Abstract
Background:
Quantitative technetium-99m-pyrophosphate cardiac single photon emission computed tomography (99mTc-PYP SPECT/CT) is an emerging method for estimating myocardial burden of transthyretin cardiac amyloidosis (ATTR-CA), but its efficacy in monitoring longitudinal changes remains uncertain. We aimed to investigate longitudinal changes in cardiac ATTR amyloid burden following transthyretin stabilization therapy using visual and quantitative 99mTc-PYP SPECT/CT and to relate these with changes in cardiac biomarkers and function.
Methods:
This prospective longitudinal cohort study investigated changes in 99mTc-PYP SPECT/CT in 23 participants with ATTR-CA on transthyretin stabilization therapy (median 2.6 years). Quantitative analysis included left ventricular (LV) standardized uptake values (SUVmax, SUVmean), cardiac amyloid activity (CAA; SUVmean*LV activity volume), and percent injected dose (%ID) (mean activity concentration*LV activity volume/injected activity), calculated using a threshold of >1.5 times left atrial blood pool activity concentration on SPECT/CT. Longitudinal changes of paired continuous and ordinal variables were analyzed using Wilcoxon signed-rank test.
Results:
Following therapy, visual grade decreased significantly (p=0.003). Several quantitative 99mTc-PYP metrics also decreased significantly: SUVmax (median −0.75, p=0.011), CAA (median −406.6, p<0.001), and %ID (median −0.45, p<0.001). Serum transthyretin levels improved (median +6.5 mg/dL, p=0.008). Echocardiographic parameters (global longitudinal strain, LV mass index, LV wall thickness), N-terminal pro-B-type natriuretic peptide, and estimated glomerular filtration rate remained stable.
Conclusion:
Favorable changes in 99mTc-PYP myocardial uptake were observed in participants on transthyretin stabilization therapy, while echocardiographic parameters and biomarkers remained stable. These results likely signify myocardial ATTR amyloid stabilization rather than regression of amyloid mass. Further investigation is needed to understand the implications of these findings.
Graphical Abstract
INTRODUCTION:
Transthyretin cardiac amyloidosis (ATTR-CA) is an important and treatable cause of heart failure in older adults.1–3 ATTR-CA has been increasingly recognized due to a simplified, non-invasive diagnostic approach, and the clinical availability of transthyretin stabilizers.4 Bone-avid radiotracer cardiac scintigraphy or single photon emission computed tomography (SPECT), and ideally SPECT/CT, using 99mtechnetium(Tc)-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), pyrophosphate (PYP), or hydroxymethylene diphosphonate (HDP), is an established non-invasive standard for diagnosis of ATTR-CA.5,6 Current approaches to scan interpretation, which are based on a visual grading system, are sufficient for the initial diagnosis of ATTR-CA but may be inadequate for estimating myocardial amyloid burden and longitudinally tracking disease progression and response to therapy.
Transthyretin stabilizers, such as tafamidis, effectively slow disease progression, but do not result in changes in cardiac structure or function on echocardiography.4 Furthermore, echocardiography lacks the specificity to quantify amyloid burden for accurate treatment evaluation.1 There is considerable interest in more sensitive and specific methods to assess myocardial amyloid burden and changes following transthyretin (TTR) directed therapy.
Given high specificity for ATTR-CA and robust quantification afforded by advanced SPECT/CT technology, quantitative 99mTc-PYP/DPD/HMDP metrics could be pivotal in assessing treatment response.7–9 Emerging data show changes in these metrics with TTR stabilization using 99mTc-DPD9 and with silencing therapies using 99mTc-PYP/DPD/HMDP.8,10 However, data on quantitative 99mTc-PYP, a related but distinct tracer from 99mTc-DPD, for monitoring longitudinal changes following TTR stabilization therapy are lacking.
The objective of this study is to evaluate longitudinal changes in visual and quantitative 99mTc-pyrophosphate (PYP) SPECT/CT myocardial metrics after long-term transthyretin stabilization therapy in ATTR-CA and to relate these changes with changes in cardiac biomarkers, structure, and function.
