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Purpose: Hyperpolarized [1- 13C]pyruvate MRS can measure cardiac metabolism in vivo. We investigated whether [1- 13C]pyruvate MRS could predict left ventricular remodeling following myocardial infarction (MI), long-term left ventricular effects of heart failure medication, and could identify responders to treatment. Methods: Thirty-five rats were scanned with hyperpolarized [1- 13C]pyruvate MRS 3 days after MI or sham surgery. The animals were re-examined after 30 days of therapy with β-blockers and ACE-inhibitors (active group, n = 12), placebo treatment (placebo group, n = 13) or no treatment (sham group, n = 10). Furthermore, heart tissue mitochondrial respiratory capacity was assessed by high-resolution respirometry. Metabolic results were compared between groups, over time and correlated to functional MR data at each time point. Results: At 30 ± 0.5 days post MI, left ventricular ejection fraction (LVEF) differed between groups (sham, 77% ± 1%; placebo, 52% ± 3%; active, 63% ± 2%, P 13C]pyruvate MRS and respirometry, neither differed between groups nor between baseline and follow-up. Three days post MI, low bicarbonate + CO 2/pyruvate ratio was associated with low LVEF. At follow-up, in the active group, a poor recovery of LVEF was associated with high bicarbonate + CO 2/pyruvate ratio, as measured by hyperpolarized MRS. Conclusion: In a rat model of moderate heart failure, medical treatment improved function, but did not on average influence [1- 13C]pyruvate flux as measured by MRS; however, responders to heart failure medication had reduced capacity for carbohydrate metabolism.

The effect of limb remote ischaemic conditioning (RIC) on myocardial infarct (MI) size and left ventricular ejection fraction (LVEF) was investigated in a pre-planned cardiovascular magnetic resonance (CMR) substudy of the CONDI-2/ERIC-PPCI trial. This single-blind multi-centre trial (7 sites in UK and Denmark) included 169 ST-segment elevation myocardial infarction (STEMI) patients who were already randomised to either control (n = 89) or limb RIC (n = 80) (4 × 5 min cycles of arm cuff inflations/deflations) prior to primary percutaneous coronary intervention. CMR was performed acutely and at 6 months. The primary endpoint was MI size on the 6 month CMR scan, expressed as median and interquartile range. In 110 patients with 6-month CMR data, limb RIC did not reduce MI size [RIC: 13.0 (5.1–17.1)% of LV mass; control: 11.1 (7.0–17.8)% of LV mass, P = 0.39], or LVEF, when compared to control. In 162 patients with acute CMR data, limb RIC had no effect on acute MI size, microvascular obstruction and LVEF when compared to control. In a subgroup of anterior STEMI patients, RIC was associated with lower incidence of microvascular obstruction and higher LVEF on the acute scan when compared with control, but this was not associated with an improvement in LVEF at 6 months. In summary, in this pre-planned CMR substudy of the CONDI-2/ERIC-PPCI trial, there was no evidence that limb RIC reduced MI size or improved LVEF at 6 months by CMR, findings which are consistent with the neutral effects of limb RIC on clinical outcomes reported in the main CONDI-2/ERIC-PPCI trial.

Background Cadmium is a toxic element in cigarette smoke associated with ischemic vascular disease. Its association with cerebral aneurysm is unknown. Methods We retrospectively analyzed the medical records of patients with headache who underwent imaging studies between March 2014 and August 2016. An unruptured intracranial aneurysm (UIA) was confirmed by brain magnetic resonance angiography or computed tomography angiography. A control group included age- and sex-matched patients without an UIA. Whole blood and random urine tests were used for detection of cadmium and arsenic levels, respectively. Student t-test was used to compare subject characteristics, mean cadmium and arsenic levels between groups, and differences between groups with small (2.0 mcg/L (OR, 1.39; 95% CI, 1.15–1.84; P=0.043) were associated with aneurysm incidence. Conclusion UIA incidence was associated with pack-years of smoking and serum cadmium level, but aneurysm size was not associated with serum cadmium level.

The purpose of the study was to validate by histopathology, contrast enhanced cine steady-state free precession and T2-weighted CMR for the assessment of ischemic myocardial area-at-risk (AAR) in the presence of microvascular obstruction (MVO). Eleven anesthetized pigs underwent CMR 7 to 10 days post infarction. The area-at-risk was measured from T2-weighted fast spin echo (T2-STIR) and contrast-enhanced steady-state free precession magnetic resonance imaging (CE-SSFP) images using semi-automated algorithms based on a priori knowledge of perfusion territory. Also, late gadolinium enhancement (LGE) was performed to measure final infarct size (FIS). Histopathological comparison with Evans blue dye to define AAR and triphenyltetrazolium chloride to define FIS served as the reference. All infarcts demonstrated MVO on LGE images. Bland-Altman analysis showed no significant bias in AAR or myocardial salvage between T2-STIR and CE-SSFP or between CMR and histopathology. The mean differences ± 2SD from Bland-Altman analysis were: AAR: Evans Blue vs. T2-STIR [0.7%; + 13.5%; - 12.1%]; AAR: Evans Blue vs. CE-SSFP [0.1%; + 13.8%; - 13.7%]; AAR: T2-STIR vs. CE-SSFP [0.7%; + 6.2%; - 4.9%]; Salvage: Evans Blue - TTC vs. T2-STIR-LGE [0.8%; + 11.1%; - 9.6%]; Salvage: Evans Blue - TTC vs. CE-SSFP-LGE [0.1%; + 9.9%; - 9.6%]; Salvage: CE-SSFP-LGE vs. T2-STIR-LGE [0.7%; + 6.2%; - 4.9%]. Both T2-STIR and CE-SSFP sequences allow for unbiased quantification of AAR in the presence of ischemia/reperfusion injury when analysed by semi-automated algorithms. These experimental data, which was validated by histopathology, supports the use of CMR for the assessment of myocardial salvage during the subacute phase.

Background Stroke is a serious complication in patients with type 2 diabetes (T2DM). Arterial stiffness may improve stroke prediction. We investigated the association between carotid-femoral pulse wave velocity [PWV] and the progression of cerebral white matter hyperintensities (WMH), a marker of stroke risk, in patients with T2DM and controls. Methods In a 5-year cohort study, data from 45 patients and 59 non-diabetic controls were available for analysis. At baseline, participants had a mean (± SD) age of 59 ± 10 years and patients had a median (range) diabetes duration of 1.8 (0.8–3.2) years. PWV was obtained by tonometry and WMH volume by an automated segmentation algorithm based on cerebral T2-FLAIR and T1 MRI (corrected by intracranial volume, cWMH). High PWV was defined above 8.94 m/s (corresponding to the reference of high PWV above 10 m/s using the standardized path length method). Results Patients with T2DM had a higher PWV than controls (8.8 ± 2.2 vs. 7.9 ± 1.4 m/s, p Conclusions PWV is associated with cWMH progression in patients with type 2 diabetes and non-diabetic controls. Our results indicate that arterial stiffness may be involved early in the pathophysiology leading to cerebrovascular diseases.

