IK1) conducted through Kir2.X channels contribute to repolarization of the cardiac action potential and to stabilization of the resting membrane potential in cardiomyocytes. Our aim was to investigate the effect of the recently discovered IK1 inhibitor PA‐6 on action potential repolarization and refractoriness in isolated rat hearts. Transiently transfected HEK‐293 cells expressing IK1 were voltage‐clamped with ramp protocols. Langendorff‐perfused heart experiments were performed on male Sprague–Dawley rats, effective refractory period, Wenckebach cycle length, and ventricular effective refractory period were determined following 200 nmol/L PA‐6 perfusion. 200 nmol/L PA‐6 resulted in a significant time‐latency in drug effect on the IK1 current expressed in HEK‐293 cells, giving rise to a maximal effect at 20 min. In the Langendorff‐perfused heart experiments, PA‐6 prolonged the ventricular action potential duration at 90% repolarization . In parallel, PA‐6 significantly prolonged the ventricular effective refractory period compared to baseline . PA‐6 increased the short‐term beat‐to‐beat variability and ventricular fibrillation was observed in two of six hearts. Neither atrial ERP nor duration of atrial fibrillation was altered following PA‐6 application. The results show that pharmacological inhibition of cardiac IK1 affects ventricular action potential repolarization and refractoriness and increases the risk of ventricular arrhythmia in isolated rat hearts.The inwardly rectifying potassium current ( IK1) contributes to repolarization in cardiomyocytes , and in cardiac tissue Kir2.1 is the predominant expressed protein. Loss of function mutations in KCNJ2, which encodes Kir2.1, is reported in Andersen–Tawil syndrome   are associated with IK1 currents were investigated in transiently transfected HEK‐293 cells, which were grown in Dulbecco's modified Eagle's medium  supplemented with 10% fetal bovine serum  and 1% streptomycin  at 37°C in a 5% CO2 atmosphere.ir2.1 (GenBank ACC. NM_000891) were subcloned into the pXOOM vector, as previously described in . Transfections were performed using Lipofectamine 2000  according to the manufacturer's instructions. The cells were used for patch‐clamp recordings 36–48 h after transfection.Complementary DNAs encoding human K2 2, MgCl2 1, HEPES 10, D‐Glucose 10 (pH 7.4 with NaOH). The pipette solution consisted of (in mmol/L) KCl 140, Na2ATP 1, EGTA 2, HEPES 10, CaCl2 0.1, MgCl2 1, D‐Glucose 10 (pH 7.4 with KOH).The following physiological extracellular solution was used for the electrophysiological experiments, containing (in mmol/L): NaCl 140, KCl 4, CaClPatch‐clamp recordings were performed as previously described . On the day of the experiment the rats were weighed (BW 300–400 g) and anesthetized with a subcutaneous injection of fentanyl‐midazolam mixture, 5 mg/mL, dose 0.3 mL/100 g BW.3 25.0, KCl 4.0, MgSO4 0.6, NaH2PO4 0.6, CaCl2 2.5, Glucose 11.0, all in mmol/L) saturated with 95% O2 and 5% CO2. The aortic perfusion pressure was determined with an ISOTEC transducer  and the coronary flow was measured with an ultrasonic flowmeter . Both were connected to an amplifier . The electrical activity of the rat hearts were measured by using volume conducted electrocardiograms (ECGs) and by placing two epicardial monophasic action potential (MAP) electrodes on the right ventricle. The hearts were immersed into a temperature‐controlled and carbonated bath containing Krebs–Henseleit buffer. Perfusion pressure, coronary flow, ECG and MAP analog signals were sampled at a frequency of 1k/s and were converted by a 16/30 data acquisition system from PowerLab systems  and monitored by using LabChart 7 software The rats were ventilated (4 mL/60 strokes/min) through a rodent ventilator . Tracheostomies were performed and the hearts were excised and cannulated through a small puncture of the aorta, near the aortic arch, and connected to the Langendorff retrograde perfusion setup . The hearts were retrogradely perfused at a constant perfusion pressure of 80 mm Hg with a 37°C, pH 7.4, Krebs–Henseleit buffer  regular pulses followed by a premature extra stimulus (S2) with the time between the S1 and the S2 stimuli increased by 2 msec increments until the refractory period was identified. Furthermore, the Wenckebach cycle length (WCL) was determined by pacing with decreasing cycle lengths until a 2:1 AV block appeared.The hearts were left to stabilize for 30 min at intrinsic heart rhythm. A bipolar pacing electrode was placed on the right atrial appendage and a second pacing electrode was positioned on the right ventricle. Epicardial pacing‐stimulation was applied using square pulses of 2 msec durations at twice diastolic threshold at 150 basic cycle lengths (BCL). Right atrial and right ventricular effective refractory periods (ERPs) were measured by application of 10 , WCL, and ventricular ERP (vERP) were determined and the heart preparations were randomized into treatment with either 200 nmol/L PA‐6 to the drug‐treated group or equivalent amount of DMSO to the time‐matched control (named DMSO) group. The same parameters were determined every 15 min over a 90 min drug infusion period.The pentamidine analog PA‐6 (C31H32N4O2) was synthesized by Syngene, Bangalore, India. The compound was dissolved in DMSO and the DMSO concentration in the experiments was 0.002%. The compound was added from a 10 mmol/L stock to the Krebs–Henseleit solution used in the experiments yielding a final concentration of 200 nmol/L.Whole‐cell patch‐clamp data were analyzed using IGOR Pro  and GraphPad Prism software . Data are presented as mean ± SEM.All Langendorff data were analyzed using Labchart 7  and figures were processed in GraphPad Prism .90). The APD90s were a mean of 40 monophasic action potentials.*P < 0.05 was considered significant. **P < 0.01, ***P < 0.0001. The heart rate variability was evaluated using a Poincare plot. Consecutive R–R intervals from the right ventricle were plotted as 40 n + 1 from ventricular maps. The instability of the beat‐to‐beat heart rate was characterized by short‐term variability (STV) and was calculated from 40 subsequent APD90s using (STV = ∑|Dn+1−Dn|/[40×2]).Data represent the mean ± standard error of mean. Two‐tailed paired t‐tests were used to compare baseline with the effect of 90 min perfusion of 200 nmol/L PA‐6 on aERP, vERP, WCL, and action potential duration at 90% repolarization  and −110 mV (inward K+ current)  and ECG electrodes.IK1 PA‐6 was applied to the perfusion buffer for 90 min   was observed , 71% compared to baseline, P < 0.05, n = 6)     Figs. G. In theed Figs. C. The ti6) Figs. F. Intere 6) Fig. E and nei 6) Fig. H. Neithe 6) Fig. A–D.The effect of PA‐6 on beating frequency, conduction and action potential activation current (rheobase) was analyzed prior to PA‐6 and DMSO application (baseline) and after 90 min of application Fig. A–D. PA‐690 value against the preceding APD90 value. In the DMSO group the beat‐to‐beat variability was not changed after application of DMSO compared to baseline, t = 0 and at t = 90   preparation. The onset of PA‐6 mediated effects showed a time‐latency in the Langendorff‐preparations, reaching a plateau after 90 min. The slow onset of effect is probably due to PA‐6 blocking the channel pore from the cytosolic side as reported by De Boer et al. who applied the pentamidine compound from either the extracellular or the intracellular side of the membrane using the whole‐cell or inside‐out patch‐clamp technique  prolonged vERP, and (3) reduced sodium channel availability caused by a depolarized RMP.The atrial‐ventricular conduction time was also increased by IK1 is believed to play a central role, but other repolarizing potassium currents, including IK,ACh and IK,Ca are also important in the later part of the action potential and in setting the resting membrane potential . However, superfusion of PA‐6 had no effect on the electrophysiological properties of neither isolated atrial nor ventricular tissue, possibly due to low tissue penetrance of the drug as permeability is indeed reduced in a superfused tissue strip as compared to a coronary‐perfused Langendorff heart. Such permeability issues were previously observed for other compounds (Skibsbye et al. IK1 in Langendorff‐perfused rat hearts, resulting in prolonged ventricular action potentials and increased refractoriness. Moreover, block of IK1 in the rat ventricles also increases beat‐to‐beat variability and STV, as well as the risk of electrical stimulated ventricular arrhythmias. Atrial electrophysiology was not altered following IK1 block. These results suggest that blocking IK1 in rat hearts is proarrhythmic and may lead to increased susceptibility to ventricular arrhythmia.PA‐6 inhibits cardiac None declared.


Cardiac MRI is the gold standard for assessing cardiac function, but requires contour tracing of the left ventricular (LV) myocardium through multiple cine steady-state free precession (SSFP) short axis images. Despite advancements in semi-automated software, contour detection and manual readjustments of multiple slices throughout the cardiac cavity remains a tedious process. Our goal is to assess LV functional parameters using 3-slice segmentations in comparison to conventional multi-slice segmentation in patients with a wide range of pathologies.We retrospectively studied 1.5T cardiac MR images of 62 patients with various clinical indications. All patients had a stack of EKG gated segmented SSFP cine images through the LV. Semi-automated cardiac MR software (Argus) was used to trace LV contours both at multiple slices from base to apex as well as just 3 slices  by two readers. End diastolic volume (EDV), end systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) were calculated using both assessment methods.There were no statistically significant differences between EF and LV volumes obtained by multi-slice vs 3-slice analysis for both readers (P > 0.05). For reader 1 (and 2), Bland-Altman plot revealed the mean difference in LVEF between multi-slice and 3-slice analysis was 0.4% (0.5%) with limits of agreement of -4.3% to 5.1% (-3.9% to 4.9%) (Figure The LVEF obtained from either 3-slice or multi-slice evaluation of SSFP cine images closely correlate across various cardiac pathologies, thereby offering a method to reduce post-processing time. Of note, although the decreased LV volumes obtained by 3-slice segmentation are statistically significant, the difference of < 3.7% may not be clinically significant.None.


