To generate a patient-friendly, time-efficient cardiac MRI examination protocol, a highly accelerated real-time CINE MR sequence (SSIR) was acquired in the idle time in between contrast injection and late gadolinium enhancement phase. 20 consecutive patients underwent a cardiac MRI examination including a multi-breath-hold sequence as gold standard (Ref) as well as SSIR sequences with (SSIR-BH) and without breath-hold (SSIR-nonBH). SSIR sequences were acquired 4 minutes after gadolinium injection. Right- (RV) and left-ventricular (LV) volumetric functional parameters were evaluated and compared between Ref and SSIR sequences. Despite reduced contrast between myocardium and intra-ventricular blood, volumetric as well as regional wall movement assessment revealed high agreement between both SSIR sequences and Ref. Excellent correlation and narrow limits of agreements were found for both SSIR-BH and SSIR-nonBH when compared to Ref for both LV  and RV  analyses. Even when acquired in the idle time in between gadolinium injection and LGE acquisition, the highly accelerated SSIR sequence delivers accurate volumetric and regional wall movement information. It thus seems ideal for very time-efficient and robust cardiac MR imaging protocols. Cardiac magnetic resonance imaging (CMR) is widely accepted as the standard of reference for the non-invasive assessment of cardiac function. With CMR, the change of both right- (RV) and left-ventricular (LV) volume can be measured throughout the cardiac cycle. LV and RV ejection fractions (EF), basic surrogate parameters of cardiac function, can be derived from those volumetric assessments. As the degree of EF reduction and its development over time provide both information about the severity of the individual patient’s disease as well as the prognosis, this value can influence decision making in the therapy of various acute and chronic, congenital and acquired cardiac pathologies1In clinical routine, a stack of short-axis views covering the entire LV and RV is acquired using ECG-gated segmented cine sequences for the volumetric and wall movement assessmentsBesides the volumetric parameters, CMR provides information about myocardial fibrosis by using late gadolinium enhancement (LGE) imaging45Various new techniques have been developed to reduce acquisition time and allow artifact-free imaging even in severely ill patients with reduced breath-hold capabilities, of which compressed sensing techniques are considered to offer a highly promising approach in this field789Aim of this study was to evaluate the accuracy of a comparable SSIR sequence for quantitative and qualitative right- and left-ventricular assessment acquired after GBCA admission in the idle time prior LGE acquisition. This was done in order to create a lean, time-efficient imaging protocol including both sequences for volumetric as well as LGE assessment.In all 20 patients, Ref, SSIR-BH and SSIR-nonBH sequences were acquired successfully according to the imaging protocol . The patIn the visual RMW assessment of the 320 LV segments, 6 segments were rated as dyskinetic and 44 as hypokinetic using Ref. Our findings demonstrate that a SSIR sequence can be used to acquire short-axis datasets for LV and RV volumetric analysis in the idle time between gadolinium injection and LGE acquisition. Despite the reduced contrast between myocardium and intra-ventricular blood, both endocardial and epicardial border for LV and endocardial border for RV could be delineated with high accuracy in both SSIR sequences, which thus can be used for volumetric as well as regional wall movement assessment.For both SSIR sequences, LVEDV was statistically significantly lower compared to Ref. This could be explained partly by the difference of using prospective triggering in the SSIR sequences, which leads to missing of the very late diastole. In contrast, Ref uses retrospective gating and thus covers the full cycle. However, with a difference of about 3 ml, this variance can be considered not clinically relevant. This is also supported by the LVEF results, which were equal to Ref in both SSIR sequences.modules such as early enhancement or rest perfusion studies during the first 4 minutes after gadolinium injection. This additional protocol steps would not influence the overall acquisition time. Fourth, in single-dose gadolinium injection protocols, LGE acquisition should start even earlier than when using double-dose protocols. This could allow for an even more time-efficient protocol with SSIR short-axis stack acquisition after 4 minutes, directly followed by LGE acquisition. Even though not evaluated in this study, it is very likely that the SSIR technique can also be used in single-dose injection protocols.In order to create a time-efficient protocol, gadolinium-based contrast agents can be injected at the start of the examination when using conventional cine techniques. Such protocols are widely used in clinical practice. In our opinion, using a highly accelerated technique in this setting provides four distinct advantages. First, using conventional sequences, patients will have to follow consecutive breath-hold commands throughout the entire examination. Depending on the patients’ overall condition, their ability to follow entire breath-hold intervals typically decreases over the course of the examination. This is especially true as such time-optimized protocols typically cannot include sufficiently long recreational phases. Using the approach proposed in our study , patientBesides critically ill patients, pediatric patients needing sedation for MRI examinations can profit from the proposed protocol. As the SSIR short-axis stack can also be acquired under free breathing, the proposed protocol can be used in sedated patients, minimizing acquisition and subsequently sedation time.42, Circle Cardiovascular Imaging Inc., Canada) on 10 patients and found that the implemented automatic contouring algorithms worked more efficiently when using the Ref datasets. This lead to a longer time required for the volumetric analysis of SSIR sequences when including semiautomatic volumetric techniques . Especially for the epicardium, the automatically assigned contours had to be corrected considerably in the SSIR datasets. However, with improvements of automatic contouring algorithms, this limitation might be overcome. The relatively low number of patients included has to be considered as the main limitation of this study. Additionally, the patients included in this study showed pathologies mainly affecting LV. The results regarding the SSIR sequence’s robustness in the detection of RV pathologies are thus somewhat limited. Further evaluation in a larger patient cohort, preferably with pathologies involving RV, are necessary to confirm the results found in this study.In contrast to previous works on a similar SSIR sequence9In conclusion, the highly accelerated SSIR sequence delivers accurate volumetric and regional wall movement information, even when acquired in the idle time in between gadolinium injection and LGE acquisition. It thus seems ideal for very time-efficient and robust cardiac MR imaging protocols.20 consecutive patients  with different suspected or known cardiac pathologies that were planned for late gadolinium enhancement studies were included in this prospective. The institutional review board  approved this study and performed in adherence to the Declaration of Helsinki. Written informed consent was obtained.sparse data sampling and non-linear, iterative SENSE-type reconstruction (SSIR) implementing spatio-temporal regularization using redundant Haar waveletsAll patients were examined with a clinical whole-body 3 T system  using the inbuilt 32-element spine matrix coil and an 18-element body matrix coil. After localizer sequences, standard views including a stack of short-axis views were acquired according toLate gadolinium enhancement sequences were acquired starting 10 min p.i. The examination protocol is shown in 42 Version 5.1, Circle Cardiovascular Imaging Inc., Canada) for volumetric and wall motion assessment. The following 9 parameters were assessed for Ref as well as both SSIR-BH and SSIR-nonBH: LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV stroke volume (LVSV), average LV mass (LVMass), RV ejection fraction (RVEF), RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV) and RV stroke volume (RVSV). Volumetric assessment was performed by a radiologist with 4 years of experience in CMR. Papillary muscle mass was attributed to the LV chamber volume for calculation of LV mass and functional parameters. The end-systolic and end-diastolic phases were picked manually as being the phases with lowest and highest ventricular volumes, respectively. For intra-observer variability assessment, the parameters were measured in 10 randomly selected patients twice. For inter-observer variability assessment, the same 10 patients were evaluated by a second reader with 4 years of experience in CMR.All examinations were exported to a dedicated, off-line software  was assessed using a 16-segment model for LVAll readers were blinded to the clinical history of the patients and to whether a SSIR sequence was performed with or without breath-hold. The datasets of the different patients were assessed in a random order.2 and slope. A p-value of < 0.05 was considered statistically significant.Statistical analysis was performed using a dedicated software . Shapiro-Wilk test was applied to test for normal distribution of data. The 9 volumetric values of SSIR-BH and SSIR-nonBH were compared to Ref using Bland-Altman and linear regression analysis as well as paired two-sided t-testing. For the inter-observer variability assessment, volumetric values obtained by both readers were compared using linear regression analysis and paired t-testing for the parameters LVEF and RVEF. For RWM analysis, agreement between Ref and both SSIR sequences as well as the intra- and inter-observer agreements were calculated using Cohen’s kappa statistics. Results of Bland-Altman analysis are given as mean difference ((Ref - SSIR)/2), its standard deviation, as well as lower and upper limits of agreement. Linear regression analysis results are given as rHow to cite this article: Budjan, J. et al. Rapid functional cardiac imaging after gadolinium injection: Evaluation of a highly accelerated sequence with sparse data sampling and iterative reconstruction. Sci. Rep.6, 38236; doi: 10.1038/srep38236 (2016).Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson’s correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-β and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-β1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis.The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired  The human heart is vulnerable to hemodynamic changes, and both kidneys play an important role in fluid and hemodynamic regulation. As such, there are dynamic and bidirectional interactions between cardiac dysfunction and renal dysfunction. These interactions comprise the so-called cardiorenal syndrome (CRS). The pathUrolithiasis affects approximately 5–10% of the population in industrialized countries and may cause inflammation, infection, or hydronephrosis. It is thAcute hydronephrosis abruptly impacts kidney hemodynamics, thus affecting left ventricular (LV) function, particularly diastolic function. Furthermore, in both rats and mice, unilateral hydronephrosis has been shown to induce salt-sensitive hypertension, which may alter cardiac diastolic function., 6 ThereThe protocol for this study was approved by the Institutional Ethics Review Board of National Taiwan University Hospital (Registry Number: 201205117RIC), and all subjects provided written informed consent. This study was carried out according to the International Conference on Harmonisation (ICH) / WHO Good Clinical Practice (GCP) guidelines and conformed to the principles outlined in the Declaration of Helsinki.This was a prospective, single-center study. Consecutive adult patients with hydronephrosis admitted to the urology ward of National Taiwan University Hospital between July 2012 and December 2012 were screened for enrollment. The exclusion criteria included a history of atrial fibrillation, valvular heart disease, chronic kidney disease, lung disease diagnosed by X-ray, and systolic dysfunction with congestive heart failure. After applying the exclusion criteria, the study population consisted of 87 patients . All patients presented with acute unilateral hydronephrosis caused by ureteral stones, which was diagnosed by ultrasonography or computed tomography. After enrollment, the patients underwent echocardiographic examination on the day of the operation and 24 hours after placement of the double J catheter under intravenous anesthesia with propofol infusion (120 mcg/kg/min) and bolus fentanyl (1–2 mcg/kg) adjusted according to vital sign. A 6F/7.5F semi-rigid URS was introduced into the ureter in a retrograde fashion along with a safety guide wire. Any stones were disintegrated using a Holmium:YAG laser that was operated through the URS. Ipsilateral double J stents and left indwelling Foley catheters were inserted.Twenty control patients  were selected from a population of patients with benign prostate hypertrophy (BPH) who underwent elective urologic surgery. The subjects enrolled in the control group were without symptoms of heart failure and had normal ejection fractions and renal function. To comply with data privacy regulations, the personal identities of the patients were encrypted, and all data were analyzed in a de-identified manner.Patients were imaged in the supine position using an ultrasound system . Two-dimensional images were acquired with the standard parasternal and apical  views at a frame rate of 30 frames per second, and 3 cardiac cycles were recorded. The gains and filters were carefully adjusted to eliminate background noise and allow for a clear tissue signal. The study results were digitally stored for subsequent offline analysis. Between the 2 echocardiography evaluations, the patients’ volume statuses and hemodynamic conditions remained stable. LV end-diastolic volume (EDV), LV end-systolic volume (ESV), ejection fraction (EF), left atrium maximal volume index (LAVI), and left ventricle mass index (LVMI) were measured according to recommendations from the American Society of Echocardiography. LVEDV vaTo avoid errors in tissue Doppler measurements caused by angle dependence, we maintained the angle between the PW-Doppler beam and the movement direction of the wall at < 15°. The early (E’) and late (A’) diastolic peak velocities were measured at the lateral and septal sites.-1. In each view, a global longitudinal strain and strain rate curve were obtained and included all LV myocardial segments (6 segments per view).).). 4) AfterCardiac dysfunction can cause renal dysfunction and vice versa through multiple mechanisms. In type 3 and type 4 CRS, which are characterized by renal dysfunction leading to cardiac dysfunction, many possible pathophysiological mechanisms have been proposed. These mechanisms include volume expansion, drop in glomerular filtration rate, sympathetic activation, renin-angiotensin-aldosterone system activation, vasoconstriction, electrolyte imbalance, and inflammatory and humoral factors. Thus, thImpaired LV relaxation and increased LV diastolic stiffness are the major causes of diastolic dysfunction that lead to elevated LV filling pressure and LA stretch. Diagnostic evidence of diastolic dysfunction can be obtained noninvasively by tissue Doppler E/ E’ > 15), trans-mitral inflow velocities , and plasma levels of natriuretic peptides (BNP). However,, trans-mIVR could predict LV filling pressure more precisely than E/ E’, and SRIVR has a better correlation with the time constant of LV relaxation (τ) when measured invasively.[IVR and increased SRIVR after surgical correction of hydronephrosis, which reflected the decreased LV filling pressure and improved LV diastolic function.It was recently demonstrated that E/SRvasively. In agreeE, SRL was not related to LV relaxation and compliance.[L may reflect the combined result of LV passive recoil process and left atrial “kick”.[L implied increased atrial function after surgery, probably resulting from relief of LA stretch (caused by diastolic dysfunction), as reflected by decreased LAVI.In contrast to SRmpliance. During al “kick”. In the cBecause of the early improvement in LV diastolic function and performance after surgical relief of hydronephrosis, it is logical to speculate that the mechanism may occur through hormonal or inflammatory responses. Accordingly, we found a corresponding decrease in serum TGF-β levels after surgical correction of hydronephrosis by double J insertion.TGF-β is a multifunctional peptide that plays a central role in regulating extracellular matrix formation and cell matrix adhesion processes. It has been shown that TGF-β plasma levels increase in rats with unilateral ureteral obstruction and in children with congenital obstructive uropathy. TGF-β alTGF-β also plays a critical role in myocardial fibrosis, which also causes diastolic dysfunction. Fernando et al. showed that unilateral nephrectomy causes early cardiac apoptosis, fibrosis, and diastolic dysfunction in rats. ThereforIVR after surgery and TGF-β may be the underlying cytokine involved in hydronephrosis-related subclinical CRS.Our patients were in the early stages of unilateral hydronephrosis without kidney injury. However, at this early stage, cardiac diastolic dysfunction could be been detected. In addition, we found that TGF-β levels paralleled the changes in E/ SRB-type natriuretic peptide (BNP) and its cleavage fragment, NT-proBNP, are known to be influenced by preload and ventricular abnormalities and are good markers of myocardial damage and stress in patients with renal failure. ComparedFrom this study, we found satisfactory agreement that patients with hydronephrosis had decreased plasma NT-proBNP levels and increased urine NT-proBNP levels after effective relief of hydronephrosis. This change is rapid and could be detected soon after surgery either by serum or urine analysis of NT-proBNP. Based on these findings, we concluded that NT-proBNP is a helpful, inexpensive, simple, and reliable biomarker for reflecting the clinical condition of patients with subclinical CRS.In summary, we proved that surgical correction of hydronephrosis can improve diastolic function. Patients with unilateral hydronephrosis had reduced levels of serum TGF-β, reduced levels of blood NT-proBNP and increased NT-proBNP clearance in the urine. Relieving hydronephrosis resulted in improved LV relaxation, decreased LV filling pressure, decreased LA volume, and enhanced LA function with a corresponding reduction in serum TGF-β levels. Our study implied a strong association between biochemical markers and echocardiographic abnormalities. According to these results, we can improve efforts for the early diagnosis of CRS and prevent further deterioration of cardiac or renal function when treating patients with hydronephrosis.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.


