Autoimmune AV block is usually seen in association with autoimmune antibodies in mother that cross the placenta and damage the AV node of fetus. A 24-year-old primigravida, diagnosed to have SLE, at 25 weeks period of gestation found to have fetal bradycardia. Her ANA was moderately positive, SS-A (Ro) antibodies and SS-B (La) antibodies were positive. Fetal ECHO showed no structural defect but heart rate was 55 - 60 beats per minute. She was put on dexamethasone (4 mg/day). She was lost on follow up and presented at term in emergency with labor pains and fetal bradycardia, underwent a lower segment caesarean section. Baby underwent a temporary cardiac pacing within 10 hours of birth followed by permanent pacing on day 3 of birth. Baby is doing well on follow up. Neonates with isolated congenital heart block who are monitored antenatally and delivered in a planned fashion at an institution capable of early pacing can have favorable outcomes. Congenital heart block can occur in fetal life due to maternal disease or due to congenital heart defect in fetus which can manifest at any time before or after birth. Congenital heart block in a structurally normal heart is isolated congenital heart block or with congenital heart disease is complex congenital heart block. Autoimmune AV block occurs in approximately 1 per 14,000 - 20,000 live births [In 2012, a 24-year-old primigravida referred as a case of 25 weeks pregnancy with fetal bradycardia to Obstetrics and Gynecology OPD of a tertiary care centre in North India. She had a history of photosensitivity and oral ulcers off and on. On examination, she was thinly built, mildly anemic without any pedal edema, and normotensive with normal vital parameters. On abdominal examination, the uterus was about 24 weeks size. The fetal heart sound was located by CTG machine and rate being alarming, 68 beats/minute. Fetal movements were felt during examination. Her hemoglobin at admission was 9.8 g/dL and peripheral blood smear showed microcytic hypochromic picture with mild anisocytosis. Her blood sugar levels, kidney and liver function tests were within normal limits. She was VDRL negative. Her ESR was 60 mm, CRP 2.2 and TSH 3.05, DCT was negative. Immunological tests revealed serum ANA moderately positive, and SS-A (Ro) antibodies and SS-B (La) antibodies strongly positive and APTT 27.4 seconds (control 27 seconds). Ultrasound examination on admission, showed a single live fetus of 24 weeks maturity, adequate liquor, and fetal heart rate of 56 beats/minutes. Fetal echocardiography showed no structural defect but the fetal heart rate was 55 - 60 beats/minute suggestive of congenital heart block. Maternal echocardiography findings were within normal limits. Her history, clinical findings and investigations were suggestive of SLE as in accordance to the American Rheumatism Association she had 4 of 11 criteria present she was diagnosed as a case of SLE with pregnancy with congenital heart block in fetus. She and her husband were counseled regarding the prognosis of the fetus. She was put on medication with low dose aspirin (75 mg once a day), dexamethasone (4 mg/day), and iron, calcium and vitamin supplementation. She was lost on follow up. She reported back in emergency at 37 weeks with labor pains and fetal bradycardia due to congenital heart block. A lower segment cesarean section was performed on Dec 7, 2012 and a live female baby weighing 2.1 kg was born. The heart rate at birth was 60 beats/minute and APGAR score at 1 minute and 5 minutes was 6 and 9 respectively. Respiratory rate was 66/minute and a grade 3 systolic murmur was heard in left parasternal area. The baby was immediately transferred to the neonatal intensive care unit (NICU). ECG was done which showed signs of complete heart block. Cardiac consultation was taken and advised to monitor vitals. After 9 hours of birth, heart rate dropped to 48/minute. Hence, cardiac pacing was done in the CTVS unit of the same centre. Initially temporary pacing was done through trans-femoral route at about 10 hours of birth. Post procedure heart rate was 130/minute and baby was monitored in NICU. Permanent pacing was planned on Dec 10, 2012 (namely after 3 days of birth), done by sub-xiphoid approach. Pacemaker was put through right ventricle, connected to power source in the abdomen through subcutaneous plane. Post-operatively, baby required inotropic support (Dopamine and Dobutamine) and received one packed cell transfusion. Gradually as the general condition stabilized inotropes were tapered off and chest tube removed. Thus with the help of a multidisciplinary team, the patient was discharged after 2 weeks with a healthy baby accepting feeds and gaining weight.Isolated congenital heart block is presumed to be caused by injury from the placental passage of maternal anti-Ro and anti-La (or related) antibodies, which are present in more than 90% of mothers during pregnancy or at the time of delivery. These autoantibodies damage the AV conduction tissue possibly by inflammation or direct ion channel interaction in the early stage and later by fibrosis -5. The pSLE with pregnancy is rare, the incidence being 1 in 1,600.The disease remains stable in about 30% but pregnancy at times may cause flare ups . IdentifRegular and close monitoring for heart block and transplacental therapy with fluorinated steroids (dexamethasone) have shown satisfactory results as first evidence of heart block. Prophylactic therapy is not currently indicated as they may have maternal and fetal side effects -10. InfoThere is a 14% mortality rate before 3 months of age, the cumulative probability of survival at 3 year age is 79% and 635 of live born eventually require pacemakers .Management of fetus with congenital heart block is early diagnosis; close fetal monitoring, use of maternal steroids followed by planned delivery at an institution and early but staged pacing procedure.


Atrial fibrillation (AF) adversely affects surgical outcomes of cardiac valve surgery. Surgical ablation is an effective way to treat valvular AF. The aim of this study was to evaluate the late outcome of surgical radiofrequency ablation and explore the risk factors of AF recurrence in Chinese patients undergoing cardiac valve surgery.Three hundred ninety six consecutive patients with persistent valvular AF were enrolled in this study. They underwent concomitant modified Maze IV and were completed follow-ups. Cox survival regression model was used to screen independent risk factors for predicting late recurrence of AF.During the follow-up period of 28 (6 ~ 61) months, AF recurred in 151 patients (38.1%). In multivariate survival regression, factors predictive of AF late recurrence were AF duration, pre-operative serum B-type natriuretic peptide (BNP), pre-operative heart rate and left atrial diameter (LAD), post-operative atrial tachyarrhythmias and AF at discharge. According to receiver operating characteristic curve analysis, the best cutoff values for AF duration, BNP, heart rate and LAD were 66.5 months, 251 pg/ml, 82 beats/min and 67.9 mm, respectively.Longer AF duration, larger LAD, higher BNP level and lower heart rate indicated a poor late outcome of surgical radiofrequency ablation in persistent AF patients undergoing cardiac valve surgery. Therefore, indication to radiofrequency ablation should be carefully considered in these patients.The online version of this article (doi:10.1186/s13019-017-0627-z) contains supplementary material, which is available to authorized users. Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in patients undergoing cardiac valve surgery, contributing to increased risks of systemic embolization, anticoagulant-related hemorrhage and mortality . The MazMost randomized trials have demonstrated an excellent conversion rate of the sinus rhythm (SR) with surgical radiofrequency ablation , but 20%We consecutively recruited 510 valvular AF patients with written informed consent admitted to the Affiliated Drum Tower Hospital of Nanjing University Medical School between April 2010 and November 2014. A pre-ablation 7-day Holter and comprehensive transthoracic echocardiographic examination were performed to establish that all patients had persistent valvular AF. The study was conducted according to the Helsinki Declaration and approved by the ethics committee of Nanjing University.Complete clinical data were collected before discharge. There were 114 patients excluded: 11 cases died in hospital due to low cardiac output syndrome and multiple organ failure; 2 cases died of sudden death after discharge; 2 case died of heart failure after discharge; 8 cases died of trauma or cerebrovascular accident; 7 cases had a history of implanted pacemaker before surgery; 8 cases received pacemaker implantation because of sinus long-intermission rhythm and advanced atrioventricular block. And another 76 cases were lost at follow-up. Therefore, a total of 396 patients had complete follow-ups and clinical information.All surgical procedures were performed in standard fashion by the same surgical team through median sternotomy. All patients underwent either a mitral valve repair or replacement by cardiopulmonary bypass with a mild hypothermia (32-34 °C), antegrade cold blood cardioplegic arrest, and local hypothermia with ice-slash; cardioplegic solution was readministered every 20 to 30 min. Radiofrequency ablation was performed using a mono-polar radiofrequency device . Left and right atrial appendages and the ligament of Marshall were incised routinely. We did vertical right atrial incision between the superior and inferior vena cava in all patients. Maze IV was performed before the other intra-cardaic procedures. The lines performed included isolation of the right and left pulmonary veins firstly and the connective lines between them. Next lines were from isolating line of the left pulmonary vein to the base of left atrial appendage amputation site and to the posterior mitral valve annulus. In the right atrium, the isthmus ablation runs from the inferior caval vein, across the interatrial septum, up to the caudal aspect of the coronary sinus ostium and over to the posterior tricuspid valve annulus. If patients had a huge left atrium, we would add several auxiliary ablation lines across left atrial roof and posterior wall. Epicardial temporary pacing wires were implanted in all patients.Heart rhythm was continuously monitored after surgery. Dual-chamber stimulation at 80 bpm through epicardial temporary pacing wires was used in most of patients for the first 48 h post-operatively to avoid severe brady arrhythmias. After that, all patients received amiodarone and metoprolol to stable rhythm except these patients whose heart rate is too slow to tolerate these antiarrhythmic drugs. AF recurrences after surgery were treated by resuming amiodarone infusion and correcting, in the case, electrolyte abnormalities. In patients in whom AF persisted despite optimal medical therapy, at least one attempt of electronic cardioversion was performed before discharge.Late recurrence was defined as any episode of AF, atrial flutter or atrial tachycardia that lasted greater than 30 s at least 6 months after surgery . AF-free2 test was utilized for categorical variables. Cox survival regression model was used to determine factors predictive of AF late recurrence. Factors for which the univariate analysis gave a p