This analysis aims to assess the prognostic value of pre-operative right ventricular echocardiographic parameters in predicting short-term adverse outcomes and long-term mortality after coronary artery bypass graft (CABG).Study design: Observational retrospective cohort. Pre-operative echocardiographic data, perioperative adverse outcomes (POAO) and long-term mortality were retrospectively analyzed in 491 patients who underwent isolated CABG at a single academic center between 2006 and 2014.2 (LAVI) (OR (95% CI): 1.98 (1.03–3.82), P = 0.04), mitral E/A >2 (1.97 (1.02–3.78), P = 0.04), right atrial size >18 cm2 (1.86 (1.14–3.05), P = 0.01), tricuspid annular plane systolic excursion (TAPSE) <16 mm (1.8 (1.03–3.17), P = 0.04), right ventricular systolic pressure (RVSP) ≥36 mmHg (pulmonary hypertension) (1.6 (1.03–2.38), P = 0.04) and right ventricle myocardial performance index (RVMPI) >0.55 (1.58 (1.01–2.46), P = 0.04) were found to be associated with increased 30-day POAO. On 3.5-year follow-up, cumulative survival was decreased in patients with myocardial performance index (MPI) ≥0.55  and in patients with mitral valve E/e′ ≥14 .Average age of enrolled subjects was 66 ± 11.5 years with majority being male (69%). 227/491 patients had 30 days POAO (46%); most common being post-operative atrial fibrillation (27.3%) followed by prolonged ventilation duration (12.7%). On multivariate analysis, left atrial volume index ≥42 mL/mPre-operative right ventricle dysfunction (RVD) is associated with increased perioperative complications. Furthermore, pre-operative RVD and increased left atrial pressures are associated with long-term mortality post CABG. Coronary artery bypass graft (CABG) is the most common cardiac surgical procedure in the United States with 1 CABG being performed per 1000 individuals , 3 with Patients with advanced coronary artery disease, LV systolic and diastolic dysfunction often develop some degree of pulmonary hypertension (PH) and RVD. Left heart pathology is responsible for 65–80% of cases of PH  and 44% The importance of RV systolic and diastolic echocardiographic parameters as a prognostic tool in patients with symptomatic heart failure has already been established . IdentifIn the current study, we tested the hypothesis that pre-operative RVD is associated with adverse post CABG outcomes. Specifically, we evaluate whether parameters of RVD were associated with post-operative complications and long-term mortality after CABG.n = 1270). At our institution, patients who are at moderate-to-high risk for developing post-operative cardiac complications commonly receive a pre-operative echocardiogram. Therefore, we chose a study period of 9 years so as to allow inclusion of a reasonable number of these patients with pre-operative echocardiograms for the final analysis. Echocardiographic results were then correlated with the prospectively collected institutional cardiac surgical database as defined by the Society of Thoracic Surgeons Adult Cardiac Surgery Database. We included all patients over the age of 18 years that underwent isolated CABG (n = 491). Patients undergoing concomitant carotid surgery, atrial septal defect repairs or atrial fibrillation ablation procedures were excluded from the study. In order to study the impact of right-sided function on outcomes we wanted to have echocardiographic information as close to the surgery date as possible. Majority of our patients were worked up prior to surgery as outpatient and we felt that 3 months will be a reasonable period to complete pre-operative work-up including having an echocardiogram. Therefore, patients who did not have a pre-operative echocardiogram within a 3-month period prior to surgery were omitted. In addition, patients who had incomplete or missing echocardiographic data and those with both CABG and concomitant valve surgeries were also excluded from the final analysis . The images were reviewed and all echocardiographic variables were remeasured by two readers who were both formally trained in echocardiography . To reduce bias, both readers were blinded to the post-operative outcomes during the review process. The echocardiographic measurement protocol and reference cutoffs were based on recommendations by the American Society of Echocardiography , 15, 16.2 for male and >61 mL/m2 for female and LVESV >31 mL/m2 for male and >24 mL/m2 for female. LV left atrial volume was measured by the biplane area length method indexed to patient’s body surface area. Moderately enlarged left atrium was our abnormal cutoff defined as LAVI ≥42 mL/m2. Mitral peak E and A wave velocities were measured from the apical four-chamber view by placing the pulsed-wave Doppler sample volume between the mitral leaflet tips while pulsed-wave tissue Doppler imaging (TDI) e′ velocity was obtained by placing the pulsed-wave Doppler sample volume at the lateral mitral basal region. Grade III diastolic dysfunction was defined as E/A >2 and increased left atrial pressure was suggested by E/e′ >14. Right atrial area was obtained by planimetry in the apical four-chamber view at the end systole. Enlarged right atrial size was defined as RA area >18 cm2. Basal RV diameter was measured in the basal one-third of RV inflow at end diastole in the RV focused view. RV enlargement defined by basal RV diameter >4.2 cm. Right ventricular fractional area change (RVFAC) was measured by tracing the RV border in the RV focused view at end diastole and end systole (LV ejection fraction and LV volume were measured by the biplane method of disks (modified Simpson’s rule) from the apical two- and four-chamber views. The left volume was indexed to the patient’s body surface area. Reduced LV function defined as LVEF <40% and enlarged LV volume defined as LVEDV >74mL/m systole  and usin systole  was meas systole , abnorma systole  and RVMPWe had a total of 16 patients (3%) who had atrial fibrillation during the time of their echocardiogram. In this group, both mitral E/a and tricuspid E/a were kept as missing variables in the final analysis due to the absence of the ‘a wave’. We also chose to use the tissue Doppler method for estimating RV MPI rather than the pulsed Doppler method in order to avoid matching the R–R intervals of the analyzed beats.Composite outcome (POAO) was defined as occurrence of any one of the following adverse events within 30 days of CABG; prolonged mechanical ventilation duration of more than >48 h, re-intubation, intensive care unit readmission, post-operative atrial fibrillation, myocardial infarction, renal failure, stroke, cardiopulmonary arrest, multi-system failure/shock, cardiac-related hospital readmission for either congestive heart failure, myocardial infarction or arrhythmia and death. Long-term mortality was defined as death due to any cause starting from the time of surgery to three and half years post CABG. According to literature the mortality rate post CABG is highest in the first year (3.2%) which then decreases by the third year (0.9%) . Thus, wt tests were used to assess differences in continuous variables and discrete variables were assessed with Fisher’s exact tests or chi-square test as appropriate. Simple correlations between left- and right-sided echocardiographic parameters with outcomes were conducted. Correlations were expressed with r+ correlation coefficient and P values were placed. P value of <0.05 (two sided) was considered statistically significant. Binary logistic regression analysis, multinomial logistic regression and backward elimination stepwise regression were used to assess the association of each of the echocardiographic parameters with 30-day adverse outcomes after CABG.Continuous variables are reported as mean ± standard deviation and categorical variables are reported as count (percent). Two sample To assess intra-observer agreement, 29 patients with good echocardiographic images were randomly selected and the right-sided parameters were remeasured by the first reader (MAC). Inter-observer agreement was assessed by repeating the RV measurements from those same patients by a second reader (J C) who was blinded to previous measurements. Bland–Altman analysis and intraclass correlation (ICC) was used to assess intra-observer and inter-observer variability.A Kaplan–Meier method was performed to estimate the cumulative survival. A comparative log rank test was used to compare the survival rates between different subgroup. IBM SPSS Statistics for Windows  was used to conduct the statistical analysis.n = 338, 69%) with an average BMI of 30.5 ± 6.1 kg/m2 and the mean LV ejection fraction was 50.7% ± 12.6. Baseline clinical characteristics and echocardiographic variables have been outlined in A total of 774 patients underwent isolated CABG at our institute from January 2006 to December 2014. After review of the inclusion and exclusion criteria, a total of 491 patients (63%) were included in the final analysis. The average age of patient population was 66 ± 11.5 years, majority of patients were male  and RV MPI >0.55 were associated with 30-day POAO. After adjusting for STS PMMS, left atrial volume index ≥42 mL/m2 (LAVI) (OR (95% CI): 1.98 (1.03–3.82), P = 0.04), mitral E/A >2 (1.97 (1.02–3.78), P = 0.04), right atrial size >18 cm2 (1.86 (1.14–3.05), P = 0.01), TAPSE <16 mm (1.8 (1.03–3.17), P = 0.04), right ventricular systolic pressure (RVSP) ≥30 mmHg (1.66 (1.14–2.43), P = 0.01), PH (RVSP >36 mmHg) (1.6 (1.03–2.38), P = 0.04) and RVMPI >0.55 (1.58 (1.01–2.46), P = 0.04) were found to be associated with 30-day POAO . Post-operative atrial fibrillation was the most common POAO followed by prolonged ventilation duration, 27.3 and 12.7% respectively . Patientday POAO .Table 2P = 0.03), RVSP ≥36 mmHg (PH) (1.8 (1.04–3.06), P = 0.03) and mitral valve E/e′ >14 (2.78 (1.58–4.79) P = 0.00) were associated with prolonged ventilation duration (>48 h), while PH was found to be associated with the development of post-operative atrial fibrillation (1.8 (1.2–2.70) P = 0.01).We also investigated associations between all the individual POAO and the echocardiographic variables, we found the following: MPI >0.55 (2.1 (1.07–4.06), r = 0.182, P = 0.00), increased right atrial size  and RVSP ≥36 mmHg (PH)  correlated with having more than one adverse event within the 30-day period.Out of the 227 patients with 30-day POAO, 80 patients (35%) had more than one post-operative event within the 30-day period. Increased left atrial pressure  and LVEF ≤39% . In patients with LVEF >40%, LAVI >42 mL/m2 , E/e′ >14  and MPI >0.54  were associated with 30-day POAO. While in patients with reduced LV function none of the echocardiographic parameters were seen to have any association with 30-day POAO. The comparatively lesser number of subjects in the LVEF ≤39% group could be a possible reason for not finding any associations between RV echocardiographic indices and 30-days POAO.To study the impact of ejection fraction and