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We present the case of a 69-year-old woman with diabetes mellitus, left bundle branch block, and obesity who develops cardiogenic shock after undergoing myocardial perfusion imaging and diagnostic left heart catheterization, but prior to coronary revascularization. This case highlights the risk of cardiac decompensation awaiting surgery in patients with multivessel coronary artery disease. It also emphasizes the subtleties involved in imaging patients with diabetes mellitus and left bundle branch block, as well as the risk of developing complete heart block in the setting of ischemia with underlying conduction disease.

Rationale, Aims, and Objectives: To both examine the impact of preprint publishing on health sciences research and survey popular preprint servers amidst the current coronavirus disease 2019 (COVID-19) pandemic., Methods: The authors queried three biomedical databases (MEDLINE, Web of Science, and Google Scholar) and two preprint servers (MedRxiv and SSRN) to identify literature pertaining to preprints. Additionally, they evaluated 12 preprint servers featuring COVID-19 research through sample submission of six manuscripts., Results: The realm of health sciences research has seen a dramatic increase in the presence and importance of preprint publications. By posting manuscripts on preprint servers, researchers are able to immediately communicate their findings, thereby facilitating prompt feedback and promoting collaboration. In doing so, they may also reduce publication bias and improve methodological transparency. However, by circumventing the peer-review process, academia incurs the risk of disseminating erroneous or misinterpreted data and suffering the downstream consequences. Never have these issues been better highlighted than during the ongoing COVID-19 pandemic. Researchers have flooded the literature with preprint publications as stopgaps to meet the desperate need for knowledge about the disease. These unreviewed articles initially outnumbered those published in conventional journals and helped steer the mainstream scientific community at the start of the pandemic. In surveying select preprint servers, the authors discovered varying usability, review practices, and acceptance polices., Conclusion: While vital in the rapid dispensation of science, preprint manuscripts promulgate their conclusions without peer review and possess the capacity to misinform. Undoubtedly part of the future of science, conscientious consumers will need to appreciate not only their utility, but also their limitations., (© 2020 John Wiley & Sons Ltd.)

Background: The diagnosis of coronary artery disease (CAD) remains challenging. It is uncertain whether hybrid imaging can improve diagnostic accuracy for CAD., Methods: This is a systematic review and multivariate meta-analysis. We searched PubMed and The Cochrane Library for recent (≥ 2010) systematic reviews of diagnostic test accuracy studies on non-invasive imaging for CAD. Study-level data were extracted from them, and pooled with pairwise and multivariate meta-analytic methods, using invasive coronary angiography (ICA) or invasive fractional flow reserve (FFR) as reference standards, focusing on sensitivity and specificity., Results: Details from 661 original studies (71,823 patients) were pooled. Pairwise meta-analysis using ICA as reference showed that anatomic imaging was associated with the best diagnostic accuracy (sensitivity = 0.95 [95% confidence interval 0.94-0.96], specificity = 0.83 [0.81-0.85]), whereas using FFR as reference identified hybrid imaging as the best test (sensitivity = 0.87 [0.83-0.90], specificity = 0.82 [0.76-0.87]). Multivariate meta-analysis confirmed the superiority of anatomic imaging using ICA as reference (sensitivity = 0.96, specificity = 0.83), and hybrid imaging using FFR as reference (sensitivity = 0.88 [0.86-0.91], specificity = 0.82 [0.77-0.87])., Conclusions: Non-invasive hybrid imaging tests appear superior to anatomic or functional only tests to diagnose ischemia-provoking coronary lesions, whereas anatomic imaging is best to diagnose and/or rule out angiographically significant CAD., Systematic Review Registration: PROSPERO Registry Number CRD42018088528.

"A quick glance at selected topics in this issue" aims to highlight contents of the Journal and provide a quick review to the readers.

Competing Interests: Conflict of interest: P.G. Camici is consultant for Servier. R.S. Rosenson reports research grants to his institutions from Akcea, Amgen, Astra Zeneca, Medicines Company and Regeneron. R.S. Rosenson reports speaking engagements at Amgen and Kowa, research consulting for Akcea and Regeneron, royalties from UpToDate, Inc. and stock holdings in MediMergent. All other authors have nothing to disclose.

