Cardiovascular Magnetic Resonance (CMR) imaging is accurate and reproducible for the assessment of right ventricular (RV) morphology and function. However, the diagnostic accuracy of CMR derived RV measurements for the detection of pulmonary hypertension (PH) in the assessment of patients with suspected PH in the clinic setting is not well described.We retrospectively studied 233 consecutive treatment naïve patients with suspected PH including 39 patients with no PH who underwent CMR and right heart catheterisation (RHC) within 48hours. The diagnostic accuracy of multiple CMR measurements for the detection of mPAP ≥ 25 mmHg was assessed using Fisher’s exact test and receiver operating characteristic (ROC) analysis.2 and PA relative area change ≤ 15% predicted the presence of PH with a high degree of diagnostic certainty with a positive predictive value of 98%, 97%, 95% and 94% respectively. No single CMR parameter could confidently exclude the presence of PH.Ventricular mass index (VMI) was the CMR measurement with the strongest correlation with mPAP (r = 0.78) and the highest diagnostic accuracy for the detection of PH (area under the ROC curve of 0.91) compared to an ROC of 0.88 for echocardiography calculated mPAP. Late gadolinium enhancement, VMI ≥ 0.4, retrograde flow ≥ 0.3 L/min/mCMR is a useful alternative to echocardiography in the evaluation of suspected PH. This study supports a role for the routine measurement of ventricular mass index, late gadolinium enhancement and the use of phase contrast imaging in addition to right heart functional indices in patients undergoing diagnostic CMR evaluation for suspected pulmonary hypertension. Pulmonary Hypertension (PH) is defined as a mean pulmonary artery pressure (mPAP) greater than or equal to 25 mmHg measured at cardiac catheterisation . It rangRight heart catheterisation (RHC) is the gold standard test used to assess for the presence or absence of PH by directly measuring mPAP and allows measurement of cardiac output (CO) and index (CI), right atrial pressure, mixed venous oxygen saturation and PVR, which are used as markers of disease severity. However, although safe in expert hands it is an invasive test and its role is limited to confirming a diagnosis of PH and in selected cases assessing the response to treatment. Echocardiography is currently the most commonly used non-invasive test in patients with suspected PH, however, this technique has a number of limitations and does not perform well for certain aetiologies of PH ,5, signiSeveral studies have shown significant relationships between cardiovascular magnetic resonance (CMR) derived measurements with mPAP and PVR in patients with PH; including ventricular mass index (VMI) -11, inteThe aim of this study was to compare the diagnostic accuracy of a variety of CMR parameters to identify PH confirmed at cardiac catheterisation in unselected patients with suspected PH attending a referral centre.Consecutive treatment naive patients undergoing RHC and CMR for suspected PH were identified between January 2008 and March 2010 at a high volume nationally designated PH referral centre. All incident patients with suspected PH routinely undergo CMR as part of their diagnostic work-up. Inclusion criteria required the patients’ RHC and CMR to be within 48 h, and patients were excluded if the imaging was of non-diagnostic quality. Other exclusion criteria were as per standard criteria for patients undergoing CMR. Approval for retrospective analysis of imaging techniques was granted by the local research ethics committee.CMR was performed on a 1.5 T whole body scanner GE HDx , using an 8 channel cardiac coil. 4 chamber and short axis cine images were acquired using a cardiac gated multi-slice balanced steady state free precession sequence . A stack of images in the short axis plane with slice thickness of 8 mm (2 mm inter-slice gap) were acquired fully covering both ventricles from base to apex. For short axis imaging end-systole was considered to be the smallest cavity area. End-systole was defined as maximal RV shortening on the 4 chamber slice images. End-diastole was defined as the first cine phase of the R-wave triggered acquisition for both short axis and four chamber imaging. Ten minutes following gadolinium contrast injection , late-enhancement imaging was performed using a 3D-gradient spoiled echo sequence . Selective 180° inversion-recovery images were acquired in the short axis obtaining limited 3–5 slices through the ventricles. We have corrected our MR parameters where appropriate for body surface area, as previously reported in the literature . Phase cImage analysis was performed on a GE Advantage Workstation 4.1 by a pulmonary vascular radiologist (AS)  who was blinded to the patient clinical information, and cardiac catheter parameters. Patient’s scans were defined as non-diagnostic when image quality significantly affected cardiac measurements or volumetric analysis could not be accurately performed.2, see Figure Endocardial surfaces were manually traced from the stack of short-axis cine images, using our MR workstation software (GE Advantage Workstation ReportCard) to obtain RV end-diastolic and end-systolic volumes. From end-diastolic volume and end-systolic volumes, the RVEF and RVSV were calculated. RVSVI was defined as RVSV/body surface area (BSA) measured in ml/m2. The LV epicardial and endocardial borders on each end-diastolic short axis slice were outlined, LV end diastolic mass was thus derived. VMI was defined as RV mass divided by LV mass, Figure The RV epicardial and endocardial borders on each end-diastolic short axis slice image were outlined. The IVS was considered as part of the LV. The myocardial volume for each slice was calculated by multiplying the area of the RV wall by the slice thickness. The product of the sum total of the myocardial slice volumes for each ventricle and the density of myocardium 1.05 g/cm3) gave an estimate of RV mass. RV mass.05 g/cm3The endocardial contours at end-diastole and end-systole were manually segmented. RVRAC expressed as a percentage was calculated from the 4 chamber plane images using the following formula: RAC = 100[(Diastolic area-Systolic area)/Diastolic area].fractional-TAAD) and was calculated as TAPSE divided by the tricuspid annulus-apex dimension at end-diastole expressed as a percentage. This method was previously described by Kind et al. [Longitudinal RV motion was assessed using Tricuspid Annular Plane Systolic Excursion (TAPSE), a measurement previously evaluated using echocardiography and MRI -22. TAPSTransverse RV function was determined from the change of the septum-free-wall perpendicular distance (SFD) at the mid-point between the apex and the base. This was measured manually as the change between the SFD at end-diastole and SFD at end-systole on the 4-chamber images. Fractional-SFD was calculated as for fractional longitudinal function .Left ventricular eccentricity measurements have been traditionally expressed as the ratio of the length of two LV perpendicular minor-axis diameters . SystoliPhase contrast CMR was performed at our institution beginning May 2009. Phase contrast Q flow CMR was analysed using Reportcard software. The following indices were generated: average velocity (cm/s), retrograde flow (L/min) and percentage retrograde flow (%) Maximal and minimal pulmonary artery areas were recorded, and relative area change (RAC) was defined by the following: /minimum area.Late enhancement images were qualitatively assessed for hyper-intensity at the inter-ventricular septal hinge points or along the septum as previously described. The presence or absence of delayed enhancement was recorded.2 . Saline agitation was not used. Right atrial pressure was estimated from the diameter and respiratory variation of the inferior vena cava. Estimates of right atrial pressure and TRJV were used to estimate PA systolic pressure . For the purpose of comparison with right heart catheter measures of MPAP and CMRI estimates, MPAP was defined as 0.61 x PA systolic pressure + 2 mmHg [Echocardiography was performed using Powervision 6000 and 8000 machines  by trained cardiac physiologists as part of routine clinical care at a high volume PH referral centre using a standard protocol for these patients. Multiple windows were used to obtain the optimal Doppler estimation of tricuspid regurgitant jet velocity (TRJV) and tricuspid gradient (TG) calculated using the modified Bernoulli equation, TG = 4 x TRJVRHC was performed using a balloon-tipped 7.5 Fr thermodilution catheter . Patients referred for the investigation of suspected PH also underwent clinical evaluation including; blood testing, echocardiography, computed tomography scanning, lung function testing, exercise testing and perfusion lung imaging. Diagnostic classification of the form of PH was by standard criteria following multidisciplinary assessment .t-test for continuous data, the chi-square for categorical data and anova testing with bonferroni corrections for multiple variables. Pearson’s correlation coefficient was used to assess the correlations between CMR parameters and RHC values. Receiver operating characteristic (ROC) analysis was used to test the diagnostic strength of CMR parameters for the detection of the presence or absence of PH. ROC curve analysis results are presented as area under the curve (AUC). The sensitivity, specificity, negative and positive predictive values of CMR indices for determining the presence or absence of PH was assessed using Fisher’s exact test. A p-value < 0.05 was considered statistically significant. To perform and display the statistics, SPSS 18  and GraphPad Prism 5.03  software were used.Comparisons of CMR measurements between ‘No PH’ and PH patients were analysed using the independent 548 incident, treatment naïve patients who had undergone investigation for suspected PH with a right heart catheter based approach were identified from our PH database between January 2008 and March 2010. 244 patients underwent CMR and RHC within 48 h of each other. 