Up to 30 % of all ischemic heart disease patients present with some degree of ischemic mitral regurgitation. It is proven that any grade adversely affects long-term outcomes. Surgical revascularization and restoration of the valvular function both trigger left atrial and ventricular reverse remodeling and improve the prognosis.To evaluate the actual reverse remodeling and its influence on the outcomes we perform follow-up on 71 patients subjected to combined surgical revascularization and mitral valve repair for mild to moderate ischemic mitral regurgitation. Mean follow-up was 28 (6 to 52) months. Left atrial and ventricular dimensions and volumes were evaluated preoperatively and at the follow-up.The mean effective ejection fraction increased from 18 ± 6% to 39 ± 13% (p << 0.05) at the follow-up. Left ventricular end-systolic volume index decreased from 44 ± 24 ml/m2 to 39 ± 26 ml/m2 (p = 0.002). Significant left ventricular reverse remodeling (≥ 15% reduction of LVESVI) was observed in 55 % of all survivors. Recurrent IMR was detected in only 2.8% (2/71) of the evaluated patients. Left atrial volume index decreased from 43 ± 15 ml/m2 to 36 ± 14 ml/m2 (p = 0.000003) and left atrial reverse remodeling was significant for 57 % of all survivors.Despite the advanced process of left atrial and ventricular remodeling in the setting of chronic ischemic mitral regurgitation, left chambers can be effectively addressed by combined revascularization and mitral repair.


Assessing left ventricular (LV) systolic function in a rapid and reliable way can be challenging in the critically ill patient. The purpose of this study was to evaluate the feasibility and reliability of, as well as the association between, commonly used LV systolic parameters, by using serial transthoracic echocardiography (TTE).Fifty patients with shock and mechanical ventilation were included. TTE examinations were performed daily for a total of 7 days. Methods used to assess LV systolic function were visually estimated, "eyeball" ejection fraction (EBEF), the Simpson single-plane method, mean atrioventricular plane displacement (AVPDm), septal tissue velocity imaging (TDIs), and velocity time integral in the left ventricular outflow tract (VTI).r values for all 7 days ranging from 0.79 to 0.95 (P < 0.01). the Simpson correlations with the other LV parameters showed substantial variation over time, with the poorest results seen for TDIs and AVPDm. The repeatability was best for VTI (interobserver coefficient of variation (CV) 4.8%, and intraobserver CV, 3.1%), and AVPDm , and worst for the Simpson method .EBEF, AVPDm, TDIs, VTI, and the Simpson were obtained in 100%, 100%, 99%, 95% and 93%, respectively, of all possible examinations. The correlations between the Simpson and EBEF showed EBEF and AVPDm provided the best, and Simpson, the worst feasibility when assessing LV systolic function in a population of mechanically ventilated, hemodynamically unstable patients. Additionally, the Simpson showed the poorest repeatability. We suggest that EBEF can be used instead of single-plane Simpson when assessing LV ejection fraction in this category of patients. TDIs and AVPDm, as markers of longitudinal function of the LV, are not interchangeable with LV ejection fraction. Echocardiography is a useful tool for assessing cardiac function in hemodynamically unstable patients in the intensive care unit (ICU) . For exaThe study was approved by the Regional Ethics Review Board, Lund, Sweden (Dnr.187/2005). Informed consent was sought from the patient or, if not possible, from the next of kin. The study design was a single-center prospective observational cohort study of critically ill patients. Patients admitted to the mixed-bed ICU of Malmö University Hospital, Sweden, were screened for eligibility, and we included 55 consecutive patients with shock, defined as failure to maintain mean arterial pressure ≥70 mm Hg despite adequate fluid resuscitation according to the surviving sepsis campaign algorithm . All patTTE examinations were performed within 12 hours of inclusion into the study. Subsequent studies were conducted daily for 7 days or until death or discharge from the ICU. The examinations were performed by either of four experienced echocardiographers . Images were acquired by using a Hewlett-Packard Sonos 5500  scanner and a 3-MHz transthoracic transducer. Two-dimensional (2D) imaging examinations were performed in the standard apical four- and two-chamber views. Tissue harmonic imaging was used to enhance 2D image quality. These images were used to estimate LVEF by the EBEF and modified single-plane Simpson method. M-mode images were obtained at the LV septal, lateral, anterior, and posterior borders of the mitral ring  in the aU test was used. For comparison of paired values, a Wilcoxon signed-rank test was used, with a Bonferroni correction applied for multiple analyses. The intra- and interobserver variability was measured by the coefficient of variation (CV). CV was defined as the ratio of the standard variation to the mean multiplied by 100. Significance was set at P < 0.05. The analyses were performed by using SPSS 17.0 for Windows.Data are presented as median (lower quartile: upper quartile). Normality was tested for using the Kolmogorov-Smirnov test. For temporal changes, a repeated-measure ANOVA  was applied. For correlation between two variables, the Spearman rank correlation was used, and for differences between two groups, the Mann-Whitney The original study included 55 consecutive patients. Two patients were excluded because of lack of written consent. One patient died 4 hours after study inclusion and before echocardiographic examination; one patient was morbidly obese and TTE was not possible; and one patient was incorrectly registered in the echocardiography database. These five patients were excluded from statistical analysis. Of 350 expected echocardiographic examinations, 91 were missing because of death or discharge from the ICU before Day 7 (25 of 50 patients). Another 28 examinations were lost during the installation of a new offline storage and analysis system. Thus, in total, 231 examinations were available for analysis. Patient characteristics are shown in Table P < 0.05). All measured LV systolic function parameters were significantly improved on day 6 compared with day 1 . AVPDm, TDIs, and LVOT VTI correlated with the Simpson method, although these correlations were weaker than those seen between Simpson and EBEF  and on average for all measurements , but varied considerably between days . This is somewhat surprising, given a commonly accepted view that TTE imaging is difficult in mechanically ventilated patients. However, our results are in agreement with recent studies, in which the feasibility of acceptable TTE images in ICU patients was as high as 97% to 99% ,35, withPost hoc analyses showed that all markers of LV systolic function were significantly improved on day 6 compared with day 1, reflecting the clinical observation that most (44 of 50) patients were weaned of vasopressors and inotropes by day 6.Regardless of the method used, LV systolic function improved significantly over time, reflecting the clinical course of the patients. AVPDm and TDIs, as markers of the long-axis function of the LV, seemed to mirror clinical improvement, as did all other indices of LV systolic function. The biplane Simpson method is a widely recommended method for the evaluation of LVEF . QuantifAVPD and TDI may be superior in detecting subtle abnormalities of LV systolic function  and in pWe showed that LVOT VTI was easily accessible and had a good intra- and interobserver repeatability. This is in line with previous studies in patients with aortic valve stenosis  and in oet al. in critically ill patients [The Simpson method showed the worst repeatability, which is comparable with the results of Lamia patients . The repThe influence of vasopressors, inotropes, and mechanical ventilation on echocardiographic measurements is uncertain. We have not excluded patients with previous known heart failure or atrial fibrillation, nor have we excluded patients with onset of atrial fibrillation during their critical illness, which might have influenced our results. Our intention was to investigate echocardiographic parameters that are well established in patients with cardiac disease, but less investigated in critically ill, mechanically ventilated patients with shock. We could have used contrast agents to facilitate the endocardial border detection, but this was not advisable at the time of data collection . The strMeasurement of LV systolic function was feasible in hemodynamically unstable, mechanically ventilated patients. The different methods for the assessment of LV systolic function all reflected improvement in clinical state over time. However, the different methods did not all correlate well to one another, probably because they measure different components of LV systolic function and presumably do not change uniformly over time. EBEF and AVPDm provided the best, and Simpson, the worst feasibility. Additionally, Simpson showed the poorest repeatability. We suggest that EBEF can be used instead of single-plane Simpson when assessing LVEF and that combining different left ventricular indices, like EBEF and AVPD, when measuring LV systolic function, might be valuable in this category of patients.• Assessment of left ventricular (LV) systolic function by transthoracic echocardiography (TTE) using five different echocardiographic parameters over a 7-day period in ventilated patients with shock.r = 0.101 to 0.949) over time.• All parameters were easy obtainable (93% to 100%) and had acceptable repeatability ; their correlation to one another showed substantial variation  can be used instead of single-plane Simpson when assessing LV ejection fraction, but markers of the LV longitudinal function, such as tissue Doppler and atrioventricular plane displacement, are not interchangeable with LV ejection fraction.AVPDm: atrioventricular plane displacement mean; CO: cardiac output; CV: coefficient of variation; EBEF: eyeball ejection fraction; EF: ejection fraction; ICU: intensive care unit; LV: left ventricular; LVOT: left ventricular outflow tract; TDIs: tissue Doppler imaging septal; TTE: transthoracic echocardiography; VTI: velocity time imaging.The authors declare that they have no competing interests.LB made substantial contributions to the conception and design of the study, participated in interpretation of data, made substantial contributions in acquisition and analysis of data, and helped to draft the manuscript. RW and AE made substantial contributions to conception and design of the study. MC made substantial contributions to conception and design of the study, participated in interpretation of data, and helped to draft the manuscript. PG made substantial contributions to conception and design of the study and made substantial contributions to acquisition and analysis of data. JD made substantial contributions to conception and design of the study and made contributions to the acquisition of data. HO participated in interpretation of data and helped to draft the manuscript. LI made contributions to the acquisition of data. All authors have made substantial intellectual contributions to the manuscript and have given final approval of the version to be published.