Background: Depressed left ventricular ejection fraction (LVEF), LV mechanical dyssynchrony (LVMD), and prolonged QTc interval predict poor outcomes in end-stage renal disease (ESRD). Renal transplantation improves mortality in ESRD patients but the effects of transplantation on these indices remain undefined., Methods: We identified patients with myocardial perfusion imaging (MPI) before and after renal transplantation. A control group consisted of ESRD patients who underwent 2 MPIs but did not receive a transplant. Changes in LVEF, LVMD indices [phase standard deviation (SD) and bandwidth (BW)] by MPI, and electrocardiogram (ECG) indices were determined., Results: The study population consisted of 32 ESRD patients (53% male, 50 ± 11 years, 59% African American, 65% diabetic). The second MPI was performed 31 months (13-59 months) after renal transplantation. LVEF (72 ± 10% vs. 67 ± 10%, P < 0.001) but not SD (22 ± 15° vs. 22 ± 11°, P = 0.9) or BW (58 ± 35° vs. 57 ± 29°, P = 0.9) improved after transplantation. There were no changes in these indices in the control group. QTc (425 ± 30 ms vs. 447 ± 32 ms, P = <0.001) but not QRS (90 ± 21 ms vs. 90 ± 21 ms, P = 0.9) improved significantly after renal transplantation., Conclusions: LVEF and QTc improved after renal transplantation but LVMD indices and QRS did not change, which suggests that LVMD and electrical dyssynchrony may be irreversible in ESRD.

Background: Adenosine or regadenoson are often used with pharmacologic stress testing. Adenosine may trigger atrioventricular block (AVB). Despite its higher selectivity, regadenoson has also been associated with AVB. We studied the incidence of de novo AVB with these agents., Methods: A comprehensive search of SCOPUS was performed from inception to March 2016. Studies of at least 10 patients, using adenosine and/or regadenoson with SPECT-MPI, reporting rates of AVB were selected for further review., Results: Thirty four studies were pooled including 22,957 patients. Adenosine was used in 21 studies and regadenoson in 15. Both were administered in two studies. The estimated incidence of overall and high-grade AVB was 3.81% (95% CI 1.99%-6.19%) and 1.93% (95% CI 0.77%-3.59%), respectively. The incidence of AVB (8.58%; 95% CI 5.55%-12.21% vs 0.30%; 95% CI 0.04%-0.82%, respectively, P < .001) and high-grade AVB (5.21%; 95% CI 2.81%-8.30% vs 0.05%; 95% CI < .001%-0.19% respectively, P < .001) were higher with adenosine compared to regadenoson., Conclusion: AVB is seen in about 4% of patients undergoing vasodilator stress test. Both overall and high-grade AVB are more frequent with adenosine compared to regadenoson.

Background: In patients with right dominant coronary circulation, the right ventricular (RV) myocardium and the inferior region of the left ventricular (LV) myocardium share a common source of blood flow. We hypothesized that stress/rest SPECT myocardial perfusion imaging (MPI) could detect reversible perfusion defects in the RV in some patients with LV inferior wall perfusion abnormalities., Material and Methods: We identified 2 groups of patients with LV inferior wall perfusion defects (with or without defects in other regions of LV myocardium) from our database. Patients in group 1 (n = 17) had reversible perfusion defects in the RV free wall by visual analysis, while patients in group 2 (n = 17) did not. The images were processed with filtered back projection and, separately, with iterative reconstruction. The images were then re-processed using an automated quantitative software that is specifically designed to include the RV in the region of interest., Results: There were 76% men in group 1 and 94% in group 2 (P <0.05). The mean age was 65±20 in group 1 vs. 63±18 years in group 2 (P < 0.05). The stress type was exercise in 30% in group 1 and 35% in group 2, with the remaining patients studied with pharmacological stress testing (P = NS). The presence of RV reversible perfusion defects using filtered back projection was more evident in 13 patients (75%), while it was better seen with iterative reconstruction in 4 patients (25%). By automated analysis, the RV reversible perfusion defect size was 19 ± 14% of RV myocardium., Conclusion: This proof-of-principle study demonstrates that reversible RV perfusion defects suggestive of ischemia can be detected by SPECT myocardial perfusion imaging in some patients with LV inferior ischemia by visual analysis and can be quantitated by automated programs. Further studies on the diagnostic and prognostic relevance of assessing RV ischemia on SPECT MPI are needed.

