Andreas A. Giannopoulos

Imaging the event-prone coronary artery plaque

Acute coronary events, the dreaded manifestation of coronary atherosclerosis, remain one of the main contributors to mortality and disability in the developed world. The majority of those events are associated with atherosclerotic plaques-related thrombus formation following an acute disruption, that being rupture or erosion, of an event-prone lesion. These historically termed vulnerable plaques have been the target of numerous benchtop and clinical research endeavors, yet to date without solid results that would allow for early identification and potential treatment. Technological leaps in cardiovascular imaging have provided novel insights into the formation and role of the event-prone plaques. From intracoronary optical coherence tomography that has enhanced our understanding of the pathophysiological mechanisms of plaque disruption, over coronary computed tomography angiography that enables non-invasive serial plaque imaging, and positron emission tomography poised to be rapidly implemented into clinical practice to the budding field of plaque imaging with cardiac magnetic resonance, we summarize the invasive and non-invasive imaging modalities currently available in our armamentarium. Finally, the current status and potential future imaging directions are critically appraised.

Hybrid Imaging in Ischemic Heart Disease

Hybrid imaging for ischemic heart disease refers to the fusion of information from a single or usually from multiple cardiovascular imaging modalities enabling synergistic assessment of the presence, the extent, and the severity of coronary atherosclerotic disease along with the hemodynamic significance of lesions and/or with evaluation of the myocardial function. A combination of coronary computed tomography angiography with myocardial perfusion imaging, such as single-photon emission computed tomography and positron emission tomography, has been adopted in several centers and implemented in international coronary artery disease management guidelines. Interest has increased in novel hybrid methods including coronary computed tomography angiography-derived fractional flow reserve and computed tomography perfusion and these techniques hold promise for the imminent diagnostic and management approaches of patients with coronary artery disease. In this review, we discuss the currently available hybrid noninvasive imaging modalities used in clinical practice, research approaches, and exciting potential future technological developments.

Impact of cardiac hybrid imaging-guided patient management on clinical long-term outcome

BACKGROUND Although randomized trials have provided evidence for invasive fractional flow reserve to guide revascularization, evidence for non-invasive imaging is less well established. The present study investigated whether hybrid coronary computed tomography (CCTA)/single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) can identify patients who benefit from early revascularization compared to medical therapy. METHODS This retrospective study consists of 414 patients referred for evaluation of known or suspected coronary artery disease (CAD) with CCTA/SPECT hybrid imaging. CCTA categorized patients into no CAD, non-high-risk CAD and high-risk CAD. In patients with CAD (n = 329), a matched finding (n = 75) was defined as a reversible perfusion defect in a territory subtended by a coronary artery with CAD. All other combinations of pathologic findings were classified as unmatched (n = 254). Death, myocardial infarction, unstable angina requiring hospitalization, and late coronary revascularization were defined as major adverse cardiac events (MACE). Cox hazards models included covariates age, male gender, more than two risk factors, previous CABG, high-risk CAD and early revascularization. RESULTS During median follow-up of 6.0 years, 112 patients experienced a MACE (27%). Early revascularization (n = 50) was independently associated with improved outcome among patients with a matched finding (p < 0.001). There was no benefit among patients with an unmatched finding (p = 0.787), irrespective of presence (p = 0.505) or absence of high-risk CAD (p = 0.631). CONCLUSIONS Early revascularization is associated with an outcome benefit in CAD patients with a matched finding documented by cardiac hybrid imaging while no benefit of revascularization was observed in patients with an unmatched finding.

Triple hybrid imaging of a high-risk coronary plaque: morphology, perfusion, and haemorheology

A sixty-one-year-old man with a history of hyperlipidaemia, arterial hypertension, positive family history, smoking, and atypical angina pectoris was referred for investigation of coronary artery disease. (Panel A) Coronary computed tomography angiography (CCTA) revealed a non-stenotic atherosclerotic plaque located in the left main (LM) and the proximal left anterior descending artery (pLAD), exhibiting high-risk plaque features including napkin-ring sign, low attenuation, and positive external remodelling. Non-stenotic calcified lesions were also found in the mid-LAD and proximal right coronary artery. (Panel B) The patient underwent a N-NH3 positron emission tomography–myocardial perfusion imaging (PETMPI) test, which showed no perfusion abnormalities and normal myocardial flow reserve (MFR). (Panel C) Hybrid imaging allowing coregistration of CCTA and PETMPI demonstrated normal perfusion in the LAD territory. (Panel D) Computational simulation of local haemorheological parameters revealed (Panel Da) an area of normal endothelial shear stress (ESS) and normal velocity at LM, (Panel Db) an area of high ESS and high velocity at the most stenosed part of the high-risk lesion, and (Panel Dc) an area of low ESS and turbulent flow at the downstream plaque shoulders. Sustained low ESS increases local thrombogenicity and holds a proatherogenic role activating molecular cascades implicated in thin-cap fibroatheroma formation. The patient was prescribed high-dose statin and a short 2-year follow-up with non-invasive imaging was recommended. Such non-invasive triple hybrid imaging integrating coronary morphology, myocardial perfusion, and local haemorheology may provide a novel comprehensive multi-parametric assessment of coronary atherosclerotic risk, advance our pathophysiological understanding of atherothrombotic complications, and inform decision-making towards optimal patient management.