Combination therapy with deferoxamine and oral deferiprone is superior to deferoxamine alone in removing cardiac iron and improving left ventricular ejection fraction (LVEF). The right ventricle (RV) is also affected by the toxic effects of iron and may cause additional cardiovascular perturbation. We assessed the effects of combination therapy on the RV in thalassaemia major (TM) using cardiovascular magnetic resonance (CMR).We retrieved imaging data from 2 treatment trials and re-analyzed the data for the RV responses: Trial 1 was a randomized controlled trial (RCT) of 65 TM patients with mild-moderate cardiac siderosis receiving combination therapy or deferoxamine with placebo; Trial 2 was an open label longitudinal trial assessing combination therapy in 15 TM patients with severe iron loading.In the RCT, combination therapy with deferoxamine and deferiprone was superior to deferoxamine alone for improving RVEF . The increase in RVEF was greater with lower baseline T2* 8-12 ms  than with T2* 12-20 ms . In patients with severe cardiac siderosis, substantial improvement in RVEF was seen with open-label combination therapy .In the RCT of mild to moderate cardiac iron loading, combination treatment improved RV function significantly more than deferoxamine alone. Combination treatment also improved RV function in severe cardiac siderosis. Therefore adding deferiprone to deferoxamine has beneficial effects on both RV and LV function in TM patients with cardiac siderosis. In transfusion-dependent thalassaemia major (TM) patients, iron chelation therapy is mandatory to prevent or reverse iron accumulation caused by excess intake from transfusional iron and the increased gastrointestinal absorption. Deferoxamine was the first clinically available iron chelating agent, introduced over 40 years ago, and life expectancy in TM increased dramatically with its use. ,2 HoweveDeferiprone is an orally active chelator with a lower molecular weight that is uncharged at physiological pH, and which is both hydrophilic and lipophilic enabling it to readily penetrate myocardial cells. It has been shown to be superior to deferoxamine in removing iron from the myocardium, and is associated with improved cardiac outcomes. -9 Due toHowever, despite this success for LV function, the importance of combination therapy on right ventricular (RV) function has not been reported, even though the RV can be affected by the toxic effects of myocardial iron. ,14 CardiIn order to examine the effects of combination treatment on the RV, we reanalyzed imaging data from 2 previously reported trials. The first was a randomized, double-blind, placebo controlled trial (RCT) comparing combined therapy of deferoxamine with deferiprone against deferoxamine with placebo in mild-moderate myocardial siderosis.  The seco9/L) at screening; thrombocytopenia ( < 50 ×109/L) at screening; liver enzymes > 3 times upper limit of normal; any condition making CMR impossible or inadvisable. Of the 167 patients screened, 108 had significant myocardial siderosis (T2* < 20 ms), of whom 22 (13%) had severe myocardial loading (T2* < 8 ms). Patients with mild to moderate cardiac iron loading who satisfied the trial entry criteria  were invited for further detailed assessment by CMR. Of these, 65 were subsequently randomized to receive either deferoxamine plus deferiprone  or deferoxamine plus placebo , and were followed-up for 12 months.In the RCT, 167 adult TM patients  were screened for quantification of myocardial iron loading using myocardial T2*. Inclusion criteria for patient screening were: diagnosis of TM currently maintained on subcutaneous deferoxamine monotherapy; age > 18 years; and maintaining pre-transfusion haemoglobin > 9 g/dL. Exclusion criteria were: patients who had received deferiprone for a total of > 6 months over the last 5 years; patients with previous reaction to deferiprone; neutropenia (absolute neutrophil count < 1.5 × 10Patients with severe cardiac siderosis (T2* < 8 ms) were excluded from the RCT and it was at the treating clinician's discretion to determine best clinical practice for chelation therapy. Of the 22 patients with severe myocardial siderosis, 15  received open-label combination therapy according to locally developed protocols, and were followed prospectively over one year. These patients were used in a secondary comparative analysis against patients from the randomised trial who were on combination therapy.A mobile 1.5 Tesla CMR scanner  was transported to Cagliari for this research. Myocardial and hepatic T2* were assessed using the bright-blood single breath-hold multi-echo technique as previously described.  T2* analDoppler echocardiography studies were performed at baseline and at 12 months to look for pulmonary hypertension. Pulmonary artery systolic pressures (PAP) were determined by peak velocity of the tricuspid regurgitation jet plus estimation of right atrial pressures using standard methodology. Pulmonary hypertension was defined as PAP > 40 mmHg.Laboratory measures included weekly full blood count (due to the risk of agranulocytosis with deferiprone), serum ferritin (Abbott AXSYM System), B-type natriuretic peptide , and liver function tests .Categorical data are presented as frequency and percentage (%). Continuous variables are presented as mean ± standard deviation (SD), except for BNP, which is displayed in median and interquartile range; and for T2* and ferritin, which use the geometric mean (anti-log of the mean of the log data) ± coefficient of variation (CV). Baseline characteristics of both treatment groups were compared using an unpaired two-tailed t-test for continuous variables  and a chi-squared test for categorical variables. Analysis of variance (ANOVA) was used to compare changes in T2* and RVEF over 12 months with treatment and baseline measures entered as covariates. Changes in RVEF over 12 months within individual groups were compared with a paired t-test. Correlations of myocardial T2* with ventricular function were performed using the Spearman's rank test. Subgroup analysis was performed according to severity of myocardial iron loading with cut-offs of 8 ms and 12 ms used to define patients with mild (T2* 12-20 ms), moderate (T2* 8-12 ms) and severe (T2* < 8 ms) iron loading. Intraobserver and interobserver variability was assessed using the method of Bland and Altman.  The coefThe baseline findings and the results of the RCT comparing combination treatment against deferoxamine alone for changes in myocardial T2* and LV EF have been previously published, and are In the combination group RVEF increased from 60.2 ± 7.2% at baseline to 63.8 ± 5.9% at 12 months (p < 0.01), whereas in the deferoxamine group RVEF did not change significantly . There was a significant difference in the RVEF response between groups favouring combination therapy  and moderate iron loading , and this was in accord with the cut-offs used in the original trials. Both subgroups were then analysed according to the chelation regime. Comparing the individual treatment arms, we observed a significant improvement in RVEF in patients with T2* between 8 and 12 ms on combination therapy , and borderline significant improvement in patients with T2* between 12 and 20 ms . Conversely, patients on deferoxamine alone had no significant improvement in RVEF, whether the baseline T2* was 8-12 ms  or 12-20 ms . Comparison of the between groups effects showed that combination therapy was superior to deferoxamine alone in improving RVEF in patients with baseline T2* below 12 ms  but not in those with T2* above 12 ms  evaluating combination treatment for changes in myocardial T2* and LVEF have been previously published, and are In 12 of the 15 patients (80%), the baseline RVEF was low compared to a reference TM population with a normal T2*.  The baseWhen grouping the patients on combination therapy (the 32 patients from the combination arm in the RCT plus the 15 unblinded patients on open-label combined therapy), we found an inverse relation between myocardial T2* at baseline and improvement in RVEF over one year Figure . PatientIn the cohort of 80 patients with myocardial iron loading, a significant correlation was observed between baseline myocardial T2* and baseline RVEF  and baseline LVEF . Accordingly, there was a strong correlation between RVEF and LVEF at baseline . The improvement in RVEF during the study period also correlated with the improvement in LVEF (r = 0.79, p < 0.01; Figure With the development of the T2* technique, CMR has provided new insights into iron-overload cardiomyopathy, as the myocardial iron concentration and its toxic effect on ventricular function can be assessed at the same time with the same high-fidelity technique. In the first T2* publication by Anderson et al, normal T2* levels were associated with normal LVEF, but when T2* fell below 20 ms, there was a progressive fall in LVEF, showing that increasing iron loading is associated with worsening of LV function.  Similar Chelation with deferoxamine has been one of the cornerstones for the treatment of TM. It has been extensively studied over the past decades and has shown to decrease the total body iron burden, prevent complications of iron overload and improve survival in TM. ,2,29 HowIt is well recognized that RV performance depends not only on intrinsic contractility but also on RV afterload, which is the resistance that the RV has to overcome during ejection. Increased pulmonary artery pressures reflecting increased pulmonary vascular resistance may thus impair RV function.  However,Our data are unusual, because reversible RV dysfunction in the setting of a cardiomyopathy is a rarely documented phenomenon. The magnitude of recovery in RV function parallels the recovery in LV function, and this correlates with the response to chelation therapy. This is in keeping with the findings of other studies in non-ischaemic cardiomyopathies, where it has been observed that LV and RV function is usually affected in a similar way and to a similar extent. ,36 The cThis is a retrospective analysis of 2 trials designed to assess the change on myocardial T2* with iron chelation regimes in which RV parameters were not planned as primary end-points. Nevertheless, all data was prospectively collected and the current RV analysis was blinded to the patients' details and chelation regimes.In the RCT of mild to moderate cardiac iron loading, combination treatment improved RV function significantly more than deferoxamine alone. Combination treatment also improved RV function in severe cardiac siderosis. Therefore adding deferiprone to deferoxamine has beneficial effects on both RV and LV function in TM patients with cardiac siderosis.FA has received speaker's honoraria from Novartis. GCS is a consultant to Novartis. DJP is a consultant to Novartis and ApoPharma, and a director of Cardiovascular Imaging Solutions. DJP has received research support and speaker's honoraria from Siemens, Novartis, and ApoPharma. JPC has received speaker's honoraria from Swedish Orphan and ApoPharma. SN has received financial assistance from both Novartis and Swedish Orphan for attendance at conferences.FA and GCS participated in the design of the study, data collection, and drafted the manuscript. JPC, SVN and MAT participated in the data collection. WB performed the statistical analysis. CD, RG, JMW helped to draft the manuscript. DJP conceived of the study, participated in the design of the study and helped to draft the manuscript. All authors read and approved the final manuscript.


Global myocardial edema, a surrogate measure of myocardial inflammation, has been reported in patients with chronic dilated cardiomyopathy (DCM) based on T2-weighted STIR imaging. However, STIR imaging is prone to motion artefact and issues related to cardiac cycle timing and coil sensitivity. We hypothesised that a novel quantitative CMR T2 mapping technique would provide a reliable and reproducible measure for the detection of myocardial edema in chronic non-ischemic DCM.Consecutive DCM patients with disease duration greater than 3 months and age/sex matched healthy volunteers were prospectively enrolled. Exclusion criteria included coronary artery disease, systemic inflammatory disease, acute myocarditis or raised cardiac biomarkers. A mid-ventricular short axis slice was acquired  using a T2-prepared single-shot SSFP readout [Ninety DCM , mean LVEF 41%) and 28 healthy volunteers , mean LVEF 68%) were studied. Subjects with DCM had a significantly higher myocardial T2 compared to healthy controls . T2 had good interobserver variability  and interstudy reproducibility .Quantitative T2 mapping is highly reproducible. Myocardial T2 times are significantly higher in DCM patients than those in healthy controls, suggesting that myocardial inflammation is present in chronic DCM. Further studies are needed to assess the clinical and prognostic impact of these findings in the DCM population.This study was supported by the UK NIHR Cardiovascular Biomedical Research Unit of Royal Brompton Hospital and Imperial College, London. Dr Feng is a visiting academic supported by the National Basic Research Program of China (973 Program) (Grant No. 2010CB732502) and National Natural Science Funds of China (Grant No.30800254). Dr He was supported by Wellcome Trust Value In People (VIP) award and now holds a British Heart Foundation (BHF) Intermediate Basic Science Fellowship (FS/08/26225).


