REVIEW ARTICLE Multi-modality imaging: Bird’s-eye view from the 2014 American Heart Association Scientific Sessions Wael A. AlJaroudi, MD, FACC, FAHA, FESC,a Andrew J. Einstein, MD, PhD, FACC, FACP, FAHA, FASNC,b Farooq A. Chaudhry, MD, FACP, FACC, FASE, FAHA,c Steven G. Lloyd, MD, PhD, FACC,d,e and Fadi G. Hage, MD, FASH, FACCd,e a

American University of Beirut Medical Center, Beirut, Lebanon Columbia University Medical Center/New York Presbyterian Hospital, New York, NY c Icahn School of Medicine at Mount Sinai, New York, NY d University of Alabama at Birmingham, Birmingham, AL e Birmingham Veterans Affairs Medical Center, Birmingham, AL b

Received Jan 4, 2015; accepted Jan 4, 2015 doi:10.1007/s12350-015-0076-9

A large number of studies were presented at the 2014 American Heart Association Scientific Sessions. In this review, we will summarize key studies in nuclear cardiology, computed tomography, echocardiography, and cardiac magnetic resonance imaging. This brief review will be helpful for readers of the Journal who are interested in being updated on the latest research covering these imaging modalities. Key Words: SPECT Æ CT Æ echocardiography Æ MRI

INTRODUCTION The 2014 American Heart Association (AHA) Scientific Sessions held in Chicago, IL from Nov 15 to 19 was an eventful scientific conference that highlighted late-breaking clinical trials in several areas including trials covering the risks and benefits of dual antiplatelet therapy, anti-lipid therapy and prevention of coronary artery disease (CAD), treatment of structural heart disease, and drugs, devices, and systems of care for ischemic heart disease. Similar to the reviews covering the 2014 American College of Cardiology Scientific Sessions1 and European Society of Cardiology Congress,2 we review here key abstracts presented at AHA 2014 in the imaging arena. Four authors were invited with expertise in nuclear cardiology (WAA), cardiac computed tomography (CT, AJE), echocardiography (FAC), and cardiac magnetic

Reprint requests: Fadi G. Hage, MD, FASH, FACC, University of Alabama at Birmingham, Lyons Harrison Research Building 314, 1900 University BLVD, Birmingham, AL 35294; [email protected] 1071-3581/$34.00 Copyright Ó 2015 American Society of Nuclear Cardiology.

resonance imaging (CMR, SGL). Each was charged with summarizing abstracts that they found of most interest in their area. An Associate Editor (FGH) integrated these parts together in this review. We hope that this bird’seye view from the AHA Scientific Sessions will keep you updated on the newest imaging studies presented here whether or not you were able to attend the conference.

NUCLEAR CARDIOLOGY AHA 2014 witnessed several breakthrough and scientific advances in the realm of cardiac single-photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging. In patients with acute coronary syndrome, the measured infarct zone often underestimates the true myocardial injury area that includes the area at risk. A new tracer, Tc-99-duramycin, was investigated by Johnson et al3 as surrogate marker to measure the global myocardial injury area based on changes in cellular membrane organization. Using a pig model of acute myocardial infarction (coronary occlusion followed by mechanical reperfusion