Background To investigate if acute pulmonary vasodilation by sildenafil improves right ventricular function in patients with acute intermediate-high risk pulmonary embolism (PE). Methods Single center, explorative trial. Patients with PE were randomized to a single oral dose of sildenafil 50 mg (n = 10) or placebo (n = 10) as add-on to conventional therapy. The time from hospital admission to study inclusion was 2.3 ± 0.7 days. Right ventricular function was evaluated immediately before and shortly after (0.5–1.5 h) randomization by right heart catheterization (RHC), trans-thoracic echocardiography (TTE), and cardiac magnetic resonance (CMR). The primary efficacy endpoint was cardiac index measured by CMR. Results Patients had acute intermediate-high risk PE verified by computed tomography pulmonary angiography, systolic blood pressure of 135 ± 18 (mean ± SD) mmHg, increased right ventricular/left ventricular ratio 1.1 ± 0.09 and increased troponin T 167 ± 144 ng/L. Sildenafil treatment did not improve cardiac index compared to baseline (0.02 ± 0.36 l/min/m2, p = 0.89) and neither did placebo (0.00 ± 0.34 l/min/m2, p = 0.97). Sildenafil lowered mean arterial blood pressure (− 19 ± 10 mmHg, p p = 0.97). Conclusion A single oral dose of sildenafil 50 mg did not improve cardiac index but lowered systemic blood pressure in patients with acute intermediate-high risk PE. The time from PE to intervention, a small patient sample size and low pulmonary vascular resistance are limitations of this study that should be considered when interpreting the results. Trial Registration: The trial was retrospectively registered at www.clinicaltrials.gov (NCT04283240) February 2nd 2020, https://clinicaltrials.gov/ct2/show/NCT04283240?term=NCT04283240&draw=2&rank=1.

Renal ischemia-reperfusion injury (IRI) is one of the most common types of acute kidney injury. Spironolactone has shown promising kidney protective effects in renal IRI in rats. We investigated the hemodynamic and metabolic effects of spironolactone (100 mg/kg) administered immediately after 40 min unilateral kidney ischemia in rats. Hyperpolarized MRI using co-polarized [1-13 C]pyruvate and [13 C,15 N2 ]urea as well as 1 H dynamic contrast-enhanced (DCE) MRI was performed 24 h after induction of ischemia. We found a significant decrease in renal blood flow (RBF) in the ischemic kidney compared with the contralateral one measured using DCE and [13 C,15 N2 ]urea. The RBF measured using [1-13 C]pyruvate and [13 C,15 N2 ]urea was significantly altered by spironolactone. The RBFs in the ischemic kidney compared with the contralateral kidney were decreased similarly as measured using both [13 C,15 N2 ]urea and [1-13 C]pyruvate in the spironolactone-treated group. Spironolactone treatment increased the perfusion-corrected pyruvate metabolism by 54% in both the ischemic and contralateral kidney. Furthermore, we showed a correlation between vascular permeability using a histological Evans blue analysis and the ratio of the volumes of distribution (VoDs), ie VoD-[13 C,15 N2 ]urea/VoD-[1-13 C]pyruvate. This suggests that [13 C,15 N2 ]urea/[1-13 C]pyruvate VoD ratio may be a novel indicator of renal vascular permeability associated with renal damage in rodents.

Purpose: Owing to its noninvasive nature, hyperpolarized MRI may improve delineation of myocardial metabolic derangement in heart disease. However, consistency may depend on the changeable nature of cardiac metabolism in relation to whole-body metabolic state. This study investigates the impact of feeding status on cardiac hyperpolarized MRI in a large animal model resembling human physiology. Methods: Thirteen 30-kg pigs were subjected to an overnight fast, and 5 pigs were fed a carbohydrate-rich meal on the morning of the experiments. Vital parameters and blood samples were registered. All pigs were then scanned by hyperpolarized [1- 13 C]pyruvate cardiac MRI, and results were compared between the 2 groups and correlated with circulating substrates and hormones. Results: The fed group had higher blood glucose concentration and mean arterial pressure than the fasted group. Plasma concentrations of free fatty acids (FFAs) were decreased in the fed group, whereas plasma insulin concentrations were similar between groups. Hyperpolarized MRI showed that fed animals had increased lactate/pyruvate, alanine/pyruvate, and bicarbonate/pyruvate ratios. Metabolic ratios correlated negatively with FFA levels. Conclusion: Hyperpolarized MR can identify the effects of different metabolic states on cardiac metabolism in a large animal model. Unlike previous rodent studies, all metabolic derivatives of pyruvate increased in the myocardium of fed pigs. Carbohydrate-rich feeding seems to be a feasible model for standardized, large animal hyperpolarized MRI studies of myocardial carbohydrate metabolism.

Purpose We aimed to identify and assess cardiac abnormalities by cardiovascular magnetic resonance (CMR) in a non-ischaemic aborted sudden cardiac death (SCD) population and to establish possible predictors of SCD. Methods Thirty-six consecutive SCD survivors [median age 37.6 years (IQR 24.1-43.2), 31% female] with no previous cardiac history or evidence of ischaemic heart disease underwent CMR on day 6 (IQR 4-10) after admission. Data on ventricular volumes and the extent of late gadolinium enhancement (LGE) were collected. Systolic strain analysis was performed using feature tracking software. Results Left ventricular (LV) and right ventricular (RV) indexed diastolic volumes were 92.9 ± 28.4 ml/m2 and 94.1 ± 29 ml/m2, respectively. LV ejection fraction (EF) and RV EF were 56.8 ± 10.7% and 53.7 ± 10.7%, respectively. Global peak endocardial longitudinal, circumferential, and radial strain were −17.9 ± 4.28%, −23.2 ± 5.8%, and 32.8 ± 10.6%, respectively. Compared to normal range, global longitudinal endocardial strain, longitudinal epicardial strain, circumferential endocardial strain, radial strain, and circumferential endocardial strain rate were impaired. Median volume of LGE was 0.25% (IQR 0.12-1.12) of the LV myocardium with highest prevalence in the inferolateral wall. Patients with cardiomyopathy diagnosis (n = 16) had lower LV strain rate compared to patients without cardiomyopathy (n = 20). Conclusions CMR findings in young patients with aborted SCD due to non-ischaemic heart disease seem to be minor. Although only present in small amounts, LGE appears to have a predilection towards the inferolateral wall in this population.

Purpose Deranged metabolism is now recognized as a key causal factor in a variety of heart diseases, and is being studied extensively. However, invasive methods may alter metabolism, and conventional imaging techniques measure tracer uptake but not downstream metabolism. These challenges may be overcome by hyperpolarized MR, a noninvasive technique currently crossing the threshold into human trials. The aim of this study was to image metabolic changes in the heart in response to endogastric glucose bolus and to acute hypertension. Methods Five postprandial pigs were scanned with hyperpolarized [1-13 C]pyruvate cardiac MR at baseline, after oral glucose bolus, and after infusion of angiotensin-II. Results No effect of glucose bolus was seen using hyperpolarized [1-13 C]pyruvate MR despite changes in circulating substrates. During angiotensin-II infusion, blood pressure increased 179% (P = 0.008) and ejection fraction decreased from 54 ± 2% to 47 ± 6% (P = 0.03) The hemodynamic changes were accompanied by increases in the hyperpolarized [1-13 C]pyruvate MR derived ratios of lactate/alanine (from 0.58 ± 0.13 to 0.78 ± 0.06, P = 0.03) and bicarbonate/alanine (from 0.55 ± 0.12 to 0.91 ± 0.14, P = 0.007). Conclusion Glucose loading did not alter cardiac metabolism, but during acute hypertensive stress, cardiac aerobic, carbohydrate metabolism, and pyruvate-lactate exchange was altered. Hyperpolarized MR allows noninvasive evaluation of acute changes in cardiac metabolism. However, hemodynamics must be taken into account when interpreting the results.