Type 2 diabetes mellitus (T2DM) is associated with coronary microvascular dysfunction in the absence of obstructive coronary artery disease (CAD). Cardiovascular magnetic resonance (CMR) T1-mapping at rest and during adenosine stress can assess coronary vascular reactivity. We hypothesised that the non-contrast T1 response to vasodilator stress will be altered in patients with T2DM without CAD compared to controls due to coronary microvascular dysfunction.Thirty-one patients with T2DM and sixteen matched healthy controls underwent CMR (3 T) for cine, rest and adenosine stress non-contrast T1-mapping (ShMOLLI), first-pass perfusion and late gadolinium enhancement (LGE) imaging. Significant CAD  was excluded in all patients by coronary computed tomographic angiography.p = 0.008). There was no difference in rest native T1 values (p = 0.59). During adenosine stress, T1 values increased significantly in both T2DM patients  and controls . T2DM patients showed blunted relative stress non-contrast T1 response  due to a blunted maximal T1 during adenosine stress .All subjects had normal left ventricular (LV) ejection and LV mass index, with no LGE. Myocardial perfusion reserve index (MPRI) was lower in T2DM than in controls (1.60 ± 0.44 vs 2.01 ± 0.42; Patients with well controlled T2DM, even in the absence of arterial hypertension and significant CAD, exhibit blunted maximal non-contrast T1 response during adenosine vasodilatory stress, likely reflecting coronary microvascular dysfunction. Adenosine stress and rest T1 mapping can detect subclinical abnormalities of the coronary microvasculature, without the need for gadolinium contrast agents. CMR may identify early features of the diabetic heart phenotype and subclinical cardiac risk markers in patients with T2DM, providing an opportunity for early therapeutic intervention. Type 2 diabetes mellitus (T2DM), independent of coronary artery disease (CAD) or hypertension, directly affects the structure and function of the myocardium , leadingCMR non-contrast T1-mapping may be used to assess myocardial ischaemia and coronary vasodilatory function. In CMR, T1 (or proton spin-lattice) relaxation time is a magnetic property of tissue. Each tissue type has a normal range of T1 values, deviation from each may indicate disease or a change in physiology. T1 is prolonged by increased free water content , which mWe hypothesize that patients with T2DM but without obstructive CAD will have microvascular dysfunction detectable using adenosine stress and rest T1-mapping. In this study, we compared native myocardial T1 values at rest and during adenosine stress, as well as myocardial perfusion reserve index (MPRI) in patients with T2DM without obstructive CAD and in matching healthy controls using CMR at 3 Tesla.The study was granted a favourable opinion by the National Research Ethics Committee REC Ref 13/SW/0257), and written informed consent was obtained from each participant. The main project was set out to investigate the intricate interplay of perfusion, oxygenation and metabolic changes during stress in the diabetic heart. The wider aims and methods of the main project has been published elsewhere [/SW/0257,T2DM was diagnosed according to the World Health Organization criteria . PatientHealthy subjects were age-, gender- and weight-matched to patients and served as controls. Healthy controls had no history of heart disease, DM, hypertension, or high cholesterol and were taking no medications. They had normal physical examinations and ECG.BP was recorded as an average of 3 supine measurements taken over 10 min . Fasting venous blood was drawn for glucose, triglyceride, haemoglobin A1c and renal function tests as previously described .CCTA scans were performed on a 64-slice CT scanner  in accordance with performance guidelines from the Society of Cardiovascular Computed Tomography . In the CMR was performed on a 3-Tesla system . All participants were instructed to refrain from caffeine ingestion in the 24 h preceding the study. All subjects were scanned after fasting overnight. Cine imaging was performed in long- and short-axis covering the left ventricle (LV) using standard balanced-steady state free precession (bSSFP) methods .At rest, mid LV native T1 map was acquired using the shortened modified Look-Locker inversion recovery (ShMOLLI) prototype sequence as previously described , matchedFor late gadolinium enhancement (LGE) CMR, a top-up bolus of 0.09 mmol/kg of contrast  followed by a 15-mL saline flush was administered immediately after the rest perfusion image acquisition . The LGE images were acquired using a T1-weighted phase-sensitive inversion recovery sequence 8–12 min after the last intravenous administration of contrast agent in the same long- and short-axis images as cine imaging, using imaging parameters as previously described . A singlFor each patient, LV volumes, ejection fraction, and mass were calculated using cmr42© software  by manually tracing the endocardial and epicardial contours in end-diastolic and end-systolic images, as previously described .2 maps; ~11% of segments were excluded due to any combination of: off-resonance artifacts, partial-volume effects, poor T1 fit on the R2 maps, patient movement or low signal to noise, similar to previous publications using T1-mapping from our center [.For the analysis of ShMOLLI T1-maps, the LV myocardium of the mid ventricular short axis slice acquired at baseline was contoured by two operators , using dedicated software, as previously described , providir center . The myoT1 reactivity to adenosine stress was expressed in absolute terms: ΔT1(ms) = T1stress–T1rest and as percentages: (ΔT1) (%) = ΔT1÷T1rest × 100. T1rest and T1stress represent mean T1 values at rest and during adenosine stress, respectively. Inter-observer variability of mid-ventricular ShMOLLI T1-map stress reactivity was assessed by further analysis performed by another independent operator in a blinded fashion (RSW). Inter-study variability of mid-ventricular ShMOLLI T1-map stress reactivity was assessed in 5 healthy subjects of another study performed at our research centre (REC reference: 13/SC/0376). These scans were anonymized and analyzed in random order in a blinded fashion (AL).For analysis of myocardial perfusion, signal intensity over time curves were generated by tracing endocardial and epicardial contours  after manual correction for displacement during breathing, by two operators . A region of interest was drawn in the LV blood pool, avoiding any papillary muscles, to permit the derivation of an arterial input function. The myocardium was divided into equiangular segments on the basis of the American Heart Association 16-segmentation model. Rest and stress myocardial perfusion up-slopes were calculated using a 5-point linear-fit model of SI versus time and normalized to the LV blood pool upslope. Myocardial perfusion reserve index (MPRI) was defined as the ratio of stress to rest relative upslope, as previously described .For LGE analysis, areas of contrast enhancement were visually scored as absent or present by 2 operators with at least 3 years of CMR experience . LGE was considered present only if myocardial enhancement was confirmed on both short-axis and perpendicular long-axis locations. Consistent with established methods of estimating myocardial ECV using a delayed postcontrast bolus protocol , 30, we p-value <0.05 was considered significant. All statistical analyses were performed with SPSS Statistics .All data are expressed as mean ± standard deviations and checked for normality using the Kolmogorov–Smirnov test. Categorical data are presented as numbers and percentages. Comparisons between the 2 groups were performed by Student’s t-test. The chi-square test or Fisher’s exact test was used to compare discrete data as appropriate. Bivariate correlations were performed using Pearson’s or Spearman’s method as appropriate. A Demographic, clinical, and biochemical data of patients with T2DM and controls matched for age, gender and body mass index (BMI) are shown in Table p = 0.001).CMR results for LV volumes and function are summarized in Table On visual assessment of LGE images, there were no areas of myocardial enhancement indicative of myocardial infarction or focal replacement fibrosis in either patients or healthy controls.p = 0.206). Despite the absence of significant obstructive epicardial CAD on CCTA and adequate response to adenosine vasodilatory stress, MPRI was significantly reduced in T2DM patients compared to controls . A sub-group analysis of lean T2DM patients (BMI < 25) vs lean controls for the MPRI was performed and our results showed in the absence of obesity or even overweight status T2D is associated with reduced MPRI .Rest and stress rate pressure product values are summarised in Table The inter-study reproducibility, inter-observer and intra-observer variability of mid-ventricular ShMOLLI T1-map stress reactivity were assessed.p = 0.55.5 healthy subjects . All 10 scans anonymized and analyzed in random order. The interval between scans for these participants undergoing test-retest inter-study reproducibility was 3 ± 2 years apart. There was a good agreement between the first and second scans (0.33 ± 1.13%). Mean ΔT1 for the first scan (6.2 ± 1.0%) was not significantly different compared to the second scan (6.5 ± 1.0%), paired t-test 2 = 0.759) and intra-observer (r2 = 0.837) assessments.There was a good agreement for inter-observer (−0.3 ± 1.7%) and intra-observer assessments (−0.2 ± 1.4%) by Bland-Altman plotting. Coefficient of determination showed strong relationship for inter-observer (rP < 0.001) and healthy controls  . However, stress T1 response was significantly blunted in T2DM patients compared to healthy controls  , as was the maximal T1 during adenosine stress . A sub-group analysis of lean T2DM patients (BMI < 25) vs lean controls for the ΔT1 was performed and our results showed in the absence of obesity or even overweight status T2D is associated with T1 .There were no significant differences in native myocardial non-contrast T1 values between T2DM patients and healthy controls at rest. During adenosine stress, T1 values increased significantly in both T2DM patients , when there was no significant correlation between rest T1 and MPRI .There was no significant correlation between the percent change of T1 and MPRI. However, there was a significant correlation between the adenosine stress T1 and MPRI  and LV concentricity (LV mass to LV EDV ratio) in the study group as a whole, but no significant correlation in separate groups.Maximal T1 during adenosine stress and T1 reactivity (ΔT1) correlated negatively with LV mass index (p = 0.91).There was no significant difference in ECV between T2DM patients and controls  over the applicable range of T1 values in phantoms and simulations at 1.5- and 3.0-Tesla . TherefoDespite statistical differences in stress ΔT1 between T2DM patients (4.1 ± 2.9%) and healthy controls (6.6 ± 2.6%), there are numerical overlaps between these values. The effect size to detect significant differences between diabetic patients and healthy controls using stress ΔT1 is respectable (Cohen’s d 1.2), which is comparable to the difference in myocardial perfusion reserve index between fractional flow reserve -negative (MPRI 1.8 ± 0.5) and fractional flow reserve-positive (MPRI 1.2 ± 0.3) epicardial coronary lesions using gadolinium-enhanced stress perfusion CMR (Cohen’s d 1.4 ). Liu etAdenosine is the most commonly used agent for CMR perfusion studies, and it increases blood flow mostly by non-endothelial-dependent mechanisms via receptors on microvascular smooth muscle cells that modulate intracellular calcium . Thus, tAbsolute quantification of myocardial perfusion would have been interesting for direct comparison with absolute T1 quantification under stress and rest conditions. However, quantitative perfusion analysis is relatively cumbersome, requiring specialized computational software with mathematical assumptions and some recognized limitations .The incidence of T2DM is driven predominantly by the obesity epidemic, and there is no doubt that obesity is a strong contributor to diabetic cardiomyopathy . There iFinally, CCTA was not performed in the healthy cohort to prevent unnecessary ionizing radiation exposure. Significant CAD was deemed to be very unlikely in this cohort.Patients with well controlled T2DM, even in the absence of arterial hypertension and significant epicardial CAD, exhibit blunted maximal T1 response during adenosine vasodilatory stress, likely reflecting coronary microvascular dysfunction, as well as early signs of LV concentric remodelling without overt LVH. Adenosine stress and rest T1 mapping can detect subclinical functional abnormalities of the coronary microvasculature, without the need for gadolinium contrast agents.In the future, CMR and particularly T1 mapping at stress may be used to identify early features of diabetic heart disease and subclinical risk markers in patients with T2DM, providing an opportunity for early therapeutic intervention.