RVD on POAO, we divided the study population into two groups: LVEF ≥40% (n = 352) of patients had single- or two-vessel CABG while 28.1% (n = 139) had multi-vessel CABG. Patients with multi-vessel CABG were found to have more POAO compared to single- or two-vessel CABG . No relationship between number of grafts and long-term mortality was observed.Overall, 71.7%  patients underwent cardiopulmonary bypass during surgery while the remaining patients had off pump bypass surgery. No significant difference in the incidence of POAO was observed in patients who underwent cardiopulmonary bypass vs those who underwent off pump bypass surgery .r = −0.129, P = 0.12), RVSP , TAPSE , RVFAC , RV diameter , right atrial area , mitral E/a , mitral E/e′  and left atrial size . Showing that decreasing LV function results in LV diastolic dysfunction, increased left atrial pressure, increased RVSP, enlarged right atrium and RV dysfunction. While left atrial pressure (E/e′) correlated with RVSP , right atrial pressure , right atrial size , TAPSE  and dP/dt . Showing that increasing left atrial pressure increases RVSP, right atrial pressure and size and decreases RV systolic function. Left ventricular dysfunction (LVD) was defined as having an ejection fraction less than 40% and 49 out of 491 patients had isolated LVD (10%). Right ventricular dysfunction (RVD) was defined as having an abnormal RV echocardiographic parameter; right atrial size >18 cm2, TAPSE <16 mm, RVSP ≥30 mmHg or RVMPI >0.55 (n = 52/80) of patients with both LV and RVD, 49% (24/49) of patients with isolated LVD and 48.5% (n = 127/262) of patients with isolated RVD (n = 15/80) patients with both LV and RVD, 12.2% (n = 6/49) with isolated LVD and 10.3% (n = 27/262) with isolated RVD expired on long-term follow-up  and long-term mortality . While both isolated LV and RVD had similar incidences of short- and long-term adverse outcomes. There were lesser number of patients in the isolated LVD group compared to isolated RVD group (49 vs 262) suggesting that the incidence of POAO and long-term mortality is probably increased in isolated LV compared to isolated RV. However, these observations were not statistically significant.Combined LV and RVD was found to be significantly associated with POAO , shortness of breath  and congestive heart failure exacerbation . While the remaining 70% were due to miscellaneous reasons including follow-up echocardiogram for valvular disease, PH, rule out pericardial effusion, syncope and pre-syncopal episodes, arrythmias and post-CABG cardiac arrest. Following CABG, majority of patients had no change in their LVEF  and TAPSE , had an improvement in left atrial pressures  but had worsening of their left atrial size , right atrial size , RVSP  and RVMPI . Both the left and right atria showed significant changes in size post CABG. Mean pre-operative left atrium volume index was 28 ± 12 mL/m2, which increased post CABG to 31 ± 14 mL/m2 (P = 0.038). Similarly, mean pre-operative right atrial area was 29 ± 16 cm2 which increased post CABG to 32 ± 15 cm2 (P = 0.00). Therefore, both the left and the right atrium undergo remodeling post CABG. Percentage change in pre and post CABG echocardiographic variables did not show any association with POAO or long-term mortality. Post CABG, the following persistently abnormal echocardiographic parameters were found to be associated with 30-day POAO; right atrial size >18 cm2 (2.77 (1.26–6.08), P = 0.01), RVSP >30 mmHg (2.32 (1.25–4.29), P = 0.01) and MPI >0.55 (3.29 (1.64–6.61), P = 0.00). Interestingly we can conclude that persistent RVD which does not improve following CABG could potentially be a marker for 30-day POAO. Unfortunately, we did not have sufficient data to study the association between persistent RVD post CABG and long-term mortality.Only 169 patients (34%) had post CABG echocardiogram on follow-up within a median of 2.5 (IQR: 1–12) months from the procedure. We looked at the indication for the post-procedure echocardiogram and the major reasons were the following: chest pain (P = 0.02). Long-term mortality included all patients who died within 30 days and also those who died within three and half years after CABG. A total of 53 patients died over the follow-up period (11%). Cumulative survival was decreased in patients with RVMPI ≥0.55  and in patients with mitral valve E/e′ ≥14  . Within the 30 days following CABG, nine patients had multisystem failure out of which seven died (78%) and 13 patients had cardiopulmonary arrest out of which seven died (54%). Thirty-day mortality was found to be associated with increased left atrial pressures as measured by mitral E/e′ >14 (2.9 (1.15–7.1), = 0.026) .Figure 42; basal RV diameter, −0.08 ± 0.228 cm; RVFAC, 1.7 ± 9.2%; TAPSE, 0.07 ± 0.2 cm; TDI S′, 0.05 ± 0.22 cm/s; tricuspid valve E/e′, −0.09 ± 0.59; RVSP, 1 ± 3 and RVMPI, 0.01 ± 0.04. ICC for the variables were the following: right atrial size, 0.98; basal RV diameter, 0.95; RVFAC, 0.89; TAPSE, 0.95; TDI S′, 0.99; tricuspid valve E/e′, 0.98; RVSP, 0.99 and RVMPI, 0.98.Bland–Altman analysis of intra-observer variability of the RV echocardiographic parameters showed the following: right atrial size, 0.09 ± 0.98 cmBland–Altman analysis of inter-observer variability of the RV echocardiographic parameters showed the following: right atrial size, −0.38 ± 2.39; basal RV diameter, −0.035 ± 0.42, RVFAC, 4.85 ± 10.3; TAPSE, 0.01 ± 0.24; TDI S′, 0.1 ± 2.29; tricuspid valve E/e′, 0.26 ± 1.3; RVSP, 4.44 ± 8.59 and RVMPI, −0.01 ± 0.1. ICC for the variables were the following: right atrial size, 0.88; basal RV diameter, 0.88; RVFAC, 0.84; TAPSE, 0.92; TDI S′, 0.9; tricuspid valve E/e′, 0.93; RVSP, 0.94 and RVMPI, 0.835.A value between 0.75 and 0.9 is an indicator of good reliability, whereas a value more than 0.9 is an indicator of excellent reliability . In the Our study shows the importance of pre-operative echocardiography as a screening modality for patients scheduled for CABG and highlights the role of RV and its relationship with short-term and long-term post-surgical outcomes. Increased left and right atrial size, grade III diastolic dysfunction, TAPSE, PH and abnormal RVMPI were found to be strongly associated with 30-days POAO while RVMPI ≥0.55 and mitral valve E/e′ ≥14 were associated with long-term mortality.Reduced right ventricular function following myocardial infarction is a major risk factor for death, heart failure, stroke  and longPre-operative RVD is a predictor of POAO following CABG , 24. Then = 71, 14%) and advanced heart failure. This could well be the reason why we did not find any association between POAO and RVFAC or TDI S′. Therefore, MPI which takes into account both the RV systolic and diastolic functional status and TAPSE are relatively better in detecting subclinical RVD as demonstrated by our findings.RV MPI globally estimates both the systolic and diastolic function of the RV. Its main advantage being that it is independent of geometric assumptions while being relatively independent of preload and afterload . The impIncreased left atrial size is not only a surrogate marker for LV diastolic dysfunction and chronically elevated left atrial pressures but also for RVD. Increased left atrial pressures over time increases pulmonary venous pressures and eventually affects RV function. After myocardial infarction, the scared myocardium affects LV relaxation and filling pressures and with time eventually results in left atrial dilation. Adverse LA remodeling following STEMI has been reported to be associated with unfavorable prognosis . SimilarDiastolic dysfunction with elevated LV end diastolic pressure has been reported to increase perioperative mortality and morbidity . In our The impact of PH on patients undergoing cardiac valve surgeries has already been established , 33, 34,On long-term follow up, patients with pre-operative RV MPI >0.55 (RVD) or mitral valve E/e′ >14  had increased all-cause mortality at the end of three and half years. This finding highlights the fact that patients who develop RVD as a result of elevated left atrial pressures and pulmonary venous hypertension are at increased risk for long-term mortality. The observed mortality trend on long-term follow-up suggests that the RV might have a larger contributory role to the overall cardiac function than previously thought. It is possible that even after CABG, in the presence of persistent LV stiffness; the RV might continue to undergo remodeling which with time eventually leads to long-term mortality. Therefore, post CABG, there might be a benefit in regularly monitoring such at-risk patient population and adequately optimizing their heart failure management.The major limitation is that this is a retrospective study with a small sample size. The study was conducted in a single center and involved patients with similar ethnic characteristics. Conducting the study in two to three centers would have increased the sample size and the diversity of the patient population resulting in increased validity of the observed findings. Our study sample could potentially reflect a sicker population since moderate-to-high-risk patients are usually evaluated with pre-operative echocardiograms. This could explain the high number of POAO observed in our study. The quality of the echocardiographic images and RV functional assessment was limited in some of the patients by their body habitus. We also had a limited number of follow-up echocardiograms post CABG, which restricted our post-operative analysis. Finally, only 53 patients were found to have a mortality event on post CABG follow-up. Since this is a relatively smaller number of events, we did not pursue further multivariate survival analysis. Even though, the mortality data are small it does suggest a relationship between pre-CABG E/e′ and RVMPI with long-term mortality and larger sample sized prospective studies will help to further validate this observation.In our study, we showed the importance of echocardiography as a non-invasive screening tool for identifying patients at high risk for post-operative complications. We also demonstrated the importance of right ventricle for the overall function of the heart since pre-operative RVD was associated with both POAO and long-term mortality. In addition, we highlighted the importance of left atrial pressures and atrial size and its impact on short-term outcomes. Thus, patients identified to have increased left atrial pressures, PH or RVD prior to CABG might benefit from optimization of volume status prior to surgery in order to improve outcomes, reduce post-operative complications and medical costs. In addition, patients with RVD or increased left atrial pressures will need long-term monitoring and medication optimization in order to decrease long-term mortality.The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.This work did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.


