[99mTc]Tc-pyrophosphate (PYP) Scintigraphy Findings of Cardiac Amyloidosis: is It a Predictor for Survival?

doi:10.21203/rs.3.rs-4002705/v1

Background

Association [99mTc]Tc-pyrophosphate (PYP) uptake with survival of cardiac amyloidosis (CA) is still unkown. This study aimed to describe the scintigraphic findings of CA suspected cases and determine the prognostic value of scintigraphy.

Methods

Between September 2020-December 2023, all [99mTc]Tc-PYP scintigraphy images of CA suspected cases were evaluated retrospectively. The scintigraphy images were obtained 1h and 3h after intravenous injection of 740 MBq [99mTc]Tc-PYP. The quantitative and semiquantitative results of scintigraphy were analyzed, and their correlation with clinical outcomes was explored.

Results

Among the 268 cases (147 female, 121 male; median age:65), 12 (4.5%) were diagnosed with ATTR CA, 19 (7.1%) with AL CA. The median follow-up time was 386 days. ATTR CA cases exhibited significantly higher [99mTc]Tc-PYP uptake than AL CA and non-CA cases. The 1h and 3h heart-to-contralateral lung ratios were positively high degree correlated each other and SPECT/CT imaging reduced equivocal results from 82–37%. Eight of 19 patients with AL CA, one of 12 with ATTR CA, and 15 of non-CA cases died on follow-up. Median survival was 22 days in ATTR CA, 201 days in AL CA, and 105 days in non-CA ex cases. Survival analysis indicated significantly lower survival in non-CA cases compared to ATTR CA and AL CA.

Conclusion

[99mTc]Tc-PYP scintigraphy demonstrated varying uptake patterns in different CA forms. The study emphasizes the importance of combining scintigraphic findings with laboratory tests for accurate CA diagnosis and highlights the poor survival of individuals investigated for CA, even if the diagnosis is not confirmed.

ATTR

AL

cardiac amyloidosis

PYP

scintigraphy

prognosis

Misfolded amyloid proteins formed from light chain (AL) or transthyretin (ATTR) accumulation in the myocardium cause cardiac amyloidosis (CA). These depositions result in thickening of different parts of the heart and affect heart function. It is one of the reasons for restrictive cardiomyopathy. Although amyloidosis is a multisystem disease, generally, cardiac involvement determines the prognosis.

AL amyloidosis is a rare disease with an incidence of 8–12/million [1, 2]. Due to its short survival, this malignancy is considered a hematologic emergency. Life-saving chemotherapy, bone marrow transplantation, and monoclonal antibodies are treatment options for this hematologic malignancy.

The prevalence of ATTR amyloidosis is 10%-16% in older patients with heart failure with preserved ejection fraction or severe aortic stenosis stenosis [3–5]. Subtypes are identified based on mutation status as wild-type (ATTRwt) and hereditary. ATTRwt amyloidosis is more common. In recent years, there have been some developments in treatment options, including suppressing transthyretin production (liver transplantation, patisiran, inotersen), stabilizing amyloid fibrils (tafamidis, NSAID diflunisal), and destroying already existing fibrils (doxycycline, tauro-ursodeoxy-cholic acid, and monoclonal antibodies) [6].

Echocardiography (ECHO) is a non-invasive, accessible method to assess the functional and structural status of the myocardium. Ventricle and valvular thickening, biatrial enlargement, restrictive filling pattern with generally reserved systolic function, and low voltage are commonly detected in CA.

Laboratory tests could be used to differentiate these two forms of amyloidosis and serve as prognostic biomarkers. Cardiac magnetic resonance imaging (CMR) provides important clues for distinguishing amyloidosis in hypertrophic hearts. T1 values, extracellular volume and late gadolinium enhancement are significant parameters in both the differential diagnosis and prognostic assessment.

Endomyocardial biopsy was accepted as the gold standard in the diagnosis of CA. However, it is an invasive procedure and could yield false negatives due to patchy involvement.