Introduction. Hypertrophic cardiomyopathy (HCM) is burdened with morbidity and mortality including tachyarrhythmias and sudden cardiac death. These complications are attributed in part to the formation of proarrhythmic scars in the myocardium. The presence of extensive LGE is a risk factor for adverse outcomes in HCM. Late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (cMRI) is the standard for the noninvasive evaluation of myocardial scars. However, echocardiography represents an attractive screening tool for myocardial scarring. The aim of this study was to compare the suitability of echocardiography to detect myocardial scars to the standard of cMRI-LGE. Methods. The cMRI studies and echocardiograms from 56 consecutive children with HCM were independently evaluated for the presence of cMRI-LGE and echocardiographic evidence of scarring by expert readers. Results. Echocardiography had a high sensitivity (93%) and negative predictive value (94%) in comparison to LGE. The false positive rate was high, leading to a low specificity (37%) and a low positive predictive value (35%). Conclusions. Given the poor specificity and positive predictive value, echocardiography is not a suitable screening test for the presence of myocardial scarring in children with HCM. However, children without echocardiographic evidence of myocardial scarring may not need to undergo cardiac magnetic resonance imaging to “rule in” LGE. Hypertrophic cardiomyopathy (HCM) is the most common cardiomyopathy, occurring in approximately 1 in 500 individuals . MyocardClinical practice suggests that scars in the myocardium may also be suspected based on cardiac ultrasound: fibrotic myocardium appears hyperechoic due to increased reflectivity of the ultrasound waves, in comparison to nonfibrotic myocardium. This difference is thought to be due to the concentration of collagen within fibrotic myocardium causing increased reflectivity , 17. UltFollowing approval by the institutional research ethics board, imaging studies from 56 consecutive children with HCM who had undergone both cMRI and echocardiography were retrospectively reviewed while serial studies in the same patient were excluded from analysis. Patient demographic data can be found in Echocardiographic studies were performed using a Vivid 7 or E9 unit  or a Philips IE33 unit . Images were obtained in standard parasternal and apical views and evaluated on a Syngo V5.1 workstation .The CMR examinations were interpreted by an experienced senior reader (LGW) using the American Heart Association 17 segment model  to descrFor the assessment of LGE, the “magnitude images” of the acquisition were used. The reader was blinded to the clinical details and to the results of other testing. Fibrosis and myocardial scarring on ultrasound is identified as hyperechogenicity of the affected myocardium in comparison to background normal myocardium. The echocardiograms were interpreted by a senior echocardiography reader (LN) who was blinded to the results of the cMRI as well as the patients clinical details. This is similar to the appearance of hepatic fibrosis on ultrasound which is related to the severity of fibrosis . An educStatistical Analysis. Kappa correlation coefficients were calculated to assess the agreement between the 2 modalities both for all patients and secondarily for only those deemed positive by cMRI for myocardial fibrosis.The median time difference between the echocardiogram and cMRI was 30 days with a range of 0 days to 15 months. Late gadolinium enhancement was identified on cMRI in 15 (27%) of the 56 children. Based on a total of 1008 total segments assessed , LGE was seen in 76 segments or 7.5% of all segments analyzed. In the individual child the number of segments with LGE ranged from 1 to 15. In those with LGE, more than 2 segments were affected in 67% of the cohort. The myocardial segments most commonly affected were 8 and 9 , in 73% of the children, and segment 2  was the next most commonly affected in 60% of the cohort. Segments 5, 6, 11, 16, and 17  and the papillary muscles were the least commonly affected.The evaluation of the echocardiograms identified 40 of the 56 children (71%) as positive for the presence of myocardial fibrosis. One child who had LGE on cMRI was not identified by echocardiography. On the echocardiograms, myocardial fibrosis was most commonly suspected in segments 3 and 8 , both of these segments were positive in 87% of the ultrasound positive studies, with segment 14  being the next most common at 73% of the studies. The least commonly affected segments in children deemed positive for myocardial fibrosis were segments 4 and 12 .Kappa analysis comparing echocardiography and cMRI yielded an overall agreement (Po) of 0.53 for the presence or absence of myocardial fibrosis. The kappa value of 0.05 between the 2 modalities indicates poor agreement, similar to that of chance. When comparing the agreement for positive segments, kappa analysis yielded a value of 0.45 and moderate agreement with a Po of 0.73. The sensitivity of echocardiography for the detection of fibrosis, compared to cMRI detected LGE as the gold standard, was 93%, with a specificity of 37% . The negLate gadolinium enhancement on cMRI is the clinical standard for the identification, quantification, and assessment of the distribution of myocardial fibrosis, achieving excellent agreement with myocardial scarring on histology –24. The The most commonly scarred myocardial segments by cMRI in our cohort were the basal-anteroseptal, midanteroseptal, and midinferoseptal segments. These segments include the right ventricular insertion points into the interventricular septum. These findings are similar to that reported in adult HCM patients , with ththe condition screened for should be an important one,there should be an acceptable treatment for patients with the disease,the facilities for diagnosis and treatment should be available,there should be a recognized latent or early symptomatic stage,the screening should have high specificity and sensitivity,the test should be acceptable to the population,the cost, including diagnosis and subsequent treatment, should be economically balanced in relation to expenditure on medical care as a whole.Despite its established role in the detection and quantification of myocardial scarring cMRI has limitations. It is time consuming and costly, requires intravenous access for the injection of contrast, and is not always readily available. Echocardiography on the other hand is not burdened by such limitations and at least in theory makes an attractive imaging modality as a screening test for fibrosis in HCM. The WHO criteria  for a goEchocardiographic screening for myocardial scarring fulfills many of these requirements: it is relatively inexpensive, readily available, and noninvasive. Myocardial fibrosis is present in a significant proportion (27% to 73%) of the pediatric population and there is data in adults and preliminary experience in children that LGE is associated with increased risk for adverse outcomes, including sudden cardiac death. Prior to life-threatening arrhythmias, many patients are asymptomatic; that is, there is a latent or early symptomatic stage as per the WHO criteria. Appropriate monitoring and the placement of an implantable defibrillator can abrogate the associated morbidity and mortality, due to sudden cardiac death and arrhythmias.In this cohort, echocardiography identified myocardial scarring with a high sensitivity and negative predictive value when compared to the presence of LGE by cMRI. However, the specificity and positive predictive value of echocardiography in the detection of myocardial scarring were poor, as a result of a large number of false positives. As a consequence, the agreement between cMRI and echocardiography was not much better than chance and as such echocardiography screening cannot substitute for cMRI. Within the group of LGE-cMRI positive children there was a moderate level of agreement between echocardiography and cMRI with regard to the AHA segments that were either involved or spared. Another shortcoming of echocardiography is the fact that the extent of scarring, that is, the percentage of involved myocardium, cannot be quantified. Amount of LGE by cMRI, on the other hand, is a discriminator between increasing risk levels for adverse outcomes .Despite these shortcomings echocardiography may be useful because of its role in the routine diagnostic work-up: virtually every patient with HCM undergoes serial echocardiography. As a consequence fibrosis screening by echocardiography, albeit far from perfect, does not incur an extra cost or burden for the patient. Furthermore, for a screening test, sensitivity and negative predictive value (which were high by echocardiography) are more important than sensitivity and positive predictive value. In their 2011 guidelines the American College of Cardiology Foundation and the American Heart Association recommend LGE-cMRI “when sudden cardiac death risk stratification is inconclusive after documentation of the conventional risk factors” as a Class IIb recommendation, level of evidence C . One couSeveral limitations of this study warrant discussion: firstly, the relatively low number of patients that had LGE on cMRI in the study population limits the statistical power. Secondly, the use of two different types of ultrasound machines used for the clinical tests in this retrospective study may have resulted in different imaging characteristics which may in turn have influenced the appearance and interpretation of myocardium as healthy or fibrosed. However, the cohort size was too small to assess this effect. Finally, while the median interval between echocardiography and cMRI was only 30 days the longest interval was slightly over a year. We elected to include those children with longer intermodality gaps if there was no change in clinical status, as myocardial scarring was thought not to change significantly over a span of months.Echocardiography does not reliably identify myocardial fibrosis in children and adolescents with HCM as evidenced by cMRI-LGE. The poor performance of echocardiography is largely due to its high rate of false positives. Despite this shortcoming, and given the excellent negative predictive value and its role as the primary imaging modality in HCM, echocardiography may be useful in preselecting those who may benefit from cMRI imaging to either confirm or refute the finding of myocardial scarring.


Left ventricle (LV) function parameters such as stroke volume and ejection fraction (EF) are vital physiological parameters in the management of heart diseases. In cardiac MR, these parameters are currently derived from multiple short-axial cine images acquired under breath hold, which requires extensive scan planning and patient cooperation. The post-processing workflow is also labor-intensive as a human operator is required to manually trace the endocardium border on every slice. Also, the calculated LV volume may be inaccurate due to low resolution in slice direction and slice mismatch from inconsistent breath hold positions. In this work, we propose to combine a recently developed free-breathing 4D MRI technique and atlas-based image segmentation to calculate the LV function parameters fully automatically.MR data were collected with a self-gated, contrast-enhanced, spoiled gradient echo pulse sequence using a 3T clinical scanner  on healthy volunteers (N = 5) with informed consent and IRB approval. From each dataset, a 16-phase whole-heart cine series was reconstructed using the methods proposed in  with a dFig. In this work, we developed a fully automated method to segment LV from 4D MR images. The proposed technique showed excellent agreement with expert manual segmentations in our preliminary evaluation, and may emerge as a favorable method for fast and accurate LV function analysis with minimal operator dependency. Future works will be focused on performance tuning and further validations on both healthy subjects and patients.