Objective Perturbations in the insulin-like growth factor (IGF) system may contribute to the accelerated cardiovascular disease (CVD) that occurs in patients with type 2 diabetes (T2D). However, it remains unknown whether the IGF system is also involved in the development of early, subclinical CVD. We characterised the IGF system in T2D patients and matched controls and examined the associations with markers of subclinical target organ damage. Methods The study included 99 patients with recently diagnosed T2D and 99 age- and sex-matched controls. IGF-1 and IGFBP-1 to -4 were measured by immunoassays, as were pregnancy-associated plasma protein-A (PAPP-A) and the PAPP-A-generated N-terminal (NT) and C-terminal (CT) IGFBP-4 fragments, which are novel CVD risk markers. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (PWV). Cerebral white matter lesions (WMLs) and carotid artery remodelling were determined by MRI. Results After multivariate adjustments, patients with T2D had lower concentrations of IGFBP-2, IGFBP-4, NT- and CT-IGFBP-4, when compared with controls. IGFBP-2 was inversely correlated to PWV in all subjects in multivariate analysis (P P P = 0.011). Levels of NT- and CT-IGFBP-4 were reduced in T2D patients receiving metformin compared to those in controls and patients not receiving metformin. Conclusions Even in recently diagnosed and well-controlled T2D patients, IGF protein levels are altered and associated with CVD risk factors.

Nonalcoholic fatty liver disease (NAFLD) is very prevalent worldwide and is associated with insulin resistance and metabolic syndrome. Stress is a physiological and biological response to maintain homeostasis of the body against stressors while severe stress response is an important contributor to various illnesses, including metabolic syndrome and brain disorders. We have evaluated the effects of intermittent restraint stress on NAFLD in a high-fat diet (HFD)-fed mouse model. C57/BL6 mice had free access to a 60% HFD for 8 wk, with or without intermittent restraint stress (3 h) conducted three times a week. HFD administration increased fat accumulation in liver tissues. Unlike the stressed standard diet group, the levels of hepatic total cholesterol and triglycerides were significantly ameliorated in the HFD with stress group compared with the HFD alone group. These beneficial results were in accordance with serum levels of liver enzymes (aspartate transaminase, alanine transaminase) and hepatic levels of TNF-α and oxidative stress parameters (reactive oxygen species, nitric oxide, and malondialdehyde). The intermittent restraint stress significantly attenuated the HFD-derived alterations in serum insulin levels, hepatic protein kinase B activity, and gene expression, especially related to lipogenesis. This intermittent restraint stress also elevated the serum epinephrine concentration and activated the adrenergic receptor β2 or β3 in livers or white adipose tissue (WAT). Activation of energy expenditure markers (uncoupling protein 1, peroxisome proliferator-activated receptor-γ coactivator-1α) in brown adipose tissue and the browning of WAT were also observed in the HFD with stress group. Taken together, our findings showed the beneficial effects of sympathetic activation by intermittent restraint stress on HFD-induced hepatic steatosis and partial inflammation.NEW & NOTEWORTHY In modern society, stress is a part of daily life, and a certain level of stress is inevitable to most of the general population. Uncontrolled severe stress is obviously harmful; however, certain kind/level of stress could be beneficial on lipid metabolism via sympathetic activation. Our data suggest that a sympathetic activation by intermittent restraint stress could play a positive role in maintaining the balance of hepatic lipid metabolism, especially under high-fat diet conditions.

Background Myocardial external efficiency (MEE) is defined as the ratio of kinetic energy associated with cardiac work [forward cardiac output (FCO)*mean systemic pressure] and the chemical energy from oxygen consumed (MVO2) by the left ventricular mass (LVM). We developed a fully automated method for estimating MEE based on a single 11C-acetate PET scan without ECG-gating. Methods and Results Ten healthy controls, 34 patients with aortic valve stenosis (AVS), and 20 patients with mitral valve regurgitation (MVR) were recruited in a dual-center study. MVO2 was calculated using washout of 11C -acetate activity. FCO and LVM were calculated automatically using dynamic PET and parametric image formation. FCO and LVM were also obtained using cardiac magnetic resonance (CMR) in all subjects. The correlation between MEEPET-CMR and MEEPET was high (r = 0.85, P

Background: As one of forces extrinsic to the myocardium, we hypothesized that epicardial fat may contribute to diastolic dysfunction. The objective of this study was to evaluate epicardial fat as a contributing factor to diastolic function. Methods: Two hundred and twenty-one patients without significant arrhythmia, left ventricular hypertrophy, significant valvular disease, decreased left ventricular systolic function, or coronary artery disease were studied. Epicardial fat thickness on the free wall of the right ventricle was measured at end-diastole from the parasternal long-axis views of 3 cardiac cycles. Diastolic function was evaluated using the left atrium volume index, mitral inflow parameters (E, A, E/A, DT [deceleration time]) and mitral annular tissue-Doppler imaging parameters (E’, A’, E/E’). Results: Two hundred and twenty-one patients were divided into 2 groups according to diastolic pattern (normal versus abnormal mitral inflow pattern). There were significant differences in epicardial fat thickness (0.31±0.11 mm vs. 0.48±0.2 mm; P

Objectives This study sought to determine the effect of contact force (CF) on atrial lesion size, quality, and transmurality by using a chronic porcine model of radiofrequency ablation. Background CF is a major determinant of ventricular lesion formation, but uncertainty exists regarding the most appropriate CF parameters to safely achieve permanent, transmural lesions in the atria. Methods Intercaval linear ablation (30 W, 42°C, 17 ml/min irrigation) was performed in 8 Gottingen minipigs by using a force-sensing catheter with CF >20 g (high force) or Results Mean CF was 22.6 ± 11.4 g and 7.8 ± 4.0 g in the high and low CF regions. Acute tissue edema was greater with high CF, both caudally (7.0 mm vs. 4.6 mm; p = 0.016) and cranially (6.9 mm vs. 4.6 mm; p = 0.038). There was no difference in chronic lesion size (voltage mapping) or volume (late gadolinium enhancement CMR) between high and low CF regions. There was no difference in scar density (assessed by low-voltage criteria and late gadolinium enhancement signal intensity) or histological transmurality between high and low CF regions. Conclusions Although high CF (>20 g) resulted in more acute tissue edema than low CF (

Remote ischemic conditioning (RIC) protects against acute ischemia-reperfusion injury and may also have beneficial effects in patients with stable cardiovascular disease. We investigated the effect of long-term RIC treatment in patients with chronic ischaemic heart failure (CIHF). In a parallel group study, 22 patients with compensated CIHF and 21 matched control subjects without heart failure or ischemic heart disease were evaluated by cardiac magnetic resonance imaging, cardiopulmonary exercise testing, skeletal muscle function testing, blood pressure measurement and blood sampling before and after 28 ± 4 days of once daily RIC treatment. RIC was conducted as four cycles of 5 min upper arm ischemia followed by 5 min of reperfusion. RIC did not affect left ventricular ejection fraction (LVEF) or global longitudinal strain (GLS) in patients with CIHF (p = 0.63 and p = 0.11) or matched controls (p = 0.32 and p = 0.20). RIC improved GLS in the subgroup of patients with CIHF and with NT-proBNP plasma levels above the geometric mean of 372 ng/l (p = 0.04). RIC did not affect peak workload or oxygen uptake in either patients with CIHF (p = 0.26 and p = 0.59) or matched controls (p = 0.61 and p = 0.10). However, RIC improved skeletal muscle power in both groups (p = 0.02 for both). In patients with CIHF, RIC lowered systolic blood pressure (p < 0.01) and reduced NT-proBNP plasma levels (p = 0.02). Our findings suggest that long-term RIC treatment does not improve LVEF but increases skeletal muscle function and reduces blood pressure and NT-proBNP in patients with compensated CIHF. This should be investigated in a randomized sham-controlled trial.

