its specificity and positive predictive value for identifying flow-limiting stenosis are modest. Radionuclide myocardial perfusion imaging offers accurate quantitative assessment of myocardial ischemia, which helps with risk stratification and patient management especially the potential need for revascularization. Routine accurate quantifications of myocardial blood flow and flow reserve are major advantages of PET MPI, which are especially useful when used in patients at intermediate-high clinical risk.

State-of-the-art radionuclide imaging in cardiac transthyretin amyloidosis.

Cardiac amyloidosis, once considered untreatable, is now gaining well-deserved attention due to advances in imaging and the recent approval of targeted breakthrough therapies. In this paper, we discuss the role of radionuclide imaging in the evaluation and management of patients with the most common form of amyloidosis-cardiac transthyretin amyloidosis (ATTR). We provide a comprehensive summary of the literature interspersed with our institutional experience as appropriate, to deliver our perspective.