11 patients (5%) were excluded as their CMR scans were degraded by artefact and hence cardiac measurements and volumetric analysis could not be reliably performed in these patients. Of the remaining 233 patients, 194 had PH as defined by mPAP ≥ 25 mmHg, the remaining 39 were labelled as ‘no PH’. Patients with PH were divided into subgroups according to the Dana Point classifications, see Table Demographic information and RHC data are shown in Table p < 0.0001) and PVR . Echo predicted mPAP correlated well with mPAP , and with PVR , Figure p < 0.0001) and PVR , dEI demonstrated a significant though weaker correlations with mPAP,  and PVR . PA average velocity and PA relative area change demonstrated moderate negative linear correlations with mPAP r = −0.55, p < 0.0001 and r = −0.54, p <0.0001 respectively. Table Ventricular mass index demonstrated the strongest correlation of all quantitative MR measurements with mPAP , Figure 2 demonstrated sensitivity (82%) and specificity (71%) for the detection of pulmonary hypertension, more accurate than percentage retrograde flow with lower sensitivity (73%) and specificity (56%). PA area measured in systole (AUC 0.77) was a weaker marker of PH than diastolic PA area (AUC 0.82). Table PA relative area change (AUC 0.87), PA retrograde flow (AUC 0.84), diastolic PA area (AUC 0.82) and average PA velocity (AUC 0.80) were the measurements made from phase contrast sequence images with the highest diagnostic accuracy for the detection of PH. PA relative area change < 15% was sensitive (86%) and specific (70%) for the detection of the presence of PH. PA retrograde flow greater than 0.3 L/min/m.The bias between observers for CMR derived RV mass was −2.1 g (standard deviation 10.8) with limits of agreement −23.3 to 19.1 g. For VMI measurements the bias between observers was 0.02 (standard deviation 0.1) with limits of agreement of −0.21 to 0.24. See Figure 5The diagnostic accuracy of TRJV and echo derived mPAP had good diagnostic accuracy for predicting the presence of PH, AUC 0.86, and AUC 0.88 respectively,This study has demonstrated that VMI and sEI were the CMR metrics with the strongest correlation with mPAP and PVR in the largest population of patients with suspected pulmonary hypertension studied to date undergoing CMR as part of their routine diagnostic work-up. VMI also demonstrated the highest diagnostic accuracy for the diagnosis of PH of all measured MR indices. In addition, late gadolinium enhancement at the inter-ventricular hinge points was sensitive and specific for the identification of PH and was present in 95% of patients with IPAH and 97% of patients with CTPEH, supporting a role for the routine measurement of these MR metrics in patients undergoing diagnostic CMR evaluation for suspected pulmonary hypertension.CMR provides accurate and reproducible measurements of RV morphology and function, including mass, RVEDVI, RVEF, and RVSVI . CurrentIn the work-up of patients with suspected PH CMR may be particularly useful in patients in whom echocardiography is suboptimal, and this study identifies VMI and late gadolinium enhancement as the metrics of greatest diagnostic value. However, there is currently no reliable fully automated method for calculating RV mass, therefore RV muscle wall has to be manually segmented on each SA image slice. This is a time consuming process and is difficult to perform in patients with low RV mass as the wall is thin and is difficult to accurately measure, further work refining methods of determining RV mass are required ,9. RV maSimple functional measurements such as left ventricular eccentricity indices have the advantage over other more labour intensive MR indices that they are easy and quick to measure, and can be performed in routine clinical practice whilst reviewing the SA images. Although these measurements have been investigated with echocardiography, there is little published evidence for their clinical utility using MRI. Given that the reproducibility of right ventricular measurements from echocardiography is accepted as challenging, validation of such measures with MRI is desirable. sEI assesses the effect of the ventricular pressure differential on the shape of the left ventricle, with values increasing as the septum bows further to the left side deforming the LV cavity and has been shown to correlate with pulmonary arterial and RV pressure using echocardiography in patients with PH . Our MR 2 and average velocity (10 cm/s) had reasonable diagnostic accuracy for the detection of PH in this studyl. Sanz et al. suggest that average velocity is the most robust phase contrast diagnostic measurement at the pulmonary artery [Patients with PH have significantly more retrograde PA flow and significantly reduced average PA velocity than patients without PH. Retrograde PA flow >0.3 L/min/my artery , with rey artery .We have also summarised the differences in haemodynamic and CMR parameters between the larger sub-groups of patients in this study, Table The MRI measurements were acquired retrospectively. Echocardiography was performed several weeks prior to admission for RHC, this limits the direct comparison of the diagnostic accuracy of CMR versus echocardiography for the detection of PH. Echocardiography is a well-established screening tool in the evaluation of patients with suspected PH, implementation of CMR as a replacement for echocardiography would be associated with several challenges, including cost, availability and expertise. The control or “No PH” group includes patients referred with suspected PH due to clinical signs/symptoms or an abnormal echocardiogram suggestive of PH, but were found to have a normal pulmonary artery pressure at RHC. These patients frequently had co-morbidities and cannot be considered to be healthy controls. This importantly, however, represents the target population that one would consider performing such diagnostic tests and prevents some of the errors inherent in analysing data exclusively from particular sub-groups. Several patients in the ‘No PH’ group, however, had right ventricular dysfunction on CINE cardiac MRI scans in the absence of significant pulmonary vascular disease which may have contributed to the reduced accuracy of MR indices.MRI is a robust alternative to echocardiography in the evaluation of patients with suspected PH. VMI showed a linear relationship with mPAP and had the highest accuracy of all CMR measurements for the identification of PH. Late gadolinium enhancement, PA relative area change and retrograde flow are other useful markers that should be evaluated in patients with suspected pulmonary hypertension who undergo CMR.dEI, Diastolic eccentricity index; PA, Pulmonary artery; PH, Pulmonary hypertension; RVEDVI, Right ventricular end-diastolic volume index; RVEF, Right ventricular ejection fraction; RVSVI, Right ventricular stroke volume index; sEI, Systolic eccentricity index; TRJV, Tricuspid regurgitant jet velocity; VMI, Ventricular mass index.SR is funded by an unrestricted educational grant from Pfizer. DC funded by Bayer. JH is part funded as a clinical research fellow by an unrestricted educational grant from Actelion and has received conference funding from Actelion, GSK and Pfizer. CD has received conference funding from Pfizer. CH has received conference funding from Pfizer. CAE has sat on advisory boards for, received consultancy and lecturing fees from and been funded to attend conferences from Actelion, Bayer, Encysive, GSK, Pfizer and United Therapeutics. RC has received honoraria for lecturing from Actelion and GSK, has sat on advisory boards for Actelion and Bayer and has received conference funding from Actelion, GSK, Pfizer and United Therapeutics JMW has received unrestricted educational grants from GE and GSK and conference funding from Bayer. DGK has sat on advisory boards for, received consultancy and lecturing fees from and been funded to attend conferences from Actelion, Bayer, Encysive, GSK, Pfizer, Lilley and United Therapeutics..AS and DGK conceived the idea for the study. AS, SR, JH, RC, CAE, JW and DGK participated in the study design. AS, SR, DC acquired the MRI data. Image analysis was performed by AS and SR. AS, RC, JMW, DGK analysed and interpreted the MR data. AS, SR, JMW and DGK drafted the manuscript. All authors read and approved the final manuscript


Mitral valve prolapse (MVP) is associated with concentric basal hypertrophy of the left ventricle. We found a strong correlation between the excursion of the mitral valve annulus and the degree of relative hypertrophy suggesting the possibility that locally increased myocardial function may be responsible for the hypertrophy.Recently, basal left ventricular hypertrophy has been suggested as a new form of hypertrophic cardiomyopathy. However, we have noticed that substantial focal basal hypertrophy often occurs in patients with mitral valve prolapse Figure .Our objective was to characterize the extent and distribution of focal basal left ventricular hypertrophy in patients with MVP and assess the correlation between the degree of focal hypertrophy and various myocardial structural parameters.Sixty-two patients  with MVP and 20 age-matched normal volunteers  were assessed using cardiac magnetic resonance imaging. We compared the ratio of basal to mid end-diastolic wall thickness in both groups and correlated it with various parameters such as age, left ventricular dimensions, degree of prolapse, mitral regurgitation volume, and mitral annular excursion.Fourty-three (70%) patients had posterior leaflet prolapse, 2 (3%) patients had anterior leaflet prolapse and 17 (27%) patients had bileaflet prolapse. There was a significantly increased ratio of basal to mid end-diastolic wall thickness in all segments of the left ventricle in MVP patients when compared to controls (Figure MVP is associated with concentric basal hypertrophy of the left ventricle. A moderate correlation between the excursion of the mitral valve annulus and the degree of relative hypertrophy suggests the possibility that locally increased myocardial function may be responsible for the hypertrophy. It is important to consider this mechanism when evaluating patients with basal hypertrophy to exclude the incorrect diagnosis of hypertrophic cardiomyopathy.None.