METHODS:
We enrolled 23 participants with ATTR-CA, comprising 21 with wild-type ATTR-CA and 2 with hereditary ATTR-CA, who underwent baseline 99mTc-PYP SPECT/CT at Brigham and Women’s Hospital. All participants with a baseline scan underwent follow-up 99mTc-PYP SPECT/CT (>1 year after baseline, median 2.8 years between scans). All participants received transthyretin stabilization therapy, 22 with tafamidis 61 mg once daily and 1 with diflunisal 250 mg twice daily, for a median duration of 2.6 years, and three participants were concurrently enrolled in a transthyretin silencer clinical trial, 2 in HELIOS-B (NCT04153149) and 1 in CARDIO-TTRansform (NCT04136171). Diagnosis of ATTR-CA was based on baseline 99mTc-PYP SPECT/CT scan positivity and the absence of clonal abnormality.5 The study was approved by the Mass General Brigham Human Research Committee, and all participants provided written informed consent. All procedures followed were in accordance with institutional guidelines.
SPECT/CT Acquisition:
A 15-minute chest SPECT/CT was performed after injection of 99mTc-PYP at a median of 2.7 (IQR 2.6–2.9) hours (baseline) and 2.8 (IQR 2.6– 3.1) hours (follow-up), respectively. The median difference between injection and scan start time at follow-up vs. baseline was minimal (2 minutes, IQR −3–12.25 minutes after intravenous injection of 99mTc-PYP). A median activity of 23.2 (IQR 20.7–24.5) mCi and 25.2 (IQR 23.5–26.2) mCi of 99mTc-PYP was administered intravenously at baseline and follow-up, respectively. Residual radiotracer activity in the syringe was measured and subtracted to estimate injected activity. A general-purpose cadmium-zinc-telluride-scanner (CZT; Veriton-CT; Spectrum Dynamics Inc) was used for all baseline and follow-up scans. In one patient, NaI SPECT/CT scan was performed at baseline and CZT scan was performed at follow-up. Attenuation correction was based on the low-dose, unenhanced CT scan (with an effective exposure of 20 mAs, tube voltage of 120 kVP, and free tidal breathing). Patient weight was recorded. 99mTc-pyrophosphate images were reconstructed onto a 256 × 256 matrix (2.46 × 2.46 × 2.46 mm voxel size) using ordered-subsets expectation maximization (4 iterations, 8 subsets). Additionally, a proprietary filter (convolution filter and postmedian filter) was applied, with corrections for radiotracer decay, point-spread function, scatter, and attenuation.7
Qualitative Metrics
All images were de-identified prior to analysis. Visual uptake was graded by a single, experienced physician reader in all participants at both time points, with grade 0 indicating absent myocardial uptake, grade 1 indicating myocardial < rib uptake, grade 2 indicating myocardial = rib uptake, and grade 3 indicating myocardial > rib uptake.
Quantitative Metrics
Myocardial uptake was volumetrically assessed using PMOD software (PMOD Technologies LLC). Using CT images for guidance, we manually traced epicardial volumes of interest (VOI) of the left ventricle (LV), including interventricular septum, on fused 99mTc-PYP SPECT/CT images. This epicardial VOI included the LV blood pool. Endocardial contour was not manually traced to avoid bias. Blood pool activity concentration was measured using a 6 mm diameter spherical volume of interest in the left atrium. To ensure methodological rigor, maintain consistency, and mitigate potential bias from manual tracing, we employed automatic iso-contouring procedure in PMOD, choosing an iso-contouring threshold of >1.5 times the left atrial blood pool mean activity, since it optimally excluded LV blood pool and defined the myocardium. An example of PMOD manual epicardial contouring and automatic epi- and endocardial iso-contouring is shown in Figure 1.
Figure 1:
PMOD Manual Contour Tracing and Automatic Iso-contouring
This figure shows method of manual and automatic contouring with PMOD software using an example of a baseline scan (Figure 1a) and a follow-up scan (Figure 1b). First (column 1), the epicardial LV VOI was manually traced, and blood pool mean activity concentration was measured using a 6 mm spherical VOI in the LABP. Then (column 2), the automatic iso-contouring function of PMOD software was employed, choosing an iso-contouring threshold of mean + 1.5 standard deviations of LABP activity.
Abbreviations: LABP: left atrial blood pool, LV: left ventricle, VOI: volume of interest.
Left ventricular (LV) uptake quantitative metrics included percent injected dose (%ID), which was defined as the VOI mean activity concentration multiplied by VOI volume and divided by injected activity (decayed to scan start time). %ID, thus, adjusts for injected activity rather than body weight. We also measured standardized uptake values (SUV) (SUVmean, SUVmax), defined as VOI activity concentrations (mean activity for SUVmean and maximum activity for SUVmax) divided by injected activity per unit body weight. We also measured cardiac amyloid activity (CAA), defined as the product of VOI volume and SUVmean.11 Quantitation was not feasible in two participants due to technical challenges (N=1) and use of a different scanner (NaI SPECT/CT) between baseline and follow-up (N=1).
