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99mTechnetium pyrophosphate scintigraphy with cadmium zinc telluride cameras is a highly sensitive and specific imaging modality to diagnose transthyretin cardiac amyloidosis

La gammagrafía con tecnecio 99 m pirofosfato (99mTc-PYP) con cámaras de teluro de zinc y cadmio es una modalidad de imagen con alta sensibilidad y especificidad para diagnosticar amiloidosis cardíaca por transtiretina

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Journal of Nuclear Cardiology Aims and scope

Abstract

Background

Transthyretin cardiac amyloidosis (ATTR) is a rare, but underdiagnosed, cardiomyopathy. Traditionally diagnosed invasively, ATTR can be diagnosed with non-invasive 99mTechnetium pyrophosphate (99mTc-PYP) planar scintigraphy. Non-planar imaging has not been validated for ATTR diagnosis. Here, we develop and validate a Cadmium Zinc Telluride (CZT) protocol for diagnosing ATTR.

Methods

Forty-three subjects (24 ATTR, 19 non-ATTR) were imaged with Philips Dual-Head Anger (planar) and General Electric CZT cameras. Myocardial uptake was quantified by heart-to-contralateral (H/CL) ratios. CZT scans were quantified by two readers blinded to planar H/CL, with one repeating blinded quantification. Using the previously validated diagnostic threshold (H/CL ≥ 1.5), sensitivity and specificity of CZT scintigraphy was measured. McNemar’s test and Pearson’s correlation coefficient were calculated.

Results

Among subjects (76.7% male, age 77 ± 9), there was no significant difference in proportion of ATTR-positive identification between modalities. There was high correlation between CZT and planar H/CL ratios (r = 0.92, P < 0.0001), with low intra- [ICC = 0.89 (0.80-0.94)] and inter-observer [ICC = 0.80 (0.65-0.89)] variability. CZT scintigraphy had 100% sensitivity and specificity for diagnosing ATTR.

Conclusion

99mTc-PYP CZT imaging is as highly sensitive and specific diagnosing ATTR as planar imaging. These findings are clinically salient given the emergence of disease-modifying ATTR therapies, as it could expand diagnostic capability.

Spanish Abstract

Antecedentes

la amiloidosis cardíaca asociada a transtiretina (ATTR) es una cardiomiopatía poco frecuente y poco diagnosticada. Tradicionalmente el diagnóstico se realiza de forma invasiva, aunque se puede diagnosticar con gammagrafía planar con tecnecio 99m pirofosfato (99mTc-PYP). En el presente trabajo se desarrolla y se valida un protocolo diagnóstico de ATTR.

Método

Se estudiaron 43 sujetos (24 con diagnóstico de ATTR y 19 sin ATTR) las imágenes fueron adquiridas con las cámaras Philips Dual-Head Anger (planar) y General Electric CZT. La captación miocárdica se cuantificó con proporción corazón-contralateral (H/CL). La adquisición con las cámaras CZT se cuantificaron mediante 2 lectores cegados a la proporción H/CL planar, con una cuantificación ciega repetida. Utilizando el umbral de diagnóstico previamente validado (H/CL ≥ 1.5), se midió la sensibilidad y la especificidad de la gammagrafía con CZT. Para el análisis estadístico se utilizó la prueba De McNemar y el coeficiente de correlación de Pearson.

Resultados

entre la población de estudio (76.7% varones, edad 77 ± 9), no hubo diferencias estadísticamente significativas en la proporción de identificación de ATTR positiva. Se identificó una alta correlación entre la cámara CZT y la proporción planar H/CL (r = 0.92, p < 0.0001), así como una baja variabilidad intraobservador (ICC = 0.89 (0.80-0.94)) e interobservador (ICC = 0.80 (0.65-0.89)). La gammagrafía con CZT tuvo una sensibilidad y especificidad del 100% para el diagnóstico de ATTR.

Conclusión

La imagen con 99mTc-PYP en cámaras CZT es altamente sensible y específica para el diagnóstico de ATTR. Estos hallazgos son de relevancia debido a la aparición de terapias modificadoras de la enfermedad.

Chinese Abstract

背景

甲状腺素转运蛋白相关型心脏淀粉样变 (ATTR) 是一种罕并且难以诊断的心肌病。 传统的诊断方法是有创的, ATTR 可以通过无创99m锝标记的焦磷酸钙 (99mTc-PYP) 平面闪烁扫描进行诊断。而其它非平面成像方法尚未得到验证。本研究中我们探讨了一种镉锌碲化物(CZT)成像方案用于ATTR的可行性。

方法

43 名受试者 (24名ATTR, 19名非ATTR) 分别使用飞利浦公司双探头显像仪平面扫描,以及通用公司CZT探头显像仪进行扫描。 心肌摄取采用心/对侧肺 (H/CL) 放射性计数比值作为定量方法。CZT 图像由2位研究者在不知道(双探头)平面扫描 H/CL 值的情况下进行定量测量。 以既往验证的 H/CL ≥ 1.5 作为 ATTR 诊断阈值,评价 CZT 扫描的诊断敏感性和特异性。 (统计学上) 计算了配对卡方检验和皮尔逊相关系数。

结果

在受试者中 (男性占76.7%,年龄77 ± 9岁), ATTR 阳性诊断率无显著差异。 CZT 与平面扫描 H/CL 值相关性高 (r = 0.92, p  < 0.0001), 观察者内部 (ICC = 0.89(0.80-0.94)) 和观察者之间 (ICC = 0.80(0.65-0.89)) 的变异系数低。 CZT 扫描诊断 ATTR 的敏感性和特异性均为 100%。

结论

99mTc-PYP CZT 扫描对 ATTR 的诊断具有与双探头扫描类似的高灵敏度和特异性。 鉴于 ATTR 疾病调节疗法的出现,这种新的扫描方法由于提高了诊断能力将具有重要的临床价值。

French Abstract

Contexte

L’amyloïdose cardiaque à transthyrétine (ATTR) est une cardiomypathie rare, mais sous-diagnostiquée. Traditionnellement diagnostiquée de façon invasive, l’ ATTR peut être évaluée par scintigraphie planaire au 99mTechnetium (99mTc-PYP). Dans cette étude, nous avons développé et validé un protocole avec detectors Cadmium Zinc Telluride (CZT) pour le diagnostic de l’ATTR.

