Cardiac magnetic resonance imaging of the pressure overloaded right ventricle (RV) of precapillary pulmonary hypertension (PH) patients, exhibits late gadolinium enhancement at the interventricular insertion regions, a phenomenon which has been linked to focal fibrosis. Native T1-mapping is an alternative technique to characterize myocardium and has the advantage of not requiring the use of contrast agents. The aim of this study was to characterize the myocardium of idiopathic pulmonary arterial hypertension (IPAH), systemic scleroderma related PH (PAH-Ssc) and chronic thromboembolic PH (CTEPH) patients using native T1-mapping and to see whether native T1-values were related to disease severity. Furthermore, we compared native T1-values between the different precapillary PH categories. Native T1-mapping was performed in 46 IPAH, 14 PAH-SSc and 10 CTEPH patients and 10 control subjects. Native T1-values were assessed using regions of interest at the RV and LV free wall, interventricular septum and interventricular insertion regions. In PH patients, native T1-values of the interventricular insertion regions were significantly higher than the native T1-values of the RV free wall, LV free wall and interventricular septum. Native T1-values at the insertion regions were significantly related to disease severity. Native T1-values were not different between IPAH, PAH-Ssc and CTEPH patients. Native T1-values of the interventricular insertion regions are significantly increased in precapillary PH and are related to disease severity. Native T1-mapping can be developed as an alternative technique for the characterization of the interventricular insertion regions and has the advantage of not requiring the use of contrast agents. Precapillary pulmonary hypertension (PH) is characterized by an increase in pulmonary vascular resistance (PVR) and right ventricular (RV) adaption to the increased load is one of the main determinants of patient outcome . A well-An alternative technique to characterize the myocardium is native T1-mapping. T1-mapping quantifies the T1 relaxation time per pixel tissue and different tissues show a characteristic range of T1-values –11. NatiTherefore, the aim of this study was to characterize the myocardium of idiopathic pulmonary arterial hypertension (IPAH), systemic scleroderma related PH (PAH-Ssc) and chronic thromboembolic PH (CTEPH) patients using native T1-mapping and to see whether native T1-values were related to disease severity. Furthermore, since the difference in presence of histologically confirmed myocardial fibrosis between these forms of precapillary PH vary between studies –23, we cWe retrospectively analyzed all available native T1-mapping data of IPAH patients (n = 46), PAH-SSc patients (n = 14) and CTEPH patients (n = 10) scanned between June 2011 and March 2014 in the VU University Medical Center. Data was acquired in the context of an ongoing prospective research program to investigate the role of CMRI in the evaluation of PH patients. The study was approved by The Medical Ethics Review Committee of the VU University Medical Center. Since this study did not fall within the scope of the Medical Research Involving Human Subjects Act (WMO), the study was approved without requirement of an informed consent statement. IPAH, PAH-SSc and CTEPH were diagnosed according to ATS/ERS guidelines . Both trNative T1-mapping was acquired on a Siemens 1.5 T Avanto scanner. A single breath-hold Modified Look-Locker Inversion-recovery (MOLLI) pulse sequence was used on a mid-ventricular short axis imaging plane. Three, three, and five non-segmented images were acquired at end-diastole within 17 heart beats to sample the recovery of longitudinal magnetization after the inversion pulse. Minimal inversion time was 100 ms . InplaneNative T1-values were assessed using regions of interest (ROIs) at the interventricular insertion regions, the RV free wall, LV free wall, interventricular septum and interventricular insertion regions on mid-ventricular short axis T1-maps. ROIs were manually drawn as illustrated in Fig. Data are presented as mean ± standard deviation, unless stated differently. In PH patients, native T1-values between the RV free wall, LV free wall, interventricular septum and interventricular insertion regions were compared using repeated measures one-way ANOVA with Bonferroni post-hoc correction. In control subjects, native T1-values between the LV free wall, interventricular septum and interventricular insertion regions were compared using repeated measures one-way ANOVA with Bonferroni post-hoc correction.Native T1-values of the different regions of the myocardium between IPAH, PAH-SSc and CTEPH patients and healthy controls were compared using one-way ANOVA with Bonferroni post-hoc correction.In PH patients, Pearson correlation analysis were applied to assess the relation between native T1-values and hemodynamic and cardiac parameters of disease severity: right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index (CI), RV stroke volume index (SVI), RV end-diastolic volume index (RVEDVI), RV end-systolic volume index (RVESVI), RV ejection fraction (RVEF) and NT Pro-BNP.p values <0.05 were considered statistically significant.All analyses were performed using SPSS for Windows version 20.0 and Graphpad Prism for Windows version 5.0. p < 0.001). 40% of the control subjects were female. Heart rate (HR) was not significantly different between control subjects (74 ± 11 bpm) and PH patients (79 ± 14 bpm).Patient characteristics, hemodynamics and standard CMRI measurements are summarized in Table In PH patients, native T1-values of the interventricular insertion regions (1060 ± 70 ms) were significantly higher than the native T1-values of the RV free wall, LV free wall and interventricular septum Figs. , 3. NatiIn control subjects, no differences were found between native T1-values of the LV free wall 961 ± 26 ms), interventricular septum (958 ± 23 ms) and interventricular insertion regions (957 ± 27 ms) , RVEDVI , RVESVI (Pearson r = 0.358 p = 0.002), RVEF  and NT pro-BNP , but not to CI, PVR, RVSVI and mPAP (Fig. In PH patients, native T1-values of the interventricular insertion regions were significantly related to RAP (Pearson r = 0.310; PAP Fig. .Fig. 4CoNative T1-values of the RV free wall, LV free wall, interventricular septum and the interventricular insertion regions were not significantly different between IPAH, CTEPH and PAH-SSc patients.Native T1-values of the LV free wall were not significantly different between control subjects and PH patients. Native T1-values of the interventricular septum was significantly higher in IPAH and CTEPH patients compared to control subjects. Native T1-values of the interventricular insertion regions were significantly higher in all PH categories compared to control subjects Fig. .Fig. 5CoThis is the first study using the native T1-mapping technique to characterize the myocardium in precapillary PH patients. In PH patients, native T1-values of the interventricular insertion regions were significantly increased compared to the native T1-values of the RV free wall, LV free wall and interventricular septum. Furthermore, native T1-values of the interventricular insertion regions were related to disease severity.LGE studies in PH showed the late enhancement of the interventricular insertion regions and it has been suggested that this phenomenon most likely reflect locally increased focal fibrosis –5. This Increased native T1-values of the interventricular insertion regions were moderately, but significantly related to disease severity. This is in line with previous LGE studies showing comparable correlations between the late enhancement of the interventricular insertion regions and RVEF, RV volumes and mPAP , 4, 5. FIn a recent study, native T1-values were assessed in the RV of healthy subjects and the authors found increased native T1-values in the RV free wall compared to the LV free wall and suggested that this finding could be due to a higher collagen content of the RV free wall . In the Native T1-values of the LV free wall were not significantly different between PH patients and control subjects and were in the same range as native T1-values of the LV free wall conducted in a large cohort of healthy subjects of the same age . This isA recent study of Ntusi et al  found inWe could not assess native T1-values of the total RV free wall, since in most patients the RV free wall was too thin to avoid partial volume effects. Only the inferior part of the RV free wall could be accurately assessed in all patients. Although we did not assess the total RV free wall, large variances in native T1-values between different regions of the RV free wall are not expected in a pressure overloaded RV.Our study is a retrospective analysis and we included both treatment naïve and treated PH patients. From our data we cannot rule out any treatment effects on the measured native T1-values.The control subjects were significantly younger compared to PH patients. It is known that age can influence native T1-values of the myocardium, with higher native T1-values found at a younger age . Since nThe MOLLI technique as we applied is known to slightly underestimate native T1 values at higher heart rates . The maiNative T1-values of the interventricular insertion regions are increased compared to native T1-values of the LV free wall, RV free wall and interventricular septum in patients with precapillary PH and are related to disease severity. Native-T1 values are not different between IPAH, PAH-SSc and CTEPH patients. Native T1-mapping can be an alternative for the characterization of the interventricular insertion regions without the use of contrast agents.