A 53-year-old man with depressed ejection fraction (EF) of 35% and QRS width of 88 ms at rest was admitted to our institution with a complaint of exertional chest discomfort and dyspnea. During treadmill exercise, left bundle-branch block (LBBB) with a QRS width of 152 ms occurred at a heart rate of 100 bpm. During LBBB, the patient showed significant mechanical dyssynchrony as evidenced by a two-dimensional speckle tracking radial strain of 260 ms (≥130 ms), defined as the time difference between anterior-septum and posterior wall. Five-month after carvedilol and candesartan administration, EF had improved to 49% and LBBB did not occur until a heart rate of 126 bpm was attained during treadmill exercise. It appears that pharmacological therapy may be useful for patients with heart failure and exercise-induced LBBB. The occurrence of left bundle branch block (LBBB) during exercise testing is a relatively rare occurrence. In fact, only approximately 0.5%-1.1% of all patients who undergo exercise testing develop a transient LBBB during exercise. While tLBBB is characterized by early septal radial inward thickening, followed by late posterior inward thickening, which then results in a significant LV dyssynchrony. LV dyssynchrony has emerged as an important mechanism contributing to progression of heart failure and ventricular remodeling, and appears to play a major pathophysiologic role in heart failure. LV dyssynchrony affects LV diastolic function, right ventricular and left atrial function as well as LV systolic function. This report concerns a 53-year-old man with exercised-induced LBBB and subsequent mechanical LV dyssynchrony, which was resolved with pharmacological therapy.A 53-year-old man was admitted to our institution with a complaint of exertional chest discomfort and dyspnea. Physical examination and chest radiography findings were normal. The 12-lead electrocardiogram taken at rest revealed normal sinus rhythm with a QRS width of 88 ms Figure . Echocar2. Histological examination of the excised right ventricle showed none of the significant features of cardiomyopathy.Coronary angiography did not reveal significant stenosis, and LVEF was 35%, pulmonary capillary wedge pressure 11 mmHg, pulmonary artery pressure 23/6 mmHg, and cardiac index 3.01 l/min/mThe patient was treated with final daily dosages of 20 mg carvedilol and 4 mg candesartan for depressed LV systolic function. Five-month after administration of the medication, LVEF had improved to 49% as calculated with biplane Simpson's rule (Additional file The case reported here concerns a patient with exercise-induced LBBB and subsequent significant mechanical LV dyssynchrony assessed by two-dimensional speckle tracking radial strain. The most important aspect of this case is that exercise-induced LBBB and LV function were resolved with pharmacological therapy. To the best of our knowledge, this is the first report in the literature of such a case.The occurrence of LBBB during exercise testing is a relatively rare finding. In fact, only approximately 0.5%-1.1% of all patients who undergo exercise testing develop a transient LBBB during exercise. The preLV dyssynchrony impairs LV diastolic, right ventricular and left atrial function as well as LV ejection efficiency. LV dyssynchrony has therefore emerged as an important mechanisms contributing to the progression of heart failure and ventricular remodeling, and appears to play a major pathophysiologic role in heart failure. Since roughly one-third of heart failure patients with a wide QRS width do not show significant LV dyssynchrony,12, the Exercise-induced LBBB with significant mechanical LV dyssynchrony may constitute an important prognostic finding for patients with heart failure. Moreover, pharmacological therapy using drugs such as carvedilol and candesartan may be useful for the treatment of exercise-induced LBBB. Because ours was an isolated case, further clinical studies are required to validate this finding.EF: ejection fraction; LBBB: left bundle-branch block; LV: left ventricular.The authors declare that they have no competing interests.Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.HT designed the study, carried out subject recruitment, performed echocardiography, analysed the data, and wrote the manuscript. MH, TM, TT, AK, KR, KY, YF, KN, KT, KM, HK, and KH assisted recruitment and manuscript revision. All authors read and approved the final manuscript.Apical 4-chamber view at baseline, showing left ventricular ejection fraction of 35% determined with biplane Simpson's rule.Click here for fileApical 4-chamber view with left bundle branch block during treadmill exercise, showing left ventricular mechanical dyssynchrony.Click here for fileApical 4-chamber view 5-month after pharmacological therapy, showing left ventricular ejection fraction of 49% determined with biplane Simpson's rule.Click here for file


RFCA has been established as an effective and curative therapy for severely symptomatic PVC from the outflow tract in structurally normal hearts. However, it is unknown whether PVCs originating from the left ventricular septum, are effectively eliminated by RFCA. This study aimed to investigate electrophysiologic characteristics and effects of Radiofrequency catheter ablation (RFCA) for patients with symptomatic premature ventricular contraction (PVC) originating from the left ventricular septum without including fascicular PVCs.Characteristics of body surface electrocardiogram (ECG) and electrophysiologic recordings endocardiogram in a successful RFCA target were analyzed in 20 patients with symptomatic PVCs originating from the left ventricular septum. RFCA was performed using pace mapping and activation mapping.The QRS morphology of PVCs originating from the left ventricular septum is similar to that seen in fascicular tachycardia. Most of the PVCs originated from the left septum appears in the form of ventricular parasystole. The incidence of ventricular parasystole was 70%. Sustained ventricular tachycardia was not inducible by electrical stimulation and isoproterenol infusion in all 20 patients, ablation at the site recording the earliest Purkinje potential was not effective in all 20 patients, and Purkinje potentials were not identified at successful sites during point mapping. Sixteen patients were successful with RFCA using pace mapping and activation mapping, 3 failed, and 1 recurrent.Although the ECG characteristics of the PVCs arising from the left ventricular septum are similar to that seen in fascicular tachycardia, the electrophysiologic characteristics are different between the two types of PVCs. The distinguishing characteristic of the PVCs is that Purkinje potentials were not present at the site of successful ablation, suggesting a myocardial as opposed to fascicular substrate. RFCA is an effective curative therapy for symptomatic PVCs originating from the left ventricular septum (not from the left anterior and posterior fascicle). Isolated premature ventricular complexes (PVCs) are the most common arrhythmias observed in patients without structural heart disease . In receFrom September 2006 to May 2010, a total of 318 patients without structural heart disease were presented for catheter ablation for PVCs in our hospital. Only patients with idopthic PVCs from the left ventricular septum were enrolled in the present study. All patients were verified as having no structural heart disease, including coronary artery disease, valvular heart disease, congenital heart disease, left ventricle hypertrophy, and right ventricle abnormalities by routine biochemistry tests, X-ray, color echocardiography examination, exercise electrocardiogram testing, and/or cardiac catheterization with coronary angiography. Before RFCA, a 12-lead ECG was obtained, and 24 hours ambulatory ECG monitoring (Holter) was carried out at least once. The ECG was monitored for 24 hours just before catheter ablation.The selection criteria of patients were the following reasons: (1) frequent PVCs occurrence, the average PVC count ≥ 10000 times/24 h; (2) inability of the patient to tolerate PVCs or unsuccessful treatment with at least two antiarrhythmic drugs; (3) no structural heart disease; and (4) consent for the catheter ablation procedure.Twelve-lead electrocardiograms of the clinical arrhythmia were available for all patients with PVCs originating from the left ventricular septum. The analysis of ECG pattern was focusing on the following characteristics: (1) The QRS morphology of the PVC in all 12 leads, (2) the duration of QRS complex, (3) the axis deviation.Electrophysiologic study was performed after withdrawal of all anti-arrhythmic drugs for at least five half-lives. Under fluoroscopic guidance, two quadripolar electrode catheter  were advanced from the right femoral vein and positioned in the right ventricular apex and near the His bundle. One additional catheter was inserted via the internal jugular vein and positioned in the coronary sinus. A 12-lead surface electrocardiogram was monitored and recorded on a multichannel oscilloscopic recorder. Programmed electrical stimulation was performed from right ventricular apex at basic drive cycle lengths of 600, 500, and 430 msec, delivering a maximum of three extrastimuli. A 7F quadripolar deflectable catheter was advanced into the left ventricle using retrograde aortic approach via the right femoral artery for mapping and ablation . The mapping/ablation catheter has a 4 mm distal electrode, with interelectrode spacing of 2-5-2 mm. Pace mapping and endocardial activation mapping were performed. If the clinical arrhythmia did not occur spontaneously and was not induced in the baseline, intravenous isoproterenol (2-4 μg/min) was administered to induce arrhythmia.The target site of RFCA was determined by two steps:1) a careful search was firstly performed for Purkinje potentials preceding the onset of QRS during sinus rhythm along the left ventricular septum in all patients, and radiofrequency energy was delivered at sites demonstrating local endocardial recording with earliest presystolic Purkinje potentials during PVCs, or in sinus rhythm if there was insufficient ectopy to permit activation mapping; 2) next step is to obtain the complete or near complete pace mapping with the earliest local activation time if RFCA is not successful, and when the PVC occurred rarely during the electrophysiologic study, only pace mapping was performed, aiming to identify the site where pacing reproduced QRS morphology that is similar to the clinical PVC (≧ 11/12-lead concordance of major and minor deflections). After the target site was located, the energy of RFCA was delivered using maximum power of 40 W, maximum temperature of 60°C and impedance of 80-140 Ωin the temperature-controlled mode. If the PVC was terminated within 10 seconds or frequently PVCs and/or nonsustained ventricular tachycardia occurred during ablation at the target site, additional current was applied for another 60 to 180 seconds. Successful ablation was defined as complete elimination of spontaneous or inducible ventricular arrhythmias. Programmed electrical stimulation was repeated at 30 minutes after the last application of radiofrequency energy to confirm the absence of inducible ventricular arrhythmias before removing all catheters and sheaths. If PVC did not terminate within 10 s, the radiofrequency energy application was terminated