[99mTc]Tc scintigraphy with bone-seeking radiotracers such as pyrophosphate (PYP), 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), and hydroxymethylene diphosphonate (HDMP) are reliable diagnostic tools with high sensitivity and specificity in CA [7]. Positive PYP scintigraphy along with negative serum free light chain (FLC) in serum/ and urine immunofixation electrophoresis can provide the noninvasive diagnosis of ATTR CA without cardiac biopsy.

Beyond the diagnostic power, recent data highlighted the prognostic potential of Tc-PYP scintigraphy in CA [8]. However, there is still disparity about the prognostic value of [99mTc]Tc-PYP scintigraphy in the litgerature. In this single-center retrospective study, we aimed to describe our scintigraphic findings and determine the prognostic value of scintigraphy.

Study Population

The study cohort was consisted of patients who were referred from a tertiary cardiac center between September 2020 and December 2023 for the suspect of CA involvement, based on clinical, laboratory, and imaging findings. All patients had heart failure with preserved ejection fraction or diastolic dysfunction with thickened myocardial wall on echocardiography with the absence of other loading conditions. There was at least one finding in cardiac imaging methods raising suspicion of amyloidosis in study population. The serum FLC level and the immunofixation electrophoresis of serum and urine were measured in the cohort to eliminate AL CA.

All participants underwent [99mTc]Tc-PYP scintigraphy and images were retrospectively evaluated by two experienced nuclear medicine specialists. Vital status was ascertained through telephone contact and/or by contacting referring physicians.

This study was performed in line with the principles of the Declaration of Helsinki. All patients provided written informed consent. Approval from our institute's ethics committee was obtained (Date: 2023.05 /No: 213).

Imaging Procedure

After the intravenous injection of 740 MBq [99mTc]Tc-PYP, 1-hour and 3-hour anterior-posterior planar, and single photon computed tomography/computed tomography (SPECT/CT) images were obtained over the thoracic region using a 140 keV 15%-20% energy window, a 128x128 matrix, and a low-energy general-purpose collimator according to the guidelines [9]. Low dose CT was used for attenuation correction.

Imaging Analysis

For quantitative evaluation, the heart to contralateral lung (H/CL) ratio was calculated on the anterior planar images as the total counts in a region of interest (ROI) over the heart divided by the identical size of ROI over the contralateral chest. A ratio greater than 1.5 at 1 hour and greater than 1.3 at 3 hours is accepted as positive. Ratios lower than 1 are accepted as negative, and those between 1-1.5/1.3 are considered equivocal [9].

The uptake of [99mTc]Tc-PYP in the heart was evaluated using a semiquantitative visual score on SPECT/CT images. Upon evaluating all images, we observed variations in bone uptake intensities in each case. Although current guidelines still suggest comparison to rib uptake [9], in order to better differentiate from blood pool activity, scoring was performed comparing the myocardial uptake (MU) to left ventricular cavity activity (LVBP) (Score 0: MU uptake < LV BP, Score 1: MU = LVBP, Score 2: MU > LVBP). We paid particular attention to the activity uptake degree in the interventricular septum, as septal uptake may reflect the early involvement of CA. In terms of ATTR CA, Score 0 is classified as negative, Score 1 is equivocal, and Score 2 is positive (Fig. 1).

CA was defined by endomyocardial biopsy-proven congophilic deposits, or histological documentation of congophilic deposits in at least 1 noncardiac organ and echocardiographic findings of restrictive cardiomyopathy defined as LV wall of 12 mm or greater in thickness without another etiological factor of LV hypertrophy, or positive PYP scintigraphy along with the absence of serum FLC in serum/and urine immunofixation electrophoresis and the presence of echocardiolographic findings related to heart failure with preserved ejection fraction [10].

The median follow-up time was 386 days. The cardiac [99mTc]Tc-PYP uptake and scintihgraphic findings were correlated with follow up data.

Statistical Analysis

Statistical analyses were performed using SPSS software version 15. Descriptive analyses were presented using the median (range). Mann-Whitney U test and Kruskal-Wallis test were conducted to compare non-parametric ordinal and nominal values between groups. The Spearman test was used to investigate the correlation coefficients and their significance between the variables.

