Abstract Stress MPI using SPECT is widely used for CAD detection and risk stratification. While exercise is the preferred mode of stress in the majority of patients, pharmacologic stress is recommended for patients who have exercise limitations and patients with ventricular pre-excitation, LBBB, or artificially paced rhythms. Pharmacologic stress agents produce coronary hyperemia by completely different sets of mechanisms than exercise, but the hyperemia achieved with these agents is at least as intense as that achieved by maximal exercise. This chapter will discuss the pharmacology, mechanisms of action, hemodynamic effects, safety, and side effect profiles of the pharmacologic stress agents used for MPI and the protocols used with these agents either alone or when combined with exercise. The chapter also includes a description of the utility of pharmacologic stress MPI data on clinical management.

BACKGROUND Implantable cardioverter-defibrillators (ICDs) improve outcomes in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) <= 35%. Less is known about whether outcomes varied between the 2 noninvasive imaging modalities used to estimate LVEF-2-dimensional echocardiography (2DE) and multigated acquisition radionuclide ventriculography (MUGA)-which use different principles (geometric vs countbased, respectively). OBJECTIVE The purpose of this study was to examine whether the effect of ICD on mortality in patients with HF and LVEF <= 35% varied on the basis of LVEF measured by 2DE or MUGA. METHODS Of the 2521 patients with HF with LVEF <= 35% in the Sudden Cardiac Death in Heart Failure Trial, 1676 (66%) were randomized to either placebo or ICD, of whom 1386 (83%) had LVEF measured by 2DE (n 5 971) or MUGA (n 5 415). Hazard ratios (HRs) and 97.5% confidence intervals (CIs) for mortality associated with ICD were estimated overall, checking for interaction, and within the 2 imaging subgroups. RESULTS Of the 1386 patients in the present analysis, all-cause mortality occurred in 23.1% (160 of 692) and 29.7% (206 of 694) of patients randomized to ICD or placebo, respectively (HR 0.77; 97.5% CI 0.61-0.97), which is consistent with that in 1676 patients in the original report. HRs (97.5% CIs) for all-cause mortality in the 2DE and MUGA subgroups were 0.79 (0.60-1.04) and 0.72 (0.461.11), respectively (P 5.693 for interaction). Similar associations were observed for cardiac and arrhythmic mortalities. CONCLUSION We found no evidence that in patients with HF and LVEF <= 35%, the effect of ICD on mortality varied by the noninvasive imaging method used to measure LVEF.

In this issue, two highly respected authors (Steven Port, MD and Timothy Bateman, MD) debate the use of coronary angiography vs. nuclear imaging in a hypothetical patient with symptoms consistent with anginal chest pains and who has a high coronary calcium score.This topic is central to patient care and the debate is likely to be helpful to patient care providers and to the imaging community.

1,2 I combined both titles for my last Editor's Page.The new team, with my good friend Marcelo Di Carli, MD as the 4th EIC, will start their term on July 1, 2023.My team will continue through the end of December 2023, handling manuscripts in the revision stages awaiting disposition, and the last three printed issues of 2023.The JNC underwent transformation during its third decade, when major changes occurred in the field, such as the increased use of positron emission tomography, myocardial blood flow measurements, imaging of infiltrative, vascular, inflammatory, and infective diseases, and the use of artificial intelligence to mention only few.These changes were accompanied by increases in the number of submissions, especially from outside the USA (Figures 1 and2).The Journal also diversified the types of published manuscripts (Table 1).We also began translating the abstracts of lead articles to three languages handled by members of our Board.The original articles and brief reviews have accompanying Power-Point slides, Twitter, and audio recordings.Each printed issue has a photo, a meaningful quote, and a poem; the late Barry

We have shown that silent myocardial infarction (SMI) on 12-lead ECG is associated with increased cardiovascular disease (CVD) risk in patients awaiting renal transplantation (RT). In this study, we evaluated the prevalence of SMI in patients undergoing RT and their prognostic value after RT. MI was determined by automated analysis of ECG. SMI was defined as ECG evidence of MI without a history of clinical MI (CMI). The primary outcome was a composite of CVD death, non-fatal MI and coronary revascularization after RT. Of the 1189 patients who underwent RT, a 12-lead ECG was available in >99%. Of the entire cohort 6% had a history of CMI while 7% had SMI by ECG. During a median follow-up of 4.6 years, 147 (12%) experienced the primary outcome (8% CVD death, 4% MI, 4% coronary revascularization) and 12% died. Both SMI and CMI were associated with an increased risk of CVD events and all-cause deaths. In a multivariable adjusted Cox-regression model, both SMI (adjusted hazard ratio 2.03 [1.25-3.30], p = .004) and CMI (2.15 [1.24-3.74], p = .007) were independently associated with the primary outcome. SMI detected by ECG prior to RT is associated with increased risk of CVD events after RT.

perspectives (background, prior work, summary of current report), 2. Outline strengths and limitations and new findings if any and their application, and 3. Outline future directions.