Hypertrophic cardiomyopathy (HCM) has a wide clinical spectrum. An important subgroup of patients are at risk of major complications and sudden cardiac death. However risk stratification in these patients is still a challenge. The degree of hypertrophy and myocardial fibrosis are important predictors of prognosis. There are several papers showing the possibility of areas of abnormal left ventricular (LV) perfusion in patients with HCM. Some studies focused on stress-induced perfusion defects , demonstrating the presence of epi-endocardial gradients of perfusion in the LV due to microvascular dysfunction. Some other studies  have focused the attention on LGE-related rest perfusion abnormalities. These are due to areas of microvascular disruption and do not contribute necessarily towards the LV ischemic burden. Mixed defects are also possible. The aim of the study was to analyse in retrospective a group of patients with HCM that underwent stress perfusion and LGE-CMR and to describe the prevalence of perfusion defects of each type.This study included 33 consecutive patients with HCM. The images were analysed by consensus of 2 expert CMR readers. The results were reported on segmental basis, indicating the presence or absence of perfusion abnormalities on stress perfusion scans, the presence of a perfusion gradient, the presence of areas of scar related perfusion abnormalities or the presence of mixed perfusion defects.Hypertrophy, LGE and perfusion defects involved more frequently the inter-ventricular septum. No patients in this group had severe LV hypertrophy (max LV thickness > 30 mm). LGE had a prevalence of 76%, while perfusion abnormalities with a gradient pattern were seen in 87% of patients in at least 1 LV segment. Perfusion abnormalities were present with a pure gradient pattern in 55% of the LV segments. LGE-correlated abnormalities were seen alone in 15% of the segments. Mixed perfusion abnormalities were seen in 30% of the segments.Our results demonstrate that CMR is a useful tool to identify perfusion abnormalities in patients with HCM. Stress-induced perfusion defects are frequently present in patients with HCM also in the absence of severe LV hypertrophy. The intrinsic high spatial resolution allowed by perfusion and LGE-CMR enables the differential diagnosis of perfusion abnormalities indicative of microvascular dysfunction, contributing to the LV ischemic burden, and those related to the presence of scar. Combined perfusion and LGE-CMR has the potential to increase the accuracy of quantification of the true LV ischemic burden in patients with HCM.The Centre of Excellence in Medical Engineering is funded by the Wellcome Trust and EPSRC under grant number WT 088641/Z/09/Z. The authors acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London.


Insulin resistance, as a key mediator of metabolic syndrome, is thought to be associated with pathogenesis of calcific aortic valve disease and altered left ventricular (LV) function and structure. However, in patients with aortic valve sclerosis (AVS), the association between insulin resistance and subclinical impairment of LV function is not fully elucidated.We studied 57 patients  with asymptomatic AVS but normal LV ejection fraction in echocardiography. LV longitudinal and circumferential strain and strain rate was analyzed using two-dimensional speckle tracking echocardiography. Patients with uncontrolled hypertension and diabetes mellitus, chronic kidney disease, and concomitant coronary artery disease were excluded. They were divided into the insulin-resistant group  and no insulin-resistant group  according to the median value of homeostatic model assessment index. Computed tomography scans were also performed to measure the aortic valve calcium score and the visceral adipose tissue (VAT) area. In addition, age- and sex- adjusted 28 control subjects were recruited for the comparison.P = 0.022) and a larger VAT area  than the AVS-IR group. Notably, LV global longitudinal strain, strain rate (SR), and early diastolic SR were significantly lower in the AVS+IR group than in the AVS-IR group and in control subjects , whereas circumferential function were not significantly different. Multiple linear regression analyses revealed insulin resistance as an independent determinant of LV longitudinal strain (P = 0.017), SR (P = 0.047), and early diastolic SR (P = 0.049) regardless of LV mass index or VAT area.There were no significant differences in LV ejection fraction or mass index among the groups. The AVS+IR group had a higher aortic valve calcium score (median 94 versus 21, Insulin resistance is a powerful independent predictor of subclinical LV dysfunction regardless of concomitant visceral obesity and LV hypertrophy. Thus, it may be a novel therapeutic target to prevent subsequent heart failure in patients with AVS. Aortic valve sclerosis (AVS) is a common echocardiographic finding in the elderly and is defined as calcified and thickened aortic leaflets without restriction of leaflet motion. This ismetabolic syndrome/22.5), and a H2.7 ..16].Cardiac CT examinations were performed using a 64-multidetector scanner . Areas of abdominal fat were simultaneously measured from an image at the level of the umbilicus using commercially available software . Subcutaneous adipose tissue (SAT) was defined as the extraperitoneal fat between the skin and muscles, with attenuation ranging from -150 to -50 Hounsfield units. The intraperitoneal portion with the same density as the SAT layer was defined as visceral adipose tissue (VAT). VAT and2 test. The Student t test or Mann-Whitney U test was used to compare CT parameters between the AVS groups (AVS+IR versus AVS-IR). Pearson’s correlation coefficient was calculated to evaluate the associations among HOMA index, adiposity measures, LV mass, and strain and SR. Multivariate linear regression analysis was used to identify independent determinants of LV global strain, systolic SR, and early diastolic SR. A tolerance of >0.5 was set to avoid multicollinearity between the univariate predictors. A probability value of P < 0.05 was considered significant. All statistical analysis was performed using SPSS 21.0 .Continuous data with normal distribution are expressed as mean ± SD and those with skewed distribution as median (interquartile range). Categorical variables are presented as number (percentage). The Kruskal-Wallis test or 1-way ANOVA was used for group comparisons of continuous variables, and post-hoc testing was performed using the Tukey’s test or the Steel-Dwass method for variables with and without normal distribution, respectively. Group comparisons of binary variables were performed using Fisher exact or χ2. Mean systolic blood pressure, diastolic blood pressure, and heart rate were 124 ± 14 mm Hg, 76 ± 7 mm Hg, and 65 ± 10 beats/min, respectively. Four patients medicated using β blockers. LV hypertrophy was found in 6 patients (10.5%).The AVS population comprised 35 men and 22 women with a mean age of 70 ± 8 years. Mean body mass index was 23 ± 3 kg/mTable Table P = 0.035 with post hoc analysis), mid LV , and apex  was significantly reduced in the AVS+IR group compared with the AVS-IR group. In addition, the magnitude of the decrease in each segmental strain value in the AVS+IR group was clearly observed in order of apex, mid LV, and base . Circumferential strain and SR, however, were preserved in all groups and did not differ significantly , but not with longitudinal strain and SR. In addition, VAT area was positively correlated with HOMA index  and LV mass index . None of the LV parameters was related to SAT area.Table P = 0.017), longitudinal SR , and longitudinal diastolic SR . VAT area was also closely associated with longitudinal systolic and diastolic function in the univariate analyses , but the value of VAT area diminished with further adjustment for HOMA index .The present study demonstrates that LV longitudinal function has been already impaired in a group of patients with AVS and that IR is a powerful independent predictor of subclinical abnormalities of LV longitudinal function in patients with AVS. This negative contribution of IR to LV function remained significant even after adjustment for demographic variables, LV mass index, and visceral adiposity on multiple linear regression analysis.This study demonstrates subclinical abnormalities of global LV systolic and diastolic function, as reflected by reduced LV longitudinal, not circumferential, strain and SRs, which are more sensitive indices of LV contractility than LV ejection fraction, in patients with AVS. Recent cross-sectional sub-studies of the ASTRONOMER trial have pointed out the impact of metabolic syndrome not only on progression of aortic stenosis, but also on progression of LV hypertrophy and reduced myocardial velocities in patients with mild and moderate aortic stenosis,18. FurtIn the Cardiovascular Health Study, AVS hasOur results also suggest that IR is an important mediator of the association between AVS and subclinical LV dysfunction. IR, a central feature of metabolic syndrome and diabetes mellitus, has been a causative or contributing factor in the pathogenesis of AVS. Several prospective studies have shown that metabolic syndrome is associated with increased prevalence and incidence of AVS. Also in2+ homeostasis[Previous studies have indicated the close relationship between impaired LV longitudinal function and dysmetabolic state, such as diabetes mellitus, normal-eostasis. Recent eostasis. Also ineostasis suggesteeostasis.The present study also provides the interesting finding that LV longitudinal strain alteration shows mid-apical predominance. Possible mechanisms include the distribution of insulin receptor, the chaper se could be held responsible to the subclinical LV dysfunction independently of the metabolic syndrome with all its risk factors. However, we could reach the statistical significance in the multiple linear regression models including visceral obesity . Second, in this study, the serum level of high-sensitivity C-reactive protein was not associated with IR and impairment of LV function. However, a previous article[First, although our data support the notion that IR is an important factor in the pathogenesis of LV dysfunction in patients with AVS, causality cannot be fully established because this is a cross-sectional study. Furthermore, larger prospective and larger-population studies are needed to clarify whether IR  article demonstr article, the lowthrough-plane motion. In particular, the values of radial strain and SR are likely to be susceptible to this effect. Thus, we omitted data in the radial direction. However, the easy availability and non-invasiveness of two-dimensional speckle-tracking echocardiography may allow assessment of patients with AVS and concomitant insulin-resistant cardiomyopathy and observation of disease progression.Finally, current two-dimensional speckle-tracking analysis is affected by cardiac motion; namely, IR is an independent determinant of subclinical abnormalities of LV longitudinal function in patients with AVS, as assessed by two-dimensional speckle-tracking echocardiography, even after adjustment for concomitant visceral obesity and LV hypertrophy. Our results may have important clinical implications with regard to life style modification and raise the possibility that optimizing IR proves an effective approach to preventing subclinical LV dysfunction in this setting.AVS: Aortic valve sclerosis; LV: Left ventricular; IR: Insulin resistance; SR: Strain rate; CT: Computed tomography; HOMA: Homeostatic model assessment; SAT: Subcutaneous adipose tissue; VAT: Visceral adipose tissue.The authors declare that they have no competing interests.HU devised the study, designed the protocol, participated in fund raising, interpretation of results and prepared the manuscript draft. EK performed all the statistical analysis. HY participated in the study design, analytical methods, fund raising and corrected the final version of the manuscript. TH participated in data collection and interpretation of results. YK participated in the final review of the manuscript. Finally, all authors reviewed and approved the final version of the manuscript.