We compared Kaplan-Meier curves for all time-to-event outcome measures with the standard log-rank test. Overall survival was defined as the time from randomization to death from any cause. A p-value of less than 0.05 was considered significant.

A total of 268 cases (147 females, 121 males) were included in this study. The median age was 65 (range: 21-90). Median proBNP and troponin T values were 2198 pg/ml and 96 ng/ml (range: 10-37905 pg/ml and 0.008-1762 ng/ml), respectively.

Among the 268 patients, 12 (4.5%) were diagnosed with ATTR CA, and 19 (7.1%) with AL CA. According to genetic test results, only 2 (17%) of ATTR CA cases were mutation positive; others were accepted as wild-type. AL diagnoses were confirmed with biopsy in 8 cases, while the rest were AL-suspected according to laboratory test results. All AL CA cases were consultated to hemathology department in order to plan life-saving chemotherapy.

Quantitative and semiquantitative results of 99mTc-PYP scintigraphy were shown in Table 1. The first-hour and 3-hour H/CL ratios were highly positively correlated (r=0.80, p<0.001) with each. A significant but moderately correlated relationship was detected between quantitative and semiquantitative results (r=0.52, p<0.001). Comparing with H/CL ratio, semiquantitative assessment decreased the equivocal result ratio from 82% to 37% (Table 2).

First hour H/CL ratio median values were 1.7 (range: 1.4-2.1) in ATTR CA cases, 1.2 (range: 0.9-1.6) in AL CA. We observed significantly higher PYP uptake in ATTR patients compared to AL CA ( p< 0.001 ).

The median follow-up was 386 days (range: 10-1075 days). During the follow-up term, 1 (8.3%) of ATTR CA cases and 8 (42.1%) of AL CA cases died. Fifteen cases (6%) with non-amyloid heart failure with preserved ejection fraction (non-CA ex cases) also died. Median survival was 22 days for ATTR CA ex-case, 201 days (range: 26-626 days) in AL CA ex-cases, and 105 days (range: 10-313 days) in non-CA ex-cases.

The H/CL ratio median values 1.3 (range: 1.1-1.5) in non-CA nonsurvivors. Both quantitative and semiquantitative results were significantly different between ATTR CA, AL CA, non-CA ex, and others (p<0.001). In ATTR CA cases, PYP uptake was more prominent than others ( Table 3). Semiquantitative and quantitative results were also shown in Table 3 for ex-cases groups. As only one patient with ATTR CA died on follow-up, survival could not be compared between ATTR CA cases and other groups.

The median overall survival (OS) was 261 days (range: 22-694) for ATTR-CA patients, 281 days, (range: 26-937) for AL CA patients, 105 day (range: 10-313) for non-CA ex cases and 456 days (range: 57-1075) for non-CA survivors. We noticed that OS was significantly lowest for non-CA ex cases (p<0.001) (Table 4). We observed that visual scores and H/CL ratios significant overlapped between AL CA patients and non-CA diagnosed non survivors.

When a subgroup analysis was performed by categorizing the patients with CA and patients who died of cardiac events as one group and the survivors without CA as the other. Then, possible prognostic factors such as age, gender, 1-hour and 3-hour H/CL ratios, semiquantitative results, proBNP, and troponin T values were analyzed between groups. Among these parametres, 1-hour and 3-hour H/CL ratios, semiquantitative results, proBNP, and troponin T values were significantly higher in the group consisted of CA and nonsurvivors that survivors (Table 5).

When myocardial PYP uptake was analyzed for prognostication within the whole cohort, we observed that OS deteriorated with increasing LV PYP uptake. We observed that the one-hour H/CL ratios and quantitative results were significantly correlated negatively between overall survival, however the correlation degree was low (r= -0.16, p= 0.04). When visual scoring was tested for OS prediction, we observed worsening OS with increasing visual score. The median was 960 days (range: 883-1036 days) for patients with score 0, whereas OS was 806 days (range: 709-904 days) and 618 days (range: 519-717 days) for patients with Score 1 and Score 2, respectively. However, the difference did not reach statistical significance (p:0.18).

