Cardiac denervation is associated with progressive left ventricular (LV) dysfunction, ventricular arrhythmias, and sudden cardiac death (SCD) in heart failure (HF). In this regard, it is important to evaluate cardiac-specific sympathetic nervous system (SNS) function. The radiotracer Iodine-123 meta-iodobenzylguanidine (¹²³I-mIBG) can noninvasively evaluate presynaptic SNS function. Recent multicenter trials have shown ¹²³I-mIBG to have strong predictive value for fatal arrhythmias and cardiac death in HF. ¹²³I-mIBG was initially developed in the USA in the 1970s. In 1992, the Japanese Ministry of Health and Labour approved ¹²³I-mIBG for the assessment of cardiac function. Following approval, the Japanese nuclear cardiology community developed ¹²³I-mIBG imaging services in various medical centers. Japanese groups have been trying to establish the clinical utility of ¹²³I-mIBG and standardize parameters for data acquisition and image analysis. The US Food and Drug Administration (FDA) has approved clinical use of ¹²³I-mIBG for cardiac and non-cardiac imaging. However, clinical use of ¹²³I-mIBG in the US has been very limited. The number of 1¹²³I-mIBG studies in Japan has also been limited. There are similarities and differences between the two countries. To establish the clinical utility of ¹²³I-mIBG in both countries, it is important to characterize the situations of ¹²³I-mIBG in each.

View full abstract

Objective: It has been reported that granulocyte-colony-stimulating-factor (G-CSF) induces myocardial regeneration and revascularization after acute myocardial infarction (AMI) by mobilizing bone marrow stem cells and suppressing apoptosis of endothelial cells in the injured heart. This study investigated whether hyper early G-CSF therapy was beneficial for AMI patients.
Methods: Forty consecutive patients with initial ST-segment elevation AMI were randomized to receive intravenous infusion of G-CSF at 2μg/kg over 30 min (G-CSF group) or infusion of normal saline (control group) once daily for 5 days. The first dose was administered during primary percutaneous coronary intervention just after hospitalization. In the subacute period and 6 months after AMI, all patients underwent myocardial scintigraphy, including ^99mTc-sestamibi imaging of myocardial perfusion and ¹²³I-beta-methyl-p-iodophenylpentadecanoic-acid (¹²³I-BMIPP) imaging to assess fatty acid metabolism.
Results: The two groups had a similar myocardial area at risk, as evaluated by the extent score on subacute ¹²³I-BMIPP imaging. Compared with the control group, the G-CSF group had a significantly smaller (p<0.05) total defect score on ^99mTc-sestamibi and ¹²³I-BMIPP imaging at 6 months. In addition, the left ventricular ejection fraction and regional wall motion score were larger in the G-CSF group than in the control group during the subacute period and after 6 months.
Conclusions: Hyper early G-CSF therapy improves myocardial perfusion, fatty acid metabolism, and cardiac function after AMI.

View full abstract

Background: Myocardial perfusion imaging (MPI) by single photon emission computed tomography is widely performed in patients with coronary artery disease (CAD). These days, the relation between MPI findings and the prognosis of CAD has been reported.
Methods: A total of 188 consecutive patients with stable CAD were retrospectively enrolled. They all had ischemic findings in the initial stress/resting MPI and underwent a repeat stress/resting MPI within one year of the initial test. We evaluated the summed stress score, summed rest score, and summed difference score (SDS). We defined %residual ischemia as the percent SDS on repeat MPI relative to that on initial MPI (post SDS×100/pre SDS). We followed the patients until occurrence of an adverse event or for at least one year after repeat MPI to assess adverse events including cardiac death, nonfatal myocardial infarction, hospitalization for heart failure, revascularization by percutaneous coronary intervention or coronary artery bypass grafting, stroke, and non-cardiac death.
Results: Fifty-four patients (28.7%) experienced adverse events. According to multivariate Cox proportional hazards regression analysis of adverse event rates, more extensive %residual ischemia was associated with a higher incidence of adverse events (HR 1.025, p=0.018). According to Kaplan-Meier analysis, patients with significant %residual ischemia had a higher risk of adverse events than those with mild %residual ischemia (p=0.001, log rank test).
Conclusion: In patients with CAD, significant residual ischemia on repeat MPI may predict a worse prognosis for CAD patients receiving optimal medical therapy with or without coronary revascularization.