Background The prevalence of Non-alcoholic fatty liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH) has increased by 15–39% worldwide, but no pharmaceutical therapeutics exists. Hypothesis/Purpose This study investigated anti-hepatosteatotic effect of CGplus (a standardized herbal composition of Artemisia iwayomogi, Amomum xanthioides, and Salvia miltiorrhiza) and its underlying mechanisms in a tunicamycin-induced NASH model. Methods C57/BL6J male mice were orally administrated CGplus (50, 100, or 200 mg/kg), dimethyl dimethoxy biphenyl dicarboxylate (DDB, 50 mg/kg) or distilled water daily for 5 days. 18 h after a single injection of tunicamycin (ip, 2 mg/kg), the parameters for hepatic steatosis and inflammation were measured. Results Pretreatment with CGplus significantly attenuated the accumulation of triglycerides and total cholesterol as well as lipid peroxidation, evidenced by quantitative and histopathological analyses in liver tissues. The elevations of serum aspartate transaminase, alanine transaminase and lactate dehydrogenase were significantly ameliorated by CGplus. Also, it normalized the altered activities of pro- (TNF-α, IL-1β and IL-6), anti-inflammatory (IL-10) cytokines and lipid metabolism-related molecules in protein and gene expression analyses. Conclusion Our data present experimental evidence for the potential of CGplus as an herbal therapeutic against NAFLD and NASH. Its underlying mechanisms may involve the modulations of pro- and anti-inflammatory cytokines, but further study is required especially for the actions of CGplus on lipid metabolisms.

Background— Currently, no pharmacological treatment can modify the natural history of aortic valve stenosis (AS). This underlines the critical need to explore novel treatment strategies, which could postpone or prevent the need for aortic valve replacement in patients with asymptomatic AS. The objectives of this study were to investigate whether metoprolol reduce the hemodynamic and metabolic burden imposed by AS. Methods and Results— In a double-blinded design, 40 patients with moderate-severe asymptomatic AS (aortic valve area, 0.5±0.1 cm 2 /m 2 ; peak gradient, 53±19 mm Hg) were randomized to placebo or metoprolol treatment for 22 weeks. Patients were evaluated by echocardiography, cardiovascular magnetic resonance, and 11 C-acetate positron emission tomography. Compared with placebo, metoprolol (100±53 mg/d) decreased heart rate; mean difference (95% confidence interval) −8 minute − 1 (−13, −3; P =0.003) and increased ejection time 26 ms (2, 50; P =0.03). Furthermore, metoprolol reduced aortic valve peak −7 mm Hg (−13, 0; P =0.05) and mean −4 mm Hg (−7, −1; P =0.03) gradients, without affecting stroke volume 3 mL/m 2 (−2, 8; P =0.16). Valvuloarterial impedance (ie, global afterload) and myocardial oxygen consumption were reduced by −11% and −12% ( P =0.03 and 0.01), respectively; and decreased heart rate correlated with lower valvuloarterial impedance, myocardial oxygen consumption, and improved myocardial efficiency defined as stroke work/myocardial oxygen consumption ( r =0.63–0.65; all P Conclusions— In patients with asymptomatic AS, metoprolol increases systolic ejection time and reduces aortic valve gradients, global afterload, and myocardial oxygen requirements. Thus, metoprolol displays favorable hemodynamic and metabolic effects and could improve outcome in patients with asymptomatic AS. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02076711.

The concept of vulnerable coronary atherosclerotic plaques prone to cause acute coronary syndrome (ACS) was originally promoted by histopathologic autopsy studies in patients dying from myocardial infarction [(1)][1]. Because traditional risk factors are ineffective in predicting cardiovascular risk

Background— Circulating lipid levels and myocardial lipid content (MyLC) is increased in type 2 diabetes mellitus. This may cause a state of lipotoxicity that compromises left ventricular function and aggravate heart failure. We investigated the relationship among circulating lipid levels, MyLC, and cardiac function together with the acute cardiac effects of high as opposed to low circulating free fatty acid (FFA) and triglyceride levels in patients with type 2 diabetes mellitus and heart failure. Methods and Results— Eighteen patients underwent 8-hour intralipid/heparin-infusion (high FFA) and hyperinsulinemic-euglycemic clamping (low FFA) in a randomized crossover–designed study. We applied magnetic resonance proton spectroscopy to measure MyLC. Cardiac function was assessed by advanced echocardiography, cardiopulmonary exercise, and MRI. MyLC correlated positively with circulating triglyceride ( r =0.47; r 2 =0.22; P =0.003) and FFA ( r =0.45; r 2 =0.20; P =0.001) levels and inversely with left ventricular ejection fraction ( r =−0.54; r 2 =0.29; P =0.004). Circulating FFA concentrations differed between study arms (0.05±0.04 mmol/L [low FFA] versus 1.04±0.27 mmol/L [high FFA]; P P P =0.02). Peak exercise capacity and oxygen consumption did not differ between the study arms, and neither did postexercise measurements of left ventricular ejection fraction, global strain, and S′max. Conclusions— Our findings indicate that the failing heart of patients with type 2 diabetes mellitus can adapt to short-term extreme changes in circulating substrates and does not display features of acute myocardial lipotoxicity. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01192373.

Background Myocardial oxygen consumption (MVO 2 ) and its coupling to contractile work are fundamentals of cardiac function and may be involved causally in the transition from compensated left ventricular hypertrophy to failure. Nevertheless, these processes have not been studied previously in patients with aortic valve stenosis (AS). Methods and Results Participants underwent 11 C‐acetate positron emission tomography, cardiovascular magnetic resonance, and echocardiography to measure MVO 2 and myocardial external efficiency (MEE) defined as the ratio of left ventricular stroke work and the energy equivalent of MVO 2 . We studied 10 healthy controls (group A), 37 asymptomatic AS patients with left ventricular ejection fraction ≥50% (group B), 12 symptomatic AS patients with left ventricular ejection fraction ≥50% (group C), and 9 symptomatic AS patients with left ventricular ejection fraction 2 did not differ among groups A, B, C, and D (0.105±0.02, 0.117±0.024, 0.129±0.032, and 0.104±0.026 mL/min per gram, respectively; P =0.07), whereas MEE was reduced in group D (21.0±1.6%, 22.3±3.3%, 22.1±4.2%, and 17.3±4.7%, respectively; P P 2 and MEE (area under the curve 0.98, 0.48, and 0.61, respectively; P Conclusions AS patients display a persistent ability to maintain normal MVO 2 and MEE (ie, the ability to convert energy into stroke work); however, patients with left ventricular ejection fraction

OBJECTIVE Patients with type 2 diabetes have a high incidence of cardiovascular events including stroke. Increased arterial stiffness (AS) predicts cardiovascular events in the general population. Cerebral white matter lesions (WMLs) are associated with an increased risk of stroke. It is unknown whether AS in patients with type 2 diabetes is associated with WMLs. RESEARCH DESIGN AND METHODS We examined 89 patients recently diagnosed with type 2 diabetes ( RESULTS The diabetic population had excellent glycemic control (HbA1c, 6.5% [6.2–6.8]; median [interquartile range {IQR}]) and had, compared with the controls, lower office blood pressure (BP) (127 ± 12/79 ± 8 vs. 132 ± 14/84 ± 10 mmHg) and total cholesterol (4.3[3.9–4.7] vs. 5.6 [5.1–6.4]; mmol/L; median [IQR]), (P < 0.01 for all). Despite this, PWV was higher in the patients with diabetes compared with controls (9.3 ± 2.0 vs. 8.0 ± 1.6 m/s; P < 0.0001). PWV was associated with Breteler score (OR 1.36 [95% CI 1.17–1.58]; P < 0.001) and WML volume (OR 1.32 [95% CI 1.16–1.51]; P < 0.001) per 1 m/s increase in PWV. These associations remained significant when adjusted for age, sex, diabetes, 24-h mean arterial BP, BMI, heart rate, and use of antihypertensives and statins (Breteler score: OR 1.28 [95% CI 1.03–1.60]; P < 0.05 and WML volume: OR 1.30 [95% CI 1.06–1.58]; P < 0.05). CONCLUSIONS PWV was higher among patients with well-controlled type 2 diabetes compared with controls and was independently associated with WMLs. PWV may represent a clinically relevant parameter in the evaluation of cerebrovascular disease risk in type 2 diabetes.