Sports Behavior in Middle-Aged Individuals with Anomalous Coronary Artery from the Opposite Sinus of Valsalva

Objectives: Recommendations regarding sports restriction are lacking for middle-aged athletes with anomalous coronary arteries originating from the opposite sinus of Valsalva (ACAOS). Methods: Sixty-three patients with ACAOS were subdivided into ACAOS with (n = 38) or without (n = 25) an interarterial course (IAC). Sports behavior, either competitive (COMP) or recreational (REC), was evaluated at the time of diagnosis and after a median follow-up of 4.2 years. Results: Mean age was 56 ± 11 years and 48 (76.2%) patients were engaged in sports. Three individuals (4.8%) were surgically corrected after diagnosis. Thirty-eight (60.3%) patients were aware of their diagnosis at follow-up and 12 (19.0%) were counseled by their physician about sports restrictions. Sports behavior at the time of diagnosis and at follow-up did not differ significantly, neither in patients engaged in COMP (17.5 vs. 12.7%, p = 0.619) nor those engaged in REC (58.7 vs. 61.9%, p = 0.856). Sport-related symptoms were not significantly different between ACAOS patients with and without IAC. No athlete had died at follow-up. Conclusions: The majority of middle-aged individuals with ACAOS were involved in sports activities at the time of diagnosis and at follow-up. Awareness and counseling about ACAOS diagnosis had no significant effect on sports behavior. IAC did not have an impact on sport-related symptoms, and outcomes were favorable in all athletes, regardless of surgical correction.

Age- and sex-dependent changes in sympathetic activity of the left ventricular apex assessed by 18F-DOPA PET imaging

Background Sexual dimorphism in cardiac sympathetic outflow has recently gained attention in the context of Takotsubo cardiomyopathy. Previous studies suggest that there are sex- and age-dependent differences in peripheral autonomic control, however, data on cardiac-specific sympathetic activation in aged women and men are lacking. Methods and results Regional quantitative analysis of cardiac fluorine-18 (18F)- Dihydroxyphenylalanine (DOPA) uptake was retrospectively performed in 133 patients (69 females, mean age 52.4±17.7 years) referred for assessment of neuroendocrine tumours (NET) by Positron-Emission-Tomography. Cardiac 18F-DOPA uptake was significantly higher in women as compared to men (1.33±0.21 vs. 1.18±0.24, p<0.001). This sex-difference was most pronounced in the apical region of the left ventricle (LV, 1.30±0.24 in women vs. 1.13±0.25 in men, p<0.001) and in individuals >55 years of age (1.39±0.25 in women vs. 1.09±0.24 in men, p<0.001). Women showed a prominent increase in myocardial 18F-DOPA uptake with age with the strongest increase seen in the LV apical region (r = 0.34, p = 0.004). Accordingly, sex and age were selected as significant predictors of LV apical 18F-DOPA uptake in a stepwise linear regression model. No age-dependent changes of cardiac 18F-DOPA uptake were observed in men or in the right ventricular region. Conclusion Our study suggests that aging is related to sex-specific changes in regional cardiac sympathetic activity. Future studies will have to assess whether the increase in LV apical 18F-DOPA uptake with age in women is of pathogenic relevance for the higher susceptibility of postmenopausal women to conditions associated with increased sympathetic activity.

