Perfusion Defect Area Research Articles

Experimental validation of coronary stenosis severity and development of ischemic myocardium

Introduction and objectivesThe current study aimed to evaluate the causal association between hemodynamically significant stenosis and the occurrence of ischemic myocardium using an experimental animal model of coronary artery stenosis. MethodsIn Yorkshire swine (n=10), coronary stenosis in the left anterior descending artery was induced using a customized vascular occluder to create varying degrees of occlusion severity (40%-99%). Serial changes in coronary pressure and flow velocity were measured in the left anterior descending artery before and after the implantation of the vascular occluder. At 1 month, 13N-ammonia positron emission tomography (PET) was performed, followed by the collection of isolated hearts for 2,3,5-Triphenyltetrazolium chloride (TTC) staining to quantify the percent area of necrotic myocardium. Three animals in the control group were evaluated using the same protocols, but without the implantation of a vascular occluder. ResultsThe median diameter stenosis after vascular occluder implantation was 61.3% (Q1-Q3: 55.9%-72.3%). Significant differences were observed in hyperemic stenosis resistance, fractional flow reserve (FFR), stress perfusion defect and reversibility in PET, as well as in necrotic myocardium in TTC staining based on stenosis severity (control group: <50%, 50%-70%, 70%-90%, and >90%) (all P<.010). Animals with FFR <0.75 at 1 month exhibited a significantly higher area of stress perfusion defect (30.7±3.1% vs 6.0±4.2%, P<.001), reversibility in PET (11.0±4.0% vs 0.0±0.0%, P=.006), and necrotic myocardium in TTC staining (15.8±6.4% vs 0.0±0.0%, P<.001) than those with FFR ≥ 0.75. ConclusionsIn a porcine model, the induction of hemodynamically significant stenosis with FFR <0.75 was associated with the development of stress perfusion defects and reversibility in PET, as well as necrotic myocardium identified by pathology.

To PE or Not to PE: Perfusion SPECT/CT Avoids Overdiagnosis.

A 41-year-old woman with metastatic breast cancer presented with dyspnea, hypoxia, and elevated d -dimer. Perfusion planar imaging followed by SPECT/CT of the chest was performed due to the patient's iodinated contrast allergy. Planar images showed multiple pleural-based wedge-shaped defects concerning for bilateral pulmonary embolism (PE). Perfusion SPECT/CT of the chest confirmed multiple areas of perfusion defects but was considered negative for PE and attributed the perfusion defects to the compressing of pulmonary vasculature from metastatic lymph nodes and pulmonary masses. Given the high pretest probability of PE, a CT pulmonary angiogram was performed after premedication for contrast allergy confirming absence of PE.

Inadequate response to adenosine infusion during cardiac stress magnetic resonance imaging.

ABSTRACTAim:To determine the factors associated with an inadequate response to adenosine infusion during cardiac stress magnetic resonance imaging (MRI).Study Design:It is a retrospective cohort study.Introduction:Stress cardiac MRI is a highly accurate and non-invasive method to diagnose coronary artery disease (CAD). Stress MRI is performed by inducing stress with adenosine infusion. There is an increase in systemic and myocardial blood flow (MBF) with vasodilator agents. Capillaries are maximally dilated in a diseased artery and cannot sustain increased myocardial oxygen demand. It results in delayed delivery of contrast, which leads to an area of perfusion defect in the myocardium. These perfusion defects can be accurately seen by cardiovascular magnetic resonance (CMR) and help in the prognosis of patients.Methods:A retrospective study on patients subjected to cardiac stress MRI was conducted in a Tertiary Care Cardiac Center from January 2019 to January 2022. In total, 99 patients underwent adenosine stress perfusion cardiac MRI. All patients received an adenosine infusion of 140 mcg/kg/min for 2 min. Subsequently, the dosage was increased by 20 mcg/kg/min every 2 min to a maximum of 210 mcg/kg/min until an adequate stress response was achieved. Adequate stress was defined as two or more of the following criteria: 1) Increase in heart rate >/= 10 beats per minute. 2) Decrease in systolic blood pressure SBP by >/= 10 mm Hg Symptoms like chest discomfort, breathlessness, and headache. Patients who satisfied two or more of the above criteria were labeled as responders and the patients who did not satisfy the above criteria with the maximum dose of 210 mcg/kg/min of adenosine infusion were labeled as non-responders. Multivariable logistic regression analysis with forward and backward stepwise selection was used to identify predictors in non-responders. Basic demographic variables with P value </= 0.2 were examined for inclusion in the model. A P value </= 0.05 was considered significant.Results:Nine patients (9.1%) showed inadequate stress response to adenosine infusion even with a maximum dose of 210 mcg/kg/min. Multivariate logistic regression analysis showed that left ventricular end-diastolic volume (LVEDV) was a predictor of inadequate response to adenosine infusion.Conclusion:Inadequate stress response to adenosine occurred in 9.1% of subjects with an infusion of 140–210 ug/kg/min. LVEDV is an independent and strong predictor in non-responders.

