Author + information
- Published online July 13, 2016.
- Arnault Galat, MD,
- Axel Van der Gucht, MD,
- Aziz Guellich, PhD,
- Diane Bodez, MD,
- Anne-Ségolène Cottereau, MD,
- Soulef Guendouz, MD,
- Luc Hittinger, MD, PhD,
- Jean-Luc Dubois-Randé, MD, PhD,
- Violaine Plante-Bordeneuve, MD, PhD,
- Emmanuel Itti, MD, PhD,
- Michel Meignan, MD, PhD,
- Thibaud Damy, MD, PhD∗ ( and )
- Jean Rosso, MD
- ↵∗Department of Cardiology, GRC Amyloid Research Institute Mondor Amyloidosis Network, DHU A-TVB, UPEC and APHP, Henri-Mondor Teaching Hospital, 51 Avenue Marchal de Lattre de Tass, Créteil, F-94000, France
Although bisphosphonate scintigraphy has emerged as a valuable modality for cardiac amyloidosis (CA) diagnosis and typing with transthyretin CA showing strong cardiac uptake (1), the procedure in its current form is time consuming and may be regarded as inadequate especially in frail patients. In clinical practice, images are acquired at 10 min (soft tissue or early phase) and at 3 h (bone phase or late phase) following radiotracer injection. However, all studies have focused on late phase. Indeed, the Perugini’s visual score, which is by far the most used to estimate heart retention is on the basis of late-phase images (2).
Little is known about the kinetic of bisphosphonates’ cardiac uptake and the diagnostic value of the early phase scintigraphy in the 3 major forms of CA: light-chain (AL), hereditary transthyretin-related (m-TTR), and wild-type transthyretin-related (wt-TTR) amyloidosis (3). The aim of our study was to compare the accuracy of early (10 min) versus late (3 h) cardiac fixation of 99mTc-hydroxyl-methylene-diphosphonate (HMDP) in diagnosing and typing CA.
A total of 135 patients referred for suspected CA were enrolled prospectively and consecutively. All patients had in addition to standard exams a 99mTc-HMDP bisphosphonate-scintigraphy as part of their diagnostic work-up. The study protocol has been approved by local ethical committees. Written consent was obtained. The diagnosis of CA was performed as previously described (4).
99mTc-HMDP was performed after intravenous injection of 10 MBq/kg of the tracer (Cisbio International, Saclay, France). Planar images were acquired using a dual-head gamma camera (Philips-Precedence, Amsterdam, the Netherlands). Whole-body scans were acquired both at 10 min and 3 h. A single-photon emission computed tomography of the thorax was also performed immediately after the whole-body scan.
For the soft-tissue phase, radiotracer accumulation was graded as 0 (negative) if there was no visible myocardial uptake and 1 (positive) in case of tracer binding within the myocardium. 99mTc-HMDP cardiac uptake was evaluated semiquantitatively by 2 means: 1) early heart retention ratio was calculated by dividing the geometric mean of the left ventricular (LV) region of interest (ROI) by the geometric mean of whole-body counts; and 2) we calculated a heart-to-mediastinum (H/M) ratio on the anterior view of the whole-body scan by copying the LV ROI and placing it on the mediastinum at the large thoracic vessels level (middle of the chest, just above the left ventricle ROI).
Regarding the bone phase, visual scoring was performed according to Perugini’s method (2): 0 = no cardiac uptake and normal bone uptake; 1 = slight cardiac uptake, less marked than bone uptake; 2 = moderate cardiac uptake with attenuated bone uptake; and 3 = strong cardiac uptake with slight/absence of bone uptake. Late heart retention (LHR), whole-body retention, and geometric mean in the skull were obtained as previously prescribed (4,5). LHR/whole-body retention and LHR/skull ratios were calculated.
Thresholds of early H/M to diagnose late-cardiac fixation and to discriminate TTR-CA versus AL-CA were determined using receiver-operating characteristic curve followed by Youden’s test. We considered p values <0.05 statistically significant.
Of the 135 subjects referred for suspected amyloidosis and who underwent 99mTc-HMDP-scintigraphy, 93 were diagnosed as having amyloidosis or genetic TTR mutation. Nineteen had AL, 41 had m-TTR, and 33 had wt-TTR. Cardiac involvement was found in all patients with AL or wt-TTR amyloidosis. For subjects with m-TTR, 33 had CA, 3 were asymptomatic carriers and 5 had neurological symptoms with no evidence of CA. Thirty-one patients with LV hypertrophy and without amyloidosis served as controls. Interestingly, early phase 99mTc-HMDP-scintigraphy cardiac uptake perfectly predicts late-phase finding, as it was found in 68 patients for whom late visual score was ≥1 and was undetectable in all the 57 patients with a null visual score at late phase.
As shown in Figure 1A, an H/M ratio ≥1.115 predicted late cardiac 99mTc-HMDP accumulation (visual score ≥1) with a sensitivity of 100% and a specificity of 97%, whereas an early H/M ratio ≥1.210 discriminated TTR-CA from AL with a perfect accuracy (100% sensibility and 100% specificity). Accordingly, we suggest a new algorithm to diagnose CA and TTR-CA on the basis of the early phase 99mTc-HMDP-scintigraphy (Figure 1B).
In conclusion, our study showed that early phase 99mTc-HMDP-scintigraphy perfectly predicts late-phase finding. It is accurate to differentiate TTR- from AL-CA and from other causes of LV hypertrophy. This could be of particular benefit for frail patients and should increase availability of scintigraphy and cost effectiveness.
Please note: The authors thank all the physicians involved in the Amyloidosis Network of the Henri Mondor Hospital who participated in the assessment and care of the patients included in this study. Drs. Plante-Bordeneuve and Damy have received speakers honoraria from Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Galat and Van der Gucht contributed equally to this work. Drs. Damy and Rosso are joint senior authors.
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