Morphometrically, infarct wall thickness was greater in treated rats. The improvement of LV function by atorvastatin was associated with a decrease in hydroxyproline content and in the number of apoptotic cardiomyocyte nuclei. We conclude that atorvastatin therapy during the peri-infarct period significantly improves LV function and limits adverse LV remodeling following MI independent of a reduction in infarct size. These salubrious effects may be due in part to a decrease in myocardial fibrosis and apoptosis.Although statins impart a number of cardiovascular benefits, whether statin therapy during the peri-infarct period improves subsequent myocardial structure and function remains unclear. Thus, we evaluated the effects of atorvastatin on cardiac function, remodeling, fibrosis, and apoptosis after myocardial infarction (MI). Two groups of rats were subjected to permanent coronary occlusion. Group II (n = 14) received oral atorvastatin (10 mg/kg/d) daily for 3 wk before and 4 wk after MI, while group I (n = 12) received equivalent doses of vehicle. Infarct size (Masson's trichrome-stained sections) was similar in both groups. Compared with group I, echocardiographic left ventricular ejection fraction (LVEF) and fractional area change (FAC) were higher while LV end-diastolic volume (LVEDV) and LV end-systolic and end-diastolic diameters (LVESD and LVEDD) were lower in treated rats. Hemodynamically, atorvastatin-treated rats exhibited significantly higher dP/dt Myocardial infarction (MI) frequently causes left ventricular (LV) dilatation associated with myocyte hypertrophy and interstitial fibrosis of the noninfarcted myocardium. These changes in LV geometry, referred to as remodeling, contribute to the development of depressed cardiac performance The 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors, statins, lower plasma cholesterol levels and have been associated with reduced morbidity and mortality in patients with coronary artery disease Guide for the Care and Use of Laboratory Animals . The animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of the University of Louisville (# 08137).All studies were performed in accordance with the guidelines of the Animal Care and Use Committee of the University of Louisville (Ky) School of Medicine and with the Female Fischer 344 rats  received oral atorvastatin  or an equivalent volume of vehicle  daily for 7 weeks starting 3 weeks before and continuing for 4 weeks after MI. To adjust the daily dose of the drug, the body weight was measured twice a week. The dose of atorvastatin used in this study is considered safe Serial echocardiographic studies were performed 4 days before surgery  and at 48 h and 4 wk after infarction under light anesthesia  max, end-systolic elastance (Ees), and preload recruitable stroke work (PRSW) were calculated using the PVAN software program (Millar) Hemodynamic studies were performed at 4 wk after MI, just before euthanasia. Rats were anesthetized with ketamine (37 mg/kg) and xylazine (5 mg/kg), intubated, and mechanically ventilated. Anesthesia was maintained with 1% isoflurane and the core temperature kept at 37.0°C with a heating pad throughout the study. A 2F microtip pressure-volume (PV) catheter  was inserted into the right carotid artery and advanced into the LV cavity. The right jugular vein was cannulated for fluid administration. After 20 min of stabilization, the PV signals were recorded continuously with an ARIA PV conductance system (Millar Instruments) coupled with a Powerlab/4SP A/D converter (AD Instruments), stored, and displayed on a personal computer. PV relations were assessed by transiently compressing the inferior vena cava with a cotton swab. Parallel conductance from surrounding structures was calculated by injecting a small bolus of 15% NaCl through the jugular vein. LV end-diastolic pressure (LVEDP), dP/dtAfter the hemodynamic measurements, a polyethylene catheter filled with phosphate buffer  and heparin (100 IU/ml) was advanced to the ascending aorta via the right carotid artery. In rapid succession, the heart was arrested in diastole by injecting 1.0 ml of a mixture of cadmium chloride (100 mM)/potassium chloride (3 M) through the aortic catheter. The heart was then excised and perfused retrogradely with phosphate buffer for ∼3 min to flush out residual blood in the coronary circulation, followed by perfusion with 10% neutral buffered formalin solution for 15 min. Perfusion pressure was maintained between 60 and 80 mmHg while end-diastolic pressure was kept at 8 mmHg. After perfusion-fixation, the atria and right ventricle were dissected from the left ventricle. The LV weight was measured. The heart was cut into four transverse slices (∼2-mm thick), which were processed, embedded in paraffin, sectioned at 4-µm intervals, and stained with Masson's trichrome. Images were acquired digitally and analyzed using NIH ImageJ (1.37v). From the Masson's trichrome-stained images, morphometric parameters including LV chamber diameter and infarct wall thickness were measured in each section. All anatomical parameters were corrected according to a uniform sarcomere length Hydroxyproline was assayed using a procedure described previously T*GGTCTAGCGCA-3′5′-GCGCTAGACC; T* represents biotinylated deoxythymidine [dT]) Apoptosis was determined in heart sections with in situ hairpin-1 ligation .Data are reported as mean±SEM. Measurements were analyzed by ANOVA followed by unpaired Student t-tests with the Bonferroni correction. A value of A total of 40 rats (20 in each group) were initially enrolled in the study. Eight rats in the vehicle-treated group (group I) and 6 in the atorvastatin-treated group (group II) died within the first 24 h after coronary ligation due to ventricular fibrillation. An additional 5 rats died after the initial 24 h during the 4-wk follow-up period (3 in the vehicle-treated and 2 in the atorvastatin-treated group), so that a total of 9 and 12 rats completed the protocol in groups I and II, respectively. There were no significant differences in mortality, body weight, heart weight, and heart/body weight ratio between the two groups of rats.The infarct area fraction  was similar in atorvastatin- and vehicle-treated rats , indicating that the extent of myocardial cell death produced by the coronary ligation was comparable in both groups .At baseline (4 days before surgery), all parameters of LV function, measured by echocardiography, were similar in groups I and II . At 48 hmax, LVEDP) and load-independent  parameters of LV performance were improved in the atorvastatin-treated group.Consistent with the echocardiographic data, invasive assessment of cardiac function using the conductance catheter showed improved LV function in atorvastatin-treated animals. At 4 wk after MI, echocardiographic assessment showed an increase in LVEDD, LV end-diastolic area, and LVEDV in vehicle-treated rats, consistent with postinfarction LV remodeling . HoweverMorphometric analysis confirmed the echocardiographic findings. Compared with the vehicle-treated group, the LV chamber diameter was smaller and the infarct wall thickness and infarct wall thickness/chamber diameter ratio were greater in the atorvastatin-treated group .Because myocardial fibrosis contributes to the pathology of ventricular remodeling The major finding of this study is that administration of atorvastatin during the peri-infarct period improves LV function and attenuates adverse LV remodeling after MI independent of a reduction in infarct size. This salubrious effect was associated with a decrease in myocardial fibrosis and in cardiomyocyte apoptosis.th day after MI) Our observations of preserved LV function and mitigated LV remodeling are consistent with previous studies of statins in acute MI. In animal models of MI, cerivastatin (started on the 7The precise mechanism(s) whereby atorvastatin improved LV function is unclear. The drug did not reduce infarct size . In contThe finding that atorvastatin therapy led to a substantial reduction of myocardial collagen content is novel. Although reduction in collagen content by atorvastatin has been demonstrated in animal models of diabetic cardiomyopathy Hairpin positivity reflects DNA break points, characteristic of apoptosis Our data have obvious translational implications. They suggest that the use of atorvastatin during the peri-infarct period might be useful for limiting adverse LV remodeling and improving LV function after MI. This approach might have a potential use in clinical settings such as cardioprotection before surgical procedures, including cardiac and major non-cardiac vascular surgery, and patients with acute coronary syndromes. The exact mechanism(s) of this protective effect, the minimal effective dose, and the minimal duration of treatment required to achieve a beneficial effect need further elucidation.