value ≤0.1 were included in the multivariate analysis. Hazard ratio (HR) and 95% confidence interval (CI) were calculated. Youden index (Sensitivity + Specificity-1) of receiver-operating characteristic (ROC) curve was calculated to single out the best cutoff values of AF duration, pre-operative B-type natriuretic peptide (BNP), pre-operative heart rate and left atrial diameter (LAD) predicting AF late recurrence. Sensitivity, Specificity and Accuracy were investigated by the Fisher’s exact test. Survival curves for the incidence of AF recurrence by AF duration, pre-operative BNP, pre-operative heart rate and LAD were calculated with the Kaplan-Meier method and a log-rank test was used to assess statistical significance. p < 0.05 was considered statistically significant, and all statistical tests were two-sided. The statistical analysis was performed with the GBSTAT statistical analysis package .For the comparison between the two groups, Student’s t–test  or Mann–Whitney test  was used for continuous variables, and χn = 245, AF group n = 151, see Table The 396 patients were divided into two groups according to whether AF late recurrence took place or not , 251 pg/ml , 82 beats/min  and 67.9 mm , respectively (Table p < 0.001). However, Patients with pre-operative heart rate > 82 bpm had a much lower proportion of AF late recurrence than patients with pre-operative heart rate ≤ 82 bpm (p < 0.001)  Fig. .Fig. 1KaSurgical ablation of valvular AF by means of radiofrequency is a well-accepted strategy to treat concomitant AF. Bando et al. in a study of 812 patients, who had undergone mitral valve replacement and Maze procedure, reported a 97% 8-year freedom from stroke in presence of restored SR as compared with 89% in presence of recurrent AF , 10. MorLate outcomes for our group after radiofrequency ablation were encouraging. Our 61.8% success rate at an average follow-up time of 28 months compares similarly with other literature reports . AlthougIn present investigation, we found a lower sinus conversion rate was associated with a longer AF duration and a larger LAD. Of particular interest, left atrial size and AF duration are significantly and mutually related to each other. Many clinical investigations have recognized left atrial dilatation as a cause of AF . Left atBaseline serum BNP had been previously found predicting short-term recurrence in patients undergoing catheter ablation of AF . Herein,Herein, we also found that early post-operative atrial tachyarrhythmias and AF at discharge was another two predictors for late recurrence of AF. It was in agreement with the results of previous reports , 23. TheMoreover, pre-operative lower heart rate (≤82 bpm) was found for the first time as a risk factor for predicting late recurrence of AF in our population. Heart rate was collected from the average ventricular rate of a preoperative 7-day Holter. The possible mechanism is that the function of sinus node is degrading in patients with chronic AF. The effective refractory period, which is associated with the formation and maintenance of atrial reentrant cycle, is prolonging accompanied with the advance of degraded sinus node . Thus, bSeveral limitations of this study require consideration. First, the nonrandomized design may have affected the results because of unmeasured confounders, procedure bias or detection bias, despite the use of rigorous statistical adjustment. Second, because of the initial deficiency of mono-polar radiofrequency device, defined as the lack of intra-operative lesion integrity assessment, it may have left some patients with gap lesions, ultimately affecting outcome. Third, all procedures were performed in a single institution. A related potential bias may result from the reliance on self reporting. So a multi-center study with a large population is warrant to confirm our findings. Moreover, observed freedom from AF varies with the rigor of rhythm assessment. As compared with continuous long-term monitoring, spot electrocardiographic recordings tend to overestimate success by approximately 12 percentage points . TherefoOur data suggest that indication to surgical treatment of AF should be carefully weighted in patients with long AF duration, pre-operative high serum BNP level, low heart rate and enlarged left atrium. Early post-operative atrial tachyarrhythmias and AF at discharge indicate a worse late outcome of surgical radiofrequency ablation. Thus, identification of these risk factors may improve selection of subjects to obtain long-term results in patients with persistent AF undergoing cardiac valve surgery.


DYS) and non-ischemic fibrosis (NIF). Echocardiography (echo) is widely used to assess iMR, but performance of different indices as markers of RVDYS and NIF is unknown.Ischemic mitral regurgitation (iMR) predisposes to right ventricular (RV) pressure and volume overload, providing a nidus for RV dysfunction (RViMR patients prospectively underwent echo and cardiac magnetic resonance (CMR) within 72 hours. Echo quantified iMR, assessed conventional RV indices , and strain via speckle tracking in apical 4-chamber  and parasternal long axis orientation (transverse strain). CMR volumetrically quantified RVEF, and assessed ischemic pattern myocardial infarction (MI) and septal NIF.DYS (EF<50%) on CMR among whom LVEF was lower, PA systolic pressure higher, and MI size larger . CMR RVEF was paralleled by echo results; correlations were highest for RV-GLS (r = 0.73) and lowest for RV-S’ . RVDYS patients more often had CMR-evidenced NIF . Whereas all RV indices were lower among NIF-affected patients , percent change was largest for transverse strain (48.3%). CMR RVEF was independently associated with RV-GLS  and transverse strain  . Overall diagnostic performance of RV-GLS and transverse strain were similar , and yielded near equivalent sensitivity and specificity (85%|83% and 80%|79% respectively).73 iMR patients were studied; 36% had RVCompared to conventional echo indices, RV strain parameters yield stronger correlation with CMR-defined RVEF and potentially constitute better markers of CMR-evidenced NIF in iMR. DYS). Echocardiography (echo) is widely used to assess iMR, but performance of different indices as markers of RVDYS and tissue remodeling has not been fully elucidated. Given that RVDYS impacts morbidity and mortality ) and septal NIF among patients with iMR; (2) compare the ability of conventional and multiplanar strain RV echo indices to act as markers of CMR-defined RVDYS and NIF.This study examined RV performance among a prospective cohort of patients with iMR undergoing echo and CMR. Goals were to (1) assess prevalence of CMR-evidenced RV2) were excluded. Clinical indices (including prior MI and coronary revascularization) were attained in a standardized manner using uniform patient questionnaires (administered by research personnel at time of study imaging) and supplemented by review of medical records.Patients were enrolled prospectively from September 2015 to May 2016 as part of an established protocol examining iMR associated remodeling—approximately 20% of patients recruited agreed to enrollment. Eligible patients had documented history of MR (≥mild) and were recruited from those being considered for invasive coronary angiography at Weill Cornell Medical College, in the context of known obstructive coronary artery disease (CAD) or abnormal stress test. All patients had either obstructive CAD based on angiography or prior history of coronary revascularization/myocardial infarction (MI). Patients with primary MR , papillary muscle rupture, prior mitral valve replacement, or contraindications to CMR  or gadolinium . The Cornell Institutional Review Board approved this study (Protocol #: 1505016238R002), which was in compliance with the Declaration of Helsinki. Written informed consent was obtained at time of patient enrollment.Echo and CMR were performed within a 3-day (72-hour) interval using a standardized protocol:DYS by each parameter  | 30–40%: 23% [n = 6] | 41–49%: 58% [n = 15]). Obstructive CAD was confirmed via invasive angiography in 95% (69/73) of patients (84% multivessel CAD)–all remaining patients had a history of prior PCI and/or ECG/imaging localized inferolateral MI. Clinically reported MI was present in nearly 2/3 (64%) of patients . MI incidence as identified by DE-CMR (i.e. CAD pattern infarction) was slightly higher (83%) than that of clinical MI: Nearly a third of patients in the overall cohort (29%) had multiple DE-CMR evidenced infarcts in distinct coronary arterial territories.The population comprised 73 patients with iMR who underwent CMR and echo within mean interval of 0.2±0.6 days (96% same day). Over one third (36%) of patients had RVDYS. As shown, patients with RVDYS were similar with respect to CAD risk factors, but were more likely to require heart failure medications such as ACE inhibitors or loop diuretics, consistent with larger MI size and higher pulmonary artery (PA) pressure . Both CMR and echo demonstrated patients with RVDYS to have more advanced adverse LV remodeling, whether measured by LVEF or LV chamber size (both p<0.05). Consistent with this, MR severity was strongly linked to RV contractile impairment, as evidenced by nearly a 2.5-fold increase in prevalence of advanced (≥moderate) MR among patients with, compared to those without, RVDYS . In multivariate analysis, RVDYS was independently associated with advanced MR  even after controlling for magnitude of CMR-defined LV dysfunction (OR 2.0 per 10-point decrement in LVEF [CI 1.4–2.6] p< 0.001)   independent of global LV dysfunction  .p<0.001) . SubstitRV volumetric measurements were compared to echo strain and conventional indices of RV performance as measured in apical 4-chamber orientation: Nearly all exams (93%) yielded full datasets inclusive of TAPSE, RV-S’, FAC, and RV-GLS. RV-GLS, in particular, was obtained in 97% (71/73) of exams.DYS. As shown, whereas all echo variables differed significantly between groups , percent changes were larger for longitudinal strain compared to conventional indices. For example, RV-GLS was 1.6-fold lower among patients with RVDYS, whereas TAPSE, RV-S’ and FAC yielded differences of 1.3–1.4 fold. Consistent with this, data shown in DYS . Patients with NIF had more advanced RVDYS and adverse remodeling on cine-CMR, as evidenced by lower RVEF , larger chamber size , and higher PA pressure . Regarding distribution, NIF most commonly localized to the anteroseptum (anteroseptum only: 59%|inferoseptum only: 12%|anterior and inferoseptum: 29%).Despite angiographic-evidenced CAD, tissue characterization via CMR demonstrated septal NIF to be common in patients with iMR: NIF was present in 24% of the population, and was 8-fold more common in patients with RVGiven that NIF commonly localized to the anteroseptum (not encompassed via 4 chamber orientation), strain analysis was also performed in PLAX . PLAX derived RV transverse strain was obtainable in 92% (67/73) of exams.Reproducibility was good for both RV-GLS and transverse strain, with small mean differences  although limits of agreement were wider for transverse strain than for RV-GLS  .DYS –magnitude of difference in terms of “effect size” was equivalent to that yielded by RV-GLS . Consistent with this, data shown in As shown in Diagnostic performance parameters of strain and conventional indices are reported in DYS. Major findings are as follows: (1) Among a cohort of patients with iMR, RVDYS was common and strongly associated with LV dilation and contractile dysfunction  measured by both CMR and echo. (2) Conventional and longitudinal strain indices differed between patients with and without CMR-evidenced RVDYS, but RV-GLS yielded higher correlations with RVEF (r = 0.73) than did FAC, TAPSE, and RV-S’ . Transverse strain yielded similar correlation with CMR RVEF  as did RV-GLS, as well as similar overall diagnostic performance for RVDYS (EF<50%) . (3) Despite epicardial CAD, patients with iMR commonly had CMR-evidenced NIF (24%), which was 8-fold more prevalent among those with RVDYS . NIF was associated with lower RV-GLS (measured in 4-chamber orientation) and transverse strain (measured in PLAX) (both p<0.001). Percent change between patients with and without NIF was highest for RV transverse strain (48.3%) compared to RV-GLS (34.0%), TAPSE (26.3%), RV-S’ (23.3%), and FAC (27.9%).This study yields new insights regarding RV pathophysiology in patients with iMR, as well as novel echo methods for assessment of RVDYS reflects a global process in patients with iMR (due to regurgitation-associated increments in RV afterload) that can be well assessed via multiplanar imaging.Our finding of an association between volumetric RVEF and transverse strain–a measure of RV free wall contractility–builds upon a growing body of literature concerning utility of multiplanar echo for RV assessment. 