QT prolongation on the surface ECG is associated with sudden cardiac death. The cause of QT prolongation in ischaemic heart disease (IHD) patients remains unknown, but may be due to a complex interplay between genetic factors and impaired systolic and/or diastolic function through as yet unexplained mechanisms. It was hypothesised that QT prolongation before elective coronary angiography is associated with an increased mortality at six months.Complete records of 321 patients who underwent coronary angiography were examined for QT interval corrected for heart rate (QTc), left ventricular ejection fraction (LVEF), left ventricular end-diastolic pressure (LVEDP) and known ischaemic heart disease risk factors. Patients were designated long QTc (LQTc) when they had prolonged QTc intervals or normal QTc (NQTc) when the QTc interval was normal. Patients with atrial fibrillation, bundle branch blocks, no ECG in the 24 hours before angiography, or a creatinine level > 200 μmol/l were excluded. Survival was determined telephonically at six months.p < 0.01), and with lower but normal LVEF , higher LVEDP at LVEF > 45% , hypercholesterolaemia and a negative family history of IHD.Twenty-eight per cent of the total population had LQTc. During follow up, 15 patients (4.7%) died suddenly, 73% of whom had a LQTc. LQTc was significantly associated with mortality (LQTc 12% vs NQTc 1.7%; In patients with sinus rhythm and normal QRS width, QTc prolongation before coronary angiography predicted increased mortality at six months. QTc also associated strongly with left ventricular systolic and diastolic dysfunction, hypercholesterolaemia and a negative family history of IHD. The QT interval represents ventricular electrical depolarisation and repolarisation on the surface ECG. It increases with age and varies with gender, time of day, season of the year and heart rate.5forme fruste of QT prolongation is congenital long QT syndrome (LQTS), an inherited cardiac ion-channel disease associated with syncope, malignant ventricular tachydysrhythmias and sudden cardiac death. LQTS, by exclusion, occurs in structurally normal hearts.6A prolonged QTc interval (LQTc) is a manifestation of a complex interplay between genetic and environmental factors, and is a risk factor for life-threatening dysrhythmias and sudden death. The Recently, polymorphisms in the gene for NOS1AP, which regulates nitric oxide production and thus coronary perfusion, have been shown to prolong cardiac repolarisation.10QT prolongation is an independent prognosticator of cardiac and all-cause mortality, especially in the context of cardiovascular disease.14The fact that interventional cardiologists are more interested in the ‘ST’ segment than the ‘QTc’ is underscored by the paucity of QTc studies peri-angiography. In only one study has an LQTc in the period immediately before coronary angiography been directly correlated with outcome, but the authors described QT peak interval instead of QTc.16IHD is a cause of systolic and diastolic dysfunction of the left ventricle, and both of these are independent predictors of mortality.20QT prolongation may also reflect autonomic neuropathy in patients with diabetes mellitus.The purpose of our study was to evaluate LQTc as an independent prognostic indicator with regard to mortality and systolic and diastolic dysfunction in the context of IHD. Furthermore, we endeavoured to assess, in a state hospital setting in the Western Cape, whether LQTc correlated with triple-vessel coronary artery disease (TVCAD), or was significantly associated with hypercholesterolaemia, diabetes mellitus, smoking, hypertension or a family history of IHD.The study was approved by the Committee for Human Research, Faculty of Health Sciences, Stellenbosch University. All patients signed informed consent before coronary angiography. All data were collected and recorded as part of routine clinical care.This was a single-centre, prospective study, enrolling a cohort of patients who were eligible for coronary angiography from 2006 to 2009 at Tygerberg Academic Hospital. Due to the time limit imposed by the authors collecting data, rotating through the coronary care unit, not all eligible patients could be enrolled. Patients with atrial fibrillation, bundle branch blocks, no ECG in the 24 hours before angiography, or renal failure (creatinine ≥ 200 μmol/l) were excluded from the study.26QTc intervals were recorded on the last ECG taken during the 24 hours before coronary angiography, and designated long QTc (LQTc) or normal QTc (NQTc). The primary outcome was six-month survival. Secondary outcomes included correlation of QTc intervals with left ventricular ejection fraction (LVEF), left ventricular end-diastolic pressure (LVEDP), TVCAD, diabetes mellitus, smoking, systemic hypertension, a family history of IHD and dyslipidaemia.As the accuracy of automated measurements of the QT interval is questionable, partly because of inconsistency between manufacturers in terms of the digital algorithms employed in various instruments, the QT intervals were measured manually.The QT interval was measured from the start of the QRS complex to the end of the T wave, using a Digimatic® digital caliper  with an autostopper . When a T wave was biphasic, or nearly so, the QT interval was measured to include the final return to baseline. No U waves were encountered, and therefore no decision as to the endpoint of measurement in such instances had to be taken. The digitally calculated heart rate was obtained from the ECG, and the QTc was computed by means of Bazett’s formula.5The QTc was considered prolonged if > 440 ms in males and > 460 ms in females. The follow-up period started on the day of coronary angiography (day 0), and ended after six months (day 180) had elapsed. Survival was determined telephonically at the end of six months. The LVEF (as an index of systolic function) was determined either by ventriculography at the time of coronary angiography or, in the case of ventriculography not having been performed, by transthoracic or trans-oesophageal echocardiography. The LVEDP (as an index of diastolic function) was measured at the time of coronary angiography via a fluid-filled endocardiac catheter.TVCAD was defined as a > 70% stenosis of all three of the following vessels: the right main coronary artery, the left circumflex artery and the left anterior descending coronary artery or the right main coronary artery, in conjunction with the left main stem, as assessed at the time of coronary angiography. The interventional cardiologist decided how to treat stenosed coronaries, i.e. medically, percutaneously or surgically, and the investigators were blinded to subsequent treatment.Diabetes mellitus was defined as symptoms of diabetes plus a random blood glucose concentration of ≥ 11.1 mmol/l, or fasting plasma glucose of ≥ 7.0 mmol/l. This accords with the American Diabetes Association clinical practice recommendations of 2006.Smoking was defined as the use of any tobacco on a daily basis at any stage of the patient’s life. Systemic hypertension was defined as a blood pressure recording of ≥ 140/90 mmHg as per National Cholesterol Education Program Adult Treatment Panel III Guidelines of 2004.28Hypercholesterolaemia was defined as a total, non-fasting serum cholesterol level > 5 mmol/l. The non-fasting nature was accepted as a result of the short period of hospitalisation of most patients undergoing angiography.p-value. NQTc and LQTc groups were compared with regard to LVEF, LVEDP and serum cholesterol with a Mann–Whitney U test. Categorical data  were tested for an association with LQTc using a chi-square test. Statistical significance was defined as p < 0.05.Data were analysed by the Stellenbosch University Centre for Statistical Consultation (CSC) using STATISTICA version 9 . The Kaplan–Meier method was used to create survival curves for NQTc and LQTc groups and a log-rank test was used to compare the two curves and generate a p = 0.168). Ninety patients (28%) had LQTc.Of the 2 023 patients who were catheterised, 321 were enrolled   p < 0.01) At six months, 15 (4.7%) of the total population had died, 73% of whom had a LQTc. Eleven patients (12%) died in the LQTc group and four (1.7%) in the NQTc group (p < 0.01) p < 0.05) LQTc patients had normal LVEF but lower than that of the NQTc cohort  p = 0.96).A family history of IHD was significantly less common among those with LQTc  and beta-blockers have been prescribed, patients are often seen only weeks later for follow up at the outpatient clinic, where they are assessed by a junior colleague. The routine ECG is studied for new Q waves and cardiac arrhythmias. The blood pressure is checked, drug compliance with DAT is reiterated, and the patient is given a six-month follow-up appointment. Our data suggest that more than 10% of patients with QTc prolongation prior to coronary angiography will not return for their six-month appointment because they have died suddenly.The association of LQT with a lower but normal LVEF is interesting. While there is no internationally agreed threshold of a ‘low’ LVEF, it has been characterised in a report of the American Society of Echocardiography and the European Association of Echocardiography by gradation: mild (45–54%), moderate 30–44%) and severe (< 30%) left ventricular dysfunction.–44% and The mechanism by which a decreased LVEF results in QT prolongation is unknown, but may involve ion-channel remodelling and/or intracellular calcium transport.The association of LQT with an elevated LVEDP  is striking. Diastolic dysfunction is a relatively new concept when compared with LVEF. The commonest cause of diastolic dysfunction is hypertensive heart disease. Often these patients have thicker, stiffened left ventricles with good systolic function, but impaired relaxation and compliance. Again, exactly how diastolic dysfunction in IHD patients is associated with QT prolongation remains unknown, but recently an association was found between down-regulation of the hERG gene and QT prolongation in rats with cardiac hypertrophy.34Ion-channels are embedded in a phospholipid bi-layer primarily composed of cholesterol esters. Both congenital LQTS and familial hypercholesterolaemia are more common in South Africans of European descent. Co-segregation of ion-channel disease and hypercholesterolaemia has not yet been described in humans, but in Langendorff-perfused rabbit hearts, hyperlipidaemia led to significant QT prolongation compared with normocholesterolaemia, which can be reversed by administering simvastatin.35This single-centre study in a state hospital setting may be prone to selection bias due to the fact that patients were enrolled only during rotations of the authors collecting the data through the coronary care unit. However, all eligible patients were enrolled during these intervals, leading us to believe that the cohort was truly representative.More than 80% of the studied population were of mixed racial ancestry. One should therefore be careful to draw conclusions about race and QT prolongation.Prescribed medications were not checked and these may well have prolonged the QT interval after discharge. However, this study addressed the relationship between QTc prior to coronary angiography and mortality at six months.The effects of coronary revascularisation on QTc were also not investigated but it was assumed that significant coronary stenosis would have been treated appropriately by the interventional cardiologist. Mortality in the LQT cohort remained high regardless of coronary revascularisation. Follow up was relatively short owing to the vast extent of the geographical catchment area of the hospital.Genetic screening was also not performed on the study patients. Diastolic pressure was used as an indicator of diastolic function; however, echocardiographic parameters of diastolic function were not assessed.This is the first description of LQTc in a cohort of IHD patients in a South African setting. The study confirms that QTc, which can be determined by a simple, non-invasive, inexpensive method, is an index of subsequent sudden death in patients who undergo coronary angiography for suspected IHD.QTc prolongation before coronary angiography is also a reflection of systolic and diastolic dysfunction  of the left ventricle, both of which are independent predictors of mortality rate. Furthermore, LQTc correlates with hypercholesterolaemia and a negative family history of IHD.