Background— Arrhythmogenic cardiomyopathy (AC) is a hereditary cardiac condition associated with ventricular arrhythmias, heart failure, and sudden death. The disease is most often caused by mutations in the desmosomal gene for plakophilin-2 ( PKP2 ), which is expressed in both myocardial and epidermal tissue. This study aimed to investigate protein expression in myocardial tissue of patients with AC carrying PKP2 mutations and elucidate whether keratinocytes of the same individuals exhibited a similar pattern of protein expression. Methods and Results— Direct sequencing of 5 AC genes in 71 unrelated patients with AC identified 10 different PKP2 mutations in 12 index patients. One patient, heterozygous for a PKP2 nonsense mutation, developed severe heart failure and underwent cardiac transplantation. Western blotting and immunohistochemistry of the explanted heart showed a significant decrease in PKP2 protein expression without detectable amounts of truncated PKP2 protein. Cultured keratinocytes of the patient showed a similar reduction in PKP2 protein expression. Nine additional PKP2 mutations were investigated in both cultured keratinocytes and endomyocardial biopsies from affected individuals. It was evident that PKP2 mutations introducing a premature termination codon in the reading frame were associated with PKP2 transcript and protein levels reduced to ≈50%, whereas a missense variant did not seem to affect the amount of PKP2 protein. Conclusions— The results of this study showed that truncating PKP2 mutations in AC are associated with low expression of the mutant allele and that the myocardial protein expression of PKP2 is mirrored in keratinocytes. These findings indicate that PKP2 haploinsufficiency contributes to pathogenesis in AC.

OBJECTIVE: Microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH) are known complications of myocardial ischaemia-reperfusion injury. Whereas MVO is an established marker for a poor clinical outcome, the clinical significance of IMH remains less well defined. Cardiovascular MR (CMR) and T2 weighted short tau inversion recovery (T2-STIR) imaging have been used to detect IMH and to explore its clinical importance. IMH is typically identified within the area-at-risk as a hypointense signal core on T2-STIR images. Because MVO will also appear as a hypointense signal core, T2-STIR imaging may not be an optimal method for assessing IMH. In this study, we sought to investigate the ability of T2-STIR to discriminate between MVO with IMH in a porcine myocardial ischaemia-reperfusion model that expressed MVO with and without IMH.METHOD: MVO with and without IMH (defined from both macroscopic evaluation and T1 weighted CMR) was produced in 13 pigs by a 65-min balloon occlusion of the mid left anterior descending artery, followed by reperfusion. Eight days after injury, all pigs underwent CMR imaging and subsequently the hearts were assessed by gross pathology.RESULTS: CMR identified MVO in all hearts. CMR and pathology showed that IMH was present in 6 of 13 (46%) infarcts. The sensitivity and specificity of T2-STIR hypointense signal core for identification of IMH was 100% and 29%, respectively. T2-values between hypointense signal core in the pigs with and without IMH were similar (60.4±3 ms vs 63.0±4 ms).CONCLUSIONS: T2-STIR did not allow identification of IMH in areas with MVO in a porcine model of myocardial ischaemic/reperfusion injury in the subacute phase of a reperfused myocardial infarction.

Objectives This study sought to develop an actively tracked cardiac magnetic resonance-guided electrophysiology (CMR-EP) system and perform first-in-human clinical ablation procedures. Background CMR-EP offers high-resolution anatomy, arrhythmia substrate, and ablation lesion visualization in the absence of ionizing radiation. Implementation of active tracking, where catheter position is continuously transmitted in a manner analogous to electroanatomic mapping (EAM), is crucial for CMR-EP to take the step from theoretical technology to practical clinical tool. Methods The setup integrated a clinical 1.5-T scanner, an EP recording and ablation system, and a real-time image guidance platform with components undergoing ex vivo validation. The full system was assessed using a preclinical study (5 pigs), including mapping and ablation with histological validation. For the clinical study, 10 human subjects with typical atrial flutter (age 62 ± 15 years) underwent MR-guided cavotricuspid isthmus (CTI) ablation. Results The components of the CMR-EP system were safe (magnetically induced torque, radiofrequency heating) and effective in the CMR environment (location precision). Targeted radiofrequency ablation was performed in all animals and 9 (90%) humans. Seven patients had CTI ablation completed using CMR guidance alone; 2 patients required completion under fluoroscopy, with 2 late flutter recurrences. Acute and chronic CMR imaging demonstrated efficacious lesion formation, verified with histology in animals. Anatomic shape of the CTI was an independent predictor of procedural success. Conclusions CMR-EP using active catheter tracking is safe and feasible. The CMR-EP setup provides an effective workflow and has the potential to change the way in which ablation procedures may be performed.

Aims Tailored heart failure treatment and risk assessment in patients following ST-segment elevation myocardial infarction (STEMI) is mainly based on the assessment of the left ventricular (LV) ejection fraction (EF). Assessment of the final infarct size in addition to the LVEF may improve the prognostic evaluation. To evaluate the prognostic importance of the final infarct size measured by cardiovascular magnetic resonance (CMR) in patients with STEMI. Methods and results In an observational study the final infarct size was measured by late gadolinium enhancement CMR 3 months after initial admission in 309 patients with STEMI. The clinical endpoint was a composite of all-cause mortality and admission for heart failure. During the follow-up period of median 807 days (IQR: 669–1117) 35 events (5 non-cardiac deaths, 3 cardiac deaths, and 27 admissions for heart failure) were recorded. Patients with a final infarct size ≥median had significantly higher event rates than patients with a final infarct size

The association between reperfusion delay and myocardial damage has previously been assessed by evaluation of the duration from symptom onset to invasive treatment, but results have been conflicting. System delay defined as the duration from first medical contact to first balloon dilatation is less prone to bias and is also modifiable. The purpose was to evaluate the impact of system delay on myocardial salvage index (MSI) and infarct size in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention (PCI).In patients with ST-elevation myocardial infarction, MSI and final infarct size were assessed using cardiovascular magnetic resonance. Myocardial area at risk was measured within 1 to 7 days, and final infarct size was measured 90 ± 21 days after intervention. Patients were grouped according to system delay (0 to 120, 121 to 180, and180 minutes).In 219 patients, shorter system delay was associated with a smaller infarct size (8% [interquartile range 4-12%], 10% [6-16%], and 13% [8-17%]; P.001) and larger MSI (0.77 [interquartile range 0.66-0.86], 0.72 [0.59-0.80], and 0.68 [0.64-0.72]; P = .005) for a system delay of up to 120, 121 to 180, and180 minutes, respectively. A short system delay as a continuous variable independently predicted a smaller infarct size (r = 0.30, P.001) and larger MSI (r = -0.25, P.001) in multivariable linear regression analyses. Finally, shorter system delay (0-120 minutes) was associated with improved function (P = .019) and volumes of left ventricle (P = .022).A shorter system delay resulted in smaller infarct size, larger MSI, and improved LV function in patients treated with primary PCI. Thus, this study confirms that minimizing system delay is crucial for primary PCI-related benefits.