Although cardiac auscultation remains important to detect abnormal sounds and murmurs indicative of cardiac pathology, the application of electronic methods remains seldom used in everyday clinical practice. In this report we provide preliminary data showing how the phonocardiogram can be analyzed using color spectrographic techniques and discuss how such information may be of future value for noninvasive cardiac monitoring.Gold Wave http://www.goldwave.com in 55 infants and adults with cardiac structural disease as well as from normal individuals and individuals with innocent murmurs. Color spectrographic analysis of the signal was performed using Spectrogram (Version 16) as a well as custom MATLAB code.We digitally recorded the phonocardiogram using a high-speed USB interface and the program Our preliminary data is presented as a series of seven cases.We expect the application of spectrographic techniques to phonocardiography to grow substantially as ongoing research demonstrates its utility in various clinical settings. Our evaluation of a simple, low-cost phonocardiographic recording and analysis system to assist in determining the characteristic features of heart murmurs shows promise in helping distinguish innocent systolic murmurs from pathological murmurs in children and is expected to useful in other clinical settings as well. During the cardiac cycle, the normal heart produces repeatable physiological sounds. However, under some pathologic conditions, such as valvular disease or ventricular septal defects, the presence of turbulent blood flow leads to the production of additional sounds, called murmurs, which are random rather than deterministic in nature. Although the stethoscope has been used for almost two centuries, it is still frequently difficult to determine whether a heart murmur is abnormal or innocent murmur. Furthermore, detecting structural abnormities of the heart such as mitral stenosis or insufficiency remains an important clinical problem. Although many such abnormities can be detected by careful auscultation, generally only experienced cardiologists are able to detect important but subtle auscultatory findings with reliability -6. AlthoThe present study seeks to apply a relatively new technique, known herein as Color Spectrographic Phonocardiography (CSP), to develop a noninvasive instrument to assist in the detection and characterization of heart murmurs. The study builds on the work of others in the field of classical and digital phonocardiography. In particular, techniques such as time-frequency analysis of acoustic emissions, neural network methods, acoustic spectral averaging, and wavelet techniques have all been are used for the analysis of heart sounds and murmurs -18.a priori approval by the institution's human research committee. Data were collected from a total of 55 patients, including 5 normal cases, with an age range of 1 month to 14 years. Written informed consent was obtained from the patients for publication of the case reports and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. The patients and the normal ones had a history of heart murmur, which included 20 with a ventricular septal defect (VSD), 7 with an atrial septal defect (ASD), 4 with Tetralogy of Fallot (TOF), 10 with aortic stenosis (AS), 5 with pulmonary stenosis (PS), and 4 having mitral regurgitation (MR). In all cases, the diagnosis was confirmed by echocardiography. The summary of medical history and diagnostic findings for some samples can be seen in Table We collected the heart sounds at the pediatric clinic of Modares Hospital in Tehran between 2009 to 2010. The study was approved by the ethics committee of the hospital and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in The data were recorded using a laptop computer-based phonocardiographic recording system developed at the Science and Research Branch of Islamic Azad University. Figure Microphone calibration was performed using a Sound Level Calibrator, 94dB Model 407744 which produces a sinusoidal wave in 1 KHz and 94 dB SPL intensity. Comparing the recorded sound to the calibration recordings, it was then possible to obtain the absolute intensity measurements.In order to achieve high-quality recordings, the recording environment was kept completely silent, with the patients lying in the supine position. Each recording was divided into five sections of 3 minutes each. Care was taken to ensure that borborygmi sounds (from stomach and intestines) and other artifacts were not present. The Figure All sounds were recorded using the Goldwave software (version 5.55), which includes tools for recording, playing, filtering, and analyzing sounds. Using this software, we also deleted any electrical utility frequency (50 Hz) from the ECG recordings. Next, we wrote code in the MATLAB software programming environment, based on the FFT function, which enabled us to display the phonocardiographic graphs in color spectrographic form.  of the atria and ventricles are much less than for the arterial walls. It is known from vibration theory that a vibrating mechanical system with small elastic modulus oscillates with lower frequency than a system with higher elastic modulus. Therefore, a smaller elastic modulus results in a lower frequency of oscillation . Also, sWe found out each of the heart sounds take more than 0.1 second, S1:0.14 s and S2: 0.11s. Both of these sounds are low-frequency sounds but S1 more so than S2. Furthermore, the S2 duration was found to be less than that for S1, presumably in part because the attenuation of S2, from the arterial walls, is more rapid than for S1, from the ventricular walls.Investigating the spectrogram of the VSD patient in Figure Our eventual aim is to collect a sufficient number of cases to allow us to separately investigate the time-domain and spectrographic characteristics of each form of cardiac disease, so as to establish what characteristics each condition has in common that are not present in a collection of normal recordings. This would first require a careful examination of the two sets of data  to find candidate parameters that would help distinguish the two groups. This would likely be followed by formal pattern recognition methods to identify which parameters or set of parameters best separate the recording into "normal" and "abnormal" groups. In addition, we are exploring the possibility of developing "digital subtraction phonocardiography" methods that we hope will be able to separate any murmurs from underlying deterministic heart sounds. Our hope here is to develop an easily-implemented and inexpensive non-invasive approach to distinguish the murmurs from the underlying normal heart sounds by processing the acquired phonocardiogram and electrocardiogram of a patient. This approach will be developed and evaluated first by applying advanced signal processing techniques on mathematical simulations of signals containing both deterministic heart sounds and random (as in stochastic) murmurs. The information obtained from this preliminary analysis will be evaluated on healthy volunteers to determine the clinical factors that may affect the implementation of the new approach. Our hope is that the new technique will be evaluated in a cohort of patients with pathological murmurs to determine its clinical potential through a comparison of the results with those from classical auscultation and echocardiography on these patients.Finally, some limitations of the present study should be emphasized. First, we expect that inexperienced clinical examiners need some guidance in the form of rules about how to read the spectrograms. Such rules have not yet been well researched. Another limitation is that the source of the continuous low frequency energy found in many recordings is not yet known; one possible cause we are considering is poor skin contact of the chest piece. Finally, studies on a large number of patients with homogeneous cardiac defects like VSDs will be necessary to make this technology more useful.Recently, Noponen et al.  studied AS: aortic stenosis; ASP: atrial septal defect; CSP: Color Spectrographic Phonocardiography; ECG: electrocardiogram; Hz: Hertz; PCG: phonocardiogram; MR: mitral regurgitation; USB: Universal Serial Bus; TOF: Tetralogy of Fallot; VSD: ventricular septal defect.The authors declare that they have no competing interests.RRS and HT conducted the data sampling and wrote the MATLAB code required for converting the murmurs into signals. JDD and MN supervised the research and JDD revised the manuscript and offered the research proposal. KH wrote the manuscript and coordinated the research. All authors have read and approved the final manuscript.Appendix.Click here for fileTable S1. The shape of different murmurs [Redrawn from reference 20].Click here for file


This study aimed at assessing left ventricular (LV), left atrial (LA) and right ventricular (RV) volumes in patients before and after MitraClip™ implantation by cardiac magnetic resonance imaging (CMR).The MitraClip™ is a novel device for percutaneous mitral valve repair. Recent studies demonstrated a reduction of LV volumes after MitraClip™ implantation using echocardiography. CMR is currently the reference method to assess cardiac volumes but has not been used to assess LV remodeling after MitraClip™ implantation so far.Twelve patients with functional (n=7) or degenerative (n=5) mitral valve regurgitation grade 3 to 4 underwent CMR at baseline (BL) before and at 6 month follow-up (FU) after successful MitraClip™ implantation. CMR protocol consisted of short- and long-axis slices using a steady-state-free-precession cine sequence for the assessment of LV, LA and RV volumes.2; p=0.03) as well as LVESV (82 (54-91) vs. 69 (48-99) ml/m2; p=0.03) indices significantly decreased from BL to FU. No significant difference was found for RVEDV (94 (75-103) vs. 99 (77-123) ml/m2; p=0.91), RVESV (48 (42-80) vs. 51 (40-81) ml/m2; p=0.48) and LAV (87 (55-124) vs. 92 (48-137) ml/m2; p=0.20) indices between BL and FU.Minor device-related artifacts were observed, enabling reliable delineation of endocardial borders in all patients at FU. Figure CMR enables reproducible measurements of cardiac volumes in patients with implanted MitraClip™ devices. Significantly decreased LV but unchanged LA and RV volumes were found at 6 month after successful MitraClip™ implantation.No external funding.


Dear Editor,We read with great interest the article by Malatesta-Muncher et al. entitled “Early cardiac dysfunction in pediatric patients on maintenance dialysis and post kidney transplant”, where the authors discussed the problem of “cardiorenal syndrome” which seems to be of high predictive importance in young patients with chronic kidney disease (CKD) on renal replacement therapy .The authors investigated heart changes, using imaging techniques for structural study and sensitive biomarkers to assess myocardial function and metabolism, in order to examine the association of these parameters with left ventricular hypertrophy (LVH). They calculated that cardiac magnetic resonance (CMR) and MR spectroscopy (MRS) allow the detection of cardiac dysfunction earlier. They also concluded that young patients with advanced CKD and normal ejection fraction demonstrated early cardiac impairments accompanied by increased LV mass index, which suggested a development of maladaptive hypertrophy.In this regard, we would like to pay attention to our observations made in children with CKD, which revealed the usefulness of a non-invasive 87-electrode electrocardiographic method, BSPM , in early detection of intraventricular conduction disturbances of various degrees.We have used isochrone maps that precisely reflect ventricular activation time (VAT maps). In the examined CKD children treated conservatively  or with Our results, being in strong relevance to the findings of Malatesta-Muncher et al., suggest that children with CKD, regardless of mechanisms responsible for LVH, adaptive or maladaptive, are at risk of developing progressive abnormalities in the intraventricular heart conduction system. Such disturbances of electrical activation propagation lead to delayed ventricular depolarization, which results in hemodynamic dyssynchrony and, consequently, with simultaneous left ventricular hypertrophy, worsen the global systolic function of the heart. Bearing this in mind, any possibilities enabling detection of subclinical cardiac dysfunction in CKD seem beneficial.


Treatment of myocardial infarction has undergone great evolution since introduction of percutaneous coronary intervention. The purpose was to assess the outcome of patients with myocardial infarction undergoing early surgical revascularization with coronary artery bypass grafting (CABG).A total of 62 consecutive patients underwent CABG therapy within 14 days after the onset of myocardial infarction between September 2009 and January 2013 at our institution. Prospectively recorded preoperative, intraoperative, and postoperative data were retrospectively screened for in-hospital mortality and major adverse postoperative events .Overall in-hospital mortality was 3.2%. Low cardiac output syndrome was found in 27.4%, prolonged mechanical ventilation in 9,7%, prolonged intensive care stay in 48,4% and hospital stay >7 days in 64,5%. Age, female sex, EuroSCORE, extent of preoperative myocardial necrosis, low left ventricular ejection fraction and cardiogenic shock were the most potent predictors of major adverse postoperative events.CABG within 14 days after the onset of myocardial infarction can be performed with acceptable risk by incorporating adequate management strategies. However, age, female sex, extent of preoperative necrosis, preoperative cardiogenic shock and calculated high operative risk are major variables of morbidity results.


