Likewise, a lower RV80 was associated with a better pre-CRT RV ejection fraction by CMR  and predicted post-CRT improvements in myocardial oxygen uptake (p = 0.01) better than the biventricular-paced QRS (p = 0.38), while a lower LV80 with BIV pacing predicted lower post-CRT B-type natriuretic peptide (BNP) (p = 0.02). RV pacing improved LV function with smaller |LV80-RV80| (p = 0.009). In conclusion, 3-D electrical mapping predicted favorable post-CRT outcomes and informed effective pacing strategies.The aim was to test the hypothesis that left ventricular (LV) and right ventricular (RV) activation from body surface electrical mapping  identifies optimal cardiac resynchronization therapy (CRT) pacing strategies and outcomes in 30 patients. The LV80, RV80, and BIV80 were defined as the times to 80% LV, RV, or biventricular electrical activation. Smaller differences in the LV80 and RV80 (|LV80-RV80|) with synchronized LV pacing predicted better LV function post-CRT (The online version contains supplementary material available at 10.1007/s12265-023-10418-1. Cardiac resynchronization therapy (CRT) can be a life-saving intervention for many patients with heart failure –3 and isbefore CRT to guide patient selection [after CRT is considered a valuable predictor of long-term response [Current guidelines recommend using the QRS duration (QRSd) and the type of bundle branch block election , and theresponse . A knownresponse .In this present study, we provide a novel approach for the study of electrical activation in CRT using three-dimensional electrical body surface mapping , 17 to aAll procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation  and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study. This prospective cohort study was approved by the Institutional Review Board for Human Subjects Research at the University of Virginia. The cohort included 30 adult patients aged 25 to 89 years old with an indication for a de novo CRT device or an upgrade to a CRT device from an existing pacemaker or ICD. All participants were required to have chronic systolic heart failure, left ventricular ejection fraction (LVEF) 35% or less, and a guideline-based class I or II indication for CRT. Exclusion criteria included inability to provide informed consent, pregnancy, metal implants, cerebral aneurysm clips, cochlear implants, other metallic implants contraindicated with MRI, severe claustrophobia, acute kidney injury, acute renal failure or chronic kidney disease with GFR less than 45 cc/minute, history of liver transplant, and gadolinium allergy.Prior to CRT, patients had echocardiography and cardiac magnetic resonance (CMR) for baseline data on global cardiac function, left ventricular volumes, and myocardial substrate. The research CMR protocol included steady-state free precession cine imaging to obtain ventricular geometries and cavity volumes, cine DENSE imaging to determine circumferential strain for characterization of mechanical dyssynchrony , 23, andNoninvasive electro-anatomical mapping of electrical activation timing was performed with CardioInsight body surface mapping of electrocardiographic signals during the CRT procedure and 6 months later. The CardioInsight system uses a 252-electrode vest to map electrocardiographic signals recorded on the chest onto the epicardial surface of the heart based on the contours defined by a cardiac CT scan recorded prior to the CRT procedure. During both the baseline and 6-month follow-up visits, CardioInsight mapping was performed at the following pacing settings: atrial-only pacing, atrioventricular sequential pacing using only the RV lead for ventricular pacing (RVP), atrioventricular pacing using only the LV lead for ventricular pacing (LVP), atrioventricular pacing with simultaneous biventricular pacing (BIVP), and BIVP with an LV-first offset of 30 ms. Atrioventricular timing during CRT pacing was determined either with a device-based algorithm or electrocardiogram (ECG) optimization.POST-CRT − LVESVIPRE-CRT)/LVESVIPRE-CRT.The standard 2D echocardiography protocol performed prior to CRT was performed 6 months after CRT with imaging sets from four different pacing settings corresponding to the CardioInsight electrical mapping pacing configurations during electrical 3D mapping. Specifically, the imaging sets were performed with atrial-only pacing, atrioventricular sequential pacing with RVP, atrioventricular pacing with LVP, atrioventricular pacing with simultaneous BIVP, and BIVP with an LV-first offset of 30 ms. LVESVI fractional change (LVESVI-FC) was defined as the , 80% of RV myocardial surface area would be expected to have activation within the RV80 time. As 100% of the RV myocardial surface is assumed to be activated within the QRS duration, the slope of the RV80/QRS regression line would be expected to be 0.8 with linear RV electrical activation over time. The same reasoning applies to the LV80/QRS and BIV80/QRS lines. Deviation from 0.8 can then be interpreted as electrical activation that is variable over time.t-tests were used to determine whether the ratios of the time to 80% RV, LV, or total ventricular activation to the QRS duration  were different than the default value of 0.8 in a particular grouping of patients. In other words, the null hypothesis for this test was that a particular ratio