Author + information
- Received August 29, 2019
- Revision received October 7, 2019
- Accepted October 11, 2019
- Published online June 1, 2020.
- Maria Beatrice Musumeci, MDa,∗,
- Francesco Cappelli, MDb,∗∗ (, )
- Domitilla Russo, MDa,
- Giacomo Tini, MDc,
- Marco Canepa, MD, PhDc,
- Agnese Milandri, MDd,
- Rachele Bonfiglioli, MDe,
- Gianluca Di Bella, MD, PhDf,
- Filomena My, MDg,
- Marco Luigetti, MDh,i,
- Marina Grandis, MDj,k,
- Camillo Autore, MDa,
- Stefano Perlini, MDl,
- Federico Perfetto, MD, PhDb and
- Claudio Rapezzi, MDd
- aCardiology Department, Clinical and Molecular Medicine Department, Sapienza University of Rome, Rome, Italy
- bTuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy
- cCardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino, and IRCCS Italian Cardiovascular Network & Department of Internal Medicine, University of Genova, Genova, Italy
- dCardiology, Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater University of Bologna, Bologna, Italy
- eNuclear Medicine, Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater University of Bologna, Bologna, Italy
- fClinical and Experimental Department of Medicine and Pharmacology, University of Messina, Messina, Italy
- gDivision of Neurology, Vito Fazzi Hospital, Lecce, Italy
- hFondazione Policlinico Universitario A. Gemelli IRCCS, UOC Neurologia, Rome, Italy
- iUniversità Cattolica del Sacro Cuore, Sede di Roma, Rome, Italy
- jDepartment of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genova, Genova, Italy
- kIRCCS Ospedale Policlinico San Martino, Genova, Italy
- lEmergency Medicine, Department of Internal Medicine, Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
- ↵∗Address for correspondence:
Dr. Francesco Cappelli, Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Heart Lung and Vessels, Largo Brambilla 3, Florence 50134, Italy.
Objectives The aim of this study was to assess the diagnostic accuracy of bone scintigraphy in a large multicenter cohort of patients with cardiac amyloidotic involvement and Phe64Leu transthyretin (TTR) mutation.
Background Diagnostic accuracy of bone scintigraphy for transthyretin-related cardiac amyloidosis (TTR-CA) is considered extremely high, enabling this technique to be the noninvasive diagnostic standard for TTR-CA. Nevertheless, this approach has not been systematically validated across the entire spectrum of TTR mutations.
Methods A total of 55 patients with Phe64Leu TTR mutation were retrospectively analyzed and evaluated between 1993 and 2018 at 7 specialized Italian tertiary centers. Cardiac involvement was defined as presence of an end-diastolic interventricular septum thickness ≥12 mm, without other possible causes of left ventricular hypertrophy (i.e., arterial hypertension or valvulopathies). A technetium-99m (99mTc)–diphosphonate (DPD) or 99mTc–hydroxyl-methylene-diphosphonate (HMDP) bone scintigraphy was reviewed, and visual scoring was evaluated according to Perugini’s method.
Results Among 26 patients with definite cardiac involvement, 19 underwent 99mTc-DPD or 99mTc-HMDP bone scintigraphy. Of them, 17 (89.5%) patients had low or absent myocardial bone tracer uptake, whereas only 2 (10.5%) showed high-grade myocardial uptake. The sensitivity and the accuracy of bone scintigraphy in detecting TTR-CA were 10.5% and 37%, respectively. Patients with cardiac involvement and low or absent bone tracer uptake were similar to those with high-grade myocardial uptake in terms of age, sex, and electrocardiographic and echocardiographic findings.
Conclusions The sensitivity of bone scintigraphy (DPD and HMDP) in detecting TTR-CA is extremely low in patients with Phe64Leu TTR mutation, suggesting the need to assess diagnostic accuracy of bone scintigraphy to identify cardiac involvement across a wider spectrum of TTR mutations.
↵∗ Drs. Musumeci and Cappelli contributed equally to this study.
Dr. Canepa has received personal fees from Novartis, Pfizer, Pfizer/Bristol-Myers Squibb, Vifor Pharma, Menarini, and Sanofi. Dr. Milandri had a consultancy agreement with Alnylam. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Cardiovascular Imaging author instructions page.
- Received August 29, 2019.
- Revision received October 7, 2019.
- Accepted October 11, 2019.
- 2020 American College of Cardiology Foundation
This article requires a subscription or purchase to view the full text. If you are a subscriber or member, click Login or the Subscribe link (top menu above) to access this article.