Myocardial perfusion scintigraphy in myocardial infarction - impact of ST-segment elevation and of Diabetes mellitus.

Myocardial perfusion scintigraphy (MPS) is frequently used in the evaluation of patients with coronary artery disease, either stable or with the prior remote acute coronary syndrome. The goal of the present work was to evaluate changes in MPS according to the nature of the infarction (ST-elevation vs non-ST elevation status) as well as according to the presence or absence of Diabetes mellitus. A prospective study of 124 consecutive patients with myocardial infarction (MI) was carried out using MPS. Patients with ST-segment elevation MI (STEMI) had significantly larger values both for percentage and absolute areas of perfusion defects, both at rest and in a stress situation, when compared to patients without ST-segment elevation (NSTEMI). These patients had significantly lower values for left ventricular ejection fractions (EF), in a similar comparison. The values for perfusion defects at rest for STEMI patients were more than double the values for NSTEMI patients (17.1 ± 14.6% vs 6.5 ± 7.8%, P < .001). Concerning resting left ventricular EF, STEMI patients had a mean value of 47.6 ± 13.6% and NSTEMI patients had a mean value of 53.2 ± 12.4% (P.026). Regarding the comparison between patients with and without Diabetes mellitus, none of the parameters under study showed significant differences. Linear regression analysis, taking the percentage of perfusion defect, as the dependent variable, yielded an overall significant result, however, only ST-segment elevation was shown to have an individually significant result. We conclude that the presence of ST-segment elevation but not the presence of Diabetes mellitus is associated with different patterns of MPS in patients with MI.

Cardiac schockwave therapy in the treatment of ischemic heart disease patiens with refractive angina pectoris

Objective: To evaluate of the effectiveness of cardiac shockwave therapy in the treatment of ischemic heart disease with refractive angina pectoris. Subject and method: A prospective, cross-sectional study with comparison and follow-up for 6 months on 50 patients with refractive angina pectoris from January 2017 to January 2020. The protocol application of 100 shocks/spot at 0.09mJ/mm2 energy flux density for 3 - 6 spots each time, with three times per week at each series for three series at 1, 5, 9 weeks. Result: The average age was 71.32 ± 10.5 years, men accounted for 78%. The symptoms of angina improved significantly (amount of chest pain 5.87 ± 2.7 to 0.28 ± 0.45 times; Nitrat consumed per week from 6.3 ± 3.5 to 0.3 ± 0.5 tablets/week). The 6-minute walking test all improved (278.1 ± 71m compared with 390.5 ± 42.3m). CCS angina class improved significant. NYHA grade improved significantly (NYHA III from 40.7% to 11.1%, NYHA II from 51.9% to 33.3%). Pro-BNP decreased (994.99 ± 1708.9 to 429.0 ± 453.9 pg/ml). WSMI decreased from 1.49 ± 0.22 to 1.24 ± 0.12, GLS improved from -9.79 ± 2.68 to -12.7 ± 2.42. Average score of SSS, SRS, SDS markedly improved with p&lt;0.05 by SPECT. The degree of severe perfusion defect and the wide perfusion defect area decreased significantly after treatment by 52% to 12% and 58% to 28%, respectively. Conclusion: Cardiac shockwave therapy improved clinical symptoms and increased myocardial perfusion in ischemic heart disease with refractive angina pectoris.

Visualization of Dynamic Expression of Myocardial Sigma-1 Receptor After Myocardial Ischemia and Reperfusion Using Radioiodine-Labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) Imaging.

This study chronologically evaluated the expression of the intensity and distribution of the sigma-1 receptor (σ1R) demonstrated by radiolabeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) in a rat model of myocardial ischemia and reperfusion. The left coronary artery was occluded for 30 min, followed by reperfusion. Dual-tracer autoradiography with 125I-OI5V and 99 mTc-MIBI was performed to assess the spatiotemporal changes in 125I-OI5V uptake (n=5-6). Significant and peaked 125I-OI5V uptake in the ischemic area was observed at 3 days after reperfusion, and the 125I-OI5V uptake ratio of ischemic area to normally perfused left ventricular area decreased gradually from 3 to 28 days (mean value±SD; 0.90±0.12 at 1 day, 1.89±0.19 at 3 days, 1.52±0.17 at 7 days, 1.34±0.13 at 14 days, and 1.16±0.14 at 28 days, respectively). Triple-tracer autoradiography with 125I-OI5V, 99 mTc-MIBI, and 201TlCl was performed to evaluate 125I-OI5V uptake in the ischemic area in relation to the residual perfusion at 7 days (n=4). The 125I-OI5V uptake ratio of the non-salvaged area was higher compared to that of the salvaged area in the ischemic area. 123I-OI5V and 99 mTc-MIBI SPECT/CT was performed 3 days after reperfusion (n=3), and the in vivo images showed clear uptake of 123I-OI5V in the perfusion defect area. The present study confirmed the spatiotemporal expression pattern of σ1R expression. Non-invasive σ1R imaging with 123I or 125I-OI5V was feasible to monitor the expression of σ1R after myocardial ischemia and reperfusion.