Hypertrophic cardiomyopathy is an important cause of sudden cardiac death throughout life and progressive heart failure. There are limited data on the prognostic significance of fibrosis in patients with HCM specially in the pediatric age group.Our aim was to detect the presence of fibrosis in the pediatric age group and study its correlation with other demographic and LV functional parameter to detect additional risk stratification.We studied 30 pediatric patients diagnosed as HCM by echocardiography. All patients were submitted to clinical examination in which the NYHA classification was determined for each patient, echocardiography and CMR. 2D echocardiography was done with measuring the pressure gradient across the LVOT. CMR was done on a 1.5T Philips Achieva scanner in SSFP with delayed myocardial enhancement. Images were analyzed on the Philips workstation for functional parameters and on Diagnosoft program for percentage of myocardial enhancement. All demographic and functional parameters as well as pressure gradient were correlated with the percentage of myocardial enhancement. Written approval was obtained from the patients guardian as well as the approval of the local ethical committee.We studied 11 female and 19 male patients from 45 days up to 18yrs. Eight patients showed positive family history for HCM. The mean for percentage of myocardial enhancement was 9.7 ± 9. Only 5 patients didn't show enhancement. We found significant correlation between the NYHA classification and the pressure gradient across the LVOT (P = <0.001) as well as the percentage of myocardial enhancement (P = 0.004). The percentage of myocardial enhancement showed positive correlation with LV myocardial mass index (p = 0.042). It didn't correlate with any other demographic or LV functional cardiac parameters . A good positive correlation was detected between the percentage of myocardial enhancement and the severity of pressure gradient measured by echocardiography (r = 0.69 and P=<0.001).We found a significant correlation between the percentage of myocardial enhancement in pediatric HCM and the pressure gradient, NYHA classification and LV myocardial mass . This may help in further management of those patients, planning of follow up and prognosis of the disease.


Poor glycemic control is associated with impaired left ventricular (LV) diastolic function in patients with type 2 diabetes mellitus (T2DM). Inappropriate LV mass increase and accelerated aortic stiffening were suggested to participate on deterioration of diastolic function. The present study investigated the inter-relationships between glycemic control, early diastolic and systolic longitudinal velocity of mitral annulus, LV mass and aortic stiffness in T2DM patients free of cardiovascular disease and with preserved LV ejection fraction, and compared them with those observed in healthy volunteers of similar age and sex distribution.125 T2DM patients and 101 healthy volunteers underwent noninvasive measurement of systolic (s′) and early diastolic (e′) velocities of mitral annulus, LV mass, carotid-femoral pulse wave velocity (cfPWV) and local carotid blood pressure (BP).P < 0.0001), 34 (27.2%) had cfPWV higher than that expected for age and mean BP , and 71 (56.8%) had LV mass higher than that expected for body size and stroke work . Carotid systolic BP was higher in T2DM patients . In multivariate analysis, e′ velocity was independently related to age, carotid BP and s′ velocity in healthy volunteers, and to male sex, age, carotid BP, heart rate and LV mass in T2DM. Glycosylated hemoglobin (HbA1c) was independently related to cfPWV and LV mass in T2DM patients. T2DM patients with HbA1c ≥6.5% (N = 85) had higher cfPWV (P < 0.05), central BP (P = 0.01), prevalence of LV hypertrophy (P = 0.01) and lower e′ and s′ velocity  as compared to those with HbA1c <6.5%.Forty-four (35.2%) T2DM patients had e′ velocity lower than that expected for age  have lower diastolic and systolic LV longitudinal performance, together with increased aortic stiffness and a higher prevalence of LV hypertrophy. Left ventricular (LV) diastolic dysfunction is considered an early manifestation of diabetic heart disease –3, and tLV diastolic function is determined by relaxation rate, restoring forces and passive compliance of LV wall. There is no single noninvasive measure that can describe all these mechanisms, yet the LV lengthening velocity e′, measured by tissue Doppler imaging, represents a valuable parameters of diastolic function as it reflects both relaxation and restoring forces , 16. In Therefore, the present cross-sectional study evaluated the inter-relationships between LV diastolic longitudinal velocity e′ and LV mass, aortic and carotid stiffness, central blood pressure (BP), systolic velocity s′ and indicators of glycemic exposure (plasma levels of fasting glucose and glycosylated hemoglobin and duration of diabetes) in T2DM patients free of clinical cardiovascular disease and with preserved LV ejection fraction (EF). Observed associations were compared with those obtained in a group of healthy volunteers of comparable age and sex distribution.2). They were selected from those referred for a complete vascular and cardiac examination to the Clinic for Cardiometabolic Risk Prevention of the Department of Surgical and Medical Pathology, University of Pisa. The second population consisted of 101 apparently healthy volunteers, comparable for age and sex distribution, selected from those participating on the study Relationship between Insulin Sensitivity and Cardiovascular Risk (RISC) , and were logarithmically transformed for parametric statistical analysis. ANOVA was used to compare continuous variables, and a χP < 0.0001) had cfPWV higher than that expected for age and mean BP [The two populations were analyzed separately and their main characteristics are reported in Table  mean BP .Table 1CP at least <0.05), separately for T2DM patients and healthy volunteers. In healthy volunteers, ccaPWV correlated with age, heart rate, systolic BP, LV mass and cfPWV , and in T2DM patients ccaPWV correlated with waist circumference, BMI, heart rate, systolic BP and cfPWV .Table P < 0.0001) was described by the equation e′ velocity (cm/s) = −0.168 * Age (years) + 21.03, and by the lower 95% tolerance interval of −2.47 cm/s. Applying this equation and the lower 95% tolerance interval as previously described [P < 0.0001) having diastolic dysfunction.In healthy volunteers, the inverse linear relationship between e′ velocity and age  in healthy subjects than in T2DM patients.A correlation between e′ and s′ velocity was observed both in healthy volunteers and in T2DM patients Fig. ; the relR2 = 0.40; P < 0.0001), and by heart rate, systolic BP and hypertensive treatment in T2DM patients .The independence of the associations of e′ velocity, cfPWV, LV mass and ccaPWV with their univariate correlates was tested in multiple regression models with stepwise removal, adjusted for sex and smoking habit and, in T2DM patients, also for BP-lowering, lipid-lowering and anti-diabetic treatment Table . Early dT2DM patients were divided according to HbA1c levels (<6.5% and ≥6.5%) . Table 5In T2DM patients free of cardiovascular disease and with preserved LV EF, HbA1c levels were positively associated with LV mass and aortic stiffness, both of which showed a negative independent impact on early diastolic velocity e′, the latter through an increase in central systolic BP. T2DM patients with suboptimal glycemic control (HbA1c ≥ 6.5%) had a higher prevalence of LV diastolic dysfunction, together with a higher prevalence of LV hypertrophy and increased aortic stiffness.LV diastolic dysfunction is an early manifestation of diabetic heart disease , 20, 21,E′ velocity of mitral annulus is considered a valuable noninvasive parameter of LV diastolic function, as it reflects myocardial relaxation and restoring forces , 16 as wFasting plasma glucose and HbA1c levels were not independently related to e′ velocity, yet HbA1c was directly and independently associated with LV mass and aortic stiffness, as assessed by cfPWV. The association between glycemic control and LV mass has been previously described in both non-diabetic and diabetic patients , 37, andThe association between glycemic control and aortic stiffness is supposed to reflect AGEs-related collagen cross-linking within the arterial wall . StiffenIn contrast to aortic stiffness, which was negatively influenced by fasting plasma glucose in healthy volunteers and by HbA1c in T2DM patients, the local carotid stiffness was not independently related to metabolic parameters. This finding is consistent with results of previous studies demonstrating a different impact of modifiable cardiovascular risk factors on aortic and carotid stiffness , 44.It should be emphasized that other T2DM-related factors, not evaluated in this study, like insulin-resistance and altered myocardial metabolism , 46, myoEarly diastolic longitudinal velocity e′ is determined not only by LV relaxation rate but also by restoring forces , 16 geneAsymptomatic T2DM patients with sub-optimal glycemic control (Hb1Ac ≥ 6.5%)  had signThe cross-sectional design of the study cannot elucidate cause-and-effect relationships. Silent inducible ischemia was not assessed by stress testing in T2DM patients. Data on other T2DM-related factors that might influence LV mass and arterial stiffness, like plasma insulin and adiponectin, were not available. In healthy volunteers, HbA1c was not determined. LV longitudinal function was estimated by a simple measure of mitral annulus velocity and not by a more complex measurement of LV strain, since speckle tracking–based strain imaging has low achievable frame rates , and sinChronic increase in plasma glucose level in T2DM patients is associated with aortic stiffening and consequent increase in LV afterload, as well as with LV mass increment. Increase in both LV afterload and mass showed a negative impact on e′ longitudinal myocardial velocity used as a marker of LV diastolic function. LV systo-diastolic coupling and systolic myocardial performance seem to be also negatively influenced by diabetes and increased plasma glucose, even if the chamber function is still preserved. An adequate control of plasma glucose level and central BP might prevent the development of LV myocardial dysfunction and its eventual transition towards heart failure.