Other Variables Analyzed:
We analyzed echocardiograms performed at baseline and at follow-up, within a median of 2 and 12 days of the respective 99mTc-PYP SPECT/CT scans, to measure global longitudinal strain (GLS), LV mass, and LV wall thickness. We analyzed serum levels of high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), serum transthyretin, estimated glomerular filtration rate (eGFR), New York Heart Association (NYHA) functional class, and National Amyloidosis Centre (NAC) prognostic stage at baseline and at follow-up.12
Statistical Analysis:
Continuous variables were presented and compared using Wilcoxon rank-sum tests. Categorical variables were displayed as frequency with percentage and paired data analyzed using McNemar’s test. Correlations were quantified using Spearman’s ρ. Longitudinal changes of paired ordinal and continuous variables were analyzed using Wilcoxon signed-rank test. All analyses were performed using R version 4.3.1 (R Foundation for Statistical Computing), and a 2-sided P value less than 0.05 was considered significant. Figures were created using GraphPad Prism (version 10.0.0) and BioRender.com.
RESULTS:
Detailed baseline and follow-up demographic, clinical, laboratory, echocardiographic, and 99mTc-PYP SPECT/CT characteristics, and changes between baseline and follow-up are provided in Table 1. All participants commenced transthyretin stabilization treatment after baseline 99mTc-PYP SPECT/CT and remained on treatment through their follow-up scan. Between baseline and follow-up, there was a statistically significant increase in Troponin T (median change 7 ng/mL, p=0.007) and in serum transthyretin (median change 6.5 mg/dL, p=0.008). Improvement in New York Heart Association class was also observed (p=0.008). There were no significant changes in NAC stage or serum biomarkers (NT-proBNP, eGFR) during this period.
Table 1:
Baseline, Follow-up, and Change Between Baseline and Follow-up Characteristics
| Variable | Baseline | Follow-Up | Change Between Baseline and Follow-Up | p-value |
|---|---|---|---|---|
| Demographic/Clinical Variables | N = 23 | N = 23 | N = 23 | |
| Age (years) | 75 (71, 78.5) | 79 (73, 81) | +3 (+2, +3) | - |
| Male Sex | 22 (96%) | - | - | - |
| White Race | 21 (91%) | - | - | - |
| Hypertension | 18 (78%) | 19 (83%) | +0 (+0, +0) | >0.999 |
| Current/Former Smoking | 9 (39%) | 9 (39%) | +0 (+0, +0) | NA |
| Coronary Artery Disease | 6 (26%) | 8 (35%) | +0 (+0, +0) | 0.480 |
| Atrial Fibrillation | 12 (52%) | 17 (74%) | +0 (+0, +0) | 0.074 |
| Carpal Tunnel Syndrome | 21 (91%) | 21 (91%) | +0 (+0, +0) | NA |
| Rotator Cuff Injury | 9 (39%) | 9 (39%) | +0 (+0, +0) | NA |
| Biceps Tendon Rupture | 9 (39%) | 9 (39%) | +0 (+0, +0) | NA |
| Spinal Stenosis | 8 (35%) | 9 (39%) | +0 (+0, +0) | >0.999 |
| Pacemaker or ICD | 2 (9%) | 9 (39%) | +0 (+0, +1) | 0.023 |
| Body Mass Index (kg/m2) | 28.0 (26.8, 30.5) | 27.5 (25.5, 30.0) | −0.24 (−1.7, +0.35) | 0.223 |
| Concomitant Medications | N = 23 | N = 23 | N = 23 | |
| Anticoagulant | 16 (70%) | 17 (74%) | +0 (+0, +0) | >0.999 |
| Beta-blocker | 13 (57%) | 13 (57%) | +0 (+0, +0) | NA |
| Diuretic | 13 (57%) | 17 (74%) | +0 (+0, +0) | 0.134 |
| ACE-inhibitor | 7 (30%) | 4 (17%) | +0 (+0, +0) | 0.248 |