3D echo has been shown to improve RV quantification compared to conventional echo approaches derived from data acquired in a single orientation, and yield improved agreement with CMR –36. UtilDYS have demonstrated stronger correlations between echo strain and CMR. For example, among 57 patients with ischemic cardiomyopathy (LVEF<40%), Park et al. reported that RV-GLS correlated well with CMR RVEF (r = 0.80)  Pr = 0.80) , consistDYS) had NIF identified by CMR tissue characterization. To the best of our knowledge, this is the first study to assess the impact of NIF on RVDYS in the setting of patients with iMR as well as its relationship with RV strain. Our finding of an association between NIF and iMR is consistent with prior basic science studies showing MR to induce up-regulation of pro-inflammatory cell-signaling pathways promoting adverse remodeling [DYS. Among patients with non-ischemic cardiomyopathy, Taylor et al. demonstrated NIF to be associated with decreased global LV circumferential strain (p = 0.004) as measured via feature tracking CMR [Beyond RV function, it is important to note that whereas our cohort consisted of iMR patients with epicardial CAD, 24% of all patients . Given that apical 4 chamber derived measurements are increasingly being applied for analysis of segmental RV strain [DYS in this subgroup differed from the remainder of our population and that heterogeneity in prior revascularization confounded our results. Moreover, our study population underwent imaging at a single center, and clinical status or prognostic outcomes in this cohort were not tested in relation to either RV function or NIF.Several limitations should be noted. First, this study assessed RV physiology in patients with iMR and thus it is uncertain whether results can be extrapolated to other etiologies of MR. On the other hand, a primary sequela of MR (irrespective of etiology) is right-sided pressure and volume overload–known stimuli for RVV strain , future V strain –36, its V strain ,45, it iDYS in patients with iMR is commonly associated with NIF on CMR and provides proof of concept concerning utility of multiplanar strain assessment for evaluation of RVDYS and altered tissue substrate. Further studies are warranted to elucidate novel structural risk factors for iMR itself, whether NIF or strain based indices distinguish between iMR patients with persistent or reversible RV functional impairment, as well as prognostic implications of RVDYS among patients with iMR.In conclusion, this study demonstrates that RV


Left ventricular longitudinal strain (LVLS) is a modern measurement for LV function. However, strain measurement is often difficult in critically ill patients. We sought to show LVLS can be estimated using M-mode-derived longitudinal wall fractional shortening (LWFS), which is less dependent on image quality and is easier to perform in critically ill patients.n = 50) and was validated in a separate validation set (n = 30).Transthoracic echocardiographic records were retrospectively screened and 80 studies suitable for strain and M-mode measurements in the apical 4-chamber view were selected. Longitudinal wall fractional shortening was derived from conventional M-mode (LWFS) and curved anatomical M-mode (CAMMFS). The relationships between LVLS and mitral annular plane systolic excusion (MAPSE) and M-mode-derived fractional shortening were examined using univariate generalized linear model in a training set . LWFS was the best unbiased predictor for LVLS . Intra- and inter-rater agreement and reliability for LWFS measurement were good.MAPSE, CAMMFS, and LWFS demonstrated very good correlations with LVLS  contains supplementary material, which is available to authorized users. Global longitudinal strain (GLS) is a modern clinical utility that has superior sensitivity in detecting early cardiac dysfunction before clinical manifestations , 2. For Myocardial strain is most commonly defined as “deformation of the myocardium” and is usually measured by speckle-tracking echocardiography in modern machines , 7. To mMitral annular plane systolic excursion (MAPSE) is a reliable marker for LV systolic function and is less dependent on image quality . We proped is the ventricular length for the entire U-shaped LV at end-diastole and Les is the LV length at end-systole  is the change in length, which is the sum of the change in length in both the medial (∆Lmed) and lateral (∆Llat) walls:From Fig. The negative sign represents myocardial shortening. LVLS can thus be re-written as:ed and CAMMLes are the largest and smallest separations of the medial and lateral mitral annuli, and represent the end-diastolic length and end-systolic length of the LV, respectively  measurements. Figures ely Fig. . We defied ≈ Led and CAMMLes ≈ Les, it follows thatBy comparing Eqs.  and 4),,4), sincmed and MAPSElat are approximately equal to ΔLmed and ΔLlat, respectively. Therefore,MAPSE is the longitudinal excursion of the mitral annulus from end-diastole to end-systole Fig. . Comparitotal) is:Figure LV longitudinal wall fractional shortening (LWFS) is defined as:total approximates Led  records retrieved from the Intensive Care Unit Cardiovascular Ultrasound Laboratory in a tertiary hospital in Sydney.n = 21), inadequate study quality (n = 31) and angulated heart axis (n = 15) were the main reasons. “Inadequate study quality” includes studies that did not satisfy any of points (2) to (7) of the inclusion criteria.TTE studies between June to November 2016 were screened for suitability for inclusion into the study. To cover a wider range of LVLS, hence predictability, a priori decision was made to extend the range of LVLS by including approximately 40% of TTE studies that showed abnormal LV systolic function, defined as the presence of one or more segmental wall dysfunction or LV ejection fraction (LVEF) < 50%. Inclusion criteria were: (1) the TTE study must contain a apical 4-chamber (A4C) view with at least three cardiac cycles recorded, (2) the image quality must be of adequate quality to allow successful speckle tracking , (3) all LV inferoseptal and anterolateral segments and the mitral annulus must be visible throughout the cardiac cycle, (4) the LV long axis must lie along the midline of the sector for proper M-mode measurement, (5) the LV should not be foreshortened, (6) there should not be significant translational artefacts causing out-of-plane displacement, (7) the two-dimensional (B-mode) frame rate must be 50 fps or higher, and (8) the patient must be in sinus rhythm. A total of 127 studies (patients) were included in the first round of screening for LV systolic function. Of these, 65 patients had abnormal LV systolic function. Forty-seven studies were excluded upon further screening for quality. Most of these studies were excluded for more than one reason: low frame rate  and EchoPac software  was used for analysis. LVLS from the A4C were measured offline using speckle tracking. One complete cardiac cycle, excluding the first and the last cycles, was used in strain analysis. After optimizing the overall gain, the endocardial border was traced manually from the medial to the lateral mitral annulus making sure the trabeculae and papillary muscles were excluded. The width of the region of interest was adjusted to exclude the pericardium. The software automatically tracked the myocardial speckles and calculated the LVLS. For comparison, LVEF in this study was measured using Simpson’s monoplane method in the A4C view.ed and CAMMLes were the distances (ventricular lengths) between the medial and lateral annuli at end-diastole and end-systole, respectively. Inner edge was used in the measurements and post-systolic shortening was excluded when measuring CAMMLes . 95%CI was presented wherever possible and when effect size was more informative, otherwise P value was presented  and ± 3.539, respectively. The ICC was 0.91 . These indicate non-bias agreement and good intra-rater reliability. On the other hand, very small but insignificant bias was observed between two independent observers . Good inter-rater reliability was observed .The present study shows that, using univariate linear model, both CAMMFS and LWFS exhibited very good correlations with LVLS in the apical 4-chamber view. Between CAMMFS and LWFS, the latter provides a better goodness-of-fit with LVLS. LWFS measurement was repeatable and reliable.To date, strain studies in critically ill patients are scarce. Most studies were performed on intensive care septic patients . The mair = 0.76). A similar correlation between LVEF and LVLS (r = 0.7) has been reported recently [The present study supports the notion that LVLS and longitudinal M-mode indices  are closely related and highly correlated with each other. The results are not surprising because all of these indices, including LVLS, measure the motion of myocardial in the longitudinal plane. On the other hand, the correlation between LVEF and LVLS was also highly correlated but less ideal than M-mode indices (recently . One expsum with LVEF (r = 0.70). Although MAPSE only demonstrates the longitudinal motion of the LV, it was more sensitive than LVEF in detecting early LV dysfunction, such as in hypertensive patients [sum with LVLS (r = 0.82).MAPSE was first described in 1932 by Hamilton and Rompf as caudal-cephalad movement of the atrioventricular plane . Since tpatients , 27. In patients . Similarpatients , the prelat/left ventricular length (MAPSE/L) as an index for LV longitudinal function in children where adjusting for age-dependent ventricular length is important, GLS was found to be moderately correlated with MAPSElat/L even when the study was not originally designed to investigate the relationship between the two (r = 0.56) [Theoretically, LVLS, CAMMFS and LWFS measures the same phenomenon – the change in LV length normalized to its original (end-diastolic) length. In a study that purported