A further step towards getting cardiac respiratory motion under control

Single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) is a widely available and well-established non-invasive modality for the evaluation of ischemic coronary artery disease. Although technological advances have enabled implementation of other functional cardiovascular imaging modalities into clinical practice, SPECT-MPI promises to continuously hold a pivotal role into the diagnostic assessment of the cardiovascular patient whereby the ongoing departure from the conventional orbiting sodium iodide (NaI) detector-based SPECT cameras and introduction of cadmium-zinc-telluride (CZT) solidstate detector-based gamma cameras has certainly played a crucial role. The superior sensitivity of CZT detectors over traditional NaI detectors and sophisticated newest generation iterative reconstruction algorithms in combination with instantaneous acquisition of tomographic data without the need of detector rotation provides superior count rate, reduction of image noise and significant improvement in spatial resolution and overall superior image quality while enabling decreased acquisition time and/or radiotracer activity and intermittent scanning. However, on a per-patient basis, the diagnostic performance of the modern-era cameras has not yet been proven to be superior to conventional SPECT gamma cameras. Moreover, the cost of CZT camera systems remains a controversial topic, alongside several other inherent limitations. Among the latter, detection and correction of patient and respiratory motion constitute a field of ongoing research. While reduced acquisition time enabled by CZT technology may substantially reduce the prevalence of artifacts due to patient motion, respiratory motion remains a more delicate source of artifacts as it is a quite complex threedimensional movement occurring predominantly in— but not limited to—the craniocaudal axis, potentially causing artifacts in the inferior wall. While several approaches have been proposed for cardiac respiratory motion detection, including external respiratory sensors or infrared cameras, motion correction remained challenging for SPECT-MPI with conventional gamma cameras using rotating detectors in a step-and-shoot mode. By contrast, the stationary design of a CZT system with data acquisition in list mode has paved the way for a more elegant solution, namely, through purely data-driven cardiac respiratory motion detection and correction. To date, however, quantification of a potentially beneficial impact of such algorithms on SPECT-MPI is lacking. In the current issue of the Journal of Nuclear Cardiology, Daou et. al. assess the impact of such purely data-driven cardiac respiratory motion correction on the extent and severity of (apparent) myocardial perfusion defects. After demonstrating applicability and feasibility of a motion detection and correction software algorithm (REGAT), the authors now translate their preliminary findings into clinical routine by examining its practical implementation in a small sample of patients: In 25 patients undergoing 1-day stress/rest Tc-tetrofosmin SPECT-MPI acquired on a CZT camera, the severity and extent of myocardial perfusion defects were compared with and without respiratory motion correction on a visual as well as on a semi-quantitative basis in a total of 49 combined stress and rest studies. On visual assessment, correction for respiratory motion had an impact on the extent and/or severity of a myocardial perfusion defect in 7 of 49 studies (14%), leading to a Reprint requests: Ronny R. Buechel, MD, Cardiac Imaging, Department of Nuclear Medicine, University Hospital Zurich, Raemistrasse 100, Zurich 8091, Switzerland; ronny.buechel@usz.ch J Nucl Cardiol 2018;25:1310–2. 1071-3581/

Cardiovascular risk prediction models with myocardial perfusion imaging in chronic kidney disease: ACCESSing digits or focusing on the patient?

34.00 Copyright 2017 American Society of Nuclear Cardiology.

Do we really need to look at volumetric measurements with 99mTc single photon emission computed tomography (SPECT) myocardial perfusion imaging

Cardiovascular disease (CVD) remains the leading cause for mortality worldwide. Prevention strategies and the pursuit for predictors of CVD as well as the associated mortality have given rise to several statistical models and algorithms aiming to predict future events. The multifactorial nature of CVD and the interactions between genetic, social, and environmental risk factors complicate accurate risk assessment. Commonly, multiparametric prediction models include well known risk factors such as age, gender, smoking, dyslipidemia, hypertension, and diabetes and have been shown to improve our ability for prevention and enhanced screening of patients at risk for cardiovascular events. Nevertheless, in the clinical world such prediction models face several issues that humper its implementation. While the demand for population-adjusted risk scores has increased, the dynamic nature of the disease as well as of the risk factors aggravates the creation of an integrated risk assessment scoring system for all populations. In addition to the eminent Framingham study numerous different models have been investigated such as the Europe British/Scottish Regional HeartStudies or the Munster Cardiovascular Study (PROCAM). On top of clinical risk factors, incorporation of cardiac imaging test results has been shown to possess incremental value for the development of new risk stratification strategies. To that end, nuclear imaging primarily with the stress myocardial perfusion single-photon emission-computed tomography (SPECT) myocardial perfusion imaging (MPI) represents one of the best investigated modality for risk assessment with regards to myocardial infarction. In addition to sole risk stratification, SPECT-MPI further influences management decisions since patients with moderate to large areas of inducible ischemia are more likely to have a survival benefit from revascularization therapy vs. medical treatment. In order to develop a risk score for the Japanese population, the J-ACCESS studies-family, that initiated close to 20 years ago, established a database including more than 4000 patients and investigated the prognostic value of Tc-tetrofosmin SPECT-MPI in the prognosis of patients with ischemic heart disease. Cardiac event risk estimation was based amongst others on myocardial perfusion defects during stress (using summed stress score), left ventricular ejection fraction (LVEF), age, and presence of diabetes mellitus. Although annual cardiovascular events were significantly lower in Japan compared to those in the USA and Europe, it was shown that cardiovascular event rates were higher in patients with larger perfusion defects and reduced LVEF. Follow-up studies, such as the JACCESS-3 demonstrated the ability and usefulness of SPECT-MPI to predict 3-year outcomes in patients with chronic kidney disease (CKD), a condition well associated with the risk of death, hospitalization as well as cardiovascular events. To complement these previous findings, in the current issue of the Journal, Nakajima et al. investigated the accuracy of three risk models derived from the J-ACCESS study to predict major events in a new cohort Reprint requests: Andreas A. Giannopoulos, MD, PhD, Cardiac Imaging, Department of Nuclear Medicine, University Hospital Zurich, Ramistrasse 100, 8091 Zurich, Switzerland; andreas.giannopoulos@usz.ch J Nucl Cardiol 2020;27:51–2. 1071-3581/

Acute right ventricular myocardial infarction

34.00 Copyright 2018 American Society of Nuclear Cardiology.