Blood flow between the right and left ventricles is subject to the continuity equation and systolic ventricular interdependence. Quantification of this relationship might aid in understanding inter-ventricular function. The purpose of this study was to evaluate and quantify ventricular interdependence by directly comparing right and left ventricular systolic function though echocardiographic surrogates of right and left ventricular systolic function such as MAPSE, TAPSE, RV TVI and LV TVI.This study prospectively evaluated 51 healthy participants  by resting echocardiography. In addition to standard measurements, tricuspid annular plane of systolic excursion, (TAPSE), mitral annular plane of systolic excursion (MAPSE), and the peak annulus systolic velocity of the right ventricular (RVs) and left ventricular (LVs) free walls were measured by M-mode and pulsed wave Doppler tissue echocardiography and further evaluated for variance across age, gender, and body surface area.TAPSE (22.1 ± 2.9 mm) was over 54.5% greater than MAPSE (14.3 ± 2.6 mm) and RVs was 64.4% greater than LVs. The LV to RV systolic relationship measured by MAPSE/TAPSE and LVs/RVs ratios were 0.66 ± 0.14 and 0.76 ± 0.21 respectively. These values were not significantly affected by age, gender or body surface area (BSA).MAPSE/TAPSE and LVs/RVs ratios appear stable across age, gender, and BSA potentially making them good surrogates of systolic ventricular relationship and interdependence. The differences between the right and left ventricle go far beyond differences in shape and thicknesses and further include differences in cardiac myofibril concentration and orientation leading to complex differences in the way each ventricle ejects blood . HoweverAlthough there are many surrogates of LV systolic function, the complex shape of the right ventricle (RV) makes its' functional assessments much more challenging. Despite newer techniques such as three-dimensional echocardiography and cardiac magnetic resonance, the cost and expertise required to utilize these modalities currently make them impractical for both screening and follow up evaluation . HoweverThis previous MRI study by Dirk et al as well as a study by Qin et al  revealed6 and even poor image resolution [Similarly, measurements of peak mitral and tricuspid valvular velocities using pulsed wave Doppler tissue imaging (DTI) have also been shown in multiple studies to correlate well with ejection fraction,6,12,13.solution .Based on the simplicity and reproducibility of these surrogate markers of systolic function, we chose the longitudinal systolic motion of the lateral walls of both ventricles as measured by TAPSE and MAPSE as well as the peak systolic annulus velocity (S) of the same segments as measured by Doppler Tissue Imaging (DTI).2, LV or RV hypertrophy, LV or RV enlargement, or more than mild valvular heart disease were also excluded.After Institutional Review Board approval, data was collected on fifty one healthy adult volunteers without any known history of cardiac disease using two-dimensional and Doppler echocardiography at our non-invasive imaging laboratory. All echocardiograms were done according to the recommendations and standards of the American Society of Echocardiography using a standard commercially available ultrasound systems , and stored digitally for subsequent analysis using software . Participants were excluded from the study if they had a rhythm other than sinus rhythm, a history of pulmonary hypertension, atrial fibrillation, complete right or left bundle branch block, pacemakers, defibrillators or more than mild valvular disease. Participants with a history of heart failure, myocardial infarction, previous cardiac surgery, an LVEF < 55%, a left atrial index > 28 cc/mBaseline variables collected included age, BSA, gender, LVEF, left ventricular interventricular septal thickness, left atrial volume index, and right ventricular systolic pressure (RVSP). Eligible participants were then divided by age into 3 groups; group I < 30, group II 30-50, and Group III > 50 years old.2 when appropriate. The study population was also divided into 3 groups by age including those < 30 years, 30-50 years, and > 50 years old as well as by sex. Analysis of variance (ANOVA) was performed in order to compare multiple echo measurements across age groups. Age and BSA dependencies of MAPSE/TAPSE and LVs/RVs measurements were evaluated by linear regression analysis. An intra and interobserver agreement analysis using the Kappa statistic was performed to determine consistency among evaluators. For all measurements, a two-sided P value of less than 0.05 was considered statistically significant. All statistical analysis was performed using SPSS for Windows, version 17.0, SPSS Inc, Chicago, Illinois, USA) and GraphPad Prism version 5.0 .From the four chamber view, TAPSE and MAPSE Figure  were meaBasic demographic and echocardiographic data were collected and were separated by gender. All variables were similar between the two groups except for an increased BSA among male subjects Table .P = 0.51), sex (P = 0.19), or BSA (P = 0.78)  was over 54.5% greater than MAPSE (14.3 ± 2.6 mm) and when MAPSE was directly compared to TAPSE, the resultant MAPSE/TAPSE systolic interventricular ratio was 0.66 ± 0.14. When these values were further analyzed for variance, this relationship was remarkably consistent regardless of age (P = 0.24), BSA (P = 0.70) and gender (P = 0.80)  regardless of age, BSA or gender. Although these results were somewhat unexpected, the reason for this might be suggested by a separate study by Carrlson et al. which showed that despite the different contributions of longitudinal motion toward RV and LV total stroke volume, the actual percentage of total stroke volume contributed by each ventricle remained relatively consistent, even when compared between healthy adults, athletes, and patients with dilated cardiomyopathy with reduced LVEF [A second finding is that the measurements of TAPSE (2.1 cm ± 0.35), MAPSE (1.4 cm ± 0.26), RVs (13.02 cm/s ± 2.4) and LVs (9.76 cm/s ± 2.58) fell within relatively tight dispersions across the population. Furthermore, when each of the LV surrogates was directly compared to its respective RV surrogate, the resultant systolic interventricular ratios remained tightly distributed  granted an exemption to review the data in echocardiograms retrospectively.No authors associated with the writing of this manuscript have conflicts of interest to report.All the authors contributed equally to this manuscript and have read and approved the final manuscript.