Animal studies have shown that shear deformation of myocardial sheets in transmural planes of left ventricular (LV) wall is an important mechanism for systolic wall thickening, and normal and shear strains of the LV free wall differ from those of the interventricular septum (IVS). We sought to test whether these also hold for human hearts.Thirty healthy volunteers  from Outpatient Department of the University of Tokyo Hospital were included. Echocardiographic images were obtained in the left decubitus position using a commercially available system  equipped with a 3.5-MHz transducer. The ECG was recorded simultaneously. The peak systolic radial normal strain (length change), shear strain (angle change) and time to peak systolic radial normal strain were obtained non-invasively by two-dimensional speckle tracking echocardiography.The peak systolic radial normal strain in both IVS and LV posterior wall (LVPW) showed a trend to increase progressively from the apical level to the basal level, especially at short axis views, and the peak systolic radial normal strain of LVPW was significantly greater than that of IVS at all three levels. The time to peak systolic radial normal strain was the shortest at the basal IVS, and increased progressively from the base to the apical IVS. It gradually increased from the apical to the basal LVPW in sequence, especially at short axis views. The peak of radial normal strain of LVPW occurred much later than the peak of IVS at all three levels. For IVS, the shear deformation was clockwise at basal level, and counterclockwise at mid and apical levels in LV long-axis view. For LVPW, the shear deformations were all counterclockwise in LV long-axis view and increased slightly from base to the apex. LVPW showed larger shear strains than IVS at all three levels. Bland-Altman analysis shows very good agreement between measurements taken by the same observer and by two independent observers.“Myocardial sheets” theory also holds true for intact human LV. Moreover, dyssynchrony exists even in healthy human subjects, which should be considered when evaluating the diseased hearts. Assessment of regional left ventricular (LV) function is essential for the evaluation and management of patients with heart disease, and it is of great importance to know how the normal LV behaves before we make a diagnosis of cardiac dysfunction. Newly developed two-dimensional (2D) speckle tracking echocardiography based on tracking of the speckles produced by the interaction of ultrasound with the ventricular structures has made the quantification of LV regional function more accurate and simpler compared to the other techniques -4.Using sonomicrometry and magnetic resonance imaging tagging as reference methods, a number of researchers verified that speckle tracking echocardiography could provide accurate measurement of LV deformation -9. RelatRecent descriptions of the laminar organization of myocardium have provided a possible structural link between transmural shear and wall thickening ,12. It hTo test the hypothesis, we evaluated the radial normal strain, which refers to the wall thickness change in the radial direction perpendicular to the endocardium of a given segment, and shear strain, which refers to the angle change of the line between the endocardium and epicardium of a given segment, in the LV free wall (LVPW) and IVS of healthy subjects, with 2D speckle tracking echocardiography.Thirty healthy volunteers  from Outpatient Department of the University of Tokyo Hospital were included and proved to have no cardiopulmonary diseases by inquiry, physical examination, blood pressure measurement, electrocardiogram, echocardiogram, and lung function examination. The study protocol was approved by the Committee of University of Tokyo Hospital. All participants gave informed consent to attend this study.Echocardiographic images were obtained in the left decubitus position using a commercially available system  equipped with a 3.5-MHz transducer. The ECG was recorded simultaneously. Images were acquired in cine loops triggered to the QRS complex and saved in digital format to a magneto-optical disk for off-line analysis.Two-dimensional echocardiographic parasternal long-axis view recorded at a frame rate of 60–70 frames/s were obtained using standard parasternal and modified apical LV long-axis views at basal, mid and apical levels. The modified apical LV long-axis view was acquired by slightly tilting towards the apex from the standard parasternal LV long-axis view. The spatial resolution is less than 3 mm. The basal level was defined as the position just below the mitral leaflet, the mid level was defined as the place of the papillary muscle, and the apical level was defined as the position below the papillary muscle.From an end-systolic single frame of the long-axis view, 2 points were designated at the basal , mid, and apical levels in the IVS (the LV-side endocardium and the RV-side endocardium) and corresponding 2 points was designated at the same levels in the LVPW (the endocardium and the epicardium) by a point-and-draw approach , shear strain  and time to peak systolic radial normal strain  were obtained Figure . Each vaRoutine two-dimensional and Doppler echocardiography were performed and the ejection fraction (EF), fractional shortening (FS) and E/A ratio were obtained in accordance with the recommendations of the American Society of Echocardiography Committee .To assess inter- and intra-observer variability, ten echocardiographic recordings were randomly selected and then the measurements difference in peak radial normal strain and time to peak systolic normal radial strain were analyzed.Data were expressed as mean ± SD and are analyzed with paired t-test between LVPW and IVS. Statistical differences are considered significant at P < 0.05.LV dimensions and systolic function: LV end-diastolic and end-systolic dimensions, EF, FS and E/A ratio of 30 study subjects were shown in Table 1. Peak systolic radial normal strain: Peak systolic radial normal strain in both IVS and LVPW showed a trend to increase progressively from the apical level to the basal level, especially at short axis views, and the peak systolic radial normal strain of LVPW was significantly greater than that of IVS at all three levels   Figure A and B a) Figure C and D.This study showed that the “myocardial sheets” theory was also applicable in healthy human subjects, and significant differences of peak systolic radial normal strain, time to peak systolic radial normal strain as well as shear strain existed between LVPW and IVS even in healthy human subjects.According to law of conservation of mass, shortening in longitudinal and circumferential direction should result in thickening in the radial direction. In this study, we analyzed the radial normal strain , which are actually the systolic wall thickenings. As reported by LeGrice et al. and illustrated in Additional file Despite the evident importance of shear deformation in normal LV function, little direct information is available about the shear properties of human LV wall. In animal studies, it showed that the myocardial sheets or cleavage planes approached the LV endocardium obliquely from the apical direction, becoming nearly parallel to the endocardial surface in LVPW while, in the IVS, the sheets approached the LV endocardium rather vertically from the opposite direction . This diTraditional M-mode is also at a high temporal and spatial resolution and allows the definition of regional myocardial thickening/thinning parameters. However, the normal strain based on 2D speckle tracking technique allows the study of both regional radial thickening and thinning, and regional longitudinal and circumferential shortening and lengthening, and thus can measure three aspects of regional function as opposed to only the radial parameters measured by traditional grey-scale M-mode. Although anatomical M-mode can measure the wall thickening at multiple places, it is still restricted to one aspect. Besides, the traditional M-mode does not allow the shear strain analysis.The 2D speckle tracking technique  used in the present study showed that time to peak radial strain could be used to assess the intra and inter-ventricular synchrony. However, in most other studies, measured strain or strain rate were acquired by averaging the data from multiple points throughout the target segment, which might mask the true myocardial mechanical properties of the individual segments, rendering that the myocardial strains seem to reach the peak at the same time in normal hearts -8. HowevRecently, a number of indexes of intra and inter-ventricular dyssynchrony were used to differentiate responders to cardiac resynchronization therapy (CRT) from non-responders -18. IntrOur study showed that the peak radial normal strain delayed in LVPW than in IVS even in healthy human subjects. It demonstrated that the time to peak radial normal strain was shortest at the base of IVS, and then increased progressively from the mid to the apical of IVS to the apical, mid and base of LVPW. This peak time difference may be explained by the direction of electrical conduction. Note that when employing the index of time to peak radial normal strain for patient selection and assessment of CRT. When these indexes were utilized, the presence of physiological dyssynchrony as shown in this study should be taken into consideration.In this study, there is no analysis of differences at the three levels within the same wall. Instead, we focused on the comparison of the strains that occurred in different wall (IVS and LVPW) at the same LV level since the main purpose of this study was to verify the myocardial sheets theory in the human hearts. For the same reason, only two walls (IVS and LVPW) are considered in this study although this system allows the evaluation of six myocardial points from a single LV short-axis view.There are some technical limitations. The first is that speckle tracking echocardiography is dependent on frame rates, as well as image resolution. The second is that the user interface required for the endocardial border tracing, and care must be taken to manually fine-tune the region of interest. The third is that speckle tracking echocardiography is two-dimension, out-of-plane movement and the reproducibility could also be the factors that influence the accuracy of this technique. In the present study, high frame rate was acquired and only the subjects with high quality cardiac images were adopted for analysis. Further studies with MRI validation need to be done. In addition, the present study that covered a group of young healthy subjects does not apply to the entire populations, and a separate study covered patients with heart diseases was being performed and the data were not included in the present study. In addition, the superiority of these new parameters over classic longitudinal, circumferential and radial strain in clinical practice needs to be further studied.The present Two-Dimensional Echocardiographic Speckle Tracking System can be used to assess cardiac mechanics from different perspectives and the data from the current study may be used as reference value. The findings of peak systolic radial normal strain of LVPW was much greater than that of IVS and occurred much later, and LVPW showed different shear strain on LV long-axis view from that of IVS, indicated that “myocardial sheets” theory also holds for intact human LV. In addition, the physiological dyssynchrony existed in healthy human subjects was quantified, which should be considered when evaluating the diseased hearts by this technique.LV: Left ventricular; IVS: Interventricular septum; LVPW: Left ventricular posterior wall; 2-D: Two-dimensional; LVFW: Left ventricular free walls; EF: Ejection fraction; FS: Fractional shortening; E/A: Early peak flow velocity/atrial peak flow velocity across the transmitral valve; CRT: Cardiac resynchronization therapy; SPWMD: Septal-to-posterior wall motion delay; SPWTD: Septal-to-posterior wall thickening delay; LAX: Long-axis view of left ventricle; SAX: Short-axis view of left ventricle.The authors declare that they have no competing interests.YLJ carried out the echocardiographic data acquisition, analysis and interpretation, drafted the manuscript and gave final approval of the version to be published. TK participated in the study conception and design, analysis and interpretation of data, revising the manuscript and gave the final approval of the version to be published. UK, EA, SK, KT, SM and NR substantially contributed to analysis and interpretation of data, and gave final approval of the version to be published.Animation illustrating the myocardial sheets motion proposed by LeGrice et al. [. On the cross-section of LV, myocardial sheets with the width of 4 myocytes separated by cleavage planes of loose connective tissue could be identified. When myocardial cells contract, the myocardial sheets slide on each other causing shear strain. The myocardial sheets approached the LV endocardium obliquely from the apical direction, becoming nearly parallel to the endocardial surface in LVPW while, in the IVS, the sheets approached the LV endocardium rather vertically from the opposite direction. This difference in sheets orientation at end-diastole would cause difference in systolic radial strain between IVS and LVPW. Myocardial sheets slide relative to each other and change orientation from end diastole to end systole, and this sliding (shearing) motion pushes the endocardium towards the LV cavity, which is more prominent in LVPW than IVS. As a result, both radial normal strain and shear strain are significantly larger in LVPW than in IVS. et al. . On theClick here for fileMeasurements of radial normal strain of IVS and LVPW at mid level in parasternal LV long axis view . Right panel shows radial normal strain curves for left ventricular posterior wall (LVPW) and interventricular septum (IVS). IVS strain peaks is earlier than LVPW strain, and peak strain value is about 2 times larger in LVPW than in IVS.Click here for file