AlJaroudi et al. Multi-modality imaging: Bird’s-eye view

using balloon angioplasty), Tc-99m-duramycin SPECT/ CT images acquired on day 1 after injury showed significant uptake in infarcted (validated against tetrazolium staining) and non-infarcted but ischemically damaged myocardium (using Evan blue dye). The latter area consisted histologically of a heterogenous mix of viable and non-viable cells, thus a potential substrate for arrhythmias. Imaging the global myocardial injury area may have prognostic value. The role of PET fludeoxyglucose 18F (FDG) in evaluating hibernating myocardium is well established. The PET and Recovery Following Revascularization-2 or PARR-2 trial randomized patients with ischemic cardiomyopathy to PET-guided vs standard care for decision on revascularization based on the presence of hibernating myocardium. In a post hoc analysis, Ardle et al4 presented the 5-year outcome of the trial (n = 231). Although there was no difference in composite endpoint (cardiac death, myocardial infarction, re-hospitalization) between the groups, there was significantly lower events among those who adhered to the imaging recommendations (HR 0.72, 95% CI 0.540.97). Furthermore, there was significant interaction between presence of hibernating myocardium and outcome and benefit from revascularization when the hibernating myocardium burden was [4% of the LV mass. Therefore, the use of PET FDG to direct revascularization may improve long-term outcomes. These data challenge the results of the STICH trial. Although the prognostic value of PET myocardial perfusion imaging (MPI) is well established, there are limited data in patients with diabetes. Skali et al5 studied 6,037 patients (27% with diabetes) that underwent stress PET imaging. While diabetic patients had more than twofold risk for cardiac death vs those without diabetes, adding results of the MPI stress testing resulted in net reclassification of half of the patients in each group. Hence, PET MPI is a strong independent predictor of cardiac events in diabetic and non-diabetic patients and adds incremental value beyond traditional risk factors in both groups. Coronary flow reserve (CFR) by PET has been demonstrated to have prognostic and incremental values. In patients who had coronary artery bypass grafting (CABG), CFR is often impaired but little is known about its prognostic value. Kato et al6 studied 567 patients with prior CABG undergoing stress PET MPI for chest pain assessment (median time between CABG and MPI was 10 years). After adjusting for clinical risk score, history of myocardial infarction, time from CABG, ischemia and scar score on MPI, and left ventricular ejection fraction (LVEF), a higher CFR was associated with lower primary endpoint (all-cause death) (HR 0.93, 95% CI 0.90-0.97 per 0.1 unit increase) and secondary

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endpoints (all-cause death and non-fatal myocardial infarction) (HR 0.94, 95% CI 0.91-0.97, per 0.1 unit increase). CFR measurement in patients with prior CABG improves risk stratification and is a useful addon tool. In 2010, the US Food and Drug Administration issued an initiative to reduce unnecessary radiation exposure from medical imaging. Russo et al7 reviewed the medical records of patients that underwent cardiac stress testing in a single institution over 10 years period (2003-2012) during which time more than 50 thousand patients underwent 88 thousand stress tests. Adopting a stress-first/stress-only protocol (if normal stress imaging), based on a normal test rate of 57% over the study period, would have decreased the aggregate radiation exposure by 25%. Assessment of cardiac sarcoidosis using multimodality imaging has received a lot of attention in the last few years. PET imaging using FDG and rubidium82 is a useful non-invasive semi-quantitative technique in the diagnosis and management of cardiac sarcoidosis (Figure 1).8 The presence of active inflammation can also be quantified using standardized uptake value (SUV). Bazylevska et al9 retrospectively analyzed 83 patients with proven or suspected cardiac sarcoidosis undergoing cardiac PET imaging and assessed SUV in relation to PET interpretation and prognostic value. Patients with abnormal FDG uptake had threefold increased risk of death, sudden cardiac death, new ventricular tachycardia, shock, or heart transplantation. Using quantitative assessment, SUV heterogeneity (maximal-minimal SUV [ 0.56 g
mL-1) accurately represented abnormal FDG uptake (ROC area under curve of 0.82) with independent prognostic value (HR 3.77, 95% CI 1.15-12.4). Nuclear cardiac imaging may have a novel role in the assessment of arrhythmic risk. Indeed, abnormal cardiac innervation plays a critical role in ventricular arrhythmia. Klein et al10 evaluated 15 patients with ischemic cardiomyopathy undergoing sympathetic innervation imaging using 123I mIBG SPECT prior to ventricular tachycardia ablation. The 123I mIBG innervation defect zone was significantly larger than the traditional voltage defined-scar zone. The focus of the ventricular arrhythmia was identified in the area of preserved voltage but abnormal innervation (area at risk). Hence, 3D mIBG innervation mapping may play a role in guiding ventricular tachycardia ablation in patients with ischemic cardiomyopathy. CARDIAC COMPUTED TOMOGRAPHY The 2014 AHA Scientific Sessions witnessed numerous important scientific advances in the field of cardiac

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AlJaroudi et al. Multi-modality imaging: Bird’s-eye view

Figure 1. FDG-PET imaging protocol for cardiac sarcoidosis. After appropriate patient preparation, rest perfusion scanning is performed first. Intravenous heparin is then given in divided doses after which the patient is injected with FDG. After an uptake phase of at least 60 minutes, both a whole body and a dedicated cardiac scan are performed with CT attenuation correction (CTAC) scans performed before each PET scan (Reproduced with permission from Ref. 8).