Standard measures of left ventricular systolic and diastolic function often fail to identify left ventricular dysfunction in patients with heart failure and do not correlate with measures of functional capacity.To determine if speckle tracking echocardiography (STE)–determined measures of global and regional myocardial contractility have a linear association with functional capacity in patients with and without preserved ejection fraction.In 68 adult patients, functional status was estimated with the Duke Activity Status Index (DASI), left ventricular ejection fraction was determined with Simpson’s biplane method, and QLAB advanced quantification software  was used to determine peak measures of strain.Global and regional measures of longitudinal, circumferential, and radial strain had a strong linear association with the DASI score. Longitudinal strain in the inferolateral segments had the strongest correlation with DASI . In patients with an ejection fraction ≥45%, ejection fraction and E/e’ had no correlation with DASI, whereas longitudinal strain in the inferolateral segments had significant correlation with DASI .STE–determined measures of global and regional left ventricular function have a strong linear association with estimates of functional capacity in patients with and without preserved ejection fraction. STE–determined measures of strain, especially longitudinal strain, are likely to be important targets for therapy and should be considered in future studies aimed at improving our diagnosis of left ventricular inadequacy in patients with heart failure, especially those with preserved ejection fraction. Measurements of left ventricular (LV) function are important for estimating prognosis and guiding the management of patients with multiple forms of cardiac disease . LV systAdvances in non-invasive imaging have allowed for newer measurements of LV function that have enhanced the understanding of the mechanical deficits that may lead to clinically apparent LV dysfunction. These newer measures of myocardial contractility include quantification of the deformation of a myocardial segment using speckle tracking echocardiography (STE) . STE allThis study was approved by the University of Florida institutional review board. Adult patients who were referred for an echocardiogram for clinically indicated reasons and who had echocardiographic images that were determined to be adequate for evaluation of regional LV systolic function were approached for enrollment. The patients’ functional status was estimated with the Duke Activity Status Index (DASI) questionnaire . DASI isEchocardiograms were obtained with an iE33 . Parasternal short axis views were obtained at the basal, midventricular, and apical levels . AdditioAnalysis was performed using QLAB advanced quantification software version 7.1 . Automated tracking of myocardial speckles was reviewed and manually adjusted as minimally as possible. The tracking quality of each segment was visually evaluated and if tracking was felt to be inaccurate, strain analysis of that segment was not included. Speckle tracking analysis provided measures of peak circumferential, radial, and longitudinal strain in 18 LV segments  and rotation in the basal and apical LV regions. Strain was determined for the entire myocardial segment, not just the endocardial or epicardial portion. LV twist was calculated as the maximal apical rotation minus the maximal basal rotation. Average global circumferential, radial, and longitudinal strain were calculated. Further, average circumferential, radial, and longitudinal strain in each of the 6 walls of the LV was calculated. If fewer than 2/3 of the variables for a computed variable were available, then that computed variable was not included in the analysis. QLAB software also used the automated endocardial borders to determine the fractional area change (FAC) in each of the LV regions  by comparing the LV luminal area at end-diastole and end-systole.P value <0.05 was considered statistically significant.Analysis was completed with SPSS Version 20. Continuous variables were compared between groups using a Kruskal Wallis test. Continuous variables were compared between groups A and B using a Mann–Whitney U test. Correlations between continuous variables are presented as Pearson correlation coefficients. The magnitude of correlation coefficients between EF/DASI and EF/regional measures of LV strain were then compared . CategorA total of 88 patients were enrolled in this study. Seven patients with moderate or severe valve disease were excluded from analysis. Further, 13 patients with clear non-cardiac causes of a decreased functional capacity, such as interstitial lung disease, were excluded from the analysis. Of the remaining 68 patients, 19 were identified as controls as they had no symptoms and normal LV systolic and diastolic function as described above. The baseline characteristics for the 19 controls and 49 patients with a reduced functional capacity or asymptomatic LV systolic or diastolic function are shown in Table Speckle tracking echocardiography strain analysis was attempted on 1224 LV segments (18 segments for each of 68 patients). Importantly, because of inadequate tracking quality, STE-derived measures of LV function could not be determined for all segments. Circumferential strain could be determined in 913 (75%), radial strain in 781 (64%), and longitudinal strain in 804 (66%) of the LV segments analyzed. To test the inter-observer reliability between the two investigators who completed strain analysis for this project , each independently determined circumferential, radial, and longitudinal strain in a total of 48 LV segments from 8 different subjects. Inter-observer reliability was very strong for longitudinal strain  and good for circumferential strain  and was similar to previously reported inter-observer reliability of speckle software [In the 49 patients with a reduced functional capacity or asymptomatic LV systolic or diastolic function , global longitudinal, radial, and circumferential strain had a strong linear association with the DASI score of functional status Table . The linIn the patients included in this study, longitudinal, circumferential, and radial strain in the various walls of the LV had significant linear associations with the DASI score of functional status Table . As detaAs shown in Table In the 34 patients included in this study who had an EF ≥45%, biplane EF did not have a linear association with the DASI score of functional status . Further, traditional echocardiographic measures of “diastolic function”, such as E/e’, had no correlation with the DASI score of functional status . However, similar to what was shown in all patients, longitudinal strain in the inferolateral segments had significant correlation with DASI score in these patients with preserved EF .We aimed to determine if novel measures of LV contractility had a strong linear association with functional capacity. STE-determined measures of global and regional LV function had a strong linear association with the DASI score of functional capacity. The strength of the association between most STE-determined measures of strain and the DASI score of functional capacity was not statistically different than the association of EF with the DASI score in this small cohort. However, the difference in the strength of the correlation of anteroseptal longitudinal strain with the DASI score and the strength of the correlation of EF with the DASI score was near statistically significant despite the small sample. Further, in patients with preserved EF, STE-determined measures of regional strain had a strong correlation with functional capacity, whereas EF and traditional Doppler echocardiographic parameters of LV diastolic function had no correlation with functional capacity. These findings support previous work which has demonstrated decreased systolic myocardial strain in patients with heart failure but preserved EF ,14. FinaRegional longitudinal strain appeared to have stronger correlation with functional capacity than did radial or circumferential strain both in the entire cohort and in just those with preserved EF. Previous work has shown that longitudinal motion of the LV is an important aspect of normal and efficient LV contraction . While tThe strong correlation of longitudinal strain in the inferolateral and anterior/anteroseptal walls of the LV with the DASI score of functional status could be explained by an important aspect of efficient blood flow through the LV. In normal hearts the inflow of blood into the LV gives rise to rotational/vortical blood flow patterns. The dominant vortex is under the anterior mitral leaflet, and this vortex gives rise to asymmetric flow of blood in the LV during diastole with redirection of blood toward the superior and medially located LV outflow tract. This flow pattern allows for efficient circulation by preventing collision of flow, and by allowing the slinging of blood toward the LV outflow tract just prior to ejection . EffectiThere are limitations to this study. First, our measure of functional status was provided through a questionnaire. Although the DASI score of functional status has been shown to correlate with peak oxygen consumption, has been used as a marker of improved function after various interventions, and recently was shown to have superior prediction of outcome as compared to a 6 minute walk test , the queSTE-determined measures of global and regional LV function have a strong linear association with the DASI score of functional capacity in patients with and without preserved EF. In patients with preserved EF, STE-determined measures of regional strain have a strong linear association with functional capacity, whereas EF and traditional Doppler echocardiographic parameters of LV diastolic function have no correlation with functional capacity. STE-determined measures of strain, especially longitudinal strain, are likely to be important targets for therapy and should be considered in future studies aimed at improving our diagnosis of LV inadequacy in patients with heart failure, especially those with preserved EF.DASI: Duke Activity Status Index; E: Peak early left ventricular filling velocity; e': Peak early mitral annular velocity; EF: Ejection fraction; LV: Left ventricular; STE: Speckle tracking echocardiography.The authors declare no competing interests related to this research.JP developed the concept and research design and drafted the article. JP, TN, and LL collected the data, and all authors contributed substantially to analysis and interpretation of data and critical revision of the manuscript. All authors have read and approved the final manuscript.


BMMC n = 9, p = 1.00; vs. PBMC n = 10, p = 0.67. VT: control n = 9 vs. BMMC n = 9, p = 0.80; vs. PBMC n = 11, p = 0.69). SAE occurred in 2 patients in the PBMC group and 1 patient in the control group. In conclusion, intracoronary cell therapy is not associated with an increase in ventricular arrhythmias or SAE.To reduce long-term morbidity after revascularised acute myocardial infarction, different therapeutic strategies have been investigated. Cell therapy with mononuclear cells from bone marrow (BMMC) or peripheral blood (PBMC) has been proposed to attenuate the adverse processes of remodelling and subsequent heart failure. Previous trials have suggested that cell therapy may facilitate arrhythmogenesis. In the present substudy of the HEBE cell therapy trial, we investigated whether intracoronary cell therapy alters the prevalence of ventricular arrhythmias after 1 month or the rate of severe arrhythmogenic events (SAE) in the first year. In 164 patients of the trial we measured function and infarct size with cardiovascular magnetic resonance (CMR) imaging. Holter registration was performed after 1 month from which the number of triplets (3 successive PVCs) and ventricular tachycardias  was assessed. Thirty-three patients (20%) showed triplets and/or VTs, with similar distribution amongst the groups (triplets: control  Although the short-term mortality after acute myocardial infarction has decreased over the last decades, long-term morbidity remains high due to congestive heart failure caused by post-infarction remodelling –3. To reBetween August 2005 and April 2008, the HEBE trial was conducted to assess the effect of intracoronary infusion with autologous mononuclear cells derived from either bone marrow (BMMCs) or peripheral blood (PBMCs), compared with standard therapy on recovery of regional and global left ventricular function after a revascularised acute myocardial infarction. The trial did not show an effect of either BMMCs or PBMCs on functional improvement at short-term follow-up . To evalThe study design of the HEBE trial has been reported in detail previously . In shorIn all participating patients, CMR was performed at least 48 h after PCI in a clinical 1.5 Tesla MR scanner with the use of a phased-array cardiac receiver coil. Functional imaging was performed by using ECG-gated steady-state free precession cine imaging with breath-holding, for the acquisition of short-axis images covering the entire left ventricle (i.e. from base to apex). From these images, left ventricular volumes were measured and ejection fraction (LV EF) calculated . Late gaOne month after PCI, 24-hour Holter registration was performed. Analysis was done automatically by external core laboratories, including analyses of the rhythm and morphology of each individual complex . Results were manually verified. The arrhythmias were defined as follows: triplet PVCs were defined as a series of 3 successive ventricular complexes with a maximal RR interval of less than 600 ms (i.e. frequency of >100/min). Ventricular tachycardia (VT) was defined as any series of 4 or more successive ventricular complexes with a maximal RR interval of less than 600 ms (i.e. frequency of >100/min). By correcting for the total recording time, the mean number of triplets and/or ventricular tachycardias per 24 h for each patient was calculated for standardisation. Together with the Holter registration, a resting 12-channel electrocardiogram (ECG) was made from which the QRS width and corrected QT time (QTc) were measured.Statistical analyses were performed on the basis of the intention-to-treat principle. Tests were performed using the Standard Package for the Social Sciences (SPSS 15.0).n = 60, PBMC n = 53, control group n = 51). No differences were found in the baseline characteristics between the treatment groups for infarct size, LV volumes or LV function  and ventricular tachycardias . In these 33 patients, a median of 1 triplet  per 24 h and a median of 1 ventricular tachycardia (IQR 1–3) occurred during registration. Again, no differences existed between the treatment groups (Fig. During the Holter registration at 1 month, 33 patients showed either triplet PVCs, ventricular tachycardia or both. Distribution was similar amongst the treatment groups for both triplets (control Of all 200 patients, 9 suffered from a severe arrhythmogenic event during the first year of follow-up. One patient assigned to the PBMC group died of VF during the first year of follow-up, 13 days after cell therapy; autopsy revealed an in-stent thrombosis. Two patients had documented VF with successful resuscitation without sequelae and received an ICD implantation. One of these patients was also assigned to the PBMC and suffered from VF a few hours after cell infusion. The other patient was assigned to the control group and VF occurred 3 days after randomisation. Additionally, 6 patients received an ICD for primary prevention of late arrhythmias due to a low EF as indicated by the guidelines of the European Society of Cardiology [This HEBE trial substudy focused on the safety of cell therapy with mononuclear cells after a revascularised STEMI, with regard to arrhythmogenesis and the prevalence of SAE, defined as either sudden cardiac death or documented ventricular arrhythmias for which external defibrillation or ICD therapy was required. One month after PCI and cell therapy, the amount of triplet PVCs or ventricular tachycardias are similar between the three treatment groups. Secondly, no significant differences were found in the rate of severe arrhythmogenic events in the first year of follow-up. This shows that the current method of cell therapy, i.e. intracoronary infusion of mononuclear cells, does not harbour an increased risk of arrhythmogenesis. The choice to discriminate between triplet PVCs and ventricular tachycardia was made in line with the results of the recently published MERLIN-TIMI 36 substudy. This study demonstrated that ventricular arrhythmias of 4 beats or more are associated with worse prognosis . Our finAn important issue that needs to be addressed is that no positive effects of cell therapy have been found for the main endpoints of the HEBE trial . TherefoCell therapy by intracoronary infusion of mononuclear cells is not associated with either an increase or decrease in the amount of triplets or ventricular tachycardias. Secondly, no increased incidence in severe arrhythmogenic events was found in the first year of follow-up. Therefore, cell therapy consisting of intracoronary infusion of mononuclear cells does not impose additional dangers with regard to ventricular arrhythmias.