Left ventricular concentric remodeling and impaired cardiorespiratory fitness in patients with heart failure and preserved ejection fraction.

Left ventricular (LV) concentric remodeling refers to a process by which increased LV relative wall thickness alters myocardial geometry, resulting in reduced LV end-diastolic volume (LVEDV) and stroke volume (SV). While the degree of concentric remodeling is a negative prognostic factor in heart failure with preserved ejection fraction (HFpEF), it is not known how it contributes to cardiorespiratory fitness (CRF). We performed a retrospective analysis of patients with HFpEF who underwent treadmill single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) and cardiopulmonary exercise testing (CPX). From exercise SPECT-MPI, we recorded postexercise LVEDVi, LVESVi, SVi, LVEF, the presence and extent of perfusion defects, and perfusion reversibility. Peak oxygen consumption (VO<inf>2</inf>), the oxygen uptake efficiency slope (OUES), oxygen (O<inf>2</inf>) pulse, ventilatory efficiency (V<inf>E</inf>/VCO<inf>2</inf> slope), ventilatory anaerobic threshold, respiratory exchange ratio, exercise time, and maximum heart rate were obtained from CPX. Data are expressed as mean (±standard deviation). Univariate and multivariate linear regression was performed. We identified 23 subjects who had completed both an exercise SPECT-MPI and a CPX. Patients were more commonly women (83%), black (65%), middle age (50 [±7.3] years), and obese (Body Mass Index [BMI] 39.7 [±6.0] kg/m2). Greater LVEDVi and LVESVi correlated positively with peak VO<inf>2</inf> (R=+0.648, P=0.001; R=+0.601, P=0.002), O<inf>2</inf> pulse (R=+0.686, P<0.001; R=+0.625, P=0.001) and OUES (R=+0.882, P<0.001; R=+0.779, P<0.001). The LVEF correlated inversely with peak VO<inf>2</inf> and OUES (R=-0.450, P=0.031; R=-0.485, P=0.035). Perfusion defect area, grade of severity, and presence of reversibility were not associated with CRF variables. Postexercise reduced LV volumes correlate with measures of impaired CRF in patients with HFpEF, thus supporting a pathophysiologic role of concentric remodeling in impaired CRF in HFpEF.

Abstract P165: Cardiac Capillary Pericytes Constriction Mediates Sleep Deprivation Induced Coronary Microcirculation Dysfunction

Background: Lack of sleep can lead to a variety of adverse cardiovascular events and even sudden death. In most cases, there is no obstructive coronary artery. Coronary microcirculation dysfunction (CMD) is thereby thought to play an important role in cardiovascular events caused by sleep loss. Pericytes regulate blood flow and mediate neurovascular signaling in brain. Here, we hypothesized that cardiac capillary pericytes mediate sleep loss related CMD. Methods and Results: Eight-week-old male C57BL/6J mice were deprived sleep for 6 hours or 72 hours. Cardiac function was detected by transthoracic echocardiography before and after sleep deprivation (SD). Vascular endothelial dyes were perfusion before tissue harvest to evaluate cardiac perfusion. By whole heart clearing, 3D immunolabeling and imaging, the effect of pericytes on cardiac capillary was accessed. Acute 6-hours total sleep deprivation or 72-hours severe sleep deprivation led to decreased cardiac systolic and diastolic dysfunction. Left ventricular end diastolic diameter and left ventricular end systolic diameter increased by 10.12% (0.32 mm of 3.14 mm) and 19.00% (0.31 mm of 1.63 mm). Although coronary flow velocity reserve showed no differences between sleep deprivation and control groups, the basal and maximum coronary blood velocity were increased in acute and severe total sleep deprivation mice, which illustrated CMD. Compared with mice in the control group, the area of cardiac perfusion in the sleep deprivation group was significantly reduced (33.42 ± 4.30% vs. 53.81 ± 7.42%, P &lt; 0.05; SD group, n=7; control group, n=6). Whole mount heart imaging showed pericytes were widely distributed around the microvascular, without difference in regional distribution in the heart. In the area of cardiac perfusion defect, capillary blockages colocalized with pericytes, and the capillary diameter at the pericyte body was significantly reduced in sleep deprived mice (2.01 ± 0.12 μm vs. 2.92 ± 0.07 μm, P &lt; 0.05; SD group, n=10; control group, n=10). Conclusion: Sleep restriction led to cardiac dysfunction and CMD, that pericytes mediated contraction of capillaries might contribute to the process. Cardiac pericytes would be a novel therapeutic target in sleep loss associated heart disease.

