Background: While the non-invasive assessment of cardiac sympathetic nerve dysfunction is readily accessible, its applicability in invasive intervention for structural heart disease has received limited investigation. Our study aimed to clarify the cardiac sympathetic nerve function in patients with severe Aortic stenosis (AS) and its postoperative changes after transcatheter aortic valve implantation (TAVI) using ¹²³I-metaiodobenzylguanidine scintigraphy (MIBG) in combination with 5-year mortality prediction model.
Methods: Consecutive 26 patients (83 ± 5ys, male 4) with severe AS who underwent MIBG prior TAVI procedures were retrospectively enrolled. Of those, 15 patients underwent postoperative-follow up MIBG. The early and delayed heart-to-mediastinum ratio (e- and d-H/M), and washout rate (WR) were obtained from MIBG planner imaging. The MIBG 5-year mortality prediction model was employed to compare pre and after TAVI. Cardiac function and wall thickness were evaluated with transthoracic echocardiography.
Results: Preoperative e-H/M, d-H/M, and WR were 2.4 ± 0.5, 2.3 ± 0.4, and 29 ± 14% respectively, and WR showed significant correlation to LVEF and BNP (r=-0.4 and 0.6; p=0.03, and 0.001 for LVEF and BNP, respectively). 102 ± 28 days after TAVI, either H/M or WR did not show significant improvement among enrolled patients (2.5 ± 0.3, 2.3 ± 0.4, and 30 ± 11% for e-, d-H/M, and WR for after TAVI), while the BNP level was significantly reduced (128 ± 691 and 94 ± 194 pg/dl, for pre vs. after, p=0.008). Five patients showed a significant recovery in WR (37.0 ± 13.8 and 28.8 ± 8.5% for pre and post, p=0.04), and left ventricular wall thickness was significantly thinner compared to those who did not recover (15.2 ± 3.2 vs 11.2 ± 2.4, p=0.02; 14.2 ± 2.9 vs 10.8 ± 1.8, p=0.02 for intraventricular septum and posterior wall, respectively). In 5-year prediction risk model, 7 patients showed a significant reduction in mortality risk, and the patients who did not show risk reduction had significantly reduced renal function (eGFR 57.5 ± 18.8 vs. 38.2 ± 11.3 ml/min/1.73m², p=0.03 for recovered vs. not recovered).
Conclusion: After a 3-month follow-up after TAVI, diverse response in cardiac MIBG parameters were observed among patients with severe AS, despite successful valve replacement. Cardiac MIBG serves as a non-invasive tool that can comprehensively evaluate and surrogate the severity of heart failure resulting from a multi-factorial condition.

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Purpose: We aimed to clarify the clinical characteristics of global and regional myocardial perfusion in patients with transthyretin type of cardiac amyloidosis (ATTR) using dual single-photon emission computed tomography (SPECT) with ^99mTc pyrophosphate (PYP) and ²⁰¹TL (TL).
Methods: Consecutive 178 (mean age 78 ± 12, male 79) patients known or suspect of ATTR who underwent PYP-TL dual SPECT were retrospectively enrolled. Patients were categorized according to the visual grading for planar PYP uptake using Perugini grading, and the patients with grade greater than or equal to 2 were analyzed. In planar analysis, the heart/ contralateral ratio (H/CL) for PYP, and heart/lung ratio (H/L) for TL were obtained to evaluate global myocardial uptake. In TL-SPECT polar map analysis, the heterogeneity of myocardial uptake was evaluated using segmental mean %uptake. Cardiac function and left ventricular function and end-diastolic ventricular mass (LVmass) were measured by echocardiography.
Results: Among 178 patients, 39 patients showed PYP uptake with grade 2 or 3 and H/CL >1.3 (81 ± 5 ys, male 28). Of those, 4 patients showed significant perfusion defect in TL scan. Among 35 patients without perfusion defect, H/L showed a significant inverse correlation to H/CL, and LVmass (r=-0.3, p=0.02; r=-0.4, p=0.03. 95% confidence interval -0.4 to 0.2, and -0.7 to -0.04 for H/CL and LVmass). Polar map analysis demonstrated significantly lower mean %uptake for TL in septum compared to lateral (79.4 ± 8.4 vs. 84.3 ± 6.2, p=0.006 for TL in septum vs. lateral, respectively).
Conclusion: In ATTR, TL uptake surrogated the reduction of global myocardial perfusion. A significant regional heterogeneity was observed with a notable reduction in septum despite the diffuse hypertrophy.