Aim. To assess the effect on left ventricular (LV) function of atrioventricular (AV) and ventricular pacing at the LV apical or lateral wall and to compare the normal torsional and deformation pattern of the intact LV myocardium with those created by the aforementioned LV pacing modes and sites. Methods. Experiments were conducted in pigs (n = 21) with normal LV function to investigate the acute hemodynamic effects of epicardial AV and ventricular LV pacing at the LV apical or lateral wall. Torsional and deformation indices of LV function were assessed using speckle tracking echocardiography. Results. AV pacing at the apex revealed a significant reduction in the radial strain of the base (P < 0.03), without affecting significantly the ejection fraction and the LV torsion or twist. In contrast, AV pacing at the lateral wall produced, in addition to the reduction of the radial strain of the base (P < 0.01), significant reduction of the circumferential and the radial strain of the apex (both P < 0.01) as well as of the ejection fraction (P < 0.002) and twist (P < 0.05). Conclusions. In pig hearts with intact myocardium, LV function is maintained at sinus rhythm level when AV pacing is performed at the LV apex. Temporary epicardial pacing is commonly indicated in cardiac surgical patients, when right ventricular (RV) and/or right atrial (RA) pacing wires are used to prevent postoperative bradyarrhythmia and atrioventricular (AV) block. Patients with atrial fibrillation receive only RV pacing wires, which conventionally have been used because of their easy application to the anterior wall of the RV, prior to disconnection from cardiopulmonary bypass. There is growing interest in seeking methods that use different pacing modes and/or pacing sites to maximize the benefits and minimize the harmful effects of artificial cardiac stimulation on LV function . In thesNovel two-dimensional speckle tracking echocardiography (STE) allows detailed evaluation of LV mechanics, including LV mechanical dyssynchrony, LV strain, and LV torsion , 3. ThisThe aim of this study was to assess the effect on LV function of AV and ventricular LV pacing at the LV apical or lateral wall and to compare the normal torsional pattern of the intact LV myocardium with those created by the aforementioned LV pacing modes and sites.The protocol complied with the “Principles for the Care of Experimental Animals” and the “Guidelines for the Care and Use of Experimental Animals” issued by the US National Academy of Sciences and National Institute of Health  and was approved by the Scientific Committee of the “Alexandra” University Hospital.Twenty-one healthy pigs, weighing 35 ± 5 kg, were sedated with intramuscular administration of midazolam 5 mg/kg and ketamine potassium 5 mg/kg, anesthetized with intravenous (IV) thiopental sodium 5 mg/kg, intubated, and controlled by mechanical ventilation . Anesthesia was maintained with IV propofol 0.1-0.2 mg/kg. During the experiment, analgesia was maintained with the administration of opioid-fentanyl. Additional anesthetic was administered during the experiment as needed. A 7F sheath was inserted into the right internal jugular vein for the delivery of drugs and fluids. Fluid loss was compensated for by continuous infusion of saline into the right jugular vein. Through a left external carotid artery a 6F pigtail catheter was placed into the LV cavity and used for LV pressure monitoring. Lead II of the standard electrocardiogram (ECG), LV pressure, and hemoglobin oxygen saturation were monitored throughout the experiment. After catheter insertion, a 5000 IU heparin bolus was administered to avoid endovascular thrombus formation. Loading conditions were kept constant during the different maneuvers. A regular median sternotomy was performed after thymic resection and a longitudinal pericardiotomy was performed. Temporary myocardial pacing leads  were attached to the surface of the right atrium and to the epicardium of the LV apex and of the LV lateral wall (approximately 2 cm below the base). The leads were connected to an external pacemaker . The two LV electrodes were connected to a two-channel external pulse stimulator (Medtronic model 2883), allowing setting of thresholds for each electrode separately and pacing through each of the electrodes separately. Pacing was unipolar with an indifferent electrode positioned in between the intercostal muscles. During AV pacing the AV delays were short enough to produce an activation wave originating from the ventricular pacing lead. Under all conditions, pacing was performed at about twice the stimulation threshold. The pacing rate was set at 10 beats/min above the intrinsic heart rate in each case.i digital ultrasound system  and a 3.5 MHz phased array transducer. Two-dimensional gray-scale echocardiographic images were obtained using 2nd harmonic imaging. Instrument settings were held constant for each experiment. At each stage of the experiment, with or without pacing, the following parameters were measured [e) diastolic flow velocity was measured and the early diastolic (e′) wave of the lateral mitral annulus was obtained by tissue Doppler imaging from the apical 4-chamber view. The ratio e/e′ was calculated. To determine the timing of cardiac events, mitral inflow and LV outflow were recorded using pulsed Doppler echocardiography. Three consecutive cardiac cycles were stored in cineloop format for offline analysis. Averaged values were calculated for each parameter.The echocardiographic study was performed using a Vivid measured : LV end-Assessment of LV rotation and twist was obtained by acquisition of specific short-axis planes with internal landmarks: the basal plane was acquired at the level of the mitral valve leaflets, while excluding the mitral annulus, and the apical plane was acquired distally to the papillary muscles. The frame rate range was 65–80/s. In each phase, three consecutive cardiac cycles' cineloop images were stored for offline analysis with a dedicated platform EchoPac PC . The software automatically defined the ventricular centroid for the midmyocardial line on a frame-by-frame basis and calculated the time domain LV strain , rotation, and rotational velocity for each segment in both short-axis planes. Regional strain curves were then analyzed, and peak radial strain and peak circumferential strain were measured for each segment at both planes. The averaged LV rotation and rotational velocity profile were used for the calculation of LV twist and twist velocity. As viewed from the apex, counterclockwise rotation was expressed as a positive value, whereas a clockwise rotation was denoted as a negative value [max). After completion of the surgical preparations, a steady-state period of 15 min was allowed. Baseline measurements were obtained in sinus rhythm and then repeated during ventricular pacing at the LV apex and the LV lateral wall and during dual AV pacing at the LV apex and the LV lateral wall, in random order. Measurements were performed after two minutes' pacing at each site separated by two-minute intervals in sinus rhythm.Throughout the experiment, surface ECG lead II from the limb lead electrodes was monitored and recorded at a speed of 100 mm/s by a multichannel device . A pigtail catheter was placed through an arterial sheath and advanced retrogradely across the aortic valve into the LV cavity for the measurement of LV pressure and peak rate of LV pressure increase .Results are presented as mean ± SD. Statistical analysis was performed on absolute values, and each experiment served as its own control. The normality of distributions was checked using the Kolmogorov-Smirnov test. One-way analysis of variance for repeated measurements was used to evaluate the significance of the effect of pacing mode and site on each variable. The Bonferroni correction was used for post hoc comparisons. Pearson correlations were studied and linear regression analysis was performed to define the relationship between parameters. The level of significance was set at P < 0.001), dP/dtmax (P = 0.005), and the eccentricity index Ld/Sd (P = 0.02); in contrast, ESV (P < 0.05) and the diastolic function index e/e′ ratio, which denotes an elevated LV filling pressure (P = 0.04), increased significantly; dP/dtmin, which denotes ventricular lucitropy, decreased significantly (P < 0.001), (P < 0.001) and torsion (P = 0.002), and apical rotation (P = 0.002) and apical peak systolic rotation rate (P = 0.005), as well as the deformation variables, radial strain of the apex (P < 0.01) and the base (P = 0.004), together with circumferential strain of the apex (P < 0.001) and the base (P = 0.02), deteriorated significantly , . Moreove, . Moreod P = 0.0; in contficantly .P = 0.03), without affecting significantly the EF and the LV torsion or twist. In contrast, AV pacing at the lateral wall produced, in addition to the reduction of the radial strain of the base (P < 0.01), significant reduction of the circumferential and the radial strain of the apex (both P < 0.01) as well as of the EF (P = 0.002), torsion (P = 0.04), and twist (P < 0.05).AV pacing at the apex showed the least significant changes for LV function in comparison to sinus rhythm Tables  and 2. TP < 0.001) and peak systolic circumferential strain of the apex (P = 0.04), while pacing at the lateral wall also led to a reduction in SV and LV systolic pressure (both P < 0.001), while producing a significant decrease in EF (P < 0.001), dP/dtmax (P < 0.01), dP/dtmin (P < 0.001), apical rotation (P < 0.001) and rotation rate (P = 0.03), and LV torsion (P = 0.007) or twist (P = 0.003).Ventricular pacing at the apex showed less significant changes than pacing at the lateral wall in comparison to sinus rhythm. It produced a significant reduction of the SV and LV systolic pressure , torsion, or twist (both P = 0.04), as well as rotation and rotation rate of the apex (both P = 0.02) were all significantly lower.AV pacing showed only minor changes in comparison to sinus rhythm Tables  and 2. AP < 0.001 all).For every pacing mode and pacing site the heart rate was significantly higher and the QRS duration significantly longer in comparison to sinus rhythm  with LV systolic pressure and dP/dtmax.EF was correlated negatively with pacing and QRS duration and positively with peak systolic radial strain of the apex  while dPSs ratio , twistinb = −0.07, P < 0.001) while twist was independently affected by apical rotation rate , untwisting rate , and heart rate . Rotation of the apex and base was excluded from the analysis.Multivariate regression analysis showed that EF was independently related to pacing , torsional , and deformation  indices of LV function. During sinus rhythm, the electrical impulse travels from the rapid His-bundle conduction system towards the apex. During LV pacing, activation is more asynchronous due to the longer QRS duration. This widening of the QRS duration is primarily due to the propagation of the electrical impulse through the slowly conducting myocardium instead of the His-Purkinje system. QRS widening negatively affects EF, twist, and apical rotation. AV pacing at the LV apex provides a fairly physiological sequence of stimulation, although activation is more asynchronous due to longer QRS duration. However, a good sequence of electrical activation is sufficient to allow a near normal LVEF for AV and ventricular apical pacing but not for pacing at the lateral wall, although QRS duration did not differ significantly between them. The importance of a proper sequence of activation is further supported by the finding that, in normal hearts, biventricular and multisite pacing does not improve LV function as compared with LV apex pacing alone, even though QRS duration is shorter in the former pacing modes [max changes produced by pacing were correlated with the acute remodeling of the LV, as expressed by the changes in Ls/Ss ratio, while a more spherical LV is associated with depressed systolic function. Moreover, a reduced apical rotation during pacing was correlated with a reduced dP/dtmax. The data from the present study extend earlier findings on the beneficial hemodynamic effects of LV apical pacing in an acute hemodynamic study [The results of the present study, comparing the impact of various temporary LV pacing modes and sites on indices of LV systolic and diastolic function using hemodynamic, strain, and torsional analysis, demonstrate that LV pacing mode and lead location have a significant impact on LV function. In particular, LV pacing produced a significant deterioration in the main hemodynamic  and patients undergoing surgical implantation. However, the LV apex is relatively easy to access using a subxiphoid approach, so that, after the development of proper tools, positioning of a pacing lead at this site could become feasible for many more patients. Moreover, with the currently available pacing leads, the LV apex could be reached using the transcoronary venous approach if the lead can be advanced far enough. AV pacing at the LV apex may help to reduce the morbidity and mortality after cardiac surgery. Its early postoperative use may reduce the need for postoperative inotrope support.In pig hearts with intact myocardium, LV function is maintained at sinus rhythm level when AV pacing is performed at the LV apex, possibly because pacing from this site creates a more physiological propagation of electrical conduction. Further studies are necessary to prove the beneficial effects of AV pacing at the LV apex on the postoperative morbidity and mortality after cardiac surgery.