Efficacy and Safety of Emergency Extracranial–Intracranial Bypass for Revascularization within 24 Hours in Resolving Large Artery Occlusion with Intracranial Stenosis

Endovascular treatment (EVT) is less effective for intracranial atherosclerosis-induced emergent large vessel occlusion. Extracranial-intracranial (EC-IC) bypass surgery is a possible treatment option to augment cerebral blood flow in the perfusion defect area. We compared the efficacy and safety of EC-IC bypass surgery with those of EVT and maximal medical treatment for acute ischemic stroke. The data from 39 patients, for whom vessel revascularization had failed despite mechanical thrombectomy, were retrospectively analyzed. Of the 39 patients, 22 had undergone percutaneous transluminal angioplasty or intracranial stenting (PTA/S), 10 had undergone emergency EC-IC bypass surgery within 24 hours of symptom onset, and 7 had received maximal medical treatment (MMT) only. The patency, perfusion status, and postoperative infarct volume were evaluated. The clinical outcomes were assessed at 6 months postoperatively using the modified Rankin scale. The mean reperfusion time was significantly longer for the EC-IC bypass group (14.9 hours) compared with that in the PTA/S group (4.1 hours) and MMT group (7.5 hours; P < 0.05). The postoperative infarct volume on diffusion-weighted magnetic resonance imaging was significantly lower in the emergency EC-IC bypass group (11.3 cm3) than in the MMT group (68.0 cm3) but was not significantly different from that of the PTA/S group (14.0 cm3; P < 0.05). The proportion of patients with a modified Rankin scale score of 0-2 at 6 months after surgery was significantly higher in the EC-IC bypass group (80%) than in the PTA/S (59%) and MMT (14%) groups (P < 0.05). Emergency EC-IC bypass surgery is an effective and safe treatment option for intracranial atherosclerosis-induced acute ischemic stroke for which EVT is inadequate.

Left ventricular concentric remodeling and impaired cardiorespiratory fitness in patients with heart failure and preserved ejection fraction

Left ventricular (LV) concentric remodeling refers to a process by which increased LV relative wall thickness alters myocardial geometry, resulting in reduced LV end-diastolic volume (LVEDV) and stroke volume (SV). While the degree of concentric remodeling is a negative prognostic factor in heart failure with preserved ejection fraction (HFpEF), it is not known how it contributes to cardiorespiratory fitness (CRF). We performed a retrospective analysis of patients with HFpEF who underwent treadmill single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) and cardiopulmonary exercise testing (CPX). From exercise SPECT-MPI, we recorded postexercise LVEDVi, LVESVi, SVi, LVEF, the presence and extent of perfusion defects, and perfusion reversibility. Peak oxygen consumption (VO<inf>2</inf>), the oxygen uptake efficiency slope (OUES), oxygen (O<inf>2</inf>) pulse, ventilatory efficiency (V<inf>E</inf>/VCO<inf>2</inf> slope), ventilatory anaerobic threshold, respiratory exchange ratio, exercise time, and maximum heart rate were obtained from CPX. Data are expressed as mean (±standard deviation). Univariate and multivariate linear regression was performed. We identified 23 subjects who had completed both an exercise SPECT-MPI and a CPX. Patients were more commonly women (83%), black (65%), middle age (50 [±7.3] years), and obese (Body Mass Index [BMI] 39.7 [±6.0] kg/m2). Greater LVEDVi and LVESVi correlated positively with peak VO<inf>2</inf> (R=+0.648, P=0.001; R=+0.601, P=0.002), O<inf>2</inf> pulse (R=+0.686, P<0.001; R=+0.625, P=0.001) and OUES (R=+0.882, P<0.001; R=+0.779, P<0.001). The LVEF correlated inversely with peak VO<inf>2</inf> and OUES (R=-0.450, P=0.031; R=-0.485, P=0.035). Perfusion defect area, grade of severity, and presence of reversibility were not associated with CRF variables. Postexercise reduced LV volumes correlate with measures of impaired CRF in patients with HFpEF, thus supporting a pathophysiologic role of concentric remodeling in impaired CRF in HFpEF.