Background. B-type natriuretic peptide has been shown to be a very sensitive and specific marker of heart failure. In this study, we aimed to investigate the effect of percutaneous closure of ventricular septal defects with Amplatzer septal occluders on brain natriuretic peptide levels. Methods. Between 2008 and 2011, 23 patients underwent successfully percutaneous ventricular septal defect closure in 4 cardiology centers. Brain natriuretic peptide levels were measured in nine patients  who underwent percutaneous closure with Amplatzer occluders for membranous or muscular ventricular septal defects were enrolled in the study. Brain natriuretic peptide levels were measured one day before and one month after the closure. Patients were evaluated clinically and by echocardiography one month after the procedure. Results. Percutaneous closures of ventricular septal defects were successfully performed in all patients. There was not any significant adverse event in patients group during followup. Decrease in brain natriuretic peptide levels after closure were statistically significant . Conclusion. Brain Natriuretic Peptide levels are elevated in patients with ventricular septal defects as compared to controls. Percutaneous closure of Ventricular Septal Defect with Amplatzer occluders decreases the BNP levels. Ventricular Septal Defect (VSD) is the most common congenital heart defect and seen in approximately 30% of all congenital heart lesions –5. Up toBrain natriuretic peptide (BNP) is a neurohormone released by cardiac ventricles in response to volume and pressure load , 12, 13.Between 2008 and 2011, total of 23 patients underwent successfully percutaneous VSD closure attempt in 4 cardiology centers. BNP levels were measured in nine patients  who underwent percutaneous closure with Amplatzer occluders for membranous or muscular Ventricular Septal Defects enrolled in the study. BNP levels were measured day before and thirty days after the closure. Patients were evaluated clinically and by echocardiography one month after the procedure. Inclusion criteria: clinical and/or echocardiographic evidence of a significant left-to-right shunt through the VSD if there were one of those criteria: cardiomegaly on chest X-ray, left atrial enlargement, defined as left atrial to aortic ratio >1.5, left ventricular enlargement (left ventricular volume overload), defined as a left ventricular end-diastolic diameter ≥2 standard deviations (SD) above the average for the patient's age, symptoms including frequent respiratory infections and/or failure to thrive, and a New York Heart Association functional class II or greater. Frequent respiratory infections were defined as more than six events a year. Failure to thrive was defined according to the literature [Patients or parents of the children gave their written informed consent to the procedure. The patients' general characteristics are reported in A written consent was obtained from all patients, and our local ethical committee approved the study.The muscular or membranous Amplatzer VSD occluder device and Amplatzer duct occluder II device were  used for closure in all patients as was described previously –11, 15. Right femoral vein and artery sheaths were placed. Right and left cardiac catheterization was performed firstly. The shunt volume was calculated by echocardiographic and oximetric measurements . Left veImplantation of the VSD occluder was performed according to standard techniques previously described under the guidance of transthoracic and transesophageal echocardiography –11. VSD BNP levels were measured one day before and one month after the percutaneous closure of VSDs with Amplatzer occluders. One month later, all patients were evaluated clinically and by echocardiography. Written informed consent was obtained in all patients.t-test. P value of <0.05 was considered as statistically significant in all cases.Statistical analysis was performed using the Statistical Package for Social Sciences , version 15.0 software for Windows. Descriptive statistics were made, and all data were expressed as mean ± standard deviation and % ratio. The quantitative values between pre- and postprocedures were compared using paired sample Tables There was not any death or urgent cardiac surgery required complication. There was one device embolization which was seen in patient number 3. The embolized device was stuck in abdominal aorta, and snare retrieval was tried before but yielded unsuccessful. Device was rescrewed and replaced to the VSD defect region successfully.Third-degree atrioventricular block was occurred in one patient, and temporary pace maker was inserted for 24 hours. Normal sinusal rhythm was restored after 12 hours monitoring, and 1 mg/kg cortisone was administered for this patient by intravenous route. Intradevice residual shunt remained in 3 patients for 3 days and residual shunt was remained in one patient. Mild groin hematoma was occurred in three patients.There was not death, endocarditis, or device-related complication in the follow-up period. Residual shunt was remained in one patient in whom the defect was closed by ADO II and simultaneous ASD closure.P = 0.013), Mean preprocedural BNP level obtained one day before the closure was 97.3 ± 78.6 pg/mL. BNP levels measured one month after the closure decreased in all patient compared with the preprocedural values (26.8 ± 15.6). This decrease was statistically significant (VSDs with left ventricular volume overload require closure in order to prevent ventricular dilatation and dysfunction, arrhythmias, aortic regurgitation, pulmonary artery hypertension, and endocarditis –18. PercIn our study, percutaneous closures of VSDs were successfully performed in 23 patients, and none of the patients need emergency cardiac surgical. The rate of major complications reported in the literature ranges between 0 and 8.6% –17. In oBNP is a neurohormone released by cardiac ventricles in response to volume and pressure load. These natriuretic hormones are thought to be a sensitive and specific indicator of ventricular function , 19. RecIn conclusion, BNP is relatively cheap, noninvasive, rapid, and widely available cardiac biomarker. The current study suggests that serum BNP level may provide a useful clinical tool in evaluation of patients with VSD after the closure. Decrease in serum BNP levels may indicate hemodynamic improvement, so measurement of BNP level may offer an objective method in the clinical evaluation of the patients who underwent percutaneous closure of VSD.