and another target site was sought.Successful ablation was defined as the absence of spontaneous or induced clinical PVC and ventricular tachycardia, both with or without isoproterenol at the end of the procedure. Absence of PVC or ventricular tachycardia in ECG monitoring over 48 hours without anti-arrhythmia drugs. No recurrence of arrhythmia in the absence of anti-arrhythmic drug therapy during follow-up.After RFCA, all patients underwent 72-hour ECG monitoring. Holter was carried out one week after RFCA. Patients were not given any antiarrhythmic drugs after RFCA, and underwent color echocardiography and Holter examination three month after RFCA. ECG echocardiography and 24-hour ECG monitoring were performed whenever the patient had symptoms suggestive of recurrence of ventricular arrhythmias..PVC was considered to originate from the left ventricular septum, not from the left anterior and posterior fascicles, based on (1) the local endocardial recordings; (2) the characteristic of left ventricular septum location and motion (when viewed in the right and left anterior oblique fluoroscopic views after successful RFCA); (3) programmed electrical stimulation could not induce sustained ventricular tachycardia; (4) unsuccessful ablation at Purkinje potential site, and (5) purkinje potentials were not identified at successful sites during point mapping.Ethical approval was obtained from the Ethics Committee of the Second Affiliated Hospital of Wenzhou Medical College, and all patients gave informed consent before participation in the study.A total of 20 patients  were enrolled in the present study. Among patients with idiopathic ventricular ectopy, the incidence of left septal ventricular arrhythmias was 6.29%  by pace mapping and activation mapping, not by searching for Purkinje potential in the left ventricular septum, and found that most cases with the PVCs arising from the left ventricular septum behaved with parasystolic activity.In this study, we found that PVCs originating from the left ventricular septum have distinctive ECG characteristics. First, the electrocardiographic patterns are different at the different sites of origin of left septal PVC. For PVCs originating from left anterosuperior septum, their QRS complex morphology were qR or qRs in leads II, III, aVF, Rs (R/s > 1) in leads V5~V6, rs(S) in leadsI, aVL and Qr in lead aVR. For PVCs originating from left posteroinferior septum, their QRS complex morphology were rS in leads II, III, aVF, R(r)S (R/S < 1) in leads V5~V6, qR(s) in leadsI,aVL and qR in lead aVR. The QRS morphology of PVCs originating from the left ventricular septum is similar to that seen in fascicular tachycardia . Why areIn this study, ventricular parasystole was often observed, sustained ventricular tachycardia was not inducible by electrical stimulation and isoproterenol infusion in all 20 patients, ablation at the site recording the earliest Purkinje potential was not effective in all 20 patients, and Purkinje potentials were not identified at successful sites during point mapping. These suggest enhanced antomaticity, but not reentry as the most likely mechanism of PVCs originating from the left ventricular septum in the study ,14. The In this study, we demonstrated PVCs arising from the left ventricular anterosuperior and posteroinferior septum can be safely and effectively eliminated with catheter ablation techniques. The immediate ablation success rate was 85%, and the chronic success rate was 80% (16 of 20 patients) during a mean follow-up period of 20.2 months. One patients experienced significant recurrence of PVCs with associated symptoms. The overall success rate for ablation of PVCs originating from the left ventricular septum in the present study nearly corresponded with the results of previous reports for ablation of PVCs originating from RVOT and/or other sites of origin ,15,16. TFirst, the mechanism of the PVCs arising from the left ventricular septum is thought to be due to enhanced antomaticity, but not reentry, but this remains speculative in the limited clinical study. Second, although the PVCs may occur from the myocardium of the septum, instead of the Purkinje network, it is unknown that how distributed were these septal sites. To increase the accuracy of our study, our results need to be confirmed in a larger prospective randomized patient population.Although the ECG characteristics of the PVCs arising from the left ventricular septum are similar to that seen in fascicular tachycardia, the electrophysiologic characteristics are different between the two types of PVCs. Most cases with the PVCs arising from the left ventricular septum behaved with parasystolic activity. The results of the present study confirm the high success rate and safety of RFCA using conventional techniques in the management of PVCs originating from the left ventricular septum.The authors declare that they have no competing interests.LJF and LYC designed the whole study, LJF, LJ, LYC, JKT, ZND, LJX, ZWW, YPL, and TJF performed the experiment, LJF and LYC wrote the paper. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/11/27/prepub


To determine the reliability of inline ventricular function (VF) tracking with cardiac MRI compared to a manual technique.Computer-based inline VF software can aid in the quantitative analysis of left ventricular (LV) function. Inline VF automatically locates the LV base and apex, detects endo- and epicardial contours in each cardiac slice and phase, and performs a volumetric calculation to determine ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV). The method presents an opportunity to reduce data processing time and hence reporting time. We compare three methods of post-processing: automatic, semi-automatic, and manual.A stack of 9-12 SA steady state free precession (SSFP) slices from the base of the myocardium to the apex were obtained on a 1.5 Tesla scanner . Scanning was achieved using developmental cardiac Day Optimizing Throughput (DOT) engine technology. DOT technology uses landmark based guided scan planning to define long and short axis views. The mitral valve annulus is detected on long-axis cine SSFP images which are subsequently used in the automated analysis.SA SSFP cine images with inline contours were loaded in Argus . In the semi-automatic group, Argus appointed contours were manually corrected when more than 50% of the LV was visualized and adjusted to exclude areas of the outflow tract. The source stack of SA cines were also manually segmented and contoured. Results of all three methods were compared for EF, EDV, ESV, and measuring time.Complete results are presented in table 3We found that automated basal slice contours in end-systole can cause significant discrepancy in VF estimation. The decision to include the basal slice is the largest potential source of error in the accuracy of LV assessment. We suggest a semi-automated technique using a mix of automated and manual apical and basal correction of contours, to strike a balance between the precision of VF analysis and time when evaluating cardiac function.


A 62-year-old man without structural heart disease underwent electrophysiological testing for ventricular tachycardia (VT). Hemodynamically unstable VT was induced after isoproterenol (ISP) provocation. Electroanatomical mapping using a multipolar catheter identified the earliest activation originating from the posterior papillary muscle (PPM) where prepotentials preceding the local ventricular electrogram were observed. Irrigated radiofrequency current guided by the shadow of a multipolar catheter eliminated the VT. This case suggested that multipolar catheters may be helpful for identifying tachycardia origins arising from the PPM. It has been reported that catheter ablation of idiopathic focal ventricular arrhythmias originating from papillary muscles (PAMs) is challenging . The complex structure of the PAMs may cause difficulty with the catheter manipulation during mapping and ablation. We report a case of a ventricular tachycardia (VT) originating from the LV posterior PAM (PPM), which was successfully eliminated by catheter ablation guided by the shadow of a multipolar catheter.A 62-year-old man was admitted to our hospital for catheter ablation of premature ventricular complexes (PVC). The 12-lead electrocardiogram (ECG) recorded during the PVCs exhibited a QRS with a right bundle branch block morphology and left axis deviation, consistent with a posterolateral left ventricular (LV) origin. A cardiac computed tomography (CT) scan was obtained 1 day before the procedure. After left ventriculography, a transseptal puncture was performed for LV mapping. The LV geometry was created using a duodecapolar catheter  guided by an LV angiogram for the integration of CT images into the NavX system using Fusion . This system allowed the visualization of a multipolar catheter, and the outline of the complex structure of the papillary muscle (PAM) integrated into the CT images. Programmed ventricular stimulation did not induce any PVCs. After provocation with isoproterenol (ISP), frequent monomorphic PVCs and nonsustained VT with a QRS morphology similar to that of the PVCs emerged . HoweverRecently, the PAMs in the LV have been reported to be arrhythmogenic in human hearts after a myocardial infarction. In addition, idiopathic focal ventricular arrhythmias have been reported to originate from both the posterior and anterior PAM in the LV. In identifying the origin of idiopathic LV ventricular arrhythmias (VAs) arising from a PAM, activation mapping is the most reliable method, although pace mapping usually provides helpful clues. The use of noncontact mapping for idiopathic LV tachycardias was also reported, however no reports so far are available regarding the use of mapping for PAM VAs. Noncontact mapping may have been suitable in this case, because the conventional point by point mapping was difficult due to the hemodynamically unstable condition. In this case, contact mapping using a multipolar catheter identified the site of the earliest ventricular activation at the mid portion of the PPM. A low amplitude prepotential which preceded the QRS onset at the successful ablation site on the PPM was recorded whereas a previous study reported that a Purkinje potential often preceded the QRS onset at the successful ablation site of PAM VAs. There is still controversy as to whether a Purkinje potential always can be recorded at the successful ablation sites of PAM VAs. This discrepancy may be explained by the heterogeneity of the VAs ablated around the PAM, with some being endocardial (close to the Purkinje fibers) and other intramyocaridal. It also should be noted that the use of an irrigated catheter, as was used in this case, has been required to achieve a lasting ablation of PAM origin VAs because the origin is deep relative to the endocardial surface of the PAMs.RF catheter ablation of idiopathic LV PAM VAs is particularly challenging. To the best of our knowledge, this is the first report describing the efficacy of a multipolar catheter for mapping around the PPM region. The anatomically complex structure of the papillary muscle complicates the manipulation and stability of catheters during unstable hemodynamic conditions during an ISP infusion. This case suggested that the multipolar catheter may be helpful for predicting the earliest site of VAs arising from the PPM.