Background: The drug-eluting stent (DES) decreases the rate of coronary restenosis and re-obstruction. The aim of this study was to assess prospectively the effectiveness of the new generation DES on the left ventricular (LV) systolic and diastolic functions in patients with isolated severe proximal left anterior descending (LAD) coronary artery stenosis.Methods: A prospective study was conducted on 50 patients with isolated severe proximal LAD stenosis. Successful percutaneous coronary intervention (PCI) with Everolimus-eluting stents was performed for the whole study population. All the patients underwent transthoracic echocardiography within 24 hours before and one month after PCI, and LV systolic and diastolic parameters were compared before and after PCI using the paired samples t-test. Results: The mean age of the study population was 57.68 ± 8.82 years. Within the study population, 26 (52%) patients were male and 24 (48%) were female. There was a significant 10.6% and 5.2% increase in the early diastolic mitral annular motion (e') and the LV ejection fraction following PCI, respectively . Before PCI, wall motion abnormality was seen in 2.21 ± 2.91 segments, which significantly decreased to 1.49 ± 2.58 segments  after the procedure. Also, the wall motion score index was 1.18 ± 0.26 before PCI, which significantly decreased to 1.13 ± 0.23 after PCI . Also, there was a trend toward a higher ratio of transmitral peak early diastolic velocity to peak late diastolic velocity after PCI .Conclusion: Our study showed that the use of the Everolimus-eluting stents improved the LV systolic and diastolic functions in patients with isolated severe LAD stenosis.  Therefore, obstruction at this site causes ischemia in a large portion of the myocardium.2Lesions in the proximal segment of the left anterior descending (LAD) coronary artery present a high-risk lesion, as this important anatomical location of atherosclerotic plaques is associated with increased mortality.3 Echo Doppler studies have reported that patients with asymptomatic LV diastolic dysfunction have a higher incidence rate of all-cause mortality. Mild diastolic dysfunction and moderate-to-severe dysfunction were associated with 8.3-fold and 10.2-fold increased risks of mortality, respectively. The overall mortality rates of symptomatic patients with diastolic or systolic heart failure are very similar.4New angioplasty techniques have led to higher success rates of percutaneous coronary intervention (PCI), and drug-eluting stents have decreased the rate of restenosis and re-obstruction.5 The left atrial diameter, early filling deceleration time (DT), mitral annular early diastolic velocity (e'), ratio of transmitral peak early diastolic velocity to mitral annular early diastolic velocity (E/e'), and peak atrial reversal flow velocity of the pulmonary veins are relatively independent of preload and are a more reliable index of the LV relaxation. Additionally, the LV ejection fraction (LVEF) and peak systolic velocity (s') of the mitral annulus have been used as indices of the global LV systolic function.Transmitral Doppler flow velocities have previously been used for evaluating the variations in the LV diastolic function after PCI.Therefore, our study was designed to determine the changes in the LV systolic and diastolic functions after successful PCI and Everolimus-eluting stenting of isolated stenosis of the proximal LAD.single-photon emission computerized tomography and who underwent successful angioplasty after displaying isolated severe proximal LAD stenosis  in a recent angiography. The diagnosis of non-ST-segment elevation myocardial infarction was based on the elevation in cardiac biomarkers (creatine kinase MB or troponin) and evidence of ischemia based on symptoms, electrocardiography, or imaging. From 2012 to 2013, a prospective clinical study was conducted in Fatemeh Zahra teaching hospital. In total, 50 consecutive patients were considered for enrollment who presented with typical chest pain and documented myocardial ischemia or previous non-ST-segment elevation myocardial infarction with a considerable amount of anterior or anteroseptal ischemia on The study was performed according to the guidelines of the Helsinki Declaration and was approved by the ethics committee of the hospital. Written informed consent was obtained from all the patients.Patients with lesions in the first diagonal branch, total occlusion of the LAD, or multivessel coronary artery disease were excluded from our study. None of the study patients had congenital, significant valvular heart disease (≥ moderate severity) or cardiomyopathy. Additionally, patients with systemic diseases such as cancer, collagen vascular diseases, and amyloidosis were excluded.Transthoracic echocardiography was performed at baseline within 24 hours before PCI and was repeated one month after PCI for all the patients using a Vivid S5 , 1-3 MHz transducer. All the measurements represent the average of three consecutive beats within the normal heart rate range, 60 - 100 beats per minute. The images were stored on a hard disc for better offline measurements, and the results were confirmed by an echocardiographer, who was blind to the patient’s information. Patients with a poor echo window were excluded from the study.To assess the reproducibility of the echocardiographic measurements, these indices were measured (according to systematic sampling method) in 10 randomly selected patients and were repeated one day later to calculate the intra-observer correlation coefficients, which was found to be 0.9.6 Pulse Doppler recordings of the diastolic transmitral flow velocity were obtained with the sample volume located at the tips of the mitral leaflets from the apical four-chamber view.Estimates of the LV systolic and diastolic dimensions were derived from the LV minor-axis dimensions with the transducer in the parasternal position so that the cursor was perpendicular to the interventricular septum and posterior wall at mid-papillary muscle level. The ejection fraction (EF) and wall motion abnormalities (WMA) were determined. The EF was defined as the end-diastolic volume (EDV) minus the end-systolic volume (ESV) divided by the EDV from the biplane apical two- and four-chamber views using a modified Simpson technique. Also, the wall motion score index (WMSI) was determined. The total score was derived by assigning a grade of 1 through 5 . The scores for each segment were added and then divided by the number of segments graded for a total wall motion score.The peak early diastolic velocity (E wave), peak late diastolic velocity (A wave), early filling deceleration time (DT), and the peak early diastolic velocity/peak late diastolic velocity (E/A) were measured. Tissue Doppler imaging of the mitral annulus was obtained from the apical four-chamber view. A 5-mm sample volume was placed at the septal and lateral mitral annuli.The following measurements were determined: the peak systolic velocity (s') and early diastolic velocity (e'). An analysis was performed for the average of each velocity at the two annular sites. Then, the E/e' ratio was calculated. The pulmonary venous flow velocity profile was obtained from an apical four-chamber view. The pulse Doppler sample volume was placed 1-2 cm into the pulmonary vein, and the peak systolic flow velocity (S wave), peak diastolic velocity (D wave), and peak atrial reversal flow velocity (AR) were determined. The left atrial diameter was measured in the parasternal long- axis view from a two-dimensional image at end systole.. The systolic and diastolic blood pressures were measured after 5 minutes of rest. The height and weight were measured, and the body mass index was calculated as the body weight divided by the height squared. Hypertension was defined as a systolic blood pressure ≥ 140 mmHg, a diastolic blood pressure ≥ 90 mmHg,7 or requirement for antihypertensive medication. Diabetes mellitus was defined according to the criteria of the American Diabetes Association or requirement for insulin or oral hypoglycemic drugs.8 A family history of coronary artery disease was defined as having a first-degree relative  with a history of myocardial infarction, coronary revascularization, or sudden death.9 The history of smoking was determined via a face-to-face questionnaire. Coronary angiography was performed for all the patients using a cardiac angiography system , and they all underwent PCI. PCI was performed via standard techniques, and XIENCE stents  were used. Procedural success was defined as the successful deployment of the stent and residual stenosis < 30%.10 Procedural anticoagulation was achieved with unfractionated Heparin; glycoprotein IIb/IIIa inhibitors were used whenever needed (intravenous Eptifibatide). The patients received 300 mg of Aspirin before the intervention. A 300 mg oral dose of Clopidogrel was recommended before the procedure. Thereafter, 80 mg of Aspirin and 75 mg of Clopidogrel were prescribed daily. Other standard drugs  remained unchanged during the study in order to minimize the effects of alterations on the echocardiographic variables. During the follow- up period, all the patients were asymptomatic. Blood samples were obtained during fasting, and the levels of plasma glucose, total cholesterol, high-density lipoprotein cholesterol, Low-density lipoprotein cholesterol, and triglycerides were measuredThe continuous variables are expressed as mean ± SD. The paired samples t-test was used to compare the means of the variables before and after PCI. A p value < 0.05 was considered statistically significant.For the statistical analyses, the statistical software SPSS version 18.0 for Windows  was used.A total of 50 patients were enrolled in the study. The mean age of the study population was 57.68 ± 8.82 years. Within the study population, 26 (52%) patients were male; 23 (46%) were diabetic; 8 (16%) were smokers; 15 (30%) had a positive family history of coronary artery disease; and 34 (68%) were hypertensive. Ten (20%) patients were admitted with non-ST-segment myocardial infarction. The other demographic and measures of common cardiovascular risk factors of the study population are presented in Before performing PCI, the percentage diameter stenosis was 89.29 ± 11.17%. Again, after performing PCI, it decreased to 5.07 ± 6.17% . Additionally, the stent diameter was 2.81 ± 0.27 mm; the stent length was 24.41 ± 7.86 mm; and the stent number was 1.05 ± 0.23. The changes in the echocardiographic indices of the LV systolic and diastolic functions following coronary stenting were assessed via the paired samples t-test.PCI created a statistically significant increase in the LVEF (5.28%) and e' velocity (10.49%). Before PCI, the WMA was observed in 2.21 ± 2.91 segments, which significantly decreased to 1.49 ± 2.58 segments  after the procedure. Also, the WMSI was 1.18 ± 0.26 before PCI, which significantly decreased to 1.13 ± 0.23 after PCI . 