View full abstract

Background: The relationship between myocardial perfusion imaging (MPI) and aortic calcification (AoC) in chronic kidney disease (CKD) patients remains unclear.
Methods: The Japanese Assessment of Cardiac Events and Survival Study by quantitative gated single-photon emission computed tomography (J-ACCESS 3) is a multicenter, prospective cohort study investigating the ability of MPI to predict cardiac events in 529 CKD patients. In J-ACCESS 3, the sum of myocardial perfusion defect score at stress (SSS) was a useful predictor of cardiac major events in CKD patients. However, aortic calcification was not examined. We examined the prognosis of patients with CKD according to the presence or absence of AoC using data from the J-ACCESS 3 cohort.
Results: There were 60 major cardiac events (three cardiac deaths, six sudden deaths, five non-fatal myocardial infarctions, 46 hospitalization cases for heart failure). In the univariate analysis, patients with AoC had a higher left ventricular (LV) ejection fraction, smaller LV volume, and lower SSS by MPI. Kaplan–Meier curves showed a significantly higher incidence of major cardiac events in the AoC group (P=0.0041). Patients were categorized into the following four groups: Group A (non-AoC and SSS<4; normal score of 0–3); Group B (AoC and SSS<4); Group C (non-AoC and SSS≥4); Group D (AoC and SSS≥4). Kaplan–Meier curves showed that the major cardiac events rates were A<B<C<D (P=0.002). The difference was most pronounced between the AoC and no-AoC groups with SSS<4.
Conclusions: The combination of SSS using MPI and AoC is a useful predictor of cardiac major events in CKD patients.

View full abstract

Hybrid imaging using PET/CT have various applications in cardiology. Anatomy, physiology or both can be evaluated. Routine attenuation correction can be performed and improve accuracy for nuclear cardiology studies. The extent of availability and utilization of hybrid imaging technology worldwide is currently unknown. The International Atomic Energy Agency (IAEA) in cooperation with QUANTA performed a web-based survey among physicians working with nuclear imaging to evaluate the current availability of hybrid imaging and its use for nuclear cardiology (NC). Contact e mails of physicians working in the field of nuclear cardiology were available from a data base at the human health department of the IAEA in Vienna, Austria and an international network of nuclear cardiologist at QUANTA in Curitiba, Brazil. Data from 80 countries in both high-income countries (HIC, n=16) and low-and-middle income countries (LMIC, n=64) representing all world regions, was obtained. At the country level, PET/CT is available in all world regions being widely available in North and Latin America, Europe, Asia and Oceania with a heterogeneous availability in Africa. Nevertheless, only 22.4% of centers in HIC and 10.9% in LMIC that have PET/CT available use it for NC applications. These data will help us to work with scientific societies and institutions to design strategies to diffuse information for physicians so they can take full advantage of PET/CT technology to obtain additional information that could impact patient care.

View full abstract

Myocardial perfusion imaging (MPI) using positron emission tomography (PET) has high diagnostic accuracy and prognostic value in patients with known or suspected coronary artery disease (CAD). In addition, PET MPI can be used to quantify global left ventricle (LV) and regional LV myocardial blood flow (MBF) and myocardial flow reserve (MFR). Currently, there are four major PET perfusion tracers: ⁸²rubidium, ¹³N-ammonia, ¹⁵O-water, and ¹⁸F-flurpiridaz. The characteristics of each tracer have been described and fully compared. Given increasing clinical needs for accurate MBF and MFR measurements, the use of PET MPI should be expanded in clinical settings in the near future.