| ARB | 2 (9%) | 3 (13%) | +0 (+0, +0) | >0.999 |
| MRA | 3 (13%) | 7 (30%) | +0 (+0, +0) | 0.221 |
| Functional Status and Serum Biomarkers | N = 23 | N = 23 | N = 23 | |
| NYHA Class | 2 (1, 3) | 2 (1, 2) | +0 (−1, +0) | 0.008 |
| NAC Stage (N=22) | 1 (1, 1.75) | 1 (1, 2) | +0 (+0, +0) | 0.168 |
| Troponin T (ng/mL) (N=21) | 44.0 (28.0, 55.0) | 48.0 (35.0, 67.0) | +7.0 (+0.0, +13.0) | 0.007 |
| NT-proBNP (pg/mL) (N=22) | 1766.0 (602.8, 2525.5) | 1799.0 (574.8, 5096.8) | +44.5 (−404.2, +1628.8) | 0.463 |
| eGFR (mL/min/1.73m2) | 57.0 (49.0, 67.0) | 60.0 (51.0, 73.5) | −2.0 (−7.5, +9.0) | 0.715 |
| Serum Transthyretin (N=18) | 24.5 (21.3, 28.8) | 32.0 (27.3, 32.8) | +6.5 (+1.0, +11.8) | 0.008 |
| Echocardiogram | N = 23 | N = 23 | N = 23 | |
| LVEF (%) | 52.5 (43.0, 55.0) | 50.0 (40.0, 60.0) | −2.5 (−5.0, +6.0) | 0.909 |
| GLS (%) | −11.8 (−13.8, −9.7) | −10.5 (−12.7, −8.6) | +0.9 (−0.65, +1.8) | 0.121 |
| LV Mass (g) (N=20) | 300.7 (266.4, 374.2) | 343.8 (297.4, 426.7) | +32.2 (−20.6, +70.9) | 0.090 |
| LV Mass Index (g/m2) (N=20) | 153.0 (130.4, 184.0) | 178.9 (157.8, 191.4) | +13.6 (−5.9, +40.3) | 0.064 |
| IVS (mm) (N=20) | 17.0 (16, 18.5) | 18.5 (15.8, 22.0) | +1 (−0.25, +3.3) | 0.066 |
| PWT (mm) (N=20) | 17.0 (14.8, 19.0) | 17.0 (14.0, 19.0) | −0.5 (−1.3, +1.3) | 0.650 |
| 99mTc-PYP SPECT/CT | N = 23 | N = 23 | N = 23 | |
| Visual Grade | 3.0 (2.0, 3.0) | 2.0 (1.3, 3.0) | +0.0 (−1.0, +0.0) | 0.003 |
| Quantitative Measures | N = 21 | N = 21 | N = 21 | |
| SUVmean | 2.3 (1.8, 2.9) | 2.7 (2.3, 2.9) | +0.27 (−0.30, +0.68) | 0.321 |
| SUVmax | 4.0 (3.2, 4.9) | 3.3 (2.8, 4.0) | −0.75 (−1.4, +0.05) | 0.011 |
| CAA | 573.4 (355.8, 979.2) | 256.2 (71.3, 418.2) | −406.6 (−684.6, −173.4) | <0.001 |
| %ID | 0.71 (0.48, 1.0) | 0.31 (0.08, 0.54) | −0.45 (−0.73, −0.22) | <0.001 |
Continuous and ordinal variables presented as median (interquartile range) and paired variables were analyzed using Wilcoxon signed-rank test. Dichotomous variables presented as frequency (percentages).
Abbreviations: ACE inhibitor: angiotensin-converting enzyme inhibitor, ARB: angiotensin receptor blocker, eGFR: estimated glomerular filtration rate, GLS: global longitudinal strain, ICD: implantable cardioverter-defibrillator, IVS: interventricular septum thickness, LVEF: left ventricular ejection fraction, MRA: mineralocorticoid receptor antagonist, NT-proBNP: N-terminal pro-B-type natriuretic peptide, NAC Stage: National Amyloidosis Centre Stage, NYHA: New York Heart Association, PWT: posterior wall thickness, SUV: standardized uptake value, CAA: cardiac amyloid activity, %ID: percent injected dose.
Missing data: NT-proBNP & NAC stage (N=1); Troponin T(N=2), serum transthyretin levels, (N=5). Echocardiograms (N=3, GLS and LVEF still available by report). Quantitative PYP analysis (N=2).
On follow-up 99mTc-PYP SPECT/CT scans (after a median of 2.8 years), visual grade decreased significantly (p=0.003), with significant reduction in multiple quantitative metrics (see an example in Figure 2). We observed a significant reduction in SUVmax (median change −0.75; IQR: −1.4, 0.05 p=0.011), CAA (median change −406.6; IQR: −684.6, −173.4, p<0.001), and %ID (median change −0.45; IQR: −0.73, −0.22, p<0.001) (Figure 3). There was no significant change in SUVmean.