CT. In a late-breaking clinical trial presentation, Dr. Brent Muhlestein presented the primary results of the Screening for Asymptomatic Obstructive Coronary Artery Disease among High-Risk Diabetic Patients Using CT Angiography, Following Core 64 Trial (FACTOR-64), which was simultaneously published in JAMA.11 This trial randomized 900 patients in a single healthcare system with type I or II diabetes but no documented atherosclerotic CAD to standard guidelinesbased optimal diabetes care or to diabetes care guided by CAD screening with coronary CT angiography. Patients in the control group were treated by their primary care physicians with target hemoglobin A1c \ 7%, lowdensity lipoprotein cholesterol (LDL-C) \100 mg
dL-1, and systolic blood pressure \130 mmHg. Patients in the CT-guided group were treated more aggressively if they were found to have a calcium score [10 or at least mild stenosis on CT angiography; the more aggressive targets were hemoglobin A1c \ 6%, LDL-C \ 70 mg
dL-1, high-density lipoprotein cholesterol [50 mg
dL-1 in women and 40 mg
dL-1 in men, triglycerides \150 mg
dL-1, and systolic blood pressure\120 mmHg. For patients with more abnormal CT findings, their physicians received a recommendation to perform stress testing or invasive angiography and revascularization, according to a prescribed algorithm. The prespecified primary endpoint was the composite of all-cause mortality, non-fatal myocardial infarction, or hospitalization for unstable angina, and patients were followed for a mean of 4 years. The event rate for this primary outcome was not significantly different between CT-guided treatment (28 events, 6.2%) and the control group (34 events, 7.6%), with a hazard ratio of 0.80 (P = .38); nor was it significant for the secondary outcome measure which limited deaths to CAD-related deaths. Of note, risk factors were very well managed even for patients in the control group, who at baseline

had mean LDL-C of 87.7 mg
dL-1 (nearly a third had LDL-C B 70 mg
dL-1), systolic blood pressure of 130.5 mmHg, and hemoglobin A1c of 7.5%. This outstanding baseline care led to smaller-than-expected changes in risk factors, e.g., even in the group randomized to CT, LDL-C decreased by only 2.64 mg
dL-1 at 1 year, and hemoglobin A1c did not significantly change in either group. In turn, the small changes in risk factors resulted in lower-than-expected differences in event rates and the study being underpowered to detect its primary endpoint. Thus, FACTOR-64 joins the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study12 of screening stress MPI as a ‘‘negative’’ study, failing to demonstrate a role for cardiac imaging in screening asymptomatic individuals. Nevertheless, there still may be a role for imaging in risk stratification and therefore potential to demonstrate improved patient outcomes using an imagingbased screening strategy in future studies. Evidence toward this was presented at AHA by Mahabadi et al13 from the Heinz Nixdorf Recall Study, a German urban population-based cohort study which between 2000 and 2003 enrolled 4200 individuals aged 45-75, who underwent non-contrast CT for calcium scoring; by prespecification individuals with overt cardiovascular disease were excluded from primary analyses. The AHA presentation evaluated the additive role of multiple noncoronary CT parameters derived from the non-contrast scan, on the prediction of hard cardiovascular events (cardiovascular death, myocardial infarction, or stroke). Building upon several previous studies evaluating single CT-derived parameters,14-18 the authors developed a multivariable model which demonstrated significant hazard ratios for epicardial adipose tissue volume (1.15, 95% CI 1.05-1.41) and left atrial index (1.22, 95% CI 1.05-1.41), with borderline significance (P = .08) for thoracic aortic calcium (1.33, 0.97-1.81).