Enhanced Role for Apoptosis in a Hepatic Ischaemia-Reperfusion Injury Model

Background:Prior to reperfusion, a variable period of ischaemia occurs in transplanted donor organs There is growing evidence that apoptosis contributes to the ischaemia-reperfusion injury conundrum that follows, but its extent has not been precisely quantified. Understanding its extent and effects can help find ways to mitigate or counteract such an injury in the liver. We therefore evaluated the extent of apoptosis semi-quantitatively from the expression of Caspase-3 and M30 in a porcine ex-vivo hepatic ischaemia-reperfusion injury model and correlated the timing of expression of M30 antibody with that of Caspase-3.Method:Livers were harvested from three healthy white Landrace Cross pigs and perfused for six hours using oxygenated extracorporeal circuits with heparinized autologous blood at 380C as described in our previous work [1]. A 2-hour delay prior to perfusion represented the period of ischaemia. All the livers were uniformly perfused. Three biopsies were taken for each of 7 time points (total 21); before dissection of the liver (BD) of the livers, after dissection (AD), after connection (AC) to the circuit, at one hour perfused (1hrP) &amp; non-perfused (1hrNP), at 4 hours perfused (4hrP) and non-perfused (4hrNP). Samples were stained with standard Haematoxylin–Eosin (HE) and immunohistochemically with Caspase-3 and M30 monoclonal antibodies. Positive cells were quantified using an ocular grid and expressed as number per square area. Cells positive for Caspase-3 &amp; M30 antibodies were counted on the whole section. Data were expressed as median number per square millimetre. Statistical analysis was done using AVOVA and t-test.Results: After four hours of perfusion, multiple areas of perfusion defects appeared macroscopically in all 3 livers. HE staining confirmed that these non-perfused areas were ischaemic. There was a gradual increase in Caspase-3 expression over time in all samples. There was no statistically significant difference in the Capase-3 and M30 between the 9 specimens at 1hrP (P=0.06) but there was a highly significant difference between Caspase-3 and M30 at 1hrNP (0.001). Caspase-3 expression peaked at 4hrP (P=0.001) and 4hrNP (P=0.03). A similar pattern was noted with M30 which peaked at 1hrP (P=0.001) and maintained a non-significant expression at 4hrP (P=0.07) and 4hNP (P=0.1).Conclusion: The significant expression of Caspase-3 and M30 confirms that apoptosis plays an important part in tissue loss in this model of liver ischemia-reperfusion injury. Inhibiting both Caspase-3 and M30 might be useful in alleviating hepatic reperfusion injury.?

Myocardial stress perfusion magnetic resonance in children with hypertrophic cardiomyopathy.

Microvascular dysfunction in hypertrophic cardiomyopathy has been associated with poor clinical outcome. Several studies have demonstrated a reduced perfusion reserve proportional to the magnitude of the hypertrophy. We investigated the utility of stress perfusion cardiac MRI to detect microvascular dysfunction in children with hypertrophic cardiomyopathy. From January 2016 to January 2017, 13 patients, with a mean age of 15.3 years, with hypertrophic cardiomyopathy underwent regadenoson stress perfusion cardiac MRI (1.5-T Siemens Aera). A single-shot, T1-weighted saturation recovery gradient echo was used for first-pass perfusion in a multiple-slices group, including three short-axis slices and one four-chamber slice. Coronary vasodilatory stress was achieved using bolus injection of regadenoson (lexiscan 0.4 mg/5 ml) and dynamic perfusion during rest and stress performed by administering 0.05 mmol/kg of gadolinium contrast agent (gadoteridol) injected at a rate of 3.5 ml/s, followed by assessment of viability using two-dimensional phase-sensitive inversion recovery of the entire myocardium. All patients completed protocols with no interruptions. In all, seven patients developed perfusion defects after the administration of regadenoson. Asymmetric septal hypertrophy was the most common pattern of hypertrophic cardiomyopathy (n=4) in those with abnormal perfusion. A total of four patients with perfusion defects had a maximum wall thickness <30 mm. The finding of perfusion defects in areas without late gadolinium enhancement in some of our patients indicates that gadolinium enhancement by itself could underestimate the true extension of microvascular disease. Out of seven patients, five patients with positive stress cardiac MRI have undergone implantable cardioverter defibrillator placement based on current guidelines. Regadenoson stress cardiac MRI is feasible and clinically valuable in paediatric patients. It is particularly effective in unmasking abnormal myocardial perfusion in the presence of microvascular dysfunction in children with hypertrophic cardiomyopathy.

Acute macular neuroretinopathy type 2: an unusual case

PurposeAcute Macular Neuroretinopathy (AMN) is a rare retinal disease distinguished in two different types. In type 1 the lesion occurs above the outer plexiform layer (OPL) interesting the inner nuclear layer (INL), differently in type 2 the lesion occurs below the OPL interesting the outer nuclear layer (ONL). Type 1 is more common among elderly, males, and associated with cardiovascular risk factors while type 2 is more usual in young and females.MethodsA 68 years‐old white man presented to Ophthalmic Emergency Room complaining the acute‐onset of a paracentral superonasal scotoma in his left eye. His medical history was significant for systemic arterial hypertension in good control with diuretics and sartans. He also refers primary open angle glaucoma in treatment with prostaglandin analogous in both eyes. We performed fluorescein and indocyanine green angiographies, spectral domain‐Optical Coherence Tomography (SD‐OCT), OCT angiography (OCTA), standard automated perimetry (SAP), microperimetry, and multifocal electroretinogram (mfERG).ResultsFluorescein and indocyanine green angiographies were unremarkable. SD‐OCT revealed a focal hyperreflective band that involved the OPL and ONL localized in the parafoveal inferior region. The SAP showed a superonasal scotoma that was confirmed by the mfERG trace decrease and the inferotemporal reduced retinal sensibility at microperimetry. OCTA revealed a deep retinal capillary plexus perfusion defect area inferotemporally to the fovea.ConclusionsOur case describes an unusual AMN type 2 that occurs in an elderly male patient affected by systemic arterial hypertension typical for type 1. These evidences suggest a closer pathogenic relationship between the two forms of AMN. Further studies will be able to determine whether AMN type 1 and AMN type 2 rapresent single or multiple entities.