Figure 2:
Changes in Visual Grade and Quantitative 99mTc-PYP Metrics Between Baseline and Follow-up SPECT/CT Images
Sagittal, coronal, and axial fused 99mTc-PYP SPECT/CT images of a 93-year-old male at baseline and after 2 years of tafamidis 61 mg PO daily therapy. 99mTc-PYP images are shown in color and CT images are shown in grey scale. These images show a reduction in visual grade from an initial grade of 3 (myocardial uptake > rib uptake) to a follow-up grade of 1 (myocardial uptake < rib uptake). Quantitative metrics decreased significantly as well.
Abbreviations: 99mTc-PYP SPECT/CT: 99mTechnetium-pyrophosphate single photon emission computed tomography/computed tomography, PO: per os (by mouth)
Figure 3:
Changes in %ID, SUVmax, CAA, and GLS Between Baseline and Follow-up 99mTc-PYP SPECT/CT Images
This figure shows 99mTc-PYP A) %ID, B) SUVmax, C) CAA and D) GLS at baseline and at follow-up. Data points from patients on concomitant silencer therapy are shown in red. These images show significant decrease in SUVmax, %ID and CAA with no significant change in GLS.
Abbreviations: 99mTc-PYP: 99mTechnetium-pyrophosphate, %ID: percent injected dose, CAA: cardiac amyloid activity, GLS: global longitudinal strain, SUVmax: maximum standardized uptake value
We evaluated the relation between improvement in 99mTc-PYP metrics as a function of the time to follow-up scan. Participants with follow-up time ≥ 2.8 years (median) vs. <2.8 years, tended to show improvement in quantitative metrics (100% vs. 63.6%, p=0.090). But, there were no significant correlations between change in %ID, CAA, SUVmax and follow-up time interval (Figure 4). In the 21 participants with available quantitative analysis, four did not exhibit a decrease in CAA or %ID. In the 20 patients who had both quantitative analysis and NT-proBNP available, 7 had clinically significant worsening of NT-proBNP (>=30% increase from baseline and >300 pg/mL).13 There was no significant difference in change of quantitative 99mTc-PYP SPECT/CT metrics between those with or without clinically significant worsening of NT-proBNP. Moreover, among 12 participants who had no change in visual grade, 8 showed improvements in SUVmax, CAA, and %ID at follow-up, highlighting the improved sensitivity of SPECT quantitation compared with visual grading.
Figure 4:
Correlation Between Time Interval from Baseline to Follow-Up 99mTc-PYP SPECT/CT and Changes in %ID, CAA, and SUVmax.
This figure shows the relationship between change in 99mTc-PYP A) %ID, B) CAA, and C) SUVmax and the time interval (in days) between baseline and follow-up 99mTc-PYP SPECT/CT. Data points from patients on concomitant silencer therapy are shown in red. These images show no significant correlation between change in %ID, CAA, SUVmax and time interval.
Abbreviations: 99mTc-PYP: 99mTechnetium-pyrophosphate, %ID: percent injected dose, CAA: cardiac amyloid activity.
On follow-up echocardiograms (median 2.4 years), there were no significant changes in GLS, LV mass index, interventricular septal wall thickness, posterior wall thickness, and left ventricular ejection fraction (Table 1).
DISCUSSION:
In this prospective study of 23 participants with ATTR-CA on transthyretin stabilizer therapy, we found reduction in visual grade and marked reduction in quantitative estimates of 99mTc-PYP myocardial uptake, including SUVmax, CAA, and %ID, along with an improvement in transthyretin levels. Notably, serum biomarkers, cardiac structure and cardiac function remained stable.