View full abstract

Rubidium-82 is the most well-established cardiac PET flow tracer with over 6 decades of literature. Due to its robust supply, short physical half-life, ease of use, low radiation dose and favorable kinetics it can deliver comprehensive clinical information with minimal risk and maximum convenience to patients and clinical staff. Optimized ⁸²Rb protocols can deliver high quality myocardial perfusion imaging, functional cardiac images and absolute myocardial blood flow and flow reserve from a single session 30 minutes clinical protocol–benefiting patient convenience and clinical throughput. In a high volume setting the cost of ⁸²Rb PET can be dramatically lower than that of alternative PET flow tracers. These factors compound toward ⁸²Rb as the best PET flow tracer for high-throughput clinics.

View full abstract

Currently, ¹³N-ammonia and Rubidium-82 (⁸²Rb) are the only FDA-approved myocardial perfusion positron emission tomography (PET) tracers for myocardial perfusion imaging in the evaluation of suspected or known coronary artery disease (CAD), quantification of left ventricular volumes and systolic function and quantification of global and regional myocardial blood flow (MBF) and myocardial flow reserve (MFR). Nevertheless, there are physical, chemical and molecular differences between them. The ideal perfusion tracer would include 100% extraction from blood to tissue, and 100% retention, resulting in a linear relationship between MBF and the measured tracer activity over a wide range. However, both ¹³N-ammonia and ⁸²Rb have limited characteristics. In this review, we aim to analyze ¹³N-ammonia in detail, and its differences with other radiotracers for the assessment of myocardial perfusion.

View full abstract

Oxygen-15-labeled water (¹⁵O-H₂O) is used as a radiopharmaceutical tracer with positron emission tomography (PET). Its short radioactive half-life permits consecutive rest and stress imaging acquisition while requiring an on-site cyclotron near a PET imaging system. ¹⁵O-H₂O PET has the disadvantage of being less than ideal for visual assessment; however, its high extraction fraction allows for highly accurate quantification of myocardial blood flow (MBF). Therefore, ¹⁵O-H₂O is considered to be a gold standard for MBF quantification. This is one of the great advantages of ¹⁵O-H₂O PET over other PET myocardial perfusion imaging modalities. The purpose of this review is to provide the advantages and characteristics of ¹⁵O-H₂O PET.

View full abstract

Myocardial perfusion imaging (MPI) using advanced PET technology is increasingly used for non-invasive detection and evaluation of coronary artery disease (CAD), but is still limited for clinical use. Recently, ¹⁸F labeled PET perfusion tracers have been actively developed as a novel class of PET MPI agents to overcome the disadvantages of conventional PET MPI tracers (¹⁵O-labelled water, ¹³N-ammonia, and ⁸²Rb chloride). This review summarizes the advantages and the feasibility of recent developed ¹⁸F labeled tracers in clinical practice.

View full abstract

Cardiac computed tomography (CT) could provide the comprehensive morphologic and functional information of coronary artery disease. Coronary CT angiography has been well established for identification and management of symptomatic patients with or suspected coronary artery disease. However, we should know the anatomical stenosis is not the same as the functional one needed to be treated. Dynamic perfusion imaging could lead a non-invasive quantitative evaluation of myocardial ischemia with estimation of myocardial blood flow. In this review, we address the characteristics and advantages of cardiac CT, in particular dynamic perfusion CT for quantitative evaluation of myocardial ischemia.