to use MAPSE = 0.56) .sum/MMVLtotal) exhibited very good correlation with LVLS in the training set (r = 0.909) providing supportive evidence that LWFS and LVLS are two closely related, if not similar, measurements. Using a separate validation set, LWFS displayed very good predictive capability  of longitudinal strain  used in LVLS measurement. Theoretically, MMVLtotal is always less than Led. However, in an average size LV, MMVLed and the Led differ by less than 10% . Unlike M-mode, averaging over consecutive cardiac cycles is time-consuming and impossible in irregular cardiac rhythm. However, speckle-tracking strain measurement is less susceptible to angle and translational artefacts and also gives segmental information. That said, false positives of segmental wall information have been described . Inter-vThis study implies that LWFS measurement offers an alternative measurement or method of estimating LVLS. As LWFS measures the longitudinal motion of the left ventricle, in theory, it may act as a prognostic tool and offers similar sensitivity in detecting early LV systolic dysfunction as LVLS. It has the potential to be used as a follow-up tool for subclinical myocardial dysfunction and to evaluate the treatment effects. In this regard, LWFS can be useful in deciding when to initiate or terminate inotropes.Inter-vendor inconsistencies are known to be a major issue in strain measurements and may affect the applicability of the prediction model (equation). The inconsistencies are mainly due to different definitions and algorithms used by different vendors , 31. EveAs this was a retrospective study, we were unable to determine the true feasibility of measuring LWFS in ICU patients. Many echocardiograms (37%) were not optimized for the purpose of measuring LWFS and LVLS in this study. As a result, they were excluded due to inadequate image optimization, low frame rate, deviated heart axis and foreshortened apical view. Although patient characteristics played a contributory role in image quality, the experience of the echocardiographers, some of whom were receiving basic level critical care echo training, also contributed. We expect the feasibility of measuring LWFS should improve with experience. Also, as the apical 2 and 3 chamber views were not optimized for strain or M-mode measurement purposes, we were not able to obtain GLS and a “global” LWFS value for comparison. Theoretically, “global” LWFS should have a similar predictability capacity as LWFS in this study. Unfortunately, we were unable to determine the true feasibility of LWFS measurements when compared to LVLS, which is best done in a prospective study on consecutive patients. We were also unable to track the changes in LV systolic function with treatment.For the purpose of this association study, the patients (studies) included in this study were not randomly selected and hence subject to selection bias. First, we selected only those studies which were optimal for LVLS and M-mode measurements, hence might have excluded those very sick and difficult patients. Second, to extend the predictable range, we deliberately included a large proportion of patients with abnormal LVEF (approximately 40%), thereby creating two distinct populations. These patients were unlikely to represent the usual mix of ICU patients. We omitted presenting the clinical data and treatment data which could be biased and misleading in this study. Of note, this selection bias did not affect the validity of the model as diagnostic tests on the assumptions of normality, equal variance and linearity were not violated.This study demonstrated that LWFS is an unbiased predictor of LVLS. In fact, indices that measured LV longitudinal function, namely MAPSE, CAMMFS and LWFS, displayed good correlations with longitudinal strain in this study. Compared to speckle-tracking strain measurements, LWFS only requires simple M-mode measurements which are reproducible and reliable, requires minimal training and are available in all machines. LWFS could potentially be a useful index for clinical use. Research into the clinical utility of LWFS is however required.


Cardiac involvement of sarcoidosis hallmarked by inflammatory myocardial processes and subsequent fibrotic myocardial alterations is a life threatening condition that makes early diagnosis favorable. Native T1- as well as T2-mapping have been proposed as reliable methods to non-invasively assess diffuse myocardial fibrosis and edema respectively. Our aim was to examine the value of both methods for the differentiation between healthy and diseased myocardium.Patients with sarcoidosis who previously underwent a CMR examination at our hospital were invited for a follow up scan. The follow up scan performed on a 1.5T Philips INGENIA scanner comprised a clinically routine CMR-protocoll with additional T1- and T2-mapping in midventricular short axis (SA) slice. T1-mapping was performed using MOdified Look Locker Inversion Recovery Imaging (3-3-5 MOLLI) and T1-relaxation times were quantified within the septal myocardium (CONSEPT-approach). For T2 mapping an optimized 6-echo gradient spin echo (GraSE) sequence was used measuring T2 relaxation times within the whole SA slice. CMR exams were classified as "cardiac involvement" if at least one of the following pathologies occured: pathological relative enhancement, late enhancement findings consistent with (post-) inflammatory changes, myocardial edema, pericardial effusion. According to CMR results patients were divided into 4 different groups: group 1 (n = 10): patients with positive findings in both exams, group 2 (n = 6): patients with positive findings only in the initial exam; group 3 (n = 8): patients with sarcoidosis but inconspicuous initial CMR exam and group 4 (n = 20): a control group of healthy age matched volunteers with no medical history of sarcoidosis or cardiac disease.Results are shown in Table T1 relaxation times were significantly longer in patients with positive CMR findings in both the initial examination and the follow-up scan (group 1) in comparison to all other groups . However no significant difference in T1 relaxation time could be revealed in patients with history of cardiac involvement of sarcoidosis (group 2) as well as patients with sarcoidosis but no CMR findings . No significant difference in T2 relaxation times could be revealed between all 4 groups .Patients with consistent cardiac involvement of sarcoidosis have significantly increased T1 relaxation times as a sign of diffuse cardiac fibrosis whereas no relation between diffuse myocardial edema and cardiac involvement of sarcoidosis could be revealed.


The aim of this study was to investigate whether STONE sequence is useful for the assessment of regional variability of LV native T1 time in HCM patients.The presence of myocardial fibrosis is associated with worse clinical outcome in hypertrophic cardiomyopathy (HCM) patients. Due to the substantial variations in left ventricular (LV) wall thickness and fibrosis in HCM, volumetric coverage of entire LV myocardium is essential for the accurate assessment of myocardial fibrosis. Slice-interleaved T1 mapping was performed using STONE sequence which enables acquisition of 5 slices in the short-axis plane within a 90 sec free-breathing scan. The sequence was acquired in a free-breathing ECG-triggered slice-selective bSSFP with the following parameters: 5 slices, in-plane resolution = 2.1x2.1 mm2, slice thickness=8 mm, slice gap=4 mm, field of view=360x352 mm2, TR/TE/α=2.8 msec/1.4 msec/70 ;, SENSE-factor=2, linear ordering, 10 linear ramp-up pulses and acquisition window=240 msec. We measured LV native T1 time and maximum LV wall thickness in each 16 segments from 3 slices . Late gadolinium enhanced (LGE) MRI was acquired to assess presence or absence of myocardial enhancement.Twenty-four septal HCM patients (56 ± 16 years) and 10 healthy adult control subjects (57 ± 15 years) were studied. Native T1 time was significantly elevated compared to healthy controls, regardless of presence or absence of LGE  segments (n = 27), 1139 ± 55 msec; LGE (-) segments (n = 351), 1118 ± 55 msec; healthy control (n = 160),1065 ± 35 msec; p < 0.001 by one-way ANOVA, 6 segments were excluded from analysis due to artifacts). Among 351 segments without LGE, native LV T1 time was diffusely elevated over the 16 segments . Significant positive correlation was found between LV wall thickness and native LV T1 time .In HCM patients, LV native T1 time, and native T1 time was correlated with LV wall thickness. Slice-interleaved T1 mapping by using STONE sequence could be advantageous to overcome limited cardiac coverage of conventional single-slice T1 mapping technique and to accurately detect the diffuse myocardial fibrosis in HCM patients.In HCM, substantial number of segments without LGE showed elevated native T


Delayed washout of Gadolinium (Gd) contrast in the presence of myocardial scar, fibrosis, or infiltration is the basis for late Gd enhancement (LGE) imaging using cardiovascular magnetic resonance (CMR). It is also known that shortening of native, non-contrast myocardial T1 time is proportional to the degree of myocardial damage. We thus hypothesized that, compared to normal myocardium, native, non-contrast myocardial T1 time would be significantly longer in areas that would have greater Gd deposits on LGE sequences. If confirmed, this approach could potentially be used to detect damaged myocardium without contrast enhancement in patients who cannot receive Gd-based contrast agents.18 patients  with cardiomyopathy were prospectively imaged using a 1.5-T scanner (Philips). Modified Look-Locker Imaging (MOLLI) was performed for T1 mapping prior to contrast administration. LGE images were obtained 10 minutes after the administration of Gd-based contrast using a T1-weighted gradient echo pulse sequence with a phase sensitive inversion recovery reconstruction . An inversion time between 250-300 ms was used to achieve nulling of normal myocardium. Both sets of images were acquired in the short axis plane at the left ventricular basal, mid and apical levels. T1 measurements (Medis) were made in triplicate on pre-contrast MOLLI images in a region of interest confirmed to have LGE and in an area of normal myocardium based on post-contrast images. T-tests were used to compare T1 times in areas with and without LGE .The reason for CMR included viability assessment in 11 patients, cardiac amyloid in 2 patients, non-ischemic cardiomyopathy evaluation in 3 patients, heart transplant follow-up in 1 and cardiac mass evaluation in 1. Mean T1 time in myocardial regions with LGE was 1269 ± 167 msec, in non-LGE segments 1032 ± 118 msec and in the myocardial cavity 1644 ± 113 msec (p < 0.001 LGE positive versus LGE negative segments). A difference in T1 times between LGE and non-LGE segments of <5 % was seen in one case of amyloid with diffuse LGE pattern and in one case of mid-wall stripe suggesting that in cases of diffuse and sparse LGE, T1 time may have difficulty in distinguishing between abnormal and normal myocardium.Measured T1 is significantly higher in non-contrast myocardium with confirmed LGE deposits than in normal myocardium. Our findings suggest that it may be feasible to use T1 times to identify regions of damaged myocardium in patients who cannot receive myocardial contrast such as in those with renal failure.