Background and Purpose: Rupture of vulnerable carotid atherosclerotic plaques is a major cause of stroke. Stress levels may reflect risk of rupture in patients with carotid atherosclerotic plaques. Features thought to influence the risk of plaque rupture include the degree of stenosis, lipid-rich necrotic core (LR-NC) size, and thickness of the protective fibrous caps. We used computational models to investigate the effect of these variables on fibrous cap stress levels. Methods: Two-way coupled fluid-structure interaction longitudinal 2D simulations were performed on a bifurcation model based on idealized geometry derived from a symptomatic patient. Models with varying degrees of stenosis (50%-95%), fibrous cap thicknesses (0.05-1 mm), and LR-NC sizes (2 × 1 mm-6 × 3 mm) were simulated. The stress distribution for each model was calculated and peak principal stresses extracted. Regression analysis was used for assessing the relationship between the variables and stress levels. Results: Mechanical stresses increased with decreasing fibrous cap thicknesses ( β= -0.905, p Conclusions: Thin-capped plaques with large atheromas, known predictors of plaque vulnerability, were shown to exhibit the greatest mechanical stress levels.

Background In patients with ST-segment elevation myocardial infarction (STEMI) pre-infarction angina, pre-procedural TIMI flow and collateral flow to the myocardium supplied by the infarct related artery are suggested to be cardioprotective. We evaluated the effect of these factors on myocardial salvage index (MSI) and infarct size adjusting for area at risk in patients with STEMI treated with primary percutaneous coronary intervention. Methods and Results Cardiac magnetic resonance (CMR) was used to measure myocardial area at risk within 1-7 days and final infarct size 90±21 days after the STEMI in 200 patients. MSI was calculated as (area-at-risk infarct size) / area-at-risk. Patients with pre-infarction angina had a median MSI of 0.80 (IQR 0.67 to 0.86) versus 0.72 (0.61 to 0.80) in those without pre-infarction angina, P = 0.004). In a regression analysis of the infarct size plotted against the area-at-risk there was a strong trend that the line for the pre-infarction angina group was below the one for the non-angina group ( P = 0.05). Patients with pre-procedural TIMI flow 0/1, 2 and 3 had a median MSI of (0.69 (IQR 0.59 to 0.76), 0.78 (0.68 to 0.86) and 0.85 (0.77 to 0.91), respectively ( P

Ectopic sebaceous glands in the esophagus have rarely been reported and, thus, represent an obscure medical condition. The aim of this study is to identify the prevalence rate and clinical characteristics of this lesion in an asymptomatic population. We prospectively enrolled health screen examinees who underwent esophagogastroduodenoscopy for gastric cancer screening. An esophageal biopsy was performed in the cases in which esophageal ectopic sebaceous glands were suspected. The general characteristics of the examinees were analyzed based on their medical records. A total of 9989 examinees were enrolled, and five examinees were diagnosed with esophageal ectopic sebaceous glands between December 2012 and June 2014. The endoscopic findings of the esophageal ectopic sebaceous glands indicated multiple yellowish patches or papules, which varied in size. The histopathological findings indicated several lobulated sebaceous glands in the squamous epithelium with inflammatory infiltration. The follow-up endoscopic findings indicated that there was no grossly discernible change. In conclusion, esophageal ectopic sebaceous glands are present in 0.05% of asymptomatic subjects. This lesion is thought to be benign and is not related to clinical symptoms. Therefore, esophageal ectopic sebaceous glands do not require further treatment or follow-up, which makes endoscopists free from active efforts for differential diagnosis with other malignant diseases.

Background— Patients with type 1 diabetes and nephropathy maintain an excess cardiovascular mortality compared with diabetic patients with normoalbuminuria. We sought to evaluate coronary and aortic atherosclerosis in a cohort of asymptomatic type 1 diabetic patients with and without diabetic nephropathy using cardiovascular magnetic resonance imaging. Methods and Results— In a cross-sectional study, 136 subjects with long-standing type 1 diabetes without symptoms or history of cardiovascular disease, including 63 patients (46%) with nephropathy and 73 patients with normoalbuminuria, underwent cardiovascular magnetic resonance imaging. All subjects underwent cardiac exercise testing and noninvasive tests for peripheral artery disease and autonomic neuropathy. Coronary artery stenoses were identified in 10% of subjects with nephropathy (versus 0% with normoalbuminuria; P =0.007). Coronary plaque burden, expressed as right coronary artery mean wall thickness (1.7±0.3 versus 1.3±0.2 mm; P P P =0.28) and abdominal aortic plaque (22% versus 16%; P =0.7) was similar in both groups. Subjects with and without abdominal aortic plaques had similar coronary plaque burden. Conclusions— In asymptomatic type 1 diabetes, cardiovascular magnetic resonance imaging reveals greater coronary plaque burden in subjects with nephropathy compared with those with normoalbuminuria.

We evaluated the anti-atopic dermatitis (AD) effect of Atofreellage (AF), a herbal formula composed of 10 medicinal plants. AD was induced on the dorsal skin areas of NC/Nga mice (male, seven weeks old) by daily application of 2,4-dinitrochlorobenzene (DNCB) for five weeks. After three weeks of DNCB application, 200 μL of AF (0, 25, 50 or 100 mg/mL) was applied to the skin lesions. Histological findings, blood cell populations, serum levels of immunoglobulin E (IgE), histamine, pro-inflammatory cytokines, and inflammatory signaling in the skin tissue, and T-helper cell type 2 (Th2)-related cytokines in splenocytes were analyzed. Histopathological findings showed AF treatment notably attenuated the thickness of dorsal skin, and eosinophil infiltration. AF treatment (especially 100 mg/mL) also demonstrably ameliorated the blood cell population abnormalities, as the notable elevation of serum concentrations of IgE, histamine, TNF-α, IL-6 and IL-1β were remarkably normalized by AF treatment. Western blot analysis evidenced the apparent normalization of inflammatory signals (ERK, p38 MAP kinase, JNK, and NF-κB) in the skin tissue. Additionally, AF treatment notably attenuated the activation of Th2-dominant cytokines (IL-13, IL-4, and IL-5) in Con A-treated splenocytes in an ex vivo assay. In conclusion, this study provides experimental evidence for the clinical relevance of Atofreellage.

AIMS: The clinical diagnosis of acute myocarditis is based on symptoms, electrocardiography, elevated myocardial necrosis biomarkers, and echocardiography. Often, conventional echocardiography reveals no obvious changes in global cardiac function and therefore has limited diagnostic value. Myocardial deformation imaging by echocardiography is an evolving method used to characterize quantitatively longitudinal systolic function, which may be affected in acute myocarditis. The aim of our study was to assess the utility of echocardiographic deformation imaging of the left ventricle in patients with diagnosed acute myocarditis in whom cardiovascular magnetic resonance (CMR) evaluation was performed.METHODS AND RESULTS: We included 28 consecutive patients (mean age 32 ± 13 years) with CMR-verified diagnosis of acute myocarditis according to the Lake Louise criteria. Cardiac function was evaluated by a comprehensive assessment of left ventricular (LV) function, including 2D speckle-tracking echocardiography. We found no significant correlation between the peak values of cardiac enzymes and the amount of myocardial oedema assessed by CMR (troponin: r= 0.3; P = 0.05 and CK-MB: r = 0.1; P = 0.3). We found a larger amount of myocardial oedema in the basal part of the left ventricle [American Heart Association (AHA) segments 1-6] in inferolateral and inferior segments, compared with the anterior, anterolateral, anteroseptal, and inferoseptal segments. In the mid LV segments (AHA segments 7-12), this was more pronounced in the anterior, anterolateral, and inferolateral segments. Among conventional echocardiographic parameters, LV function was not found to correlate with the amount of myocardial oedema of the left ventricle. In contrast, we found the wall motion score index to be significantly correlated with the amount of myocardial oedema, but this correlation was only present in patients with an extensive amount of oedema (>11% of the total left ventricle). Global longitudinal systolic myocardial strain correlated significantly with the amount of oedema (r = 0.65; P < 0.001). We found that both the epicardial longitudinal and the endocardial longitudinal systolic strains were significantly correlated with oedema (r = 0.55; P = 0.003 and r = 0.54; P < 0.001).CONCLUSION: In patients with acute myocarditis, 2D speckle-tracking echocardiography was a useful tool in the diagnostic process of acute myocarditis. Global longitudinal strain adds important information that can support clinical and conventional echocardiographic evaluation, especially in patients with preserved LV ejection fraction in relation to the diagnosis and degree of myocardial dysfunction.