AlJaroudi et al. Multi-modality imaging: Bird’s-eye view

Other CT parameters considered, namely ascending and descending aortic diameter and aortic and mitral valve calcification, while significant on univariable analysis, were not significant when adjusted for coronary artery calcium score and Framingham Risk Score. In comparison to a model including just coronary calcium score and Framingham Risk Score, a model adding epicardial adipose volume, left atrial index, and thoracic aortic calcium was modestly but significantly more predictive of events (area under receiver-operator characteristic curve of 0.762 vs 0.749, P = .019). Another interesting imaging study was presented by Habis et al from France, and published in Radiology.19 While we typically think of exercise testing as a possibility for stress echocardiography and SPECT MPI, some centers perform exercise stress CMR20 and PET MPI.21 To these, we can now add exercise stress CT, performed with a treadmill secured to the CT table (Figure 2). Habis et al performed CT MPI in 32 consecutive patients without previous acute coronary syndrome or revascularization, with a total of 55 stenoses of at least 50%, and determined the myocardial enhancement ratio between stenotic and normally perfused territories. Based on receiver-operator characteristic curve analysis with invasive fractional flow reserve of 0.8 as the reference standard, a ratio cutoff of 0.8 was optimal for identifying functionally significant stenoses. Sensitivity and specificity were 97% (29 of 30 stenoses) and 96% (23 of 24 stenoses) in lesion-based analysis and 95% (21 of 22 patients) and 90% (9 of 10 patients) in patient-based analysis, respectively. This diagnostic performance was not evaluated with a separate validation cohort, however, and further study is needed. A CT highlight of the scientific sessions was the AHA Council on Cardiovascular Radiology and Intervention’s annual Charles T. Dotter Memorial Lecture, given by Dr. Joa˜o Lima. He focused on two themes: the growing worldwide burden of ischemic heart disease, which together with stroke killed 12.9 million people in 201022 and is projected to kill 23.3 million in 2030,23 and the remarkable advances made in CT over the past decade. Lima and coauthors have played leading roles in many of these CT studies, including the Multi-Ethnic Study on Atherosclerosis (MESA), which demonstrated the power of coronary artery calcium scoring for predicting coronary events,24 even over and above the inflammatory biomarker C-reactive protein,25 the Coronary Artery Evaluation Using 64-Row Multidetector Computed Tomography Angiography (CORE 64) study26 which serves as one of the three major multicenter studies demonstrating the high accuracy of coronary CT angiography in comparison to a reference standard of invasive angiography, the FACTOR-64 trial discussed above,11 and the Coronary Artery Evaluation using 320-row Multidetector Computed Tomography

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Figure 2. Exercise stress CT angiography. Image courtesy Dr. Michel Habis.

Angiography and Myocardial Perfusion (CORE320) study27 which demonstrated the additional diagnostic ability of CT myocardial perfusion in addition to coronary CT angiography in predicting flow-limiting stenoses. Lima reviewed the methodology and diagnostic accuracy of fractional flow reserve assessment by CT, where most recently the Analysis of Coronary Blood Flow Using CT Angiography: Next Steps (NXT) trial28 demonstrated high diagnostic accuracy with invasive fractional flow reserve as the reference standard, but he questioned the concept of fractional flow reserve-guided percutaneous coronary intervention,29 pointing out that the difference in myocardial infarction rates between fractional flow reserve-guided and angiography-guided intervention in the Fractional Flow Reserve vs Angiography for Multivessel Evaluation (FAME) study30 was attributable to events occurring during the first few days after randomization. Putting the CT literature together, Lima addressed his suggested approach, illustrated in Figure 3, for the evaluation of patients presenting with chest pain, where CT angiography plays a primary role for patient with a low-tointermediate risk of acute coronary syndrome. The Dotter lecture continued with a taste of the next important clinical trials that will address CT in 2015, comparing it to functional imaging as the initial diagnostic test for stable, symptomatic patients. The

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Figure 3. Suggested management algorithm for patients presenting with chest pain. Image courtesy Dr. Joa˜o Lima.

Randomized Evaluation of Patients with Stable Angina Comparing Utilization of Diagnostic Examinations (RESCUE) trial (http://clinicaltrials.gov/show/NCT0126 2625) has enrolled 1,050 patients, with final patient follow-up in April 2014 and database lock in September 2014. The Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) study31 has enrolled 10,000 patients, with a primary composite outcome of death, myocardial infarction, stroke, and hospitalization for unstable angina. Lima then returned to the worldwide burden of cardiovascular disease, focusing in particular on its growth in developing countries where it has been projected32 that deaths will increase from 9 million in 1990 to 19 million in 2020. In particular, this burden is of particular concern in the non-elderly developing world population, in which, for example, the largest increase in cardiovascular mortality rates in China has occurred. The lecture closed with a call for action to the cardiovascular imaging community, from which further research is essential to identify the phenotype of CAD in the developing world. Ultimately, CT has great potential to guide the management of CAD in the developing world, but it is up to our community to ensure that it achieves this promise. ECHOCARDIOGRAPHY Tsujimoto et al33 evaluated diastolic wall strain in 962 consecutive patients referred for echocardiography with preserved LVEF and no clinical heart failure or cardiac structure abnormalities and followed them for 43 ± 32 months for cardiovascular events including myocardial infarction, heart failure, cardiovascular death, and stroke. Cardiovascular events were significantly increased with advancing age and male sex after adjusting for comorbidities. On multivariate analysis, higher pulse pressure, diabetes, prior CAD, and