To assess cardiothoracic structure and function in patients with pectus excavatum compared with control subjects using cardiovascular magnetic resonance imaging (CMR).Thirty patients with pectus excavatum deformity  underwent CMR using 1.5-Tesla scanner (Siemens) and were compared to 25 healthy controls . The CMR protocol included cardiac cine images, pulmonary artery flow quantification, time resolved 3D contrast enhanced MR angiography (CEMRA) and high spatial resolution CEMRA. Chest wall indices including maximum transverse diameter, pectus index (PI), and chest-flatness were measured in all subjects. Left and right ventricular ejection fractions , ventricular long and short dimensions , mid-ventricle myocardial shortening, pulmonary-systemic circulation time, and pulmonary artery flow were quantified.In patients with pectus excavatum, the pectus index was 9.3 ± 5.0 versus 2.8 ± 0.4 in controls (P < 0.001). No significant differences between pectus excavatum patients and controls were found in LV ejection fraction, LV myocardial shortening, pulmonary-systemic circulation time or pulmonary flow indices. In pectus excavatum, resting RV ejection fraction was reduced , RVSD was reduced (P < 0.05) both at end diastole and systole, RVLD was increased at end diastole (P < 0.05) reflecting geometric distortion of the RV due to sternal compression.Depression of the sternum in pectus excavatum patients distorts RV geometry. Resting RVEF was reduced by 6% of the control value, suggesting that these geometrical changes may influence myocardial performance. Resting LV function, pulmonary circulation times and pulmonary vascular anatomy and perfusion indices were no different to controls. Patients with pectus excavatum, a relatively common congenital deformity, often present with symptoms such as exertional dyspnea, fatigue, chest discomfort or palpitations. The suggested etiology for this abnormality, although uncertain, has been described as an overgrowth of the costal cartilages in utero, usually ribs 4, 5, 6, 7, and 8, which then limits the elevation of the sternum . PosteriCurrently, radiographic studies such as chest X-ray or CT scan are used to quantify the severity of chest wall deformity by deriving the pectus index (PI). PI, elsewhere called pectus severity index, is defined at the level of greatest deformity as the maximum transverse diameter of the chest divided by the shortest distance between the posterior edge of the indented sternum and the anterior border of the vertebral bodies of the thoracic spine ,11. PI iChest x-rays and CT scans continue to be used mainly to assess the degree of deformity in pectus excavatum patients but both tests expose patients to ionizing radiation. Other investigations such as pulmonary function tests, maximal exercise tests, arterial blood gases and echocardiography, have also been used to evaluate patients with pectus excavatum. However, they may lack the sensitivity to detect anatomical and subtle pathophysiological abnormalities. Thus, there is a clinical need for additional objective assessment.Recent technical developments in cardiovascular magnetic resonance (CMR) and the range of its applications have highlighted the potential of this modality as a reliable, non-invasive diagnostic tool. CMR is powerful for the assessment of chest and cardiac anatomy, cardiac function, pulmonary vascular anatomy and perfusion, blood flow and blood circulation times.To our knowledge, no study has used CMR for assessment of patients with pectus excavatum. The purpose of our study, therefore, was to assess resting cardiovascular anatomy and function in patients with pectus excavatum using CMR and compare the results with healthy control subjects.Our study population was a group of patients referred or self-referred for evaluation of pectus excavatum. Between August 2004 and January 2008, they were offered the opportunity to participate in a broader study designed to evaluate cardiovascular structure and function using conventional pulmonary function tests and exercise tests as well as imaging. Thirty consecutive patients who enrolled in the broader study and had CMR scans were included in this analysis. The group with pectus excavatum deformity consisted of 23 men and 7 women aged 24.3 ± 13.3 years (age ± SD). Their CMR studies were compared to those from a convenience sample of 25 healthy adult controls within the same age range , aged 24.1 ± 3.8 years, without chest wall deformity or any other cardiovascular or pulmonary disease.All studies were performed on a 32 channel 1.5 Tesla scanner  using combined 24-element spine coil and 6-element body phased array coil. CMR compatible ECG electrodes were positioned on the anterior chest and a 22-gage intravenous cannula was sited in an ante-cubital vein for subsequent infusion of CMR contrast medium. Subjects were positioned supine on the scanner table and advanced head first into the magnet bore. From 2004-2006, the CMR contrast used was gadodiamide 0.15 mmol/kg  and after this date Magnevist  was used at a lower dose (0.1 mmmole/Kg). This contrast was administered as a controlled, timed infusion using an electronic injector .The following CMR protocol was employed for assessment of cardiopulmonary structure and function. After obtaining scout images, detailed anatomical images were acquired to derive chest wall diameters, pectus severity index, and indices of chest and cardiac distortion. Next, 4-chamber, right and left ventricular outflow tract (RVOT and LVOT) and short-axis cine images were obtained to quantify bi-ventricular function. Dynamic pulmonary parenchymal enhancement and pulmonary-systemic circulation times were then evaluated using low-dose, time-resolved 3D MR angiography with 0.035 mmol/kg gadolinium at a 3D sampling interval of 1.5 seconds. Subsequently, high-spatial-resolution contrast enhanced MR angiography was acquired to visualize detailed pulmonary vascular anatomy. Finally, blood flow in the main pulmonary artery was quantified with velocity-sensitized phase contrast CMR . The indA series of large field-of-view (FOV), single-shot, steady-state-free-precession (SSFP) survey images  were obtA stack of short axis cine (SSFP) images (10-12 short adjacent slice positions) were acquired during individual 5-6 second breath-holds, encompassing the atrio-ventricular valve plane to the cardiac apex, followed by cine images in the four-chamber, LV vertical long axis, RVOT, LVOT views and the midline sagittal plane . A segmented k-space SSFP sequence as previously described  was emplWe assessed dynamic pulmonary enhancement as an index of regional lung perfusion using an ultra fast 3D, spoiled GRE sequence  with temDual-phase, high-spatial resolution contrast enhanced MR angiography of the pulmonary vasculature was subsequently acquired using a 3D spoiled gradient-recalled-echo (GRE) sequence . Gd contrast was infused at a rate of 1.5 ml/sec followed by 30 ml of saline flush at the same rate. A 3D dataset was acquired during 20-22 seconds while subjects held their breath. The entire thorax was interrogated during these acquisitions with voxel dimensions of 1.3 × 1.0 × 1.2 mm³.°and GRAPPA×2. Images were retrospectively ECG gated with 5 segments per heartbeat and 20 calculated phases. Images were acquired during 18-20 seconds of breath-hold acquisition. The velocity mapping sequence had single direction (through-slice) flow encoding with an aliasing velocity of 150 cm/sec. Two perpendicular RVOT cine images were used to determine the optimal imaging plane. A perpendicular plane to the MPA midway between the pulmonary valve and bifurcation was used.Phase-sensitive velocity encoded cine ,21 quantThe MR images were transferred to a 3D workstation  for measurement of the following data:L) and right (LDR ) cardiac borders were measured from the midline . Then cardiac left lateral shift (%) was measured as L and LDR were measured perpendicular to the sterno-spinal line  for both groups (SVLV - SVRV). Furthermore, to evaluate myocardial contractile properties, long and short dimensions (LD and SD) of the right and left ventricles were measured during both ED and ES phases at the level of mid ventricle to calculate regional myocardial shortening .Assessment of thoracic vascular anatomy was performed by two observers in different sessions, using high-spatial-resolution pulmonary MR angiography and cardiac cine images. Processing was performed on a 3D workstation , using a maximum intensity projection (MIP) algorithm. The 3D volume source images were reconstructed into overlapping thin (10 mm) MIP sub-volumes Figure . PulmonaIn the main pulmonary artery, the following measurements were performed: peak and average velocity, peak and average volume flow , and net forward volumes (integrated forward volume flow) .sv. Chest indices were correlated with ventricular EF using Pearson correlation. A correlation coefficient (r) greater than 0.6 was considered to be a strong correlation. Inter-observer agreement between readers for the assessment of thoracic structure and cardiac function was determined by calculating the kappa coefficient.  [A two-tailed t-test was used to compare chest indices, cardiac indices, pulmonary flow measurements and pulmonary-systemic circulation times between patients with pectus excavatum and controls. In addition, the Kolmogrorov-Smironov Test was used to compare the distribution of measurement error for left and right ventricular EF and RV 0.81-1) ,27. At aThis HIPAA compliant study was approved by the Institutional Review Board of the David Geffen School of Medicine, University of California, Los Angeles. Written informed consent was obtained for all study subjects.Chest wall measurements and all indices are summarized in Table Quantitative cardiac functional indices, mean ± SD, both absolute and normalized to body surface area (BSA), are presented in Table The RV short dimension was significantly less both at end-diastole (ED)  and end-systole (ES) . The RV long dimension was significantly greater at ED . The short diameter RV shortening was significantly less in pectus excavatum patients  and the long diameter RV shortening was significantly greater in pectus excavatum patients  , P = 0.2746; For LVEF r = -0.0065  P = 0.9727).All dynamic 3-D MR angiographic studies showed symmetrical perfusion in both lungs, with no filling defects. There was no difference between both readers for pulmonary perfusion assessments.Pulmonary-systemic circulation times in pectus excavatum patients were not significantly different .One patient had an enlarged pulmonary artery trunk (3.2 cm), detected by both readers but no other vascular abnormality. Another patient had dextrocardia but no evidence of valvular or cardiac septal abnormality. Observing that this patient did have cardiac compression caused by the pectus deformity, we chose to not to exclude him/her from the overall analysis. The remaining patients were diagnosed with normal pulmonary vascular anatomy by both readers independently (κ = 1).Average flow and net forward volume indexed to BSA tended to be greater in patients; however, the differences failed to reach statistical significance (P = 0.070 and P = 0.386 respectively). The results showed no significant difference for all other flow parameters (P > 0.1). Quantitative pulmonary artery flow measurements for both patients and controls are summarized in Table The results of our study show that, compared with controls, patients with pectus excavatum deformity have reduced RV short axis diameter, increased RV long axis diameter and reduced RV ejection fraction. These findings likely reflect compression induced changes in RV anatomy and changes in the pattern of myocardial shortening in patients with pectus excavatum, potentially mimicking restrictive RV physiology. No differences were found in LV ejection fraction, LV myocardial shortening, aorto-pulmonary circulation time or pulmonary flow indices between pectus excavatum patients and controls.Most of our patients presented with complaints of increasing dyspnea with mild exercise or a decrease in stamina and endurance. Some physicians have suggested that these symptoms and their improvement after corrective surgery are, at least in part, psychological ,6. OtherOur results show that RV myocardial shortening was significantly different in patients with pectus excavatum compared with controls. Myocardial shortening and thus contractility in the direction of the short-diameter (SD) in short axis cine was reduced, whereas myocardial shortening in the direction of the long-diameter (LD) was increased. It appears that this is a compensatory mechanism in order to preserve RVEF.We did not detect any significant correlation between the EF and pectus severity index, which could potentially be explained by chest reconfiguration (i.e. an increase in maximum transverse diameter of the chest) and cardiac left lateral shift, which could be another compensatory mechanism to avoid the direct restrictive impairment of the right heart. Furthermore, pectus excavatum patients did not show significant changes in pulmonary flow quantification.Our study has certain limitations. Firstly, it was not strictly a case-control design and the normal comparison group was only matched in terms of age range. They were, however, healthy volunteers without any history of cardiovascular or lung disease and without any chest wall deformity. Furthermore, we detected no abnormalities on CMR scanning in this group. Secondly, while CMR can provide a very good visualization and measurement of LV volumes, RV contouring and volume measurements can be more challenging. This is because of the thinner wall, widespread trabeculation and geometrically non-uniform shape. RVOT imaging becomes even more difficult when the RV is distorted by sternal compression and this can exacerbate error in RV volume measurement. Finally, patients with severe pectus excavatum deformity (or even moderate pectus excavatum deformity) may be different from the mild forms in terms of cardiopulmonary function as quoted by Haller et al . UnfortuPatients with pectus excavatum deformity show varying levels of distortion of the right ventricle, associated with a 6% reduction in resting RVEF relative to controls. The degree of physiological impairment is likely related to the degree of geometrical distortion of the RV due to the sternal compression, and it is possible that, in some patients, restrictive physiology plays a role. Further work is warranted to assess whether these changes are reversible with corrective surgery.Dr. Christopher Cooper is the recipient of the grant. The rest of the authors declare that they have no competing interests'.RS: Coordinated the project, recruited volunteer subjects, performed MRI scans in volunteer subjects, performed quantitative evaluation of MRI images, performed literature review, statistical analysis and drafted the manuscript. JPF: Conceived of the comparative study design between patients and the control group, participated in the design of the study, prepared the MRI protocol for the study and participated in manuscript preparation. MF: Performed literature review and data interpretation. AM: Performed data analysis and helped to draft the manuscript. MK: Performed qualitative evaluation of MRI images for both healthy subjects and patient group. MA: Recruited study subjects, gathered subject demographic and medical history data, coordinated MRI scan schedule. AT: Performed qualitative evaluation of MRI images for both healthy subjects and patient group. RH: Performed image and data processing, participated in statistical analysis of data. EWF Participated in the study design and helped to draft the manuscript. CBC: Conceived of the study, participated in the study design, and participated in manuscript preparation. All authors participated in manuscript editing. All authors read and approved the final manuscript.