of electrical parameters was 0.8, and the alternative hypothesis was that the parameter was different from 0.8. The RV80/QRS, LV80/QRS, and BIV80/QRS were then regressed on LBBB v. RBBB status, and interaction terms were added to evaluate the influence of scar, ischemic etiology of cardiomyopathy, the QRS-LV electrogram (Q-LV) time, and QRS duration influences this relationship. In order to assess the relationship between the electrical activation parameters and multidimensional CRT response parameters , robust linear regression was used. All statistical analyses were performed using R and the statsmodels package in Python.Statistical tests were first performed to identify any differences in baseline characteristics and 6-month CRT response measures between patients with LBBB and patients with RBBB. Shapiro-Wilk tests were used to assess normality of continuous variables  and lower pre-CRT peak VO2  compared with LBBB patients. With respect to CRT response measures, the median LVESVI-FC for the entire cohort was −0.14 (IQR −0.26 to −0.0064); the median log-transformed post-CRT BNP level was 5.3 (IQR 3.9 to 5.9); and the median change in peak VO2 was 0 mL/kg/min (IQR −0.18 to 0.45 mL/kg/min). Although there were no significant differences in the fractional change in LVESVI (LVESVI-FC) in LBBB v. RBBB (p = 0.28) or log of the post-CRT BNP in LBBB v. RBBB (p = 0.23), there was more favorable coupling of the peak VO2 to the LVESVI-FC in RBBB v. LBBB (p = 0.0031).The baseline characteristics for the 30 patients  are shown in Table p = 0.005) whereas the RV80 with native conduction  and BIV80 with native conduction  were significantly greater in RBBB patients than in LBBB patients  was significantly greater in LBBB patients versus RBBB patients , respectively, and the slopes for baseline RV80 v. baseline QRS were 0.30 and 0.70 for LBBB and RBBB patients, respectively (p<0.0001 for comparison). One-sample t-tests compared to the default value of 0.8  showed significant differences from 0.8 for the LV80/QRS in both LBBB and RBBB patients (p=0.0002 for both) and the RV80/QRS in LBBB patients (p<0.0001). Based on linear regression models for the outcomes of RV80/QRS and LV80/QRS with interaction terms, the differences in the RV80/QRS in LBBB v. RBBB and LV80/QRS in LBBB v. RBBB did not depend on the presence of late gadolinium enhancement, ischemic etiology of cardiomyopathy, QRS duration, or the QRS-LV electrogram time (QLV) .As shown in Table p=0.0504 for comparison between LBBB and RBBB). In addition, neither LBBB patients nor RBBB patients had a BIV80/QRS that was significantly different from 0.8, indicating overall constant biventricular activation despite non-constant LV and RV activation, which is likely related to some cancellation of the variability of RV and LV activation functions when RV and LV activation are parameterized together as the BIV80. Although the difference in BIV80/QRS was not significantly different in LBBB and RBBB based on the p value of 0.0504, the BIV80/QRS was significantly different in LBBB and RBBB after adjustment for the QRS duration (p=0.02 for the LBBB/RBBB covariate). The p value for the interaction term LBBB*QRS was 0.03 with a positive coefficient, indicating that the BIV80/QRS is more likely to be different between LBBB and RBBB with longer QRS durations.The BIV80/QRS for LBBB and RBBB were 0.60 and 0.66, respectively ; however, the difference LV80/QRS between pacing strategies was not different in LBBB .Figure p = 0.03) was significant among the two groups. Supplemental Fig. The distributions of the LV80, RV80, and BIV80 electrical activation parameters for representative patients with LBBB and RBBB are shown in the “pacing configuration plots” in Fig. LVP; p = 0.0004); the |LVRVDIFF| performed better than the paced QRSd for this prediction scenario, as the QRSd with LVP was not significantly associated with LVESVI-FCLVP (p = 0.38) .We used robust linear regression to assess relationships between chamber-specific electrical parameters and CRT response measures, then compared them with the performance of the paced QRS duration (QRSd). Figure 38) Fig. d.Fig. 5ARVP) function was better with RV pacing , once more highlighting the importance of better electrical interventricular synchrony. Of note, the QRSd with RVP was not significantly associated with the LVESVI-FC during RVP  (p = 0.55).An analogous result was obtained with |LVRVDIFF| during RVP, as a lower |LVRVDIFF| during RVP was associated with better LV function with RVP compared to baseline , and this relationship was more apparent than when the paced QRSd was used (p = 0.038) /RV80PRE-CRT < 100% . Although there was no significant interaction, both covariates were significant predictors in the model , which had an overall R2 of 0.41 (model p=0.0028).Lower LV80 was associated with lower post-CRT BNP Fig. j (p = 0.38) Fig. l. In add00% Fig. n, while ion Fig. p. Since p values for the first two columns of Fig. p values for robust regression of LVESVI-FCLVP on LV70-RV70-DIFFLVP and LVESVI-FCLVP on LV80-RV80-DIFFLVP are on the order 10−4 (0.00013 to 0.00041), while the p values for LVESVI-FCLVP on LV90-RV90-DIFFLVP is on the order of 10−2 (0.011), and the p value using just the full QRS is not significant. This demonstrates that electrical parameters at 70–80% of