Few studies have characterized the surgical outcomes following epicardialpacemaker implantation in neonates with congenital complete atrioventricularblock (CCAVB).This study sought to assess the long-term outcomes of a minimally invasiveepicardial approach using a subxiphoid access for pacemaker implantation inneonates.Between July 2002 and February 2015, 16 consecutive neonates underwentepicardial pacemaker implantation due to CCAVB. Among these, 12 (75.0%) hadcongenital heart defects associated with CCAVB. The patients had a mean ageof 4.7 ± 5.3 days and nine (56.3%) were female. Bipolarsteroid-eluting epicardial leads were implanted in all patients through aminimally invasive subxiphoid approach and fixed on the diaphragmaticventricular surface. The pulse generator was placed in an epigastricsubmuscular position.All procedures were successful, with no perioperative complications or earlydeaths. Mean operating time was 90.2 ± 16.8 minutes. None of thepatients displayed pacing or sensing dysfunction, and all parametersremained stable throughout the follow-up period of 4.1 ± 3.9 years.Three children underwent pulse generator replacement due to normal batterydepletion at 4.0, 7.2, and 9.0 years of age without the need of ventricularlead replacement. There were two deaths at 12 and 325 days after pacemakerimplantation due to bleeding from thrombolytic use and progressiverefractory heart failure, respectively.Epicardial pacemaker implantation through a subxiphoid approach in neonateswith CCAVB is technically feasible and associated with excellent surgicaloutcomes and pacing lead longevity. This results in a high complication rate, including lead fracture andpacing/sensing dysfunction.16Several age-specific factors may contribute to the occurrence of pacemaker-relatedcomplications in pediatric patients. First, pulse generators and leads are primarilydesigned for adults. Second, small vessel size and associated intracardiac defectsmake transvenous implantation difficult or impossible. Third, there is a significantdisproportion between the size of the permanent device and the child's body size.Furthermore, the effects of growth on the leads and on the lead-myocardial junctionresult in a high incidence of exit block and lead fractures.20 Thepurpose of this study was to assess the long-term outcomes of a minimally invasiveepicardial approach using a subxiphoid access for pacemaker implantation in thispatient population.Deciding on the best surgical approach for pacemaker implantation in neonatesrequires a thorough assessment and a highly experienced cardiac surgery team, asevidence-based guidelines are still unavailable.Between July 2002 and February 2015, a total of 16 consecutive neonates underwentepicardial pacemaker implantation in a cardiovascular referral center . The Institutional Review Board of the institution approved thisstudy. Device implantation was achieved through a minimally invasive subxiphoidincision.Among the 16 patients included in the study, nine (56.3%) were female. Meanpatient age was 4.7 ± 5.3 days . Indications forcardiac pacing included signs of low cardiac output in four (25%), heart rate< 55 beats/minute in three (18.7%), and both conditions in nine (56.3%)patients. Patent foramen ovale or patent ductus arteriosus were detected in 12(75.0%) infants, and atrial septal defects were detected in four (25.0%) ofthem. In four (25.0%) neonates, congenital heart defects were not detectedbefore pacemaker implantation. One child had moderate-to-severe tricuspidregurgitation, and another had pulmonary stenosis. Baseline characteristics ofthese patients are summarized in CCAVB was diagnosed prenatally in 15 (93.8%) patients and after birth in one.Fetal echocardiography, performed in 15 (93.8%) cases, confirmed the diagnosisof CCAVB and also detected structural heart defects in two (12.5%) fetuses.Maternal dexamethasone or beta-sympathomimetic agents were administered in six(37.5%) cases due to signs of fetal myocardial dysfunction and/or fetalhydrops.Eight infants were delivered preterm . Cesareansection was carried out in all cases, except the one case in which there was noprevious diagnosis of CCAVB. Gestational age, weight, and heart rate at birthare described in Clinical diagnosis of autoimmune disease was present in 12 (75.0%) mothers . Among tNone of the neonates underwent temporary pacing. Two neonates had a pacemakerplaced immediately after birth due to low cardiac output and severe bradycardia.The remaining cases were monitored closely in the neonatal intensive care unit.If the neonate had evidence of heart failure, low cardiac output, or heart rate< 55-beats/minute, infusion of dopamine was administered to postpone the timeto pacemaker implantation.All procedures were performed with patients under general anesthesia in theoperating room. A 3 cm longitudinal incision was made at the insertion of thexiphoid process and advanced inferiorly toward the umbilicus. After resection ofthe xiphoid process, an inverted T-shaped pericardiotomy was performed.A bipolar steroid-eluting epicardial lead  was implanted in all neonates. Each of the two poles of the leadwas affixed to the visceral epicardium with 5-0 polypropylene sutures. One ofthe poles was positioned on the diaphragmatic wall of the right ventricle. Theother pole was implanted either on the anterior wall of the right ventricle orthe inferior wall of the left ventricle.Measurements of sensing, impedance, and capture threshold were obtained for bothunipolar and bipolar configurations. Once satisfactory pacing and sensingparameters were achieved, the ventricular lead and the pulse generator (VVIR)were connected and placed within a pocket located in the submuscular region ofthe epigastrium . Lead exAll patients were followed up by a pediatric cardiology team and a cardiac pacingspecialist. During follow-up, clinical assessment of all patients was performed,including careful evaluation of signs and symptoms related to heart failure.Patients with congenital heart defects were also evaluated regarding the optimaltime for surgical repair.Clinical follow-up and device interrogation visits were conducted every 6 months.In addition, subjects were periodically contacted by telephone and their medicalrecords were regularly monitored.Pacemaker programming was carried out according to individual patient clinicalcharacteristics, and pacing energy was adjusted to allow for an optimal safetymargin with respect to the ventricular pacing threshold. In the early follow-upperiod, the pacemaker was programmed at 110 to 120 beats per minute and thisminimal heart rate was incrementally decreased in the chronic period, accordingto the individual characteristics and the childhood phase.22Study data were collected and managed using Research Electronic Data Capture(REDCap) software hosted in our institution’s server.The outcomes evaluated in the study included (1) intraoperative and immediatepostoperative complications, or complications during the clinical follow-upperiod and (2) mortality from any cause. Quantitative variables are described asmean and standard deviation and qualitative variables as absolute and relativefrequencies.All procedures were successful with no perioperative lead dislodgment, bleeding,arrhythmias, or early deaths. Mean operating time was 90.2 ± 16.8 minutes. Four patients had hemodynamicinstability, which was treated by decreasing the pacing rate and intravenousinfusion of epinephrine (0.01 µg/kg/min).The cathode of the ventricular lead was implanted on the inferior wall of the leftventricle and the diaphragmatic wall of the right ventricle in 10 (62.5%) and six(37.5%) neonates, respectively. The anode was implanted on the diaphragmatic oranterior wall of the right ventricle in 13 (81.3%) and three (18.8%) patients,respectively. One neonate underwent concomitant surgical closure of the patentductus arteriosus by an independent incision . Excellent intraoperative pacing and sensing thresholds were obtainedin all patients, as described in A Microny II SR  pulse generator was used in almostall patients. In only one case, an Altrua S601 SSIR  pulse generator was chosen due to unavailability of the Microny device.After pacemaker implantation, mechanical pulmonary ventilation was maintained for aminimum of 4 hours and a maximum of 30 days . Oneneonate was maintained on mechanical pulmonary ventilation for 30 days due to lungmaturation problems. The length of stay in the neonatal intensive care unit rangedfrom 2 to 32 days  and the total hospitalizationlength ranged from 7 to 49 days .Minimal superficial wound infection was the only procedure-related complicationobserved in our patients, occurring in three (18.8%) neonates. Other complicationsobserved included pulmonary infection in two (12.5%), atelectasis in one (6.3%),urinary tract infection in one (6.3%), and renal failure in one (6.3%) neonate whoalso had superior vena cava thrombus treated with thrombolysis.The patients were followed individually for 4.1 ± 3.9 years . There were two deaths. One occurred 12 days afterpacemaker implantation due to bleeding complications secondary to thrombolytic use.The other patient, who was being followed in another hospital, died of progressiverefractory heart failure 325 days postoperatively.Overall, 11 children remain without signs/symptoms of heart failure or need forcardiovascular medication. Two children underwent surgical repair of congenitalheart defects. Percutaneous pulmonic valvuloplasty was performed in a 2-month-oldgirl with pulmonary valve stenosis. This resulted in rupture of a tricuspid valvepapillary muscle and required urgent surgical repair of the pulmonic and tricuspidvalve. A 4-year-old girl underwent surgical mitral valve repair and closure of anatrial septal defect. Concomitantly, this child was upgraded from a single-chamberto a dual-chamber pacemaker by using the previous ventricular lead and the sameepigastric pulse generator pocket. Finally, a 5-year-old boy presented withrefractory heart failure and was upgraded from a single-chamber device to abiventricular device for cardiac resynchronization therapy and 7 months laterunderwent heart transplantation .During follow-up, none of the subjects experienced loss of capture, leaddislodgement, or lead fracture. None of the patients displayed pacing or sensingdysfunction, and all pacemaker parameters remained stable throughout the follow-upperiod. Three children underwent pulse generator replacement due to normal batterydepletion at 4.0, 7.2, and 9.0 years of age without the need for ventricular leadreplacement .An echocardiogram confirmed normal cardiac anatomy and normal left ventricularfunction in five (31.3%) children. Among the cases with intracardiac defects, onlytwo underwent surgical repair due to hemodynamic compromise. Of the 13 (81.3%)patients who remain in follow-up, only one was found to have reduced leftventricular ejection fraction (LVEF = 0.51).At the last follow-up, the electrocardiogram confirmed sinus rhythm withatrioventricular dissociation in all