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Patients with suspected cardiac sarcoidosis frequently undergo fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging to assess disease activity at baseline and after treatment initiation.This study investigated the effect of immunosuppressive therapy and biopsy status to achieve complete treatment response (CTR), partial treatment response (PTR), or no response (NR) on myocardial FDG-PET/CT.This study analyzed 83 patients with suspected cardiac sarcoidosis (aged 53 ± 1.8 years, 71% were male, 69% were White, 61% had a history of biopsy-confirmed sarcoidosis) who were treatment naive, had evidence of myocardial FDG at baseline, and underwent repeat PET imaging after treatment initiation. CTR was graded visually, and PTR/NR were measured both visually and quantitatively using the total glycolytic activity. Patients were also evaluated for the occurrence of death, sustained ventricular arrhythmias, and heart failure admissions.Overall, 59 patients (71%) achieved CTR/PTR (30%/41%) at follow-up scan (P = 0.04). Total glycolytic activity and visual estimate of PTR/NR had excellent agreement (κ = 0.86 [95% CI: 0.72-0.99]; P 0.0001). In patients receiving prednisone only, the highest rates of CTR/PTR were observed in patients initiated on moderate or high dose (P 0.01). In a regression model, moderate prednisone start dose (P = 0.03) was more strongly associated with achieving CTR/PTR than was high prednisone start dose. However, the latter patients were tapered faster between start dose and follow-up scan (P 0.01). After a median follow-up of 4.7 (IQR: 3.1-7.8) years, patients who were biopsy-proven (vs non-biopsy-proven; P = 0.029) and with preserved left ventricular function (P = 002) were less likely to experience major adverse cardiac events. Outcomes based on treatment response status (CTR vs PTR vs NR; P = 0.23) were not significantly different.Among patients with suspected sarcoidosis and evidence of myocardial inflammation, treatment response by serial FDG-PET was variable, but a favorable response was more common when using moderate-to-high intensity prednisone dose. Biopsy-proven individuals and those with preserved systolic function were less likely to experience adverse outcomes during follow-up.

Representative video clips of echocardiography performed in unirradiated and irradiated mice 8 weeks post-RT.

Supplementary materials and figures

BACKGROUND: Interest in therapeutic applications of exogenous ketones has grown significantly, spanning patients with heart failure to endurance athletes. Exogenous ketones engender significant effects on cardiac function in heart failure and provide an ergogenic benefit in athletes. The aim of this study was to assess the effects of exogenous ketones on cardiac function in healthy participants. METHODS: In a single-arm intervention study, 20 fasting, healthy participants underwent comprehensive echocardiography (two-dimensional, Doppler, and strain) before and 30 min after weight-based oral ketone ester administration. The relationship between changes in log-transformed biomarker levels and change in absolute global longitudinal strain (GLS) was assessed using linear regression. RESULTS: The mean age was 30 ± 7 years, 50% were women, 45% were nonwhite, and the average body mass index was 24.3 ± 3.1 kg/m(2). Ketone ingestion acutely elevated β-hydroxybutyrate levels from a median of 0.13 mmol/L (interquartile range, 0.10–0.37 mmol/L) to 3.23 mmol/L (interquartile range, 2.40–4.97 mmol/L) (P < .001). After ketone ester consumption, systolic blood pressure, heart rate, biventricular function, left ventricular GLS, and left atrial (LA) strain all augmented, while systemic vascular resistance decreased. Displayed as mean change, increases in ejection fraction (3.1%; 95% CI, 2.0%−4.2%; P < .001), GLS (2.0%; 95% CI, 1.4%−2.7%; P < .001), right ventricular S′ (1.1 cm/sec; 95% CI, 0.4–1.8 cm/sec; P = .004), LA reservoir strain (7%; 95% CI, 3%−12%; P = .005), and LA contractile strain (4%; 2%−6%; P = .001) were observed. During robustly achieved ketosis, change in GLS was inversely associated with change in nonesterified fatty acids (P = .019). CONCLUSIONS: In a single-arm study, systolic blood pressure, heart rate, biventricular function, and LV and LA strain acutely augmented after ketone ester ingestion in healthy, fasting participants, similar to several effects observed in the failing heart. These data may provide supporting data for the ergogenic benefits observed in athletes and may become increasingly relevant with exogenous ketone consumption across a variety of cardiovascular and noncardiovascular applications.

This information statement from the Society of Nuclear Medicine and Molecular Imaging, American Society of Nuclear Cardiology, and European Association of Nuclear Medicine describes the performance, interpretation, and reporting of hot spot imaging in nuclear cardiology. The field of nuclear cardiology has historically focused on cold spot imaging for the interpretation of myocardial ischemia and infarction. Hot spot imaging has been an important part of nuclear medicine, particularly for oncology or infection indications, and the use of hot spot imaging in nuclear cardiology continues to expand. This document focuses on image acquisition and processing, methods of quantification, indications, protocols, and reporting of hot spot imaging. Indications discussed include myocardial viability, myocardial inflammation, device or valve infection, large vessel vasculitis, valve calcification and vulnerable plaques, and cardiac amyloidosis. This document contextualizes the foundations of image quantification and highlights reporting in each indication for the cardiac nuclear imager.

Heart failure with preserved ejection fraction (HFpEF) is highly prevalent, affecting approximately half of all patients with HF. The diagnosis of HFpEF can be notoriously challenging in clinical practice, given the many overlapping etiologies of dyspnea or reduced exercise tolerance in patients at risk for HFpEF. Multimodality imaging has an important role in establishing the diagnosis of HFpEF and the presence of elevated left ventricular filling pressures, identifying specific etiologies of HFpEF that can benefit from approved therapies, and discerning distinct phenogroups or mechanistic abnormalities that may inform the development of novel therapeutics.