"A quick glance at selected topics in this issue" aims to highlight contents of the Journal and provide a quick review to the readers.

Purpose: Noninvasive stress testing is commonly performed as part of pre-renal transplantation (RT) evaluation. We evaluated the prognostic value of myocardial perfusion imaging (MPI)-myocardial perfusion, left ventricular ejection fraction (LVEF) and heart rate response (HRR)-post-RT., Methods: Consecutive RT recipients were identified at our institution. MPI was considered abnormal when there was a perfusion defect or reduced ejection fraction. HRR to vasodilator stress was calculated as percentage change from baseline. The primary outcome was a composite of cardiovascular (CV) death, myocardial infarction (MI) and coronary revascularization (CR) post-RT; all-cause mortality was the secondary endpoint., Results: Among 1189 RT recipients, 819 (69%) underwent MPI. Of those, 182 (22%) had abnormal MPI, and 31 (4%) underwent CR pre-RT. During a median follow-up of 56 months post-RT, the annual CV event and mortality rates for patients who had no MPI, normal MPI and abnormal MPI were 1.5%, 3.1% and 4.3% (p < 0.001), and 1.8%, 2.6% and 3.6% (p = 0.016), respectively. After multivariate adjustment, compared to patients without MPI, the hazard ratios (HRs) for CV events for normal and abnormal MPI were 1.47 ([0.93-2.33], p = 0.1) and 1.78 ([1.03-3.06], p = 0.04). Blunted HRR was an independent predictor of CV events (HR = 1.73 [1.04-2.86], p = 0.034) and all-cause death (HR = 2.26 [1.28-3.98], p = 0.005) after adjusting for abnormal MPI. Patients with abnormal MPI who underwent CR pre-RT had annual mortality rates similar to those with no or normal MPI (1.9% vs. 1.7-2.6%, p = 0.2), while those who did not undergo CR had higher annual mortality (4% vs. 1.7-2.6%, p = 0.003)., Conclusions: One in five RT recipients who underwent screening MPI had an abnormal study, an independent predictor of CV events. A blunted HRR to vasodilator stress was associated with increased risk of CV events and death, even after adjusting for abnormal MPI. Patients with abnormal MPI who underwent CR were at low risk of mortality following RT. MPI is a useful tool to aid in risk stratification pre-RT.

Background: Myocardial perfusion imaging (MPI) has an established role in the work-up of coronary artery disease (CAD), but its comparative accuracy is debated in elderly patients. We examined a large administrative database to appraise the performance of MPI in octogenarians., Methods: Our institutional database was queried for patients undergoing MPI without recent coronary revascularization or myocardial infarction (MI). We compared baseline, procedural, diagnostic, and prognostic features in patients aged < 80 vs ≥ 80 years with bivariate and propensity-adjusted analyses., Results: From 13,254 patients, 12,737 (96.1%) were < 80 years old and 517 (3.9%) ≥ 80 years. Octogenarians were less likely to undergo exercise testing, had more severe and extensive myocardial ischemia (all P < 0.001), whereas CAD was more prevalent and diffuse in them (P = 0.012), and major adverse cardiac events more common during follow-up (P = 0.009). Diagnostic accuracy of MPI was similar or higher in octogenarians than in younger patients (e.g., sensitivity for three-vessel disease 92% in octogenarians vs 91% in younger patients), as was prognostic accuracy. Using propensity-matched analyses, MPI again yielded satisfactory prognostic accuracy in octogenarians., Conclusions: Use of MPI in octogenarians is associated with similar or better prognostic accuracy than in younger subjects.