BACKGROUND:SPECT myocardial perfusion imaging (MPI) provides an assessment of LV mechanical dyssynchrony (LVMD) which correlates with CVD outcomes in diverse populations including those awaiting renal transplant (RT). The current study examines the association of LVMD on pre-transplant MPI with long-term CVD mortality post RT.METHODS:We identified consecutive patients who underwent RT at the University of Alabama at Birmingham between 2008 and 2012 from our prospectively collected database. 675 patients in the database underwent MPI and had images amenable for phase analysis. A blinded investigator retrieved the studies and derived LVMD indices including histogram bandwidth (BW), standard deviation (SD), phase peak, phase skewness, and phase kurtosis. The primary outcome was CVD death after RT.RESULTS:The study cohort had a median age of 54 years, 56% were men, 43% had diabetes, and 7% had prior myocardial infarction. Patients were on dialysis for a median of 3.4 years prior to RT and 34% received living donor transplants. During a median follow-up time after RT of 4.7 years (IQR 3.5 to 6.3 years) 59 patients (9%) succumbed to CVD death. Patients with wider BW, wider SD, lower skewness, and lower kurtosis had an increased risk of CVD death. On multivariate adjustment, BW and skewness remained as independent predictors of CVD deaths.CONCLUSIONS:LVMD by phase analysis of gated SPECT MPI is associated with increased risk of CVD death after RT. This association is independent of demographics, comorbidities, and traditional findings on MPI and added incremental prognostic information. Assessment of LVMD should be considered for risk stratification in these patients.

The ECG findings during sudden collapse (syncope or sudden death) in severe aortic stenosis (AS) are not well defined. We conducted a comprehensive review of the literature for ECG data during sudden collapse in patients with AS and provided a case report of our own. There were 37 published cases of syncope or sudden death in patients with severe AS which were documented by ECG. Brady- or ventricular arrhythmias were documented in 34 cases (92%). Bradyarrhythmia (n = 24; 71%) was more common at the time of collapse than ventricular tachyarrhythmia (n = 10; 29%). There was slowing of the sinus rate before bradyarrhythmia in the vast majority of patients with bradyarrhythmia but not in those presenting with ventricular tachyarrhythmia (75% vs 0%; p <0.001). ECG evidence of ischemia (ST-segment depression or elevation) was present in most patients with bradyarrhythmia but not in those with ventricular tachyarrhythmia (75% vs 0%; p = 0.011). In conclusion, our findings suggest that left ventricular baroreceptor activation plays a dominant role in the pathophysiology of sudden collapse in patients with severe AS and suggest that ischemia may play a role as well.

BACKGROUND:A low right ventricular ejection fraction (RVEF) is a marker of poor outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Beta-blockers improve outcomes in HFrEF, but whether this effect is modified by RVEF is unknown. METHODS AND RESULTS:Of the 2798 patients in Beta-Blocker Evaluation of Survival Trial (BEST), 2008 had data on baseline RVEF (mean 35%, median 34%). Patients were categorized into an RVEF of less than 35% (n = 1012) and an RVEF of 35% or greater (n = 996). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) within each RVEF subgroup and formally tested for interactions between bucindolol and RVEF. The effect of bucindolol on all-cause mortality in 2008 patients with baseline RVEF (HR 0.88, 95% CI 0.75-1.02) is consistent with that in 2798 patients in the main trial (HR 0.90, 95% CI 0.78-1.02). Bucindolol use was associated with a lower risk of all-cause mortality in patients with an RVEF of 35% or greater (HR 0.70, 95% CI 0.55-0.89), but not in those with an RVEF of less than 35% (HR 1.02, 95% CI 0.83-1.24, P for interaction = .022). Similar variations were observed for cardiovascular mortality (P for interaction = .009) and sudden cardiac death (P for interaction = .018), but not for pump failure death (P for interaction = .371) or HF hospitalization (P for interaction = .251). CONCLUSIONS:The effect of bucindolol on mortality in patients with HFrEF was modified by the baseline RVEF. If these hypothesis-generating findings can be replicated using approved beta-blockers in contemporary patients with HFrEF, then RVEF may help to risk stratify patients with HFrEF for optimization of beta-blocker therapy.

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.

We at JNC, the nuclear cardiology community, the cardiovascular community, the medical profession, and humanity at large mourn the loss of Henry Gewirtz, MD.He affected each one of us in his unique way and in the process advanced our understanding of the principles and applications of coronary physiology and cardiac imaging.