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Background: This study investigated the feasibility of using a quantitative diagnostic method based on ^99mTc-pyrophosphate scintigraphy (PYP) lateral planar images to differentiate between PYP-positive (myocardial uptake) and false-positive (blood pool uptake) scans.
Methods: The study included 93 consecutive patients with suspected transthyretin amyloid cardiomyopathy (ATTR-CM) who underwent PYP between April 2022 and December 2023. Patients were categorized using planar anterior PYP images according to the Perugini visual grading system; patients with grades ≥2 were analyzed. Whether the uptake of the ventricle was in the blood pool or the myocardium was confirmed by transaxial single-photon emission tomography (SPECT). The heart-to-mediastinum ratios (H/M ratio) of the left lateral planar images at 1- and 3-h were calculated by placing a circular region of interest in the heart and cephalodorsal side of the heart to determine optimal cut-off values.
Results: Among the PYP images, the study analyzed 15 positives diagnosed as ATTR-CM and 10 false positives. Significant differences were observed in the H/M ratio at 1- and 3-h (both p <0.01), with 100% sensitivity and specificity using cut-off values of 1.22 and 1.21 at 1- and 3-h, respectively. The interclass correlation coefficients (2, 1) between the two readers were 0.919 and 0.958 for the 1- and 3-h H/M ratios, respectively.
Conclusions: Lateral planar PYP imaging can exclude PYP false-positive cases caused by blood pools in a simple and quantitative manner using only a 1-h planar image, possibly obviating the need for SPECT imaging.

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Background: Lateral planar ^99mTc-pyrophosphate (PYP) imaging is recommended as a standardized acquisition method because it helps separate extracardiac uptake from the myocardium. We evaluated its discriminatory performance in detecting myocardial PYP uptake, using single-photon emission computed tomography (SPECT) as a reference standard.
Methods: We retrospectively evaluated 170 patients who underwent PYP imaging for suspected transthyretin cardiac amyloidosis. Anterior and lateral planar imaging and SPECT were performed 3 h after PYP administration. The myocardial PYP uptake on planar and SPECT images was visually assessed and quantified using the heart-to-contralateral lung uptake (H/CL) ratio. The heart-to-mediastinum uptake (H/M) ratio was calculated as the mean count of the region of interest in the heart divided by that in the superior mediastinum on lateral planar images.
Results: Patients with PYP SPECT-positive results had significantly higher H/M ratios at 3 h than those with PYP SPECT-negative results (1.23 [interquartile range: IQR, 1.15–1.43] vs. 1.08 [IQR, 1.02–1.16]; P <0.001). A reclassification analysis that added the H/M ratio to visual scores for detecting positive PYP SPECT yielded a significant improvement with a net reclassification improvement (NRI) of 0.56 (95%CI, 0.25–0.87; P <0.001) and integrated discrimination improvement (IDI) of 0.038 (95%CI, 0.005–0.072; P=0.026). The H/M ratio significantly improved the predictive ability of SPECT findings based on the visual scores and H/CL ratio with an NRI of 0.49 (95%CI, 0.18–0.81; P=0.003) and IDI of 0.036 (95%CI, 0.004–0.069; P=0.029).
Conclusions: Adding the H/M ratio derived from lateral planar PYP imaging to visual scores or the H/CL ratio on anterior planar images improved the accuracy of detecting significant myocardial uptake on SPECT.

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Triglyceride deposit cardiomyovasculopathy (TGCV) is an emerging rare heart disease with high mortality, characterized by defective intracellular lipolysis of triglycerides (TG). We developed diagnostic criteria for TGCV, in which low washout rate of BMIPP (BMIPP-WR) is a key factor. The working group of the Japan Society of Nuclear Cardiology recently published practice recommendations for measuring BMIPP-WR. We reported that hemodialysis (HD) patients with TGCV exhibited a markedly higher cardiovascular risk than those without TGCV. Secondary carnitine deficiency is common in patients undergoing HD, as carnitine is removed from the circulation. However, clinical evidence linking carnitine levels to BMIPP-WR is limited. Here we report the effect of L-carnitine administration on the BMIPP-WR in 9 chronic HD patients with TGCV in a retrospective cohort. The mean age at TGCV diagnosis was 59 years. Following standard doses of oral L-carnitine administration, plasma free carnitine levels significantly increased. However, BMIPP-WR was not changed. In normal condition, most BMIPP taken up were esterified/incorporated into TG pool, hydrolyzed by intracellular lipases, and then transported by carnitine shuttle to mitochondria. In TGCV, intracellular TG lipolysis is defective. During the intracellular metabolism of BMIPP, carnitine shuttling occurs downstream of TG lipolysis. Therefore, even when carnitine levels were increased, BMIPP-WR did not change in patients with TGCV who underwent chronic HD. A phase IIb/III clinical trial for TGCV, is underway (jRCT2051210177). Increased awareness of the disease concept of TGCV, along with its diagnostic principles and procedures using BMIPP scintigraphy, is warranted.