View full abstract

Myocardial perfusion can be assessed with dynamic cardiovascular magnetic resonance imaging (MRI) during the passage of contrast agent bolus. Myocardial perfusion MRI has been evaluated qualitatively or semi-quantitatively. However, fully-quantitative myocardial perfusion MRI permits more objective assessment of coronary artery disease and evaluation of diffuse microvascular disease. Advances in acquisition and image analysis of cardiac magnetic resonance have enabled absolute myocardial perfusion quantification, previously only achievable with positron emission tomography. Absolute quantification of myocardial blood flow (MBF) requires knowledge of the amount of contrast agent in the myocardial tissue and the arterial input function (AIF) driving the delivery of contrast agent. However, accurate quantification of MBF is challenging due to lack of linearity between the measured blood signal and high blood contrast concentration during first pass, because sequences for perfusion MRI have been developed to optimize the contrast between normal and ischemic myocardium. Saturation correction of AIF response curve is required for the perfusion quantification. This review article will discuss saturation correction of AIF for accurate MBF measurements in perfusion MRI.

View full abstract

Diagnostic procedures of noninvasive assessment for patients with peripheral artery disease (PAD) have been advancing for decades. Among diagnostic imaging modalities, lower-limb perfusion (LLP) planar scintigraphy and SPECT/CT are exclusively used for diagnosing lower-limb ischemia, therapeutic efficacies, and risk stratification in PAD patients. Of these modalities, LLP SPECT/CT particularly shows more accuracy in providing quantitative assessment of LLP using innovative imaging devices and dedicated software.

View full abstract

Currently most stable patients referred for invasive angiography do not have obstructive disease, implying an enormous opportunity to avoid unnecessary, invasive, and expensive procedures. Cardiac positron emission tomography (PET) offers a robust and non-invasive tool for quantifying absolute blood flow as a “gatekeeper” to cardiac catheterization. It images the entire left ventricle down to branch vessels, permitting a “physiologic angiogram” while normalizing flow values for the amount of supplied myocardium. Flow imaging has been demonstrated to be accurate compared to invasive measurements, precise to 20% on test/retest assessment, and routinely achievable in >99% of daily clinical cases. Coronary flow capacity (CFC) integrates both resting and hyperemic flow together along the continuum from infarction to ischemia to normal levels. CFC predicts prognosis and identifies which patients benefit from revascularization. Emerging work allows cardiac PET to make an assessment of subendocardial hypoperfusion, relevant since this layer of the myocardium suffers “first and worst” from epicardial disease. A case example highlights many of the aspects of cardiac PET described in this review article.

View full abstract

Survey research studies are frequently done badly, resulting in unreliable data. Response rates for clinical research are commonly below 30%, far less than considered reasonable for accuracy or validity. Addressing 10 weak points common to many studies would help to improve the quality of outcomes. Careful attention to the data needed to meet the research objective, clearly defined population definition, frame, sample and implementation planning all build a foundation for rigorous research. The survey delivery method(s), questionnaire design, write-up, pre-test of the questionnaire and mixed method, multiple follow-ups all should all work toward maximizing response rates. Well cleaned data will deliver high quality final results.

View full abstract

Epicardial coronary artery disease has been highly noticed in the traditional clinical examination, while myocardial microcirculation function has been neglected for a long time, which plays a nonnegligible role in quite a few patients' clinical manifestations and prognosis. Non-invasive quantitative PET myocardial perfusion imaging has become a unique and gold standard of evaluating myocardial microcirculation function. Its clinical applications in diagnosis, risk stratification, prognosis evaluation, efficacy evaluation and treatment guidance of cardiovascular diseases are given, together with its development status in China.

View full abstract

In 2008 in Taiwan, the National Health Insurance (NHI) administration revised the guidelines regarding appropriately utilizing percutaneous coronary intervention (PCI) for patients with stable CAD to mandatory demonstration of functional ischemia by treadmill exercise test (TET), stress echocardiography (SE) or MPI. Notably, anatomic-based non-invasive imaging with coronary computed tomography (CT) angiography remains not reimbursed by Taiwan's NHI. According to the NHI database, the total number of MPI significantly increased from 34,016 in 2000 to 151,254 in 2016 with an annual growth rate of 21.5%, much higher than the 7.9% growth of overall nuclear medicine tests during this period. Recently we investigated the frequency of stress testing within 90 days prior to PCI for stable CAD and showed that 79.1% of patients had MPI, 66.4% had TET and only 0.05% had SE. We conclude that MPI currently plays a gatekeeper role for invasive coronary procedures for stable CAD in Taiwan.