patients. Chest radiography revealed properdevice location, lead integrity, and cardiac silhouettes within normal limits .20The use of cardiac pacing in neonates is still an area of significant controversy.Opinions differ with respect to the ideal pacing mode, the best surgical approach topace the heart of small infants, the optimal lead choice which provides the bestshort and long-term outcomes, and the appropriate strategy to accommodate the pulsegenerator in this subset of patients.18 On theother hand, the feasibility of transvenous pacemaker implantation has been describedin neonates, either by the tributaries of the superior vena cava or via the branchesof the iliac veins.20 The disproportion between the small body size andthe device dimensions prevents placement of the pulse generator in the chest wall.Therefore, to prevent pocket-related problems in neonates, pulse generators areusually placed in the abdominal wall.18Traditionally, an epicardial approach has been preferred, though access options may vary.20 To date, few studies have recommended the use ofmore sophisticated pacing modes or cardiac resynchronization therapy as an initialstrategy.19The debate regarding the optimal pacing mode for neonates is still ongoing. In mostexperts' opinion, a single-chamber ventricular system is the first choice, reservingdual-chamber systems or even cardiac resynchronization therapy for children withimpaired left ventricular function or poor adjustment to single-site ventricularpacing.18Regardless of the surgical approach and pacing mode, device-related complications arecommon during follow-up. Although pocket-related complications, in particular,erosions or thinning of the skin are more frequent when the device is implanted inthe chest wall, abdominal pockets may also be associated withcomplications.20 Overall, standard epicardialpenetrating leads have been associated with a high incidence of increased pacingthresholds following implantation, requiring early lead or pulse generatorreplacement. Recent studies have shown that steroid-eluting leads are associatedwith a lower rate of lead failure.12It is worth highlighting that lead fracture remains an important determinant of leadsurvival and is directly associated with the patient's growth.The technique described in this article aims to increase the safety of pacemaker usein neonates in four main ways: (1) reduction in surgical trauma by not opening thesternum or intercostal spaces; (2) safe approach and good cosmetic result for pulsegenerator accommodation in the preperitoneal space submuscularly; (3) reduction infibrosis at the lead-myocardial junction by the use of steroid-eluting leads; (4)reduction in the effect of the child's growth on the leads and on thelead-myocardial junction by using a rectilinear trajectory and by ensuring proximitybetween the lead and pulse generator.In our study, all operations were successful, and there were no perioperativecomplications. In addition, there were no complications related to surgicaltechnique during the follow-up period (maximum of 12 years). In particular, therewere no pocket-related complications (infection or skin erosion); lead-relatedcomplications (lead fracture), increases in pacing thresholds, or early batterydepletion. Finally, measurements of sensing, pacing, and impedance remainedsatisfactory during the follow-up period.Despite the use of single-site ventricular pacing, clinical signs of heart failure orechocardiographic abnormalities were not observed at last follow-up evaluation in 13of the 16 neonates included in this study. In cases where hemodynamic compromisesecondary to intracardiac defects was detected, surgical repair completely reversedthis condition. Two patients developed severe ventricular dysfunction; one underwenta heart transplant and another died.Within our study, there are several limitations. The main one is the small number ofcases, inherent to the rarity of CCAVB and other causes of bradyarrhythmiasrequiring pacemaker implantation during the neonatal period. Second, the lack of agold-standard surgical technique for pacemaker implantation in neonates does notallow for the formation of a control group with which to compare results. Even inlarger centers, it is nearly impossible to conduct a study to compare outcomesbetween different techniques of pacemaker implantation in this subset of patients.Finally, all procedures were performed by the same surgeon. This lack of operatorvariability may have influenced surgical results.Epicardial pacemaker implantation through a subxiphoid approach in neonates withCCAVB is technically feasible and results in excellent surgical outcomes and pacinglead longevity. In addition, this surgical approach solves two of the mainchallenges related to permanent cardiac pacing in neonates: pocket and lead-relatedcomplications.


A leftward motion of the ventricular septum prior to ejection, known as the septal flash (SF), is frequently observed in patients with left bundle-branch block (LBBB). We investigated whether the abnormal motion of the ventricular septum affects right ventricle (RV) contractile performance in LBBB patients with preserved left ventricular ejection fraction (LVEF). Forty-four patients with complete LBBB were selected using standard 12-lead electrocardiograms (ECGs), with 30 healthy individuals serving as controls. According to the presence of SF, patients with LBBB were allocated to two subgroups: those with SF  and those without SF . RV longitudinal strain (LS) decreased in LBBB patients with preserved LVEF compared to control subjects (p = 0.002). And RV LS decreased significantly in LBBB-SF patients compared to NSF-LBBB patients (p = 0.04). RV LS correlated negatively with involved septal myocardial segments of SF , but did not correlate with the magnitude of SF. RV contractile performance deceased in LBBB patients with preserved LVEF. SF, particularly the extent of this phenomenon, may further affect RV contractile performance. Such abnormal electric conduct and activation asynchrony may lead to early active leftward contraction of the septum within the isovolumic contraction time, followed by lengthening, while the late-activated lateral wall starts to contract5. Abnormal motion of the ventricular septum has been described by echocardiography and is referred to as a septal flash (SF)6. A previous study has reported that SF may increase LV inefficient pump function, and may be a pathophysiological mechanism of underlying heart failure in patients with LBBB9. However, whether SF simultaneously affects RV contractile performance in LBBB patients with preserved left ventricular ejection fraction (LVEF) has not been elucidated.Left bundle-branch block (LBBB) is a conductive disorder that causes electric activation dyssynchrony between the right ventricle (RV) and the left ventricle (LV), and between the septum and the left ventricle free wall10.It has been revealed that two-dimensional speckle-tracking echocardiography (2D STE) can assess RV myocardial global and regional systolic function by obtaining the myocardial strain and strain rate based on the tracking of speckles in grayscale 2D echocardiographic images, and RV longitudinal strain (LS) is less confounded by overall heart motionGiven these recent findings, using 2D STE and then measuring RV LS, we conducted this study with three objectives in mind: (1) to assess RV contractile performance in LBBB patients with preserved LVEF; (2) to further investigate the effect of SF on RV contractile performance; (3) to investigate the correlation of RV contractile performance with the extent and magnitude of SF. To the best of our knowledge, this is the first study to explore this topic.11. A normal LVEF was defined according to the recommendations of the American Society of Echocardiography criteria: LVEF ≥52% in men or ≥54% in women10. Exclusion criteria were as follows: myocardial infarction, positive exercise test result, pulmonary hypertension, acute coronary syndrome, valvular dysfunction, uncontrolled hypertension, ventricular preexcitation, atrioventricular conduction abnormalities, atrial fibrillation, paced rhythm, idiopathic cardiomyopathy, congenital heart disease, poor echocardiographic imaging or ECG, and patient unwillingness to provide informed consent. Several healthy individuals were selected for the control group, with the same exclusion criteria. Ultimately, a total of 50 patients with complete LBBB and normal LVEF  and 33 age- and sex-matched healthy controls  were enrolled. All methods were carried out in accordance with the relevant guidelines and regulations. Written informed consent was obtained from all participants, and the study was approved by the China Medical University Ethics Committee.Patients with a diagnosis of complete LBBB, and whose LVEFs were within the normal range, were consecutively selected from the outpatient and inpatient departments of The First Hospital of China Medical University. Complete LBBB was defined by baseline standard supine 12-lead electrocardiograms (ECG) as (1) QRS duration ≥140 ms in men or ≥130 ms in women; (2) QS or rS in leads V1 and V2; and (3) mid-QRS complex slurring or notching in ≥2 of contiguous leads V1, V2, V5, V6, I, and aVL10. At least three consecutive cardiac cycles were stored in cineloop format for offline analysis.All standard echocardiographic images were acquired in the left decubitus position during normal respiration using a Vivid 7 Dimension ultrasound system  equipped with a 2- to 4-MHz phased-array probe, in accordance with the recommendations of the American Society of EchocardiographyLV end-diastolic volume, LV end-systolic volume, and LVEF were computed from apical two- and four-chamber views using the biplane modified Simpson method. RV basal cavity diameter (RVD1), RV mid cavity diameter (RVD2), RV end-diastolic area (RVEDA), and RV end-systolic area (RVESA) were measured in the RV-focused apical four-chamber view. RV fractional area change (RVFAC) and the index of global RV systolic function were calculated as follows: RVFAC (%) = (RVEDA − RVESA)/RVEDA. Tricuspid annular plane systolic excursion (TAPSE), the index of RV longitudinal systolic function, was measured by M-mode echocardiography using the apical approach with the cursor optimally aligned along the direction of the tricuspid lateral annulus.Pulsed-wave TDI images were acquired by activating the TDI functions of the echocardiography unit. For the apical approach, the sample volume should be positioned on the tricuspid lateral annulus to record peak systolic velocity of the tricuspid annulus (S’), isovolumic contraction time (ICT), isovolumic relaxation time (IRT), and ejection time (ET) intervals, to achieve a view that shows parallel alignment of Doppler beam with RV free wall longitudinal excursion. RV index of myocardial performance (RIMP), the index of global RV performance, is calculated as follows: RIMP = (IVRT + IVCT)/ET.Dynamic 2D ultrasound images of three cardiac cycles from the RV-focused apical four-chamber view were