To evaluate the potential for right ventricular reverse remodelling after pulmonary valve replacement using cardiac magnetic resonance imaging, in adults with corrected tetralogy of Fallot and severe pulmonary insufficiency.Ten patients with previous correction of tetralogy of Fallot with severe pulmonary insufficiency accepted for pulmonary valve replacement were evaluated prospectively with cardiac magnetic resonance imaging preoperatively and re-evaluated 10 ± 5 months postoperatively. Follow up for survival was 100% complete with mean of 37 ± 12 months.2 to 120 ± 23 ml/m2 postoperatively, p < 0.001. The preoperative mean indexed right ventricular stroke volume was reduced from 72 ± 20 ml/m2 to 50 ± 6 ml/m2 postoperatively, p = 0.002. After pulmonary valve replacement, the right ventricular ejection fraction did not change significantly . Pulmonary insufficiency fraction decreased from 49% ± 11 to 1% ± 1 postoperatively, p < 0.001.The preoperative mean indexed right ventricular end-diastolic volume was reduced from 161 ± 33 ml/mPulmonary valve replacement leads to a favourable early reverse remodelling with a reduction in RV volumes and improved function in all patients regardless of their preoperative indexed right ventricular volume. Patients with TOF undergo cardiac surgery in the early years of childhood. Surgical correction is performed with excellent results and early mortality is low . However2 , 11. TheThe present study was a prospective, non-randomized observational study in which patients with previous correction of TOF with severe PI accepted for PVR were included. Patients were evaluated with cMRI preoperatively and re-evaluated 6 to 12 months postoperatively, according to a study protocol. Permission to proceed with this study was granted by the institutional Ethics Review Board, Lund, Sweden and individual consent was obtained from all patients enrolled.The current indications for PVR for severe PI in patients with corrected TOF according to the most recent guidelines , 11 are n = 5) [n = 5), was implanted by one expert surgeon in adults with congenital heart disease. All implantations were performed on cardiopulmonary bypass support and moderate hypothermia. The majority of the procedures (n = 8) were performed without cardioplegic arrest. When necessary, myocardial protection was achieved with cold blood anterograde cardioplegia. Valve sizing was based on preoperative magnetic resonance imaging as well as intraoperative assessment of the RV outflow tract. Adequate function of the prosthesis was assessed by intraoperative transoesophageal echocardiography immediately after weaning from cardiopulmonary bypass. Postoperative anticoagulation consisted of acetylsalicylic acid (75 mg) three months postoperatively and low-molecular-weight heparin administered during the immobilization phase in the early postoperative period.The RVOT Elan™  conduit (n = 5)  or the Shttp://segment.heiberg.se) was used for all image analysis [Cardiac magnetic resonance imaging was the primary investigation technique for evaluation of RV hemodynamics –15. Patianalysis .Follow-up was performed in February 2017 and was 100% complete for survival . Follow-up with cMRI was performed after a mean of 10 ± 5 months postoperatively and was 100% complete.2, RV end-systolic volume (RVESVI) was considered normal if ≤41 ml/m2, and mean indexed RV stroke volume (RVSVI) was considered normal if ≤65 [Postoperative bleeding was defined as bleeding leading to exploration; postoperative heart failure was defined as the need for postoperative inotropic support (norepinephrine and/or dobutamine infusion) for more than 24 h; acute myocardial infarction was diagnosed by electrocardiography (ECG) (new permanent Q-wave), echocardiogram  and cardiac enzymes (aspartate aminotransferase (AST) > 2 μkat/L or creatine kinase myocardial specific isoform (CK-MB) > 50 μg/L); postoperative atrial fibrillation (AF) was defined as one or recurrent episodes of supraventricular tachyarrhythmia after cardiac surgery, monitored by continuous telemetry ECG or with an ECG recording using atrial epicardial leads. Early mortality was defined as all-cause mortality within 30 days of surgery.Mean indexed RV end-diastolic volume (RVEDVI) was considered normal if ≤99 ml/ ml if ≤65 . Postopep-value less than 0.05 was considered statistically significant. Statistical analyses were performed with the statistical software package SPSS .Descriptive data are presented as number (%) or mean ± SD. All data were indexed for body surface area. The two-tailed paired Student’s t-test was used to compare the intra-individual pre-operative and postoperative data. In addition, Wilcoxon Rank test was used, compensating for lack of normal distribution. A Patient characteristics are presented in Table n = 1), supraventricular tachycardia (n = 1), and low cardiac output syndrome (n = 1). One patient presented with dyspnoea and flank pain three weeks postoperatively and was diagnosed with pulmonary embolism. The patient was subsequently treated with Warfarin and the medical work up revealed a heterozygote carrier for the prothrombin gene mutation. The mean length of postoperative hospitalization was 10 ± 4 days. All patients were alive at the time of follow-up.There was no intraoperative or early mortality. The mean time interval since the last intervention was 20 ± 14 years. The mean pulmonary prosthetic valve size was 25 ± 1.5 mm. Intraoperative data and postoperative outcome are demonstrated in Table p < 0.001. The preoperative RVEDVI was reduced from 161 ± 33 ml/m2  to 120 ± 23 ml/m2  postoperatively, p < 0.001  to 71 ± 21 ml/m2  postoperatively, p = 0.036. The pre- and postoperative RVEDVI for each patient is shown in Fig. p = 0.337). The preoperative RVSVI was reduced from 72 ± 20 ml/m2 (range 43 to 107 ml/m2) to 50 ± 6 ml/m2 (range 37 to 57 ml/m2) postoperatively, p = 0.002. The preoperative mean net flow in the main pulmonary artery (MPA) was 5100 ± 1500 ml/min  with an increase to mean 6100 ± 800 ml/min  postoperatively, p = 0.120.Pre- and postoperative cMRI data are in presented in Table 2  to 50 ± 6 ml/m2  postoperatively, p = 0.001. The preoperative mean indexed left ventricular end-systolic volume (LVESVI) increased from 36 ± 8 ml/m2  to 40 ± 11 ml/m2  postoperatively, p = 0.271. The preoperative mean indexed left ventricular end-diastolic volume (LVEDVI) increased from 79 ± 10 ml/m2  to 90 ± 15 ml/m2  postoperatively, p = 0.012.The preoperative mean indexed left ventricular stroke volume (LVSVI) increased from 43 ± 7 ml/m2 in the majority of the cases, there was a significant reverse remodelling with a reduction in right ventricular end-diastolic volume 6–12 months postoperatively. However, the RVEDVI did not reach normal values postoperatively in any case but one.Data in the present study indicates that even though the preoperative mean RVEDVI exceeded 160 mL/m2 have been proposed as an indication for PVR in asymptomatic adults with congenital heart disease with previously corrected TOF. Therrian et al. has previously reported that the RV does not reach normal volumes following surgery if the preoperative RVEDVI exceeds 170 ml/m2 [2 has been shown to predispose for an incomplete reverse remodelling [2. In the current study, the preoperative mean RVEDVI was 161 ± 33 ml/m2. The majority of the patients did not reach normal RVEDVI (≤ 99 ml/ m2) 6–12 months postoperatively as assessed by MRI. This incomplete pattern of reverse remodeling could also be shown for patients with RVEDVI lower than the cut-off of 160 ml/ m2. However, a significant reverse remodeling was present in all patients despite not reaching normal postoperative RV volumes. In addition, RVSVI decreased after surgery, reaching normalization. Data in the present study showing early RV reverse remodeling are consistent with those of previous studies [2) from 7 to 18 months after PVR [Optimal timing of PVR due to severe PI in TOF is still a subject of debate as beneficial effects of PVR have to be weighed against the risk for repeat PVR. Performing PVR early during follow-up could be associated with an improved RV remodelling –21, but 70 ml/m2 . Similarodelling . Accordiodelling , 11 norm studies , 25–28. fter PVR . This isp = 0.337) after PVR. However, the preoperative RVEF does not show the actual ejection fraction as approximately 50% of the stroke volume is regurgitated to the RV. This implies that the RVEF actually improves postoperatively when there is only negligible remaining PI. Furthermore, an increase in LVEDVI, LVESVI and left ventricular stroke volume could be observed postoperatively. Our findings are supported by Oosterhof et al. showing that RV dysfunction may negatively affect left ventricular (LV) function as RV volume overload due to PI correlated to lower RVEF and LVEF as well as higher BNP levels [In the present study, data indicated a positive change in right-to-left ventricular interaction after surgery. The RVEF did not change significantly, 46% versus 42% (P levels . In our This was a prospective study with a consistent cMRI protocol with the following clinical implications. The improvement in RV size following PVR compared to pre PVR measurements assists clinical decisions regarding timing of valve or conduit replacement. However, no clear cutoff for preoperative RVEDVi that “guarantees” normalization of RV size post PVR could be identified. Moreover, given that previous data  show graOne limitation of this study is the lack of a control group. The relatively small number of patients results in a loss of statistical power, requiring validation using larger groups of patients. Even though our data have been validated previously in larger studies, these have been retrospective and heterogeneous in contrast to our prospective study.PVR leads to a favourable early reverse remodelling with a reduction in RV volumes and improved biventricular function. A significant reverse remodeling was present in all patients despite not reaching normal postoperative RV volumes.