When a subgroup analyses were performed among AL CA cases, we observed that 1-hour H/CL ratio cutoff of 1.55 seems to be very sensitive (100%) and specific (91%) in predicting short survival, however, it did not reach statistical significance possibly due to the low number of patients (AUC: 0.60, p= 0.46).

Amyloidosis with cardiac involvement was recently known as a rare disease. With improvements in diagnostic modalities and increasing awareness, it was revealed that it is not as rare as thought before. Treatment modalities for the main cardiac amyloidosis (CA) forms, namely ATTR CA and AL CA, caused by different misfolded proteins with different origins, are different [11]. Considering the short survival of these two entities, early diagnosis becomes quite important.

In the past, invasive cardiac biopsy was considered the gold standard in diagnosis. Since the high sensitivity (> 99%) and specificity (86%) of scintigraphy using [99mTc]Tc-labeled bone-seeking agents were proven, the clinical diagnostic algorithm has changed [7, 12, 13]. The pathophysiology of cardiac uptake of bone seeking radiopharmaceutics is not well known. The presence of microcalcification in ATTR but not AL amyloidosis could be a possible explanation for the sensitivity of these tracers in ATTR CA [14]. Consistent with the literature, we revealed that cardiac uptake intensity was significantly higher in ATTR CA than in others [7, 12, 13].

In this study we found that 1-hour and 3-hour H/CL ratios had strong positive correlation with each. The comparison of LV myocardial uptake with the LV BP uptake by SPECT/CT improved the results and reduced the rate of equivocal results by 57%. Similar to our results, Coskun et al. found a strong positive correlation between 1-hour and 3-hour H/CL ratios [15]. They found that SPECT/CT imaging reduced the rate of equivocal results by 65%. This percentage was 57% in our study. The difference is probably due to choosing different reference points in each study (rib to blood pool). As explained in the material method section, when we evaluated our cases, we realized that rib radiopharmaceutical uptake degree was quite variable. In addition, as PYP binds to amyloid deposits in a calcium-dependent manner, it is possible to consider that the uptake of PYP may vary due to factors affecting bone mineralization. The results of this study may indicate that the BP activity may also be used as a reference method for the comparison of myocardial PYP accumulation in SPECT/CT. In our study population, an ATTR CA case, which was in the equivocal category according to quantitative scoring, was evaluated as positive by visual SPECT images. This finding is important to increase the diagnostic precision.

Expert consensus recommendations report that in the absence of a clonal plasma cell process, [99mTc]Tc-PYP scintigraphy consistent with ATTR cardiac amyloidosis combined with consistent ECHO or cardiac CMR findings obviates the need for invasive endomyocardial or extracardiac biopsy in the diagnosis of ATTR [16]. Due to the unfavorable prognosis of CA, if there is clinical suspicion of CA, PYP scintigraphy and serum and urine immunofixation and serum FLC studies are recommended to be performed simultanously. Although according to current guidelines, Grade 2–3 radiopharmaceutical uptake is considered positive for ATTR CA, as well-known, it could be seen in AL CA [9]. In our study, a significant portion of AL CA cases (58%) showed a varying degree of increased activity even in SPECT images. This finding proves once again how important laboratory tests are in addition to scintigraphic data in the diagnosis of AL CA. Since AL CA is an oncological emergency, scintigraphic findings should always interpreted in conjunction with laboratory test results to exclude AL amyloidosis.

In the largest single-center study with 292 AL CA with 99mTc-DPD scintigraphy, 39% of AL CA cases showed cardiac uptake in scintigraphy images [17]. Our discordant results may be due to the use of different radiopharmaceuticals (DPD vs PYP), patients' different systolic function, and/or different reference points. Quarta CC et al. also reported that only cardiac laboratory test results and serum bilirubin levels associated with worse survival [17]. The working group concludes that the presence of cardiac [99mTc]Tc-DPD uptake showed a trend to worse survival, but it was not significant (p = 0.056). Similarly, we did not find any significant correlation between survival and any scintigraphic findings in the subgroup analysis of AL CA patients.