ObjectivesWe compared catheter-based electromechanical mapping (NOGA system, Biosense-Webster, Haifa, Israel) with positron emission tomography (PET) and single photon emission computed tomography (SPECT) for prediction of reversibly dysfunctional myocardium (RDM) and irreversibly dysfunctional myocardium (IDM) in patients with severe left ventricular dysfunction. Furthermore, we established the optimal discriminatory value of NOGA measurements for distinction between RDM and IDM.BackgroundThe NOGA system can detect viable myocardium but has not been used for prediction of post-revascularization contractile function in patients with ischemic cardiomyopathy.MethodsTwenty patients (19 males, age [mean ± SD] 60 ± 16 years, ejection fraction [EF] 29 ± 6%) underwent viability testing with NOGA and PET or SPECT before revascularization. Left ventricular function was studied at baseline and six months after revascularization.ResultsThe EF increased to 34 ± 13% at six months (p < 0.05 vs. baseline). The 58 RDM and 57 IDM regions differed with regard to unipolar voltage amplitude (UVA) (9.2 ± 3.9 mV vs. 7.6 ± 4.0 mV, p < 0.05), normalized UVA (106 ± 54% vs. 75 ± 39%, p < 0.05), and tracer uptake (76 ± 17% vs. 60 ± 20%, p < 0.05). The NOGA local shortening did not distinguish between RDM and IDM (6.4 ± 5.8% vs. 5.4 ± 6.6%). By receiver operating characteristic curve analysis, myocardial tracer uptake had better diagnostic performance than UVA (area under curve [AUC] ± SE: 0.82 ± 0.04 vs. 0.63 ± 0.05, p < 0.05) and normalized UVA (AUC ± SE: 0.70 ± 0.05, p < 0.05). Optimal threshold was defined as the value yielding sensitivity = specificity for prediction of RDM. Sensitivity and specificity were 59% at a UVA of 8.4 mV, 65% at a normalized UVA of 83%, and 78% at a tracer uptake of 69%.ConclusionsThe NOGA system may discriminate RDM from IDM with optimal discriminatory values for UVA and normalized UVA of 8.4 mV and 83%, respectively. However, the diagnostic performance does not reach the level obtained by PET and SPECT in patients with severe heart failure.

BACKGROUND: Coronary Wave Intensity Analysis (cWIA) is a technique capable of separating the effects of proximal arterial haemodynamics from cardiac mechanics. Studies have identified WIA-derived indices that are closely correlated with several disease processes and predictive of functional recovery following myocardial infarction. The cWIA clinical application has, however, been limited by technical challenges including a lack of standardization across different studies and the derived indices' sensitivity to the processing parameters. Specifically, a critical step in WIA is the noise removal for evaluation of derivatives of the acquired signals, typically performed by applying a Savitzky-Golay filter, to reduce the high frequency acquisition noise.METHODS: The impact of the filter parameter selection on cWIA output, and on the derived clinical metrics (integral areas and peaks of the major waves), is first analysed. The sensitivity analysis is performed either by using the filter as a differentiator to calculate the signals' time derivative or by applying the filter to smooth the ensemble-averaged waveforms. Furthermore, the power-spectrum of the ensemble-averaged waveforms contains little high-frequency components, which motivated us to propose an alternative approach to compute the time derivatives of the acquired waveforms using a central finite difference scheme.RESULTS AND CONCLUSION: The cWIA output and consequently the derived clinical metrics are significantly affected by the filter parameters, irrespective of its use as a smoothing filter or a differentiator. The proposed approach is parameter-free and, when applied to the 10 in-vivo human datasets and the 50 in-vivo animal datasets, enhances the cWIA robustness by significantly reducing the outcome variability (by 60%).

Hyperglycemia upon hospital admission in patients with ST-segment elevation myocardial infarction (STEMI) occurs frequently and is associated with adverse outcomes. It is, however, unsettled as to whether an elevated blood glucose level is the cause or consequence of increased myocardial damage. In addition, whether the cardioprotective effect of exenatide, a glucose-lowering drug, is dependent on hyperglycemia remains unknown. The objectives of this substudy were to evaluate the association between hyperglycemia and infarct size, myocardial salvage, and area at risk, and to assess the interaction between exenatide and hyperglycemia. A total of 210 STEMI patients were randomized to receive intravenous exenatide or placebo before percutaneous coronary intervention. Hyperglycemia was associated with larger area at risk and infarct size compared with patients with normoglycemia, but the salvage index and infarct size adjusting for area at risk did not differ between the groups. Treatment with exenatide resulted in increased salvage index both among patients with normoglycemia and hyperglycemia. Thus, we conclude that the association between hyperglycemia upon hospital admission and infarct size in STEMI patients is a consequence of a larger myocardial area at risk but not of a reduction in myocardial salvage. Also, cardioprotection by exenatide treatment is independent of glucose levels at hospital admission. Thus, hyperglycemia does not influence the effect of the reperfusion treatment but rather represents a surrogate marker for the severity of risk and injury to the myocardium.

OBJECTIVES—To quantify the short term haemodynamic effects of biventricular pacing in patients with heart failure and left bundle branch block by using three dimensional echocardiography. DESIGN—Three dimensional echocardiography was performed in 15 consecutive heart failure patients (New York Heart Association functional class III or IV) with an implanted biventricular pacing system. Six minute walk tests were performed to investigate the effect of biventricular pacing on exercise capacity. Data were acquired at sinus rhythm and after short term (2-7 days) biventricular pacing. RESULTS—Compared with baseline values, biventricular pacing significantly reduced left ventricular end diastolic volume (EDV) by mean (SD) 4.0 (5.1)% (p

Objectives: We used tissue velocity imaging (TVI) and three-dimensional echocardiography to evaluate the effect of acute biventricular pacing on left ventricular (LV) performance and volumes in patients with severe heart failure and bundle branch block. Background: Biventricular pacing causes acute hemodynamic improvement in patients with severe heart failure, and QRS duration has been used as a predictor of improved resynchronization. Tissue velocity has the potential of demonstrating the degree of LV resynchronization and three-dimensional echocardiography enables accurate quantitation of LV volumes and function. Methods: TVI and three-dimensional echocardiography were performed during sinus rhythm and biventricular pacing in 25 consecutive patients with severe heart failure. Results: Biventricular pacing significantly improved the extent of contracting myocardium in synchrony by 15.4% and the duration of contraction synchrony by 17% (p < 0.05 for both). Furthermore, end-diastolic and end-systolic volumes decreased by 7 ± 4.5% and 13 ± 6% (p < 0.01) and ejection fraction increased by 22.8 ± 9% (p < 0.01). Baseline duration of QRS and the preejection period as well as the extent of myocardium with asynchronous contraction measured by TVI predicted pacing efficacy. In multivariate analysis, only the extent of myocardium with asynchronous contraction at the LV base predicted biventricular pacing efficacy. Conclusion: Biventricular pacing improves LV systolic performance and reduces LV volumes during short-term treatment. TVI provides important pathophysiological information on the degree of LV resynchronization and may contribute to improved patient selection.