Currently, myocardial edema monitoring after acute myocardial infarction (AMI) is based on visualization of the region with increased signal-intensity on T2-weighted images. T2-mapping is a promising novel cardiac magnetic resonance imaging (CMR) technique to quantitatively assess myocardial edema. The purpose of the study was to quantitatively evaluate resorption of myocardial edema following AMI using T2-mapping.CMR (1.5 Tesla Philips Achieva) was performed in 20 patients within seven days after a reperfused AMI (Baseline) and at one, three and six months follow-up, respectively. A free-breathing, navigator-gated multi-echo sequence was used for T2-mapping. T2-maps were calculated from fifteen echoes using a dedicated plug-in written for OsiriX software. Serial T2 values were assessed using a six-segment model . Infarcted and remote segments were defined by using information from corresponding late-enhancement images .A significant decrease of the T2 time was found in infarcted segments from baseline to one month follow-up , but not between one and three  or three and six  month follow-up. Identical T2 times were found in remote segments at baseline, one, three and six month follow-up . The T2infarct/T2remote ratio decreased from baseline to one month follow-up  and from one to three month follow-up . No significant change was found for the T2infarct/T2remote ratio from three to six month follow-up .Serial T2-mapping enables monitoring of edema resorption following acute myocardial infarction. The magnitude of edema resorption occurs in the first month after AMI and the T2 values normalize within 3 months after AMI. Thereafter, no further T2 time reduction is observed.None


Patients with transfusion-dependent beta-thalassemia major (TM) are at risk for myocardial iron overload and cardiac complications. Spatial repolarization heterogeneity is known to be elevated in patients with certain cardiac diseases, but little is known in TM patients. The purpose of this study was to evaluate spatial repolarization heterogeneity in patients with TM, and to investigate the relationships between spatial repolarization heterogeneity, cardiac iron load, and adverse cardiac events.c (SI-QTc), a standard deviation of QTc (SD-QTc), and a QTc dispersion. Left ventricular function and myocardial T2* values were assessed by cardiac magnetic resonance. Patients with TM had significantly greater SI-QTc, SD-QTc, and QTc dispersion compared to the control subjects . Spatial repolarization heterogeneity was even more pronounced in patients with significant iron overload  compared to those with normal T2* . Loge cardiac T2* correlated with SI-QTc , SD-QTc , and QTc dispersion , while all these indices had no relationship with measurements of the left ventricular geometry or function. At the time of study, 10 patients had either heart failure or arrhythmia. All 3 indices of repolarization heterogeneity were related to the presence of adverse cardiac events, with areas under the receiver operating characteristic curves (ranged between 0.79 and 0.86), similar to that of cardiac T2*.Fifty patients with TM and 55 control subjects received 64-channel magnetocardiography (MCG) to determine spatial repolarization heterogeneity, which was evaluated by a smoothness index of QTMultichannel MCG demonstrated that patients with TM had increased spatial repolarization heterogeneity, which is related to myocardial iron load and adverse cardiac events. Adoption of transfusion regimens and iron-chelating therapy has led to great improvement in life expectancy in the majority of affected individuals Magnetocardiography (MCG) is a medical technique that directly measures the weak magnetic field generated by electrical activity in the heart, using a superconducting quantum interference device (SQUID). With the advances in multichannel MCG systems, this technique has been recognized for its outstanding ability to detect coronary artery disease and cardiac allograft vasculopathy after heart transplantation, through the evaluation of various repolarization indices The study protocol was approved by the institutional review board of the National Taiwan University Hospital, and written informed consent from all participants was obtained. This study conformed to the principles of the Helsinki Declaration.From June 2008 to January 2010, patients with transfusion-dependent TM, treated at the Pediatric Hematology Department of National Taiwan University Hospital, served as the eligible population of this study. Patients were transfused every 2 to 4 weeks to keep hemoglobin levels above 10 g/dL. Among the 53 patients enrolled, 3 were excluded from further analysis because of the presence of a conduction disturbance in 12-lead surfance ECG (QRS duration >120 ms). Therefore, a total of 50 patients with TM were studied. The control group for MCG consisted of 55 healthy subjects with similar age and sex as the patient group. Control subjects were free from any cardiovascular disorder, and had no conduction disturbance after evaluation by 12-lead surface ECG.1/2 at 100 Hz, and approximately 50 fT/Hz1/2 at 1 Hz. The probe was positioned as close to the chest as possible, directly over the heart. MCG recordings were carried out at rest for 100 seconds. Premature beats and the beats just prior to the premature beats were carefully identified and then excluded from analysis. The remaining heart beat signals were averaged, centering on the R-wave peak c), using Bazett's formula . The QTc was used for the construction of the QTc contour map, with a spatial resolution of 21×21  to detect spatially distributed magnetocardiac signals  [19]. Toof 21×21 . In addic contour map, 3 indices were calculated to evaluate spatial repolarization heterogeneity. First, the smoothness index of QTc (SI-QTc), modified from previous studies S is a summed value of the total measured MCG points, and c at a fixed measured position k, summed over the total number of nearest neighbors, n. For each channel, the average absolute difference between this value and the values of the neighboring channels was calculated. SI-QTc was determined as the mean of these averaged differences over all channels. SI-QTc increases with greater deviations in QT interval duration between neighboring registration sites. Second, the standard deviation among all the QTc intervals in the QTc contour map (SD-QTc) was calculated. Third, the spatial dispersion of QTc interval (QTc dispersion) was calculated as the difference between the longest and shortest QTc interval in the QTc contour map.Based on the QTAll patients with TM were scanned with a 1.5-T magnetic resonance scanner  with multislice multiecho T2* approach, as previously described A continuous stack of short-axis cines was acquired to assess left ventricular end-diastolic and systolic volumes, masses, and ejection fractions, using standard techniques All participants recevied a 12-lead surface ECG before the MCG, to determine the QRS duration. For patients with TM, the following clinical and laboratory data were obtained from medical records and clincial evaluations at the time of study enrollment: hemoglobin and serum ferritin concentration , annual transfused-blood volume , body weight and height, presence of diabetes mellitus, regimen of iron chelation therapy, and concurrent cardiac medications.Adverse cardiac events were defined as either heart failure at the time of study enrollment or significant arrhythmia, documented by 24-hour Holter ECG, which was performed every year on a regular basis. The diagnosis of heart failure was made if the patient complained of worsening dyspnea at rest or during exercise, a left ventricular ejection fraction below 56% (assessed by CMR), and if the treating physician made the clinical diagnosis of heart failure th–75th percentile), as appropriate. Continuous variables were analyzed using the 2-sample t test or the Mann-Whitney U test, after testing for normality. Categorical variables were analyzed by the chi-squared test or Fisher's exact test, as appropriate. Linear relationships between variables were assessed after logarithmic transformation of T2* values using Pearson's correlation coefficient. Rreceiver-operating characteristic (ROC) curve analysis was conducted to test the diagnostic accuracy of indices of repolarization heterogeneity and cardiac T2* in relation to adverse cardiac events. Results were expressed in terms of the area under curve (AUC) and 95% confidence interval for this area. AUCs for various parameters were compared by the area test for correlated test results Data are expressed as percentage, mean ± standard deviation, or median  had abnormal cardiac T2* values (<20 ms). The left ventricular-ejection fraction was preserved in our study cohort. No difference in CMR-derived left ventricular measurements was apparent between patients with or without abnormal cardiac T2* values.2, p = 0.029) comparing to those without. However, there are no differences in left ventricular volumes or ejection fraction between these 2 patient groups. In addition, despite all those 4 patients with heart failure had severely depressed T2* (ranged from 3.6 to 9.9 ms), they still exhibited preserved left ventricular ejection fraction (ranged from 55 to 73%).A total of 10 patients (20%) experienced adverse cardiac events at the time of study enrollment. Four patients had heart failure , and all were receiving medical control . Nine patients had clinically significant arrhythmia  documented by 24-hour Holter monitoring. Of those 9 patients, 6 had short-run atrial tachycardia, 1 had paroxysmal atrial fibrillation and flutter, 1 had short-run atrial and ventricular tachycardia, and 1 had second-degree Morbitz type II atrioventrilar block. Overall, patients experienced adverse cardiac events had significantly lower T2*  and higher left ventricular mass index , but also significantly greater values of SI-QTc, SD-QTc, and QTc dispersion .MCG-derived parameters in both patients and healthy control subjects are shown in c, SD-QTc, and QTc dispersion all