Evaluation of Perugini score and myocardial mass and voltage abnormalities in transthyretine cardiac amyloidosis

Background Transthyretine cardiac amyloidosis (TTR-CA) is an emerging treatable disease in cardiology. Severity of TTR infiltration can be assessed by bone scintigraphy with Perugini score, depending on HPD-Tc99M myocardial intensity uptake. Less is known on how Perugini score interplays with routine cardiac structural parameters, especially cardiac mass and voltage. Aim To evaluate correlation between Perugini score and myocardial mass and voltage abnormalities in patients with TTR-CA. Methods Patients diagnosed with ATTR-CA and addressed to our center for treatment underwent complete evaluation including electrocardiogram (ECG) and transthoracic echocardiography (TTE). Routine electrical and echographic parameters were obtained such as: Sokolow indice (SV1+RV5) in millivolt (mV), PR delay (ms), QRS width (in ms), left ventricular mass (LVM, in grams) and diastolic interventricular septum (dIVS) thickness (in mm). Patients were classified in three categories according to Perugini score: I (cardiac uptake < chest bones), II (cardiac uptake = chest bones) and III (cardiac uptake > bones). Main end-point were LVM and Voltage/Mass ratio (VMR) variations, depending on Perugini score. Results Among the 17 patients included, 14 were male (82.4%) and mean age was 82±8 years old. On ECG, 6 patients (35.3%) had permanent atrial fibrillation (AF). Mean voltage according to Sokolow index, mean PR delay and mean QRS width were respectively 1.5±0.5 mV, 212±54 ms and 113±19 ms. On TTE, mean LVM and mean dIVS width were respectively 333±98 g (188±55 g/m2) and 19±4 mm. Mean voltage/mass ratio (VMR) was 0.48±0.26 uV/g (see table). On bone scintigraphy, 3 patients were scored with Perugini I (17.6%), 4 with Perugini II (23.5%) and 10 with Perugini III (58.8%). According to Pearson test, there was a strong correlation between Perrugini score and LVM (r=+0.56, p=0.03) (graph A), and a strong negative correlation between Perrugini score and VMR (r=−0.70, p=0.003) (graph B). There were a trend for correlation between Perugini score and Voltage according to Sokolow (r=−0.46, p=0.07) and between Perugini score and dIVS width (r=0.49, p=0.07). Conclusion In TTR-CA patients, Perugini score appears to strongly correlate with left ventricle mass and voltage. Larger scale studies are needed to confirm these results. FUNDunding Acknowledgement Type of funding sources: None. ECG and TEE trends according to Perugini Cardiac mass and voltage with Perugini

Prognostic value of 99mTc-HMDP scintigraphy in elderly patients with chronic heart failure

Background Bone scintigraphy is an accurate modality for diagnosis of transthyretin amyloidosis (ATTR). Purpose We evaluated the prevalence and prognostic significance of cardiac ATTR in elderly heart failure population. Methods Our retrospective study included 335 patients aged over 70 years with diagnosed heart failure who underwent 99mTc-hydroxymethylenediphosphonate (99mTc-HMDP) scintigraphy due to non-cardiac indications. A Perugini grade >2 and heart-to-contralateral ratio (H/CL) of >1.30 was considered positive for ATTR. Results There were a total of 234 deaths of which 70 were classified as cardiovascular during a median follow-up of 3±2 years. ATTR was diagnosed in 17 patients using H/CL ratio (5.1%). Patients with ATTR were older (85±5 vs. 80±5 years, p=0.002) and had higher N-terminal pro-brain natriuretic peptide (Nt-ProBNP) levels (6692±5694 vs. 3285±5233 ng/l, p=0.02). Age, presence of bone metastasis and GFR were independent predictors of overall mortality. Age, GFR, ≥grade 2 visual cardiac uptake and H/CL ratio were independent predictors of cardiovascular mortality. Conclusions ATTR was found in 5% of elderly patients with heart failure. The presence of cardiac uptake on bone scintigraphy did not convey independent prognostic value on overall mortality but was associated with cardiovascular mortality. FUNDunding Acknowledgement Type of funding sources: None.

Concordance between quantitative and semi-quantitative analysis of Tc-99m-pyrophosphate scintigraphy for the diagnosis of transthyretin cardiac amyloidosis in patients with HFpEF