To investigate the potential of T2 mapping for characterizing the process of intervertebral disc degeneration (IDD) in a rabbit model.Thirty-five rabbits underwent an annular stab to the L4/5 discs . Degenerative changes were graded according to the modified Thompson classification and quantified in T2 respectively at pre-operation, 1, 3, 6, 12 and 24 weeks postoperatively. After MRI analysis, expression analysis of aggrecan and type II collagen gene in nucleus pulposus (NP) was performed using real time polymerase chain reaction . The longitudinal changes in NP T2 and gene expressions were studied by repeated measures and ANOVA, linear regression was performed for their correlations through the process of IDD. The reliability analysis of method of measurement of NP T2 was also performed.P<0.05). The tendency was confirmed at gene expression levels. NP T2 correlated strongly with aggrecan  and type II collagen  gene expressions. The intraclass correlation coefficients for interobserver and intraobserver reliability were 0.963 and 0.977 respectively.There was a strong inverse correlation between NP T2 and Thompson grades (r = -0.85). The decline of L4/5 NP T2 through 24 weeks was nonlinear, the most significant decrease was observed in 3 weeks postoperatively (NP T2 correlates well with aggrecan and type II collagen gene expressions. T2 mapping could act as a sensitive, noninvasive tool for quantitatively characterizing the process of IDD in longitudinal study, help better understanding of the pathophysiology of IDD, assist us to detect the degenerative cascade, and develop a T2-based quantification scale for evaluation of IDD and efficacy of therapeutic interventions. Degenerative disc disease (DDD) is considered as the most common cause of low back pain, even though the pathophysiological correlation between pain and disc degeneration is not fully understood . InterveTransverse relaxation time (T2) mapping, a biochemical MRI technique to calculate relaxation time, has the potential to offer a quantitative assessment of IDD -8. T2 isThe efficacy of T2 mapping for quantitative evaluation of IDD has been demonstrated in previous studies, most of which were cross-sectional -13. HoweThirty-five healthy female New Zealand white rabbits  were used for this study. The experimental protocol was approved by the Animal Care and Experiment Committee of Shanghai Jiaotong University School of Medicine.Disc degeneration was induced via a validated rabbit puncture method . The rabThe study evaluated the L4–L5 and L5–L6 discs of twenty rabbits selected randomly at baseline pre-operation and 1, 3, 6, 12, 24 weeks post-operation for a total of 240 discs. A 3.0 T MR scanner  and standard human knee coil were used to obtain T2-weighted images  and T2 mapping images . The midsagittal MR image was identified based on spinal cord and spinous processes. Midsagittal T2-weighted images were used for conventional grading, T2 mapping images were used for quantitative measure of NP T2.Accurate T2 measure requires the clear contour definition of NP. However, it is sometimes challenging to define the clear boundary between NP and endplates of the cranial and caudal vertebral bodies in the sagittal T2-weighted images and T2 mapping images. Here we developed a color-based method to draw the contour of NP. As the first step, we applied color look-up table to the T2-weighted image Figure a to obtaIn the T2-weighted images, the L4/5 and L5/6 discs were classified by two observers , according to the modified Thompson classification from Grade 1 to 4  depicted in previous study . If the Ten rabbits were selected randomly at each time point for the interobserver evaluation of NP T2 by the aforementioned observers. In addition, the radiologist performed the same analysis twice, with a delay of two months, to assess intraobserver agreement.After MRI analysis, three rabbits selected randomly were killed at each time point for real time polymerase chain reaction  analysis. Total ribonucleic acid (RNA) was isolated from NP using Trizol reagent (Invitrogen) according to the manufacturer’s instructions. After reverse transcription reaction, real-time PCR was performed by an ABI 7500 system using SYBR Premix Ex Taq™  according to the manufacturer’s instructions. The conditions of real-time PCR were as follows: 35 cycles at 95°C for 15 s, 60°C for 34 s. Dissociation stage was added to the end of amplification procedure. There was no nonspecific amplification determined by the dissolve curve. Data were normalized to mRNA levels of GAPDH using the △△Ct method to calculate the relative mRNA levels of target gene. The primer sequences used for this analysis were listed in Table Statistical analysis was performed with SPSS 16.0 . ANOVA and repeated measures were applied for multiple comparisons of different Thompson grades and for pairwise comparisons for different time points. The correlation of NP T2 and the Thompson grading and linear regression of NP T2 versus gene expressions were performed. For inter- and intraobserver reliability analysis, we employed the intraclass correlation coefficient (ICC). The significance level was set at 0.05.The T2-weighted image-based modified Thompson classification consisted of the following: grade 1, 146 (60.8%) discs; grade 2, 40 (16.7%) discs; grade 3, 32 (13.3%) discs; and grade 4, 22 (9.2%) discs. The mean NP T2 in milliseconds for different Thompson grades is shown in Table P<0.01; Table P<0.01; Figure There was a stepwise decrease in NP T2 with increasing grade, and highly significant differences were observed between the grades , while showed no significant difference when compared to that of discs at 3 weeks postoperatively (P>0.05).The L4/5 NP T2 decreased progressively over the 24-week period. The significant decrease in T2 was observed in 3 weeks postoperatively. Then the decline began to slow, especially from 12 weeks to 24 weeks postoperatively , and the ICC for interobserver reliability was 0.963 Table . SimilarP<0.05). In contrast, the L5/6 NP relatively maintained its gene expression levels over the 24-week period (P>0.05).Figure 2 = 0.85, P<0.01). The slope of this correlation was 99.565 . The slope was 88.571 (Figure For NP, T2 and aggrecan gene expression correlated strongly (RThis study investigated the longitudinal changes in NP T2 and expressions of aggrecan and type II collagen gene as well as their correlations in the progression of IDD in a rabbit model over 24 weeks, further demonstrating the potential applications of T2 mapping in future clinical and experimental research.NP T2 decreased with increasing Thompson grade, which is consistent with other published studies on human degenerative IVDs ,12, likeT2 mapping could provide a reliable, continuous scale for quantitatively evaluating IVD and characterizing the process of IDD rather than a discrete, ordinal one as assessed by the conventional classifications that fail to identify lesser degree of progression of IDD. T2 mapping has the potential for detecting certain vital events in the process of IDD, such as the intervertebral disc degenerative cascade which refers to nonreversible cell-mediated responses leading to further disruption and is known to encompass disruption of ECM ,21. The Prior in vivo experimental studies have drawn an encouraging conclusion that emerging biologic therapies including growth factor therapy , gene thThe MR image processing method used in this study facilitates us to obtain the accurate NP T2. With a high degree of reliability and repeatability, our method deserved recommended in future clinical and experimental studies. Though some studies ,12 recomSeveral limitations are pertinent to this study. First, this animal model provided only an acute model of IDD, which may not truly represent the process of human disc degeneration. Second, other than in natural disc degeneration, the remaining disc cell viability was not affected in this annular stab-induced model. However, it is not likely to affect us to determine T2 mapping’s potential for quantitatively evaluating IVD and characterizing the process of IDD. Third, the small number of specimens and ECM-related gene limited the power of the regression analysis to demonstrate the potential of T2 mapping for characterizing the process of IDD. Furthermore, saggital T2 mapping might need to be combined with axial T2 mapping ,11 to caNP T2 correlated well with aggrecan and type II collagen gene expressions. T2 mapping proved to be a sensitive, noninvasive tool for quantitatively characterizing the process of IDD in longitudinal study. It could play an important role in our better understanding of the pathophysiology of IDD, assist us to detect certain biologic processes in the course of IDD such as the degenerative cascade, and develop a T2-based quantification scale for evaluation of IDD and efficacy of therapeutic interventions. This study provides promising new evidence to justify further application of T2 mapping in future clinical and experimental studies on IDD, particularly for longitudinal studies.DDD: Degenerative disc disease; IDD: Intervertebral disc degeneration; NP: Nucleus pulposus; PCR: Polymerase chain reaction; IVD: Intervertebral disc; ECM: Extracellular matrix; ROI: Region of interest; RNA: Ribonucleic acid; AF: Annulus fibrosus; ICC: Intraclass correlation coefficients.The authors declare that they have no competing interests.WS, KZ and JJY performed animal experiments. CQZ and WD carried out PCR analysis. JZ and WS conceived of the study and participated in its design. WS drafted the manuscript. HL and QS performed MRI evaluation.YZX and XJS performed the statistical analysis. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/14/357/prepub


Currently, the long-term prognostic application of this technique has not been evaluated.Exercise 99mTc-tetrofosmin was performed in 655 consecutive patients. Ten patients who underwent revascularization <60 days after nuclear testing were excluded from the analysis. The present data are based on 638 patients with complete follow-up. An abnormal SPECT study was defined as the presence of fixed and/or reversible perfusion defects. End points were cardiac death, nonfatal infarction, and late coronary revascularization. A total of 344 (54%) patients had an abnormal SPECT study. Perfusion defects included fixed defects alone in 186 patients (29%) and reversible defects in 158 (25%) patients. During a mean follow-up of 11.0 ± 3.3 years, 174 (27%) patients died . Nonfatal myocardial infarction occurred in 76 (12%) patients, and late coronary revascularization was performed in 194 (30%) patients. Univariable and multivariable Cox proportional hazard regression analyses showed that exercise 99mTc-tetrofosmin SPECT provided prognostic information incremental to clinical data and exercise test data. Patients with a normal SPECT had a relatively favorable long-term prognosis, in contrast to patients with an abnormal study who had a significantly increased risk of cardiac events. The SPECT parameters abnormal scan, reversible defect, and summed rest score were strong predictors of long-term outcome.Exercise 99mTc-tetrofosmin myocardial perfusion SPECT has an incremental long-term prognostic value over clinical and stress test parameters for the prediction of major adverse cardiac events.Exercise  Historically, 99mTc-labeled agents were developed to overcome some limitations of thallium.99mTc-labeled tracers in conjunction with single-photon emission computed tomography (SPECT) for the diagnosis of coronary artery disease, and the estimation of medium-term prognosis.99mTc-tetrofosmin myocardial perfusion SPECT. Long-term outcome data after exercise 99mTc-tetrofosmin myocardial perfusion SPECT are currently not available. Therefore, the aim of this study was to evaluate the long-term prognostic value of exercise 99mTc-tetrofosmin SPECT for the prediction of major adverse cardiac events in patients with known or suspected coronary artery disease.Technetium-99m  was used for computer averaging of the electrocardiographic complexes. Significant ST-segment