differed significantly between patients with and without abnormal cardiac T2* , and differed even more between patients with abnormal cardiac T2* and healthy controls . In addition, patients with abnormal cardiac T2* had greater SI-QTc and SD-QTc, compared to the control subjects. However, for mean QTc interval and QTc dispersion, the group differences between patients with normal cardiac T2* and healthy controls were minimal.Further analysis revealed an overall tendency for spatial repolarization heterogeneity to be low in the healthy control subjects, higher in patients with normal cardiac T2*, and highest in patients with abnormal cardiac T2* . SI-QTc,e cardiac T2* value and SI-QTc , SD-QTc , and QTc dispersion  . No correlations were found between all 3 indices of spatial repolarization heterogeneity and QRS duration, left ventricular dimensions, ejection fraction, mass index, age, hemoglobin, and serum ferritin level, either in the overall study patients or in those with adverse cardiac events.We observed directly negative correlations between logp<0.001) , suggestc and QTc dispersion were higher than the 95th percentile of the data from control subjects, and the cut-off value of SD-QTc was higher than the 90th percentile of the data from control subjects.The ROC curves showed the overall performance of indices of spatial repolarization heterogeneity and cardiac T2* value for predicting the presence of adverse cardiac events (either heart failure or arrhythmia) . AUCs foc interval, other measurements of left ventricular function, hemoglobin, and serum ferritin level were not related to adverse cardiac events using the ROC curve analysis.We also found that left ventricular mass index significantly correlated with the presence of adverse cardiac events . In contrast, QRS duration, mean QTThis study yielded 3 novel findings: (1) patients with TM had significantly greater spatial repolarization heterogeneity, compared to the healthy subjects; (2) the extent of spatial repolarization heterogeneity detected by MCG correlated with the severity of myocardial iron overload; and (3) spatial repolarization heterogeneity was linked to the presence of either heart failure or arrhythmia. Through the quantification of repolarization heterogeneity, our study results not only demonstrated the potential usefulness of multichannel MCG in the evaluation of TM patients who are at risk for cardiac iron overload, but also highlighted the importance of spatial repolarization heterogeneity in the pathophysiology of iron overload-related cardiac complications.c, SD-QTc, and QTc dispersion were all significantly increased in this young cohort of TM patients, whose ventricular geometry and contractility were generally preserved. There was no direct correlation between repolarization heterogeneity and ejection fraction, even in ambulatory heart failure patients and those with clinical arrhythmias. Although the measurements of left ventricular function may change over time in the progression of cardiac dysfunction in TM patients, these measurements could only identify patients with an advanced stage of heart failure Increased cardiac repolarization heterogeneity has been noted in patients with TM c duration in TM patients, but also greater values of all 3 indices of spatial repolarization heterogeneity compared to those of the healthy subjects.Several mechanisms might be responsible for increased spatial repolarization heterogeneity in patients with TM. At the cellular level, iron can alter calcium homeostasis, which in turn affects cardiac action potential c dispersion on 12-lead surface ECG) positively correlated with left ventricular mass index (estimated by echocardiography), suggesting that spatial repolarization heterogeneity may be influenced by changes in left ventricular geometry. However, we could not find correlations between any of the 3 indices of repolarization heterogeneity and left ventricular mass index in our study cohort. We speculated that the discrepancy between our study results and that reported by Ulger et al. might be related to methodological differences in assessing repolarization heterogeneity and left ventricular mass.A close relationship between spatial repolarization heterogeneity and cardiac iron load indicated that increased repolarization heterogeneity is not just an intrinsic phenomenon in TM patients, who exhibit unique cardiac physiology related to mild chronic anemia Previous studies have shown that spatial repolarization heterogeneity is linked to arrhythmia and sudden cardiac death in patients with myocardial infarction, heart failure, and long QT syndrome c and QTc dispersion reflected global repolarization heterogeneity, and SI-QTc reflected regional repolarization heterogeneity. Considering the associations with adverse cardiac events, all 3 indices exhibited similar performances. It is possible that both global and regional repolarization heterogeneity are pivotal in the development of cardiac complications related to iron overload. In addition, the cut-off value of each index of repolarization heterogeneity enabled clear separation of patients with TM from healthy subjects. Thus, the clinical use of repolarization heterogeneity detection by MCG in TM patients appeared to be justified.Of the 3 spatial repolarization indices used in this study, SD-QTAs a noninvasive, contactless diagnostic tool, MCG could provide high spatial resolution to detect the imperceptible changes in cardiac electrical properties caused by various heart diseases in adults Our present study was limited by a cross-sectional study design, and therefore the predictive role of repolarization heterogeneity indices for subsequent occurrences of adverse cardiac events could not be investigated. Studies with a longer period of observation and, thus, a higher number of cardiac events, are required to validate the findings of this study. As the size of the population was not sufficiently large, the novel results of the present study must be considered as preliminary. The sensitivity and specificity of each cut-off value should be tested in further studies.c, SD-QTc, and QTc dispersion are all related to myocardial iron load, and mark the presence of adverse cardiac events. Prospective studies are necessary to confirm the relationship between increased spatial repolarization heterogeneity and subsequent cardiac events in TM patients.Patients with TM exhibited significant changes in spatial repolarization heterogeneity, as detected by multichannel MCG. SI-QT


An asymptomatic 5-year-old girl presented with bradycardia during a routine well-child visit. Further evaluation revealed profound sinus bradycardia, exercise-induced bidirectional ventricular tachycardia, and supraventricular tachycardia. An echocardiogram showed heavy trabeculations inthe left ventricular myocardium. This patient's presentation suggested catecholaminergic polymorphic ventricular tachycardia and left ventricular noncompaction. Genetic testing revealed mutations in the cardiac ryanodine receptor (RyR2), calsequestron (CASQ2), and titin (TTN). She was effectively treated with beta-blockade to suppress tachyarrhythmias and pacemaker implantation to treat her bradycardia. While bradycardia is not uncommon in children , profounA 5-year-old girl presented to her pediatrician's office for a routine well-child visit. She was asymptomatic and developmentally normal. Parents reported that she participated in all activities but was not as active as her siblings. She was taking no medications. She had never been hospitalized or undergone surgery. Her examination was notable only for bradycardia with a heart rate (HR) of 52 beats per minute (bpm). She had normal weight, height, and blood pressure, with no evidence of thyromegaly. Both parents were healthy, as were the girl's older sister and younger brother. There was no family history of congenital heart disease, seizures, syncope, early sudden death, or family members requiring pacemakers or defibrillators.The patient's ECG showed sinus rhythm at 50–60 bpm with normal PR, QRS, and corrected QT (QTc) intervals . Due to An echocardiogram performed to assess cardiac anatomy and function revealed an overall normal appearing heart with normal LV chamber size and systolic function, but with heavy trabeculations in the LV apex, suggestive of LVNC. Cardiac magnetic resonance imaging showed similar noncompacted myocardium in the LV apex with normal LV chamber size and function and no other abnormalities. Initial laboratory testing including basic metabolic profile, inflammatory markers, complete blood count, and liver and thyroid function tests were within normal limits. The patient underwent an exercise treadmill test (ETT) to assess for inducible arrhythmias in a controlled setting. She had sinus rhythm at 55–70 bpm at rest and developed polymorphic PVCs and bigeminy at HRs greater than 110 bpm . The ETTβ-blocker, nadolol (1.0 mg/kg/day). Immediately postoperatively, she had intermittent PVCs and mild hypertension that resolved by increasing nadolol to 2.0 mg/kg/day. Prior to pacemaker implantation, there was a lengthy discussion regarding her arrhythmia substrate and possible implantable cardioverter defibrillator (ICD) placement for primary prevention. Since our patient had no history of syncope and appeared to have an excellent response to beta-blockade, the decision was made against ICD implantation for primary prevention.Beta-blocker therapy was initially considered to prevent the tachyarrhythmias, but due to her profound baseline bradycardia, a class 1C sodium channel blocker antiarrhythmic medication (flecainide) was started. A repeat ETT showed no reduction of PVCs during exercise. Therefore, the flecainide was discontinued and a beta-blocker trial was started with esmolol (infusion rate of 250 mcg/kg/min). This short-acting intravenous (IV) beta-blocker was chosen, so that the medication could be discontinued immediately if her basleine bradycardia was exacerbated or the beta-blocker resulted in hemodynamic compromise. A repeat ETT