the QRS duration had the strongest relationship with response. Progressively weaker relationships with response were observed with the use of electrical activation parameters based on 90% and 100% of the QRS complexes.Figure R2 statistic, p value of the model, and Pearson’ correlation coefficients for models with a single covariate. This demonstrates that the degree of late activation at the LV pacing site had some additional predictive value to the electrical activation parameter from 3-D mapping in some of the models. With respect to other electrical parameters, the baseline PR interval did not improve the models below. Of note, the A-V pacing delays in this study were selected based on either the device-recommended A-V delay or the A-V delay resulting in the most narrow QRS complex, as is typically performed in clinical practice.The impact of electrical activation timing at the LV pacing site for each model in Fig. r =  − 0.40, p = 0.04)    pre-CRT overall (04) Fig. a and a g25) Fig. b. This d.5) Fig. c, highli2 of at least 1 mL/kg/minute with biventricular pacing had a more favorable RV80 time with biventricular pacing, highlighting the coupling between exercise capacity and right ventricular function.Supplemental Fig. 2, and the BNP after CRT, which has been of particular interest in several CRT studies [In summary, this novel study offers a new paradigm for the application of three-dimensional body surface mapping to CRT by examining the consistency of activation rates of the RV and LV over time, employing activation parameters in the setting of variable RV and LV activation over time, evaluating the impact of cardiac pacing strategies on both parameters and overall clinical response, and assessing three-dimensional electrical activation parameters with multiple dimensions of CRT response. The main finding of this study is that RV-specific or LV-specific assessments of RV and LV activation after CRT have greater associations with CRT response outcomes than biventricular measures of electrical activation derived from the surface electrocardiogram (QRS duration or change in QRS duration result from CRT). These outcomes included improvement in LV systolic function, improvement in exercise capacity based on the peak VO studies , 24, 25. studies . This is studies .2). The observations also highlight the role of body surface mapping to assess RV electrical activation, define the pacing strategy in RBBB, and predict the functional response to biventricular pacing.In addition, important findings were demonstrated for body surface mapping in the setting of RV dysfunction, delayed RV electrical activation, and RBBB: (1) a subgroup of patients with RBBB who had favorable LV remodeling with RV pacing only was identified; (2) decreased RV function by CMR was shown to be associated with delayed RV electrical activation using body surface mapping but not with the QRSd from the surface electrocardiogram; and (3) RV electrical activation timing was associated with improvement in myocardial oxygen uptake  with LV functional improvement after synchronized LVP, the LV80 during biventricular pacing with BNP after CRT, and the avoidance of RV80 prolongation post-CRT with improvements in peak VOWhile we recognize the three-dimensional body surface electrical mapping will likely be a specialized treatment for selected CRT implants in the future, we offer a novel approach for its application to CRT and have shown its utility in specific cases for explaining different manifestations of CRT response, including coupling of LV functional improvement to improvements in exercise capacity and neurohormonal activation. We have also shown the utility of the analysis for predicting response measures based on the resynchronization pacing strategy employed, specifically biventricular or synchronized left ventricular pacing. In addition to advancing the field by demonstrating key mechanisms of CRT response relative to patterns of chamber-specific ventricular activation, we believe that these findings also demonstrate that three-dimensional body surface electrical mapping can have an important clinical impact for many patients with traditional CRT implants. Future applications in patients with conduction system pacing are also of great interest .As a comparison with other approaches to electrical mapping, we contrast the approach in this paper with the vectorcardiography-derived index . The modIn conclusion, this study demonstrates that 3-D electrical mapping predicted favorable post-CRT outcomes and informed effective pacing strategies. Specifically, the study shows that interventricular electrical dyssynchrony based on the absolute value difference in the LV80 and RV80 predicts LV functional improvement with synchronized LVP, and this same measure during RV pacing demonstrates when RV pacing is expected yield similar results to LVP and BIVP. The RV80 was shown to correlate well with pre-CRT RV function on CMR, and the fractional change in this parameter predicted the greatest increases in functional capacity with BIVP. Lastly, LV80 also predicted lower neurohormone levels with BIVP.We acknowledge that this was a pilot study with relatively small numbers of patients enrolled; however, the demonstration of statistically significant and reproducible findings in this cohort with