CXCR7/p-ERK-Signaling Is a Novel Target for Therapeutic Vasculogenesis in Patients with Coronary Artery Disease.

Coronary artery disease (CAD) is characterized by insufficient vasculogenic response to ischemia, which is typically accompanied by dysfunction of endothelial outgrowth cells (EOCs). CXC chemokine receptor 7 (CXCR7) is a key modulator of the neovascularization of EOCs to perfusion defect area. However, the mechanism underlying the role of EOCs in CAD-related abnormal vasculogenesis is still not clear. Here, we investigated the alteration of EOCs-related vasculogenic capacity in patients with CAD and its potential mechanism. Compared with EOCs isolated from healthy subjects, EOCs from CAD patients showed an impaired vasculogenic function in vitro. CXCR7 expression of EOCs from CAD patients was downregulated. Meanwhile, the phosphorylation of extracellular signal-regulated kinase (ERK), downstream of CXCR7 signaling, was also reduced. CXCR7 expression introduced by adenovirus increased the phosphorylation of ERK, which was parallel to improved function of EOCs. The enhanced adhesion and vasculogenesis of EOCs can be blocked by short interfering RNA (siRNA) against CXCR7 and ERK inhibitor PD098059. Therefore, our study demonstrates that the upregulation of CXCR7 signaling contributes to increased vasculogenic capacity of EOCs from CAD patients, indicating that CXCR7 signaling may be a novel therapeutic vasculogenic target for CAD.

Evaluation of lung function with SPECT/CT lung perfusion imaging and the potential factors of perfusion defects in patients with non-small-cell lung cancer

Objective To assess the value of SPECT/CT lung perfusion imaging (SPECT/CT-LPI) in evaluation of the regional lung function and the correlation between lung perfusion defects (LPD) and the clinical findings in NSCLC patients. Methods A total of 48 NSCLC patients (43 males, 5 females; average age 61.06 years) who underwent pulmonary function tests (PFT), CT and 99Tcm-MAA SPECT/CT-LPI from December 2006 to March 2013, were retrospectively studied. LPD were divided into four grades: grade 0 (no lung perfusion defect was identified), grade 1 (the area of lung perfusion defect (LPDA) was similar to the size of local tumor), grade 2 (the LPDA was larger than local tumor and extends to 1 pulmonary lobe), grade 3 (the LPDA exceeded 1 pulmonary lobe). χ2 test, one-way analysis of variance and Logistic regression analysis were used to analyze the correlation of the lung perfusion function and clinical findings. Results LPD were found in 44 patients (91.67%, 44/48), including 18 with grade 1, 15 with grade 2, 11 with grade 3. The abnormal results of PFT were found in 16 patients (33.33%, 16/48). The abnormal findings by SPECT/CT-LPI were more than that by PFT (χ2=34.844, P 3.0 cm and ≤5.0 cm, 3 was assigned for >5.0 cm) and hilar lymph node (1 was assigned for with metastasis, 0 was assigned for no metastasis) (Wald=8.176, 5.352, 10.100, all P<0.05). Conclusions Compared with PFT, SPECT/CT-LPI has a more significant value in assessment of the regional lung function in NSCLC patients. Tumor location, tumor size and metastasis of hilar lymph nodes may be helpful for LPD grading. SPECT-LPI may be beneficial for patients with central lung cancer, large tumor and hilar lymph nodes metastasis. Key words: Carcinoma, non-small-cell lung; Tomography, emission-computed, single-photon; Tomography, X-ray computed; MAA

Change in Imaging Findings on Angiography-Assisted CT During Balloon-Occluded Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma.

To evaluate changes in imaging findings on CT during hepatic arteriography (CTHA) and CT during arterial portography (CTAP) by balloon occlusion of the treated artery and their relationship with iodized oil accumulation in the tumor during balloon-occluded transcatheter arterial chemoembolization (B-TACE). Both B-TACE and angiography-assisted CT were performed for 27 hepatocellular carcinomas. Tumor enhancement on selective CTHA with/without balloon occlusion and iodized oil accumulation after B-TACE were evaluated. Tumorous portal perfusion defect size on CTAP was compared with/without balloon occlusion. Factors influencing discrepancies between selective CTHA with/without balloon occlusion and the degree of iodized oil accumulation were investigated. Among 27 tumors, tumor enhancement on selective CTHA changed after balloon occlusion in 14 (decreased, 11; increased, 3). In 18 tumors, there was a discrepancy between tumor enhancement on selective CTHA with balloon occlusion and the degree of accumulated iodized oil, which was higher than the tumor enhancement grade in all 18. The tumorous portal perfusion defect on CTAP significantly decreased after balloon occlusion in 18 of 20 tumors (mean decrease from 21.9 to 19.1mm in diameter; p=0.0001). No significant factors influenced discrepancies between selective CTHA with/without balloon occlusion. Central area tumor location, poor tumor enhancement on selective CTHA with balloon occlusion, and no decrease in the tumorous portal perfusion defect area on CTAP after balloon occlusion significantly influenced poor iodized oil accumulation in the tumor. Tumor enhancement on selective CTHA frequently changed after balloon occlusion, which did not correspond to accumulated iodized oil in most cases.