depression was defined as a >1-mm horizontal or downsloping ST-segment depression occurring at 80 ms after the J point.99mTc-tetrofosmin  was injected approximately 1 minute before the cessation of exercise. In rest studies, 370 MBq of tetrofosmin was administered at least 24 hours after the exercise study. Myocardial images were acquired with a triple-head gamma-camera system . For each study, six oblique (short axis) slices from the apex to the base and three sagittal  slices were defined. Each of the six short-axis slices was divided into eight equal segments. Owing to corresponding of the septal part of the two basal slices to the fibrous portion of the interventricular septum and normally exhibits reduced uptake, this region was excluded from analysis. As a consequence, 47 segments were indentified (3 long axis and 44 short axis). The interpretation of the scan was semiquantitatively performed by visual analysis and aided by circumferential profiles analysis. Exercise and rest tomographic views were reviewed side by side by an experienced observer who was blind to the patients’ clinical information. A reversible perfusion defect was defined as a perfusion defect on the exercise images that partially or completely resolved at rest in ≥2 contiguous segments or slices. A fixed perfusion defect was defined as a perfusion defect on exercise images in two or more contiguous segments or slices, which persists on rest images. The presence of a fixed and/or reversible perfusion defect was considered as an abnormal study. Each myocardial segment was assigned a score from 0 to 3 . Summed stress score (SSS) and summed rest score (SRS) were calculated by the summation of the scores of the myocardial segments at stress and at rest, respectively. The difference between stress and rest scores, summed difference score (SDS), was considered representative of the extent and severity of myocardial ischemia. Standard 17-segment-based scores were calculated and converted into percent of the total myocardium (% myocardium) by dividing the summed scores by the maximum potential score, and multiplying by 100.An intravenous dose of 370 MBq of Collection of follow-up data was performed by contacting the patient, the patient’s general practitioner, civil registries, and review of hospital records. Outcome events were overall mortality, cardiac death, nonfatal myocardial infarction, and late (>60 days) coronary revascularization. A death caused by acute myocardial infarction, significant arrhythmias, or refractory congestive heart failure was defined as cardiac death. Sudden death occurring without another explanation was included as cardiac death. Nonfatal myocardial infarction was described by cardiac biomarker levels and ECG-changes. Major adverse cardiac events were the combined endpoint of cardiac death, nonfatal myocardial infarction, or coronary revascularization.t test. The chi-squared test was used to compare categorical variables. Univariable and multivariable Cox proportional hazard regression models were performed to determine those variables which were independent predictors of late cardiac events. Variables were selected in a stepwise forward selection manner with entry and retention set of a significance level of 0.05. The risk of a variable was expressed as a hazard ratio (HR) with a corresponding 95% confidence interval. The assumption of the proportional hazards was evaluated by performing the log-minus-log survival plot. The assumption was met. Interaction terms were used to investigate collinearity; no interactions were found. The incremental value of myocardial perfusion SPECT over the clinical variables in the prediction of major adverse cardiac events was evaluated using a multivariate analysis including one pre-imaging model and three post-imaging models. Survival curves were generated using the Kaplan-Meier method to assess the probability of survival and were compared using the log-rank test. P < .05 was considered statistically significant.Continuous variables were expressed as the mean ± SD and analyzed using the Student’s The characteristics of the 638 patients are presented in Table 99mTc-tetrofosmin myocardial perfusion SPECT was associated with relatively low risk for major adverse cardiac events. Conversely, patients with an abnormal study had a significantly increased risk of major adverse cardiac events. Figure A total of 344 54%) patients had an abnormal SPECT study. Perfusion defects included fixed defects alone in 186 patients 29%) and reversible defects in 158 (25%) patients. Of these reversible defects, 56 were completely reversible and 102 were partially reversible. The means (SD) of the SPECT parameters SSS, SRS, and SDS were 3.68 (2.86), 2.43 (2.55), and 1.25 (1.30), respectively. During a mean follow-up of 11.0 ± 3.3 years, 174 (27%) patients died . Nonfatal myocardial infarction occurred in 76 (12%) patients, and late coronary revascularization was performed in 194 (30%) patients. The Kaplan-Meier survival curves are presented in Figures 9% and re4% patienPredictors of major adverse cardiac events are demonstrated in Table 99mTc-tetrofosmin myocardial perfusion SPECT has been reported in previous studies with short-to-medium-term follow-up.99mTc-tetrofosmin myocardial perfusion SPECT has not been defined. This study demonstrates that the prognostic value of exercise 99mTc-tetrofosmin myocardial perfusion SPECT in predicting major adverse cardiac events, all-cause mortality, and all-cause mortality and nonfatal myocardial infarction was maintained during a long-term follow-up of 11.0 ± 3.3 years. Univariable and multivariable analyses showed that exercise 99mTc-tetrofosmin SPECT provided prognostic information incremental to clinical data and exercise test data. Patients with a normal SPECT had a relatively favorable long-term prognosis, in contrast to patients with an abnormal study who had a significantly increased risk of cardiac events. The SPECT parameters abnormal scan, reversible defect, and SRS were strong predictors of long-term outcome.The prognostic value of exercise 99mTc-tetrofosmin myocardial perfusion SPECT for the prediction of cardiac events in patients with known or suspected coronary artery disease at short-medium term follow-up.99mTc-tetrofosmin myocardial perfusion SPECT. The annualized cardiac event rate was 0.4%/year during a 25 ± 3 month follow-up. Galassi et al99mTc-tetrofosmin myocardial perfusion SPECT. During a median follow-up of 38 months, the annualized event rate  was 0.5%/year in patients with a normal study and 4.9%/year in those with an abnormal study. Shaw et al99mTc-tetrofosmin myocardial perfusion SPECT during a mean follow-up of 2.5 years (30 months). Borges-Neto et al99mTc-tetrofosmin and 518 patients using 99mTc-sestamibi exercise myocardial perfusion SPECT. The study demonstrated that the type of 99mTc-labeled myocardial perfusion agent did not affect interpretation of results for risk stratification and prognostic assessment during the 1.5-year study period. Georgoulias et al99mTc-tetrofosmin gated-SPECT. During 8.3 ± 2.9-year follow-up of this selected population, myocardial perfusion SPECT provided incremental prognostic value. However, routine testing in asymptomatic patients is generally not recommended, and the clinical value and cost-effectiveness of routine SPECT after percutaneous coronary intervention need further investigation. Recently, Jain et al99mTc-tetrofosmin gated-SPECT. During a mean follow-up of 3.9 years, SPECT findings significantly improved accuracy of cardiac event rate prediction compared to clinical information alone.Previous studies have demonstrated the prognostic value of exercise 99mTc-tetrofosmin myocardial perfusion SPECT.Compared to these previous studies, our study included 638 patients who were followed for 11.0 ± 3.3 years. The findings of the current study extend the conclusions drawn from the previous medium-term prognostic studies. Previously, we have reported the 4.0 ± 1.3-year follow-up of these 655 patients who underwent exercise Future studies are needed to optimize risk modification to improve outcome in these patients.99mTc-tetrofosmin, medical therapy was probably optimized before a decision on referral to percutaneous coronary revascularization or surgical coronary revascularization was made. Kaplan-Meier curves demonstrated that referral to coronary revascularization was relatively low in patients with normal scan results in the first 4 years after testing. Previous studies demonstrate that the timing of revascularization requires careful consideration.The 10 excluded patients who underwent revascularization <60 days after testing represent 1.6% of the overall cohort. This percentage is relatively low because in most of the patients with ischemia according to exercise 99mTc-tetrofosmin myocardial perfusion SPECT. Application of attenuation or scatter correction may have improved the accuracy of the SPECT studies. Recent data indicate that attenuation correction may further improve risk stratification.99mTc-tetrofosmin myocardial perfusion SPECT were available to the treating physicians. Patient management decisions were made at discretion of the treating physicians. It cannot be excluded that patients with an abnormal study received more intensive medical therapy and were referred to coronary revascularization to favorably alter their prognosis. Therefore the prognostic power of exercise 99mTc-tetrofosmin myocardial perfusion SPECT may have been underestimated in the present study. Sixth, the present results were obtained in patients who underwent exercise 99mTc-tetrofosmin imaging, and cannot be automatically be extrapolated to SPECT studies using other isotopes. Finally, clinical data upon which to adjust the multivariable model were relatively limited; this could have influenced the current analysis.This study has several limitations. First, no attenuation or scatter correction was used during exercise 99mTc-tetrofosmin myocardial perfusion SPECT has an incremental long-term prognostic value over clinical and stress test parameters for the prediction of major adverse cardiac events. Patients with a normal 99mTc-tetrofosmin SPECT have a relatively favorable long-term prognosis, in contrast to patients with an abnormal study who have a significantly increased risk of cardiac events.Exercise


The prognosis of patients with acute myocardial infarction (MI) concerns multiple aspects that demonstrate myocardial aggression (such as serum markers of cardiac damage), and also adaptative mechanisms relative to the acute event (ventricular remodeling).The aim of the study was to assess the relationship of serum markers of cardiac damage and tridimensional echocardiographic (3D Echo) parameters as well as echocardiographic bidimensional (2D Echo) left ventricular ejection fraction (LVEF) in patients with acute ST-elevation MI.3, where D is left ventricular diastolic diameter on 4CH apical view. 3D SPI was compared with a group of 20 normal volunteers . The statistical analysis was performed using Pearson's correlation coefficient (r), 95% CI, P < 0.05, linear regression equation and Bland-Altman test.A prospective study of 23 patients , with acute ST-elevation MI, primarily percutaneously treated (stent). Serum cardiac markers  and serum BNP were compared with echocardiographic parameters ). The 3D SPI is defined as: LVEDV/(4/3π(D/2))r), relative to 3D LVEF: 1 - BNP: r = -0.7427, P = 0.4800.3D SPI ranged from 0.29 to 0.45 (0.35 ± 0.0 8); 3D LVEF ranged from 0.36 to 0.70 (0.50 ± 0.06); 3D EDV ranged from 72 to 159 (100 ± 27) ml; 2D LVEF ranged from 0.40 to 0.71 (0.54 ± 0.08); 2D EDV ranged from 57 to 165 (104 ± 32) ml. Troponin I ranged from 2.3 to 33 (12.9 ± 9) ng/ml; CKMB ranged from 5.7 to 258 (94.4 ± 78) ng/ml; BNP ranged from 25 to 1,058 (264 ± 128) pg/ml. Pearson's correlation coefficient (In this series, stronger correlation was observed relative to serum CK-MB, BNP and 3D Echo LVEF, when compared with 2D Echo LVEF. We did not observe association concerning LV remodeling and cardiac damage assessed by serum cardiac markers.