Infiltrative cardiomyopathies result from the deposition or anomalous storage of specific substances in the heart, leading to impaired cardiac function and heart failure. In this review, we describe the utility of a variety of imaging modalities for the diagnosis of infiltrative cardiomyopathies and provide algorithms for clinicians to use to evaluate patients with these disorders. We have divided infiltrative cardiomyopathies into two different categories: (1) infiltrative cardiomyopathies characterised by increased wall thickness (eg, cardiac amyloidosis and Anderson-Fabry disease (AFD)) and (2) infiltrative cardiomyopathies that can mimic ischaemic or dilated cardiomyopathies (eg, cardiac sarcoidosis (CS) and iron overload cardiomyopathy). Echocardiography is the first modality of choice for the evaluation of cardiomyopathies in either category, and the differential can be narrowed using cardiac magnetic resonance (CMR) and nuclear imaging techniques. The diagnosis of cardiac amyloidosis is supported with key findings seen on echocardiography, CMR and nuclear imaging, whereas AFD can be suggested by unique features on CMR. CMR and nuclear imaging are also important modalities for the diagnosis of CS, while iron overload cardiomyopathy is mostly diagnosed using tissue characterisation on CMR. Overall, multimodality imaging is necessary for the accurate non-invasive diagnosis of infiltrative cardiomyopathies, which is important to ensure appropriate treatment and prognostication.

Cardiovascular conditions can exist as part of a systemic disorder (eg, sarcoidosis, amyloidosis, or vasculitis) or have systemic consequences as a result of the cardiovascular insult (eg, myocardial infarction). In other circumstances, multisystem evaluation of metabolism and blood flow might be key for evaluation of multisystemic syndromes or conditions. Long axial field-of-view PET/computed tomography systems hold the promise of transforming the investigation of such systemic disorders. This article aims at reviewing some of the potential cardiovascular applications of this novel instrumentation device.

The difference in diagnostic accuracy of coronary artery disease (CAD) between vasodilator SPECT and PET myocardial perfusion imaging (MPI) in patients with left bundle branch block (LBBB) or ventricular-paced rhythm (VPR) is unknown. We identified patients with LBBB or VPR who underwent either vasodilator SPECT or PET MPI and subsequent coronary angiography. LBBB/VPR-related septal and anteroseptal defects were defined as perfusion defects involving those regions in the absence of obstructive CAD in the left anterior descending artery or left main coronary artery. Of the 55 patients who underwent coronary angiography, 38 (69%) underwent SPECT and 17 patients (31%) underwent PET. PET compared to SPECT demonstrated higher sensitivity (88% vs 60%), specificity (56% vs 14%), positive predictive value (64% vs 20%), negative predictive value (83% vs 50%), and overall superior diagnostic accuracy (AUC .72 (95% CI .50-.93) vs .37 (95% CI .20-.54), P = .01) to detect obstructive CAD. LBBB/VPR-related septal and anteroseptal defects were more common with SPECT compared to PET (septal: 72% vs 17%, P = .001; anteroseptal: 47% vs 8%, P = .02). PET has higher diagnostic accuracy when compared to SPECT for the detection of obstructive CAD in patients with LBBB or VPR.

Aims The ketogenic diet (KD) is standard-of-care to achieve myocardial glucose suppression (MGS) for assessing inflammation using fluorine-18 fluorodeoxyglucose–positron emission tomography (FDG-PET). As KD protocols remain highly variable between centres (including estimation of nutrient intake by dietary logs for adequacy of dietary preparation), we aimed to assess the predictive utility of nutrient intake in achieving MGS. Methods and results Nineteen healthy participants underwent short-term KD, with FDG-PET performed after 1 and 3 days of KD (goal carbohydrate intake Conclusions During highly supervised, short-term KD, approximately half of patients meet strict carbohydrate goals. Yet, in healthy volunteers, dietary review does not provide reassurance for adequacy of myocardial preparation since no clear thresholds for carbohydrate or fat intake reliably predict MGS.

Background Low QRS amplitude (QRSa), QRS fractionation (QRSf) and longer QRS duration (QRSd) are markers of myocardial fibrosis and inflammation in non-ischemic cardiomyopathy (NICM). Objective To determine if reduction of inflammation with treatment of cardiac sarcoidosis (CS) may reverse these 12 lead ECG parameter changes. Methods 21 patients (pts) with CS and VT ablation with a positive baseline positron emission tomographic (PET 1) scan were studied. All pts received prednisone ≥40 mg for 4 to 8 weeks followed by a taper and maintenance with methotrexate ± low-dose prednisone, Results Pts in PET2(+) vs PET2(−) groups has similar gender (men 89% vs 100%, p=0.42), age (57±8 vs 56±10 years, p=0.8) and LV ejection fraction (41±11 vs 46±11, p=0.31). Baseline 12-lead ECGs showed similar QRSd, ≥2QRSf contiguous leads and QRSa for PET2(+) vs PET2(−); P all >0.15 (Table 1). At 1 yr there was a lower prevalence of ≥2QRSf contiguous leads and strong trend for shorter QRS duration and larger QRSa in lead DI if PET2(−) vs PET2(+). 4 pts demonstrated loss of QRSf 2 contiguous leads and/or increase in QRSa in DI by at least 0.15 mV from baseline if PET2(−) and none if PET2(+). Conclusions In pts with CS and VT, reversal of inflammation may result in a greater QRSa and reduction in QRSf. An increase in QRSa in lead 1 by >0.15mV and/or loss of QRSf identifies a clear positive response to treatment and negative PET at 1 year. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Richard T and Angela Clark Innovation Fund in Cardiovascular Medicine, the Mark S Marchlinski EP Research and Education Fund and the Winkelman Family Fund in Cardiovascular Innovation. Table 1