3 and 43.72 ± 5.32 cm3 to 93.25 ± 9.85 cm3 and 30.95 ± 5.12 cm3, respectively. These differences were not statistically significant . Also, the s' velocity increased from 6.91 ± 1.36 cm/s to 7.09 ± 1.32 cm/s, which was not statistically significant. The ratios of S/D and atrial reversal velocity were unchanged.Also, there was a trend toward a higher E/A ratio after PCI . Both, diastolic and systolic left ventricular internal dimension (LVIDs) decreased from 4.73 ± 0.41 cm and 2.97 ± 0.53 cm to 4.69 ± 0.51 cm and 2.95 ± 0.64 cm, correspondingly. These differences were not statistically significant. Furthermore, the end-diastolic and systolic LV volumes decreased from 103.75 ± 10.12 cm11Regarding revascularization strategies for isolated proximal LAD stenosis, the results suggest that coronary artery bypass graft surgery and PCI are comparable, although with a much higher rate of repeat revascularization within the first years with bare-metal stenting. Data for drug-eluting stents are lacking.12Polymer-based Paclitaxel-eluting stents and Sirolimus-eluting stents have been shown to significantly reduce angiographic restenosis in comparison with bare-metal stents. However, the rates of primary stent thrombosis are increased. With the goal of further augmenting the security and effect of the drug-eluting stent, an Everolimus-eluting stent has been designed.13 In 2000, S. Bayata5 evaluated the early effect of PCI on the LV diastolic dysfunction in 30 patients with isolated severe LAD stenosis. All the measurements were performed within 4 hours before PCI and repeated within 24 hours after angioplasty. After angioplasty, none of the parameters , E/A, and E wave transit time), except for the A-wave transit time, was changed significantly. However, the tissue Doppler imaging (TDI) study and the calculation of the EF as well as the LV and left atrium were not included in this study. Additionally, stenting was not performed for all the patients. In a 14-day rabbit iliac model, endothelialization over the stent struts was more rapid with the Everolimus-eluting stent than with Sirolimus-, Zotarolimus-, or Paclitaxel-eluting stents.14 Impaired LV relaxation is the earliest manifestation of myocardial ischemia. The primary abnormality of myocardial relaxation is characterized by a decrease in the E wave velocity, increase in the A-wave velocity, decrease in the E/A ratio, and increase in the DT and AR velocity. Later, it is followed by an increase in the left atrial diameter. Additionally, a decrease in the early diastolic mitral annular motion (e') is related to a decreased LV elastic recoil, which is noted as an early sign of ischemia and impaired relaxation.Previous studies have shown a close inverse correlation between the ratio of transmitral peak early velocity to peak late diastolic velocity and the pressure-derived variables of the LV relaxation. Also, there is compensatory augmentation of the atrial filling in patients with impaired LV relaxation.15In our study, the percentage increase in the ratio of the peak early diastolic velocity to the peak late diastolic velocity after PCI was 9.75% (a trend toward significance). These data suggest, but do not prove, that PCI on the LAD may be accompanied by improvement in the LV relaxation. Also, there was a significant 10.6% increase in the early diastolic mitral annular motion due to improvement in the LV elastic recoil. In contrast, the LV systolic function is an important predictor of prognosis, and parameters that represent the systolic function such as the LVEF, WMA, and systolic and diastolic LV internal dimensions can be used for predicting outcomes.16We detect a significant 5.26% increase in the LVEF following PCI as an important marker of reperfusion and improved outcome. Also, there was significant improvement in the WMA and WMSI after the procedure. Using the E/e' ratio, a ratio < 8 is usually associated with normal LV filling pressures, whereas a ratio > 15 is associated with increased filling pressures. When the value is between 8 and 15, other echocardiographic indices should be used. In our study, the majority of the patients had impaired relaxation with a normal filling pressure (E/e' = 8.1 ± 2.7) before PCI. It can be an explanation for the absence of a significant change in the E/e' ratio following PCI.Our study showed that Everolimus-eluting stents may be a good selection in patients with isolated severe proximal stenosis of the LAD. These stents favorably improved the markers of the LV systolic function such as the LVEF. Also, there was significant improvement in the early diastolic mitral annular motion as a marker for improved LV elastic recoil and diastolic function.A limitation of our study was the small sample size. Non-significant differences between the S/D (pulmonary vein peak systolic/ peak diastolic velocity), E/e'  , AR , left atrial diameter, s' velocity , LVIDs , LVEDV (left ventricular end diastolic volume), and LVESV (left ventricular end systolic volume) before and after PCI may be due to the small sample size. Another limitation was the use of the left atrial diameter instead of the volume. Additionally, our follow- up period was only one month after PCI. Therefore, a longer follow-up period in future studies may produce more consistent results.Our study showed that the use of the Everolimus-eluting stents improved the LV systolic and diastolic functions in patients with isolated severe LAD stenosis.


Chronic progressive external ophtalmoplegia (CPEO) and Kearns-Sayre syndrome (KSS) belong to the broad heterogeneous group of mitochondrial myopathies (MM) - a group of neuromuscular disorders resulting from primary dysfunction of the mitochondrial chain with impaired cellular energy metabolism. Recently, a potentially characteristic myocardial fibrosis pattern with intramural late gadolinium enhancement (LGE) in the left ventricular (LV) inferolateral wall was documented by cardiovascular magnetic resonance imaging (CMR) in these patients.mitochondrial encephalopathy with lactic acidosis and stroke-like episodes - MELAS) this aspect was also evaluated.The present study aimed at characterizing the presence and pattern of cardiac abnormalities in a larger CPEO/KSS patient population by means of CMR. Based on the fact that patients with other MM syndromes may show a concentric LV remodelling/hypertrophy  underwent neurological and cardiac evaluations including CMR studies comprising cine- and LGE-CMR (1.5-Tesla). Additionally, CMR scans were performed in 25 age-, gender- and cardiac risk factor-matched asymptomatic CONTROLS  without known heart disease.In the CPEO/KSS group, 18 (55%) patients had at least one pathological finding based on the CMR results: 8 (24%) patients demonstrated an impaired LV-EF (<60%), 3 (9%) patients showed presence of LV hypertrophy and 10 (30%) patients showed non-ischemic LGE with a predominantly intramural pattern, mostly confined to the basal LV inferolateral wall.There were no significant differences in LV volumes, mass or ejection fraction between CPEO/KSS and CONTROLS. However, CPEO/KSS patients demonstrated significantly higher LV mass/ end-diastolic volume ratios as surrogate for LV concentric remodelling when compared to CONTROLS .CPEO/KSS patients frequently show myocardial fibrosis with a predominantly intramural pattern located in the LV inferolateral wall as depicted by LGE-CMR. Moreover, although overt LV hypertrophy is relatively rare, when compared to matched controls, CPEO/KSS seem to show a concentric LV remodelling already described in other MM syndromes.None.


Myocardial late gadolinium enhancement (LGE) MRI has become a standard clinical exam for characterizing myocardial viability after infarction and for assessing many nonischemic myocardial diseaseses. Typically, a 3D slab covering the myocardium is scanned within a single breath-hold. However, 3D LGE with sufficient resolution and slice coverage requires a long scan time and is challenging in cardiac patients with limited breath-hold capability. Recently, compressed sensing (CS)  has demok-space sampling: As shown in Figure Figure In this initial study, ESPIRiT with VDPDS was shown to enable higher acceleration with better image quality than conventional PI and is a promising approach for improving the robustness of 3D LGE by shortening breathholding time.


The purpose of this study was to create an epicardial electroanatomic map of the right ventricle (RV) and then apply post-operative-targeted single- and dual-site RV temporary pacing with measurement of haemodynamic parameters. Cardiac resynchronization therapy is an established treatment for symptomatic left ventricular (LV) dysfunction. In congenital heart disease, RV dysfunction is a common cause of morbidity—little is known regarding the potential benefits of CRT in this setting.n = 8) or corrected congenital pulmonary stenosis (n = 8) undergoing surgical pulmonary valve replacement (PVR) for pulmonary regurgitation underwent epicardial RV mapping and haemodynamic assessment of random pacing configurations including the site of latest RV activation. The pre-operative pulmonary regurgitant fraction was 49 ± 10%; mean LV end-diastolic volume (EDV) 85 ± 19 mL/min/m2 and RVEDV 183 ± 89 mL/min/m2 on cardiac magnetic resonance imaging. The mean pre-operative QRS duration is 136 ± 26 ms. The commonest site of latest activation was the RV free wall and DDD pacing here alone or combined with RV apical pacing resulted in significant increases in cardiac output (CO) vs. AAI pacing . DDDRV alternative site pacing significantly improved CO by 16% vs. AAI (P = 0.018), and 8.5% vs. DDDRV apical pacing (P = 0.02).Sixteen adults  with right bundle branch block (RBBB) and repaired tetralogy of Fallot (Single-site RV pacing targeted to the region of latest activation in patients with RBBB undergoing PVR induces acute improvements in haemodynamics and supports the concept of ‘RV CRT’. Targeted pacing in such patients has therapeutic potential both post-operatively and in the long term. Generation of an epicardial map of the electrical activation system of the right ventricle (RV) in the complex patient cohort.Finding that targeted single-site RV pacing is superior to apical- and dual-site RV pacing in this cohort.Implications for long-term bradyarrhythmia/cardiac resynchronization therapy therapy in these cohorts.1 The QRS duration frequently increases during follow-up in association with progressive pulmonary regurgitation (PR) and right ventricular (RV) dilatation.2 In such adults, the QRS duration has been linked with increased risk of malignant arrhythmias and sudden cardiac death, as have other depolarization and repolarization abnormalities on the surface ECG.4 Furthermore, long-term problems leading to RV dysfunction also contribute to morbidity and early mortality in this group.5Adults with tetralogy of Fallot (ToF) and significant congenital pulmonary stenosis (PS) often have a right bundle branch block (RBBB) pattern on the surface electrocardiogram (ECG) resulting from earlier corrective surgery.6 A sub-group of patients with ToF have a significantly poorer post-operative course, due to a restrictive cardiac physiology, requiring longer intensive care recovery with prolonged inotropic support.7Due to the haemodynamic consequences of progressive PR, these patients often require re-operation in their 20′s or 30′s to implant a competent pulmonary valve. This can cause acute RV dysfunction leading to increased morbidity and mortality in the short term: studies have confirmed that across all patient groups with congenital heart disease, including those with ToF, surgery is linked to a decrease in ventricular contractile function, most marked on the second post-operative day.8 these sites theoretically constitute targets for lead placement when delivering cardiac resynchronization therapy (CRT). However, this has not been formally evaluated. Preliminary evidence has raised the tantalizing prospect of using ‘sub-pulmonary RV CRT’ to improve RV performance and clinical endpoints in outpatient populations.9 This is likely to be of particular importance in the early post-operative period when the RV demand increases under haemodynamic stress. Furthermore, optimization of atrioventricular delays also appears to be important.10 At present, relatively little is known about the electrical activation sequence, underlying mechanical dyssynchrony and subsequent potential benefits of CRT in