The results of this single center study verify previously published results of the mulit-icenter study that [99mTc]Tc-PYP uptake can accurately differentiate patients with poorer survival [8]. Castano et al. reported that H/CL greater than 1.6 was associated with shorter survival in patients with ATTR CA. In our study population, treatment with tafamidis was started as early as the patients were diagnosed with ATTR CA. In the cohort, only one ATTR CA case died. The early prescription of tafamidis may have contributed to prognosis in ATTR CA patients [18].

We consider that the most remarkable result was the significantly lowest survival of non-ATTR CA cases in our study population. We hypothezied that there may have been ATTR CA patients that did not have pronounced PYP uptake among the patients with H/CL ratios ranged between 1.1–1.5. It is known that up to 28.5 percent of ATTR CA may represent with low H/CL ratios [19]. As endomyocardial biopsy was not performed for all patients, we consider that cases with early involvement of ATTR CA may have been underdiagnosed.

Even though we cannot perform a survival analysis among our ATTR CA patients, we consider that the inverse correlation observed between PYP uptake and OS in the cohort highlights the need for further evaluation and close follow-up for cardiac events for patients who have clinical suspicion of CA even the scintigraphy findings were not suggesting a clear diagnosis of ATTR CA.

There are some limitations of our study. The main limitation of this study was the retrospective design. Second, this study was a single center study with a relatively limited number of positive cases. We believe that with more power, better results for survival analysis and cut off values would have been defined. Third, we consider that a longer period of follow-up in the population with less pronounced H/CL is required to better test whether meaningful changes in the H/CL ratio occur and whether [99mTc]Tc-PYP can identify patients with early involvement. Finally, the exact aetiology of cardiac deaths among non- CA subgroup remained unexplained. The indication of endomyocardial biopsy may further be questioned in patients with high clinical suspicious of CA with negative or equivocal findings in PYP scan to prevent the underestimation of early ATTR involvement.

The results of this study showed that [99mTc]Tc-PYP cardiac imaging is highly sensitive and specific for detecting ATTR CA and differentiating from AL amyloidosis. Among patients who have clinical and laboratory and or imaging findings of CA, higher H/CL ratio was observed in non survivors irrespective of a definite ATTR diagnosis. We consider that even if the ATTR CA is not precise in patients with H/CL ratios between 1.3–1.5, close follow-up and maximum care should be performed to better monitor these patients.

Acknowledgment: None

Funding: None

Conflict of interest:

All authors have nothing to declare.

Data availability statement:

The datasets generated or analyzed during the study are not publicly available due to they relates to a novel radiopharmaceutical but are available from the corresponding author on reasonable request.

Author Contribution

EK and BEA conceived the idea and conceptualised the study. EA and UA collected the data. EA and BEA analysed the data. EA drafted the manuscript, then all authors reviewed the manuscript. All authors read and approved the final draft. Funding No external funding received to conduct this study.