This study sought to test whether relative apical sparing (RELAPS) of left ventricular (LV) longitudinal strain (LS) in cardiac amyloidosis (CA) is explained by regional differences in markers of amyloid burden (Further knowledge of the pathophysiological basis for RELAPS can help understand the adverse outcomes associated with apical LS impairment.This was a prospective study of 32 subjects (age 62 ± 7 years; 50% males) with light chain CA. All subjects underwent two-dimensional echocardiography for LS estimation andThere was a significant base-to-apex gradient in LS (-7.4 ± 3.2% vs. -8.6 ± 4.0% vs. -20.8 ± 6.6%; p 0.0001), maximal LV wall thickness (15.7 ± 1.9 cm vs. 15.4 ± 2.9 cm vs. 10.1 ± 2.4 cm; p 0.0001), and LV mass (74.8 ± 21.2 g vs. 60.8 ± 17.3 g vs. 23.4 ± 6.2 g; p 0.0001). In contrast, florbetapir RI (0.089 ± 0.03 μmol/min/g vs. 0.097 ± 0.03 μmol/min/g vs. 0.085 ± 0.03 μmol/min/g; p = 0.45) and ECV (0.53 ± 0.08 vs. 0.49 ± 0.08 vs. 0.49 ± 0.07; p = 0.15) showed no significant base-to-apex gradient in the tissue concentration or proportion of amyloid infiltration, whereas markers of total amyloid load, such as total florbetapir binding (3.4 ± 1.7 μmol/min vs. 2.8 ± 1.5 μmol/min vs. 0.93 ± 0.49 μmol/min; p 0.0001) and extracellular LV mass (40.0 ± 15.6 g vs. 30.2 ± 10.9 g vs. 11.6 ± 3.9 g; p 0.0001), did show a marked base-to-apex gradient.Segmental differences in the distribution of the total amyloid mass, rather than the proportion of amyloid deposits, appear to explain the marked regional differences in LS in CA. Although these 2 matrices are clearly related concepts, they should not be used interchangeably.

BACKGROUND: Gallium-68 Dotatate binds preferentially to somatostatin receptor (sstr) subtype-2 (sstr-2) on inflammatory cells. We aimed at investigating the potential clinical use of sstr-targeted imaging for the detection of myocardial inflammation. METHODS: 13 patients with suspected cardiac sarcoidosis (CS) based on clinical history and myocardial uptake on recent fluorine-18 fluorodeoxyglucose (FDG) PET, were enrolled to undergo Dotatate PET after FDG PET (median time 37 days [IQR 25 – 55]). Additionally, we investigated ex-vivo the immunohistochemistry expression of sstr-2 in 3 explanted sarcoid hearts. RESULTS: All FDG scans showed cardiac uptake (focal/multifocal = 6, focal on diffuse/heterogeneous = 7), and 46% (n=6) extra-cardiac uptake (mediastinal/hilar). In comparison, Dotatate scans showed definite abnormal cardiac uptake (focal/multifocal) in 4 patients, probably abnormal (heterogenous/patchy) in 3, and negative uptake in 6 cases. Similarly, 6 patients had increased mediastinal/hilar Dotatate uptake. Overall concordance of FDG and Dotatate uptake was 54% in the heart and 100% for thoracic nodal activity. Quantitatively, FDG maximum standardized uptake value was 5.0 times [3.8 – 7.1] higher in the heart, but only 2.25 times [1.7 – 3.0; P=0.019] higher in thoracic nodes relative to Dotatate. Ex-vivo, sstr-2 immunostaining was weakly seen within well-formed granulomas in all 3 examined sarcoid heart specimens with no significant staining of background myocardium or normal myocardium. CONCLUSION: Our preliminary data suggests that, compared to FDG imaging, somatostatin receptor-targeted imaging may be less sensitive for the detection of myocardial inflammation, but comparable for detecting extra-cardiac inflammation.

Background Cardiovascular disease is a major cause of mortality in patients with nonalcoholic fatty liver disease (NAFLD). However, the association of NAFLD with coronary microvascular dysfunction is, to our knowledge, unknown. Purpose To determine whether coronary microvascular dysfunction is more prevalent in patients with NAFLD and to determine whether coronary microvascular dysfunction predicts major adverse cardiac events (MACE) independently of NAFLD. Materials and Methods This retrospective study (2006-2014) included patients without evidence of obstructive epicardial coronary artery disease and healthy left ventricular ejection fraction (≥40%) at a clinical rest and stress myocardial perfusion PET/CT. NAFLD was defined by a mean hepatic attenuation of less than 40 HU at CT and coronary microvascular dysfunction as a coronary flow reserve (CFR) of less than 2.0. A composite of all-cause mortality, myocardial infarction, coronary revascularization, and hospitalization because of heart failure comprised MACE (130 of 886 patients; 14.7%). The relation between NAFLD and MACE was assessed by using multivariable Cox regression analysis. Results Among 886 patients (mean age, 62 years ± 12 [standard deviation]; 631 women [mean age, 62 years ± 12 years] and 255 men [mean age, 61 years ± 12]; and ejection fraction, 63% ± 9), 125 patients (14.1%) had NAFLD and 411 patients (46.4%) had coronary microvascular dysfunction. Coronary microvascular dysfunction was more prevalent (64.8% vs 43.4%; P < .001) and CFR was lower (1.9 ± 1.1 vs 2.2 ± 0.7; P < .001) in patients with NAFLD compared with those without NAFLD. NAFLD independently predicted coronary microvascular dysfunction (P = .01). The interaction of NAFLD and male sex predicted MACE (hazard ratio, 1.45; 95% confidence interval: 1.08, 1.69; P = .008) and coronary microvascular dysfunction remained associated with MACE (adjusted hazard ratio, 1.46; 95% confidence interval: 1.02, 2.07; P = .04). Conclusion Coronary microvascular dysfunction was more prevalent in patients with nonalcoholic fatty liver disease and predicted major adverse cardiac events independently of nonalcoholic fatty liver disease. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Ambale-Venkatesh and Lima in this issue.

This article provides a review of the latest radiotracers for planar/single-photon emission computed tomography (SPECT) and positron emission tomography (PET)/computed tomography (CT) imaging of cardiac amyloidosis, detailing their affinity, specificity, and sensitivity for cardiac amyloidosis. There are several tracers available that have differing affinities for transthyretin (ATTR) and immunoglobulin light chain (AL), and new developments in technology have allowed for disease burden quantification. Bone scintigraphy is an excellent option for visualizing ATTR cardiac amyloidosis. Negative testing does not exclude the possibility of AL cardiac amyloidosis and absolute quantitation of amyloid burden is limited.