this cohort.These patients with RBBB might therefore benefit from targeted pacing resynchronization, in both the acute and longer-term setting, provided that optimal sites within the RV can be identified. Since the outflow tract and free wall of the RV show latest activation in patients with repaired ToF,This study therefore sought to define the electrical activation pattern of the RV surface in patients undergoing surgical pulmonary valve replacement (PVR) using intraoperative mapping techniques and further, to assess the haemodynamic consequences of targeted epicardial pacing at the site of latest electrical activation.Following local ethical approval, all adults with repaired ToF or early surgical intervention of congenital PS referred for surgical PVR during March 2010 to June 2011 were approached for inclusion into this study. All had significant PR, as defined by moderate-to-severe PR on cardiac magnetic resonance imaging  with symptoms, severe RV dysfunction or dilatation, and/or impaired exercise capacity.11Participants underwent surgical PVR at our institution  done by one of two experienced surgeons . The surgical procedure has been described previously.Electroanatomic mapping was undertaken following completion of the surgical procedure, while the heart was still exposed. All patients had been rewarmed and were off cardiopulmonary bypass. All were haemodynamically stable, in sinus rhythm, and remained under general anaesthesia.V/dt min) was taken as the local activation time point and the activation times of the roving electrode were taken relative to the local activation time at the apex . Unipolar pacing electrodes were then fixed to the RV apex and at the latest activation site determined by electrophysiological mapping. This site was termed the ‘alternative site’ for RV pacing.A unipolar electrode was placed at the anatomical RV apex with the metal sternal retractor used as a unipolar reference. A second, roving, unipolar electrode was sequentially placed at preselected locations on the epicardial surface of the RV as determined by a nine-point grid system where the RV apex was Point 9. Unipolar electrograms (EGM) were recorded at 1000 Hz . The fastest downstroke of the unipolar electrogram , cardiac index (CI), and stroke volume (SV) every 20 s. It is a validated alternative to invasive haemodynamic monitoring. The Flotrac system was set up preoperatively via a peripherally placed  arterial line in all patients and calibrated as per the manufacturer's guidelines.Once a patient was clinically stable on the intensive care unit  and while still fully sedated, pacing was undertaken. A patient return electrode was attached to the right lateral chest wall and connected directly to both ports of the external pacing device . Both atrial and ventricular epicardial pacing wires were connected as necessary so as to generate dual chamber sensed, paced and response (DDD) RVA , DDD RValt , or DDD BiRV pacing. Pacing was performed in all three modes at two different atrioventricular delays  at 10% above the patients' intrinsic heart rate. Each patient also underwent atrial sensed, paced and inhibited (AAI) pacing at this same rate, to serve as a baseline with which to compare all other modalities. Each pacing cycle was programmed for 1min to achieve the steady state, and was followed by a return to intrinsic rhythm (no pacing) between bursts lasting 2 min. Pacing order was determined using an online random sequence generator and all modes repeated three times to take into account normal physiological changes that might occur during the study period. A total of 21 random pacing cycles were therefore delivered. Results for each pacing mode are presented as an average of the three pacing cycles for that mode.www.iconico.com). QRS durations in each mode were averaged for each ECG following analysis of all leads, and defined as the first positive/negative deflection to the last sharp positive/negative deflection across the isoelectric line.Electrocardiogram recordings were taken at each pacing mode for later analysis. These were scanned for online analysis using the CardioCalipers program  were used to analyse the data where appropriate. Repeated-measures ANOVA was used to compare haemodynamic and QRS parameters in all pacing modes vs. AAI pacing were followed by Fisher's PLSD post-hoc analysis; all t-tests with Bonferroni's correction as necessary. For all repeated–measures, mean values were calculated prior to statistical analysis. A P value of <0.05 was considered significant. Statistical analysis was performed using StatView statistical software  and all graphs produced using GraphPad Prism .Data are presented as mean ± standard deviation or median(range) as necessary. Student's paired or unpaired n = 8) had ToF and 50% had PS; 63% (n = 10) were females. All had significant PR with a mean CMR regurgitant fraction of 47 ± 10%. All were in sinus rhythm with RBBB pattern on surface ECG. Clinical characteristics of the study cohort are shown in Table 1. Mean age was 32 ± 11 years; mean pre-procedure QRS duration 136 ± 26 ms, mean pre-operative RV end diastolic volume (RVEDV) 183 ± 76 mL/m2. Ten (63%) of those included had undergone previous transannular patch (TAP) repair, seven at the time of original ToF repair.Sixteen adults were included in this study, 50% , electrogram analysis was not possible into two RV anterior wall segments .P = 0.0013). Post-hoc analysis identified the RV free wall as the area most likely to be subject to delay, and electrical activation here occurred, on average, 37 ± 33 ms after the earliest activation time. The RV outflow tract was also subject to activation delay; on average activation commenced 27 ± 25 ms after the earliest local RV activation time. Figure 2 shows a simple isochronal map representation of activation across the RV in both ToF and congenital PS, with and without TAP repair.A highly significant difference in electrical activation times across the RV was found in the whole group . Those with TAP repair had the greatest activation delay in the RVOT, though this did not reach statistical significance.All recruited patients were paced, and there were no pacing-related adverse events. Furthermore, all patients were haemodynamically stable throughout recovery and none required formal temporary pacing during this time. No patient included in this study required inotropic support and all remained haemodynamically stable during the study.Table 3). Mean arterial pressure did not change significantly with any mode of pacing (P = 0.49). DDDRValtpacing at the site of latest RV activation with AV delay minus 20 ms of intrinsic was associated with the greatest overall increase in CO including significant improvements over AAI pacing alone(Table 3), and this significance was maintained when directly compared with DDDRV apical pacing at the same AV delay: CO . DDDRValt pacing increased CO by 16% greater than achieved by AAI pacing (P = 0.018) and by 8.5% above DDDRV apical pacing (P = 0.02).All modes of pacing, including AAI pacing, generated increases in CO significantly above baseline (P = 0.20) or those with and without a history of TAP repair . The QRS duration did not correlate with the CO generated by any form of pacing.The mean QRS duration for the whole-cohort pre-procedure was 136 ± 26 ms. Although a visible trend is seen, there was no significant difference in QRS duration between those with a diagnosis to ToF or congenital PS . Figure 3 and Table 3 present the mean data for each pacing programme. Full QRS data on two patients  was not available.Both forms of RV apical pacing were associated with a significantly wider QRS duration than occurred during AAI pacing, though there was no significant difference in QRS duration when comparing the alternate pacing sites  single site RV pacing significantly improves cardiac haemodynamics acutely, more so than RV apical pacing or dual site RV pacing. Right ventricular apical pacing alone either exerted a minimal or detrimental effect on haemodynamics.1 Furthermore, although all these levels of block manifest different electrical activation sequences on electrophysiological mapping, they are represented by a similar RBBB pattern on the surface ECG. Therefore, when directly comparing those patients who had a transannular patch repair with those who had not, it is perhaps unsurprising to note that the former had significant delays in electrical activation compared with the latter. Thus, although both the RV free wall and RV outflow tract had similar levels of activation delay in the whole cohort, the RV outflow tract was subject to the greatest variation, depending on the anatomy and nature of the original repair.Analagous to LBBB, RBBB is a complex electrical disease. The findings of a lack of uniformity to activation across the cohort are in keeping with the knowledge that right bundle branch block can occur at different levels, proximal, distal, and terminal, depending on the location and extent of the original  insult.12 Furthermore, significant LV epicardial activation delays were also identified, indicating that RBBB in ToF is linked to LV electrical dyssynchrony. Importantly, this latter study did not examine the effects of pacing on haemodynamics. However, in a limited combined body surface mapping and biventricular pacing study of ToF patients, the infundibulum was found to be the latest site of activation and BiV  pacing improved exercise capacity and dyssynchrony parameters.13 Interestingly, targeted latest site RV pacing was not performed, only conventional RV apical pacing and BiV stimulation.These results correspond to a high density epi- and endocardial mapping study of Fallot's patients which demonstrated that the RVOT and infundibular area was the latest site of activation in 73% of the 15 cases studied—indeed the degree of delay between the apex and the RVOT was equivalent to our findings of ∼50 ms when the RVOT was the latest activation region.12 Furthermore, the degree of RV volume overload and PR was similar in the whole cohort, as was LV function (Table 1), suggesting that haemodynamic factors were not related to the electrophysiological findings.We did not find the RV apex was subject to significant delay, in keeping with previously published studies.Regardless of the underlying cause, the level of functional block and its consequent effect on the local mechanical response are of paramount importance when considering the delivery, and thus efficacy, of CRT.It is interesting to note that the haemodynamic parameters in this study improved with all forms of pacing, including AAI and RV apical pacing, from baseline values. This acute beneficial effect of pacing may well be related to rate increase or AV shortening, facilitating optimal LV diastolic filling. However, further study allowing for intrinsic sinus rate with VDD pacing would be required to investigate this further, perhaps utilizing 3D TOE and epicardial high density electrode mapping to assess both activation and haemodynamic effects.This study does demonstrate that targeted, alternate site, RV pacing leads to superior improvements in CO when compared with AAI pacing alone, or DDD RV apical pacing, in adults late after repair of ToF or congenital PS. Interestingly, the combination of targeted alternate site RV pacing and RV apical pacing (DDD BiRV) does not lead to a greater improvement in haemodynamics, and indeed also appears inferior to alternate site RV pacing alone.et al.14 reported that such therapy was associated with marked dyssynchrony of both the LV and the RV in a small cohort, though RV pacing sites were not directly targeted and dyssynchrony was most marked with RV apical pacing. The fact