Aims To provide a comprehensive histopathological validation of cardiac magnetic resonance (CMR) and endocardial voltage mapping of acute and chronic atrial ablation injury. Methods and results 16 pigs underwent pre-ablation T2-weighted (T2W) and late gadolinium enhancement (LGE) CMR and high-density voltage mapping of the right atrium (RA) and both were repeated after intercaval linear radiofrequency ablation. Eight pigs were sacrificed following the procedure for pathological examination. A further eight pigs were recovered for 8 weeks, before chronic CMR, repeat RA voltage mapping and pathological examination. Signal intensity (SI) thresholds from 0 to 15 SD above a reference SI were used to segment the RA in CMR images and segmentations compared with real lesion volumes. The SI thresholds that best approximated histological volumes were 2.3 SD for LGE post-ablation, 14.5 SD for T2W post-ablation and 3.3 SD for LGE chronically. T2-weighted chronically always underestimated lesion volume. Acute histology showed transmural injury with coagulative necrosis. Chronic histology showed transmural fibrous scar. The mean voltage at the centre of the ablation line was 3.3 mV pre-ablation, 0.6 mV immediately post-ablation, and 0.3 mV chronically. Conclusion This study presents the first histopathological validation of CMR and endocardial voltage mapping to define acute and chronic atrial ablation injury, including SI thresholds that best match histological lesion volumes. An understanding of these thresholds may allow a more informed assessment of the underlying atrial substrate immediately after ablation and before repeat catheter ablation for atrial arrhythmias.

Hyperglycemia upon admission in patients with ST-segment myocardial infarction (STEMI) is associated with larger infarct size and adverse prognosis. However, the association of hyperglycemia with area at risk and myocardial salvage has been insufficient studied. Also, exenatide, a glucagon-like

Objective: The non-specific abdominal aortic aneurysm (AAA) is a local manifestation of a systemic disease, in which inflammation may play a role. This cardiovascular magnetic resonance (CMR) study utilizes a water-sensitive, T2- weighted, short tau inversion recovery sequence (T2-STIR) to identify vessel wall edema as a marker for inflammation. Methods: Twenty-two patients were included: 10 AAA patients, 10 healthy subjects, and two patients with known inflammation. MR T2-STIR images of aorta vessel wall and intraluminal thrombi were analyzed using OSIRIX software. Signal intensity values were normalized, and values from blinded and independent viewers were then averaged and analyzed using SPSS statistical software. The Kruskal-Wallis H test was used with post hoc analysis for differences of significance. Results: Average AAA anterior-posterior diameter was 5.9 ± 0.6cm (range, 5.3-7.0cm). The Kruskal-Wallis H test revealed a significant difference between independent samples (H(3) = 20.36, P < .001). There was no significant difference in average intensities between AAA and healthy subjects ( P = .766). Conclusion: This is the first study to examine edema in walls and thrombi of AAAs using T2-STIR imaging. No evidence of edema was identified in the aortic aneurysm wall, suggesting a lack of inflammatory activity.

Drug-eluting stents (DES) minimized the occurrence of in-stent restenosis but with a penalty of increased risk of late stent thrombosis.1 In patients with late stent thrombosis, adverse vessel wall reactions such as uncovered and malapposed stent struts, coronary aneurysms, and accelerated neoatherosclerosis2 have been identified. The stent polymer is suspected to induce an inflammatory response,3 resulting in vessel wall abnormalities. Identification of patients with an inflammatory response to DES might be essential in preventing late stent thrombosis. Inflammatory processes increase vessel wall permeability, leading to edema, and both native and peri-stent vessel wall inflammation may be associated with tissue edema. Cardiovascular magnetic resonance (CMR) performed with a T2-weighted short-τ inversion recovery sequence (T2-STIR) has recently been shown to identify localized coronary edema in the culprit artery of patients with acute myocardial infarction.4 Parameters for the ECG-triggered, navigator-gated, dark-blood, T2-STIR fast-spin-echo sequence were as follows: repetition time, 2 RR intervals; echo time, 100 milliseconds; echo train length, twenty 0.68×0.68×8-mm3 voxels; and 2 signal averages. Here we present 3 patients treated with DES (Cypher Select+, Cordis, Johnson & Johnson, Miami Lakes, FL) who demonstrate peri-stent edema as a possible marker of stent-induced coronary inflammation. A 41-year-old woman experienced very late stent thrombosis 15 months after treatment with DES in the proximal left anterior descending …

Aim: Stroke is a frequent and feared complication in patients with type 2 diabetes. Arterial stiffness may improve current suboptimal risk prediction of stroke. However, studies in diabetes populations are lacking. We investigated the association between arterial stiffness progression (carotid-femoral pulse wave velocity [PWV]) and the progression of cerebral white matter lesions (WML), a marker of stroke risk, in patients with type 2 diabetes and matched controls. Methods: In a 5-year follow-up study, data from 49 patients and 58 controls were available for analysis. At baseline, participants had a mean (±SD) age of 59±10 years and patients had a median (range) diabetes duration of 1.8 (1.0–3.2) years. Fifty-two (49%) were males. At both baseline and follow-up, PWV was obtained by tonometry and WML by cerebral T2-FLAIR MRI. WML was assessed by Breteler score, and progression was defined as an upward change in category during follow-up. Results: Patients with type 2 diabetes had a higher PWV than controls at both baseline (9.2±2.2 vs. 7.9±1.4m/s, p < 0.01) and follow-up (9.8±2.4 vs. 8.6±1.9m/s, p = 0.01). Breteler scores and WML progression were similar in the two groups (p > 0.05). PWV progression was associated with WML progression in the total cohort (adjusted for age, sex, diabetes, baseline PWV and systolic blood pressure progression: OR 1.58 [95%CI: 1.09–2.28], p = 0.02). We found no interaction between diabetes and PWV progression on WML progression. Conclusions: PWV progression is associated with WML progression in patients with type 2 diabetes and healthy controls. PWV candidates as a new risk marker for stroke.

Background Cardiovascular magnetic resonance (CMR) deploying late gadolinium-enhanced inversion-recovery (IR) sequence is today’s standard reference for myocardial infarction evaluation. However, the conventional IR sequence can yield poor image contrast between infarct and intracavity blood pool which complicates precise endocardial border delineation. This compromises accurate infarct size determination and small subendocardial infarct detection. Peel et al. 2012 found that a dual IR prepulse outperformed

Background and Purpose One third of patients treated with primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction develop a secondary increase in electrocardiographic ST segment (ST peak) during reperfusion. The purpose was to determine the clinical importance of ST peak during primary PCI. Methods A total of 363 patients with ST-elevation myocardial infarction were stratified to no ST peak or ST peak. Final infarct size and ejection fraction (EF) were assessed by cardiovascular magnetic resonance. Results Patients with ST peak had a larger infarct size (14% vs 10%; P = .003) and lower EF (53% vs 57%; P = .022). Rates of cardiac mortality (8% vs 3%; P = .047) and cardiac events (cardiac mortality and admission for heart failure; 19% vs 10%; P = .018) were higher among patients with ST peak, but not all-cause mortality (8% vs 5%; P = .46). In a multivariable Cox regression analysis, ST peak remained significantly associated with cardiac events (adjusted hazard ratio, 2.03 [1.08-3.82]). Conclusion ST peak during primary PCI is related to larger final infarct size, a reduced EF, and adverse cardiac clinical outcome.