The incidence of cardiovascular disease (CVD) in rheumatoid arthritis (RA) is increased compared to the general population. Immune dysregulation and systemic inflammation are thought to be associated with this increased risk. Early diagnosis with immediate treatment and tight control of RA forms a central treatment paradigm. It remains unclear, however, whether using tumor necrosis factor inhibitors (TNFi) to achieve remission confer additional beneficial effects over standard therapy, especially on the development of CVD.Coronary Artery Disease Evaluation in Rheumatoid Arthritis (CADERA) is a prospective cardiovascular imaging study that bolts onto an existing single-centre, randomized controlled trial, VEDERA (Very Early versus Delayed Etanercept in Rheumatoid Arthritis). VEDERA will recruit 120 patients with early, treatment-naïve RA, randomized to TNFi therapy etanercept (ETN) combined with methotrexate (MTX), or therapy with MTX with or without additional synthetic disease modifying anti-rheumatic drugs with escalation to ETN following a ‘treat-to-target’ regimen. VEDERA patients will be recruited into CADERA and undergo cardiac magnetic resonance (CMR) assessment with; cine imaging, rest/stress adenosine perfusion, tissue-tagging, aortic distensibility, T1 mapping and late gadolinium imaging. Primary objectives are to detect the prevalence and change of cardiovascular abnormalities by CMR between TNFi and standard therapy over a 12-month period. All patients will enter an inflammatory arthritis registry for long-term follow-up.CADERA is a multi-parametric study describing cardiovascular abnormalities in early, treatment-naïve RA patients, with assessment of changes at one year between early biological therapy and conventional therapy.ISRCTN50167738) on 8 November 2013.This trial was registered with Current Controlled Trials (registration number:  Rheumatoid arthritis (RA) is one of the most common autoimmune diseases affecting approximately 1% of the population in the United Kingdom , and is Arterial stiffness is associated with an increased risk of CV events with a range of co-morbidities . In patiEarly diagnosis of RA and immediate intervention with conventional disease modifying anti-rheumatic drugs (DMARDs) in a treat-to-target approach, with remission the goal of treatment, is an internationally recommended, established practice . BiologiCV clinical trials of TNFi treatments in RA are challenging because of the small number of hard clinical CV mortality endpoints in study populations , and beiThe imaging modalities currently used for the assessment of CVD in RA are transthoracic echocardiography (TTE), single-photon emission computed tomography (SPECT) and cardiovascular magnetic resonance (CMR) . PET is CMR is widely recognized as a safe, sensitive, reproducible and comprehensive non-invasive imaging test to detect CVD. Both anatomical and functional assessment can be made with CMR. Left ventricular (LV) mass and function can be measured more accurately than with any other imaging method . Aortic The literature on CMR in RA is sparse. In contrast to previous TTE studies, CMR shows that patients with RA have reduced LV mass and EF . No prevWe hypothesize that the CADERA study will determine, using multi-parametric CMR, that i) subclinical CV pathology exists in patients with early, treatment-naïve RA, ii) early aggressive control of RA can reduce this subclinical CV pathology at one year from treatment initiation and iii) TNFi offer additional benefit over and above conventional DMARD in the burden of subclinical CV pathology.CADERA bolts on to the VEDERA (Very Early versus Delayed Etanercept in Rheumatoid Arthritis) trial, a prospective longitudinal intervention study of patients with early RA, randomized to either first-line TNFi therapy  and MTX or optimal synthetic DMARD therapy. VEDERA is an investigator-initiated research (IIR) study based at the Leeds Institute of Rheumatic and Musculoskeletal Medicine, and is funded by an unrestricted educational grant that is part of an IIR agreement with Pfizer. VEDERA is a phase IV, single-centre study of 120 patients with new-onset, treatment-naïve RA, randomized to either immediate ETN and MTX combination or initial MTX and a treat-to-target regimen ; with step-up in the latter group to ETN and MTX combination therapy in patients failing to achieve a pre-defined target of remission after 24 weeks. The aim of VEDERA is to assess for the depth of remission  and immunological normalization induced by the treatment arms, as well as to identify predictors of remission.VEDERA patients will be recruited to CADERA and undergo CMR at baseline (prior to treatment) as well as after one and two years of treatment .Patients eligible for VEDERA will be recruited from the Leeds Teaching Hospitals NHS Trust Rheumatology service. The recruitment period is expected to last up to 36 months. All patients recruited to VEDERA will be offered inclusion to the CADERA study. CADERA CMR scans will be performed and analyzed at Leeds General Infirmary. The study will be performed in accordance with the Declaration of Helsinki (October 2000), with all patients providing informed written consent.Inclusion criteria for VEDERA, and therefore CADERA, are patients diagnosed with RA according to the 2010 American College of Rheumatology/The European League Against Rheumatism (ACR/EULAR) criteria (Table 2), known allergy to gadolinium-based contrast agents and contraindications to adenosine (asthma or high-grade heart block)).Exclusion criteria are previous treatment with DMARDs, known CVD, contraindications to TNFi therapy (or severe co-morbidity that would in the clinician’s opinion be associated with unacceptable risk of receiving TNFi therapy) and contraindications to CMR,  <30 ml/min/1.73 m2 versus 2.6 ± 0.6 cm2 in controls. LV volumes and mass were similar between groups and LV strain and twist showed trends towards a reduction in RA patients, but without reaching statistical significance. Our pilot data therefore suggested CV abnormalities in patients with RA in several quantitative CMR parameters, with aortic distensibility reaching statistically significant difference even in the small sample size.The primary outcome measure is aortic distensibility. It will be measured and quantified at baseline and at one year in each arm of the study. Increased arterial stiffness is associated with an increased risk of CV events . It can Longitudinal changes of outcome measures in response to therapy will be measured and compared between the two treatment arms at baseline, one and two year time points. Secondary outcome measures are i) myocardial perfusion reserve, ii) LV strain and twist, iii) LVEF and iv) LV mass. Exploratory outcome measures are pre- and post-contrast T1 mapping, extra-cellular volume (ECV) and biomarker measurements.P <0.05) of CV abnormalities detected by CMR between the two treatment arms will be presented, and the magnitude of this difference will be expressed as a 95% confidence interval.Significant differences  and non-treated RA patients reported by Ikonomidis et al. [2dyne-110-6 and 4.6 cm2dyne-110-6, respectively. The standard deviation (SD) of the post-treatment measurements in the Anakinra group was 3.2 cm2dyne-110-6 and a more conservative estimate of 3.5 cm2dyne-110-6 has been used in the CADERA power calculation. Assuming an SD of 3.5 cm2dyne-110-6, a power of 70%, 80% and 90% would be achieved at 5% significance level in a two-tailed independent samples Student’s t-test with 26, 33 and 44 patients respectively in the primary outcome measure of aortic distensibility in each treatment group .Power calculations are based on a previous study by Ikonomidis et al. . We assus et al. . Mean aoBoth treatment arms will be compared with primary outcome aortic distensibility from baseline to one-year follow-up, as well as other outcome measures. Analysis will be conducted in the R environment for statistical computing . Exploratory data analysis will be used to determine if parametric (independent samples Student’s t-test) or non-parametric (Wilcoxon rank sum test) analyses are appropriate, and to summarize the distribution of aortic distensibility and change in other outcome measures across the two treatment arms. These analyses will also allow the credibility of an equal variance assumption to be assessed in parametric modeling and to be appropriately modeled . All patThe numbers of patients with missing data for one or more CMR measurements, and the number of uninterpretable images will be reported. Patients with missing data for any CMR measurement will be excluded from any comparison involving that measurement.The number of patients referred from VEDERA and failing to complete the CMR protocol will be reported, along with the reason why the test failed. The duration of the CMR scan will also be summarized.Our group has well-established multi-parametric protocols that have been validated in other populations . CMR wilLow-resolution survey, reference scans and localizers. Following survey and reference scans, the heart’s short axis, vertical long axis and horizontal long axis will be defined with a series of cine images , echo time (TE) 1.48 ms, repetition time (TR) 3.0 ms, flip angle 45°, field of view 320 to 420 mm according to patient size, slice thickness 10 mm and 30 phases per cardiac cycle).3 trigger delay at end-diastole, flip angle 35° and field of view 320 to 420 mm) [Baseline T1 mapping. One slice will be acquired at the LV short axis using an electrocardiogram (ECG)-triggered modified Look-Locker inversion (MOLLI) method to acquire 11 images  in a single end-expiratory breath hold (voxel size 1.7 × 2.14 × 10 mm 420 mm) , 47.3 acquired resolution, pre-pulse delay 100 ms, acquisition shot 123 ms/slice, three short axis slices) [Adenosine stress first-pass myocardial perfusion imaging  . Intrave slices) .3 and 30 cardiac phases) [Resting wall motion and LV function. Cine image stack covering the entire heart in the LV short axis plane at one slice per breath-hold in end-expiration and parallel to the mitral valve annulus  , 51.3, tag separation 7 mm, ≥18 phases, typical TR/TE 5.8/3.5 ms and flip angle 10°).Tissue tagging for strain analysis and diastology. Spatial modulation of magnetization pulse sequence  at the level of the PA bifurcation and the descending aorta, transverse to the vessel according to Lee et al. . For aorResting first-pass myocardial perfusion study. Pulse sequence, slice positioning and injection characteristics identical to the stress perfusion scan as above in step 3.3. Inversion time adjusted according to variable TI scout. Alternate heart beat acquisitions by navigator is an option for poor breath holders. Performed in 10 to 12 short axis slices with further slices acquired in the vertical and horizontal long axis