Aims: Prior studies using stress myocardial perfusion imaging (MPI), which examined the association between obstructive epicardial coronary disease and presence of myocardial ischemia did not provide a detailed assessment on a regional level. We examined this relationship in a large population of patients in whom the coronary anatomy was defined by invasive coronary angiography., Methods: We retrospectively extracted details on individuals undergoing MPI with single photon emission computed tomography (SPECT) who had coronary angiography within 12 months. A 17-segment model for native coronary anatomy and a 7-region model for myocardial perfusion were used with a dedicated matching algorithm., Results: A total of 2564 patients were included, yielding a total of 6279 stenoses matched with 17 948 myocardial regions. From such a cohort, 151 (5.9%) patients had normal perfusion, 1878 (73.2%) had myocardial ischemia (reversible defects), 260 (10.1%) had myocardial necrosis (scar or fixed defects), and 275 (10.7%) had ischemia and necrosis. At per-patient analysis, significant angiographic disease was more common in the ischemic group (prevalence between 69.6 and 80.0%) than other groups. At per-region analysis, abnormal perfusion in the coronary-specific regions varied depending on location of stenosis; it was 96% for left main disease, 81% for proximal left anterior descending disease, 85% for proximal left circumflex disease, and 82% for proximal right coronary artery disease and <60% for posterior descending artery disease., Conclusion: The correlation between significant coronary stenosis and presence of corresponding regional perfusion abnormality depends on the location of the lesion and the corresponding myocardial region.

Cardiac sarcoidosis has long been an evasive diagnosis with a spectrum of clinical presentations that extend from asymptomatic to ventricular arrhythmias and sudden cardiac death. The diagnosis has traditionally relied on histology which suffers from the low sensitivity of endomyocardial biopsy due to the patchy nature of the disease in addition to its invasive nature. Due to significant advancements in imaging, it is now possible to accurately identify cardiac sarcoidosis using non-invasive imaging modalities even without histological confirmation. Emerging guidelines are highlighting the role of multimodality imaging in the diagnosis and management of this challenging entity. We present the case of a 36-year-old man known to have sarcoidosis in which a variety of imaging modalities not only assisted in the diagnosis of cardiac sarcoidosis, but also played a key role in the monitoring of disease activity and response to therapy.

As the second term of our commitment to Journal begins, we, the editors, would like to reflect on a few topics that have relevance today. These include prognostication and paradigm shifts; Serial testing: How to handle data? Is the change in perfusion predictive of outcome and which one? Ischemia-guided therapy: fractional flow reserve vs perfusion vs myocardial blood flow; positron emission tomography (PET) imaging using Rubidium-82 vs N-13 ammonia vs F-18 Flurpiridaz; How to differentiate microvascular disease from 3-vessel disease by PET? The imaging scene outside the United States, what are the differences and similarities? Radiation exposure; Special issues with the new cameras? Is attenuation correction needed? Are there normal databases and are these specific to each camera system? And finally, hybrid imaging with single-photon emission tomography or PET combined with computed tomography angiography or coronary calcium score. We hope these topics are of interest to our readers.

Background: Patients with advanced chronic kidney disease (CKD) have increased risk of myocardial infarction (MI). Silent MIs (SMIs) are common in CKD patients and carry increased mortality risk. The prevalence and prognostic value of SMI in advanced CKD has not been evaluated., Methods: We identified consecutive patients with advanced CKD who were evaluated for renal transplantation at the University of Alabama at Birmingham between June 2004 and January 2006. Clinical MI (CMI) was determined by review of medical records. SMI was defined as ECG evidence of MI without clinical history of MI. The primary end-point was a composite of death, MI, or coronary revascularization censored at time of renal transplantation., Results: The cohort included 1007 patients with advanced CKD aged 48±12years (58% men, 43% diabetes, 75% on dialysis). The prevalence of SMI and CMI was 10.7% and 6.7%, respectively. The only independent predictor of SMI was older age (odds ratio for age ≥50yrs. 2.32, p<0.001). During a median follow-up of 28months, 376 (37%) patients experienced the primary outcome (33% death, 2% MI, 5% coronary revascularization). In a multivariable adjusted Cox-regression model, both SMI (adjusted HR 1.58, [1.13-2.20], p=0.007) and CMI (adjusted HR 1.67 [1.15-2.43], p=0.007) were independently associated with the primary outcome. Further, both SMI (HR 2.37 [1.15-4.88], p=0.02) and CMI (HR 4.02 [1.80-8.98], p=0.001) were associated with increased risk after renal transplantation., Conclusions: SMI is more common than CMI in patients with advanced CKD. Both SMI and CMI are associated with increased risk of future cardiovascular events., (Published by Elsevier B.V.)

A quick glance at selected topics in this issue aims to highlight contents of the Journal and provide a quick review to the readers.