Transcatheter closure of perimembranous ventricular septal defects is one of the greatest challenges in interventional cardiology. Short- and midium-term follow-up data for large samples are limited. This report presents our experience with transcatheter closure of perimembranous ventricular septal defects using an occluder.Two hundred fifty-three patients included in the database of the Second Affiliated Hospital and Yuying Children’s Hospital from January 2011– December 2015 with transcatheter closure of perimembranous ventricular septal defects and discharged from follow-up. All patients were invited for clinical and transthoracic echocardiography, electrocardiogram, and thoracic radiography check-up.Device implantation was successful in 252 of 253 patients (99.6%). The median age was 42 months (range 27–216 months). The median follow-up duration was 36 months (range 6–60 months). The mean defect diameter was 3.5 ± 1.4 mm and the mean size of the ventricular septal defect rim below the aortic valve was 3.7 ± 1.8 mm. The mean diameter of the devices used was 4 mm. Thirty-seven patients developed arrhythmia after the procedure and recovered within 24 months; four patients had hemolysis and four had moderate tricuspid valve regurgitation. No other serious adverse event occurred during the follow-up period.Transcatheter closure of perimembranous ventricular septal defects using an occluder is safe and effective in most patients.The online version of this article (10.1186/s12872-019-1188-y) contains supplementary material, which is available to authorized users. The ventricular septal defect (VSD) is one of most common congenital heart defects worldwide. Perimembranous ventricular septal defect, involve a more extensive area than normal membranous septum, also known as aortic subvalvular type. The defect is surrounded by membrane, or the upper edge is fibrous and the lower edge is muscular. With advances in imaging and screening of infants, the detection rate of confirmed cases of VSD has increased notably . Almost Admittedly, traditional surgical repair has yielded great results. Nevertheless, residual VSDs are frequently associated with complications, such as reoperation, infection, sternotomy scarring, and even death , 4. In 1This retrospective, descriptive, non-randomized study utilized data from January 2011–December 2015 from a single medical center . Two hundred fifty-three patients  were included  should be used to monitor the occluder location and sharp, and check for residual shunt and tricuspid valve, and to assess the movement of the aortic valve.The following occluder devices were used Tables , 4 and 5Immediately following the procedure, and in months 1, 3, and 6 and years 1, 2, 3, 4, and 5 of follow-up, the shape and orientation of the device and residual shunt were reevaluated through transthoracic echocardiography, electrocardiogram, and thoracic radiography.2-test or Fisher method. All statistical analyses were performed using commercially available software . P values < 0.05 were considered to be significant.Continuous data were expressed as means ± standard deviations with ranges and were compared using analysis of variance (ANOVA) and the student’s t-test, while categorical data are expressed as number and percentage, and were compared using the XThe median age at implantation was 42 months (range 27–216 months) and the median weight was 14.75 kg (range 9.5–86 kg). All patients had continuous systolic murmurs and left-to-right shunts with enlarged left ventricular diastolic dimensions. No patient received diuretics or angiotensin-converting enzyme inhibitors before the procedure for there was not any grade II or higher cardiac dysfunction after preoperative evaluation. Transcatheter femoral venous and arterial approaches were used in all patients. The mean VSD size, measured echocardiographically, was 3.5 ± 1.4 mm. Pulmonary-to-systemic flow ratio (Qp/Qs) was 2.3 ± 0.4 (range 1.5–3.0). One patient with Down syndrome underwent transcatheter closure, and a residual shunt, hemolysis, and arrhythmia was found 24 h postoperative. A surgical operation was subsequently performed. (Tables In 252 of 253 99.6%) procedures, defect closure was successful Fig. . Stable % proceduPre-operatively, four patients had moderate tricuspid valve regurgitation and nine had mild aortic valve regurgitation. No significant increase or new regurgitation of the aortic or tricuspid valve occurred during or after the procedure. All cases of valve regurgitation had resolved without treatment at the 2-year follow-up evaluation , 3 months (n = 3), 6 months (n = 7), 1 year (n = 1), and 2 years (n = 1) postoperatively. The occlusion rate at 2 years postoperatively was 96% . Echocardiography confirmed the achievement of complete closure in the remaining patients, excluding the patient with a significant shunt described above, at 1 month  patients showed erythrocyte positivity (+++) on routine urine tests during the first 24 h postoperatively, the hemolysis was not sufficiently severe in any case to warrant retrieval of the device. Blood analysis showed high values for hemolysis parameters with no relevant decrease in the hemoglobin concentration. Hemolysis regressed by 5 days postoperatively with hydration and urine alkalization. Blood transfusion was not required in any case.Minor arrhythmic complications occurred in 37 (17.4%) patients: 14 patients had incomplete right bundle branch block and were treated with a conventional dose of methylprednisolone (20–30 ml/kg/d), which was gradually tapered. 8 had complete right bundle branch block, 3 had left bundle branch block, and 12 had left anterior fascicular block. All patients had recovered, as demonstrated by ECG, at the 24-month follow-up evaluation.Patients with right bundle branch blocks were treated with a conventional dose of methylprednisolone , which was gradually tapered. As left bundle and left anterior branch blocks have been reported to lead to death due to heart failure in China, the methylprednisolone dose can be increased to 20–30 mg/kg/d to relieve ventricular septal edema.VSD closure with an occluder was performed successfully in 252 patient. The patients were followed for a median follow-up period of 36 months (range 6–60 months). And the 6 months of follow-up with clinical examination, chest radiography, TTE and ECG was completed in 250 patients (250/253), 1 year in 236 (236/243), 2 years in 190 190/208), 3 years in 151 (151/169), 4 years in 101 (101/116), 5 years in 32 (32/45)  is the most common congenital heart disease, with 40 to 60% of patients with spontaneous closure, mostly in preschool children .Surgical closure of VSD has always been a traditional treatment, but there are many complications , 9, 10. Muscular and perimembranous VSDs have been closed using transcatheter devices at our center since 2002. Use of the transcatheter approach for the treatment of congenital heart diseases is appreciated by patients and their parents because of its decreased psychological impact (avoidance of a large scar), shorter hospital time, reduced pain and discomfort, and avoidance of admission to the intensive care unit . In our The complete VSD closure rate immediately after the procedure was 86.6%, as documented by left ventricular angiography and TTE. This rate increased to 95.3% at the 6-month follow-up evaluation and 96% at the 2-year follow-up evaluation. The follow-up was remained for those children with residual shunts, and most residual shunts resolve postoperatively. These good closure rates are similar to those obtained in other studies of transcatheter VSD closure. Residual shunt is commonly seen in cases of multiple VSDs, as the occluder size must be appropriate for complete defect coverage. Thus the location of the occlusion and the type of occluder should be flexibly selected according to the specific conditions. The general principle to achieve the goal of completely closure of the defect without affecting the function of the aortic valve and the right atrioventricular valve, as well as to reduce the occurrence of complications.Hemolysis occurred in 4 (1.6%) patients in this study, in whom the mean VSD diameter was 8.1 ± 1.3 mm. All four of these patients had residual shunts. Postoperative hemolysis occurred in association with large defects, high shunt pressure, and residual shunt after closure. Squeezing and collision associated with rapid blood flow through the occluder can cause the mechanical rupture of red blood cells, leading to hemolysis. In these cases, aspirin was stopped and 5% sodium bicarbonate solution (5 ml/kg/d) was used for hydration and alkalization, after which three patients returned to normal after 5 days. The remaining patient developed severe hemolysis accompanied by arrhythmia and residual shunt, necessitating removal of the occluder via surgical thoracotomy.Thirty-seven (17.4%) patients developed arrhythmia postoperatively. Patients with right bundle branch blocks were treated with a conventional dose of methylprednisolone , which was gradually tapered. As left bundle and left anterior branch blocks have been reported to lead to death due to heart failure in China, the methylprednisolone dose can be increased to 20–30 ml/kg/d to relieve ventricular septal edema. Conduction block is related to oppression of the left and right bundle branches due to repeated stimulation of the right ventricular surface at the defect edge by the intraoperative catheter, leading to inflammation of the marginal tissue, edema, and/or exudation. Therefore, excessive long-term intracardiac procedures should be avoided, and the occluder should be slightly larger than the defect diameter of 1–2 mm to avoid compression of the irritated edge tissue (which would lead to tissue edema), thereby preventing arrhythmia. However, evaluating patients with postoperative arrhythmia, ECG monitoring and not 24 h Holter monitoring are limited.For valve regurgitation, valve insufficiency is associated with the use of an oversized occluder or an insufficient distance from the occluder edge to the valve. A left ventricular disc diameter of the occluder exceeding 50% of the circumference of the subaortic outflow tract has been reported to lead to outflow tract deformation, and thus to valve insufficiency . TherefoPostoperative follow-up chest radiography showed gradual reduction of the cardiothoracic ratio, with eventual stabilization at 50%, which is close to the normal physiological index. TTE performed immediately after occlusion and 6 months postoperatively showed gradual reduction of the left ventricular end diastolic diameter, right ventricular diameter, and left atrial diameter, indicating smaller inner diameter of the heart cavity and the restored heart structure. At the 12-month follow-up evaluation, the inner diameter indexes of patients’ hearts had increased, but were consistent with the normal developmental ranges in all age groups, suggesting the improvement of hemodynamics. The postoperative TR-PG was significantly lower than preoperatively, suggesting that the pulmonary artery pressure had decreased. The pre- and postoperative left ventricular ejection fraction values did not differ significantly, likely due to the relatively small sizes of defects in this sample.TTE showed that the left atrium of patients was reduced compared with preoperative, and gradually increased during follow-up. Preoperative left ventricular volume overload and heart enlargement was detected with TTE; postoperatively, due to disappear shunt, the load of the heart was cut down and the heart became smaller than preoperatively. During the follow-up period, the heart became larger due to children growth. For children with growth and development, it is more intuitive to use the z-values to evaluate the heart. However, the z-values commonly used in the world are mainly applicable to Western countries such as Europe and the United States, while these are not suitable for East Asian Chinese. Recently, many centers are now gradually conducting research on the application of Z-values for children’s TTE indicators in East Asian countries such as China Additional file 2:Table S2. Size of Perimembranous ventricular septal defect. (DOCX 15 kb)Additional file 3:Table S3. Data for pulmonary artery pressure. (DOCX 15 kb)