Kyle RA, Linos A, Beard CM, Linke RP, Gertz MA, O’Fallon WM, Kurtlan LT (1992) Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989. Blood 79:1817–1822. https://doi.org/10.1182/blood.V79.7.1817.1817
Pinney JH, Smith CJ, Taube JB, Lachmann HJ, Venner CP, Gibbs SD et al (2013) Systemic amyloidosis in England: An epidemiological study. Br J Haematol 161:525–532. https://doi.org/10.1111/bjh.12286
Gonzalez-Lopez E, Gallego-Delgado M, Guzzo-Merello G, de Haro-Del Moral FJ, Cobo-Marcos M, Robles C et al (2015) Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur Heart J 36:2585–2594. https://doi.org/10.1093/eurheartj/ehv338
Castano A, Narotsky DL, Hamid N, Khalique OK, Morgenstern R, DeLuca A et al (2017) Unveiling transthyretin cardiac amyloidosis and its predictors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. Eur Heart J 38:2879–2887. https://doi.org/10.1093/eurheartj/ehx350
Bennani Smires Y, Victor G, Ribes D, Berry M, Cognet T, Mejean S et al (2016) Pilot study for left ventricular imaging phenotype of patients over 65 years old with heart failure and preserved ejection fraction: The high prevalence of amyloid cardiomyopathy. Int J Cardiovasc Imaging 32:1403–1413. https://doi.org/10.1007/s10554-016-0915-z
Manolis AS, Manolis AA, Manolis TA, Melita H (2019) Cardiac amyloidosis: An underdiagnosed/underappreciated disease. Eur J Intern Med 67:1–13. https://doi.org/10.1016/j.ejim.2019.07.022
Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A et al (2016) Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation 133:2404–2412. https://doi.org/10.1161/CIRCULATIONAHA.116.021612
Castano A, Haq M, Narotsky DL, Goldsmith J, Weinberg RL, Morgenstern R et al (2016) Multicenter Study of Planar Technetium 99m Pyrophosphate Cardiac Imaging Predicting Survival for Patients With ATTR Cardiac Amyloidosis. JAMA Cardiol 1:880–889. https://doi.org/10.1001/jamacardio.2016.2839
Dorbala S, Ando Y, Bokhari S, Dispenzieri A, Falk RH, Ferrari VA Addendum to, ASNC/AHA/ASE/EANM/HFSA et al (2022) /ISA/SCMR/SNMMI Expert Consensus Recommendations for MultimodalityImaging in Cardiac Amyloidosis: Part 1 of 2—Evidence Base and Standardized Methods of Imaging. J Card Fail 28:e1-e4. https://doi.org/10.1007/s12350-020-02455-z
Dorbala S, Ando Y, Bokhari S, Dispenzieri A, Falk RH, Ferrari VA, ASNC/AHA/ASE/EANM/HFSA/ et al (2021) ISA/SCMR/ SNMMI Expert Consensus Recommendations for Multimodality Imaging in Cardiac Amyloidosis Part 2 of 2—Diagnostic Criteria and Appropriate Utilization. Circ Cardiovasc Imaging 14:e000030. https://doi.org/10.1161/HCI.0000000000000030
Siddiqi OK, Ruberg FL (2018) Cardiac amyloidosis: An update on pathophysiology, diagnosis, and treatment. Trends Cardiovasc Med 28:10–21. https://doi.org/10.1016/j.tcm.2017.07.004
Perugini E, Guidalotti PL, Salvi F, Cooke RM, Pettinato C, Riva L et al (2005) Noninvasive etiologic diagnosis of cardiac amyloidosis using 99mTc- 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. J Am Coll Cardiol 46:1076–1084. https://doi.org/10.1016/j.jacc.2005.05.073
Treglia G, Glaudemans AWJM, Bertagna F, Hazenberg BPC, Erba PA, Giubbini R et al (2018) Diagnostic accuracy of bone scintigraphy in the assessment of cardiac transthyretin-related amyloidosis: a bivariate meta-analysis. Eur J Nucl Med Mol Imaging 4511:1945-55. https://doi.org/0.1007/s00259-018-4013-4
Stats MA, Stone JR (2016) Varying levels of small microcalcification for utilizing nuclear medicine studies to subtype amyloidosis. Cardiovasc Pathol 2016;25:413-7. https://doi.org/10.1016/j.carpath.2016.07.001
Coskun N, Kartal MO, Erdogan AS, Tufekcioglu O, Ozdemir E (2022) Tc-99m pyrophosphate scintigraphy for cardiac amyloidosis: concordance between planar and SPECT/CT imaging. Int J Cardiovasc Imaging 38:2081–2088. https://doi.org/10.1007/s10554-022-02676-y
Hafeez AS, Bavry AA (2020) Diagnosis of Transthyretin Amyloid Cardiomyopathy. Cardiol Ther 9:85–95. https://doi.org/10.1007/s40119-020-00169-4
Quarta CC, Zheng J, Hutt D, Grigore SF, Manvani R, Sachchithanantham S et al (2021) 99mTc-DPD scintigraphy in immunglobulin light schain (AL) cardiac amyloidosis. Eur Heart J Cardiovasc Imaging 22:1304–1311. https://doi.org/10.1093/ehjci/jeab095
Elliott P, Gundapaneni B, Sultan MB, Ines M, Garcia-Pavia P (2023) Improved long-term survival with tafamidis treatment in patients with transthyretin amyloid cardiomyopathy and severe heart failure symptoms. Eur J Heart Fail 25:2060–2064. https://doi.org/10.1002/ejhf.2974
Pandey S, Teruya S, Rodriguez C, Deluca A, Kinkhabwala M, Johnson LL et al (2023) Diagnostic performance characteristics of planar quantitative and semi-quantitative parameters of Tc99m pyrophosphate (PYP) imaging for diagnosis of transthyretin (ATTR) cardiac amyloidosis: the SCAN-MP study. J Nucl Cardiol 30:1414–1419. https://doi.org/10.1007/s12350-023-03203-9