The objective of this systematic review was to analyze (1) prevalence of radiological posttraumatic arthritis (PA), (2) associations of PA with outcome measures and (3) predictors of PA following distal radius fractures in non-osteoporotic patients.Nineteen studies were included (10 open source data).N = 49, mean 14°, SD 6° versus N = 55, mean 17°, SD 6°, p = 0.037). No analysis could be performed regarding patient reported outcome measures, because of limited data. Articular incongruence was a significant predictor for PA.In total, 733 patients were described with a weighted mean age of 37 years (range 25–54) at the time of the injury. Follow-up ranged from 13 months to 38 years. Overall prevalence of PA was 50% and 37% in the open source data. Radial deviation was significantly worse in patients with PA (A high prevalence of PA was found in non-osteoporotic patients following a distal radius fracture. PA following a distal radial fracture was associated with a limited radial deviation and flexion, but not with grip strength. Articular incongruence predicted PA. Patient reported outcome measures should be investigated more thoroughly to be able to understand the value of using these instruments in interpreting outcome in follow-up of non-osteoporotic patients following a distal radius fracture.Level of evidence 3 (Phillips et al. Levels of Evidence—Oxford Centre for Evidence-based Medicine,  Distal radius fractures (DRFs) are common injuries. An annual incidence of 9/10,000 men and 37/10,000 women has been reported in patients aged 35 years and older , 3. In aRecent literature supports the hypothesis that increasing age is also an important risk factor for the development of PA . PA is tFunction following a DRF can be captured using clinician reported outcomes (CROs), such as range of motion (ROM) and grip strength. PA following a DRF was associated with poorer CROs in some studies , 14, 15.The patient’s opinion regarding wrist function, pain or satisfaction following a DRF can be captured in Patient Reported Outcomes (PROs). A number of studies did not find a significant association between PA and PROs , 18, 19.Conflicting results in literature have been presented on the association between outcomes and PA following DRFs. There is a need for better understanding of the clinical relevance of radiological PA following a DRF in non-osteoporotic patients. Determination of specific outcome measures predicting PA could be helpful in guiding individual treatment strategies and to decide what rehabilitation goals should be pursued in the follow-up of these patients. In addition, such outcomes could be used to prepare patients on the expected return of function and possible necessary adjustments in everyday life.The objectives of this systematic review were to analyze (1) the prevalence of PA following a DRF, (2) associations of PA with CROs and PROs and (3) predictors of PA following a DRF in non-osteoporotic patients.A systematic search of the literature was performed in PubMed, Embase, the Cochrane Library and PsycINFO without time restrictions, published until January 2015. The databases were searched with a combination of MesH terms regarding PA, CROs and PROs , which is initiated to evaluate the quality of non-randomized studies, such as case–control and cohort studies Table  28]. Th. Th28]. In all studies the classification for PA according to Knirk and Jupiter was applied; grade 0 represents no signs of PA and grade 3 representing bone-on-bone PA with osteophyte and cyst formation . To exclRange of motion was expressed in degrees. To minimize the effect of the different units of measurement of grip strength , grip strength of the injured wrist as a percentage of the uninjured wrist was calculated. No correction for dominance of hand was performed, in concordance with other studies , 29, 30.Characteristics of the PROs are described in Appendix 1.r, interpretation of effect size was performed using Cohen’s guideline  .–35.33–35ctively) . A moder= 0.029) . Five st= 0.029) , 36 In t= 0.029) , 37–39.N = 49, mean 14°, SD 6°) compared to patients without PA . All other outcomes regarding range of motion in the patients with and without PA did not differ with statistical significance  open source data, seven had data regarding ROM Table  10, 16,, 35, 37.r = 0.464, p = 0.034) [One out of the 18 studies describing grip strength found a moderate statistically significant association between severity of PA and diminished grip strength = 0.034) . In cont= 0.034) , 34, 36. . In conEight studies presented open data regarding grip strength Table  10, 16,, 35, 37.PROs were reported in few studies Table . It was r = 0.74, p < 0.001 and gap r = 0.70, p < 0.001; step r = 0.34, p < 0.05, respectively) [p = 0.02) [Eleven studies reported on predictors of PA following a DRF Table . Articulctively) , 39. Conctively) , 39, 40. = 0.02) . Gender  = 0.02) . One stu = 0.02) . Another = 0.02) .p < 0.001). Furthermore, patients with PA experienced statistically significant more often a residual step  or gap  (Table p = 0.026). All possible radiological predictors directly after fracture reduction and at the end of follow-up were not significantly associated with PA  52% of the patients had some kind of articular incongruence (step and/or gap). Patients with PA experienced statistically significant more often residual articular incongruence in comparison to patients without PA . In addition, this study shows that the prevalence of PA seems to worsen over time . Presence of PA was statistically significantly associated with diminished radial deviation and flexion, but not with grip strength. Unfortunately, no conclusions could be drawn regarding the association between PA and PROs, because of lack of data. An intra-articular step or gap had a statistical significant negative effect on the development of PA. No further associations between radiological predictors and PA were found using open source data. Operative treatment or arthroscopically assisted surgical treatment seemed to reduce the chance of developing PA , 33.The high prevalence of PA in this non-osteoporotic population is worrisome. However, from the included studies we could not derive sufficient information on the restrictions or limitations these patients experienced when executing activities of daily living, leisure time activities, work or other societal roles. Further research on PA in non-osteoporotic patients with DRF should elaborate on the impact of PA on patients’ activities or participation. Since most studies comprise of small study populations and because the open source data showed that a longer follow-up duration is associated with a higher prevalence of PA, specifically open source studies may provide unique chances to gather such data. However, currently no uniform set of evaluation instruments is available, which results in difficulty of pooling data.Wrist motion is dependent on complex articulations of the scaphoid, lunate and the radio carpal joint . BiomechNo conclusions could be drawn regarding the association between PA and PROs, because of limited data. This is indicative of a gap in knowledge on the clinical relevance of radiological PA as measured by PROs, despite the high prevalence of PA in this group.A high prevalence of PA was shown, and a longer follow-up duration was associated with a higher prevalence of PA. As such, development of PA seems to be a dynamic process and progresses over time. In addition, articular incongruence was predictive for PA: patients with a step or a gap had a higher prevalence of PA. This outcome resembles the conclusions drawn in studies regarding associations between articular incongruence and PA following a DRF –13. WhenThis study is the first systematic review presenting CROs and PROs and the association with PA following DRFs in non-osteoporotic patients. Because of the extent of this systematic review and the pooling of the open source data, we believe this study is a contribution to the insight in the prevalence and clinical relevance of PA in non-osteoporotic patients following a DRF. Recent literature has encouraged pooling of open source data from clinical trials and cohort studies and reporting this in systematic reviews and meta-analyses to compare outcome in a more reliable and efficient manner , 52. AltThe high prevalence rate of PA found in the (pooled open source) data shows that investigation of outcome in non-osteoporotic patients with a long active and working life ahead should have more attention. To direct treatment strategy, rehabilitation and to decide what an acceptable level of rehabilitation is in the follow-up of non-osteoporotic patients with a DRF there is a need for a reliable interpretation of PROs and the association with PA investigated by using randomized controlled trials with or without implementing pooling of open source data. For patients and therapists it would be of great value to be able to work towards an evidence-based rehabilitation goal. It would also be very beneficial to gain more insight in the influence of radiological characteristics following fracture reduction, such as radial shortening and radial inclination on CROs, PROs and PA.Half of all non-osteoporotic patients developed some degree of PA following a DRF. In addition, PA seems to progress over time. PA following a distal radial fracture was associated with a limited radial deviation and flexion, but not with grip strength. This suggests that rehabilitation should have a broad approach, with focus on wrist motion, and on learning to adjust daily activities to limited wrist motion to optimize functional recovery. Unfortunately no conclusions could be drawn regarding PROs and their clinical applicability in the follow-up of DRF in non-osteoporotic patients, because of limited data. PROs should be investigated more thoroughly to be able to understand the value of using these instruments in interpreting outcome in follow-up of these non-osteoporotic patients. Further research could produce evidence-based rehabilitation goals for patients and therapists. Treatment of DRF should be directed at avoiding articular incongruence, because of its statistically significant association with the development of PA. Conflicting results in literature have been reported on dorsal angulation, radial length, ulnar variance and radial inclination on predicting PA. More thorough research on other radiological factors predicting PA could show more insight on primary treatment goals to avoid PA in the follow-up of these young non-osteoporotic patients.