AlJaroudi et al. Multi-modality imaging: Bird’s-eye view

larger left atrial volume index were independent predictors of cardiovascular events. Furthermore, low diastolic wall strain was a significant predictor of cardiovascular events independent of other comorbidities (HR 2.0, 95% CI 1.1-3.36). The predictive power of the model showed that diastolic wall strain added significantly to conventional risk factors for cardiovascular outcomes. Newer sophisticated imaging technique can assess and quantify diastolic dysfunction with strain imaging. This study highlights the importance of quantifying diastolic dysfunction using diastolic wall strain to predict adverse cardiovascular outcomes. Peng et al34 evaluated the neuroprotective effects of Xenon containing echogenic liposome treatment of Sprague-Dawley rats (n = 90) with subarachnoid hemorrhage. All the treatments were administered intravenously for 5 minutes in combination with ultrasound over the carotid artery to trigger xenon release from the circulating liposomes. Furthermore, bloodbrain-barrier permeability was measured using Evans blue at 48 hours. Neurological behavioral tests were performed at days 3, 7, 21, and 35. Mortality up to 35 days was determined. Ultrasound facilitated Xenon delivery using xenon containing echogenic liposomes. Xenon containing liposomes alleviated early brain injury following subarachnoid hemorrhage and reduced longterm mortality and neurological impairment. This study highlights the importance of echogenic liposomes as vehicle for targeted delivery of novel therapeutic agents to different organs for therapeutic uses. Mousavi et al35 evaluated whether echocardiographic parameters prior to anthracycline treatment predicted the development of symptomatic heart failure or cardiac death in 2,234 patients. 12 patients experienced this outcome at a median of 173 days. LV end diastolic volume and global longitudinal strain were predictive of outcomes when adjusted for age. Furthermore, age and global longitudinal strain were also predictive of overall mortality. It is important and difficult to identify patients at risk for developing anthracycline-induced cardiotoxicity early before LV systolic dysfunction develops. Evaluation of global longitudinal strain appears to be an important quantitative parameter to predict adverse outcomes in patients on anthracycline treatment. Rowin et al36 evaluated the natural history and management implications of exercise-induced LV outflow tract obstructions in 533 patients with hypertrophic cardiomyopathy without outflow obstruction at rest. These patients underwent a symptom limited exercise echocardiogram to assess development of LV outflow obstruction and were followed for 6.5 years. LV obstruction ([30 mm
Hg-1) was present post exercise in 49% of the patients. Patients with provocable exercise

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gradients had a higher incidence of progressing to worse NYHA classification (20% vs 10% for those patients who did not develop an obstruction). Furthermore, rate of heart failure progression was significantly greater in patients with provocable obstruction (3.1%
year-1) vs non-provocable patients (1.5%
year-1). However, the majority of patients with stress-induced obstruction demonstrated substantial improvement in symptom class of heart failure after invasive septal reduction therapy. Stress echocardiography can identify provocable gradients not present at rest and is a strong predictor of future progression to heart failure and adverse outcomes. Thus, exercise echocardiography should be considered in hypertrophic cardiomyopathy patients without obstruction under resting conditions for risk stratification. Chimura et al37 studied 179 patient with dilated cardiomyopathy (LVEF 33 ± 9%, NYHA class I-IV) using CMR for late gadolinium enhancement (LGE) and echocardiography for global longitudinal strain and other conventional echo parameters. During a followup period of 3.8 ± 2.5 years, 7 patients succumbed to cardiac deaths and 40 had heart failure hospitalizations. On multivariate Cox proportional hazard regression analysis, both abnormal global longitudinal strain and LGE were independent predictors of outcomes. KaplanMeier analysis showed that worse global longitudinal strain predicts adverse outcomes in patients both with and without LGE. Thus, in patients with dilated cardiomyopathy, both global longitudinal strain and LGE are useful imaging parameters for predicting longterm outcomes. This is an important study to further risk stratify patients with dilated cardiomyopathy. Imaging may facilitate more aggressive treatment and earlier listing for cardiac transplantation in higher risk patients. CARDIAC MAGNETIC RESONANCE IMAGING Multiple CMR-based studies were presented at AHA 2014 of which we will summarize 4 high-impact abstracts. Suksaranit et al38 studied 778 patients referred for radiofrequency ablation of atrial fibrillation who underwent pre-ablation CMR with imaging of LGE of left ventricle (LV). A number of clinical and imaging characteristics were analyzed. LV-LGE was present in 46 patients (6%). The outcome of interest, a composite of cardiovascular death, myocardial infarction, and ischemic stroke were significantly more common in patients with LV-LGE (13% vs 3.7%, P = .002) during a mean follow-up time of 53 months. In univariate analyses the CHADS2 and CHADS2-VASc scores, prior stroke, age, left atrial fibrosis, and LV-LGE were all predictive of outcomes, but in multivariate analysis, only age and LV-LGE remained associated with the composite outcome. Gadolinium-enhanced CMR is