that considerable epicardial conduction delays also affect the LV in ToF has important implications for lead placement.This is the first study in this population to directly compare DDD RV apical pacing and thet best alternate site RV pacing. Although it supports the concept of ‘sub-pulmonary RV CRT’ in this cohort, long-term effects in terms of iatrogenic dyssynchrony need to be established. Thambo et al.5 describe delayed activation of the LV in an around half of the patients with repaired ToF and RBBB.5 The pattern differed from that seen in patients with dilated cardiomyopathy and RBBB, affecting the ventricular septum and not the lateral LV wall. In a retrospective analysis of 75 patients with repaired ToF, Tzemos et al.15 noted a significant association between QRS duration and adverse LV volume, activation delay and septal strain, and recently, the Toronto group published their observations of significant delays in LV activation in their study group of adults with repaired ToF. It is already well established that RV apical pacing, both acutely and in the long term in the general population, is associated with LV dyssynchrony and functional impairment. Our current findings indicate that such dyssynchrony as may be induced by additional RV apical pacing  may be sufficient to abrogate the benefits of targeted single-site resynchronization.Although RV disease is predominant in this congenital population, it does not occur in isolation and the possibility of iatrogenic dyssynchrony in the long-term should be considered in the sub-aortic LV, especially if the systolic function of this chamber is already impaired. Abd El Rahman 16 A recent study looked at the degree of excursion of the intraventricular septum, the main mediator of this phenomenon, in patients with repaired ToF. The group determined that in those with abnormal excursion there was a reduction in global and septal LV systolic function.17 A study by Tobler et al. determined that LV function improved in adults with ToF several years following surgical PVR, supporting the recovery of adverse electromechanical interactions between the two chambers.18 This finding has been documented elsewhere also;19 however in both studies patients improved when there was already LV functional impairment. Long-term RV resynchronization by pacing would be hoped to have a similar outcome on LV function but this remains to be shown.The acute nature of this current study needs to be considered also: The phenomenon of ventricular interdependence explains how early surgical intervention on the RV and the subsequent effects of progressive haemodynamic lesions may negatively impact the LV function by electromechanical uncoupling.In terms of ECG findings, the cohort was too small to determine any significant difference between the respective groups although there was a trend to QRS prolongation between different anatomic substrates  and previous surgical intervention (TAP vs. no TAP), as would be expected.10 although this did not reach statistical significance in our study. Stephenson et al.10 document subsequent shortening of the QRS duration with AV optimization, and it may be that in our cohort of patients, many of whom had QRS intervals within the normal range (RV dyssynchrony was not a prerequisite for entry), this was sufficient to facilitate electrical optimization such that targeted pacing in addition to AV optimization did not result in additional QRS shortening. Right ventricular apical pacing did significantly prolong QRS duration vs. AAI pacing, but alternate site RV pacing did not, indicating that it was inducing less electrical dyssynchrony, reflecting the improved haemodynamic response to this mode.We find that RV apical pacing promotes lengthening of the QRS width, as others have demonstrated previously,In this study, single-site, targeted RV pacing led to significant improvements in cardiac haemodynamics. In the acute setting, in those who suffer more protracted post-operative courses linked to adverse RV function, targeted resynchronization pacing could be of significant benefit in the immediate recovery period, especially since it seems clear that RV apical pacing is deleterious at worst and at best neutral in effect. In terms of routine temporary pacing wire placement, these data indicate that epicardial RV leads should be placed in the outflow tract/free wall area of the RV as opposed to the apex.P/dt may have provided more specific RV data acutely. Further, calculation of invasive SVR, not undertaken in this study, would provide more information as to the mode of increase in CO without concomitant rise in arterial BP. Care must be taken, however, with regards to fluid shifts in this early post-operative phase.This was an acute study in a small population of patients and should serve as a preliminary assessment of targeted RV pacing in this cohort. Invasive assessment of RV d20Only the site of latest activation was evaluated; it was not possible to systematically test all segments and so it is possible that other segments could have resulted in greater haemodynamic changes. Although our study patients underwent early post-operative transthoracic echocardiography, it was not possible to consistently image the RV and LV in detail due to limited accurate and reproducible acoustic windows. An imaging study would require longer-term lead placement or intraoperative 3D transoesophageal echocardiography to determine the mechanical effects of pacing. Further determination of pre-operative and post-operative LV, RV, and interventricular dyssynchrony would provide crucial information on the interrelations between these two chambers in response to single-site, targeted RV pacing. Future long-term studies utilizing endocardial pacing techniques would help to facilitate this. A future study could incorporate both high-density epicardial sock mapping and intraoperative 3D TOE to fully interrogate the acute electromechanical effects of alternate site RV pacing intraoperatively. With the evolution of MRI safe pacing technology, studies utilizing MRI could be performed to investigate RV/LV remodelling with long-term alternate site pacing targeting the region of latest RV contraction analogous to the TARGET trial of CRT.Longer-term studies will be necessary to determine the impact of alternate site pacing in a population of ToF patients with RBBB and RV impairment.There was a further limitation in the epicardial nature of our electroanatomic mapping, in that septal activation could not be assessed. This would likely change the total time taken for RV activation. Future studies incorporating endocardial mapping techniques would resolve this issue.Single-site RV pacing targeted to the region of latest intrinsic activation in patients with RBBB undergoing PVR induces acute improvements in central haemodynamics and supports the concept of sub-pulmonary ‘RV CRT’. Targeted pacing in such patients has therapeutic potential both in the post-operative and chronic settings and is superior to RV apical pacing which may be detrimental.Conflicts of interest: P.D.L. receives educational grant from Boston Scientific. C.M.P. is funded by a Clinical Research Fellowship grant from the British Heart Foundation: FS 09/041/27772. M.F. is supported by the Wellcome Trust.UCL/UCLH which receives a proportion of its funding from the Department of Health′s NHIR Biomedical Research Centres Scheme. Funding to pay the Open Access publication charges for this article was provided by University College London.The work was undertaken at


Chronic iron deposition is known to occur within reperfused hemorrhagic myocardial infarctions (MIs), and could be a source of prolonged inflammatory activity within MI territories. However, whether the stagnant blood downstream to the permanent occlusion (i.e. in territories of non-reperfused MI) could lead to chronic iron deposition is unknown. In this study, using a controlled canine model, we investigated whether chronic iron deposition could occur in non-reperfused MIs using T2* CMR and validated our findings with standard histological methods.2. Presence of iron within MI territories was detected on T2*-weighted images using the Mean - 2 Standard Deviations criterion relative to a reference ROI drawn in the remote myocardium. Subsequently, animals were euthanized and myocardial slices were stained with TTC to visualize gross histological evidence of chronic iron deposition. Perl's staining was performed for histopathological validation of iron deposition.Canines (n=19) underwent permanent ligation of the LAD and were recovered for 7 days. Breath-held, ECG-gated, 2D short axis T2* and late-gadolinium (LGE) images were acquired as contiguous slices on a clinical 3T system  at 7 days (acute) and 4 months (chronic) post-MI. T2*-weighted  and LGE images  were acquired. Commonly used imaging parameters were slice thickness = 6mm and in-plane resolution = 1.3x1.3mmSignificant T2* losses were observed within the MI territories in 13 of the 19 canines at 7 days post-MI, and in all canines at 4 months post-MI. At day 7 post-MI, mean T2* value of the MI was 42.6±10.5% lower than that of remote myocardium ; and at month 4 post-MI, T2* value of the MI was 39.1±12.1% lower than that of remote myocardium . Mean MI and iron volumes  were as follows: day 7 post MI - 14.7±8.7% and 2.1±1.6% respectively; 4 months post MI - 7.2±5.6% and 1.9±1.1%. Ex-vivo TTC staining at 4 months post-MI showed pale brown discoloration within the infarct core indicating chronic iron deposition. Perl's stain confirmed CMR findings of iron deposition within chronic MI territories.These studies demonstrated for the first time that (a) T2* signal losses within acute MI territories are not limited to hemorrhagic infarctions; and (b) chronic iron deposition can occur within non-reperfused MIs. The long-term effects of these depositions in the infarcted heart remain to be investigated.This work was supported in part by grants from American Heart Association (13PRE17210049) and National Heart, Lung, And Blood Institute (HL091989).


Type-1 diabetes mellitus (T1DM) is among the most common chronic diseases in children. Serious long-term complications include both ultra-morphologic and functional cardiac impairment. Whether these pathologic processes already take place in the early phase of T1DM yet has to be determined. Aim of this prospective, blinded, clinical study was to assess the effect of T1DM on left ventricular (LV) myocardial function in pediatric patients using quantitative stress echocardiography.We included 40 patients with T1DM (aged 11.53 ± 3.1 years) and 44 sex-matched healthy controls . Conventional and quantitative echocardiography was performed both at rest and during physical exercise on a bicycle. Myocardial strain and strain rate were measured using speckle tracking echocardiography.-1) than healthy controls . During exercise, diabetic children showed more negative values for longitudinal strain rate (-2.59 ± 0.47 s-1) than healthy controls . Furthermore, in T1DM patients, disease duration inversely correlated with myocardial strain rate and serum HbA1c levels correlated with strain both at rest and during stress testing.Children with T1DM had increased myocardial contractility both at rest and at all levels of physical stress testing when compared to healthy volunteers. At rest, T1DM patients had significantly higher circumferential strain rate (-2.05 ± 0.35 sLong-term impairment of cardiac function in diabetic cardiomyopathy may be preceded by a transient phase of increased myocardial contractility early in the course of T1DM. The extent of hyperglycemia in childhood correlates with the alteration of myocardial contractility.