Left ventricular (LV) non-compaction (LVNC) is defined by extreme LV trabeculation, but is measured variably. Here we examined the relationship between quantitative measurement in LV trabeculation and myocardial deformation in health and disease and determined the clinical utility of semi-automated assessment of LV trabeculations.n = 91), using balanced steady state free precession cine imaging at 3T. The degree of LV trabeculation was assessed by fractal dimension (FD) as a robust measure of trabeculation complexity using a semi-automated technique. FD measures were determined in healthy men and women to derive normal reference ranges. Myocardial deformation was evaluated using feature tracking. We tested the utility of this algorithm and the normal ranges in 10 individuals with confirmed LVNC  and 13 individuals with suspected disease (NC/C ratio > 2.3).Cardiovascular magnetic resonance (CMR) was performed in 180 healthy Singaporean Chinese  after adjusting for age, sex and body mass index. Increased LV trabeculation was independently associated with reduced global circumferential strain  and global diastolic circumferential and radial strain rates . Abnormally high FD was observed in all patients with a confirmed diagnosis of LVNC. Five out of 13 individuals with suspected LVNC had normal FD, despite NC/C > 2.3.Fractal analysis is a reproducible means of assessing LV trabeculation extent . The overall extent of LV trabeculation  was independently associated with increased indexed LV end-diastolic volume and mass  contains supplementary material, which is available to authorized users. Left ventricular (LV) non-compaction (LVNC) is a clinically heterogeneous myocardial disorder characterized by increased LV trabeculation and deep inter-trabecular recesses that are in continuity with the LV cavity, but not the epicardium. In patients with LVNC, the myocardium appears as two distinct layers, consisting of a thick non-compacted endocardial layer, and a thin compacted epicardial layer , 2. ThouVariable degrees of LV trabeculation have been observed in other cardiac conditions, including dilated and hypertrophic cardiomyopathies –9, congeOf the modalities available for investigating LVNC, cardiovascular magnetic resonance imaging (CMR) offers a comprehensive assessment of myocardial anatomy, function, perfusion and tissue characteristics , 17. ItsPrior studies in healthy, asymptomatic population-based cohorts are equivocal on the functional consequence of LV trabeculations –27. ThouIn this study, we sought to examine the relationship between the extent of LV trabeculation, and myocardial morphology and function in healthy Chinese in Singapore using CMR to elucidate the functional and physiological consequences of LV trabeculations. We also sought to establish age- and sex-specific reference ranges for measures of LV trabeculations and myocardial strain that are currently not available in Asians. We hypothesized that the degree of LV trabeculation in healthy individuals is associated with reduced intrinsic myocardial function.n = 180) was based on a prior study establishing comprehensive CMR reference ranges for the heart and aortic root in Singaporean Chinese , as appropriate. Statistically significant clinical variables in the univariable analyses were entered in the multivariable linear regression to determine the independent association between FD and LV morphologic structures and myocardial strain. Reference ranges were defined as 95% prediction intervals using univariable linear regression between parameters and age, stratified by sex. Indeterminate regions were defined as the 95% confidence intervals of the upper and lower reference limits, to account for the effects of sample size on the reference range . All stan = 91) were analyzed. Clinical characteristics and cardiac measurements  of the healthy subjects are shown in Table CMR images of 180 healthy individuals .Trabeculation complexity from LV base to apex was evaluated by fractal analysis and shown in Fig. p = 0.02; males: sβ = 0.35, p < 0.001; height: sβ = 0.20, p = 0.01; weight: sβ = 0.40, p < 0.001; BMI: sβ = 0.41, p < 0.001). In the multivariable regression model, age, male sex and BMI were independent determinants of global FD . Normal age- and sex-specific reference ranges for LV trabeculation and myocardial deformation measures were established  was positively associated with age, male sex, height, weight and body mass index (BMI) , but not concentricity  and left atrial volume .Extent of LV trabeculations was associated with indexed LV end-diastolic and end-systolic volumes , . Global circumferential strain alone remained independently associated with global FD, after adjusting for age, sex and BMI . Conversely, global diastolic strain rates were reduced across all three dimensions . After adjusting for potential confounders , global diastolic circumferential and radial strain rates remained independently associated with global FD .Unlike global systolic strain, global systolic strain rates showed no significant association with global FD  had higher than normal FD values based on age- and sex-specific FD reference ranges we had established . The global FD was 1.270 ± 0.045 in those with suspected LVNC . Of note, five patients with suspected LVNC had normal FD (38%), despite a NC/C ratio of >2.3 , independent of age, sex and BMI.The clinically heterogeneous nature of LVNC has led to much difficulty in achieving a consensus over the diagnostic criteria, which are currently predominantly based on semi-quantitative LV morphology assessment. A recent classification grouped LVNC into 7 different entities, of which the presence of non-compacted (trabeculated) morphology with normal systolic and diastolic function, size and wall thickness is termed as isolated LVNC . In an oFractal analysis is a novel and more objective approach of assessing the extent of LV trabeculations. Captur et al. had developed a fractal analysis plugin for the OsiriX program . Our sem2 and older participants >45 years. Our population was more homogeneous (Singaporean Chinese) with a much wider age range (20–69 years). At least 15–20 individuals were systematically recruited in each age decile in either sex. We reported higher FD values in males compared to females and an association between FD and age, particularly in males. It is likely these findings were not observed in the MESA population because of the narrower age range in their study. The maximal apical FD in our study was 1.278 compared to 1.197 in Chinese Americans [In a recent study, Captur et al. demonstrated no association between FD and age, sex and allometric parameters. The extent of LV trabeculations varied with ethnicities, highest FD in African Americans and Hispanics and least in Chinese Americans . These oUsing fractal analysis as a more sensitive technique of assessing LV trabeculation, we examined the association between extent of LV trabeculation and myocardial structure and function in the healthy subjects. Unlike NC/C ratio, FD as a measure of LV trabeculation was associated with increased cardiac volumes and LV mass (more eccentric hypertrophy phenotype), but not LV concentricity. Although reduction in myocardial deformation has been shown in LVNC patients –39, our As fractal dimension provides a dimensionless representation of endocardial trabecular complexity, it may account for only part of the LVNC phenotype – prominent LV trabeculation and deep inter-trabecular recesses . The rolWe define here the normal FD reference ranges in healthy Chinese, which is of clinical utility for diagnosing LVNC and understanding normal variation of LV trabeculations in health. We show that increased myocardial trabeculation is independently associated with increased LV volumes, myocardial mass and reduced myocardial strain that could indicate the presence of subclinical myocardial dysfunction. This suggests increased LV trabeculations likely represents a continuum of functional effects in health and disease.