respect to CRT mechanisms is impressive and justifies studies in larger cohorts. The study design may be considered both a strength and limitation. The assessment of the acute effects of CRT pacing modes at the follow-up visits over 6 months offers links between the acute mechanical effects of resynchronization with different pacing modes and electrical parameters. While many of the patients had been programmed to the CRT pacing mode studies (BIVP or synchronized LVP) at the time of echocardiographic post-CRT functional assessments, others may have been programmed to BIVP for the past six months, such that the mechanical observations would then be interpreted as more acute effects. Future studies could be designed to also focus on the effects of the pacing modes over longer periods of time as facilitated by larger numbers of patients. Additionally, electrical activation of the septum was not assessed during any pacing mode but may also be useful in predicting CRT outcome.ESM 1(TIFF 65004 kb)High resolution image (PNG 525 kb)ESM 2(TIF 709 kb)High resolution image (PNG 262 kb)ESM 3(DOCX 14 kb)


Summary: This Editorial introduces DMM's new Special Issue on ‘Moving heart failure to heart success’. The Guest Editors reflect on how articles in the issue advance the cardiac research field. Heart failure is characterised by the heart's inability to pump blood effectively, leading to reduced oxygen and nutrient supply to the body's organs and tissues, and is the leading cause of hospitalisation and of deaths in men and women worldwide . Heart fA significant risk factor for heart failure is congenital heart defects, which are structural abnormalities present at birth. Congenital heart defects occur frequently, affecting 8 out of every 1000 newborns, and are the major cause of morbidity and mortality in infants and children . AlthougBeyond disordered heart development, arrhythmias, which occur due to disruptions in the heart's electrical system, represent another important risk factor for developing heart failure. Electrical currents that initiate contraction of cardiomyocytes can be disrupted by various factors, including structural remodelling of the heart, mis-regulation of ion channels, or a malfunctioning cardiac pacemaker. A Review by Vincent Christoffels and colleagues, published in this issue, explores the genetics of sinoatrial node dysfunction and how this contributes to arrhythmias . New tecin vitro and in vivo models that faithfully recapitulate key aspects of these diseases are essential. Such models will enable the investigation into the underlying genetic mechanisms and the development of potential treatments for these conditions. Precise genome editing, as discussed in the Review from Eva Van Rooij's group  in non-coding DNA that increase the risk of developing a cardiac disease . The indHeart disease that sets the path towards heart failure can present after birth and during adulthood as a consequence of other conditions, such as coronary heart disease, infections, acute or chronic diseases that affect other organs than the heart, high blood pressure, valve disease and many others .Myocardial loss as a consequence of injury is largely irreversible. Translatable strategies to promote tissue regeneration or to mitigate tissue loss could fundamentally address myocardial deficits. Prior work showed that genetic deletion of Tip60 promotes functional recovery after experimental myocardial infarction with evidence of cell cycling . BuildinDUSP6 is a protein that has already been investigated in the context of heart regeneration in zebrafish, mice and rats. In their new article, The generation and analysis of rats with cardiac-specific knockout of Trim44 by These type of models and approaches are valuable in providing a better understanding of the complex network underlying physiological heart development and growth and its pathological remodelling, and provide a rationale for mechanistic intervention development.Finally, sometimes the treatment of heart failure, including corrective surgeries with the need for cardiopulmonary bypass, can lead to terminal inflammation. These processes are the topic of intense investigation, because reducing the unwanted side effects can significantly improve patient outcomes. Despite significant progress in understanding and treating the underlying causes of heart failure, organ transplantation remains a keystone therapeutic option, but is significantly hampered by severe donor organ shortages. Xenotransplatation has long been a faraway possibility, but, as Eckhard Wolf and colleagues discuss in their Perspective, the community is inching closer to a realistic prospect .The Research, Resource and Review-type articles in this Special Issue cover a wealth of seemingly diverse topics. However, preventing, understanding and treating heart failure are the common threads that bind these articles. Importantly, these articles are openly accessible to all interested researchers, patients and clinicians who work tirelessly to advance the field. Better models, refined analytics, richer patient datasets and innovative therapeutic interventions are already moving heart failure towards clinical success. We look forward to future research advances that will undoubtedly enrich DMM's ongoing subject collection and the field as a whole.