Ebstein’s anomaly corresponds to less than 1% of all cardiac congenital malformations. In this anomaly, there is a fail in delamination of the posterior and septal cusps of the tricuspid valve during embryogenesis, resulting in adherence of these cusps to the subjacent myocardium, rotation and apical displacement of the functional valvar annulus. This anatomical changes lead to valve dysfunction, atrialization of part of the right ventricle and dilatation of the right atrioventricular junction, with consequent impairment in the ventricular function. The apical displacement of the cusps leads to discontinuity between the fibrous valvar skeleton and the functional valvar annulus, creating an anatomic substrate for accessory conduction pathways and ventricular pre-excitation. This is reflected in the high prevalence of pre-excitation and Wolf-Parkinson-White (WPW) syndrome in these patients, with consequent increase in risk of supraventricular and ventricular tachiarrhytmias, syncope and sudden cardiac death.Elimination of the arrytmogenic substrate by means of surgery or catheter results in significant reduction in mortality and morbidity in the medium and long-term. Nevertheless, ablation, especially by means of catheter, still faces important challenges when performed both prior and subsequent to surgical correction. Before the surgical repair, the ablation is dificulted by the anatomic particularities of this malformation, such as right ventricular dilatation changing the usual landmarks, presence of tricuspid regurgitation, greater catheter instability and often presence of multiple and broad accessory pathways. After the surgical correction, there are also marked technical challenges involving catheter ablation due to the inaccessibility of the accessory pathway to the intravenous catheter, as it becomes “buried” by the surgical approach involving the tricuspid ring. These factors together reduce the success rate of catheter ablation in patients with Ebstein’s anomaly compared with other patient groups without this malformation. In an attempt to reduce risks and increase success rate in eliminating the arrytmogenic substrate, some groups have performed a combined procedure in patients with surgical indication, where the electrophysiological study and eventual ablation are performed during the surgical correction.The aim of the present study is to report our experience with the combined treatment, with emphasis on the prevalence of arrhythmias during the in-hospital period in this group of patients.We performed a retrospective observational data collection from all patients who underwent surgical correction of Ebstein’s anomaly with a biventricular or “one and a half” ventricle approach between April 2005 and March 2013 at Pequeno Principe Children’s Hospital by the same surgical team.The collected data were: related to the surgical procedure, such as aortic cross clamp time and extracorporeal circulation time; related to the immediate postoperative period, such as mechanical ventilation time, use of vasoactive substances, length of stay in intensive care; related to the prevalence of arrhythmias during hospital stay, including need for definitive cardiac stimulation (pacemaker with or without cardioverter defibrillator); related to the surgical mortality (first 30 days after surgery).Intra-operative electrophysiological study, when performed, took place subsequently to sternotomy. Catheters were positioned in the tricuspid annulus, right atrium and left ventricle for stimulation and collection of epimyocardial electrocardiograms (ECG’s). Continuous atrial stimulation was performed until the atrioventricular (Wenckebach) point was achieved. Subsequently, the slow ventricular stimulation protocol was applied for investigation of abnormal retrograde conduction pathways.When anomalous pathways were identified, an ablation catheter was positioned in the pathway’s location, and radiofrequency was applied in this region in one lesion line with 20-60 W of power, temperature between 40-50° C, impedance around 120-180 Ω and duration between 30 and 70 seconds. Subsequently, a new ventricular stimulation test was performed, where the disappearance of conduction through the accessory pathway was often observed.The surgical technique applied for correction of the anatomical abnormalities was naturally individualized according to each patient’s anatomical characteristics. Overall, extracorporeal circulation was established with moderate hypothermia at 32°C. The aorta was cross clamped and cardioplegy solution at 4°C was infused. Right atriotomy was performed. Tricuspid valvuloplasty using the cone or Carpentier techniques was performed. In case the valvar characteristics did not favour valve repair, valve replacement using biological prosthesis was undertaken. Closure of the atrial septal defect was performed using a patch of pericardium (autologous or bovine) or Goretex®. In patients with hypoplastic right ventricle, right cavopulmonary anastomosis (Glenn procedure) was performed according to the usual technique.This study was approved by the local ethical committee and performed according to recommendations stated in Helsinki II declaration.We will present the results and conclusion of this study.


The autonomic nervous system interacts in the pathophysiology of heart failure. Dysfunction of the sympathetic nervous system has been identified as an important prognostic marker in patients with chronic heart failure. At present, cardiac sympathetic nerve imaging with 123-iodine metaiodobenzylguanidine [123-I MIBG] has been employed most frequently for the assessment of cardiac sympathetic innervation and activation pattern. The majority of studies have shown that cardiac sympathetic dysfunction as assessed with 123-I MIBG imaging is a powerful predictor for heart failure mortality and morbidity. Additionally, 123-I MIBG imaging can be used for prediction of potentially lethal ventricular tachyarrhythmias in heart failure patients. At present however, the lack of standardization of 123-I MIBG imaging procedures represents an evident issue. Standardized criteria on the use of 123-I MIBG imaging will further strengthen the clinical use of 123-I MIBG imaging in heart failure patients. Chronic heart failure represents one of the most important challenges in clinical cardiology since several decades , 2. The 1. In case of a reduced cardiac function, several compensation pathways become activated that aim to preserve cardiovascular homeostasis. One of the these mechanisms that plays an essential role in patients with heart failure is the neurohormonalsystem, consisting of the adrenergic nervous system and the renin-angiotensin-aldosteron system  [RAAS] [via the release of renin from the juxtaglomerular apparatus. Renin catalyzes the conversion of angiotensinogen  [produced in the liver] into the inactive angiotensin I. Subsequently, angiotensin I is metabolized into angiotensin II by the angiotensin converting enzyme, predominantly within the vascular bed of the lungs. Angiotensin II is involved in sodium- and water retention as well as vascular constriction. Furthermore, angiotensin II can lead to activation of other compensatory mechanisms in heart failure, including the sympathetic nervous system. Moreover, a reduced cardiac stroke volume results in an increased [LV] end-diastolic volume along with a rise in LV end-diastolic pressure. Based upon the Frank-Starling principle, these increased preload conditions will enhance the force of myocardial contraction, which compensates the decline in cardiac stroke volume.Heart failure is a pathophysiologic condition characterized by a reduced myocardial pump function which lacks the ability to supply peripheral tissues with sufficient metabolic requirements. Different pathophysiologic mechanisms have been related to the development and propagation of the clinical syndrome of heart failure, as shown in Table   [RAAS] , 4. In pIn the early phase of heart failure, the hemodynamic consequences of a deteriorated cardiac pump function are compensated by the neurohormonal feedback mechanisms , 4. Howevia adrenergic fibers, located predominantly in the superficial subepicardium following the major epicardial coronary arteries . Additionally, regional abnormalities in sympathetic nerve innervation have been assessed with PET imaging and 11C-HED, as shown in Fig. (2)  and single photon emission computed tomography  [SPECT] are the only two imaging modalities that permit visualization of sympathetic innervation and activation -7. Moreoet al.  performe  ratio which is calculated by dividing the mean counts per pixel within the cardiac region of interest by the mean counts per pixel within the upper mediastinum. In addition, 123-I MIBG SPECT imaging provides information on regional sympathetic innervation of the myocardium .Currently, 123-iodine metaiodobenzylguanidine  [123-I MIBG] represents the most commonly used radiopharmaceutical agent for evaluation of the sympathetic innervation pattern in patients with heart failure, originating from ischemic or non-ischemic cause -15. MIBG3)  . From plet al. [et al. [Over the recent decades, a large number of studies have sought to determine the prognostic value of sympathetic nerve imaging with 123-I MIBG in patients diagnosed with chronic heart failure -15, 18. et al.  who souget al. [et al. [Beyond myocardial 123-I MIBG uptake, planar imaging can also be used to assess the myocardial washout rate in patients with heart failure -22. Myocet al.  who eval [et al.  who compet al. [6). Additionally, multivariate analysis revealed that late H/M ratio and LVEF were independently associated with the occurrence of adverse events. Accordingly, the study has shown that late H/M ratio could be used for identification of heart failure patients at risk for adverse events. Importantly, the study has demonstrated that the use of a standard quantitative approach yielded similar results when compared to previously findings from single-center studies, regardless of differences in imaging protocols and technical equipment.In addition to single-center studies, Agostini et al.  performe et al. [et al. [Abnormalities of the autonomic nervous system, as assessed with 123-I MIBG imaging, is also thought to interact in the pathophysiology of ventricular tachyarrhythmias . It has  et al.  performe [et al.  who evalet al. [The value of 123-I MIBG SPECT imaging for prediction of ventricular arrhythmias has also been demonstrated in several studies , 28. Recet al.  evaluateet al. [et al. [ et al. [Accordingly, abnormalities in cardiac sympathetic innervation or activation play an important role in prognostication of patients with heart failure. A detailed evaluation of abnormalities in cardiac sympathetic nervous system can be performed by cardiac 123-I MIBG imaging. Cardiac 123-I MIBG images can be acquired safely in nearly all patients with heart failure, except in patients with known hypersensitivity for MIBG compounds or MIBG sulphate. Despite the potentials of 123-I MIBG imaging, some impeding factors have been recognized that hamper the clinical implementation of sympathetic nerve imaging with 123-I MIBG . One of et al. , who sou [et al. ; the myo [et al. . Accordi[ et al.  have pubAlthough cardiac 123-I MIBG imaging can be used for risk stratification of patients with heart failure, some potential pitfalls of cardiac 123-I MIBG imaging should be addressed. First, the evaluation of 123-I MIBG SPECT images may be hampered by severely reduced myocardial uptake of 123-I MIBG in patients with advanced heart failure. Furthermore, the readers should be aware of the fact that 123-I MIBG shows a reduced uptake in the inferior wall under normal conditions . ParticuThe autonomic nervous system plays an essential role in the pathophysiology of heart failure. Dysfunction of the sympathetic nervous system represents an important prognostic marker in patients with chronic heart failure. Most commonly, 123-I MIBG imaging has been used for the assessment of abnormalities in cardiac sympathetic innervation and activation. Cardiac sympathetic denervation as assessed with 123-I MIBG represents an important predictor for heart failure mortality and morbidity. Furthermore, 123-I MIBG imaging can be used for prediction of potentially lethal ventricular tachyarrhythmias in patients with heart failure. At present however, improved standardization of 123-I MIBG imaging procedures is indicated. Standardized criteria on the use of 123-I MIBG imaging may further strengthen the clinical value of 123-I MIBG imaging in heart failure patients.