TM . CardioMEMSTM is a wireless pulmonary artery pressure (PAP) monitoring device, which continuously monitors PAP and transmits data to a healthcare provider. It rapidly identifies changes in intracardiac pressure and allows timely pharmacological management. CardioMEMSTM showed a higher reduction of HFH compared to any other devices.Heart failure (HF) is one of the leading causes of morbidity and mortality and has a large effect on the country’s economy. Although there have been major advances in HF monitoring, including more advanced pharmacological management and device-based therapy, HF-related mortality remains high. It is important to monitor HF so that HF-related hospitalization and mortality can be prevented. Due to the lower sensitivity of clinical features and biochemical markers, as well as the failure of telemonitoring in early detection of HF, more advanced techniques have been sought to more accurately predict impending HF, in order to address timely pharmacological management and prevent heart failure hospitalization (HFH). Device-based therapy has passed through various stages and culminated in the recently introduced CardioMEMS Heart failure (HF) is a clinical syndrome characterized by the inability of the heart to meet the metabolic demand of the body either by left ventricular dysfunction or right ventricular (RV) dysfunction. The prevalence is 5.8 million in the US and over 23 million worldwide . The incTM  detects cardiac filling pressure. These devices detect rising cardiac filling pressure days/weeks before the symptoms, allowing the healthcare provider to intervene in order to prevent HF hospitalizations [TM Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in New York Heart Association (NYHA) functional Class III Heart Failure Patients” (CHAMPIONS) trial [TM in the patient with chronic HF, NYHA functional class III to reduce HFH [Implantable hemodynamic monitoring device such as CardioMEMSizations . Severalizations -14. PulmS) trial . These eS) trial . HFH wasS) trial . Hence iduce HFH .History and PhysicalThe history and physical examination often help in the diagnosis of HF. The patient often presents with shortness of breath, paroxysmal nocturnal dyspnea, orthopnea, crackles, third heart sound, jugular venous distension, weight gain, and edema, but these features have limited sensitivity and are considered a late manifestation of HF Table . Using sBiochemical MarkersUse of biochemical markers to reduced HFH is still under consideration, but data is still under debate. There is no specific threshold level for these markers. Initially, Lainchbury, et al. compared N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) guided medical therapy with clinically guided medical therapy and usual care, and interestingly found decreased HF-related mortality in patient with NT-pro-BNP guided medical therapy . This beEchocardiographyWith further advancement in the medical sciences, echocardiography has been used in the management of HF in order to prevent HFH. It has its own drawback of cost, intra-observer variability, quality of the echocardiographic picture, patient anatomical characteristics, obesity, and accuracy of the test.Right Heart CatheterizationRight heart catheterization (RHC) has been increasingly used in measuring filling pressure and volume status of the patient, which provide indispensable information in guiding medical therapy in HF patient. However, its utility is limited due to invasive nature and risk of the procedure Table .Cardiac implanted electronic devices (CIEDs) are being evaluated to provide ambulatory monitoring of HF. These devices are a closed system consisting of a “sensor” to sense the response and an “effector” to initiate a response. The sensor can take different forms, including a patient, a provider, and/or a device with each form having its own advantage and disadvantage. The main advantage of a device includes continuous monitoring, objective metrics without bias and provides patient specific information Table .Electrophysiological SensorsMost commonly used CIEDs are pacemaker and defibrillator. They have the capability of sensing certain atrial and ventricular arrhythmias. Through the closed-loop system, they sense and provide appropriate response either pacing or shock. Treating arrhythmias can have a stabilizing effect on HF. Monitoring other electrophysiological variables may have a role in predicting and preventing acute decompensated HF (ADHF). As increased mean heart rate has been demonstrated before ADHF, with a returned back to baseline once ADHF is treated . Such heHemodynamic Monitoring SensorsThe main pathophysiology of ADHF is a rise in ventricular filling pressure, therefore the main focus of HF management is to lower the ventricular filling pressure without affecting cardiac output. Historically, an RHC was required to monitor hemodynamic status. This led to the development of implantable cardiac filling pressure monitoring devices. These devices have been shown to provide information almost comparable to an RHC . Early wTM Monitoring for HFCardioMEMSTM is a wireless device that monitors PAP. It is implanted in the distal pulmonary artery via an RHC. It has been seen that PAP measured by CardioMEMSTM device correlates with PAP measured by Swan-Ganz and echocardiography [TM was investigated was in the CHAMPIONS trial [TM device worked well without any sensor failure and a lower complication rate. This is the first sensor-based device which demonstrated a significantly lower risk of HFH. Due to this success, in 2014 the FDA approved the use of CardioMEMSTM sensor implant in patients with HFpEF and HFrEF with NYHA class III on optimal medical therapy and a history of HFH within the last year [TM sensor implant which led to appropriate and timely management with dose adjusted diuretics [TM sensor implant received maximal medical therapy including diuretics, vasodilators, and the neurohormonal antagonist [TM) with no implanted hemodynamic device and reported significant improvement of Kansas city cardiomyopathy questionnaire score and 6-minute walk test in the CardioMEMSTM group [CardioMEMSiography . The firNS trial , a multiNS trial . The Carast year . The rediuretics . Subgrouiuretics . During tagonist . Remote tagonist . This prtagonist . Surpristagonist . This evTM group . These fTM group . There wImproving survival with modern therapy has resulted in HF patients living longer with left ventricular assist devices (LVADs). The author further did sub-analysis of CHAMPIONS trial in order to assess the validity of PAP-directed therapy on optimization of medications, pump parameters, and timing of heart transplantation in the patient receiving LVAD . The datTM appears to be a leading innovation in the management of HF. However, given a small number of trials with small sample size, larger multicenter trials are required to make valid recommendations in order to reduce HFH, improve the quality of life, and decrease morbidity and mortality related to HF.HF continues to be a major public health problem with a significant financial burden on the country’s economy. As advances in medicine lead to longer life expectancy, more reliable and valid methods will be required to appropriately intervene in order to prevent HF-related hospitalization and death. Implantable hemodynamic devices are the newly emerging tools in the field of HF management. CardioMEMS


The efficacy of current and novel heart failure therapies is likely related to viability that denotes the presence of cardiac reserve. Previous studies assessed viability mostly on a segmental rather than patient level, and included hypokinetic segments, which by definition−given residual contractile function−are viable. Additionally, studies have suggested that long-term survival is affected by the presence of viability in akinetic, not hypokinetic, segments. Therefore, we aimed to assess viability among patients with myocardial akinesis referred for cardiovascular MRI (CMR).whole-heart" viability was defined as present if all 17 segments were deemed viable.Data analysis was performed on a cloud-based system that is currently receiving de-identified searchable data from reports with full DICOM datasets for 23,275 consecutive CMR exams performed at 4 U.S. hospitals from 2010-2014. At the time of abstract submission, 8,242 CMR datasets have been analyzed, and analysis of all 23,275 is expected by the end of 2015. All data fields were derived from reports that had been electronically signed by board-certified physicians with Level 3 CMR training. Each dataset included scores for wall motion and hyperenhancement (HE) on a standard 17 segments AHA model. We included only patients having one or more akinetic segments, defined as having no visible systolic increase in wall thickness. Patients with dyskinetic segments−showing systolic wall thinning−were also included. Segment viability was defined as HE less than 50% transmural, and "whole-heart viability. After excluding those with non-ischemic cardiomyopathy , the prevalence of whole-heart viability remained high at 32.4% (n = 235). Other sub-cohorts are shown in the figure whole-heart viability remained high in patients with severe left ventricular (LV) dysfunction (ejection fraction<30%) and in those with visible remodeling (severe LV enlargement), with prevalence of 45.3% and 50.0%, respectively.6,932 patients had cardiac scans with complete cine and delayed contrast enhancement imaging. Of these, 725 patients 10.5%) had myocardial akinesis of at least one segment. The table shows patient characteristics. Of 3091 akinetic segments, 37.6% were deemed viable. On a per patient basis, 38.2% (n = 277) had 0.5% had whole-heart viability. The prevalence of whole-heart viability is high even in groups traditionally believed to have reduced viability, such as those with severe LV dysfunction, or remodeling, or history of heart failure. CMR identification of viability may identify patients who may benefit from existing and novel therapeutics for better design of heart failure trials.In this large multi-center study of patients with myocardial akinesis, over one-third of patients had


ECV) and left ventricular mass (LVM) index (LVMI) measured by cardiovascular magnetic resonance might represent independent and opposing contributors to ECG voltage measures of left ventricular hypertrophy (LVH). Diffuse myocardial fibrosis can occur in LVH and interfere with ECG voltage measures. This phenomenon could explain the decreased sensitivity of LVH detectable by ECG, a fundamental diagnostic tool in cardiology.Myocardial fibrosis quantified by myocardial extracellular volume fraction . For all voltage‐related parameters, higher LVMI resulted in greater voltage , whereas increased ECV resulted in lower voltage . When accounting for body fat, LV end‐diastolic volume, and mass‐to‐volume ratio, both LVMI  and ECV  were independent predictors of QRS voltage .We identified 77 patients  referred for contrast‐enhanced cardiovascular magnetic resonance with ECG voltage measures of LVH. Diffuse myocardial fibrosis quantified by ECV can obscure the ECG manifestations of increased LVM. This provides mechanistic insight, which can explain the limited sensitivity of the ECG for detecting increased LVM.Myocardial mass and diffuse myocardial fibrosis have independent and opposing effects upon  R2=0.86; P<0.001)R2=0.69; P<0.01).r=0.85; P=0.01) between endomyocardial biopsies and myocardial ECV fraction by CMR in patients with dilated cardiomyopathy.Diffuse myocardial fibrosis and increased left ventricular (LV) mass may represent independent and opposing contributors to ECG voltage measures of left ventricular hypertrophy (LVH). Decreased ECG voltage from myocardial fibrosis could explain the limited sensitivity of LVH detectable by ECG, a fundamental diagnostic parameter in cardiology. LVH is broadly defined as an increased left ventricular mass (LVM)No data exist on the contributions of diffuse myocardial fibrosis to ECG changes in LVH despite the central diagnostic role that the ECG occupies in cardiology. Several criteria for LVH from both the standard 12‐lead ECG and the vectorcardiogram (VCG) have been used, including the Sokolow–Lyon index, Cornell voltage criteria, and others.2/3, a surrogate for mass‐to‐volume ratio.To evaluate the