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often performed in many patients prior to ablation for atrial fibrillation. Analysis of LGE is part of the standard in these examinations and may provide useful information in risk assessment. Surprisingly, LV-LGE may provide more prognostic information than the CHADS2VASc and other established risk indices. This work illustrates the prognostic value of LGE CMR in this patient population with atrial fibrillation. Bhatti et al39 evaluated the role of CMR in the management of patients with multiple myeloma. They studied 164 patients (mean age 63 ± 10 years) with multiple myeloma who had CMR at a single large specialized referral center and analyzed all-cause death in relation to clinical, biomarker, ECG, echocardiographic, and CMR findings. During a median follow-up of 702 days, 59 patients died. They found that typical amyloid pattern on CMR (circumferential abnormal LGE; with an odds ratio of 2.19), elevated BNP, and increased LV wall thickness (on CMR) were the significant predictors of mortality. Kaplan-Meier curves showed clear separation in survival between those with vs without LGE on the CMR, with the group having LGE showing a worse prognosis. Multiple myeloma patients often have associated systemic (including cardiac) amyloidosis, and these patients have poor outcomes. The diagnosis of cardiac amyloidosis can be challenging. CMR may be useful in predicting overall outcomes in these patients and should be considered to aid in diagnosis and risk stratification. CMR can be a useful imaging modality for the diagnosis of cardiac sarcoidosis (Figure 4).8 Murtagh et al40 examined 218 patients with normal LVEF ([50%) and biopsy-proven extracardiac sarcoidosis, to determine if those with abnormal LGE patterns on CMR are at risk of death or ventricular tachycardia. Of the 218 patients, 41 (19%) had LGE and were matched with 41 patients without LGE based on age, sex, and severity of pulmonary disease. 5.5% of patients died or had ventricular tachycardia during 41 ± 19 months of follow-up and 10 of these had LGE (P = .05). They also found that those with right ventricular dysfunction were at higher risk of death or ventricular tachycardia. Patients with cardiac sarcoidosis are at particularly high risk of sudden death or ventricular tachycardia. This study shows how use of gadolinium-enhanced CMR can stratify patients with known extracardiac sarcoidosis who are at increased risk and may be helpful in determining those who would potentially benefit from implantable cardioverter-defibrillator. In the MESA study, 5,004 participants underwent CMR allowing for the quantitation of LV sphericity index (SI; proportional to volume/length cubed).41 LV shape is known to be associated with altered LV mechanics. The study investigated whether an abnormal SI (either high or low) was associated with heart failure

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AlJaroudi et al. Multi-modality imaging: Bird’s-eye view

References

Figure 4. Images from a 58-year-old female who presented with ventricular tachycardia with normal coronary arteries on angiography. Trans-axial slice from CMR shows foci of late gadolinium enhancement in a subendocardial enhancement within the septum the right ventricle and a small focus in the basal lateral wall suggestive of cardiac sarcoidosis (A). A corresponding trans-axial slice from a co-registered/fused FDG PET and CT image showing FDG uptake also within the septum and right ventricle consistent with active cardiac sarcoidosis (Reproduced with permission from Ref. 8).

or CAD over a 10-year follow-up period. A number of other clinical and biomarker/imaging predictors were also measured in MESA. The highest and lowest quintiles of SI at end-systole (but not end-diastole) were predictive of heart failure as compared to those in the middle quintiles. The lowest quintile of SI (i.e., the most elongated or least spherical) was associated with development of CAD. LV shape is increasingly recognized as being associated with the mechanical performance of the LV, as alterations away from the optimal configuration lead to mechanical disadvantage association of shape with CAD is more surprising and is worthy of additional investigation. Disclosures Dr. Einstein reports grant support from GE Healthcare and Phillips Healthcare. Dr. Hage reports grant support from Astellas Pharma USA.

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