Non-Biopsy Diagnosis of Cardiac Transthyretin Amyloidosis

Julian D. Gillmore, Mathew S. Maurer, Rodney H. Falk, Giampaolo Merlini, Thibaud Damy, Angela Dispenzieri, Ashutosh D. Wechalekar, John L. Berk, Candida C. Quarta, Martha Grogan, Helen J. Lachmann, Sabahat Bokhari, Adam Castano, Sharmila Dorbala, Geoff B. Johnson, Andor W J M Glaudemans, Tamer Rezk, Marianna Fontana, Giovanni Palladini, Paolo MilaniPierluigi L. Guidalotti, Katarina Flatman, Thirusha Lane, Frederick W. Vonberg, Carol J. Whelan, James C. Moon, Frederick L. Ruberg, Edward J. Miller, David F. Hutt, Bouke P. Hazenberg, Claudio Rapezzi, Philip N. Hawkins

Research output: Contribution to journalArticle

307 Citations (Scopus)

Abstract

BACKGROUND—: Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal cardiomyopathy for which several promising therapies are in development. The diagnosis is frequently delayed or missed due to limited specificity of echocardiography and the traditional requirement for histologic confirmation. It has long been recognised that technetium labelled bone scintigraphy tracers can localise to myocardial amyloid deposits and use of this imaging modality for diagnosis of cardiac ATTR amyloidosis has lately been revisited. We conducted a multicentre study to ascertain the diagnostic value of bone scintigraphy in this disease. METHODS AND RESULTS—: Results of bone scintigraphy and biochemical investigations were analysed from 1217 patients with suspected cardiac amyloidosis referred for evaluation in specialist centers. Among 857 patients with histologically proven amyloid (374 with endomyocardial biopsies), and 360 patients subsequently confirmed to have non-amyloid cardiomyopathies, myocardial radiotracer uptake on bone scintigraphy was >99% sensitive and 86% specific for cardiac ATTR amyloid, with ʼfalse positivesʼ almost exclusively from uptake in patients with cardiac AL amyloidosis. Importantly, the combined findings of grade 2 or 3 myocardial radiotracer uptake on bone scintigraphy and absence of a monoclonal protein in serum or urine had a specificity and positive predictive value for cardiac ATTR amyloidosis of 100% (PPV CI 98.0-100). CONCLUSIONS—: Bone scintigraphy enables the diagnosis of cardiac ATTR amyloidosis to be made reliably without need for histology in patients who do not have a monoclonal gammopathy. We propose non-invasive diagnostic criteria for cardiac ATTR amyloidosis that are applicable to the majority of patients with this disease.

Original languageEnglish (US)
JournalCirculation
DOIs
StateAccepted/In press - Apr 26 2016

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Amyloidosis
Radionuclide Imaging
Bone and Bones
Cardiomyopathies
Amyloid
Paraproteinemias
Technetium
Amyloid Plaques
Multicenter Studies
Echocardiography
Amyloidosis, Hereditary, Transthyretin-Related
Blood Proteins
Histology
Urine
Biopsy

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Gillmore, J. D., Maurer, M. S., Falk, R. H., Merlini, G., Damy, T., Dispenzieri, A., ... Hawkins, P. N. (Accepted/In press). Non-Biopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.116.021612

Non-Biopsy Diagnosis of Cardiac Transthyretin Amyloidosis. / Gillmore, Julian D.; Maurer, Mathew S.; Falk, Rodney H.; Merlini, Giampaolo; Damy, Thibaud; Dispenzieri, Angela; Wechalekar, Ashutosh D.; Berk, John L.; Quarta, Candida C.; Grogan, Martha; Lachmann, Helen J.; Bokhari, Sabahat; Castano, Adam; Dorbala, Sharmila; Johnson, Geoff B.; Glaudemans, Andor W J M; Rezk, Tamer; Fontana, Marianna; Palladini, Giovanni; Milani, Paolo; Guidalotti, Pierluigi L.; Flatman, Katarina; Lane, Thirusha; Vonberg, Frederick W.; Whelan, Carol J.; Moon, James C.; Ruberg, Frederick L.; Miller, Edward J.; Hutt, David F.; Hazenberg, Bouke P.; Rapezzi, Claudio; Hawkins, Philip N.

In: Circulation, 26.04.2016.