orientations, or phase-swapped, if indicate based on LGE imaging obtained, wall-motion or perfusion defects.Late gadolinium enhancement (LGE). Performed between 10 and 15 minutes after step 7. Inversion recovery-prepared T1-weighted gradient echo. The optimal inversion time to null signal from normal myocardium will be determined using a modified Look-Locker approach . TypicalPost-contrast T1 mapping 15 minutes following last contrast injection at step 7. Acquisition and slice positioning as above in step 2.T1 mapping, tissue tagging and perfusion imaging are performed in three identical short-axis positions. These will be determined using the ‘three-of-five’ approach by acquiring the central three slices of five parallel short-axis slices spaced equally from mitral valve annulus to LV apical cap .Image analysis will be performed offline, blinded to patient characteristics and treatment arm, using commercially available software  according to international standards for reporting of CMR studies .LV volume and EF will be calculated from the short axis cine-stack using standard criteria to delineate cardiac borders . RegionaNative and post-contrast myocardial T1 will be measured . Care wiWhere hct is the hematocrit. Myo pre and myo post are the pre-contrast and post-contrast myocardial T1 values. Blood pre and blood post are the pre-contrast and post-contrast blood pool T1 values. Strain analysis will use data from the tagged cine series. Endocardial and epicardial contours are drawn by a semi-automated process for each slice. Peak circumferential systolic strain and rotation will be calculated for the three short axis slices at the level of apex, mid-ventricle and base. LV twist is calculated by subtracting the basal rotation from the apical rotation. The method of determining torsion takes the radius and length of the heart into account, describing the torsion as the circumferential-longitudinal shear angle. This makes the measurement comparable between hearts of different sizes and is related to fiber orientation and processes in the myocardium , 59. BasMyocardial perfusion will be assessed by visual comparison of stress and rest CMR perfusion scans (16 segments of the modified 16 segment American Heart Association/American College of Cardiology model)  with scoLGE images will be analyzed visually by two experienced observers and any relevant patterns of enhancement are described based on a 17-segment model with scores of 0 (no hyperenhancement), 1 , 2 , 3  or 4  allocated to each segment. Quantitative analysis of LGE will also be performed. LGE volume will be calculated across the whole LV stack by the modified Simpson’s method. To avoid confounding for artifacts, a conservative threshold for LGE is employed at five SDs from remote, normal myocardium. The amount of LGE will be presented as a percentage against normal myocardium.P = not significant). The coefficient of variation (CoV) in the diastolic and systolic measurements were 1.4% and 1.1%, with an intra-class correlation coefficient (ICC) of r = 0.998 and r = 0.998, respectively [CMR measurements have been validated in previous reproducibility studies. In our hands, the inter- and intra-observer reproducibility for measurement of aortic distensibility by CMR is excellent. In a clinical study of 49 volunteers, the intra-observer mean difference for diastolic (minimum) aortic volume was 0.009 ± 0.039 ml and the mean difference for systolic (maximum) aortic volume was 0.0075 ± 0.039 ml , ACPA, CRP, ESR, lipid profile, high-sensitivity CRP, serum amyloid A, fibrinogen, adiponectin, interleukin-6, TNF, intercellular adhesion molecule-1, vascular cellular adhesion molecule 1, CD40 ligand and N-terminal prohormone of B-type natriuretic peptide.Created in 2010 at the NIHR LMBRU, the IACON (Inflammatory Arthritis disease CONtinuum) study is a major longitudinal cohort study in inflammatory arthritis. This facilitates collection of CVD outcome measurements in patients with inflammatory arthritis at Leeds from disease inception onwards. On completion of the study, all CADERA study patients will enter IACON, permitting continued follow-up annually or as clinically indicated. There is no fixed endpoint for data collection and study duration of IACON. CMR findings will be linked to clinical outcome through long-term follow-up in this registry.2 will not be recruited. All serious adverse events that occur as a result of the CMR will be reported without formal statistical testing being undertaken.CMR is a standard clinical imaging modality in everyday clinical use and risks to the study participants are small. Adenosine stress agents carry a small risk of adverse effects including transient atrio-ventricular block and bronchospasm. CMR contrast agents carry a low risk of allergic reactions . To avoid the development of nephrogenic systemic fibrosis relating to some CMR contrast agents, patients with renal failure and an eGFR of less than 30 ml/min/1.73 mEarly diagnosis and immediate treatment of new, onset, treatment-naïve RA is crucial to ensure the best possible treatment outcomes. Studies demonstrate TNFi agents confer additional structural benefit but, in particular, may be able to modulate disease progression in a proportion of patients. It remains unclear whether use of non-bDMARD (MTX) impedes this potential effect. We postulate with the VEDERA study that first-line TNFi therapy is qualitatively and quantitatively superior, with better clinical, structural and immunological outcomes when compared with non-biological DMARDs. The bolt-on CADERA study will provide a comprehensive CV evaluation of the VEDERA population to assess the prevalence and severity of CVD in a treatment-naïve patient population of new-onset RA with comparison to clinical parameters, such as RA disease severity. The study will also evaluate whether effective RA disease control (remission) can improve CVD as assessed by CMR and, importantly, whether achieving remission through first-line TNFi offers any additional benefit over initial synthetic DMARD-induced remission. With linkage of CMR assessment, CVD biomarkers and long-term outcomes with follow-up in the IACON registry, we hope to improve our understanding of the pathophysiology of CVD in the RA population. The knowledge gained from these studies may contribute towards more effective use of targeted therapies for patients with RA and improve long-term health-economic benefits.This trial is ongoing. Patient recruitment and follow-up is underway. Recruitment began in February 2012 and is expected to end in June 2015.


MR Tissue phase mapping (TPM) is a non-invasive tool to detect regional and global myocardial wall motion. Evaluation of myocardial velocity in radial and longitudinal direction throughout the cardiac cycle may help us better understand myocardial mechanics. Our goal is to investigate regional and global left ventricular myocardial motion using respiratory-gated high temporal resolution TPM in children and young adults.The HIPAA compliant prospective study was IRB approved. Twelve patients  underwent cardiac magnetic resonance (CMR) (1.5-T) including TPM . Nine patients with no intrinsic myocardial abnormality based on clinical history, standard biomarkers, MRI and echocardiographic data were compared with 2 patients having cardiac dysfunction and 1 patient with hypertrophic cardiomyopathy (HCM). Short axis images at base, mid-chamber and apex were manually contoured to outline the epicardium and endocardium. Data was post-processed using software programmed in Matlab  to obtain segmental radial and longitudinal velocities of left ventricle.Regional and global assessment of radial (contraction and relaxation) and longitudinal (lengthening and shortening) myocardial motion could be detected. Peak radial and longitudinal velocity in systole and diastole were different in our age group compared to documented velocities in adults. Average peak longitudinal velocity in systole in HCM was 5.79 ± 1.82 cm/s  implies hyperdynamic function in HCM. Average peak radial velocity in systole in patients with and without cardiac dysfunction was 2.71 ± 1.48 cm/s and 3.52 ± 1.81 cm/s respectively. Reduced velocities in patients with cardiac dysfunction indicate poor systolic function. Reduced average peak radial velocity in diastole in HCM (-3.82 ± 1.37 cm/s) compared to normal population (-5.93 ± 2.48 cm/s) denotes impaired relaxation of left ventricle and diastolic dysfunction in HCM.Velocity-mapping technique quantifies regional and global systolic and diastolic myocardial motion. Our preliminary result demonstrates a role for TPM to determine systolic and diastolic dysfunction in our age group. Myocardial velocities in children and young adults were different from documented velocities in adults. Recruitment is underway to validate our results in larger cohort.None.


Altered substrate metabolism plays an important role in pathophysiology of heart failure (HF). Optimization of myocardial energy metabolism with metabolic modulators like trimetazidine (TMZ) allows more efficacious energy production.Although TMZ has been studied extensively in patients with ischemic HF, more data are needed on its role in dilated cardiomyopathy (DCM).100 patients of DCM  were randomized to TMZ  vs conventional therapy (n = 50). Functional status, BNP & echocardiographic parameters were assessed at 3-6 months.Baseline characteristics were comparable among the two groups. At three months, patients on TMZ had significant improvement in mean NYHA class , 6 min walk test , LVD-36 score  and fall in BNP . This was accompanied by significant improvement in indexed LV end-systolic  and LV end-diastolic volumes  and LVEF  along with reduction in LV wall stress . Other echocardiographic parameters also improved after three 3 month of TMZ  and TDI parameters . Patients not on TMZ had no significant change in NYHA Class, LVD-36 scores, LV volumes or LVEF at 3 months although BNP levels & LV wall stress reduced, albeit to a lesser extent than TMZ. Patients on TMZ had further improvement in NYHA Class, 6 min walk test, BNP levels & all echocardiographic parameters at 6 months.Metabolic modulators like trimetazidine have a potential role to play in altering LV remodelling and improving LV function in DCM. In this study, benefit was noted by 3 months with further improvement at 6 months.


Computed tomographic pulmonary angiography (CTPA) has been used as a standard tool for diagnosing an acute pulmonary embolism (APE). The right ventricular (RV) strain signs may be used to predict adverse outcomes. However, the results are still controversial. The primary objective of our study was to evaluate the relationship between the RV strain signs and respiratory failure requiring mechanical ventilation or death in APE. The secondary objective was to identify clinical factors which related to those outcomes.CTPA and the medical records of patients with suspected APE on admission from June 2011 to March 2013 were reviewed. RV dysfunction signs included right ventricular to left ventricular (RV/LV) diameter ratio, interventricular septal shift, main pulmonary artery to ascending aorta (mPA/AA) diameter ratio, IVC contrast reflux, SVC diameter, IVC diameter, PA diameter and azygos vein diameter. Clinical factors included cardiovascular, respiratory parameter and also time to diagnosis and treatment.P = 0.008) and respiratory failure . The sensitivity, specificity, positive predictive and negative predictive values of IVS shift to predict in-hospital death were 85.7%, 70%, 42.8% and 95.5%, respectively. The sensitivity, specificity, positive predictive and negative predictive values of IVS shift to predict respiratory failure were 70%, 73.1%, 50% and 86.4%, respectively. The ratios of RV to LV diameter and the ratio of main pulmonary artery to ascending aorta diameter tended to be higher in the nonsurvivor group. The clinical factor that predicted mortality was the PaO2 to FiO2 ratio (P/F ratio). Mean P/F ratio in survivor and nonsurvivor groups was 246.1 ± 94.1 vs. 132.2 ± 78.1, respectively (P = 0.011). P/F ratio ≤150 was the best predictor of mortality .There were total of 36 cases with suspected APE on admission. Ten patients required mechanical ventilation (27.8%) and seven patients died (19.4%). Interventricular septal (IVS) shift was a significant risk factor of in-hospital death (85.7% vs. 27.6%, The IVS shifting from CTPA and P/F ratio ≤150 helps predict poor outcomes in APE.