Background Transthyretin (TTR) cardiac amyloidosis (CA) is an underdiagnosed cause of heart failure with preserved ejection fraction (HFpEF). Cardiac scintigraphy with 99mTechnetium-pyrophosphate (99mTc-PYP) is referred as a simple, non-invasive and reliable method in the diagnosis of TTR-CA. American Society of Nuclear Cardiology Practice Points recommends two interpretative approaches: the quantitative heart-to-contralateral lung ratio (H/CL) at 1 hour or the semi-quantitative visual assessment at 3 hours after radiotracer injection. Purpose In this study, we evaluated the concordance between semi-quantitative and quantitative approaches in the diagnosis of TTR CA in patients with HFpEF. Methods This single-center, prospective study included 78 patients who had a diagnosis of HFpEF according to 2016 ESC HF guidelines. 99mTc-PYP cardiac scintigraphy was performed in 43 patients who have ≥2 red flags for TTR-CA including left ventricular hypertrophy (LVH) (wall thickness ≥12 mm), biventricular hypertrophy, sparkling pattern, reduction in longitudinal strain with apical sparing, thickening of the interatrial septum (>6mm), low-voltage, pseudo infarct pattern or atrioventricular block on ECG. In the absence of monoclonal protein in the serum and urine, Grade 2 to 3 myocardial uptake in semi-quantitative analysis at 3 hours or a H/CL ratio of ≥1.5 in quantitative analysis at 1 hour post injection of 99mTc-PYP is considered positive for TTR-CA. Grade 2–3 uptake with a H/CL ratio ≥1.5 or Grade 0–1 uptake with a H/CL ratio <1.5 were considered as concordant results. Grade 2–3 uptake with a H/CL ratio <1.5 or Grade 0–1 uptake with a H/CL ratio ≥1.5 were considered as discordant results. Results Mean age of study population was 68.26±9.97 years. 17 (39.5%) of 43 patients who underwent 99mTc-PYP cardiac scintigraphy showed a Grade 2 or 3 cardiac uptake and in these patients with Grade 2–3 uptake, 11 patients (65%) had a H/CL ratio ≥1.5 (concordant results) and 6 patients (35%) had a H/CL ratio <1.5 (discordant results). 26 (60.5%) of 43 patients showed Grade 0–1 cardiac uptake. All patients (100%) with Grade 0–1 uptake had a H/CL ratio <1.5 and therefore, showed concordant results. Overall, 37 (86%) patients had concordant and 6 (14%) patients had discordant results (Table 1). Conclusion The results of this study showed that although there was a high agreement between semi-quantitative and quantitative analysis of 99mTc-PYP cardiac scintigraphy, 14% of patients have discordant results and need further workup to confirm TTR-CA in patients with HFpEF. FUNDunding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Pfizer independent grant.

Quantitative SPECT/CT parameters of myocardial 99mTechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake in suspected cardiac transthyretin amyloidosis

Background 99mTc-labelled bisphosphonates are used for imaging assessment of patients with transthyretin cardiac amyloidosis (ATTR). Present study evaluates whether quantitative SPECT/CT measurement of absolute myocardial 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (Tc-DPD) uptake can diagnose patients with suspected ATTR. Methods Twenty-eight patients (25 male, age 80.03 ± 6.99 years) with suspected ATTR referred for Tc-DPD imaging had planar and SPECT/CT imaging of the chest. Three operators independently obtained Tc-DPD myocardial SUVmax and SUVmean above threshold (SMaT) (20, 40 and 60% of SUVmax), using a semi-automated threshold segmentation method. Results were compared to visual grading (0–3) of cardiac uptake. Results Twenty-two patients (78%) had cardiac uptake (2 grade 1, 15 grade 2, 5 grade 3). SUVmax and SMaT segmentation thresholds enabled separating grades 2/3 from 0/1 with excellent inter- and intra-reader correlation. Cut-off values 6.0, 2.5, 3 and 4 for SUVmax, SMaT20,40,60, respectively, separated between grades 2/3 and 0 /1 with PPV and NPV of 100%. SMaT20,40,60(cardiac)/SUVmean (liver) and SMaT20,40,60(cardiac)/SUVmean(liver/lung) separated grades 2 and 3. Conclusion Quantitative SPECT/CT parameters of cardiac Tc-DPD uptake are robust, enabling separation of patients with grades 2 and 3 cardiac uptake from grades 0 and 1. Larger patient cohorts will determine the incremental value of SPECT/CT quantification for ATTR management.

Comparison of low energy and medium energy collimators in the quantitative assessment of 123I-MIBG cardiac sympathetic innervation imaging

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): University Clinic Hospital of Valencia Aim The assessment of cardiac sympathetic innervation by 123I-metayodobenzylguanidine (123I-MIBG) has proved useful in patients with heart failure and neurodegenerative disorders. The standard quantification of global cardiac uptake is to obtain the heart to mediastinum (HM) ratio in planar images, while SPECT images provide better evaluation of regional extent of denervated areas. Although low energy (LE) collimator has been widely used in these patients, septal penetration of high-energy photons of 123I could affect image quality and quantification accuracy. We have compared in the same patients the effect of collimator type on image quality and quantitative assessment of HM ratio. Methods In a group of 14 patients (11 men, 57-77 y/o, 66.4 ± 5.6) submitted for cardiac sympathetic study, we obtained successive planar anterior chest images 4h after the IV administration of 10 mCi of 123I-MIBG with a low-energy-high-resolution (LEHR) and a medium-energy (ME) collimators. Images were obtained with the same gammacamera Brightview Philips for 10 min on 256x256 matrix, with 159 Kev photopeak and unchanged patient position. For quantification of HM ratio, we use in each patient the same manual heart ROI and rectangular upper mediastinum ROI in the two acquired images to obtain the corresponding HM ratio. Results The image quality was better in all the patients with ME collimator acquisition than with LEHR collimator acquisition, and the HM ratio showed higher values with ME: 1.65-2.61 (mean 2.15 ± 0.28) than with LEHR: 1.27-1.85 (mean: 1.51 ± 0.18) with a mean difference of 0.64 ± 0.15 (0.38-0.88) between ME and LEHR and a mean ratio LEHR/ME of 0.70 ± 0.04 (0.64-0.79). In 9 patients with HM ratio ≤ 1.60 obtained from LEHR collimator acquisition, the mean difference with HM ratio obtained with ME collimator was 0.61 ± 0.12 and mean ratio LEHR/ME was 0.69 ± 0.03 and in 5 patients with HM ratio(LEHR) >1.60, mean difference with HM ratio(ME) was 0.69 ± 0.19 and mean ratio LEHR/ME was 0.71 ± 0.02. Conclusion Use of a ME collimator provides better image quality than LEHR collimator in planar images and higher values of HM ratio, providing a more accurate quantification of cardiac uptake in the patients submitted for evaluation of cardiac sympathetic innervation by 123I-MIBG, and could also improve the evaluation of regional impairment and extent of denervated areas by SPECT.