Restoring blood flow following an acute myocardial infarction saves lives, but results in tissue damage due to ischaemia–reperfusion injury (I/R). Ameliorating this damage is a major research goal to improve recovery and reduce subsequent morbidity due to heart failure. Both the ischaemic and reperfusion phases represent crises of cellular energy provision in which the mitochondria play a central role. This mini-review will explore the rationale and therapeutic potential of augmenting the creatine kinase (CK) energy shuttle, which constitutes the primary short-term energy buffer and transport system in the cardiomyocyte. Proof-of-principle data from several transgenic mouse models have demonstrated robust cardioprotection by either raising myocardial creatine levels or by overexpressing specific CK isoforms. The effect on cardiac function, high-energy phosphates and myocardial injury will be discussed and possible directions for future research highlighted. We conclude that the CK system represents a viable target for therapeutic intervention in I/R injury; however, much needed translational studies will require the development of new pharmacological tools. The energy requirements of the human heart are exceptionally high, requiring the equivalent of 6 kg ATP (adenosine triphosphate) per day . This reEarly revascularisation of the ischaemic region has proved to be a highly effective strategy in the clinic, to the extent that mortality from acute myocardial infarction has fallen in recent years, with the correlate that there are now more patients living with the long-term consequences such as heart failure ,5. It isThe cellular conditions that favour reperfusion injury include elevated levels of intracellular calcium, a rising pH  and a burst of reactive oxygen species (ROS) that occurs with reoxygenation . These aWorkloads may change dramatically, yet in the normal heart, cellular ATP levels remain static. This is due to the buffering capacity of the creatine kinase (CK) phosphagen system, which involves the reversible transfer of a ‘high-energy’ phosphoryl group catalysed by CK see  10]:Cre:Cre10]:CThe forward reaction occurs within the mitochondrial intermembrane space where the octameric mitochondrial isoform of CK (Mt-CK) is functionally coupled to the adenosine nucleotide translocator (ANT), which channels newly generated ATP, and to the voltage-dependent anion channel (VDAC) . The resGATP|)  [The guanidinoacetate methyltransferase (GAMT) knockout (KO) mouse is a case in point. These mice have whole-body creatine deficiency due to an inability to synthesise creatine . When fepe (WT)] . This wain vivo cardiac function is subtle and only unmasked using sophisticated imaging techniques [ex vivo, end-diastolic pressure rose over 2-fold higher in the KO hearts, which corresponded with greater accumulation of intracellular calcium compared with WT. The consequence was a delayed functional recovery during the reperfusion period [A similar picture emerges in mice lacking both M-CK (muscle isoform of creatine kinase) and Mt-CK , where residual CK activity is ∼3% of WT . The effchniques . Neverthn period .GATP| [GATP requirements of all the major ATPases [Since M-CK is functionally coupled to SERCA, it is a reasonable hypothesis that CK deficiency may result in an early increase in ADP-to-ATP ratio thereby lowering local |ΔGATP| . This woGATP| ,26,27. N ATPases .An important caveat is that these genetic models represent innate loss of CK function, which is likely to result in long-term compensatory adaptations , even thin vivo I/R had better contractile function and preserved ATP levels compared with saline controls [ex vivo tissue lysates that could be prone to blood contamination.The earliest approach to be tested was parenteral administration of PCr at the time of, or shortly before, myocardial ischaemia . Forcontrols . Using acontrols  found thPCr is too polar to passively cross the plasma membrane  and is nAcute PCr administration has been tested in numerous small-scale clinical trials. Although much of the primary literature is in less accessible or non-English language journals, a recent meta-analysis reports overall positive outcomes on short-term all-cause mortality and reperfusion arrhythmias . For exaOral or parenteral administration of creatine has no measurable effect on myocardial creatine content , since tGATP|, closely mimicking the impaired bioenergetics observed in heart failure models [Our laboratory created a mouse with cardiac-specific overexpression of the creatine transporter (CrT-OE), leading to elevated, but highly variable, levels of myocardial creatine . Countere models –46. Furte models ,48.in vivo protocol of 45 min no-flow ischaemia and 24 h reperfusion, we found that CrT-OE hearts were protected compared with WT, exhibiting 27% less myocardial necrosis (comparable to ischaemic post-conditioning). In the standard ex vivo I/R protocol, the CrT-OE hearts showed a significantly improved recovery of contractile function. 31P-NMR (phosphorus nuclear magnetic resonance) revealed that CrT-OE mice had 49% more PCr and higher |ΔGATP|, both before onset of ischaemia and very rapidly after reperfusion. This suggests that an expeditious re-energisation of CrT-OE hearts, which if used to regain ionic homeostasis, could underpin the shortened period of reperfusion hyper-contractility [r = 0.81), and could be used as an anaerobic fuel source during ischaemia. In addition, HL-1 cells loaded with creatine were more resistant to mPTP opening in response to ROS challenge [This model has allowed us to define a safe range for creatine elevation at 20–100% above normal. Hearts in this moderate range maintain a normal PCr-to-creatine ratio, did not exhibit the detrimental metabolic changes, and exhibited normal cardiac structure and function even at 18 months of age ,49. Usinhallenge ,51. Howehallenge .The cardioprotective effect of elevated creatine via CrT-OE appears to be robust since improved functional recovery persists in both males and females, in ageing mice, and in mice with pre-existing cardiac hypertrophy. Furthermore, protection was additive to hypothermic cardioplegia .ex vivo functional recovery and reduce ischaemic contracture in rat I/R studies since phospho-cyclocreatine persists for longer during the ischaemic period thereby maintaining ATP levels for longer [An alternative strategy has been to partially replace creatine by prior feeding of a synthetic analogue, cyclocreatine, which participates in the CK reaction but at a slower reaction velocity. This has been shown to improve r longer –56. Simir longer . The potThere is substantial evidence in various model systems that augmentation of CK isoforms may also provide protection against I/R injury.Liver mitochondria from mice overexpressing ubiquitous Mt-CK (an isoenzyme not expressed in heart) were found to be resistant to mPTP opening. This requires localisation of Mt-CK within the intermembrane space and the presence of creatine, which promotes the tight functional coupling between Mt-CK, ANT and VDAC and oxidative phosphorylation ,59. Simiin vivo (29% versus 55% in WT). Isolated cardiomyocytes from Mt-CK-OE hearts exhibited delayed opening of the mPTP in response to ROS challenge, and this was confirmed independently by measuring mitochondrial swelling following high calcium challenge [The cardiomyocyte-like HL-1 cell line does express CK and is arguably more relevant . When Mthallenge .A further consideration is that Mt-CK is likely to have a structural role within the mitochondrial membrane space where it forms contact sites that span the inner and outer membranes to provide mechanical stability that may reduce opening probability of the mPTP ,64–66. Iex vivo I/R model [Conditional overexpression of M-CK in mouse heart is also protective in the /R model . At the The current findings from genetically modified mice provide compelling evidence that CK system augmentation provides substantial protection against myocardial I/R injury. However, verification of findings in large animal models is impeded by a lack of pharmacological tools. There are currently no compounds known to up-regulate activity of CK or CrT in the heart, and to our knowledge, no systematic attempts to identify such modulators.in vitro despite CrT inhibition, and although the effect size was modest, this approach deserves further study [One potential approach may be to circumvent the CrT by giving creatine analogues that can independently cross the plasma membrane. For example, di-acetyl creatine ethyl ester was recently shown to accumulate in brain slices er study .in vitro gene array approach, we identified thioredoxin-interacting protein (Txnip) as an endogenous inhibitor of CrT uptake that is switched on when intracellular creatine levels are high [Clearly, a greater understanding of how CK and CrT are regulated in health and disease would be useful. By way of example, the only verified endogenous regulator of cardiac CrT is via substrate inhibition (reviewed in ref. ). Using are high .Further study could be directed at whether there is a synergistic effect of simultaneous augmentation of enzyme and substrate. This could easily be accomplished by crossing existing CrT-overexpressing and CK-overexpressing mouse lines. Given that much higher myocardial creatine content may be safe if additional CK is available , it is p12 receptor antagonists [In recent years, there has been much concern at the poor record of translatability from preclinical I/R studies into the clinical setting ,73. In aagonists ,74,75. Iagonists .Finally, expansion of these findings to other organs at risk from I/R injury, e.g. skeletal muscle, brain, and kidney, is merited, and it remains untested whether this approach would also be beneficial in the transient ischaemia of angina.Evidence from genetically modified mice unequivocally shows that an intact CK system is essential for optimal recovery from I/R injury. Furthermore, augmentation of creatine levels or CK activity (regardless of isoform) represents a promising therapeutic strategy that deserves to be further explored.