T2 mapping using T2-prepared SSFP at 1.5T has been shown to be sensitive to oedema in acute myocardial infarction[2) were constructed with relaxation times close to normal myocardium (N) and oedematous myocardium (O)[Two gel phantoms (agarose and NiClrdium (O)3]. Thes. Thes2) Next, a T2-prepared T2 mapping sequence (Siemens WIP 447) was used, with the default 1.5T protocol[The reconstructed T2 maps were analysed using Matlab . Each protocol was evaluated for its ability to distinguish between normal and oedematous myocardium by comparing the difference between the measured T2, averaged over a ROI covering the body of the N and O phantoms. The standard deviation of measured T2 for each protocol across the three heart rates was used as a measure of heart-rate dependence. A t-test was used to determine whether the difference in T2 was statistically significant over all heart rates, and to rank the protocols, with the lowest p-value protocol providing the best discrimination between the T2 of the two phantoms.The measured reference relaxation times for the two phantoms were N: T1/T2=1152/53ms; O: T1/T2=1302/59ms. Apparently minor changes in the acquisition protocol yield wildly different T2 values using these methods Figure . No protSelected pertinent protocol details and numeric results are summarised in Table The sensitivity of myocardial T2 mapping at 3T can be significantly improved by optimising acquisition parameters. Based on this phantom study, we use a centrically ordered GRE readout with a flip angle of 18° and a T2-prep order of 32-55-0ms.We thank the NIHR Oxford Biomedical Research Centre and UK Department of Health for grant funding.


To assess the accuracy of left ventricular (LV) functional analysis derived from short axis steady-state free procession (SSFP) cine sequences following the administration of gadolinium contrast.Cardiovascular magnetic resonance (CMR) imaging is widely accepted as the gold standard in the assessment of LV volume and function. To date this assumption has been based on analysis of unenhanced gradient echo cine imaging. In certain clinical scenarios the use of gadolinium contrast is required for the evaluation of myocardial perfusion and late contrast enhancement. By performing an LV cine stack between the perfusion and late enhancement sequences the total scan duration can be reduced. However, it is possible that post contrast image acquisition alters endocardial and epicardial border detection and therefore affects the results of ventricular functional analysis Fig. .13 patients, with a variety of clinical indications, undergoing cardiac MRI requiring gadolinium contrast enhancement had pre and post contrast SSFP short axis cine acquisitions obtained. All images were acquired using a Siemens 1.5T Avanto MRI scanner. The same radiographer acquired pre and post contrast short axis stacks using identical parameters and without patient repositioning.Post processing was performed using Siemens Argus software for evaluation of left ventricular parameters including end diastolic volume (EDV), end systolic volume (ESV), stroke volume (SV), ejection fraction (EF) and mass. All data sets were analysed by three independent reporters.Mean differences were compared using a 2-tailed paired t-test. Bland-Altman analysis was performed to assess inter-observer agreement. Values are quoted ± one standard deviation.Mean difference in EF pre and post gadolinium was 0.5±6.9%.Bland-Altman analysis of inter-observer LV parameters demonstrates a mean difference in EDV pre gadolinium of 1.4±13.0 ml, post gadolinium of 2.9±13.3ml and in ESV pre gadolinium of 6.0±12.4 ml and post gadolinium of 1.5 ml±6.1.No significant difference between pre and post gadolinium assessment of LV parameters has been demonstrated. Despite the small sample size this suggests that use of post gadolinium data in LV analysis represents reasonable practice in a variety of patient groups.


Late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) has been found in about two-thirds of patients with dilated cardiomyopathy (DCM). The clinical impact of this finding is not well established.The aim of this study was to assess, in patients (pts) with DCM, the relationship of LGE with the occurrence of atrial fibrillation (AF), which is a common complication of DCM.44 consecutive pts  with DCM were included, after exclusion of ischemic heart disease (coronary angiography), secondary cardiomyopathies , non-sinus rhythm and contraindications to CMR. Functional class and plasmatic NT-pro-BNP were assessed. All pts underwent CMR: a) short-axis SSFP for left atrial area and left ventricle (LV) volumes and ejection fraction (EF); b) LGE (segmented inversion-recovery fast gradient-echo sequence), 10-15 mn after 0.2mmol/kg of Gd-DTPA acquired in long-axis and short-axis views; LGE was classified as subendocardial or midwall and quantified using plannimetry of LGE contours, 6SD from remote myocardium; a fibrosis index was obtained from LGE volume/myocardial volume. All underwent 24-hours Holter monitoring, less than one month from CMR, and the number of atrial fibrillation episodes was assessed.26 pts were in NYHA class II and 18 in class III. Mean NT-pro-BNP was 551±180pg/ml, atrial area was 35.8±11.0 cm2, LV end-diastolic volume was 155±44mL/m2, mean EF was 33±8%. LGE was found in 29 patients (69%) located in midwall, involving a mean of 7 segments per pt (range 3-14). Holter monitoring showed AF episodes in 26 pts. In comparison with pts without AF, pts with AF had higher NT-pro-BNP , larger atrial area , larger LV end-diastolic volumes  and more frequent LGE (p=0.0003). In pts with AF, no correlation was found between the functional class or the fibrosis index and the number of AF episodes. Using multivariate analysis, the atrial area and the presence of LGE were independent predictors of occurrence of AF episodes.In patients with DCM, LGE together with atrial dimensions, is significantly associated and an independent predictor of atrial fibrillation, among functional class, LV volumes, ejection fraction and NT-pro-BNP. This finding should be used for risk assessment and therapeutic decisions.


Thrombus aspiration (TA) has been shown to improve microvascular perfusion during primary percutaneous coronary intervention (PCI) for patients with ST-segment elevation myocardial infarction (STEMI). The objective of our study was to assess the relationship between TA and myocardial edema, myocardial hemorrhage, microvascular obstruction (MVO) and left ventricular remodeling in STEMI patients using cardiovascular magnetic resonance (CMR).Sixty patients were enrolled post primary PCI and underwent CMR on a 1.5 T scanner at 48 hours and 6 months. Patients were retrospectively stratified into 2 groups: those that received TA (35 patients) versus that did not receive thrombus aspiration (NTA) (25 patients). Myocardial edema and myocardial hemorrhage were assessed by T2 and T2* quantification respectively. MVO was assessed via a contrast-enhanced T1-weighted inversion recovery gradient-echo sequence.At 48 hours, infarct segment T2  was lower in the TA group. Also, infarct segment T2* was higher in the TA group . MVO incidence was lower in the TA group .At 6 months, left ventricular end-diastolic volume index  and left ventricular end systolic volume index  were lower and infarct segment systolic wall thickening was higher in the TA group .TA during primary PCI is associated with reduced myocardial edema, myocardial hemorrhage, left ventricular remodeling and incidence of MVO after STEMI. Primary percutaneous coronary intervention (PCI) is the mainstay of treatment in patients with ST-segment elevation myocardial infarction (STEMI) . DespiteCardiovascular magnetic resonance (CMR) represents the gold-standard method in assessing myocardial edema, myocardial hemorrhage, left ventricular remodeling and microvascular obstruction (MVO) -24. The Sixty patients presenting to Sunnybrook Health Sciences Centre in Toronto, with STEMI between July 2009 and March 2011 were enrolled. The main inclusion criteria were patients that met the standard diagnostic criteria for STEMI . All patAll patients were pretreated prior to revascularization with aspirin 162 mg and clopidogrel 600 mg. Choice of anticoagulant  and optional use of glycoprotein IIb/IIIa inhibitor were left to operator discretion. TA was performed with an Export Medtronic device  and its use was also left to operator discretion. Factors influencing the use of TA included target vessel size, degree of thrombus burden, no reflow phenomenon and clinical instability. Subsequently patients received aspirin, clopidogrel, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers and statins as per standard of care.Thrombolysis In Myocardial Infarction (TIMI) flow grade, myocardial blush grade and thrombus score were estimated visually using previously described methods by 2 experienced observers who were blinded to use of TA -28. ST-sEach patient was imaged at 2 time points: within 48 hours and 6 months post STEMI. Studies were performed on a 1.5 T clinical scanner  with commercially available CMR software, electrocardiographic triggering, 8-channel receive coil and breath holds at end-expiration. After performing a localizer scan, short-axis cine CMR (10-12 slices) was performed with a balanced steady-state-free-precession sequence  with the following parameters: repetition time = 3.7 ms and echo time = 1.6 ms, flip angle = 45°, slice thickness = 8 mm, acquisition matrix = 256 × 192, field of view = 35 cm, bandwidth = 125 kHz, 20 cardiac phases per slice.Myocardial edema was assessed by T2 quantification using a previously validated free-breathing cardiac-gated spiral imaging sequence with T2 preparation ,31, 8-10® MR software , and the results were the consensus of a minimum of 2 experienced observers who were blinded to use of TA. Endocardial and epicardial borders were delineated on the end-diastolic and end-systolic phases of short-axis slices for quantification of left ventricular volumes, function, mass, and infarct segment systolic wall thickening. Measurements were indexed for body surface area. End-diastolic wall thickness was measured in the infarct segment as an indicator of myocardial edema in the acute phase and wall thinning in the chronic phase. Myocardial T2 and T2* maps were constructed by fitting signal intensities at each pixel with an exponential model for the given echo times. Hemorrhage was identified as an area of hypointensity on T2-weighted images within the infarcted segment. Infarct size was quantified in a contrast-enhanced T1-weighted image using the full-width-half-maximum technique as previously described [® . MVO was also recorded as a binary variable of being present or absent, based on the contrast-enhanced images [All cine CMR images were analyzed using QMassescribed  while MVd images .t test. Categorical variables were reported as frequencies and percentages and analyzed by the chi-square or Fisher exact test, as appropriate. All tests were 2-tailed, and statistical significance was accepted at p < 0.05.The study population was divided into 2 groups: TA versus no thrombus aspiration (NTA). Primary study end points were the degree of myocardial edema , myocardial hemorrhage (T2* measurement) and occurrence of MVO at the first time point of within 48 hours post-STEMI. Secondary endpoints included the occurrence of final myocardial blush grade ≥ 2, final TIMI flow ≥ 2 on angiography, rate of ST-segment resolution post primary PCI, and parameters of left ventricular remodeling including left ventricular end diastolic volume index (LVEDI), left ventricular end systolic volume index (LVESI), left ventricular stroke volume index (LVSVI), left ventricular ejection fraction, and infarct segment systolic wall thickening at the final time point of 6 months post STEMI. Continuous data were expressed as mean +/- standard deviation and analyzed by the Student Eighty-five patients with STEMI were screened, 25 patients were excluded and 60 patients were included in the study. Reasons for exclusion included severe renal insufficiency, claustrophobia, hemodynamic instability and presence of permanent pacemaker. Clinical characteristics of both the TA and NTA group are shown in Table TA was associated with more frequent final myocardial blush grade ≥ 2  and ST-segment resolution  post primary PCI (Table The initial CMR scan was performed at a mean of 34.4 hours post primary PCI and the second scan at a mean of 243 days post primary PCI in the overall group. Table Figure Figure Our non-randomized study demonstrates that TA during primary PCI is associated with reduced myocardial edema, myocardial hemorrhage, infarct size, left ventricular remodeling, and MVO after STEMI. We postulate that TA results in less myocardial injury, evidenced by the reduced infarct size, which in turn is responsible for reduced myocardial edema and hemorrhage in the acute phase. This is the first study to use quantitative CMR parameters to evaluate the effects of TA on myocardial edema and myocardial hemorrhage. Recently, the utility of quantitative CMR in the longitudinal evaluation of myocardial edema, hemorrhage, and MVO has been demonstrated in preclinical models of acute myocardial infarction .Both myocardial hemorrhage and MVO have been extensively linked to worse clinical outcome post acute myocardial infarction ,24,33,34Myocardial hemorrhage is considered to be a sign of severe microvascular injury . HistoloExtensive preclinical and human studies have established that T2 signal hyperintensity by CMR indicates increased myocardial water content ,40. T2 mWe used a quantitative T2 mapping technique to delineate the extent of myocardial edema instead of a T2-weighted imaging approach. T2-weighted imaging techniques have known limitations, which impairs their validity ,46. SomeHemorrhage is known to not only reduce T2* values but also T2 relaxation times . An unexIn contrast to the EXPIRA  trial thIn accordance with the literature, TA also improved final myocardial blush grade and the rate of ST-segment resolution post primary PCI ,17,18,20This study represents a single-centre non-randomized experience with a limited number of patients. However, baseline demographic and angiographic characteristics appear to be well matched in our 2 study groups. In particular, time to reperfusion, culprit vessel distribution, thrombus burden, enzymatic infarct size and adjunctive glycoprotein IIb/IIIa inhibitor use were similar in both groups. The sample size is similar to published CMR studies that have investigated myocardial edema, myocardial hemorrhage and MVO in other clinical settings. TA use was left to operator discretion, which can lead to a selection bias that may impact outcomes. However, the lack of a trend towards a higher thrombus burden in the TA group suggests that most of the TA use was based on a routine use policy. Lastly, we used a surface coil which can decrease the sensitivity for detecting inferolateral edema and infarction with an opposite effect in the anteroseptal region, due to an inhomogeneous coil sensitivity profile.TA as an adjunctive therapy to primary PCI is associated with a reduction in the degree of myocardial edema, myocardial hemorrhage, infarct size, left ventricular remodeling, and MVO after STEMI. The positive impact of TA on myocardial edema, myocardial hemorrhage and left ventricular remodeling using CMR is a novel finding and therefore, we believe our data contribute important findings to the current literature on this topic. However, given the small sample size and non-randomized design the results of our study are hypothesis generating only and one cannot draw a causal relationship between favorable outcomes and use of TA in primary PCI. The results of large randomized trials to assess the utility of TA on the amount of salvaged myocardium using CMR are pending ,54.CMR: Cardiovascular magnetic resonance; LVEDVI: Left ventricular end diastolic volume index; LVESVI: Left ventricular end systolic volume index; LVSVI: Left ventricular stroke volume index; MVO: Microvascular obstruction; NTA: No thrombus aspiration; PCI: Percutaneous coronary intervention; STEMI: ST-segment elevation myocardial infarction; TA: Thrombus aspiration; TIMI: Thrombolysis in myocardial infarctionDr. Wright receives research funding from GE Healthcare.MIZ: Study design, patient identification, analysis and interpretation of data, statistics, drafting of the manuscript. NRG: Study design, analysis and interpretation of data, statistics, drafting of the manuscript. KAC: Study design, analysis and interpretation of data, statistics, revising the manuscript critically for important intellectual content. SBJ: Patient identification, analysis and interpretation of data, statistics, revising the manuscript critically for important intellectual content. BHS: Analysis and interpretation of data, revising the manuscript critically for important intellectual content. EAC: Analysis and interpretation of data, revising the manuscript critically for important intellectual content. GAW: Study design, analysis and interpretation of data, statistics, revising the manuscript critically for important intellectual content. AJD: Study design, analysis and interpretation of data, statistics, revising the manuscript critically for important intellectual content. All authors have read and approved the final manuscript.