Quantitation vs visual assessment of 99mTc-DPD cardiac uptake in patients with suspected cardiac amyloidosis

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Universitary Clinic Hospital of Valencia Aim Cardiac uptake of 99mTc-DPD has proved its diagnostic efficacy in transthyretin cardiac amyloidosis(ATTR). We compared the usual visual assessment with two quantitative methods to evaluate cardiac activity and its possible relation with clinical follow-up. Methods We have studied 37 successive patients(p):32 men, 52-90 y/o (79.6 ± 9.3), submitted by suspected cardiac amyloidosis TTR by echo/cardiac MRI. After IV administration of 21.5 ± 3.4mCi of 99mTc-DPD, we obtained early (at 5min) and late (at 3h) whole body(WB) planar images and late SPECT. We assessed cardiac uptake in planar images by visual score (0-absent, 1-cardiac uptake lower than bone uptake, 2-equal, 3- higher than bone uptake), considering 2-3 score compatible with ATTR in absence of abnormal light chains on serum-urine. We obtained quantitative evaluation by heart/contralateral thoracic activity ratio (H/CL) in late images and from early and late WB images the heart retention(HR) ratio and heart/whole body(HWB) activity ratio. Clinical follow-up (12.4 ± 8.3 months) considering as cardiac events(CE): cardiac death and heart failure(HF) admissions. Results Visual score 0(11p), 1(2p), 2(4p) and 3(20p), considering group1(0-1) not suggestive of ATTR and group2(2-3) compatible with ATTR. SPECT showed biventricular uptake with septal predominance in group2. H/CL index was 2.23 ± 0.54(group2) vs 1.05 ± 0.10(group1) p < 0.001), according to published(≥1.5 compatible with ATTR). HR and HWB ratios were also significantly higher in group2 vs group1, respectively 6 ± 3.14vs2.17 ± 0.4(p < 0.001) and 6.51 ± 1.97vs2.65 ± 0.49(p < 0.001). There were a trend to higher values in p with visual score3 than 2, not reaching statistically significant(only 4p with visual score2). There were significant correlation between H/CL-HR(r:0.66,p < 0.01), H/CL-HWB(r:0.85,p < 0.001) and HR-HWB(r:0.85,p < 0.001). After follow-up we detected 6 CE(3p with HF admission, 3p cardiac death): 5p with visual score3 and one with 2, all 6p with high mean values of H/CL: 2.28 ± 0.76, HR: 6.02 ± 3.4 and HWB:5.97 ± 1.69. Conclusion We have found excellent correlation between visual score and the evaluated methods of quantitation of 99mTc-DPD cardiac uptake in our patients referred by suspected cardiac amyloidosis. These quantitative methods could be a helpful tool to correctly identify some patients with doubtful activity and could be useful in the follow-up evaluation, although it is necessary to study a greater number of patients.

Incidental cardiac uptake in bone scintigraphy: increased importance and association with cardiac amyloidosis

Extraosseous radiotracer uptake during bone scintigraphy must be carefully assessed and it offers the potential to detect previously undiagnosed disease processes. A range of neoplastic, metabolic, traumatic, ischaemic and inflammatory disorders can cause soft tissue accumulation of bone avid radiopharmaceuticals. Accordingly, cardiac uptake in bone scintigraphy has a broad differential diagnosis and is commonly attributed to ischaemia/infarction related to coronary artery disease. However, there has been renewed focus on incidental cardiac uptake in recent years in light of significant developments in the diagnosis and management of cardiac amyloidosis.

Synthesis and Ex Vivo Biological Evaluation of Gallium-68 Labelled NODAGA Chelates Assessing Cardiac Uptake and Retention

Radiolabelled lipophilic cations can be used to non-invasively report on mitochondrial dysfunction in diseases such as cardiovascular disease, cardiotoxicity and cancer. Several such lipophilic cations are currently used clinically to...