Purpose: Radiation-induced cardiotoxicity is a significant concern in thoracic oncology patients. However, the basis for this disease pathology is not well characterized. We developed a novel mouse model of radiation-induced cardiotoxicity to investigate pathophysiologic mechanisms and identify clinically targetable biomarkers of cardiac injury. Experimental Design: Single radiation doses of 20, 40, or 60 Gy were delivered to the cardiac apex of female C57BL/6 mice ages 9–11 weeks, with or without adjacent lung tissue, using conformal radiotherapy. Cardiac tissue was harvested up to 24 weeks post-radiotherapy for histologic analysis. Echocardiography and Technetium-99m sestamibi single photon emission computed tomography (SPECT) at 8 and 16 weeks post-radiotherapy were implemented to evaluate myocardial function and perfusion. Mouse cardiac tissue and mouse and human plasma were harvested for biochemical studies. Results: Histopathologically, radiotherapy resulted in perivascular fibrosis 8 and 24 (P < 0.05) weeks post-radiotherapy. Apical perfusion deficits on SPECT and systolic and diastolic dysfunction on echocardiography 8 and 16 weeks post-radiotherapy were also observed (P < 0.05). Irradiated cardiac tissue and plasma showed significant increases in placental growth factor (PlGF), IL6, and TNFα compared with nonradiated matched controls, with greater increases in cardiac cytokine levels when radiotherapy involved lung. Human plasma showed increased PlGF (P = 0.021) and TNFα (P = 0.036) levels after thoracic radiotherapy. PlGF levels demonstrated a strong correlation (r = 0.89, P = 0.0001) with mean heart dose. Conclusions: We developed and characterized a pathophysiologically relevant mouse model of radiation-induced cardiotoxicity involving in situ irradiation of the cardiac apex. The model can be used to integrate radiomic and biochemical markers of cardiotoxicity to inform early therapeutic intervention and human translational studies.

Background: Myocardial blood flow (MBF) can be quantified using dynamic PET studies. These studies also inherently contain tomographic images of early bolus displacement, which can provide cardiopulmonary transit times (CPTT) as measure of cardiopulmonary physiology. The aim of this study was to assess the incremental prognostic value of CPTT in heart transplant (OHT) recipients. Methods: 94 patients (age 56 ± 16 years, 78% male) undergoing dynamic 13N-ammonia stress/rest studies were included, of which 68 underwent right-heart catherization. A recently validated cardiac allograft vasculopathy (CAV) score based on PET measures of regional perfusion, peak MBF and left-ventricular (LV) ejection fraction (LVEF) was used to identify patients with no, mild or moderate-severe CAV. Time-activity curves of the LV and right ventricular (RV) cavities were obtained and used to calculate the difference between the LV and RV bolus midpoint times, which represents the CPTT and is expressed in heartbeats. Patients were followed for a median of 2.5 years for the occurrence of major adverse cardiac events (MACE), including cardiovascular death, hospitalization for heart failure or acute coronary syndrome, or re-transplantation. Results: CPTT was significantly correlated with cardiac filling pressures (r =.434, P =.0002 and r =.439, P =.0002 for right atrial and pulmonary wedge pressure), cardiac output (r = − .315, P =.01) and LVEF (r = − .513, P

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease associated with increased risk of atherosclerosis. Leptin may indirectly contribute to atherogenesis, but its role in RA is not clear. Hypothesis: We aimed to study the correlation between leptin and inflammation in the abdominal aorta (AA) assessed by 18F-FDG PET/CT in RA patients. Methods: We retrospectively analyzed the data of 18 RA patients (mean age 56.0±11.9, 14 male). All patients were administered 18F-FDG intravenously, and full-body PET/CT scans were acquired 180 minutes later. Regions of interest were delineated around the wall of the AA, with a superior border at the aortic hiatus of the diaphragm and an inferior border at the bifurcation of iliac arteries. Mean standard uptake values per axial slice were averaged to calculate the average SUVmean (aSUVmean). BMI, visceral fat area (VFA), and serum logarithmically transformed leptin (ln-leptin) were obtained. Patients were divided into low- and high-BMI groups, with a cutoff of 25 kg/m2. Results: Mean BMI (kg/m2) and VFA (cm2) between the low- and high-BMI groups were 21.7 vs. 31.4 (p Conclusion: In our study, higher serum leptin levels moderately correlated with 18F-FDG uptake in the AA, which reflects inflammation and atherogenic activity. Future studies are warranted to further elucidate the role of leptin in co-morbid atherosclerosis in patients with RA.

Introduction: The prevalence of sarcoid cardiomyopathy (SCM) with female predominance is well known. However, gender differences amongst individual races remains poorly studied. Hypothesis: We sought to determine and compare within each gender and race, the rates of arrhythmias, implantable cardiac devices, and in-hospital mortality in patients with SCM after excluding those with a history of coronary artery disease. Methods: The Nationwide Inpatient Sample was queried from 2010 to 2014 using ICD-9 diagnosis code (135) for sarcoidosis among patients >18 years old. We combined it with code (425.8) for cardiomyopathy in other diseases including sarcoid and sarcoid heart muscle disease. We excluded patients with a history of prior myocardial infarction, percutaneous coronary intervention and coronary artery bypass graft. Results: From 2010 to 2014, we identified 9,063 patients with SCM (mean age = 53.11 ± 11.28 years; men 51.8% and black 52.5%). Upon comparison of gender within races, event rates per 100 patients were (white male, white female, black male, black female; p-value): atrial fibrillation (20.7, 18.8, 18, 16.1; p=0.172), ventricular fibrillation (VF) (4.1, 1.7, 2.3, 2.1; p Conclusion: White males had higher rates of VF, VT, CHB, but they also had a lower in-hospital mortality and SCA rates likely due to higher procedural rates such as EMB, ICD, CRT-D, catheter ablation and OHT as compared to others.