Our analysis builds upon recent evidence demonstrating that serum transthyretin levels increase with transthyretin stabilization therapy, and we saw a similar increase in serum transthyretin levels.14,15 Also, recent studies showed a decrease in SUV retention index with 99mTc-DPD SPECT/CT in patients on tafamidis, and our study extends these findings to 99mTc-PYP SPECT/CT and a longer-term treatment duration (median 31.3 months vs. 9 months on prior study).9 Interestingly, we showed a trend towards improvement in quantitative metrics with longer follow-up duration, with 100% of those with ≥ median 2.8 year follow-up showing improvement compared to 64% of those with < median follow-up. This is likely underpowered but suggests a greater change with longer follow-up duration. Furthermore, our study showed that quantitative measurements offered a more sensitive assessment of change compared to visual estimation, with 8 out of 12 studies showing improvement in quantitative parameters, despite no change in visual grade. Thus, a quantitative approach may be particularly advantageous for monitoring longitudinal changes. However, we found no changes in NT-proBNP and GLS, as shown in a prior study9, which may be attributable to differences in participant characteristics. In studies assessing cardiac parameters with transthyretin silencer therapy, there was an improvement in NT-proBNP with silencer therapy, but there were also no significant differences in longitudinal strain (by cardiac MRI or echocardiography) after 12 to 18 months of therapy, compared to a significant improvement in 99mTc-PYP/DPD/HMDP visual grade and quantitative parameters.8,10
Our findings suggest that improvements in quantitative 99mTc-PYP SPECT/CT metrics, after transthyretin stabilization therapy, reflect different pathophysiology than captured by echocardiography, laboratory, and clinical parameters. Castano et al16 performed serial 99mTc-PYP imaging and demonstrated no significant change in visual grade in patients not on transthyretin directed therapy despite evidence of clinical disease progression. Higher variability was reported with serial quantitative measures of 99mTc-DPD17. By contrast, our study, as well as other recent studies, demonstrate a substantial decrease in 99mTc-PYP/DPD/HMDP myocardial uptake by visual grade10 and by quantitative analysis (%ID)8, in patients on transthyretin stabilizer or silencer therapy respectively. But no significant changes were noted in cardiac structure or function in our study, as well as on prior studies. Taken together, these findings imply that the decrease in bone avid tracer myocardial uptake in the treated cohorts, in the context of no significant changes in cardiac structure and function, may reflect a molecular change indicating disease stabilization in the myocardium (or other processes such as fibrosis) rather than regression of amyloid mass. It is also possible that molecular stabilization in the myocardium appears earlier in the course of therapy and may herald future improvements in cardiac structure, function, and clinical outcomes.
Limitations:
Because our study was limited by small sample size and single-center study design, our findings may not be generalizable. However, our study design facilitated a direct comparison between baseline and follow-up quantitative 99mTc-PYP SPECT/CT. Despite the small sample size, our results were statistically significant, underscoring the substantial effect sizes of the measured parameters. However, some borderline statistical changes observed may indeed be influenced by small sample size, and these findings might change with a larger cohort of patients. In addition, the absence of serial cardiac MRI data in this patient cohort limited our ability to gather comprehensive information on changes in cardiac structure and function, which may have further enriched our findings.
CONCLUSIONS:
There is a significant decrease in quantitative 99mTc-PYP SPECT/CT myocardial uptake in participants on transthyretin stabilization therapy, and no significant change of clinical and cardiac structure and function. These combined findings suggest that the decline in 99mTc-PYP uptake reflects molecular stabilization of myocardial ATTR amyloidosis. Further studies are needed to understand the implications of these findings.
New Knowledge Gain and Clinical Perspectives:
- What is new?
- In a prospective cohort of 23 participants with transthyretin cardiac amyloidosis, 99mTc-PYP myocardial uptake and serum transthyretin levels significantly improved in those on transthyretin stabilization therapy, while echocardiographic measures of cardiac structure and function, and serum cardiac biomarker levels did not improve
- What are the clinical implications?
- Decreased 99mTc-PYP uptake over time reflects different pathophysiology than captured by echocardiographic parameters
- The improvement in 99mTc-PYP myocardial uptake may represent stabilization rather than regression of myocardial ATTR amyloid mass
- Further research is needed to elucidate the long-term implications of these observations
Acknowledgements and Disclosures:
Vijayakumar: Research funding from the Amyloidosis Foundation
Clerc: Research fellowship from the International Society of Amyloidosis and Pfizer.
Cuddy: Investigator-initiated research grant from Pfizer, consulting fees from Ionis Pharmaceuticals, Astra Zeneca, BridgeBio, and Novo Nordisk.
Falk: Consulting fees from Ionis Pharmaceuticals, Alnylam Pharmaceuticals, Caelum Biosciences, research funding from GlaxoSmithKline and Akcea.
Dorbala: Consulting fees from Pfizer, GE Health Care, Astra Zeneca, Novo Nordisk; investigator-initiated grant from Pfizer, GE Healthcare, Attralus, Siemens, Philips.
The other authors do not have any conflicts of interest to declare.
Funding:
This work was supported by the National Institutes of Health.
Vijayakumar: T32 HL 094301
Cuddy: K23 HL 166686-01; AHA 23CDA857664
Dorbala: K24 HL 157648
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