Background and Objective: Childhood obesity is one of the worldwide health problems with an increasing prevalence and accompanied by severe morbidity and mortality. It is a serious predisposing risk factor especially for the development of cardiovascular diseases and arrhythmias. Electromechanical delay (EMD) is known to be a predictor for the development of atrial fibrillation (AF). Our study aims to investigate whether EMD, which is a predictor of AF, prolongs in obese children or not. Material and Methods: The study included 59 obese patients aged between 8–18 years and 38 healthy patients as the control group with a similar age and gender. All the individuals underwent transthoracic echo and tissue Doppler echocardiography. Systolic and diastolic left ventricular (LV) functions, inter- and intra-atrial electromechanical delay were measured by tissue Doppler imaging (TDI) and conventional echocardiography. Results: Obese patients had significantly lengthened P-wave on surface ECG to the beginning of the late diastolic wave (PA) lateral, PA septum, intra- and inter-atrial electromechanical delays when compared with the control group  Inter-atrial EMD and intra-atrial EMD correlated positively with body mass index (BMI) values  BMI was significantly related with inter-atrial EMD  However, there was no relationship between inter-atrial EMD and serum glucose and platelet count. Conclusion: In our study, we declared that electromechanical delay was increased in obese children when compared to the control group and intra- and inter-atrial electromechanical delay was in correlation with body mass index. Furthermore, we discovered that BMI is an independent predictor of the inter-atrial EMD in obese children. Childhood obesity is one of the most important worldwide public health problems ,2. OverwAs well as obesity at an early age is closely related to ischemic heart disease, it is also related to non-ischemic heart diseases such as arrhythmias; obesity increases the risk of supra-ventricular arrhythmia such as atrial fibrillation ,14. ChilP wave dispersion (PWD) is a very useful non-invasive method for the use of surface electrocardiography as it shows the heterogeneity of repolarization in atrial myocardium. PWD has been evaluated in many childhood and adult diseases. However, there are few studies on PWD in childhood obesity ,17,18,19To the best of our knowledge, TDI has not been used for the detection of an atrial electromechanical delay in obese child subjects. In this study, we examined whether atrial EMD detected by TDI was prolonged in obese child subjects or not. In addition, we investigated the relationship between PWD with EMR in obese children.2) was calculated by dividing a person’s weight in kilograms by their height in meters squared.This prospective cross-sectional study included 59 obese children aged 8–18 years, who were admitted to the pediatric endocrinology and metabolism outpatient clinic of Kahramanmaraş Sütçü imam University between July 2018 and December 2018. As the control group, 38 volunteers and healthy individuals with a similar age and gender who applied to the outpatient clinic were included in the study. Patients’ anthropometric measurements such as height and weight were performed only with underwear and without shoes. BMI . Inclusion criteria were determined as follows: Volunteering to participate in the study, obese and 8–18 years of age, ECG with a sinus rhythm. Exclusion criteria were as follows: Patients with known congenital heart disease, patients with branch block in the ECG, patients with atrial septal defect, patients with anti-arrhythmic drug use for any reason , patients with rheumatic valve disease, active infection, known diabetes mellitus (DM), Cushing syndrome, patients with hypertension, chronic inflammatory disease, hypothyroidism or hyperthyroidism and patients who had previously been diagnosed with supra-ventricular tachycardia. Laboratory and demographic data of the subjects were recorded. Standard echocardiography and tissue Doppler echocardiography were performed on all the patients by the same cardiologist during the outpatient visit.After 10 min of rest, 12 lead ECGs were taken at a 50 mm/s rate and 20 mm/mV amplitude in the supine position. These ECGs were evaluated by two different cardiologists who were blinded of the clinical condition of the patients. The beginning of the P wave was determined as the first point where the first deviation of the P wave intercepted the isoelectric line and the end as the end point of the end of the deviation. PWD was measured and defined as the variation of the difference between maximum P wave (Pmax) and the minimum P wave (Pmin) time calculated from leads D2 and V5.® cardiac ultrasonography system  with 2.5- to 5-MHz probes. The supine and left lateral positions were conducted for each patient with 2D, M-mode, pulsed and color flow Doppler echocardiography. Single lead electrocardiogram continuously recorded. For all measurements, the average of at least three cardiac cycles was evaluated. For the conventional Doppler echocardiographic examinations and M-mode measurements, the European Society of Echocardiography guideline criteria were used [Transthoracic echocardiographic examinations were performed by experienced echocardiographers who were blinded about the clinical information of the subjects via, the Vivid 7ere used . Two-dimThe pulsed Doppler sample volume was placed at the LV lateral mitral, RV tricuspid and septal mitral annulus in an apical four-chamber view. The time was defined as PA and was obtained from the lateral mitral annulus , septal mitral annulus  and RV tricuspid annulus (PA tricuspid) from the starting of the P wave in the surface ECG to the beginning of the late diastolic wave (Am). While intra-atrial EMD was PA septum minus PA tricuspid, the inter-atrial EMD was calculated and defined as PA lateral minus PA tricuspid ,25 Figu.This study was approved from Kahramanmaraş Sütçüimam University Ethics Committee with the protocol code 258 on 13 July 2018. Informed consent was provided before starting the study from all individuals.p-value ≤0.05 was considered as statistically significant. Categorical variables were determined by the percentage and number of cases, while continuous variables were expressed as the mean ± standard deviation (SD) or median and interquartile range (IQR). A mean was compared by using an independent sample t-test, and in the case of an abnormal distribution Mann–Whitney U test with the median was used. A chi-square test was used for the categorical data. Correlation analyses of abnormally distributed variables were performed by Spearman correlation analysis and Pearson correlation was used in the normal distributed variables. A stepwise multiple regression analysis was used for the definition of the significant determinants of inter-atrial EMD, and incorporating variables that correlated with a p-value of less than 0.1 in the correlation analysis. A value of p < 0.05 was considered as statistically significant.Data management and analysis was performed by using the SPSS program v.14  and a two-sided p < 0.001). When laboratory characteristics of the two groups were compared, serum glucose and platelet counts (p = 0.016 vs. 0.022) were significantly higher in the obese group, while the other values were similar between the two groups. LV ejection fraction, LA diameter, septum thickness and posterior wall thickness, A velocity, E velocity and E/A ratio were similar between the two groups  number and percentage, p = 0.001, p < 0.001, p < 0.001 and p < 0.001, respectively; Compared to the healthy controls, PA septum, PA lateral, inter- and intra-atrial electromechanical delays were prolonged in the obese group  but, there was no relationship between serum glucose level and platelet count with inter-atrial EMD.Inter-atrial EMD and intra-atrial EMD correlated positively with BMI values  in childhood, as it is in the adult age group ,29,30. TAlthough the mechanism of obesity is not fully understood, it is suggested that AF develops due to mechanisms such as fat inflammation on the atrial wall, the increase in sympathetic nervous system activity, increased inflammatory process, adipokinin dysregulation and activation of pro-fibrotic signaling pathways ,33,34. TPWD, being an ECG index for reflecting heterogeneous atrial conduction through detecting abnormal atrial conduction with ECG leads to a different orientation. It has been studied for several times on patients with hypertension, metabolic syndrome, DM and obesity as a simple and noninvasive predictor of AF development ,18,19. AOur study also showed that BMI, which was closely associated with left atrial fibrosis and left atrial enlargement, was positively correlated with intra- and inter-atrial conduction, and BMI was found to be an independent predictor of inter-atrial electromechanical delay.Since the design of the study was cross-sectional, patients could not be followed up for long-term AF development. Additionally, the variability in inter-observer PA measurement was not evaluated. Inter-atrial conduction time obtained by TDI was not correlated with invasive inter-atrial conduction time. Lastly, in order to support our hypothesis, there is a need for studies including a large number of subjects and long-term follow-up.In conclusion, the delay of the electromechanical conduction time in obese patients may be due to the atrial inflammatory and fibrotic process associated with obesity. Elongation in the electromechanical period may be the early finding for atrial fibrillation that developed or will be developed in obese children. Close follow-up of these patients may help to prevent the early complications.