Méthodes

43 sujets (24 ATTR, 19 non-ATTR), ont été évaluées avec la camera Anger double tête de Philips et avec la camera CZT de General Electric. L’uptake myocardique du tracer a été quantifié en utilisant le rapport cœur- hemithorax contro-latéral (H/CL). Les scintigraphies obtenues sur camera CZT ont été analysées à deux reprises par deux experts qui n’avaient pas connaissance des résultats des images planaires obtenus au moyen de la caméra Philips. Utilisant le seuil diagnostique précédemment validé (H/CL) de 1.5, la sensibilité et la spécificité de la scintigraphie CZT ont été mesurées. Le test de McNemar et le coefficient de corrélation de Pearson ont été calculés.

Résultats

Nous n’avons pas observé de difference significative dans l’identification de l’amyloïdose cardiaque à transthyrétine (ATTR) chez les sujets étudies (76,7% d’ hommes, 77 à 9 ans) entre les deux modalitées scintigraphiques. De plus, nous avons noté une étroite correlation entre les résultats H/CL obtenus par imagerie CZT et Anger planaire (r-0,92, p-0,0001), avec une faible variabilité intra- (ICC-0,89(0,80-0,94)) et inter-observateurs (ICC 0,80 (0,65-0,89)). Le diagnostique de l’ATTR par scintigraphie à CZT a montré une sensibilité et une spécificité de 100%.

Conclusion

l’imagerie scintigraphique au 99mTc-PYP obtenue sur camera CZT est aussi sensible et spécifique que celle obtenue sur camera Anger planaire pour le diagnostiqe de l’amyloidose cardiaque ATTR. L’utilisation des caméras CZT devraient faciliter le diagnostic et par conséquent l’implémentation des nouvelles thérapies de l’amyloidose cardiaque ATTR.

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Abbreviations

ATTR:

Transthyretin cardiac amyloidosis

AL:

Light chain cardiac amyloidosis

99mTc-PYP:

99mTechnetium pyrophosphate

HFpEF:

Heart failure with preserved ejection fraction

CZT:

Cadmium zinc telluride

SPECT:

Single-photon emission computed tomography

H/CL:

Heart-to-contralateral

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Acknowledgments

We would like to acknowledge the invaluable work of the NewYork Presbyterian Hospital Nuclear Cardiology Lab, particularly Ketan Bhatia, in making this study possible. We express our sincere thanks to the patients of our study who participated in our efforts to improve medical treatment for people with cardiac amyloidosis.

Disclosure

Kathleen R. Flaherty, Rachelle Morgenstern, Ted Pozniakoff, Albert DeLuca, and Sabahat Bokhari have no potential conflicts of interest. Adam Castano is associated with Pfizer, Inc. The composition of this research and manuscript was completed prior to any association. Mathew S. Maurer received funding for research and serving on advisory boards and DSMBs from Pfizer, Inc; Alnylam Pharmaceuticals Inc; ISIS Pharmaceuticals; and Prothena Inc.

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Author notes

  1. Kathleen R. Flaherty and Rachelle Morgenstern are co-first authors.

Authors and Affiliations

  1. Division of Cardiology, Department of Internal Medicine, Columbia University Medical Center, 630 West 168th Street, P&S 10-445(4), New York, NY, 10032, USA

    Kathleen R. Flaherty BA, Ted Pozniakoff BS, RT(N)(R), Albert DeLuca MD, Adam Castano MD, MS, Mathew S. Maurer MD & Sabahat Bokhari MD

  2. Laboratory of Nuclear Cardiology, Columbia University Medical Center, New York, USA

    Kathleen R. Flaherty BA, Ted Pozniakoff BS, RT(N)(R), Albert DeLuca MD & Sabahat Bokhari MD

  3. Center for Advanced Cardiac Care, Columbia University Medical Center, New York, NY, USA

    Mathew S. Maurer MD

  4. Hospital for Special Surgery, Orthopedic Surgery, New York, NY, USA

    Rachelle Morgenstern MPH

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  1. Kathleen R. Flaherty BA
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Correspondence to Kathleen R. Flaherty BA.

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Columbia University Medical Center internally funded this research. Dr. Maurer receives funding for research and serving on advisory boards and DSMBs from Pfizer, Inc, Alnylam Pharmaceuticals Inc, ISIS Pharmaceuticals, and Prothena Inc. Dr. Castano is associated with Pfizer, Inc. The composition of this research and manuscript was completed prior to any association. No other potential conflicts of interest relevant to this article exist that may directly or indirectly influence the content of the manuscript submitted.

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Flaherty, K.R., Morgenstern, R., Pozniakoff, T. et al. 99mTechnetium pyrophosphate scintigraphy with cadmium zinc telluride cameras is a highly sensitive and specific imaging modality to diagnose transthyretin cardiac amyloidosis. J. Nucl. Cardiol. 27, 371–380 (2020). https://doi.org/10.1007/s12350-019-01831-8

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