Pulmonary Thromboendarterectomy for Chronic Thromboembolic Pulmonary Hypertension Due to Subclavian Vein Thrombosis From Bilateral First Rib Anomaly

SESSION TITLE: Pulmonary Vascular Disease Cases ISESSION TYPE: Affiliate Case Report SlidePRESENTED ON: Monday, October 26, 2015 at 11:00 AM - 12:00 PMINTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) results from unresolved pulmonary emboli originating from a site of venous thrombosis. Development of CTEPH from subclavian vein (SCV) thrombosis due to thoracic outlet syndrome has been rarely reported and none yet associated with bilateral first rib fractures.CASE PRESENTATION: A 19-year-old previously healthy female noted to have acute dyspnea and hemoptysis was diagnosed with acute pulmonary embolism. She was treated with low molecular weight heparin then warfarin at therapeutic levels. However, developed recurrent pulmonary embolism with severe right heart failure 4 months after her initial embolic event. A large left SCV thrombosis associated with thoracic outlet syndrome was identified. She was also noted to have symmetric bilateral healed first rib fractures on chest x-ray without any relatable trauma history. This was deemed to be the likely underlying cause of her thoracic outlet syndrome. She underwent successful directed thrombolysis and angioplasty of her left SCV. Right heart catheterization (RHC) was performed due to persistent dyspnea, which showed mean pulmonary artery pressure (mPAP) of 37mmHg. A computed tomography angiogram revealed abnormalities consistent with CTEPH. Patient was referred to a pulmonary thromboendarterectomy (PTE) specialty center. At the time of referral, her functional status was WHO class III with repeated presyncopal episodes and exertional dyspnea. A ventilation/perfusion (V/Q) scan showed multiple mismatched perfusion defects consistent with CTEPH. A hypercoagulability evaluation was unremarkable. A RHC preoperatively showed mPAP of 47mmHg and a pulmonary vascular resistance (PVR) of 775 dyne-second/cm5. Pulmonary angiography confirmed the presence of surgically-accessible chronic thromboembolic disease. She underwent a successful bilateral PTE with postoperative PVR of 227 dyne-second/cm5 and mPAP of 20mmHg. Postoperative V/Q scan showed improvement in the areas of preoperative perfusion defects. She was discharged home after an uneventful postoperative course.DISCUSSION: This illustrates an unusual case of CTEPH from upper extremity thrombosis associated with first rib anomaly. Also, hemodynamic and clinical improvement can be achieved with PTE for CTEPH due to this condition.CONCLUSIONS: Consideration for first rib anomaly should be included as part of evaluation of CTEPH secondary to SCV thrombosis.Reference #1: Kim N et al. Chronic Thromboembolic Pulmonary Hypertension. J Am Coll Cardiol. 2013;62:S92-9.DISCLOSURE: The following authors have nothing to disclose: Stephanie Shin, Peter Fedullo, Theodore Frank, William AugerNo Product/Research Disclosure Information SESSION TITLE: Pulmonary Vascular Disease Cases I SESSION TYPE: Affiliate Case Report Slide PRESENTED ON: Monday, October 26, 2015 at 11:00 AM - 12:00 PM INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) results from unresolved pulmonary emboli originating from a site of venous thrombosis. Development of CTEPH from subclavian vein (SCV) thrombosis due to thoracic outlet syndrome has been rarely reported and none yet associated with bilateral first rib fractures. CASE PRESENTATION: A 19-year-old previously healthy female noted to have acute dyspnea and hemoptysis was diagnosed with acute pulmonary embolism. She was treated with low molecular weight heparin then warfarin at therapeutic levels. However, developed recurrent pulmonary embolism with severe right heart failure 4 months after her initial embolic event. A large left SCV thrombosis associated with thoracic outlet syndrome was identified. She was also noted to have symmetric bilateral healed first rib fractures on chest x-ray without any relatable trauma history. This was deemed to be the likely underlying cause of her thoracic outlet syndrome. She underwent successful directed thrombolysis and angioplasty of her left SCV. Right heart catheterization (RHC) was performed due to persistent dyspnea, which showed mean pulmonary artery pressure (mPAP) of 37mmHg. A computed tomography angiogram revealed abnormalities consistent with CTEPH. Patient was referred to a pulmonary thromboendarterectomy (PTE) specialty center. At the time of referral, her functional status was WHO class III with repeated presyncopal episodes and exertional dyspnea. A ventilation/perfusion (V/Q) scan showed multiple mismatched perfusion defects consistent with CTEPH. A hypercoagulability evaluation was unremarkable. A RHC preoperatively showed mPAP of 47mmHg and a pulmonary vascular resistance (PVR) of 775 dyne-second/cm5. Pulmonary angiography confirmed the presence of surgically-accessible chronic thromboembolic disease. She underwent a successful bilateral PTE with postoperative PVR of 227 dyne-second/cm5 and mPAP of 20mmHg. Postoperative V/Q scan showed improvement in the areas of preoperative perfusion defects. She was discharged home after an uneventful postoperative course. DISCUSSION: This illustrates an unusual case of CTEPH from upper extremity thrombosis associated with first rib anomaly. Also, hemodynamic and clinical improvement can be achieved with PTE for CTEPH due to this condition. CONCLUSIONS: Consideration for first rib anomaly should be included as part of evaluation of CTEPH secondary to SCV thrombosis. Reference #1: Kim N et al. Chronic Thromboembolic Pulmonary Hypertension. J Am Coll Cardiol. 2013;62:S92-9. DISCLOSURE: The following authors have nothing to disclose: Stephanie Shin, Peter Fedullo, Theodore Frank, William Auger No Product/Research Disclosure Information