Table 1: Quantitative and semiquantitative results of all cases in [^99mTc]Tc-PYP scintigraphy. H/CL: Heart/contralateral lung.

Table 2: Graphical shown of quantitative and semiquantitative results. H/CL: Heart/contralateral lung.

Table 3

Quantitative and semiquantitative results of CA diagnosed, and ex-cases.
		H/CL RATIO median (range) (n)	VISUAL SCORE
ATTR CA (all cases) n = 12	Positive	1.7 (1.5–2.1) (11)	12
	Equivocal	1.4 (1)	0
	Negative	(0)	0
ATTR CA (ex cases) n = 1	Positive	1.7 (1)	1
	Equivocal	(0)	0
	Negative	(0)	0
AL CA (all cases) n = 19	Positive	1.6 (1.5–1.6) (2)	1
	Equivocal	1.2 (0.9–1.4) (17)	10
	Negative	(0)	8
AL CA (ex cases) n = 8	Positive	1.5 (1)	0
	Equivocal	1.3 (0.9–1.4) (7)	6
	Negative	(0)	2
Non-CA Ex Cases n = 15	Positive	1.5 (1.5–1.5) (2)	1
	Equivocal	1.3 (1.1–1.4) (13)	8
	Negative	(0)	6
H/CL: Heart/contralateral lung, AL: light chain, ATTR: transthyretin, CA: cardiac amyloidosis.

Table 4: Kaplan Meier graphic of each groups. AL: light chain, ATTR: transthyretin, CA: cardiac amyloidosis.

Table 5

Demographic, scintigraphic datas of each groups.
CA and/or Ex Cases n = 46		Non-ex Cases n = 222	p value
Age median (range)	68 (37–90)	63 (21–85)	0.03
Gender	25 Male	113 Male	< 0.001
1-hour H/CL Ratio median (range)	1.3 (0.9–2.1)	1.2 (0.8–1.5)	< 0.001
3-hour H/CL Ratio median (range)	1.3 (0.9–2.1)	1.2 (0.8–1.6)	< 0.001
Visual Scores Negative Equivocal Positive	14 18 14	125 79 18	< 0.001
ProBNP pg/ml median (range)	5666 (363-37905)	1562 (10-30935)	< 0.001
Troponin T ng/ml median (range)	46 (13–304)	(0.008–1762)	< 0.001
H/CL: Heart/contralateral lung, CA: Cardiac amyloidosis.

No competing interests reported.

[99mTc]Tc-pyrophosphate (PYP) Scintigraphy Findings of Cardiac Amyloidosis: is It a Predictor for Survival?

Status:

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Abstract

Background

Methods

Results

Conclusion

Figures

INTRODUCTION

MATERIAL METHODS

Statistical Analysis

RESULTS

DISCUSSION

CONCLUSION

Declarations

References

Tables

Additional Declarations

Status:

Version 1