Few studies have been performed on P wave indices in athletes. The aim of this study was to determine the behaviour of maximum P wave duration (Pmax), minimum P wave duration (Pmin) and P wave dispersion (PWD) in young high performance athletes, as well as the relationship of PWD with training history, heart rate (HR) and echocardiographic parameters.We performed a cross-sectional observational study in 38 athletes of high performance in sports: water polo, distance running and weight lifting compared with 34 sedentary controls.The average age in both groups was 20.6 years. Note that PWD was increased in athletes  while Pmin was significantly lower , and there was no difference when comparing Pmax . The correlation between the duration of training (r = 0.511) and resting HR (r = 0.461) with PWD was significant (p <0.01).PWD is increased in young athletes of high performance and was positively correlated with duration of training and baseline HR. The increase in PWD was secondary to a significant decrease in Pmin. AF is known to be more prevalent in trained athletes compared with sedentary controls -5. A stuConduction abnormalities occurring in patients with AF can be detected by non invasive methods through the determination of P wave dispersion (PWD) in the standard 12-lead electrocardiogram (ECG) where a discontinuous and prolonged spread of atrial depolarization can be identified. The sympathetic nervous system has also been observed to influence PWD -9.The P wave indices of maximum duration and dispersion have received increasing attention and have been examined in a broad range of clinical settings, especially in relation to AF ,10. PWD Therefore, the aim of this study was to determine the behaviour of Pmax, Pmin and PWD in young athletes of high performance and correlate PWD with duration of training, heart rate (HR) and echocardiographic parameters.Observational analytic cross-sectional study.A total of 38 high performance athletes from three sports: female water polo, distance running and weight lifting training at the Institution of Bodybuilding of Villa Clara were compared with 34 healthy sedentary control subjects.Age, duration of training, Pmin, Pmax, PWD, HR, left atrial size, interventricular septum thickness in diastole (ISTd), left ventricular posterior wall in diastole (LVPWd), left ventricular internal dimension in diastole (LVIDd) and h/r index.Difference between maximum and minimum P wave duration in a 12-lead ECG, expressed in ms.Time between R waves, taken by the average of 3 consecutive R waves, expressed in msRefers to the anteroposterior transverse diameter measured using a parasternal long axis view in ventricular systole in the echocardiogram.Has been used to assess the metabolic rate (aerobic-anaerobic) in which the heart is working; a value below 0.32 indicates an aerobic state while a  value above 0.36 indicates an anaerobic state,   determiFor the recording of the ECG we used a Nihon Kodhen Cardio fax electrocardiograph. All ECGs were digitized, allowing to amplify the image and perform a more accurate measurement. The measurements were done manually using digital calipers.Echocardiographic parameters were obtained by an equipment Aloka 4000 Japanese technology using M mode as recommended by the American Society of Echocardiography . The ECGThe data were processed using the statistical package for social sciences (SPSS) and a  simple linear correlation was applied (Pearson). The sample means were compared by student T test. The significance levels used were: p> 0.05 , p <0.05, p <0.01 and p <0.001 representing increasing levels of statistical significance.Athletes show significant lower values of HR compared with sedentary controls In Linear regression coefficient was obtained by correlating the left atrial size  and the h/r index  with the PWD noting that these parameters are weakly and negatively correlated with PWD.By applying multiple correlation to assess the combined effects of the age of athletes, duration of training and HR on the PWD, the latter shows a positive and strong correlation (r = 0.67) proved to be highly significant (p <0.001).All patients studied were screened regularly because of their top-level athlete status, and did not show any detectable cardiac dysfunction which may have influenced our results. Therefore, the data obtained from these athletes reflect the influence of systematic physical exercise on atrial electrophysiology.A recent meta-analysis based on the studies of six case controls collected 665 athletes with a mean age of 51 ± 9 years, showed that the risk of AF is higher in athletes compared with non-athletes  . They usAlthough an increase in Pmax and PWD in athletes was associated with a likelihood to develop AF, contradictory observations have been reported. Karakaya et al. concluded in their comparative study on predictors of rhythm disorders that the athlete's heart is not associated with an increase in PWD or Pmax, and claimed that these parameters cannot be used as predictors of AF  in athleWe found a lower HR in the group of athletes which is part of the physiology of well-trained athletes reported previously ,20.Our study demonstrates that years of practicing sports (duration of training) are positively correlated with PWD. This constitutes the basis of the electrophysiological observation that established a cut-off of 1500 hours of sport practice for the appearance of an increased risk of AF , i.e., iIn In spite of being aware of the existence of adrenergic AF, no studies linking the PWD with this variety of AF in athletes have been performed. Ozdemir and colleagues showed that AF induced by exercise (in non athletes) carried out through stress tests correlates well with PWD; in addition to the observation that this parameter is higher in these patients, two weeks of treatment with different β-blockers agents reduced PWD and the recurrence of AF . These rAlthough there was no correlation between atrial size and PWD, this relationship has been described in several studies -25. We bAn inverse and very weak relationship was observed between the h/r index and PWD. PWD is larger in hearts with a more aerobic metabolic state but the change was not statistically significant. It is possible that the hearts of athletes that handle larger end diastolic ventricular volumes are associated with inhomogeneous propagation of atrial electrical impulse, but more evidence is needed to support this hypothesis.Finally we highlighted that when one takes into account duration of training, the athlete's age and resting heart rate create an additive effect that increases PWD.Our data suggest that athletes undergo an increase in PWD, that could be a possible mechanism for the increased incidence of AF in this group, but could also represent a physiological type of electrical remodeling without deleterious consequences.We concluded that PWD is increased in young athletes of high performance and was positively correlated with training history and baseline HR. The increase in PWD was secondary to a significant decrease in Pmin.A limitation of our study is the limited sample size and lack of frequent monitoring.


Helical ventricular myocardial band (HVMB) is global three-dimensional anatomical model which defines principal, cumulative vectors, integrating tissue architecture and net forces developed within the ventricular mass. Objective of this study is to demonstrate functional macroscopic anatomy of the interventricular septum (IVS) and to emphasize its clinical relevance.Three bovine and two porcine hearts ware prepared according to Torrent-Guasp’s technique. Special dissection technique was undertaken with non- toothed forceps, scalpel and scissors. Blunt dissection, using finger peeling technique was applied to identify predominant direction of the linear (fiber) and laminar (layer) fiber pathways within the myocardial mass.IVS displays significant fiber disarray at the boundaries of LV and RV free walls, and contains an intriguing structure that may be freshly examined by the HVMB dissection. These dissections contradict the concept that the interventricular septum belongs to the LV, since both ventricles participate in its formation. Ascending and descending segments od the HVMB provide the origin and significance of mayor “septal fiber crossing”. Conventional low resolution ultrasound imaging of the ventricular septum previously identified the border of this crossing as hyper-echogenic “septal line”. We suspect the overlap of the crossing of descending and ascending segments creates this “bright line”. Histological analyses have shown that septal RV and LV fibers create a connective tissue true space. Coronary artery septal branches run through this space, a fact, which may be useful in Ross’ procedure.IVS belongs to both ventricles. Anatomical dissections of the IVS and boundaries of LV and RV free walls have demonstrated significant changes in principal fiber orientation, explaining IVS three-layered functional anatomy. The functional significance of this septal fiber organization has to be further examined.