Decades ago, the surgeons were asking themselves if it was possible to improve the natural history of patients with “functionally” univentricular heart . In ordeSince the first stage in both groups is a palliative approach, over the years, the progress with the available materials and technology facilitated the surgical palliations to increase the pulmonary blood flow with systemic-to-pulmonary shunt  , 3 as weThe introduction of the use of the end-to-side anastomosis of the transected main pulmonary artery to the ascending aorta (Damus–Kaye–Stansel), as source of systemic blood flow, facilitated the management of patients with “functionally” univentricular heart with obstruction to the systemic blood flow .The results of the surgical management have been substantially improved by the introduction of the bidirectional Glenn (end-to-side anastomosis of the superior vena cava to the right pulmonary artery) as second stage between the first palliation to control the pulmonary blood flow and the final stage of dividing the systemic and the pulmonary venous returns .The introduction of the extracardiac modified Fontan procedure as third surgical stage contributed to provide adequate early  and lateThe improved knowledge of the appropriate timing of indication and the adequate preparation for the third stage with Fontan circulation  togetherThe availability of adequate research laboratories allowed the performance of sophisticated experimental studies on animals to improve the available knowledge on the mechanisms of chronic hypoxia , 13 and Finally, the combination of experimental research with computational fluid dynamic studies prompted to evaluate the feasibility of the mechanical assistance for patients at high risk for modified Fontan procedure or with failure of the Fontan circulation .Several aspects of the management of patients with “functionally” univentricular heart have been investigated in the recent literature.Considering the peculiar pathophysiology with difficult balance between systemic and pulmonary blood flow, often these patients require a period of stabilization before any surgical step, sometimes including resuscitation because of cardiac arrest or severe metabolic derangement .With regard to the ventricular morphology, several studies are still investigating the long-term ventricular function to evaluate if there is a difference in the performance between the right and left ventricular morphology .Some brave surgeons, working in emergent economies, decided to proceed with a pulmonary artery banding as first palliative stage in patients with “functionally” univentricular heart at an average age much older than for the conventional management. Contrary to the expectations and the available knowledge, they have reported quite good results, with adequate long-term follow-up after the subsequent surgical steps .Z score, McGoon ratio, and Nakata index. Disagreement still exists about the growth of the pulmonary arteries following interstage procedures  and the bidirectional Glenn, and between the bidirectional Glenn and the modified Fontan procedure, using different criteria to evaluate the size of the pulmonary arteries: ocedures .The most challenging group of patients with “functionally” univentricular heart is the group with heterotaxy because of the frequently associated anomalies of the systemic and venous connections, the variable anatomy of the sinus node and conduction system, the common presence of atrioventricular valve regurgitation, and the difficulty in obtaining with surgical palliations an adequate balance between the systemic and the pulmonary blood flow .With regard to the preservation of the ventricular function for the long-term performance of the unique ventricular chamber available, in association with the best possible choice of timing and type of the surgical procedures, attempts have been done at improving the ventricular function with medical treatments potentially unloading the single ventricle .Thanks to the improved surgical results obtained in the last decades with relatively reduced mortality and morbidity, in the last few years, the attention of the caregivers has concentrated on the quality of life and the neurodevelopmental and cognitive development following the surgical procedures .The goal in patients with “functionally” univentricular heart is always to possibly reach the stage of Fontan circulation, and the recent literature has recently reported articles on the importance of imaging in the perioperative assessment of Fontan patients , on the More importantly, the data collected in the North-American and European Congenital Data Base allow a very extensive documentation of the currently available information on indication, clinical practice, and outcomes in this challenging group of patients .Despite the fact that in patients with “functionally” univentricular heart almost all surgeons are planning surgical steps toward the accomplishment of the Fontan circulation, few surgeons are still offering a ventricular septation in selected cases with double inlet left ventricle, with decent long-term outcomes .Nevertheless, in a not negligible percentage of patients, because of the failure of the conventional surgery, heart transplant has to be considered in the presence of end-stage circulatory failure after Fontan procedure , 33.Since there are still many unsolved questions and issues in the management of patients with “functionally” univentricular heart, this Research Topic has been organized to stimulate the people involved with these problems to provide their contribution to this timely and difficult matter.The patients with “functionally” univentricular heart have been taken into consideration from the moment of pre-natal diagnosis  through The decision-making process has been extensively investigated from the first surgical stage until the third stage , and parFinally, the long history of the surgical approaches used to separate the pulmonary from the systemic venous return obtaining the Fontan circulation has been reviewed, with precise analysis of the advantages and disadvantages of all the surgical techniques .The extensive review and update performed in this Research Topic will be hopefully useful to all the readers involved with the treatment of this very difficult group of patients.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Only recently have several multi-slice spiral computed tomography (MSCT) techniques been evaluated for visualisation of myocardial infarction. This review describes the different concepts of MSCT viability imaging. MSCT assessment of myocardial morphology, myocardial perfusion imaging and delayed myocardial contrast enhancement are introduced, with the latter evolving as the key concept of MSCT viability imaging. Clinical relevance of the different MSCT techniques is described.Over the last decade, imaging of myocardial viability has become a well-established indication in patients suffering from myocardial infarction. Myocardial viability imaging is routinely performed using  During the last decade, great advances in cardiac imaging have been achieved. Magnetic resonance (MR) imaging as well as multi-slice spiral computed tomography (MSCT) have become routine tools for cardiac imaging. One of the most relevant clinical applications is visualisation of myocardial viability. As dysfunctional but viable myocardium has the potential for functional recovery after reperfusion,Moreover, the extent and degree of myocardial injury determines patient outcome and survival.3The transmural extent of infarction is also of crucial importance, as this determines outcome. The global left ventricular systolic function of patients who had successful reperfusion of their first acute myocardial infarction, resulting in necrosis of less then 25% of wall thickness, improved in 67% of patients. If the extent of irreversible myocardial damage was limited to less than 50% of myocardial thickness, regional left ventricular function improved in 56% of patients.5Therefore, assessment of myocardial viability with delayed contrast-enhanced MR imaging proved essential for risk stratification and treatment planning. In addition, there is only limited time before chronically hypoperfused myocardium becomes irreversibly damaged.618F-fluorodeoxyglucose positron emission tomography (PET) and MR imaging have been established for the assessment of myocardial viability. Except for MR imaging, these techniques do not allow differentiation between transmural and non-transmural infarction. MR imaging not only allows for detailed visualisation of viable and nonviable myocardium but also assessment of contractile function. Therefore, MR imaging has evolved as the gold standard for the assessment of myocardial viability.7In clinical routine, several techniques, including low-dose dobutamine stress echocardiography, single-photon emission computed tomography (SPECT), With the introduction of MSCT in cardiac imaging, a new modality entered the ring of myocardial viability imaging. Only recently have promising results been published, proving MSCT capable of differentiating viable from non-viable myocardium and having the ability to assess the transmural extent of myocardial infarction.Ischaemic injury of the myocardium can be differentiated as reversible and irreversible, as well as in acute and chronic conditions de-novo synthesis of proteins.11Single or repeated short periods of myocardial ischaemia may result in myocardial stunning,Hibernating myocardium is characterised as viable but nonfunctional myocardium with chronically impaired regional blood flow.13The loss of the cell membrane integrity marks the point of cell necrosis and irreversible myocardial infarction. In necrotic myocytes, the intracellular space is accessible to extracellular contrast media. In addition, cytokine-mediated interstitial oedema increases the distribution volume for contrast material.In acute myocardial infarction, not all cells die simultaneously. 5Restoration of blood flow in the coronary arteries does not necessarily result in microvascular flow restoration;17Within 72 hours of acute myocardial infarction, thinning of the necrotic myocardium can be observed. Simultaneously, its endocardial surface area increases due to the reduced tensile strength of the infarcted tissue. Within six weeks, the necrotic myocardium is replaced by scar tissue that is markedly thinner than healthy myocardium. The time course of this remodelling process is influenced by several factors such as the severity of the underlying disease or secondary events.18Up to now, MR imaging has been considered as the gold standard for viability imaging. There are some limitations, however, to cardiac MR imaging. For patients with implantable devices such as pacemakers and defibrillators, alternative techniques are needed to evaluate myocardial viability.While coronary calcium scoring and coronary angiography are currently the key applications of cardiac MSCT, it also permits evaluation of the cardiac veins,23Myocardial viability can be assessed with different MSCT techniques. Most of them are based on techniques that were developed for MR imaging of myocardial infarction, including the assessment of the left ventricular wall thickness, evaluation of myocardial perfusion and delayed enhancement imaging. Most commonly, an original CT technique, the detection of hypo-enhancing myocardium during arterial phase, is used to detect myocardial infarction.Contrast enhancement of the myocardium during arterial-phase CT is directly related to myocardial perfusion. As myocardial infarction is associated with a lack of perfusion, it can be assumed that myocardium with reduced contrast enhancement during arterial-phase CT is related to coronary artery stenosis, occlusion of an epicardial coronary artery, obstruction of intramyocardial arterioles or chronic myocardial scar. This technique was developed in the 1970sThe introduction of MSCT dramatically changed the role of cardiac CT. With gantry rotation times down to 0.33 s, submillimetre spatial resolution and simultaneous development of advanced post-processing technologies, cardiac CT became popular again. As a consequence, acquisition of high-resolution MSCT angiography data allowed calculation of short-axis images and consequently, sufficient assessment of the inferior wall of the left ventricle. Recently, sensitivities and specificities ranging from 79 to 91% were reported for the detection of myocardial infarction by coronary MSCT when compared with ventriculography and MR imaging ; Table 232One main limitation is that reduced contrast enhancement during arterial phase not only represents myocardial infarction, but also reduced perfusion. As a consequence, reduced contrast enhancement can be found in viable as well as non-viable myocardium. Moreover, the size of infarction is significantly underestimated in arterial-phase CT.The use of arterial-phase stress adenosine MSCT was demonstrated by a small single-centre study.To assess the significance of a coronary artery lesion, techniques to quantify the physiological relevance are needed. First-pass myocardial perfusion imaging is suited to address this problem as decreased myocardial perfusion represents the first consequence of obstructive coronary artery disease.37Animal studies have shown the MSCT assessment of differences in myocardial perfusion to be feasible. For this purpose, rest and stress perfusion scanning were combined.When compared with MR imaging, MSCT perfusion imaging requires radiation exposure, but also offers the advantage of the linear relationship between contrast enhancement and iodine concentration.To overcome the limitations of arterial-phase CT, other CT techniques were developed to selectively depict infarcted myocardium. For CT, it was shown as early as 1978 that extracellular contrast material accumulates in areas of acutely infarcted myocardium.44This assessment changed with the introduction of MSCT. Recently, several studies in animals On delayed enhanced MSCT, myocardial infarction shows increased attenuation values when compared with healthy myocardium. No-reflow areas present as hypodense regions surrounded by hyperenhanced myocardium.In general, delayed enhanced MSCT slightly overestimates the size of infarction. This might be due to an increase of the distribution volume in the peri-infarction zone.52So far, there is no unequivocal agreement on the most suitable protocol for delayed enhanced CT imaging. One of the major issues is the mode of contrast application and the optimal delay to image acquisition. Some studies showed best contrast between infarcted and normal myocardium at five minutes after injection.When compared to MR imaging, delayed enhanced MSCT imaging of myocardial infarction presents low contrast between the area of infarction and the blood pool. While a delay of several minutes is needed to allow contrast material to accumulate in infarcted myocardium, rapid fading of contrast is a major problem for accurate delineation of myocardial infarction with MSCT. Consequently, selection of an optimal delay is crucial for late enhanced CT images, with suggested intervals ranging from five to 15 minutes. Moreover, dedicated contrast injection protocols have to be developed to optimise contrast. The total amount of contrast material should exceed 50 g of iodine to ensure a sufficient contrast on late enhanced MSCT images. So far, there is no consensus whether a continuous injection of contrast material is superior to a single bolus injection for improving the quality of late-phase MSCT images A different approach to improve contrast in delayed enhanced CT is the application of 80 kVp protocols that will result in better iodine contrast at the cost of greater image noise.et al. the lack of a hypo-enhanced area during arterial phase may indicate successful reperfusion at both the epicardial and the microvascular level.48When combining arterial- and late-phase MSCT, different contrast enhancement patterns can be observed. In some patients with delayed enhancing myocardium, an area of reduced attenuation might be present during arterial phase. According to Koyama The difference in size between arterial and late enhanced CT in a rabbit animal model was considered to reflect coronary reperfusion.48MSCT allows for the reliable assessment of myocardial viability. In patients with contra-indication to MR imaging, or if MR imaging is not available, MSCT appears to be the alternative of choice for the diagnostic work-up in patients with myocardial infarction. In combination with non-invasive coronary MSCT angiography and analysis of left ventricular function, delayed enhanced MSCT offers a comprehensive examination strategy for evaluation of the heart.