It is unclear if prolonged contrast media injection, to improve right ventricular visualization during coronary CT angiography, leads to increased detection of right ventricle pathology. The purpose of this study was to evaluate right ventricle enhancement and subsequent detection of right ventricle disease during coronary CT angiography.472 consecutive patients referred for screening coronary CT angiography were retrospectively evaluated. Every patient underwent multidetector-row CT of the coronary arteries: 128x 0.6mm coll., 100-120kV, rot. time 0.28s, ref. mAs 350 and received an individualized (P3T) contrast bolus injection of iodinated contrast medium (300 mgI/ml). Patient data were analyzed to assess right ventricle enhancement (HU) and right ventricle pathology. Image quality was defined good when right ventricle enhancement >200HU, moderate when 140-200HU and poor when <140HU.Good image quality was found in 372 patients, moderate in 80 patients and poor in 20 patients. Mean enhancement of the right ventricle cavity was 268HU±102. Patients received an average bolus of 108±24 ml at an average peak flow rate of 6.1±2.2 ml/s. In only three out of 472 patients (0.63%) pathology of the right ventricle was found (dilatation) No other right ventricle pathology was detected.Right ventricle pathology was detected in three out of 472 patients; the dilatation observed in these three cases may have been picked up even without dedicated enhancement of the right ventricle. Based on our findings, right ventricle enhancement can be omitted during screening coronary CT angiography. Previous studies have shown that multidetector-row computed tomography (MDCT) produces very high diagnostic image quality for a wide range of heart rates , 2. Due Studies on RV function have been overshadowed by studies on left ventricular (LV) function , since tAlthough RV assessment was shown to be feasible during CT angiography (CTA) of the heart, contrast timing has not yet been optimized for RV enhancement. This is due to the fact that patients are referred for CTA of the heart for suspected coronary artery disease (CAD) , and in The purpose of this study was to evaluate if contrast media (CM) injection protocols, individually tailored for optimal RV enhancement during CTA of the heart, improve visualization and evaluation of the RV. If this does not prove to be the case, contrast bolus injection protocols can in future be tailored exclusively to coronary artery enhancement.Ethics approval and informed consent for the use of the images for this study was waived according to Dutch law. In the Netherlands, research covered by the Medical Research Involving Human Subjects Act must be submitted to an accredited medical ethics committee for approval. However, the Act does not include retrospective research using data from patient’s medical record or patient images. Therefore, our medical ethics committee (MEC) concluded that the research proposal of the current study does not, under Dutch law, require medical ethics approval, since there is no extra burden placed on research subjects (decision number: MEC 14-4-048). This study complies with the ethical principles of the Helsinki Declaration of 1964, revised by the World Medical Organization in Fortaleza, Brazil in October 2013.All data regarding imaging and clinical data are digitally recorded for purposes of patient care in PACS systems and electronic patient records. Data for this retrospective analysis were anonymized beforehand; the key to this coding was determined by the coordinating radiologist (MD).509 consecutive patients referred for screening CTA of the coronary arteries between June 2012 and December 2012 were retrospectively evaluated. Patients were referred for coronary CTA (CCTA) from the cardiology outpatient department because of cardiac symptoms and suspected CAD  and no R37 of the 509 patients were excluded from CCTA: 32 due to a calcium score >1000; two due to known iodine allergy; two due to failure to obtain venous access; and one due to an inability to hold their breath during the scan. Thus, a total of 472 patients were included for retrospective image analysis.nd generation DSCT scanner  with a 128x0.6 mm slice collimation; gantry rotation time of 280 ms; tube voltage of 100–120 kV depending on the individual patient size; tube current varied between 320–370 mAseff. Different CT scan protocols were used. In patients with a stable heart rate of <60 beats per minute (bpm), a prospectively ECG-triggered “high pitch” spiral protocol was used (“Flash”-technique). In patients with a stable heart rate between 60-90bpm, a prospectively triggered “adaptive sequence” protocol was used . In patients with an irregular heart rate or a stable heart rate of >90bpm, a retrospectively gated “helical” protocol was used. A non-enhanced scan was performed to determine the coronary calcium score using the Agatston method [Every patient underwent MDCT of the coronary arteries using a 2Patients received 50 mg metoprolol tartrate orally , two hours before CCTA. When indicated, an additional dose of 5–20 mg metoprolol tartrate was administered intravenously to lower the heart rate to <60 bpm. A maximum dose of 0.8 mg nitroglycerine  was given sublingually just prior to CCTA. Heart rate and ECG were monitored during CCTA.Patients received an individualized  split-bolus of iodinated CM , which allows for the adaption of injection rate, injection duration, and contrast volume for each individual patient. The software individually adapts both the volume (ml) of the main bolus and the mixed bolus  as well as the flow rate (ml/s) based upon a nonlinear relationship between patient weight and duration of the CT data acquisition . The indImage reconstruction was performed at 0.75 mm slice thickness with an increment of 0.5 mm using dedicated cardiac reconstruction kernel (Siemens B26f).. Mean attenuation  with standard deviation (SD) was measured in all 472 patients. Image quality was defined as the enhancement level within the RV cavity and this was subjectively based on how well the RV wall could be distinguished from the RV lumen: levels >200 HU were considered to be good image quality; levels between 140–200 HU were considered to be moderate image quality and levels <140 HU were considered to be poor image quality, because of the impossibility to distinguish the RV wall from its lumen and only general dilation might be detected. The total amount of CM used and peak flow rate were read from the data acquisition program Certegra Informatics Platform (MEDRAD). Finally, all 472 scan reports were analysed by the two observers for any pathology of the RV. In case of disagreement, consensus was reached by jointly reviewing findings.Two experienced observers (a radiologist and a cardiologist), blinded to the injection technique, performed attenuation measurements in the RV using transverse sections on a medical workstation . For the right chambers, measurements were performed in the centre of the RV. Regions of interest (ROI) were made as large as possible and placed centrally, in order to avoid the myocardium, valvular structures and papillary muscles Baseline characteristics are expressed as medians (interquartile range) or percentiles. All other values are expressed as mean ± standard deviation (SD). Mean attenuation values, CM used and peak flow rates were measured and compared for statistical significance using the Independent-Samples Mann-Whitney U test, Tests of Normality being negative. To assess possible relationships between several covariates  and attenuation values, multivariable regression analysis was performed with RV enhancement (HU) as dependent variable.p-values are 2-sided, and p-values below 0.05 are considered statistically significant.Data analysis was conducted with SPSS version 20.0 . All Table 1.Mean age was 58 (49–65); 246 (52%) of the included patients were men. Age, body mass index (BMI), and cardiac risk factors such as hypertension and high heart frequency, were recorded and are listed in p = 0.71). In addition, no significant differences were found in mean bolus nor mean peak flow between the three patients with RV dilatation as compared to other patients .From the 472 analysed patients, good image quality (>200 HU) was found in 372 patients and moderate (140–200 HU) and poor (<140 HU) image quality were found in 80 and 20 patients, respectively. Patients received an average CM bolus (mean±SD) of 108±24 ml and an average peak flow rate (mean±SD) of 6.1±2.2 ml/s. Mean enhancement of the RV of all patients was 268±102 (HU±SD). Pathology of the RV was found in only three of the 472 patients (0.63%); all three were diagnosed with RV dilatation. Mean enhancement of the RV was 282±79 HU is these three patients and this was not statistically different from the overall mean enhancement . The parameter ‘flow rate’ showed—as only one—a positive association with RV enhancement, however, this was not significant (p>0.33).The results from multivariable regression analysis, incorporating CM bolus, flow rate, BMI and heart rate with RV enhancement as dependent variable, are stated in CCTA is currently the golden standard for evaluation of the coronary arteries. Yet it is unclear whether RV pathology will be picked up during CCTA in a screening population.With respect to the prevalence in the general population, hypertrophic cardiomyopathy (HCM) occurs in approximately 1:5000 , 12 and Assessment of ventricular size, mass, and function  are important factors in diagnostic imaging with respect to the detection of RV pathology. For evaluation of RV and LV volume and function, cardiac magnetic resonance (CMR) is currently considered to be the reference standard –19. HoweIn the current study, helical protocols as well as adaptive sequence protocols might have been useful to assess global RV function. For example, functional evaluation of the heart during the entire cardiac cycle (at each 10% of 0–100%) is feasible for helical protocols. However, for adaptive sequence there are only two reconstructed phases of the cardiac cycle (best systolic and best diastolic) available to evaluate ventricular function. As evaluation of the cardiac function is no part of the standard evaluation of a CCTA and this was a retrospective study, these parameters were not assessed.Besides the choice of an optimal scan protocol for evaluation of the RV, an optimized injection protocol is of importance as well. Optimization of injection parameters is necessary during CTA, in particular for cardiac applications in order to ensure high, homogeneous and consistent vascular attenuation and minimisation of artefacts –23. SeveNance et al.  evaluateAnd although RV visualisation could be improved by using  split-bolus contrast injection protocols , there i.In this study, the only pathology found was RV dilatation, the diagnosis of which could have been made without optimal enhancement of the RV: RV enlargement will normally stand out when there is optimal LV enhancement During the individualized split-bolus contrast injections of this study a large amount of CM (108±24ml) was used. This is disadvantageous for patients with a history of iodine intolerance, and might increase the risk of contrast induced nephropathy (CIN) . Using oThere are limitations to this study, and one of them concerns the study population. Every patient who received a screening CTA of the coronary arteries was evaluated, but no background information pertaining to the presence of thoracic disease, with potential impact on the RV, was available. Additionally, based on the prevalence of RV pathology, a larger group of patients (n = 5000) should be investigated to detect any pathology.We were not able to provide evidence that enhancement of the RV during screening CCTA is beneficial, as we hardly detected any RV pathology. Potentially, therefore, contrast bolus could be reduced and exclusively tailored to enhancement of the coronary arteries.