In this review management of the most common cyanotic congenital heart defects (CHDs) was discussed; the management of acyanotic CHD was reviewed in Part I of this series. While the need for intervention in acyanotic CHD is by and large determined by the severity of the lesion, most cyanotic CHDs require intervention, mostly by surgery. Different types of tetralogy of Fallot require different types of total surgical corrective procedures, and some may require initial palliation, mainly by modified Blalock–Taussig shunts. Babies with transposition of the great arteries with an intact ventricular septum as well as those with ventricular septal defects (VSD) need an arterial switch (Jatene) procedure while those with both VSD and pulmonary stenosis should be addressed by Rastelli procedure. These procedures may need to be preceded by prostaglandin infusion and/or balloon atrial septostomy in some babies. Infants with tricuspid atresia require initial palliation either with a modified Blalock–Taussig shunt or banding of the pulmonary artery and subsequent staged Fontan . Neonates with total anomalous pulmonary venous connection are managed by anastomosis of the common pulmonary vein with the left atrium either electively in non-obstructed types or as an emergency procedure in the obstructed types. Babies with truncus arteriosus are treated by surgical closure of VSD along with right ventricle to pulmonary artery conduit. The other defects, namely, hypoplastic left heart syndrome, pulmonary atresia with intact ventricular septum, double-outlet right ventricle, double-inlet left ventricle and univentricular hearts largely require multistage surgical correction. The currently existing medical, trans-catheter and surgical techniques to manage cyanotic CHD are safe and effective and can be performed at a relatively low risk. In the first paper , managemThe most important of the cyanotic CHDs are what are called the “5 Ts”  and thesSince most, if not all cyanotic CHDs need intervention, the format of this paper will be different from that used for acyanotic CHDs. For each of the cyanotic CHD, a brief description of the defect complex will be included followed by timing and methods of management concurrently; palliative and corrective therapies are discussed as appropriate for a given lesion.2) should be 0.3 (30%) to 0.4 (40%) and 100% oxygen (O2) is not necessary. If ductal-dependent pulmonary or systemic blood flow is suspected, intravenous infusion of prostaglandin E1 (PGE1) (0.05 to 0.1 mcg/kg/min) should be initiated to open and/or to maintain ductal patency while waiting for confirmatory diagnosis  ,42 2 sat1 infusion to open the ductus arteriosus do not maintain adequate O2 saturations (60% to 70% without metabolic acidosis), balloon atrial septostomy is required preparatory to the Jatene procedure. More recently, some groups of surgeons have been performing the Jatene procedure within the first few days of life, avoiding the need for balloon atrial septostomy altogether.Two types of surgical strategies, namely venous switch ,45 and aIn babies presenting beyond the neonatal period, de-conditioning of the left (pulmonary) ventricle may occur. In such patients, staged correction ,49 with 2 saturation may be accomplished by balloon atrial septostomy. Once the infant is stabilized, the Jatene procedure along with closure of VSD may be performed [CHF is the usual mode of presentation for patients with TGA and VSD in contradistinction to cyanosis and hypoxemia of TGA with an intact atrial septum. Anti-congestive measures should be instituted promptly, as detailed in Part 1. Relief of pulmonary venous congestion and improvement of Oerformed . Such su1 should be infused initially followed by modified BT shunt. In patients with dominant pulmonary valvar obstruction, balloon pulmonary valvuloplasty [Presentation of patients with TGA, VSD and PS is variable. If hypoxemia is secondary to poor mixing, balloon atrial septostomy should be performed. If the hypoxemia is due to decreased pulmonary flow, PGEloplasty ,14,15,16Eventually, most of the patients in this group require a Rastelli type of repair  consistiIn tricuspid atresia ,55,56,57The management of tricuspid atresia will be discussed under the heading of palliative management and “corrective” surgery.Nearly 80% of tricuspid atresia patients are symptomatic in the neonatal period and require effective palliation so that they may reach the age and size at which the Fontan procedure ,60 can b2 saturations, the ductus should be made to open by intravenous infusion of PGE1 in a manner similar to that described in TOF and TGA sections. After the infant is stabilized and echocardiographic definition of cardiac abnormalities is undertaken, a modified BT shunt [In neonates with markedly decreased pulmonary blood flow with low OBT shunt  is perfoBT shunt , stentinBT shunt ,24,25 anBT shunt ,13, but 2 saturations in the low 80s do not need any intervention and may be followed clinically until the time of bidirectional Glenn procedure.Babies with near normal pulmonary blood flow maintaining OIn babies with increased pulmonary blood flow and CHF, anticongestive therapy is promptly instituted. In patients with transposition (Type II), PA banding should be performed after the infant is stabilized with anticongestive treatment. If there is associated aortic coarctation, it should also be addressed at the same time. In patients with normally related great arteries (Type I) banding of the PA should not immediately be performed because of possibility of spontaneous closure of the VSD ,63,64,65The entire systemic venous return must egress via the PFO, but it rarely becomes obstructive in the neonatal period, although this can be problematic later in infancy ,10. A riSpontaneous closure of the VSD produces pulmonary oligemia in tricuspid atresia patients with normally related great arteries (Type I) and subaortic obstruction in tricuspid atresia patients with TGA (Type II) ,63,64,65Fontan , KreutzeAt the time of presentation, usually in the early infancy, palliation depending the physiological abnormality (modified BT shunt or pulmonary artery banding)  is perfoAt about the age of six months, a bidirectional Glenn procedure  is perfoIn patients with an additional persistent left SVC, a bilateral, bidirectional Glenn procedure  is perfoPrior to the bidirectional Glenn procedure, normal pulmonary artery pressures should be documented either by echo-Doppler or cardiac catheterization studies. In cases with PA stenosis and mitral valve regurgitation, these abnormalities should also be repaired at the time of bidirectional Glenn procedure. Subaortic stenosis, if present, should also be bypassed by Damus–Kaye–Stansel. If there are any other hemodynamically significant abnormalities, they should also be addressed at this stage.Between the ages of one and four years, usually one year after the bidirectional Glenn, Fontan completion is performed by redirecting the inferior vena caval flow into the PA by either a lateral tunnel  or an exThe fenestration is closed by trans-catheter device implantation  six montSome babies with tricuspid atresia may have additional rare abnormalities such as vascular ring, truncus arteriosus, absent pulmonary valve syndrome, aortopulmonary window or anomalous pulmonary venous connection . As reviIn total anomalous pulmonary venous connection (TAPVC), all the pulmonary veins drain into a common pulmonary vein which in turn is connected to the left innominate vein, SVC, coronary sinus, portal vein or other rare sites ,83. OccaIn the non-obstructive type, following control of CHF, elective or semi-elective surgical correction is recommended. Since the entire systemic flow must pass through the PFO, it may become restrictive and in such situations balloon atrial septostomy is helpful . However1 infusion may beneficial by opening the ductus and decompressing the pulmonary circuit and may potentially open the ductus venosus, thus decreasing pulmonary venous obstruction. However, urgent correction by anastomosis of the common pulmonary vein with the left atrium should be sought.In the obstructive type, the baby should be stabilized by intubation and ventilation with high airway pressure. PGEIn mixed type of TAPVC, there is no large common pulmonary venous confluence and therefore, conventional surgery described above is not feasible. Unless there is evidence for pulmonary venous obstruction, waiting until anomalous veins are large enough to be anastomosed to the left atrium is most appropriate .Truncus arteriosus is a cyanotic CHD in which by a single arterial vessel (truncus) originates from the heart which gives rise to the Ao, PAs and coronary arteries ,87,88. AThe treatment of choice for truncus arteriosus is total surgical correction under cardiopulmonary bypass  and is cHypoplastic left heart syndrome (HLHS) is a cyanotic CHD consisting of diminutive left ventricle with under developed mitral and aortic valves ,94,95,96At the present time, there are two options to treat HLHS and these are the multistage Norwood procedure ,98,99 an1 infusion should be initiated to maintain ductal patency and an echocardiogram performed to confirm the diagnosis of HLHS and to appraise the adequacy of shunting across the PFO.Due to routine obstetric ultrasound screening studies, a significant number of HLHS babies are identified prenatally. Such prenatal identification allows time for counseling parents and planning of delivery at a tertiary care hospital equipped to treat complex CHD; the latter helps avoid