We evaluated the acute impact of different cardiac pacing sites on two-dimensional speckle-tracking echocardiography (STE) derived left ventricular (LV) rotation and twist in healthy dogs.Twelve dogs were used in this study. The steerable pacing electrodes were positioned into right heart through the superior or inferior vena cava, into LV through aorta across the aortic valve. The steerable pacing electrodes were positioned individually in the right atrium (RA), right ventricular apex (RVA), RV outflow tract (RVOT), His bundle (HB), LV apex (LVA) and LV high septum (LVS), individual pacing mode was applied at 10 minutes interval for at least 5 minutes from each position under fluoroscopy and ultrasound guidance and at stabilized hemodynamic conditions. LV short-axis images at the apical and basal levels were obtained during sinus rhythm and pacing. Offline STE analysis was performed. Rotation, twist, time to peak rotation (TPR), time to peak twist (TPT), and apical-basal rotation delay  values were compared at various conditions. LV pressure was monitored simultaneously.P<0.05). The apical and basal rotation and twist values were significantly higher during HB pacing than during pacing at ventricular sites . The apical TPR during HB pacing was significantly shorter than during RVOT and RVA pacing (both P<0.05). The LV end systolic pressure (LVESP) was significantly lower during ventricular pacing than during pre-pacing and RA pacing.Anesthetic death occurred in 1 dog, and another dog was excluded because of bad imaging quality. Data from 10 dogs were analyzed. RVA, RVOT, HB, LVA, LVS, RARV (RA+RVA) pacing resulted in significantly reduced apical and basal rotation and twist, significantly prolonged apical TPR, TPT and RSI compared to pre-pacing and RA pacing (all Our results show that RA and HB pacing results in less acute reduction on LV twist, rotation and LVESP compared to ventricular pacing. Ventricular pacing could induce abnormal, asynchronous electrical activation and mechanical motion of the left ventricle (LV) Cardiac pacing site might be an important determinant for pacing-induced changes on LV mechanical motion, and pacing at some specific cardiac sites might minimize cardiac pacing-induced unfavorable effects LV twist and rotation are important elements of cardiac mechanics All animal protocols in this study were approved by the Animal Care and Use Committee, Research Institute of Medicine, Shanghai Jiao Tong University, in accordance with National Institutes of Health guidelines and public law. All surgery was performed under sodium pentobarbital anesthesia, and all efforts were made to minimize suffering.Animals  were purchased from Shanghai Jiagan biological technology CO., LTD . The study was performed in a cardiac catheterization laboratory equipped with fluoroscopy  and electrophysiology catheters . After 12 hours fasting, dogs were anesthetized with sodium pentobarbital . The 6F sheaths were inserted percutaneously into the femoral vein and artery for venous and arterial access. The external jugular vein and/or artery were prepared if more venous and/or arterial accesses are needed.With the help of fluoroscopy and an ultrasound system , the fluid filled 5F pigtail catheter  was placed in the LV across the aortic valve to monitor LV pressure during the whole experimental procedure. The steerable pacing electrodes were positioned into right heart through the superior or inferior vena cava, into LV through aorta across the aortic valve via femoral or carotid artery. The steerable pacing electrodes were positioned individually in the right atrium (RA), right ventricular apex (RVA), RV outflow tract (RVOT), His bundle (HB), LV apex (LVA) and LV high septum (LVS) for pacing (≥5 min) under fluoroscopy and ultrasound guidance, as previously described Individual pacing mode was applied at 10 minutes interval. After at least 5 minutes pacing under stabilized hemodynamic conditions, frame rate, sector width and depth were manually adjusted to achieve a quality image with frame rates from 60 to 80 frames per second using the Vivid 7 ultrasound machine equipped with 3.5-MHz transducer . Parasternal LV basal  and apical short-axis images were acquired from three consecutive cardiac cycles. Apical 4 chamber views were also obtained. LV end diastolic volume (LVEDV), LV end systolic volume (LVESV) and LVEF was measured using Simpson’s biplane method. The Maximal annular plane systolic excursion of both mitral (MAPSE) and tricuspid (TAPSE) were also measured by placing the M-mode cursor oriented to the junction of the mitral annular plane with the LV lateral wall as well as tricuspid annular plane with the RV free wall using images of the apical four-chamber view Analysis of echo images was performed offline on a Windows workstation using a customized software package  and observer was blinded to the pacing mode. A circular region of interest (ROI) was specified between endocardial and epicardial borders, at the reference end diastolic frame of the image loop. An automated tracking algorithm was used to track the speckles within the specified ROI throughout the cardiac cycle. This system follows acoustic markers in the myocardium in the subsequent frames of the image loop during a cardiac cycle and computes time-rotation and -twist curves automatically. The peak rotation and twist values were then acquired from the curves. The Q-wave to peak rotation interval  was defined as the interval from the beginning of the Q-wave to the peak apical counter-clockwise or peak basal clockwise rotation, and the Q-wave to peak twist interval  defined as the interval from the beginning of the Q-wave to the peak twist . Apical-To minimize the affection of heart rate, TPR, TPT, and RSI data were adjusted by R–R interval as follow: TPR/R-R interval, TPT/R-R interval, and RSI/R-R interval.All data are expressed as means ± standard deviation. Data were analyzed by one-way analysis of variance (ANOVA) followed by post hoc Fisher's least significant difference test. The relation among rotation and twist with LVEDP, LEVSP, LA, LVEDV, LVESV, LVEF, MAPSE, TAPSE, QRS duration, TPT and RSI was assessed with Pearson correlation analysis. Inter-observer variability of measurements was determined by two independent blinded observers on 25 randomly selected cases for twist and TPT measurements.P value <0.05 was considered to indicate statistical significance.Analyses were performed using the SPSS 14.0 statistical software . All statistical tests were two sided, and a P<0.001). The pacing rates were similar among all pacing groups . LVEDV, LVESV, LVEF, LVEDP, MAPSE and TAPSE were similar before and after pacing at various cardiac sites   .P<0.05, expect basal rotation value post RVA pacing)  .P<0.05), and aTPR value was longer post RVOT and RVA pacing compared to post HB pacing , and the bTPR post HB pacing was also smaller than that post RARV and LVA pacing (both P<0.05)  .r = 0.321 and 0.433, respectively, both P<0.01), and negatively correlated with QRS duration . There was no correlation among LVEDP, LEVSP, LVEDV, LVESV, LVEF, MAPSE and TAPSE with rotation or twist parameters. The twist was negatively correlated with TPT and RSI .The apical rotation and twist were positively correlated with LVESP (r = 0.836 at twist and 0.879 at TPT (both P<0.01) for results evaluated from two observers.The calculated sample Pearson correlation coefficient was Present study provides some insight on the acute effects of pacing at different cardiac sites on LV twist and rotation. The major finding of this study is as follows: all ventricular pacing not only acutely reduced LV rotation and twist, but also increased TPR, TPT, and rotational dyssynchrony, while the negative impacts of RA pacing and HB pacing on LV twist and rotation are not that significant compared to ventricular pacing. Moreover, reduced rotation and twist post ventricular pacing is correlated with the reduced LVESP and prolonged QRS duration.Since conventional RVA pacing had significant deleterious effects on LV function, recent efforts are made on searching for alternative pacing site, such as RVOT, HB, LVS, RARV, and bi-ventricular pacing. Several studies already reported promising results on maintaining LV function by pacing from alternative cardiac sites LV twist contributes significantly to LV function, myocardial shortening and thickening. During LV systolic phase, the base rotates in a clockwise direction, while the apex rotates in counterclockwise direction. LV twist is followed by rapid untwisting of the ventricle. The LV untwisting begins before aortic valve closure and before longitudinal and radial expansion . Because it is one of the earliest events leading to LV filling, untwisting may also be a critical determinant of early diastolic function In the present study, we showed that pacing from ventricular sites could disturb the natural sequence of the LV electrical activity because of slowed myocardial activation, and thus result in reduced LV twist Our results also demonstrated that RA pacing resulted in relatively less reduction on LV rotation and twist. LV rotation and twist values and LVESP were similar between post RA pacing andat the pre-pacing, which were much better than those post-pacing from ventricular sites. This might be explained by the fact that the RA pacing did not significantly affect electrical and mechanical activation of LV, as shown by a previous study LV twist/untwist, in addition to radial thickening and longitudinal shortening, are important elements responsible for effective LV pumping function. LV twist/untwist may be considered as a sensitive marker reflecting acute cardiac function changes in disease conditions. Thus, LV twist/untwist quantification might be helpful in monitoring early cardiac function changes or therapy effects post various therapy strategies . In our study, we showed that the time parameters of twist and rotation, such as TPT, TPR and RSI, were also changed as twist and rotation at different pacing. Therefore, results from the present study may indicate that measuring time parameters  might contribute to a better understanding of LV dyssynchrony induced by pacing at various cardiac sites,and to detect subclinical cardiac changes in some cases. Because it may be not easy to detect the acute effect of pacing on LV movement and function by using the conventional methods Several limitations exist in our study. First, the pacing rates we used were relatively fast, like inthe previous studies During cardiac pacing, a decrease in the apical and basal rotation and twist, a delay of apical TPR and TPT, and an increase in rotational dyssynchrony as well as decreased LVESP are observed with all ventricular pacing. HB and RA Pacing results in less negative effects on LV twist and rotation compared to other ventricular pacing in healthy dogs.