Sympathetic nerve damage and restoration after ischemia-reperfusion injury as assessed by (11)C-hydroxyephedrine.

An altered state of the cardiac sympathetic nerves is an important prognostic factor in patients with coronary artery disease. The aim of this study was to investigate regional sympathetic nerve damage and restoration utilizing a rat model of myocardial transient ischemia and a catecholamine analog PET tracer, (11)C-hydroxyephedrine ((11)C-HED). Transient myocardial ischemia was induced by coronary occlusion for 20min and reperfusion in male Wistar rats. Dual-tracer autoradiography was performed subacutely (7days) and chronically (2months) after ischemia, and in control rats without ischemia using (11)C-HED as a marker of sympathetic innervation and (201)TI for perfusion. Additional serial in vivo cardiac (11)C-HED and (18)F-FDG PET scans were performed in the subacute and chronic phases after ischemia. After transient ischemia, the (11)C-HED uptake defect areas in both the subacute and chronic phases were clearly larger than the perfusion defect areas in the midventricular wall. The subacute (11)C-HED uptake defect showed a transmural pattern, whereas uptake recovered in the subepicardial portion in the chronic phase. Tyrosine hydroxylase antibody nerve staining confirmed regional denervation corresponding to areas of decreased (11)C-HED uptake. Serial in vivo PET imaging visualized reductions in the area of the (11)C-HED uptake defects in the chronic phase consistent with autoradiography and histology. Higher susceptibility of sympathetic neurons compared to myocytes was confirmed by a larger (11)C-HED defect with a corresponding histologically identified region of denervation. Furthermore, partial reinnervation was observed in the chronic phase as shown by recovery of subepicardial (11)C-HED uptake.

Infectious Myocarditis on FDG-PET Imaging Mimicking Sarcoidosis

Cardiac positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) is often used for the diagnosis of cardiac involvement in sarcoidosis. Areas of segmental perfusion defects coupled with FDG uptake are considered to represent active inflammation. However, these findings may be associated with other inflammatory myocardial diseases. We describe a case of tuberculous myocarditis with imaging findings mimicking those found in cardiac sarcoidosis.

Exercise echocardiography and cardiac magnetic resonance imaging to predict outcome in patients with hypertrophic cardiomyopathy†

We have observed that wall motion abnormalities (WMAs) during exercise echocardiography (ExE) are associated to events in hypertrophic cardiomyopathy (HCM). Our objective was to evaluate ExE and cardiac magnetic resonance (CMR) to predict outcome in HCM. ExE and CMR were performed in 148 patients with HCM. During follow-up (7.1 ± 2.7 years), there were 7 hard events (Hard-E) and 26 combined events (Comb-E). Exercise WMAs were observed in 13 patients (8.8%), perfusion defects in 10 (6.8%), and late gadolinium enhancement (LGE) in 48 (32.4%). WMAs were seen in 57% of patients with Hard-E vs. 6% without (P = 0.001) and in 23 and 6% with and without Comb-E (P = 0.005). Perfusion defects were also more frequent in patients with Hard-E than without (43 vs. 5%, P = 0.007) and in patients with Comb-E than without (23 vs. 5%, P = 0.002). LGE (g) was greater in patients with Comb-E than without [median (25th-75th percentile) 0 (0-21.1) vs. 0 (0-9.3) g P = 0.04]. Univariable predictors of Comb-E included NYHA class ≥2, peak double product, ΔWMSI, and CMR data. Peak double product [Hazard ratios (HR) = 0.99, confidence intervals (CI) 95% 0.99-0.99, P = 0.02] and ΔWMSI (HR = 404, CI 95% 12-13681, P = 0.001) remained independent predictors. Peak WMSI correlated with myocardial mass with LGE (r = 0.20, P = 0.02) and with perfusion defect area (r = 0.40, P < 0.001). LGE affecting ≥15% of the left ventricle was observed in 38% of patients with exercise WMAs vs. 12% without (P = 0.009). CMR data are associated to exercise WMAs in patients with HCM. ExE and CMR may help to predict outcome in them.