Introduction/Background Sarcoidosis is a granulomatous disease with various cardiac manifestations such as arrhythmias, heart block, heart failure and sudden cardiac death. Objective We sought to determine and compare the rates of arrhythmias, implantable cardiac devices in patient with sarcoid heart disease (SHD) after excluding those with a history of coronary artery disease Methods The United States Nationwide Inpatient Sample was queried from 2010 to 2014 using ICD-9 diagnosis code (135) for sarcoidosis among patients >18 years. We combined it with code (425.8) for cardiomyopathy in others disease including sarcoid and sarcoid heart muscle disease. We excluded patients with a history of prior myocardial infarction, percutaneous coronary intervention and coronary artery bypass graft. Results From 2010 to 2014, we identified 9,063 patients with SHD (Mage = 53.11±11.28 years; men 51.8% and black 52.5%). The overall in-hospital mortality rate was 227 (2.5%). Average Length of stay (LOS) (M ± SD) was 6.15±8.964. Various arrhythmias include atrial fibrillation 1,659 (18.4%), ventricular fibrillation 223 (2.5%), ventricular tachycardia 2,248 (24.7%), complete heart block 506 (1.5%) and second degree Mobitz type II 45 (0.5%). Rates of implantable cardiac devices included implantable cardioverter-defibrillator (ICD) 881 (9.7%), Cardiac Resynchronization Therapy Defibrillator (CRT-D) 83 (3.6%), PPM 172 (1.9%). Rates of Endomyocardial biopsy were 257 (2.8%). Overall rates of sudden cardiac arrest was 161 (1.8%). On comparing the two groups, sarcoidosis without cardiac involvement and sarcoid heart disease the rates of arrhythmias, implantable cardiac devices, in-hospital mortality and sudden cardiac arrest were as follows: atrial fibrillation (9.4 vs 18.3; p Conclusions Based on the results of our study, we conclude that SHD is associated with a variety of cardiac arrhythmias and conduction defects. Sarcoidosis with cardiac involvement is associated with increased rates of atrial fibrillation, ventricular fibrillation, ventricular tachycardia, complete heart block, and second degree Mobitz type II. They also had a higher rate of pacemaker implantation, ICD, CRT-D and had a overall higher rate of sudden cardiac arrest. Based on the results of our study we conclude that sarcoidosis with cardiac involvement has worse outcomes and hence, early diagnosis and prompt treatment can prevent the progression of the disease. Funding Acknowledgement Type of funding source: None

Introduction Complete heart block (CHB), also known as third-degree heart block, occurs when there is complete dissociation of the atria and ventricles. CHB during pregnancy is extremely rare and one possible mechanism may be related to the stretching of the atria during pregnancy causing conduction defects Purpose There is limited data on the rates of CHB and pacemaker (PPM) use in pregnant patients, with only a few case reports published. In this study we sought to define the rates of permanent pacemaker implantation for CHB complicating pregnancy. Methods The Nationwide Inpatient Sample was queried from 2010 to 2014 using the International Classification of Diseases, 9th revision diagnosis codes for pregnancy and CHB and procedure codes for PPM in any procedure field for patients 18 years or older. Results From 2010 to 2014, we identified 20,451,108 pregnancies in patients above the age of 18 years. The overall rates of CHB were 643 (0.0031%). The sample consisted of 643 patients (Mage= 29.28±6.42 years) with CHB, the majority of whom were Caucasians 328 (51%). Average length of stay (LOS) (M ± SD) was 4.94±7.859 and total hospitalization charges were 51,715.04±112,345.98 ($). Moreover, the occurrence of other conditions which could lead to the development of CHB was: sarcoidosis 0 (0%), systemic lupus erythematosus 5 (0.8%), prior myocardial infarction 25 (3.8%), Lyme disease 0 (0%). Among patients with CHB, PPM implantation was done in 60 (9.3%), and TVP were 5 (0.8%). The overall composite mortality rates were 21 (3.2%). On comparing the non-PPM group to the PPM group, rates of in-hospital mortality were 3.6% vs 0%; p=0.059, LOS were 4.49±5.01 vs 12.50±15.35; p Conclusions The overall rates of CHB were 3.1 in 100,000 pregnancies. There were no reported in-hospital deaths among pregnant patients with CHB who received PPM and TVP. Relatively lower rates of PPM implantation in these patients might indicate that CHB during pregnancy is less severe and patients may have a stable narrow complex junctional escape rhythm. PPM implantation is recommended for those who are symptomatic or have a slow wide QRS complex rhythm indicating a block below the bundle of His.With this study we attempt to better define the occurrence of CHB during pregnancy, which could lead to better understanding and management of this condition. Funding Acknowledgement Type of funding source: None

Introduction Sarcoidosis is a granulomatous disease with multiorgan involvement. Cardiac involvement may be asymptomatic or present clinically as heart failure, arrhythmias or even sudden cardiac death. Objective We compared gender differences in prevalence of arrhythmias and associated outcomes in patients with sarcoidosis without established coronary artery disease. Methods The United States Nationwide Inpatient Sample was queried from 2010 to 2014 to identify patients with sarcoidosis using ICD-9 diagnosis code in patients >18 years. We excluded patients with a prior history of myocardial infarction, percutaneous coronary intervention and coronary artery bypass graft. Chi-square test was used for statistical analysis. Results The sample consisted of 308,064 patients (Mage = 55.65±11.28 years); they were mostly women 945 (65.2%) and black 957 (46.7%). In-hospital mortality in this cohort was 1,574 (2.5%). The most common arrhythmias was atrial fibrillation 29,850 (9.7%). Prevalence of ventricular fibrillation was 669 (0.2%), ventricular tachycardia 6,184 (2%), complete heart block 1462 (0.5%) and second degree Mobitz type II 245 (0.1%). Sudden cardiac death occurred in 2,059 (0.7%). Rates of various cardiac devices implanted were: implantable cardiac defibrillator (ICD) 1,452 (0.5%), cardiac resynchronization therapy-defibrillator (CRT-D) 553 (0.2%), pacemaker 1259 (0.4%). Rates of endomyocardial biopsy (EMB), radionuclide imaging, and cardiac magnetic resonance imaging were 470 (0.2%), 879 (0.3%), and 224 (0.1%), respectively. Based on gender (male vs. female), the rates of arrhythmias, cardiac device implantation and utilization of diagnostic modalities were: atrial fibrillation (41% vs 59%; p Conclusion In our study, in-hospital death was more common in females. Females had higher rates of atrial fibrillation compared to males who were found to have a higher burden of ventricular tachycardia. Males had higher rates of ICD and CRT-D placement. Males also had EMB performed more commonly than females. Funding Acknowledgement Type of funding source: None