Research output: Contribution to journalArticle

Gillmore, JD, Maurer, MS, Falk, RH, Merlini, G, Damy, T, Dispenzieri, A, Wechalekar, AD, Berk, JL, Quarta, CC, Grogan, M, Lachmann, HJ, Bokhari, S, Castano, A, Dorbala, S, Johnson, GB, Glaudemans, AWJM, Rezk, T, Fontana, M, Palladini, G, Milani, P, Guidalotti, PL, Flatman, K, Lane, T, Vonberg, FW, Whelan, CJ, Moon, JC, Ruberg, FL, Miller, EJ, Hutt, DF, Hazenberg, BP, Rapezzi, C & Hawkins, PN 2016, 'Non-Biopsy Diagnosis of Cardiac Transthyretin Amyloidosis', Circulation. https://doi.org/10.1161/CIRCULATIONAHA.116.021612
Gillmore, Julian D. ; Maurer, Mathew S. ; Falk, Rodney H. ; Merlini, Giampaolo ; Damy, Thibaud ; Dispenzieri, Angela ; Wechalekar, Ashutosh D. ; Berk, John L. ; Quarta, Candida C. ; Grogan, Martha ; Lachmann, Helen J. ; Bokhari, Sabahat ; Castano, Adam ; Dorbala, Sharmila ; Johnson, Geoff B. ; Glaudemans, Andor W J M ; Rezk, Tamer ; Fontana, Marianna ; Palladini, Giovanni ; Milani, Paolo ; Guidalotti, Pierluigi L. ; Flatman, Katarina ; Lane, Thirusha ; Vonberg, Frederick W. ; Whelan, Carol J. ; Moon, James C. ; Ruberg, Frederick L. ; Miller, Edward J. ; Hutt, David F. ; Hazenberg, Bouke P. ; Rapezzi, Claudio ; Hawkins, Philip N. / Non-Biopsy Diagnosis of Cardiac Transthyretin Amyloidosis. In: Circulation. 2016.
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abstract = "BACKGROUND—: Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal cardiomyopathy for which several promising therapies are in development. The diagnosis is frequently delayed or missed due to limited specificity of echocardiography and the traditional requirement for histologic confirmation. It has long been recognised that technetium labelled bone scintigraphy tracers can localise to myocardial amyloid deposits and use of this imaging modality for diagnosis of cardiac ATTR amyloidosis has lately been revisited. We conducted a multicentre study to ascertain the diagnostic value of bone scintigraphy in this disease. METHODS AND RESULTS—: Results of bone scintigraphy and biochemical investigations were analysed from 1217 patients with suspected cardiac amyloidosis referred for evaluation in specialist centers. Among 857 patients with histologically proven amyloid (374 with endomyocardial biopsies), and 360 patients subsequently confirmed to have non-amyloid cardiomyopathies, myocardial radiotracer uptake on bone scintigraphy was >99{\%} sensitive and 86{\%} specific for cardiac ATTR amyloid, with ʼfalse positivesʼ almost exclusively from uptake in patients with cardiac AL amyloidosis. Importantly, the combined findings of grade 2 or 3 myocardial radiotracer uptake on bone scintigraphy and absence of a monoclonal protein in serum or urine had a specificity and positive predictive value for cardiac ATTR amyloidosis of 100{\%} (PPV CI 98.0-100). CONCLUSIONS—: Bone scintigraphy enables the diagnosis of cardiac ATTR amyloidosis to be made reliably without need for histology in patients who do not have a monoclonal gammopathy. We propose non-invasive diagnostic criteria for cardiac ATTR amyloidosis that are applicable to the majority of patients with this disease.",
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T1 - Non-Biopsy Diagnosis of Cardiac Transthyretin Amyloidosis

AU - Gillmore, Julian D.

AU - Maurer, Mathew S.

AU - Falk, Rodney H.

AU - Merlini, Giampaolo

AU - Damy, Thibaud

AU - Dispenzieri, Angela

AU - Wechalekar, Ashutosh D.

AU - Berk, John L.

AU - Quarta, Candida C.

AU - Grogan, Martha

AU - Lachmann, Helen J.

AU - Bokhari, Sabahat

AU - Castano, Adam

AU - Dorbala, Sharmila

AU - Johnson, Geoff B.

AU - Glaudemans, Andor W J M

AU - Rezk, Tamer

AU - Fontana, Marianna

AU - Palladini, Giovanni

AU - Milani, Paolo

AU - Guidalotti, Pierluigi L.

AU - Flatman, Katarina

AU - Lane, Thirusha

AU - Vonberg, Frederick W.

AU - Whelan, Carol J.

AU - Moon, James C.

AU - Ruberg, Frederick L.

AU - Miller, Edward J.

AU - Hutt, David F.

AU - Hazenberg, Bouke P.

AU - Rapezzi, Claudio

AU - Hawkins, Philip N.

PY - 2016/4/26

Y1 - 2016/4/26

N2 - BACKGROUND—: Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal cardiomyopathy for which several promising therapies are in development. The diagnosis is frequently delayed or missed due to limited specificity of echocardiography and the traditional requirement for histologic confirmation. It has long been recognised that technetium labelled bone scintigraphy tracers can localise to myocardial amyloid deposits and use of this imaging modality for diagnosis of cardiac ATTR amyloidosis has lately been revisited. We conducted a multicentre study to ascertain the diagnostic value of bone scintigraphy in this disease. METHODS AND RESULTS—: Results of bone scintigraphy and biochemical investigations were analysed from 1217 patients with suspected cardiac amyloidosis referred for evaluation in specialist centers. Among 857 patients with histologically proven amyloid (374 with endomyocardial biopsies), and 360 patients subsequently confirmed to have non-amyloid cardiomyopathies, myocardial radiotracer uptake on bone scintigraphy was >99% sensitive and 86% specific for cardiac ATTR amyloid, with ʼfalse positivesʼ almost exclusively from uptake in patients with cardiac AL amyloidosis. Importantly, the combined findings of grade 2 or 3 myocardial radiotracer uptake on bone scintigraphy and absence of a monoclonal protein in serum or urine had a specificity and positive predictive value for cardiac ATTR amyloidosis of 100% (PPV CI 98.0-100). CONCLUSIONS—: Bone scintigraphy enables the diagnosis of cardiac ATTR amyloidosis to be made reliably without need for histology in patients who do not have a monoclonal gammopathy. We propose non-invasive diagnostic criteria for cardiac ATTR amyloidosis that are applicable to the majority of patients with this disease.

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