Cardiovascular events are the most common single cause of death in systemic lupus erythematosus (SLE). Several studies have described impaired systolic and diastolic function in adults with SLE.The aim of our study was to study left (LV) and right (RV) ventricular function in a population of adolescents with SLE and to discuss their clinical and prognostic implications.Cross-sectional and retrospective study of juvenile-SLE patientsÂ´ medical records. All patients underwent two-dimensional, M-mode, conventional Doppler and tissue Doppler imaging (TDI) to evaluate systolic and diastolic biventricular function.13 Juvenile-SLE female patients were included, with disease onset between 6 and 16 years of age , and mean disease duration of 6,6 years (2-15 years). One patient had moderate to severe aortic regurgitation (AoR), one had pulmonary hypertension (HTP), 5 patients had systemic hypertension (HTA); none smoked.The majority of patients presented at least one criteria of LV diastolic dysfunction. E/A ratio was normal in 6 patients and showed restrictive pattern in 4. E/E` septal ratio showed increased left atrium pressure in 2 patients. E/Vp ratio was clearly abnormal in 3 cases, predicting high mean pulmonary capillary wedge pressure. Reduced propagation velocity of the mitral valve (Vp) was observed in 4 cases, implying impaired relaxation.LV systolic function was preserved in all cases, with normal Tei index.RV systolic function was normal in all patients except for one, with AoR  14,8 mm).RV diastolic function markers were altered in some patients: decreased peak velocity of E wave in 4 patients, with increased AÂ´ wave velocity in 1 patient (HTP case). E/EÂ´and E/A ratios were normal in all cases. RV outflow tract acceleration time was decreased (implying increased mean pulmonary artery pressure) in the patient with HTP.Due to the small sample size, no correlations with other clinical or laboratorial markers were statistically significant. BNP was increased only in the AoR patient.SLE patients can have subclinical cardiac dysfunction, and diastolic changes can be an early warning sign. Subtle abnormalities of the LV/RV diastolic function were found even in the presence of a preserved systolic function. Preclinical detection of ventricular dysfunction may identify a population at risk requiring early and aggressive interventions for the prevention of cardiovascular events.


Right ventricular systolic dysfunction is associated with worsened outcomes and poor survival in patients with heart failure. However, it is unclear what mechanisms, other than the presence of RV infarction, contribute to the development of RV dysfunction in patients with severe ischemic cardiomyopathy. We sought to determine the impact of baseline demographic variables, CAD severity, LV diastolic function assessed by echocardiography, ventriculovascular coupling, LV remodeling, aortic biomechanical properties, and RV infarction, assessed by CMR, on RV ejection fraction.Patients were selected if they had undergone TTE and CMR studies within 7 days (median=1 day). 354 patients with LVEF ≤ 40% and ≥ 70% stenosis in ≥1 coronary artery but without prior mitral valve surgery, fused E/A waves, atrial fibrillation or > moderate mitral regurgitation were included. Of those, 30 patients were excluded due to suboptimal CMR image quality for adequate RV volume tracings. A total 324 charts were reviewed for demographic and laboratorial data. Diastolic function assessment was performed as per guidelines. Aortic biomechanics were measured using previously validated software  using semi-automated tracing of aortic contours with phase-contrast images and through-plane velocity encoding of the ascending and descending aorta. CMR evaluation also included long and short axis assessment of LV/RV function respectively on balanced steady state free precession images along with assessment of LV/RV myocardial scar (on phase-sensitive inversion recovery DHE-CMR sequence ~ 10-20 minutes). Multivariate linear regression analysis performed to identify the independent predictors of RVEF.Males represented 73% of the cohort with a mean age of 63 ± 11 years. Mean LVEF was 23 ± 9% and mean RVEF 42 ± 14%. DDFx was classified as either: stage 1 (44%), stage 2 (25%) or stage 3 (31%). The independent predictors of RVEF are listed on Table In patients with severe ICM, impaired ventriculovascular coupling and LV diastolic function are associated with RV dysfunction, independent of the presence of RV infarction.None.