View full abstract

Kawasaki disease (KD) has become a commonly acquired heart disease worldwide in children over the past five decades, because of the related cardiac sequelae. KD is an acute generalized medium vasculitis resulting from hypercytokinemia, and the coronary artery lesions caused by KD from childhood to adulthood lead to ischemic heart disease. To treat and manage KD appropriately, the optimal use of nuclear imaging is required.

View full abstract

The Editor-in Chief of the Journal of Nuclear Cardiology created in 2014 the “Mentorship at Distance Committee” to provide editorial assistance to foreign authors. The chair of the committee discusses in the present communication his 3-year experience with mentoring manuscripts. He addresses the selection of manuscripts, the process of mentoring and common problems encountered and resolved. The mentoring process required the full commitment by both the mentor and the author, because of necessary intensive and frequent communications by email. The average time involved from start to finish averaged about 9 weeks. Eight of 11 mentored manuscripts could be sufficiently revised and were accepted for publication.

View full abstract

Interpreting medical scans acquired with nuclear imaging equipment requires testing the equipment to assure that the best results achievable are routinely and reliably produced. Strict adherence to predetermined schedules for testing and recording the results for gamma cameras will facilitate the efficient operation of a Nuclear Cardiology laboratory, satisfy regulatory and accreditation requirements, and instill confidence in the readings obtained by interpreting the collected patient scans, for the ultimate benefit of the patients being evaluated.

View full abstract

Cardiac resynchronization therapy (CRT) has been utilized for patients with advanced heart failure since 2004 in Japan. However, it has been regarded as the problem that about 30% of the patients with CRT show poor functional improvement. For the prediction of CRT response, the importance of the quantitative assessment of left ventricular (LV) dyssynchrony has been reported. Therefore, we developed novel algorithm for quantitative assessment of LV dyssynchrony with radionuclide imaging; ECG-gated myocardial perfusion SPECT imaging (NCVC method). We applied “partial volume effect” in SPECT system for detecting regional systolic timing. Measuring the sequential change of regional myocardial counts in cardiac cycle, we determined “time to end-systole (TES)” which was the time from R-wave to maximum counts phase in each region. Then, we calculated maximum difference of TES between regions, named as “Dissynchrony Index (DI).”
For the verification of this NCVC methods, we evaluated the patients with CRT implantation. Responders showed significantly higher DI than non-responder, and also showed significant reduction of DI after CRT, however, non-responder did not show such reduction. Moreover, DI showed significant correlation to the index of LV dyssyncrhony evaluated by “phase analysis” of commercially available software: QGS (quantitative gated SPECT). From these results, our novel algorithm “NCVC method” might be useful for CRT management; such as decision of indication and evaluation of therapeutic response similar with other software.

View full abstract

Cardiac PET with assessment of myocardial perfusion and flow quantification with cardiovascular risk prediction in clinically-manifest and subclinical CAD has evolved as a mainstay in the clinical decision-making process. In this respect, cardiovascular PET continuous to expand its clinical scope with assessment of infiltrative-inflammatory cardiac disease, vasculitis, and device infections. Conversely, PET flow quantification for the identification and characterization of coronary circulatory dysfunction in conjunction with various biomarkers has provided unique “in vivo” insight into early functional stages of the CAD process that may complement or even guide experimental studies that investigate direct cause-effect relationships. Further, emerging radiotracer probes with PET may probe non-invasively myocardial receptor expressions, such as cannabinoid type 1 receptors that may play a role in heart failure development in obesity and/or diabetes mellitus deserving further clinical evaluation.

View full abstract