Objectives: This study sought to summarize the evidence on stress myocardial perfusion imaging (MPI) using cadmium-zinc-telluride (CZT) technology for the diagnosis of obstructive coronary artery disease (CAD). The CZT cameras are newly introduced, and comparative data with the conventional Anger technology (Anger-MPI) are lacking., Background: The diagnostic accuracy of Anger-MPI for detection of angiographically significant CAD is well established; however, less evidence is available on the diagnostic accuracy of CZT-MPI., Methods: Clinical studies comparing CZT-MPI and invasive coronary angiography were systematically searched and abstracted. Calculations of diagnostic accuracy, including sensitivity, specificity, likelihood ratios, and diagnostic odds ratio, were obtained with fixed and random effects, reporting point estimates and 95% confidence intervals., Results: Based on our search, a total of 16 studies (N = 2,092) were included. The sensitivity of CZT-MPI was 0.84 (95% confidence interval [CI]: 0.78 to 0.89), whereas the specificity of 0.69 (95% CI: 0.62 to 0.76) was significantly reduced. The positive likelihood ratio was 2.73 (95% CI: 2.21 to 3.39), the negative likelihood ratio was 0.24 (95% CI: 0.17 to 0.31), and the diagnostic odds ratio was 11.93 (95% CI: 7.84 to 17.42). At subgroup and meta-regression analyses, the diagnostic accuracy between D-SPECT and Discovery cameras was similar (p = 0.711) and not impacted upon by smaller sample size studies (p = 0.573)., Conclusions: CZT-MPI has satisfactory sensitivity for angiographically significant CAD, but its suboptimal specificity warrants further development and research., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

We recently showed that Quantitative Perfusion SPECT (QPS), Emory Cardiac Toolbox (ECTb) and 4-Dimension-Myocardial SPECT (4DM) yielded discordant results in the assessment of perfusion defect size (PDS) in patients with known or suspected coronary artery disease. In this report, we examined the sources of variability in the measurement of PDS using ECTb (Var ECTb ), 4DM (Var 4DM ) and QPS (Var QPS ) and found that gender is a source of variability in the assessment of PDS. In 120 patients, Var ECTb was lower in men, compared with women, whereas Var 4DM and Var QPS were similar between both genders. Among men, Var ECTb was lowest, compared with Var QPS and Var 4DM , whereas, Var ECTb , Var QPS , and Var 4DM were not different among women. Future studies should account for gender differences when comparing the 3 software programs.

Background: The prognostic value of left ventricular dyssynchrony measured by gated single-photon emission computed tomography (GSPECT) myocardial perfusion imaging (MPI) and its relationship to electrical dyssynchrony measured by QRS duration are incompletely understood. The aim of this study was therefore to examine the independent and incremental prognostic value of dyssynchrony in yet the largest group of patients with coronary artery disease (CAD)., Methods and Results: Patients presenting for GSPECT- MPI between July 1993 and May 1999 in normal sinus rhythm were identified from the Duke Nuclear Cardiology Databank and the Duke Databank for Cardiovascular Disease (N = 1244). After a median of 4.2 years, 336 deaths occurred. At 8 years, the Kaplan-Meier estimates of the probability of death were 34.0% among patients with a phase bandwidth <100° and 56.8% among those with a bandwidth ≥100°. After adjustment for standard clinical variables, QRS dyssynchrony was independently associated with death (Hazard Ratio (HR), per 10°: 1.092, 95% Confidence Interval (CI) 1.048,1.139, P < .0001). Phase bandwidth was similarly associated with death after clinical adjustment (HR per 10°: 1.056, 95% CI 1.041,1.072, P < .0001). In clinically adjusted models examining QRS duration in addition to phase bandwidth, phase bandwidth had a stronger association with mortality. After accounting for left ventricular ejection fraction (LVEF), neither QRS duration nor phase bandwidth were statistically significant. Among patients with EF >35%, QRS duration and phase bandwidth together provided value above that provided by LVEF alone (P = 0.0181). When examining cardiovascular death, results were consistent with all-cause death., Conclusions: Among patients with CAD, mechanical left ventricular dyssynchrony measured by GSPECT MPI has a stronger relationship with outcomes than electrical dyssynchrony measured by QRS duration. After adjustment for baseline characteristics and LVEF, neither mechanical nor electrical dyssynchrony is independently associated with all-cause death or cardiac death. Among patients with EF >35%, mechanical and electrical dyssynchrony together provided prognostic value above that afforded by LVEF.