showed resting sinus rates of 50–60 bpm and a peak HR of 118 bpm at 9.5 min of exercise. Rare PVCs were noted with exercise and suppressed completely at peak HRs . Due to Repeat ETT, performed 6 weeks after pacemaker implantation, showed a resting sinus rate of 70 bpm and peak HR of 117 bpm at 10 min of exercise. Rare single monomorphic PVCs noted with exercise suppressed completely at peak HRs. She reported mild fatigue during daily activities, and her pacemaker was reprogrammed on for rate response to allow more physiology heart rate with daily activities. At her 5-month followup she had improvement in her fatigue and no palpitations or syncope. She continued on nadolol with exercise restrictions. Her Holter monitor showed sinus alternating with atrial pacing with good beta-blockade effect and no ventricular arrhythmias. Her echocardiogram was unchanged.Candidate gene testing was performed due to her history of arrhythmias. A long QT syndrome panel revealed no disease-causing mutations. A pan cardiomyopathy microarray designed to identify mutations in genes associated with cardiomyopathy and CPVT revealed three mutations: ryanodine receptor (RyR2) Arg169Gln, calsequestron (CASQ2) Asp398del, and titin (TTN) Lys4455Arg. These were all single nucleotide changes resulting in missense mutations.This asymptomatic 5-year-old girl presented with bradycardia and heart rates less than the first percentile for age . Her ECGExercise-induced bidirectional VT has also been reported in CPVT. Clinical cases of CPVT were described as early as 1975 . Our patIf left untreated, CPVT has a high morbidity and mortality. Approximately 30% of those affected experience at least one cardiac arrest, and up to 80% have syncope . Beta-blMutations in both RyR2 and CASQ2, two genes that regulate intracellular calcium metabolism, have been associated with CPVT. RyR2 mutations are inherited in an autosomal dominant fashion and account for 50–55% of genotype-positive CPVT cases , 19. MutInterestingly, our patient's CASQ2 mutation had been reported in two patients with LVNC but did not segregate with the clinical disease in the families described. In addition, this mutation causes an in-frame deletion of the second to the last amino acid of the CASQ2 protein and was not considered pathologic.Although our patient initially had exercise-induced arrhythmias that were consistent with CPVT, she did not have a structurally normal heart. Her heavily trabeculated LV suggested LVNC cardiomyopathy with preserved LV function and no chamber dilation. LVNC is a rare form of cardiomyopathy, previously called spongy myocardium. Based on our current understanding of the pathophysiology of this entity, heart failure and life-threatening arrhythmias appear to be the most significant clinical manifestation. Our patient was negative for known LVNC-causing mutations. She was positive for a TTN mutation (Lys4455Arg). TTN encodes the large sarcomeric protein titin, and TTN mutations have been implicated in cardiac and skeletal myopathies. TTN truncation mutations are a common cause of dilated cardiomyopathy . HoweverThis is a unique presentation of bradycardia, exercise-induced atrial and ventricular arrhythmias, and abnormal myocardium in a young and relatively asymptomatic girl. Her tachyarrhythmias were suppressed with beta-blocker therapy, and bradycardia was treated with pacemaker implantation. Mutations in RYR2, CASQ1, and TTN were discovered, and it is uncertain if one or more of these mutations resulted in the phenotype of bradycardia, exercise-induced bidirectional VT, SVT, and LVNC. There is certainly the possibility that a primary mutation may be modified by other mutations found in this young girl. The role of genetic defects and their modifying genes in the manifestation of cardiomyopathies and inherited arrhythmias is an area of intense investigation. Further cardiac evaluation and genetic testing of family members may be helpful in understanding the spectrum of this disease. Unraveling the complex interplay between the multiple mutations in critical cardiac genes found in this patient may provide further understanding of the etiology of her mixed phenotype of arrhythmias and structural heart disease.


Left ventricular (LV) trabeculations are typically considered LV cavity volume (i.e. ignored) when analyzing cardiac magnetic resonance (CMR) images as they are difficult to manually segment, but they are not actually part of the LV bloodpool. The treatment of papillary muscles is more variable, but they too have often been considered bloodpool.To assess the impact of LV trabeculations and papillary muscles on LV volumes and ejection fraction (EF) determined from CMR images using automated segmentation software.Contiguous 10-mm thick cine CMR images encompassing the left ventricle in the short-axis orientation  from 1494 adults  in the Framingham Heart Study Offspring cohort were analyzed using semi-automated epi- and endocardial LV border detection to determine LV end-diastolic and end-systolic volumes , EF and LV mass (LVM) before and after “adjustment” (ADJ) for trabeculations and papillary muscles. ADJ was fully automated and used fuzzy grayscale thresholding capable of accounting for partial volume effects . Two-sample t-test was used to assess between-sex differences and paired t-test was used to evaluate effect of ADJ. Intra-class correlation (ICC) was used to assess reproducibility on 48 randomly selected participants from equal strata of sex and age-tertile.Prior to ADJ, men had greater EDV, ESV and LVM than women, while women had higher EF (Table LV trabeculations and papillary muscles occupy 22% of the putative LV blood pool in both sexes. Adjustment for trabecular and papillary muscle volume results in increased LV ejection fraction. Automated segmentation of LV trabeculations and papillary muscles is highly reproducible.


Cardiac involvement is a leading cause of morbidity and premature mortality in patients with scleroderma. Identification of this offers the opportunity for earlier and more stratified therapeutic intervention. Published data on the prognostic significance of left and right ventricular impairment and myocardial fibrosis in this cohort are limited. The study objective was to determine the prevalence and prognostic significance of abnormalities on cardiovascular magnetic resonance (CMR) in patients with scleroderma who have breathlessness and/or other cardiac symptoms.This is a retrospective longitudinal study of 126 consecutive patients with confirmed scleroderma and cardiac symptoms, who had undergone CMR. Completed scans were available in 124 of these. All scans were performed at 1.5 Tesla (Siemens Sonata or Avanto). Thinned myocardium was defined as thickness <4mm, right ventricular hypertrophy defined as thickness>5mm. The presence of left ventricular (LV) or right ventricular (RV) dilatation was defined as an increase in indexed LV or RV volumes compared to previously published normal ranges. Late gadolinium enhancement (LGE) was defined as an area of clearly increased signal intensity confirmed on phase swapping. All scans were analysed by two independent operators. All cause mortality was determined from review of hospital records and the national summary care database. A Cox proportional hazards model was used to determine predictors of mortality .Demographic data and CMR findings are shown in Table This is, to the best of our knowledge, the largest cohort of patients with scleroderma to have undergone CMR. In this selective cohort, cardiovascular abnormalities on CMR are detectable in the majority (81%) of patients with scleroderma and breathlessness and/or other cardiac symptoms. Significant LV dysfunction was the strongest CMR predictor of mortality. Presence of LGE did not predict mortality.NA


We aim to evaluate changes in diastolic function after ST elevation myocardial infarction (STEMI) using volumetric cardiac magnetic resonance imaging (CMR), as well as the relation of diastolic parameters to baseline variables including peak troponin-I and baseline left ventricular ejection fraction (LVEF).Diastolic dysfunction is one of the earliest manifestations of cardiac ischemia. However, the response to reperfusion of diastolic filling parameters in patients with STEMI undergoing primary percutaneous coronary intervention (PCI) is not well elucidated. Using volumetric analysis we aimed to define the temporal change in diastolic function after primary PCI.80): proportion of diastole required for recovery of 80 percentage of stroke volume as well as the ratio of the biphasic early (E) and late (A) filling profiles (E/A ratio). The change in those parameters was then correlated to peak troponin-I and baseline LVEF.23 patients with STEMI undergoing primary PCI were prospectively enrolled and sequential CMR imaging was performed within 96 hours of admission and at 1 month follow up. LV volumetric quantification was performed  with manual planimetry of the endocardial contours in all temporal phases of the contiguous short-axis slices. Systolic parameters were obtained. Diastolic CMR parameters were derived including peak filling rate (PFR) and its index normalized to end diastolic volume (NPFR), time to peak filling rate (TPFR), diastolic volume recovery  at baseline to 57% (49-62), p=0.04. There were no significant changes in LV volumes; LV end diastolic volume changed from 194.5ml ( 152.9-237.0) to 192ml (152.5-221.7), p=0.14) and LV end systolic volume from 100ml (65.0-125.8) to 87.71ml (52.8-96.0), p=0.08. The changes in the diastolic parameters are depicted in table  at basel80 and E/A ratio was not correlated with peak troponin, baseline LVEF, or baseline LV volumes.The change in DVR80 and E/A ratio. These parameters may serve as targets from future investigation in the effect of revascularization on myocardial function.Improvement in LVEF with reperfusion did not translate to improvement in PFR, NPFR and TPFR which have been traditionally used as indices of diastolic function. On the other hand, significant changes were seen in DVR