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¹²³I-BMIPP (Iodine-123 labeled beta-methyl-p-iodophenyl-pentadecanoic acid) is a radiotracer that facilitates non-invasive assessment of myocardial fatty acid metabolism through single photon emission computed tomography imaging. Given that fatty acids serve as one of the primary energy sources for cardiac muscle, reduced uptake of ¹²³I-BMIPP offers valuable insights into the pathophysiology of various cardiac conditions, particularly in coronary artery disease (CAD). Despite its reported efficacy, the use of ¹²³I-BMIPP remains limited outside Japan, primarily due to regulatory and supply challenges. However, in Japan, ¹²³I-BMIPP is clinically utilized for CAD patients with various ischemic conditions as the protocol does not require stress tests or contrast iodine and has a relatively short acquisition time. This review highlights the clinical applications of ¹²³I-BMIPP across various conditions and aims to promote its broader adoption in clinical practice, both in Japan and internationally.

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The novel positron emission tomography (PET) myocardial perfusion imaging tracer, ¹⁸F-flurpiridaz (flurpiridaz), was discussed in 2023 at the Annals of Nuclear Cardiology. In a Phase III trial in 2020 by Maddahi et al., flurpiridaz demonstrated higher sensitivity (71.9%) than ^99mTc-labeled single photon emission computed tomography (SPECT) (53.7%) for detecting ≥50% coronary artery stenosis but did not meet the non-inferiority criterion in specificity. This led to a second Phase III trial, the AURORA trial, which showed flurpiridaz PET to be more sensitive (80.3%) and not inferior (63.8%) in specificity compared to SPECT. The trial highlighted flurpiridaz's superior diagnostic accuracy, especially in women and obese patients. The tracer's ability to measure coronary blood flow reserve suggests its potential future use in clinical practice, possibly offering more accurate functional ischemia diagnostics and predicting cardiac events. The findings indicate that ¹⁸F-flurpiridaz could be a significant advancement in coronary artery disease diagnosis.

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Nuclear cardiac imaging has advanced significantly with the development of semiconductor single photon emission computed tomography (SPECT) systems using cadmium zinc telluride detectors. These systems provide superior sensitivity and resolution compared to conventional anger-type SPECT systems, improving image quality and diagnostic accuracy. This study, conducted through a multi-center survey among nuclear cardiology practitioners, assessed changes in clinical practice following the implementation of semiconductor SPECT. Results showed shorter scan times, increased examination throughput, and reduced artifacts. However, challenges associated with semiconductor SPECT systems were also identified, including system-specific artifacts and cases that are difficult to image using these systems. These findings highlighted both the advantages and limitations of semiconductor SPECT in real-world clinical practice.

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The technetium (Tc) labeled myocardial perfusion compounds are tracers that have been taken up into myocytes and retained in mitochondria several times, thus reflecting the activity of myocytes at the time of injection. However, under certain conditions, “reversed redistribution” is known to occur. This review summarized the unique properties of imaging with the Tc myocardial perfusion tracers.

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Despite recent developments in positron emission tomography technology, cardiac single photon emission computed tomography (SPECT) imaging continues to be the main stream of nuclear cardiology because of its high accessibility and wider clinical use. For SPECT imaging, cadmium-zinc telluride (CZT) based detectors have advantages over conventional Anger type detectors with more flexible camera design thanks to the small sized CZT detectors and high contrast imaging because of its high energy resolution. Approximately 15 years ago, CZT-based cardiac SPECT cameras became commercially available, resulting in great success in clinical practice. However, this was just the beginning of the CZT era. To date, CZT-based general purpose whole-body camera and 3 dimensional full-ring SPECT systems have been developed and become commercially available with promising initial results. Although there still are areas to be addressed before wider clinical use, the CZT-based technology may provide significant progresses in nuclear cardiology as new generation SPECT systems. Finally, newer materials for the semiconductor detectors are under investigation or development, suggesting that there will be more developments in cardiac SPECT technology.

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