Right ventricular (RV) pacing generates regional disparities in electrical activation and mechanical function (ventricular dyssynchrony). In contrast, left ventricular (LV) or biventricular (BIV) pacing can improve cardiac efficiency in the setting of ventricular dyssynchrony, constituting the rationale for cardiac resynchronization therapy (CRT). Animal models of ventricular dyssynchrony and CRT currently relay on large mammals which are expensive and not readily available to most researchers. We developed a methodology for double-site epicardial pacing in conscious rats. Here, following post-operative recovery, we compared the effects of various pacing modes on LV dyssynchrony in normal rats and in rats with ischemic cardiomyopathy.Two bipolar electrodes were implanted in rats as follows: Group A (n = 6) right atrial (RA) and RV sites; Group B (n = 7) RV and LV sites; Group C (n = 8) as in group B in combination with left coronary artery ligation. Electrodes were exteriorized through the back. Following post-operative recovery, two-dimensional transthoracic echocardiography was performed during pacing through the different electrodes. Segmental systolic circumferential strain (Ecc) was used to evaluate LV dyssynchrony.In normal rats, RV pacing induced marked LV dyssynchrony compared to RA pacing or sinus rhythm, as measured by the standard deviation (SD) of segmental time to peak Ecc, SD of peak Ecc, and the average delay between opposing ventricular segments. LV pacing and, to a greater extend BIV pacing diminished the LV dyssynchrony compared to RV pacing. In rats with extensive MI, the effects of LV and BIV pacing were markedly attenuated, and the response of individual animals was variable.Rodent cardiac pacing mimics important features seen in humans. This model may be developed as a simple new tool to study the pathophysiology of ventricular dyssynchrony and CRT. Dyssynchronous contraction of the left ventricle (LV) can markedly worsen the outcome of heart failure (HF) independently of traditional risk factors 2+ handling proteins and connexin 43, activation of stress response kinases and increased expression of tumor necrosis factor in the lateral LV wall. Most of these changes can be reversed by CRT Although dyssynchronous heart failure (DHF) has been extensively studied in mechanical terms and although the clinical effectiveness of CRT is remarkable, there are multiple issues that remain ill-defined at present. It is, for example, estimated that around 30% of patients do not benefit from CRT, and the clinical criteria to identify CRT non-responders remain obscure and controversial. In addition, there is variability in individual patient vulnerability to DHF progression in response to conventional RV pacing, which is difficult to predict at present One of the problems hampering progress in this field of research is the lack of suitable animal models that can be utilized for routine experimentation. Current studies almost exclusively utilize large animals (mainly dogs) and are based on the implantation of human devices. Such an experimental setting is highly demanding. In addition, the large animal models can not be manipulated genetically, an issue that is becoming increasingly critical when it is necessary to reveal molecular mechanisms. While rat and mouse models are extensively used in research on HF In the present study, using an implanted device that was developed for pacing and recordings in conscious rodents All animal studies reported in this article were approved by the institutional ethics committee, Faculty of Health Sciences, Ben-Gurion University of the Negev, Israel. At the end of all experiments animals were killed using IV KCl injection under deep isoflurane anesthesia.The implantable device that was used to pace the heart at different locations was originally designed for long-term atrial pacing and recording in freely moving rats Adult male Sprague-Dawley rats (250–300 g) were anesthetized  and mechanically ventilated. The animals were placed supine on a warmed heating and under sterile conditions a skin incision in the left thorax was performed and a subcutaneous tunnel was extended posteriorly to the upper back of the animal. The 8-pin ‘female’ connector (covered with a latex sheath) was inserted through the subcutaneous tunnel. Thereafter, lateral thoracotomy was performed and the two miniature -bipolar hook electrodes were positioned as follows: Group A; on the right atrium (RA) and RV apex (RV). Group B; on the RV and on the posterobasal aspect of the left ventricle (LV). Group C; similar electrode implantation as in group B, as well as proximal left anterior descending coronary artery ligation to induce myocardial infarction (MI). In order to insert electrodes on the right side (for positioning on the RA and RV) a small subcutaneous tunnel was done in the chest wall through which the electrodes were moved to the right side of the thorax. The coronary artery was ligated by 6/0 surgical suture and MI was confirmed by the presence of regional cyanosis in the myocardial surface. Following chest closure, each animal was placed in a prone position and the back connector was exteriorized through the skin of the back . PostopeNormal rats were evaluated 6–8 days following the surgical procedure. MI rats were evaluated 14 days following the surgical procedure. For the echocardiograpic analysis, each animal was sedated (isoflurane 1%) and placed on a heating pad. ECG recordings  were monitored online throughout the experiment and were also digitized and stored for offline analysis in each pacing mode . Electrical stimulation (2 ms square pulses) was applied through isolation units  at a double diastolic threshold. The cycle length that was used to induce override pacing in the normal rats was set to 150 ms (400 bpm) which invariably induced override pacing in these animals. In the MI rats, baseline heart rate was sometimes slightly higher than 400 bpm. Therefore, the override pacing cycle length was set to 140 ms (428 bpm), which managed to override the spontaneous heart rate of these animals. During BIV pacing, two independent isolation units were used for simultaneous but independent RV apical and LV pacing. A program developed by YE Based on the existing literature in rodents, we restricted our current analysis to circumferential strain (Ecc) which is more reliable than radial strain in the small heart of rats P<0.05.Values are expressed as means ±SE. Due to the relatively small sample size in each group, analysis of the difference between pacing conditions was done using Kruskal-Wallis one way analysis of variance on ranks with Student-Neuman-Keuls post hoc test. All statistical tests were done using SigmaStat 3.1 . The criterion for significance was set at As a first step we aimed to compare the effect of RV pacing to both no pacing and RA pacing modes. This analysis was done in order to confirm that the override pacing itself does not induce rate-dependent LV dyssynchrony compared to the no pacing mode (sinus rhythm). For that purpose, group A (n = 6) was instrumented with a bipolar RA pacing electrode and a bipolar RV pacing electrode, and override pacing in these two locations (150 ms CL) was compared to the no pacing state. The obtained Ecc traces of the different LV segments typically demonstrated no major differences between RA pacing and sinus rhythm. In contrast, RV pacing invariably induced marked changes in the segmental strain pattern. The RV pacing typically produced an early systolic contraction in the inferior or posterior segments, which was associated, in some cases, with a clear stretching effect in opposing segments . SummaryIn the next stage, we evaluated group B (n = 7) rats, which had bipolar pacing leads in the RV and LV. The effect of override pacing in these two locations alone or simultaneously (BIV pacing) was compared to the no pacing mode. In terms of electrical activity, the ECG recording indicated QRS prolongation during RV pacing as compared to LV and BIV pacing . HoweverWe next evaluated the mechanical dyssynchrony during the various pacing modes. Summary of the segmental time to peak Ecc and the segmental peak Ecc under the different pacing modes in group B are presented To elucidate the influence of ischemic HF on the electromechanical results of our model, group C (n = 8) was subjected to a combined procedure of electrode implantation and left coronary artery ligation. We analyzed the effect of pacing two weeks following surgery, at a time when prominent scar tissue and myocardial remodeling were present . Out of Evaluation of segmental Ecc in group C revealed typical akinesia or dyskinesia in the anteroseptal, anterior and lateral segments at baseline . No appaThe present study introduces a new model of ventricular pacing in an instrumented rat, which allowed us for the first time to systematically evaluate the effects of pacing site on LV synchronization in the rodent heart. We used speckle-tracking echocardiography analysis of Ecc, which has been reported to reliably and sensitively detect changes in LV dyssynchrony under various clinically relevant conditions in the rat heart The main findings of our Ecc analysis indicate that while the rodent heart has some clear differences compared to the human heart in aspects such as action potential repolarization and calcium handling The addition of MI-induced HF to the double site ventricular pacing model was performed as a proof of concept for the usefulness of our rat model in simulating a scenario that is clinically relevant. Our results indicate decreased beneficial effect of LV or BIV pacing in animals with extensive MI. These results are consistent with various clinical results indicating that the beneficial effect of CRT is highly dependent on the scar burden and is lost when the scar burden passes a certain limit The current rat model opens a window of opportunity for various studies regarding DHF and CRT using a rather simple and economically efficient model. The study might also pave the way to the application of double site pacing in genetically engineered mice models. New technical advances in the development of wireless pacing for mice, There are several limitations to the present model. The absence of atrial sensing electrode and dependence on override pacing prevents atrioventricular synchrony. However, since the main comparisons of different ventricular pacing modes all rely on override pacing, this confounder should be equal in the different ventricular pacing modes. In addition, the pseudo LBBB pattern induced by RV pacing may not necessarily represent all the features of true LBBB. In this context, the epicardial location of our RV electrodes is also important to note, since this setting differs from the most common clinical RV pacing situation, where the RV lead is endocardial. Finally, the patterns of LV dyssynchrony observed in different animals are not completely identical, as can be appreciated by comparison of the segmental time to peak patterns in The present study shows the feasibility of an electrodes implantation procedure for double site epicardial pacing in rats, and the ability to combine this technique with conventional MI surgery. By the use of ECG recordings and speckle-tracking echocardiography we found that rodent pacing mimics important electromechanical features seen in large mammals and in people. Thus, this model may become a simple new tool to study the pathophysiology of ventricular dyssynchrony and CRT.Checklist S1NC3Rs ARRIVE Guidelines Checklist.(DOC)Click here for additional data file.