Subvalvular left ventricular aneurysm is a rare disease of obscure origin suggesting unique causes such as congenital, traumatic, and inflammatory or infectious diseases. Its mortality is closely related to heart failure, mitral insufficiency, thromboembolic phenomena, and cardiac arrhythmias. Although association with coronary artery disease is not described, the compression of epicardial vessels by the aneurysm may lead to ischemic manifestations. We report here a case of mitral subvalvular left ventricular aneurysm of probable chagasic origin, in a patient with normal left ventricular function evolving with repeated episodes of monomorphic ventricular tachycardia, despite noninducible electrophysiological testing and the use of optimal medical treatment, including amiodarone. The indication for implantable cardioverter-defibrillator in patients with Chagas cardiomyopathy and segmental wall motion abnormalities but without global systolic dysfunction remains unclear in literature, even in the presence of complex ventricular arrhythmias. A brief review of the literature on morphological features, diagnosis, prognosis, and treatment will be also discussed. Mitral subvalvular left ventricular (LV) aneurysm is a rare abnormality of unclear, likely varied, etiology. Suggested origins include congenital defects, traumatic injuries, and the sequel of inflammatory or infectious diseases , 2. SimiA 42-year-old Brazilian woman presented in 2010 to the local emergency department (ED) with new-onset sustained palpitations, hemodynamically stable and denying chest pain, or dizziness. Her past medical history was negative for hospitalizations, trauma, major illness, or surgery. She took no medications and had no known drug allergies. Electrocardiogram (ECG) revealed MVT, HR = 280 bpm, with Rr' pattern in V1, late R/S transition, and left axis deviation, suggesting probable origin in the basal posterior inferior segment of the LV . The patThe patient remained asymptomatic in NSR until April 2012, when once more she was admitted to the ED with palpitations, weakness, dizziness, and presyncopal symptoms. On physical examination the patient was diaphoretic, hypotensive (BP 100/60 mmHg), and tachycardic (HR = 250 bpm). Again, ECG was consistent with MVT with the same pattern as the index event, which again converted to NSR with IV amiodarone.http://dx.doi.org/10.1155/2015/213104). Treadmill stress test was negative for inducible ischemia. Invasive coronary angiography was also normal (Supplementary File). Laboratory tests were positive for Chagas disease (hemagglutination inhibition and indirect immunofluorescence). Electrophysiology testing failed to induce sustained ventricular tachycardia after extensive endocardial and epicardial mapping: the programmed ventricular stimulation protocol was conducted in two basic cycles (450 and 600 ms) at the right ventricular apex and outflow tract with up to three extra stimuli and finalized when the ventricular refractory period or a minimum coupling of 200 ms was reached. As no sustained ventricular tachycardia was induced, the protocol was then repeated after infusion of Isoproterenol. No evidence of epicardial circuit was found. The noninducibility was taken as a reassurance of benign prognosis . At that point, electroanatomic mapping (EAM) was not available in our institution. She did not meet criteria for implantable cardioverter-defibrillator (ICD)—in the attending heart-team's point of view—and was discharged from the hospital after one week on oral amiodarone .Chest radiography was normal. Transthoracic echocardiography (TTE) revealed a subvalvular LV aneurysm  with preserved LV systolic function (LVEF = 65%), as confirmed later by ventriculography  and sustained VT for patients with LVEF <35%, as well as for secondary prevention of VT/VF, is well established  but primHowever, this case still presented a challenge in management, as the patient presented initially with signs of good prognosis: no significant abnormalities  in baseline ECG, preserved LV systolic function with no significant structural cardiac disease, noninducible VT on electrophysiologic study, and a good response to class III antiarrhythmic medication. The positive Chagas serology was only known after the second episode. Indeed, even if the Chagas serology had been known, there is some debate if ICD implantation prevents mortality in this population. Though the total proportion of patients with Chagas disease was low, a retrospective case review of patients with ventricular tachycardia and normal LV function showed increased all-cause mortality in patients treated with ICD plus antiarrhythmic drugs versus amiodarone alone . SpecifiSome doubts remain regarding substrate ablation in Chagas heart disease. It is known that the disease leads to slowly progressive but incessant myocarditis, with widespread destruction of myocytes, diffuse fibrosis, mononuclear cell infiltration of the myocardium, and scarring of the conduction system , 13. ThuGiven this case, we recommend routine testing for Chagas in patients presenting with VT of unclear etiology who reside in or have traveled to endemic areas. And we await more specific recommendations for indication of ICD in the context of primary prevention of sudden death in patients with Chagas disease that will be answered by the on-going CHAGASICS trial . Though Coronary angiogram showing no significant coronary artery disease, and left ventriculography showing the mitral subvalvular aneurysm ,in right anterior oblique and left anterior oblique views.


ECG-gated cardiac MRI is the gold standard for volumetric evaluation of patients, and clinically, ejection fraction is used as a surrogate for function. We hypothesized that the use of arrhythmia rejection in the presence of ectopic beats compromises the accuracy of hemodynamic measurements. Real-time MRI, coupled with ECG telemetry and semi-automated LV endocardial segmentation, can be used to identify multiple beat morphologies and derive global hemodynamic measurements for each beat.Short-axis golden angle radial bSSFP projections (8000 projections/slice) were reconstructed using Gadgetron  with 34 projections per frame, and slice volume was measured via segmentation of LV endocardial contour with ITK-SNAP. ECG was synchronously recorded with the acquisition, and each image frame was assigned a time point on the ECG (~22 seconds/slice). QRS detection was used to identify cardiac cycles, and similar beats (across slices) were grouped via RR-duration of the beat of interest as well as the previous (loading) beat. The use of the loading beat duration allowed for accurate grouping of premature ventricular contractions (PVCs). For each beat morphology, global volume was obtained by summation of slice volume curves allowing for hemodynamic evaluation via EDV, ESV, SV, and EF.10 patients were imaged: 5 in sinus rhythm, 3 with PVCs with 19%, 24%, and 33% prevalence, 1 in regular bigeminy, and 1 in irregular bigeminy. All beats detected beats were assigned a morphology, excluding the first beat of each acquisition since the loading conditions of these beats were unknown. A single beat morphology was observed in patients in sinus rhythm while patients with rhythm disturbances demonstrated multiple beat morphologies with large variations in measured volumes and EF. Figure ECG-gated cardiac MRI is unable to capture the hemodynamics associated with arrhythmic events. As a result, values such as EF are acquisition - dependent (desired RR-duration determines arrhythmia rejection). By combining real-time volume measurements with ECG recordings, we categorized beat morphologies and provided a more comprehensive evaluation of ventricular function during arrhythmia.We would like to acknowledge the National Institutes of Health for support through grants: F31-HL120580, R00-HL108157, R01-EB014346, R01-HL103723, R01-HL63954, T32-HL007954, T32-EB009384.


Myocardial deformation analysis is an important task in the evaluation of heart failure. We and other previously showed that myocardial strain is a more sensitive marker for the prediction of cardiac events compared with left-ventricular ejection-fraction (LV-EF). The current gold standard technique to quantify myocardial deformation is CMR tagging. However, additional pulse sequences and specialized software are necessary with tagging, so that alternative ways for the estimation of strain in CMR using conventional steady-state-free-precession (SSFP) cine images would be preferable. In this regards, feature tracking is a novel tool, which can be run on conventional cine images and can help estimating myocardial strain and strain rate without the need of specialized tagging sequences. The aim was to investigate the prognostic impact of myocardial strain using feature tracking cardiac magnetic resonance in patients with dilated cardiomyopathy.©, TomTec Imaging Systems GmbH). Circumferential, longitudinal and radial strains were quantitatively assessed. Patient follow-up evaluation included the composite endpoint for the occurrence of cardiac death, heart transplantation and aborted sudden cardiac death. Patients were divided in subgroups by the appearance and absence of the composite endpoint, respectively, by left-ventricular ejection-fraction (LV-EF≤35% and EF > 35%) and by the presence or absence of late gadolinium enhancement (LGE).Patients with dilated cardiomyopathy (n = 210) were examined in a 1.5T CMR-scanner. SSFP cine sequences of the three short and the three long axis views were analyzed using a prototype feature tracking software algorithm  and in those without LGE . Global longitudinal strain < -12.5% on the other hand, predicted favorable outcome even in patients with severely impaired EF < 35%  and in those with LGE .The predefined primary endpoint, a combined endpoint of cardiac death, heart transplantation and aborted sudden cardiac death occurred in 26 subjects during the median follow-up period of 5.3 years. Global LV longitudinal strain < -12.5% was a significant predictor of survival. Using multivariable analysis global longitudinal strain exhibited an independent prognostic value for the composite endpoint surpassing the value of NYHA functional class, NT-proBNP, LV-EF, global LV radial and circumferential strain as well as LGE . Reduced global longitudinal strain (≥-12.5%) was strongly predictive for worse outcomes even in patients with non-severely impaired LV-EF (≥35%; HR = 0.025, χMyocardial strain calculation using CMR feature tracking in patients with dilated cardiomyopathy is related to survival and may aid the risk stratification of such patients independent of age, clinical parameters and established cardiac risk markers as the presence of LGE and reduced LV-EF.None.