Obstructive sleep apnea (OSA) has deteriorating effect on LV function, whereas its impact on RV function is controversial. We aimed to determine the effect of OSA and continuous positive airway pressure (CPAP) treatment on left and right ventricular  function using transthoracic echocardiography (TTE) and 2 dimensional speckle tracking (2D ST) analysis of RV deformation capability.82 patients with OSA and need for CPAP therapy were prospectively enrolled and underwent TTE at study inclusion and after 6 months of follow up (FU). Multivariate regression analysis revealed an independent association between baseline apical right ventricular longitudinal strain (RV-Sl), BMI and the severity of OSA . After CPAP therapy, LV functional parameters , and apical RV-Sl (P = 0.001) improved significantly. The effect of CPAP therapy was related to severity of OSA .OSA seems to have deteriorating effect on LV and RV function. We found a beneficial effect of CPAP on LV and RV functional parameters predominately in patients with severe OSA. 2D speckle tracking might be of value to determine early changes in global and regional right ventricular function. Obstructive sleep apnea (OSA) is a frequent sleep-related breathing disorder with an incidence of 5–20% in the middle-aged population in Europe and Northern America Using conventional Doppler echocardiography, several studies have recently reported the detrimental effect of untreated severe OSA on systolic and diastolic left ventricular (LV) function The aims of this prospective cohort study were (i) to investigate the impact of OSA and its severity on left and right ventricular function measured with echocardiography and two-dimensional strain analysis and (ii) to determine the effect of effective OSA therapy on measurable left/right ventricular functional parameters.Patients admitted between May 2009 and December 2009 to the Department of Pneumology of our hospital, for OSA screening and initiation of continuous positive airway pressure therapy (CPAP) were included in the study. Clinical follow-up examinations were scheduled after 1 and 6 months for the adjustment of CPAP therapy. Echocardiography for the detection of CPAP related changes in LV/RV function was planned at study initiation and after 6 months (±14 days) of follow up.Study endpoints were (i) prevalence of echocardiographically detectable pathologic myocardial left and right ventricular functional parameters in patients undergoing OSA screening before initiation of CPAP therapy, and (ii) the evaluation of changes in measurable LV/RV functional parameters after OSA therapy with CPAP.According to current research we hypothesized that OSA has a deteriorating effect on LV function (defined as significant decrease in LV EF) and that after a 6 months CPAP therapy the impairment could in part be ameliorated. Furthermore we assumed RV function to be likewise impaired by OSA (defined as significant decrease in RV strain) and likewise ameliorated by CPAP. All patients had to provide written informed consent prior to study inclusion; the study was approved by local ethics committee and was in accordance with the Declaration of Helsinki. Exclusion criteria were presence of predominant central sleep apnea (CSA), non compliance to CPAP (<4 h use/night) and AHI<5. However, the number of patients not compliant with CPAP or AHI<5 and willing to comply with the study protocol was too small to serve as a meaningful control group.All patients underwent an overnight polysomnographic study at baseline  and polygraphy controls after one week and 6 months .2O to the effective pressure, with a maximum of 12 cm H2O. The appropriate fixed pressure was chosen as the pressure abolishing or significantly decreasing obstructive events. Patients underwent polygraphy controls after one week and 6 months . According to current guidelines, subjects with more than five obstructive apneas and hypopneas were considered as suffering from OSA. In addition, central apneas and snoring were measured. Analysis and interpretation of sleep study data were performed without knowing the patients clinical condition.On the day of the overnight sleep study, classic baseline characteristics were assessed Table 1.CPAP was recommended to all patients who had more than 30 episodes of apnea or hypopnea per hour of sleep. CPAP was also recommended if the AHI was between 5 and 30 and the patient complained of severe daytime sleepiness that interfered with daily activities.Compliance with CPAP was checked by readings of the built in time counter of the patient’s device. Only those patients for whom calculation of the time of use per night gave a value higher than four hours were considered compliant with. The adherence to CPAP in the whole patient cohort was 4.8±1.4 hours per night, whereas the time of used CPAP showed to be 6.5±1.1 hours per night in the study cohort. Effective OSA therapy was defined as ≥25% drop in AHI or AHI<5 after 6 months of CPAP treatment and mean reduction in Epworth Sleepiness Score of 3 points Each patient had a complete standardized two-dimensional transthoracic echocardiography study for the determination of LV/RV functional parameters and dimensions according to the recommendations of the American Society of Echocardiography LV and RV myocardial performance indices (MPI) were assessed, following the original approach of Tei and colleagues and were therefore calculated as the ratio between the sum of times of the isovolumetric periods and ejection time for the right ventricle For the determination of longitudinal RV contractility, tricuspidal annular systolic excursion (TAPSE) was measured in the four-chamber view Two cine loops from apical four chamber view were digitized and stored in an echocardiographic imaging server . Offline 2D-ST-analyses of the gray scale images obtained by 2D echocardiography were done using commercially available software . The endocardium of the free RV wall was manually traced starting from the lateral tricuspdial annulus to RV apex, and was tracked by the 2D strain software along the border throughout two cardiac cycles. Accuracy of border tracking was manually verified and adjusted if needed. The free right ventricular wall was segmented visually in a basal, midventricular and apical segment. For the determination of OSA related changes in RV contractility, we compared global as well as regional RV functional parameters of the RV free wall.Exploratory data analysis was performed and no adjustment was made for multiple tests. Two-tailed P-values were calculated and considered to be significant if ranging below 0.05. Continuous data were expressed as mean values ± standard deviation. For comparisons between groups normalcy tests were done for each parameter. Continuous variables were tested for differences with the Kruskal-Wallis or One-way ANOVA test, when comparing more than two groups. For categorical variables, the Chi square or Fisher’s exact test were used for further analysis. Demographic and echocardiographic variables were evaluated for their association with severity of OSA; a variable was selected for further multivariate analysis if the level of significance in univariate logistic regression was ≤0.2 and tested in a stepwise regression model, using the severity of OSA as the dependent variable.For the assessment of inter-observer agreement, two different investigators analyzed 10 randomly chosen patients independently. For the evaluation of inter- and intraobserver reproducibility of strain measurements intra-class correlation coefficients were calculated with good agreement defined as having a coefficient >0.8.Statistics were performed using SPSS for Windows  and MedCalc statistical software .150 patients, submitted to our clinic because of suspected OSA, were screened. Only in 90 of patients significant OSA requiring CPAP therapy could be found. 5 of those declined participation in the study. 3 patients did not attend the follow up examinations and were therefore excluded from the final analysis. 82 consecutive patients with polysomnographic proven OSA were included in the study.. Overall, patients presented significant levels of daytime sleepiness (ESS 10.07±5.42) and severe OSA (AHI 30.75±5.5 n/h). Body mass index  correlated significantly to the severity of the sleep disordered breathing (P = 0.0007) .Patients were divided into three groups according to the severity of OSA following the recommendation of the American Academy of Sleep Medicine guidelines Patients in group 3 were more often obese, had significantly lower left ventricular ejection fraction and stroke volume. Values for global, apical and basal longitudinal strain were lower as compared to patients with moderate or low AHI score Table 1.Severity of OSA at baseline was significantly correlated with a decrease in measurable systolic LV function (P = 0.005) , only apical RV-Sl and BMI were independently associated with severe OSA . Severe OSA was defined as AHI>30, according to definitions by the American Academy of Sleep Medicine (9). These variables entered comparative receiver-operated-characteristic-curve (ROC) analysis  was significantly correlated with clinical and echocardiographic baseline data: r = 0.72, (P<0.0001) for correlation with AHI, r = 0.4 (P<0.0001) for global 2D RV-Sl, r = 0.36 (P = 0.001) for apical 2D RV-Sl, r = 0.35 (P = 0.001) for BMI, r = −0.17 (P = 0.13) for LV EF. These correlations were similar to correlations with AHI.The patients included in the analysis  were all highly compliant to CPAP; it was used 6.5±1.1 hours per night .AHI index and ESS decreased relevantly as evidence for clinical and subjective amelioration of obstructive sleep apnea syndrome ., After 6 months of treatment with CPAP therapy, we found a significant increase in systolic LVEF Figure 3Interestingly, in patients with severe OSA and AHI over 30, the benefit from CPAP therapy was pronounced when compared to patients with lower rates of AHI concerning RV and LV functional parameters. In those patients, even global RV-Sl improved after FU. .2D RV-Sl showed a good intra- and inter-observer agreement, which was more robust, when compared to 2D ST regional function analysis Table 3.The main findings of our study are as follows:OSA has a detrimental effect on LV and RV function, which increases with severity of disease. (ii) This effect is in part reversible under effective OSA therapy and (iii) patients with severe OSA and associated myocardial dysfunction benefit most from CPAP therapy.To the best of our knowledge, this is one of the first studies to examine the impact of severe OSA on global and regional right ventricular function as determined with 2D ST and the effect of CPAP therapy on measurable right ventricular functional parameters.The impact of obstructive sleep apnea on left and right ventricular function and structure is controversial. Theoretically, OSA relevantly influences RV and LV hemodynamics by an increase of pulmonary artery pressure during apnea episodes In the Framingham Heart study, the effect of sleep-disordered breathing on right heart structure and function was examined by Guidry and colleagues. They demonstrated that diameters of the RV cavities of the right heart and LV systolic function were not significantly diverging between two groups of patients with different severity of sleep disordered breathing The impact of OSA on systolic and diastolic LV function has been largely addressed by several authors This complies with our findings of structural and functional cardiac alterations in patients with sleep related breathing disorder and the favorable effects of CPAP.The results of a recently published study by Altekin and colleagues are, also, in line with our findings, that there is a strong correlation of RV strain and the severity of OSA. In this study RV strain was even able to detect RV dysfunction in a subclinical phase of RV function deterioration The partially discrepant findings from the cited studies concerning RV functional parameters might be due to the fact that follow up time as well as definition of OSA were not consistently defined. Furthermore, the determination of RV function is not standardized. Indirect parameters for deteriorated RV function such as RV diameter or wall diameters might not be eligible to monitor early and subtler changes in RV function.BMI was significantly related to AHI frequency and was the only demographic parameter shown to be independently associated with the severity of OSA. Nevertheless, the correlation between apical 2D RV-Sl and AHI frequency was stronger as confirmed with comparative ROC curve analysis. This emphasizes the independent and important relation of apical RV impairment and severity of OSA.2D strain imaging has been established for assessment of regional left and right ventricular function and offers a good correlation with right ventricular ejection fraction as well Furthermore, 2D strain derived parameters have been found superior to conventional echocardiographic parameters for identification of patients with severe pathological alterations in RV function such as arrhythmogenic right ventricular dysplasia (ARVD) In our study on patients with different stages of OSA, we found a significant correlation of regional and global RV strain parameters with the severity of OSA and of note, a relevant increase of RV deformation capabilities after CPAP therapy. Our data indicates that apical RV function alteration might be a sensitive parameter to detect early and even subclinical deterioration in RV function.These findings are in line with the results from Fernandez-Friera et al. who used CMR for RV function imaging in a cohort of 192 patients with different stages of pulmonary hypertension (PH). The author and colleagues found that basal RV ejection fraction (RVEF) did not differ between patients with mild or moderate PH. However, they showed that patients with moderate PH had significantly lower apical RVEF, with an apical RVEF<50% that was more sensitive than global RV dysfunction for the detection of PH Since OSA is closely related to left and right ventricular dysfunction which improves with effective CPAP therapy, we suggest an early start of CPAP therapy in all patients with relevant OSA to prevent permanent impairment of the left and right ventricular function and structure.The study is limited by its not randomized, not blinded and single side character. Our sleep clinic cohort may not reflect the findings in the general community because of the limited number of patients. Our sleep clinic cohort may not reflect the findings in the general community because of the limited number of patients. Whilst significant cardiovascular co morbidities were present at baseline in our study cohort we can not fully exclude that changes in RV or LV function could have been mediated by an indirect effect of CPAP therapy on these co morbidities. The observational design of the study does not allow for this concern to be addressed. Furthermore, there are many other confounding factors that might alter global and regional RV function in the general population. Our conclusion applies therefore specifically to a pre-selected population with proven OSA.OSA seems to have deteriorating impact on left and right ventricular function. After 6 months of therapy, we found a beneficial effect of CPAP on LV and RV functional parameters which was pronounced in patients with severe OSA. 2D speckle tracking might be of value to determine early changes in global and regional right ventricular function.Table S1Multivariate stepwise regression analysis of all echocardiographic parameters and baseline demographics.(DOCX)Click here for additional data file.