transport-related morbidity and mortality. Immediately after the baby is born, PGE1, death rapidly ensues. The same symptoms may also be found if an abrupt drop in pulmonary vascular resistance (PVR) occurs. Infants with restrictive PFO, though rare, present with respiratory symptoms and severe cyanosis secondary to pulmonary venous obstruction.Neonates who are not diagnosed prenatally are usually born at term and appear normal at first. As the ductus arteriosus starts to constrict, generally over the first 24 to 48 h after birth, symptoms such as tachypnea, respiratory distress, cyanosis, pallor, lethargy, metabolic acidosis and oliguria appear. Without immediate reopening the ductus arteriosus by PGEManagement prior to surgical intervention involves three major principles, namely: (1) maintain sufficient systemic blood flow by keeping the ductus open, (2) limit excessive pulmonary flow, particularly by balancing with systemic circulation and (3) ensure adequate egress of the left atrial blood.1 should be started as soon as the diagnosis of HLHS is made/suspected so that ductal patency is established, and adequate systemic perfusion is provided. As mentioned in the preceding sections, an initial dose is 0.05 to 0.1 mcg/kg/min is administered. After ductal patency is established, the rate of PGE1 infusion may be gradually (stepwise) reduced down to 0.02 mcg/kg/min. It is important to recognize that ductal patency should be maintained with the lowest effective dose of PGE1 so that the dose-dependent side effects of PGE1 such as hypotension, prompting volume resuscitation and respiratory depression and apnea, requiring mechanical ventilatory support, are minimized.The systemic circulation in infants with HLHS completely depends on the patency of ductus arteriosus. Consequently, intravenous infusion of PGE1 and establishing ductal patency, attempts should be made to balance systemic and pulmonary resistances by decreasing the SVR or augmenting the PVR or a combination thereof. If the infant is stable with O2 saturations in the mid 80s, it is prudent to just observe the baby and not administer supplemental O2. If the systemic O2 saturations trend upwards, intervention is appropriate. Maneuvers to increase PVR are more effective. Intubation and controlled ventilation with sedation and paralysis prevents hyperventilation and allow hypoventilation to keep arterial PCO2 between 45 and 50 mmHg. Metabolic acidosis should be corrected with sodium bicarbonate and the hematocrit maintained between 40% and 45% to provide adequate oxygen carrying capacity and to increase the blood viscosity; the latter may also assist in increasing PVR. Supplemental O2 should be avoided at all costs. If the above described methods fail to achieve balancing of SVR/PVR, sub-ambient O2 (FIO2 of 15% to 19%) with supplemental nitrogen or carbon dioxide may be utilized to increase PVR and permit larger systemic blood flow. Although this is an attractive concept, it should not be applied for long time periods since severe pulmonary hypertension is likely to adversely influence the postoperative recovery. However, such therapy does not seem to adversely influence the pulmonary vasculature on long-term follow-up [The PVR is somewhat higher than the systemic vascular resistance (SVR) at birth, but begins to fall after birth. In babies with HLHS, as the PVR decreases, progressive increase in pulmonary blood flow takes place with concurrent decrease in systemic blood flow. This will result in systemic hypo-perfusion and consequent metabolic acidosis and shock. Subsequent to infusion of PGEollow-up .The left atrial blood must egress into the right atrium, across the PFO, because of the obstructed mitral valve/LV. In some infants, the PFO may be small at birth or may become restrictive with time. Mild degree of narrowing may be beneficial in that it will increase the PVR which in turn may help adequate systemic flow. However, severe restriction produces pulmonary edema with consequent hypoxemia. Consequently, it is important to perform periodic echo-Doppler studies in order to monitor the size of the PFO and the degree of restriction. When the obstruction becomes severe, enlargement of the PFO by trans-catheter techniques ,42,43,702 saturations in the 70s and 80s (by pulse oximetry). Inotropic drugs may be administered only in severely ill babies with severe CHF, acidosis, concomitant sepsis, or cardiogenic shock. Since the inotropic agents negatively affect the balance between the PVR and SVR, these drugs should be weaned off as soon as the baby becomes stable. Diuretics may be given to control pulmonary over circulation prior to Norwood operation. It is important to recognize that the status of PVR changes quickly and frequent monitoring of these infants until palliative surgery is critical.The objective of pre-operative management is to keep the babies in room air with OThe objective of the management of infants with HLHS is to ultimately separate the pulmonary and systemic circulations by multistage surgical reconstruction ,98,99. AIn the Norwood procedure ,98,99, tSome of the poor results following Norwood have been attributed to lower diastolic coronary perfusion pressures and to address this problem, Sano and his associates ,106 replThese stages are similar to those described in the “Tricuspid Atresia” section and will not be repeated . However1 to maintain the ductus arteriosus patent while waiting for a donor heart. Nearly 20% of the babies listed for transplantation die while waiting for the heart to become available. Following successful heart transplantation, multiple medications for prevention of graft rejection are required. Frequent outpatient visits and periodic endomyocardial biopsy to identify rejection very early are important in the management of these children. Scarcity of cardiac donor hearts has forced the majority of institutions to perform the Norwood procedure initially followed by staged Fontan [Transplantation of the heart is another surgical alternative . After md Fontan ,94,95,96Due to relatively high morbidity and mortality rates following the Norwood procedure, a hybrid approach  was sugg1 to keep the ducts open has been used in premature infants with a plan for Norwood later with varying degrees of success [Simple bilateral pulmonary artery banding without ductal stent, but with continuation of PGE success .Pulmonary atresia with intact ventricular septum is characterized by total obstruction of the pulmonary valve, two separate ventricles, a patent, though small tricuspid valve, and no VSD ,114,115.1 infusion should be started immediately and careful assessment of the anatomy by echocardiography and if necessary, by cardiac catheterization and selective cineangiography, should be made.The objective of management plans is to accomplish a four-chamber, biventricular, completely separated pulmonary and systemic circulations ,114,115.If the RV is of reasonable size and tripartite or bipartite in nature , trans-cAn alternative approach used in some centers is surgical pulmonary valvotomy. Surgical pulmonary valvotomy along with RV outflow tract patch may also be performed. Some other centers use the hybrid approach; perforation of the atretic pulmonary valve is undertaken via a needle introduced through RV outflow tract exposed by sternotomy. Serial balloon dilatations of the pulmonary valve follow ,117.If the RV is very small  or right ventricular-dependent coronary circulation exists, modified Blalock–Taussig shunt along with atrial septostomy should be undertaken. Stenting of the ductus ,24,25 isIf the RV size is somewhere in between, one and one-half ventricular repair should be considered. In this method of treatment, the marginal-sized RV is allowed to pump into the PA, the PFO is closed and bidirectional Glenn shunt performed. The RV is likely to tolerate pumping smaller quantities of blood because of removing SVC flow by bidirectional Glenn.Orderly and well-planned treatment algorithms on the basis of RV size and other factors as alluded to above may help improve survival rate ,114,115.In DORV both the PA and Ao arise from the morphologic RV ,120,121.In babies with subaortic VSD without PS, surgical closure of the VSD in such a way as to divert the LV blood into the Ao is performed. Due to high PVR, these babies usually do not manifest CHF until a few weeks of life. If they present in severe CHF, appropriate anticongestive measures are instituted prior to surgery. Initial pulmonary artery banding with later surgical correction is not used in the current day practice. In babies with subaortic VSD and PS, surgical correction is the same as that used for TOF repair, including relief of subpulmonary and valvar obstruction, but ensuring the VSD patch is placed in such manner to avoid LV outflow tract obstruction. If the anatomic arrangement is not suitable for surgery in the early infancy, a modified BT shunt  is perfoIn patients with a Taussig–Bing anomaly (subpulmonary VSD), an arterial switch procedure  along wiDORV patients with uncommitted VSD are indeed problematic and usually require individualized plans to either correct or palliate these children.In double-inlet left ventricle (DILV), both atrioventricular valves empty into the ventricle which most often has LV morphology ,120,121.The pathophysiology produced by multiple defects in the above two entities is similar to that described for tricuspid atresia and consequently the management is similar ,120,121.Discussion of management of other cardiac defects such as coronary artery anomalies  includin