Thalamic abnormality in temporal lobe epilepsy (TLE) is well known from imaging studies, but evidence is lacking regarding connectivity profiles of the thalamus and their involvement in the disease process. We used a novel multisequence magnetic resonance imaging (MRI) protocol to elucidate the relationship between mesial temporal and thalamic pathology in TLE.1-weighted , diffusion tensor imaging (tissue connectivity), and T1 and T2 relaxation (tissue integrity) MRI across the whole brain. We used connectivity-based segmentation to determine connectivity patterns of thalamus to ipsilateral cortical regions . We subsequently determined volumes, mean tractography streamlines, and mean T1 and T2 relaxometry values for each thalamic segment preferentially connecting to a given cortical region, and of the hippocampus and entorhinal cortex.For 23 patients with TLE and 23 healthy controls, we performed T2 relaxation time in ipsilateral hippocampus and entorhinal cortex. There was bilateral volume loss, mean streamline reduction, and T2 increase of the thalamic segment preferentially connected to temporal lobe, corresponding to anterior, dorsomedial, and pulvinar thalamic regions, with no evidence of significant change in any other thalamic segments. Left and right thalamotemporal segment volume and T2 were significantly correlated with volume and T2 of ipsilateral (epileptogenic), but not contralateral (nonepileptogenic), mesial temporal structures.As expected, patients had significant volume reduction and increased TThese convergent and robust data indicate that thalamic abnormality in TLE is restricted to the area of the thalamus that is preferentially connected to the epileptogenic temporal lobe. The degree of thalamic pathology is related to the extent of mesial temporal lobe damage in TLE. Dr. Simon Kelle is a lecturer and senior research scientist using advanced neuroimaging techniques in peoplewith epilepsy.1-weighted volume scans). Given (1) the opportunities to examine thalamocortical connectivity and integrity afforded by combining conventional MRI sequences with diffusion tensor imaging (DTI) and whole-brain relaxometry, and (2) the growing understanding of how network disruption may underlie seizure onset in focal and generalized epilepsies,The thalamus modulates seizure activity and influences the propagation of seizures regardless of the location of the epileptogenic focus.1-weighted, T2-weighted, and fluid-attenuated inversion recovery [FLAIR] scans). All patients had a history of complex partial seizures. In two cases, complex partial seizures were rare, and recurrent simple partial seizures were the primary seizure type. No patient had evidence of lesions other than unilateral hippocampal sclerosis diagnosed by an expert neuroradiologist. All patients had quantitative MRI evidence of unilateral hippocampal pathology ipsilateral to the side of the seizure focus determined by (1) volume loss on T1-weighted images, (2) increased hippocampal T2 values,2) the mean of controls. Calculation of whole hippocampal volume and mean hippocampal T2 values is described in the Supporting Information. TableWe recruited 23 patients with well-characterized unilateral mesial TLE  attending King's College Hospital London and 23 healthy controls . Diagnosis and localization of TLE was determined by comprehensive evaluation including detailed history and seizure semiology, scalp electroencephalography (EEG), intracranial EEG with video telemetry where necessary, and clinical MRI (T2-weighted sequences), a three-dimensional (3D) T1-weighted structural volume , a DTI sequence,1 and T2 mapping (Driven Equilibrium Single Pulse Observation of T1 / T2 [DESPOT]).All patients and controls were scanned using an identical MR protocol on a 3 Tesla GE Signa HDx system , with actively shielded magnetic field gradients (maximum amplitude 40 mT/m). The protocol consisted of routinely prescribed localizers, routine diagnostic sequences  was used to obtain thalamic seeds and lobar cortical targets  for CBS analyses, and hippocampal and entorhinal regions-of-interest from each participant's IR-SPGR image. CBS of the thalamus was performed using FMRIB's  Diffusion Toolbox (FDT) for probabilistic tractography running in FSL  based on DTI and IR-SPGR data. The volume of each thalamic segment preferentially connecting with a cortical target region , and of the hippocampus and entorhinal cortex, was calculated. Thalamocortical segment, hippocampal, and entorhinal volumes were analyzed, both corrected and uncorrected, for total intracranial volume (ICV); ICV was automatically obtained from Freesurfer segmentations. In order to visualize the topology of thalamocortical connectivity across individuals, thalamocortical segments were nonlinearly spatially normalized to Montreal Neurological Institute (MNI) space and averaged (see Supporting Information).We used connectivity-based segmentation (CBS) of the thalamus based on the original work of Behrens et al.1 and T2 relaxation values for each thalamocortical segment, hippocampus, and entorhinal cortex was obtained by coregistering the T1 and T2 maps determined using DESPOT acquisitions with the DTI and IR-SPGR images. Furthermore, we recorded the number of streamlines between thalamus and lobar target as a proportion of the number going to all target areas. As in previous studies,We additionally determined three further MRI measures for each structure. Mean T1 and T2 as dependent variables. Given the large number of comparisons , post hoc Bonferroni corrections were performed to resolve the direction of main effects and correct for multiple comparisons. Although there was no significant difference in mean age between patients and controls, we included age as a nuisance factor in analyses given the slightly older age of patients. Pearson's correlations were used to examine relationships between volume, mean streamlines, mean T1 and T2 values, and clinical variables. We restricted correlations between brain regions to values from the same MRI sequence . Given that mean streamlines are obtained only for each thalamocortical segment, streamlines were only correlated with clinical variables and not mesial temporal values from other sequences.Analyses were performed using SPSS . Volumetric, streamline, and relaxometry data for mesial temporal and thalamocortical segments were analyzed in each subject's native space using a multivariate analysis of variance (ANOVA) including group  as a fixed factor, and brain structure volume, mean number of streamlines, and mean TAll main effects and F-values are tabulated in the Supporting Information.2 , right entorhinal volume  and T2 , left hippocampal volume , T1 , and T2 , and right hippocampal volume  and T2 . Post hoc Bonferroni corrected results  and hippocampus  in patients relative to controls. There was also a significant increase in mean T2 of the contralateral entorhinal cortex in patients with left TLE relative to controls (p = 0.02).There were significant main effects of left entorhinal volume  and T2  and left and right thalamotemporal mean number of streamlines . Table2 and mean number of streamlines between patients and controls were restricted to the left and right thalamotemporal segments. This included reduction in ipsilateral  and contralateral  volume, increased ipsilateral  and contralateral  mean T2, and reduced ipsilateral  and contralateral (left TLE only p = 0.001) mean number of streamlines, in patients relative to controls. These combined thalamotemporal alterations are illustrated in FigureThere were significant main effects of the volume of the left thalamoparietal segment , thalamopostcentral segment , thalamotemporal segment , whole thalamus , and right thalamotemporal segment . The remaining significant main effects were restricted to left and right thalamotemporal mean T2 values were correlated with ipsilateral  and contralateral  thalamotemporal segment mean T2. Ipsilateral mesial temporal and thalamotemporal correlations are shown in Figure2 was correlated with duration of epilepsy  and seizure frequency . Ipsilateral thalamocortical segment mean number of streamlines was also correlated with seizure frequency . There were no other statistically significant relationships.Given that significant differences between patients and controls were limited to mesial temporal structures and thalamotemporal segments, we restricted correlation analyses to these regions. Furthermore, because patients with left and right TLE showed similar mesial temporal and thalamotemporal segment alterations, we combined patients with left- and right-sided TLE into one sample for correlational analyses to increase statistical sensitivity, and treated structures as ipsilateral and contralateral to the epileptogenic focus. Correlational analyses indicated that ipsilateral hippocampal and entorhinal volume were significantly correlated with ipsilateral  and contralateral  thalamotemporal segment volume. Similarly, ipsilateral hippocampal and entorhinal mean TThe thalamus is known to be a crucial component of the seizure-generating network in generalized spike-wave, which is characteristic of idiopathic (or genetic) generalized epilepsy (IGE).2 relaxometry) in patients with TLE. Our data are consistent with, build on, and integrate previous studies that reportThe organization of thalamocortical connections in this paper is consistent with the work of Behrens et al.that dorsomedial thalamic regions have an excitatory influence on the hippocampus in animal models;7neuronal loss and physiologic alterations in the dorsomedial thalamus in animal models of limbic epilepsy;5shape alterations of the thalamus in regions hypothesized—but not demonstrated—to be connected to the temporal lobe in TLE;13preferential gray matter loss of a region corresponding to the dorsomedial area of the thalamus in a recent review of voxel-based morphometry studies of TLE;1118F]fluoro-d-glucose and [11C]flumazenil positron emission tomography (PET) abnormalities of the dorsomedial thalamic region in patients with TLE;292-deoxy-2-[ictal changes in the pulvinar during mesial temporal lobe seizures based on stereoelectroencephalographic (SEEG) data in a small number of cases.91-weighted MRI scans only, which provides very little—if any—information on brain connectivity. Our data are more consistent with that of Bernhardt et al.Despite the fact that structural and metabolic alterations of the medial temporal lobeThe etiology of thalamotemporal abnormalities in TLE is difficult to resolve. Competing hypotheses of excitotoxic damage and deafferentation have been proposed to explain extrahippocampal atrophy in TLE, and it is possible that both mechanisms play a role in thalamic damage. Our finding of correlations between the extent of ipsilateral mesial temporal and thalamotemporal segment damage are somewhat consistent with that of Mueller et al.,34On the other hand, Bonilha et al.2, the calculation of which is not dependent on the CBS technique.It is important to highlight pertinent methodologic issues. Firstly, we present data on a sample size smaller than many structural MRI studies of TLE, including work from some members of our research team.Thalamic abnormality in TLE is restricted to the area of the thalamus that is preferentially connected with the epileptogenic temporal lobe. Although it is impossible to determine the directionality of any influences between brain regions using these neuroimaging data , we do provide convincing evidence of a relationship between the degree of circumscribed thalamotemporal segment pathology and the extent of abnormality within the epileptogenic mesial temporal lobe.