relationship between diffuse myocardial fibrosis and ECG voltage, we evaluated LVH‐associated changes in the ECG with respect to LVM indexed to body surface area (LVMI) and ECV, as well as body fat, end‐diastolic volume (EDV), and LVM/EDV2, body mass index (BMI) <18 or >30 kg/m2, previous cardiac surgery, pathologic cardiac stress perfusion CMR, cardiac amyloidosis, severe valvular disease, and significant coronary artery stenosis by invasive angiography.In this cross‐sectional observational study, patients were identified from a prospectively acquired database of 1707 enrolled patients who had undergone a clinically indicated CMR scan at University of Pittsburgh Medical Center  between 2010 and 2014. Inclusion criteria were ECG with sinus rhythm with a heart rate <100 beats/min and an ECG acquired within 30 days of CMR. The study was approved by the UPMC Institutional Review Board, and all participants provided written informed consent. Exclusion criteria were ECG confounders such as previous myocardial infarction (MI) or nonischemic myocardial scar as determined by late gadolinium enhancement (LGE) CMR, treatment with digitalis, atrial fibrillation or flutter, bundle branch‐ or fascicular block, abundant premature ventricular contractions (bigeminy/trigeminy), abundant premature atrial contractions, QRS duration >110 ms, paced rhythm, LV end‐diastolic volume (EDV) index (EDVI) >120 g/mr) of 0.4, our power calculationBased on an alpha of 0.05, power of 0.9, and a minimum detectable correlation coefficient , BMI, body surface area (BSA), tobacco use, hypertension, diabetes mellitus, treatment with beta‐blockers, angiotensin‐converter enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and diuretics as reflected in the medical record. Body fat was derived from BMI, as described by Deurenberg et al,2 based on the distribution of LVMI in the study population; see below); (2) normal ECV and high LVMI (>55 g/m2); (3) increased ECV (≥28.5%) and low LVMI; and (4) both increased ECV and high LMVI.From a database of 1707 patients, 1170 met the exclusion criteria and 537 had data for both LVMI and myocardial ECV measurements, as shown in Table 2 as the cutoff between high and low LVMI in the population.There are several sources for LVMI reference ranges in the literature with varying limits., rendering signal intensity proportional to T1 recovery and corrected for surface coil intensity variation. When patients could not breath hold, single‐shot SSFP, averaged PSIR, motion‐corrected images were acquired.CMR images were acquired with a 1.5 Tesla scanner  and a 32‐channel phased array cardiovascular coil by dedicated CMR technologists. The exam included standard breath held segmented cine imaging with a steady‐state free precession (SSFP) sequence. LVM and LVEF were measured from short‐axis stacks of end‐diastolic and end‐systolic cine frames without geometric assumptions. Ten minutes after a 0.2‐mmol/kg intravenous gadoteridol bolus  LGE imaging was performed. To optimize LGE, a phase‐sensitive inversion recovery (PSIR) pulse sequence was usedECV measures in myocardium without infarction or nonischemic scar were acquired after the gadolinium bolus, with minimal variation related to time elapsed following the bolus or to heart rate. T1 measures were recorded using an ECG‐gated single‐shot–modified Look Locker inversion recovery sequence. To avoid partial ECV effects, the middle third of the myocardium was the traced region of interest (ROI). A circular ROI was traced in the center of the blood pool as large as possible while avoiding the papillary muscles.myocardium/ΔR1bloodpool and ΔR1=1/T1precontrast−1/T1postcontrast. ECV was measured in 2 short‐axis slices in the basal and midventricular level in precontrast and postcontrast T1 images. Postcontrast T1 mapping images were acquired after acquisition of LGE images. These images were usually acquired 20 minutes after the contrast bolus. Hematocrit was acquired on the day of CMR and analyzed in the clinical laboratory. The final ECV measures were averaged from the basal and midventricular short‐axis slices. Because of obliquity between myocardium and the image plane, which could introduce partial volume error, ECV was not measured in apical slices.MI was identified when LGE involved the subendocardium in a coronary distribution. Nonischemic scar was defined as not having a distribution of LGE corresponding to MI. We quantified ECV from the myocardium without any apparent scar with the following formula:1 (SV1) plus the larger of the R wave voltage in lead V5 or V6 (RV5 or RV6), where LVH is defined as >3.5 mV; Cornell voltage, defined as SV3+RaVL, where LVH is defined as >2.8 mV for men and >2.0 mV for women; Cornell voltage product, defined as Cornell voltage times QRS duration, where LVH is defined as >244 mV×ms; the 12‐lead QRS voltage sum as the sum of the peak of R to nadir of S in each of the 12 leads; the QRS maximum spatial magnitude, defined as the maximum instantaneous amplitude, in millivolts, of the vectorcardiographic QRS loopECG data for each subject were collected from the local UPMC‐based ECG system  and exported into anonymized .xml files with coded subject identification. Data were analyzed digitally using semiautomatic software developed in‐house. The following variables of the ECG were analyzed: Sokolow–Lyon index, defined as the sum of S wave voltage in lead Vt test. Non‐normally distributed measures were described using median and interquartile range and compared using the Mann–Whitney U test. Linear correlations were evaluated using Pearson's correlation coefficient (r) and expressed as its square (R2). Multivariable linear regression was used to evaluate the relative contributions of ECV, LVMI, EDV, body fat, and LVM/EDV2/3 to the investigated ECG variables. Nonsignificant univariable measures were not included in the multivariable analysis. A P<0.05 was considered statistically significant.Statistical analysis was performed using SPSS software . The Kolmogorov–Smirnov test was used to determine whether continuous variables were normally distributed. Differences between the subgroups' baseline data were tested using ANOVA, the Kruskal–Wallis test, or the chi‐square test, as appropriate. Normally distributed measures were described using mean and SD and compared using the Student Baseline characteristics of the population are presented in Table P<0.05 for all). However, QRS duration did not differ by either ECV or LVMI.ECG measures for low/high LVMI and normal/increased ECV were compared, respectively. All ECG voltage variables, including Sokolow–Lyon, Cornell, 12‐lead, and QRS maximum spatial magnitude voltages, were higher with greater LVMI and lower with increased ECV (P<0.05). Thus, each unit of myocardial mass contributed less ECG voltage in the setting of increased ECV.Figure As shown in Figure 2/3 they could explain ≈40% of voltage. For the other ECG voltage parameters, ECV was the only independent predictor of voltage. Univariable correlations between Cornell voltage and Cornell product and LVMI and ECV, respectively, were similar in magnitude and significance, as well as the multivariable adjusted R2. Figure R2=0.02; P=0.25). There was a weak correlation between LVEF and LVMI , but there was no correlation between LVEF and ECV .Table 2/3, a surrogate for mass‐to‐volume ratio, we found that both LVMI and ECV were sole independent predictors of QRS voltage.The major finding of this study is that there is a positive relationship between ECG voltage amplitude and LVMI as well as an inverse relationship between ECG voltage amplitude and ECV. ECV and LVMI were not related to each other. After excluding confounding conditions, and when accounting for body fat, EDV, and LVM/EDVTo our knowledge, this is the first investigation to show the influence of diffuse myocardial fibrosis upon ECG criteria for LVH. A plausible physiological explanation for these findings is that increased LVM may give rise to larger and longer living activation boundaries, which thereby increase QRS amplitude. However, the complex process beyond the increased LVM, such as myocyte hypertrophy and apoptosis, changes in contractile and electrical phenotype, and alterations in the quantity and composition of the extracellular matrix, are additional factors that have been shown to affect QRS voltage.ECV and LVMI did not correlate with each other, and this has previously been postulated by others.2/3, was correlated with all ECG voltage variables; however, it was not an independent predictor for ECG voltage. However, mean LVM was lower in the current study compared to a previous study,2/3 values. It may be that LVM/EDV2/3 may predict ECG voltage in the higher ranges of LVM/EDV2/3.We found no relationship between LVMI (or LVM) and QRS duration, nor a relationship between QRS duration and ECV. Previous studies have found a relationship between QRS duration and LVM measured by echocardiography or CMR.The ECG has repeatedly been shown to lack both sensitivity and specificity in diagnosing LVH.Because of the characteristics of the subjects available for the study, the cohort was grouped according to high/low LVMI based on values above or below the median of the population as opposed to above or below the upper limit of normal values, which may vary by technique. However, we judged this grouping strategy suitable for studying the basic relationships between ECG, ECV, and LVMI, respectively. A further limitation was that neither age nor sex was taken into account when exploring these relationships. Stratifying the population according to age and sex would require increased sample size to maintain adequate power, and such studies are justified. Notably, age and sex distribution did not differ across the 4 subgroups of high/low LVMI and normal/increased ECV. The current study did not address the effects of focal myocardial scarring attributable to infarction or nonischemic scar upon the ECG, and thus the current findings may not be applicable to such a population. However, the current study was specifically designed to enroll a carefully selected population without myocardial scar in order to specifically address the isolated and respective effects of diffuse myocardial fibrosis and LVM on ECG. We believe that such a carefully selected study population was an important and unique strength of the study necessary to address the hypothesis.The present study provides the first in vivo data supporting a novel mechanistic explanation behind the lack of sensitivity of voltage‐based ECG criteria for detecting increased LVM. Also, the results illustrate that some patients may have pathologically increased ECV that can normalize voltages and thereby disguise ECG detection of LVH.Myocardial mass and diffuse fibrosis have independent and opposing effects upon ECG voltage measures of LVH. Thus, diffuse myocardial fibrosis may disguise the ECG manifestations of increased LVM. These competing effects reflect LV structural and electrical remodeling of the hypertrophied myocardium and provide mechanistic insight into the limited sensitivity of the ECG for detecting increased LVM.The study was funded, in part, by the Swedish Research Council, Swedish Heart and Lung Foundation, Stockholm County Council, and Karolinska Institutet. This work was supported by a grant from The Pittsburgh Foundation (PA), Grant M2009‐0068; and an American Heart Association Scientist Development grant (09SDG2180083) including a T. Franklin Williams Scholarship Award; funding provided by: Atlantic Philanthropies, Inc., the John A. Hartford Foundation, the Association of Specialty Professors, and the American Heart Association . This work was also supported by Grant No. UL1 RR024153 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research.Dr Schlegel reports ownership interest; Modest; Nicollier‐Schlegel Sarl. Dr Schelbert has accepted contrast material from Bracco Diagnostics for research purposes beyond the scope of this work. Dr Wong is supported by a grant from the American Heart Association and the Children's Cardiomyopathy Foundation. Dr Ugander is principal investigator for the Karolinska Cardiovascular Magnetic Resonance Group, and Karolinska University Hospital has a collaborative research and development agreement with Siemens regarding cardiovascular magnetic resonance imaging.