acquired using conventional ultrasound, with a frame rate of 57 to 72 frames per second. Image analysis was performed off-line using customized software within the EchoPAC work station . The endocardial boundary of the RV was delineated manually, after which the software automatically drew the epicardial boundary. The widths of the regions of interest were adjusted manually to match the actual endocardial and epicardial boundaries. Automatic frame-by-frame tracking of speckle patterns during the cardiac cycle yielded a measure of strain. Subjects with inadequate tracking of more than one segment in the RV-focused apical four-chamber view were excluded from the study. The peak systolic LS of the basal, middle, and apical portions of the RV lateral wall were obtained Fig. . By averThe existence of SF was assessed by 2D STE in the apical four- and three-chamber views. SF was defined as the presence of early leftward motion (pre-ejection shortening) and rightward septal motion (early systolic lengthening) within the isovolumic contractile period  was considered statistically significant.Of 83 potential study individuals, one (1.2%) patient was excluded due to poor ECG quality, which may have been a result of an unstable ECG signal. During the analysis of RV strain by 2D STE, five (6.0%) patients with LBBB and three (3.6%) controls were excluded because of poor echocardiographic images and inadequate tracking quality of more than one segment in the RV-focused apical four-chamber view. The data of the remaining 74 subjects (44 LBBB patients with preserved LVEF and 30 controls) were used for statistical analysis.Baseline characteristics of the study population are shown in Table The QRS duration among patients with or without LBBB differed significantly. LBBB patients with preserved LVEF had a wider QRS duration (p < 0.001). Further, the QRS duration of LBBB-SF patients was wider than LBBB-NSF patients .LBBB patients had a lower LVEF, although LVEFs of both groups were in the normal range Table . LVEF ofValues for RV chamber dimensions and contractile performance of the study population are presented in Table The effect of SF on RV contractile performance in LBBB patients with preserved LVEF was further analyzed. RV LS of the LBBB-SF patients was significantly lower than controls and the LBBB-NSF patients , but did not correlate with the magnitude of SF .The intra-observer and inter-observer concordances on identifying SF by 2D STE were 20/20 (100%) and 19/20 (95%). Mean differences of intra-observer and inter-observer variability of RV LS were 0.48% (95% CI: −1.04 to 0.72%) and 0.82% (95% CI: −1.66 to 1.04%).The findings of the present study can be summarized as follows: (1) SF was present in 54.5% of LBBB patients with preserved LVEF; (2) RV contractile performance deteriorated in LBBB patients with preserved LVEF; (3) SF may further affect RV contractile performance of LBBB patients with preserved LVEF, and may be the main determinant; (4) the degree of the impairment of RV contractile performance in LBBB patients with preserved LVEF correlates with the extent (but not the magnitude) of SF.et al.5 using an experimental model. They attributed the leftward motion to septal active contraction, through analysis of pressure-segment length loops, and showed that delayed LV lateral wall contracting, septal flattening, and RV volume reduction may be due to the paradoxical rightward motion of the septum. However, in patients with LBBB diagnosed by current, new, and rigorous ECG criteria, SF does not always appear. In this study, we investigated the prevalence of SF (54.5%) in LBBB patients with preserved LVEF, the results of which were different from a study by Corteville et al. (45.2%)12. In their study, 125 LBBB patients with a wider range of LVEF (37%–61%) were selected. Differences in the restriction point of LVEF in the study population, and the sample size, may explain the difference in SF prevalence. In our study, we selected patients with normal ranging LVEF to avoid the effect of LV pump function on RV contractile performance.The mechanisms of septal flash  during LBBB were expounded by Gjesdal 6. Moreover, septal infraction and other factors that can affect the transseptal pressure gradient may also affect the presence and magnitude of SF13.In addition to the presence of SF, we counted the involved myocardial segments of SF and measured the magnitude of SF in each patient in the LBBB-SF group. The presence, extent, and magnitude of SF were varied in LBBB patients. All LBBBs were not absolutelyequal. This heterogeneity may relate to the variable anatomy of the left bundle, the different sites of LV breakthrough, and the different levels and/or extent of conduction block in the left bundleet al.12 revealed a significant correlation between the presence of SF and longer QRS duration. In line with their findings, we also found that the QRS duration of LBBB-SF patients was wider than LBBB-NSF patients and controls. In spite of this, surface ECG recordings may not be adequate to precisely identify the presence, extent, and magnitude of SF, which highlights the advantages of echocardiography in identifying further subtypes of LBBBs.A previous study by Corteville 17. Moreover, asynchronous electric activation may lead to LV remodeling caused by regional differences in workload, including asymmetric myocardial hypertrophy and LV dilatation, which may aggravate preexisting LV pump performance18. When SF occurs, septal active contraction, followed by lateral wall passive stretch and delayed lateral wall shortening, followed by septal lengthening, has a further negative effect on LV stroke volume, which is similar to the effect of an aneurysm during LBBB5. In line with these findings, we also found that the LVEF of LBBB patients was lower than controls, and that LBBB-SF patients had a lower LVEF than LBBB-NSF. Additionally, we found the LV global LS of LBBB-SF patients was lower than LBBB-NSF and controls.Other studies have been reported regarding the effect of LBBB on LV function. Electric activation asynchrony as a result of LBBB may lead to abnormal inter-ventricular, intra-ventricular, and atrioventricular coupling, which impairs the ability of the LV to fill or eject blood. In addition to its direct effect on LV mechanical function, asynchronous electric activation may affect coronary flow throughout the coronary vasculature from the epicardial arteries to the microvascular bed. This can lead to subsequent changes of myocardial perfusion, oxygen demand, glucose metabolism, and have an ultimately deleterious effect on LV function during LBBBet al.20 suggested that LBBB patients with normal LV dimensions and EF at rest may present with an abnormal increase in mean pulmonary artery pressure during exercise. Moreover, they performed myocardial biopsy from the RV septum and found abnormal ultrastructural findings in myocardial cells, such as degeneration, interstitial fibrosis, mitochondrial and myofibrillar changes, among others, in LBBB patients with normal LV. However, thus far, no study has provided data about RV myocardial systolic performance using a reliable method in LBBB patients with preserved LVEF. 2D STE is a novel technique enabling more reliable assessment of RV myocardial performance by obtaining myocardial strain, which is angle independent and less confounded by overall heart motion. In this study, we measured RV LS using 2D STE and found that RV contractile performance decreased in LBBB patients with preserved LVEF. The reasons for these changes are not well understood. We speculated preliminarily that, besides LV, electric activation asynchrony caused by LBBB may also lead to RV mechanical asynchrony, an abnormal perfusion of the right coronary artery, and myocardial remodeling of the RV. These remain to be explored in a series of large future studies.Compared to LV, studies about RV function in patients with LBBB in the published literature are limited. A previous study by Kuhn 21. However, patients with no SF had a shorter transseptal conduction time, probably because of activation within the proximal left bundle; this correlated more with intra-ventricular mechanical delay. It was well known that inter-ventricular mechanical asynchrony may affect both LV and RV function; but intra-ventricular mechanical asynchrony may not have a direct effect on RV function.In the current study, we found SF to be the main determinant of RV contractile performance, and the more involved the segments of SF were in the septal myocardium, the worse the RV contractile performance was in LBBB patients with preserved LVEF. However, the magnitude of SF did not correlate with RV contractile performance. These findings may relate to the different levels of conduction block within the left bundle conduction system. It has been revealed that patients with a large SF may have a proximal block in the left bundle, longer transseptal conduction time, and a greater degree of inter-ventricular mechanical delay18. Previous researchers found normal LV function, abnormal ultrastructural changes of myocardial cells from the RV septum at rest, and slight changes during exercise in patients with isolated LBBB, and they suggested that LBBB may be the early stage of a dilative cardiomyopathy22. In the current study, we revealed abnormal RV contractile performance in LBBB patients with normal LVEF at rest. This emphasizes the importance of paying attention to these patients, especially those with a large extent of SF, and monitoring RV function by measuring RV LS, which may provide a theoretical basis for timely clinical treatment and management before the patient develops dilative cardiomyopathy or other worse conditions.It appears that LBBB occurs in several cardiac conditions, such as dilative cardiomyopathy or myocardial infarction, and may aggravate preexisting conditions. However, in some cases, LBBB may be isolated without any other abnormal findings24.A major limitation of this study was that the manufacturers had not yet developed dedicated software for RV analysis. Software for measuring RV LS has been designed for LV measurements. However, recent studies have shown that the evaluation of RV deformation using 2D STE by the same software is feasible and reproducibleAnother limitation was that the measurement of RV LS was from a single image plane  because of the complex RV geometry and limited acoustic window. We would have preferred to obtain LS from the complete RV cavity.Moreover, we found that the extent of SF correlated with RV contractile performance. However, we did not define high-risk clinical criteria for involved myocardial segments of SF, which could have identified patients whose RV performance required special attention. In future studies, we will use larger sample sizes and make follow-up observations of the patients.RV contractile performance decreased in LBBB patients with preserved LVEF. SF, particularly the extent of the phenomenon, may further affect RV contractile performance in these patients.