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes coronavirus disease 2019 (COVID-19) has resulted in a global health crisis. Prior to the arrival of this viral pandemic, the world was already plagued with a significant burden of cardiovascular disease. With the introduction of the novel virus, the world now faces a double jeapordy. Early reports have suggested an increased risk of death in individuals with underlying cardio-metabolic disorders. The exact effects of COVID-19 on the cardiovascular system are not well determined, however lessons from prior viral epidemics suggest that such infections can trigger acute coronary syndromes, arrhythmias and heart failure via direct and indirect mechanisms. In this article, we aimed to discuss the effects and potential underlying mechanisms of COVID -19 as well as potential implications of treatments targeted against this virus on the cardiovascular system.El síndrome respiratorio agudo severo coronavirus 2 (SARS-CoV-2) que causa la enfermedad por coronavirus (COVID-19) ha provocado una crisis en la salud global. Antes de la llegada de esta pandemia, se tenia una carga importante de enfermedad cardiovascular a nivel mundial. Con la introducción del nuevo virus, el mundo ahora se enfrenta a un doble peligro. Los primeros informes han sugerido un mayor riesgo de muerte en personas con trastornos cardio-metabólicos de base. Los efectos causados por el COVID-19, en el sistema cardiovascular aun no están bien determinados, sin embargo, el conocimiento sobre otras epidemias virales previamente ocurridas en el mundo, sugieren que estas infecciones pueden desencadenar síndromes coronarios agudos, arritmias e insuficiencia cardíaca a través de mecanismos directos e indirectos. En este artículo, nuestro objetivo fue analizar los efectos y los posibles mecanismos subyacentes de COVID -19, así como las posibles implicaciones de los tratamientos dirigidos contra este virus en el sistema cardiovascular.

Objectives: Elevated blood pressure from cocaine can increase left ventricular (LV) metabolic activity, leading to structural changes such as hypertrophy. We aimed to assess the association between blood pressure and LV myocardial uptake of FDG, hypothesizing that HIV individuals with raised blood pressure will have higher FDG uptake. Methods: University of Pennsylvania enrolled patients with HIV on antiretroviral therapy with viral load Results: aSUVmean was higher in HIV patients with cocaine use (U(Ncocaine = 11, Nno cocaine=11) = 93, p=0.0336). In patients with cocaine use, there was a positive correlation between blood pressure and aSUVmean (SBP: r=0.70, p=0.0164; DBP: r=0.69, p=0.0185; MAP: r=0.72, p=0.0120). No significant correlations were found in HIV patients without cocaine use (SBP: r=0.03, p=0.9239; DBP: r=-0.50, p=0.1153; MAP: r=-0.32, p=0.3345). Conclusions: LV myocardial metabolism was more strongly positively correlated with blood pressure in HIV patients using cocaine compared to HIV patients without cocaine. These data suggest FDG-PET/CT can be used to monitor LV metabolic activity and allow for timely assessment of structural changes caused by cocaine use and hypertension.

The difference in diagnostic accuracy of coronary artery disease (CAD) between vasodilator SPECT and PET myocardial perfusion imaging (MPI) in patients with left bundle branch block (LBBB) or ventricular-paced rhythm (VPR) is unknown.We identified patients with LBBB or VPR who underwent either vasodilator SPECT or PET MPI and subsequent coronary angiography. LBBB/VPR-related septal and anteroseptal defects were defined as perfusion defects involving those regions in the absence of obstructive CAD in the left anterior descending artery or left main coronary artery.Of the 55 patients who underwent coronary angiography, 38 (69%) underwent SPECT and 17 patients (31%) underwent PET. PET compared to SPECT demonstrated higher sensitivity (88% vs 60%), specificity (56% vs 14%), positive predictive value (64% vs 20%), negative predictive value (83% vs 50%), and overall superior diagnostic accuracy (AUC .72 (95% CI .50-.93) vs .37 (95% CI .20-.54), P = .01) to detect obstructive CAD. LBBB/VPR-related septal and anteroseptal defects were more common with SPECT compared to PET (septal: 72% vs 17%, P = .001; anteroseptal: 47% vs 8%, P = .02).PET has higher diagnostic accuracy when compared to SPECT for the detection of obstructive CAD in patients with LBBB or VPR.

OBJECTIVES: The purpose of this study was to determine phenotypes characterizing cardiac involvement in AL amyloidosis by using direct (fluorine-18-labeled florbetapir {[(18)F]florbetapir} positron emission tomography [PET]/computed tomography) and indirect (echocardiography and cardiac magnetic resonance [CMR]) imaging biomarkers of AL amyloidosis. BACKGROUND: Cardiac involvement in systemic light chain amyloidosis (AL) is the main determinant of prognosis and, therefore, guides management. The hypothesis of this study was that myocardial AL deposits and expansion of extracellular volume (ECV) could be identified before increases in N-terminal pro-B-type natriuretic peptide or wall thickness. METHODS: A total of 45 subjects were prospectively enrolled in 3 groups: 25 with active AL amyloidosis with cardiac involvement (active-CA), 10 with active AL amyloidosis without cardiac involvement by conventional criteria (active-non-CA), and 10 with AL amyloidosis with cardiac involvement in remission for at least 1 year (remission-CA). All subjects underwent echocardiography, CMR, and [(18)F]florbetapir PET/CT to evaluate cardiac amyloid burden. RESULTS: The active-CA group demonstrated the largest myocardial AL amyloid burden, quantified by [(18)F]florbetapir retention index (RI) 0.110 (interquartile range [IQR]: 0.078 to 0.139) min(−1), and the lowest cardiac function by global longitudinal strain (GLS), median GLS −1 1% (IQR: −8% to −13%). The remission-CA group had expanded extracellular volume (ECV) and [(18)F]florbetapir RI of 0.097 (IQR: 0.070 to 0.124 min(−1)), and abnormal GLS despite hematologic remission for >1 year. The active-non-CA cohort had evidence of cardiac amyloid deposition by advanced imaging metrics in 50% of the subjects; cardiac involvement was identified by late gadolinium enhancement in 20%, elevated ECV in 20%, and elevated [(18)F]florbetapir RI in 50%. CONCLUSIONS: Evidence of cardiac amyloid infiltration was found based on direct and indirect imaging biomarkers in subjects without CA by conventional criteria. The findings from [(18)F]florbetapir PET imaging provided insight into the preclinical disease process and on the basis of interpretation of expanded ECV on CMR and have important implications for future research and clinical management of AL amyloidosis. (Molecular Imaging of Primary Amyloid Cardiomyopathy [MICA]; NCT02641145)

Background: We used (18)F-sodium fluoride (NaF) to assess early atherosclerosis in the global heart in asymptomatic individuals with a coronary calcium score of zero and without a formal diagnosis of hypertension. We hypothesized that these individuals might present with subclinical atherosclerosis that correlates with systolic, diastolic and mean arterial pressure (SBP, DBP, and MAP). Methods: We identified 20 asymptomatic individuals (41.6 ± 13.8 years, 8 females) from the CAMONA trial with C-reactive protein ≥3 mg/L, no smoking history, diabetes (fasting blood glucose 40 mg/dL. All underwent PET/CT imaging 90 minutes after NaF injection (2.2 Mbq/Kg). The global cardiac average SUVmean (aSUVmean) was calculated for each individual. Correlation coefficients and linear regression models were employed for statistical analysis. Results: Significant positive correlation was revealed between global cardiac NaF uptake and all blood pressures: SBP (r=0.44, P=0.05), DBP (r=0.64, P=0.002), and MAP (r=0.59, P=0.007). After adjusting for age and gender, DBP and MAP were independent predictors of higher global cardiac NaF uptake. Conclusion: NaF-PET/CT for detecting and quantifying subclinical atherosclerosis in asymptomatic individuals revealed that cardiac NaF uptake correlated independently with DBP and MAP.

Coronary microvascular dysfunction and, its functional consequence, myocardial ischemia are common pathologic features in patients with hypertrophic cardiomyopathy (HCM). Both have been commonly invoked as potential triggers of and/or contributors to the underlying pathophysiological processes leading to heart failure, and malignant ventricular arrhythmias. Positron emission tomography (PET) with myocardial blood flow quantification provides a unique opportunity to evaluate the integrity and function of the coronary microcirculation in HCM. The purpose of the present review is to summarize all the pertinent literature and future perspectives of the role of PET in the evaluation and risk stratification of patients with HCM.

IMPORTANCE: Mental stress–induced myocardial ischemia is a recognized phenomenon in patients with coronary heart disease (CHD), but its clinical significance in the contemporary clinical era has not been investigated. OBJECTIVE: To compare the association of mental stress–induced or conventional stress–induced ischemia with adverse cardiovascular events in patients with CHD. DESIGN, SETTING, AND PARTICIPANTS: Pooled analysis of 2 prospective cohort studies of patients with stable CHD from a university-based hospital network in Atlanta, Georgia: the Mental Stress Ischemia Prognosis Study (MIPS) and the Myocardial Infarction and Mental Stress Study 2 (MIMS2). Participants were enrolled between June 2011 and March 2016 (last follow-up, February 2020). EXPOSURES: Provocation of myocardial ischemia with a standardized mental stress test (public speaking task) and with a conventional (exercise or pharmacological) stress test, using single-photon emission computed tomography. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of cardiovascular death or first or recurrent nonfatal myocardial infarction. The secondary end point additionally included hospitalizations for heart failure. RESULTS: Of the 918 patients in the total sample pool (mean age, 60 years; 34% women), 618 participated in MIPS and 300 in MIMS2. Of those, 147 patients (16%) had mental stress–induced ischemia, 281 (31%) conventional stress ischemia, and 96 (10%) had both. Over a 5-year median follow-up, the primary end point occurred in 156 participants. The pooled event rate was 6.9 per 100 patient-years among patients with and 2.6 per 100 patient-years among patients without mental stress–induced ischemia. The multivariable adjusted hazard ratio (HR) for patients with vs those without mental stress–induced ischemia was 2.5 (95% CI, 1.8-3.5). Compared with patients with no ischemia (event rate, 2.3 per 100 patient-years), patients with mental stress–induced ischemia alone had a significantly increased risk (event rate, 4.8 per 100 patient-years; HR, 2.0; 95% CI, 1.1-3.7) as did patients with both mental stress ischemia and conventional stress ischemia (event rate, 8.1 per 100 patient-years; HR, 3.8; 95% CI, 2.6-5.6). Patients with conventional stress ischemia alone did not have a significantly increased risk (event rate, 3.1 per 100 patient-years; HR, 1.4; 95% CI, 0.9-2.1). Patients with both mental stress ischemia and conventional stress ischemia had an elevated risk compared with patients with conventional stress ischemia alone (HR, 2.7; 95% CI, 1.7-4.3). The secondary end point occurred in 319 participants. The event rate was 12.6 per 100 patient-years for patients with and 5.6 per 100 patient-years for patients without mental stress–induced ischemia (adjusted HR, 2.0; 95% CI, 1.5-2.5). CONCLUSIONS AND RELEVANCE: Among patients with stable coronary heart disease, the presence of mental stress–induced ischemia, compared with no mental stress–induced ischemia, was significantly associated with an increased risk of cardiovascular death or nonfatal myocardial infarction. Although these findings may provide insights into mechanisms of myocardial ischemia, further research is needed to assess whether testing for mental stress–induced ischemia has clinical value.

Aims Cardiac allograft vasculopathy (CAV) is a leading cause of death in orthotopic heart transplant (OHT) survivors. Effective non-invasive screening methods are needed. Our aim was to investigate the added diagnostic and prognostic value of myocardial blood flow (MBF) to standard myocardial perfusion imaging (MPI) with positron emission tomography (PET) for CAV detection. Methods and results We studied 94 OHT recipients (prognostic cohort), including 66 who underwent invasive coronary angiography and PET within 1 year (diagnostic cohort). The ISHLT classification was used as standard definition for CAV. Positron emission tomography evaluation included semiquantitative MPI, quantitative MBF (mL/min/g), and left ventricular ejection fraction (LVEF). A PET CAV severity score (on a scale of 0-3) was modelled on the ISHLT criteria. Patients were followed for a median of 2.3 years for the occurrence of major adverse events (death, re-transplantation, acute coronary syndrome, and hospitalization for heart failure). Sensitivity, specificity, positive, and negative predictive value of semiquantitative PET perfusion alone for detecting moderate-severe CAV were 83% [52-98], 82% [69-91], 50% [27-73], and 96% [85-99], respectively {receiver operating characteristic (ROC area: 0.82 [0.70-0.95])}. These values improved to 83% [52-98], 93% [82-98], 71% [42-92], and 96% [97-99], respectively, when LVEF and stress MBF were added (ROC area: 0.88 [0.76-0.99]; P = 0.01). There were 20 major adverse events during follow-up. The annualized event rate was 5%, 9%, and 25% in patients with normal, mildly, and moderate-to-severely abnormal PET CAV grading (P

The ketogenic diet (KD) is standard-of-care to achieve myocardial glucose suppression (MGS) for assessing inflammation using 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET). However, failure to suppress physiologic glucose uptake remains a significant diagnostic barrier. While extending the duration of KD may be effective, exogenously delivered ketones may provide a convenient, reliable, and same-day alternative. The aims of our study were to determine 1) whether exogenous ketone administration is non-inferior to the KD to achieve MGS, and 2) whether serum beta-hydroxybutyrate [BHB] levels can predict MGS. Methods: KEETO-CROSS is a crossover, non-inferiority trial of the KD (endogenous ketosis) versus ketone ester (KE, exogenous ketosis) drink. Twenty healthy participants were enrolled into three arms: 1) weight-based KE drink 2) 24-hour KD, and 3) 72-hour KD (N = 18 completed all arms). The primary outcome was achievement of complete MGS on PET (non-inferiority margin 5%). The area under receiver operating characteristics (AUROC) of endogenous BHB levels (analyzed in a laboratory and by point-of-care device) for predicting MGS was analyzed in 37 scans completed on the KD. Results: Mean age was 30±7 years, 50% were female, 45% were non-white. Median (25th-75th percentile) achieved BHB levels (mmol/L) were 3.82 (2.55-4.97) (KE drink), 0.77 (0.58-1.02) (24-hour KD), and 1.30 (0.80-2.24) (72-hour KD). The primary outcome was achieved in 44% (KE drink), 78% (24-hour KD), and 83% (72-hour KD) of participants (non-inferiority P = 0.97 and 0.98 for KE vs. 24-hour and 72-hour KD). Endogenous BHB levels robustly predicted MGS (AUROC 0.88, 95%CI 0.71, 1.00). BHB >0.58 correctly classified 92% of scans. A point-of-care device provided comparable predictive value. Conclusion: In healthy volunteers, KE was inferior to KD for achieving MGS. Serum BHB is a highly predictive biomarker for MGS and can be clinically implemented upstream of FDG-PET, with rapid facilitation by point-of-care testing, to reduce false positive scans.

PURPOSE: To perform automated myocardial segmentation and uptake classification from whole-body fluorine 18 fluorodeoxyglucose (FDG) PET. MATERIALS AND METHODS: In this retrospective study, consecutive patients who underwent FDG PET imaging for oncologic indications were included (July–August 2018). The left ventricle (LV) on whole-body FDG PET images was manually segmented and classified as showing no myocardial uptake, diffuse uptake, or partial uptake. A total of 609 patients (mean age, 64 years ± 14 [standard deviation]; 309 women) were included and split between training (60%, 365 patients), validation (20%, 122 patients), and testing (20%, 122 patients) datasets. Two sequential neural networks were developed to automatically segment the LV and classify the myocardial uptake pattern using segmentation and classification training data provided by human experts. Linear regression was performed to correlate findings from human experts and deep learning. Classification performance was evaluated using receiver operating characteristic (ROC) analysis. RESULTS: There was moderate agreement of uptake pattern between experts and deep learning (as a fraction of correctly categorized images) with 78% (36 of 46) for no uptake, 71% (34 of 48) for diffuse uptake, and 71% (20 of 28) for partial uptake. There was no bias in LV volume for partial or diffuse uptake categories (P = .56); however, deep learning underestimated LV volumes in the no uptake category. There was good correlation for LV volume (R(2) = 0.35, b = .71). ROC analysis showed the area under the curve for classifying no uptake and diffuse uptake was high (> 0.90) but lower for partial uptake (0.77). The feasibility of a myocardial uptake index (MUI) for quantifying the degree of myocardial activity patterns was shown, and there was excellent visual agreement between MUI and uptake patterns. CONCLUSION: Deep learning was able to segment and classify myocardial uptake patterns on FDG PET images. Keywords: PET, Heart, Computer Aided Diagnosis, Computer Application-Detection/Diagnosis Supplemental material is available for this article. ©RSNA, 2021

Background: Narrower retinal arterioles and wider retinal venules have been associated with negative cardiovascular outcomes. We investigated whether retinal vessel calibers are associated with cardiovascular outcomes in long-term follow-up and provide incremental value over the 2013 American College of Cardiology/American Heart Association Pooled Cohort Equations in predicting atherosclerotic cardiovascular disease events. Methods: A total of 10 470 men and women without prior atherosclerotic cardiovascular disease events or heart failure in the ARIC Study (Atherosclerosis Risk in Communities) underwent retinal photography at visit 3 (1993–1995). Results: During a mean follow-up of 16 years, there were 1779 incident coronary heart disease events, 548 ischemic strokes, 1395 heart failure events, and 2793 deaths. Rates of all outcomes were higher in those with wider retinal venules and narrower retinal arterioles. Subjects with wider retinal venules (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.08–1.18; HR, 1.18; 95% CI, 1.07–1.31; and HR, 1.10; 95% CI, 1.00–1.20 per 1-SD increase) and narrower retinal arterioles (HR, 1.06; 95% CI, 1.01–1.11; HR, 1.14; 95% CI, 1.03–1.26; and HR, 1.13; 95% CI, 1.03–1.24 per 1-SD decrease) had a higher risk of death and stroke in both sexes and incident coronary heart disease in women but not men (interaction P =0.02) after adjustment for the Pooled Cohort Equations risk score variables. The association between retinal vessel caliber and heart failure was nonsignificant after adjustment for systolic blood pressure. Among women with Pooled Cohort Equations–predicted 10-year atherosclerotic cardiovascular disease event risk 5%). Conclusions: Narrower retinal arterioles and wider retinal venules conferred long-term risk of mortality and ischemic stroke in both sexes and coronary heart disease in women. These measures serve as an inexpensive, reproducible biomarker that added incremental value to current practice guidelines in atherosclerotic cardiovascular disease event risk prediction in low-risk women.