Some patients with pulmonary atresia with an intact ventricular septum (PA/IVS) or a left ventricle dominant atrioventricular canal defect (LDAVC) with a hypoplastic right ventricle (RV) and univentricular (1 V) circulation may be candidates for conversion to either a complete biventricular (2 V) repair or a one-and-a-half ventricle repair (1.5 V). We sought to identify pre-operative cardiovascular magnetic resonance (CMR) findings associated with successful conversion from 1V to 1.5V or 2V circulation.In this single center retrospective study, subjects with PA/IVS or LDAVC and no conotruncal abnormalities were included if they had a 1 V circulation at the time of CMR followed by a surgical intervention intended to convert them to a 1.5 V or 2 V circulation. Conversion failure was defined as any of the following: (1) oxygen saturation < 90% at the most recent follow-up, (2) conversion back to a 1.5 V or 1 V circulation, or (3) death.2. In the LDAVC cohort , 1 patient underwent surgical conversion to a 1.5 V circulation and 14 patients to a 2 V circulation. In the attempted 1.5 V group, the 1 conversion was a failure and had an RV EDV of 15 ml/m2. In the attempted 2 V group, there were 2 failures, and these cases had a smaller RV:LV stroke volume ratio (p = 0.05) and a lower RV ejection fraction (p = 0.05) compared to the successes. Among the successful 2 V group patients, the minimum RV EDV was 22 ml/m2.In the PA/IVS cohort , 10 patients underwent surgical conversion to a 1.5 V circulation and 5 to a 2 V circulation. In the attempted 1.5 V group, there were 2 failures, and these cases had a lower RV mass (p = 0.04). In the attempted 2 V group, there was 1 failure, and no CMR parameters were significantly different compared to the successes. Among the successful 2 V group patients, the minimum RV end-diastolic volume (EDV) was 27 ml/mWe identified multiple CMR parameters associated with successful conversion from 1 V circulation to 1.5 V or 2 V circulation in patients with PA/IVS and LDAVC. This information may improve patient selection for conversion procedures and encourage larger studies to better define the role of CMR.The online version contains supplementary material available at 10.1186/s12968-023-00965-6. A range of right ventricular underdevelopment may be seen in congenital heart disease. At one end, patients with severe ventricular hypoplasia and/or valve stenosis require a single ventricle (1 V) palliative approach, culminating in a Fontan circulation. Alternatively, patients less severely affected may be suitable candidates for a biventricular (2 V) circulation or a one-and-a-half ventricular (1.5 V) circulation  to pulmonary arteries, and a small or no atrial septal defect (ASD)). Deciding which management strategy to pursue has major implications for a patient’s long-term health and can be difficult.This challenge most commonly arises in patients with one of two anatomic diagnoses: 1) pulmonary atresia with an intact ventricular septum (PA/IVS) and (2) left-dominant atrioventricular canal (LDAVC). Choosing a 1 V palliative approach places them at risk for the long-term complications of a Fontan circulation including ventricular dysfunction, protein losing enteropathy, plastic bronchitis, arrhythmias, thromboembolism, and liver failure  pulmonar. AlternaIn such patients with small right hearts, multiple factors are reviewed to determine whether 1.5 V or 2 V circulation can be supported. These include right heart pressure measurements at catheterization and anatomic measurements by echocardiography such as the tricuspid valve annulus z-score, RV to left ventricle (LV) length ratio, RV/LV area ratio, tricuspid valve function, and ratio of tricuspid and mitral valve area –11. DataA retrospective database review of all patients who underwent a CMR at Boston Children’s Hospital from January 2005 through December 2020 was conducted. Subjects were included if they had the following: (1) PA/IVS or LDAVC, (2) no conotruncal abnormalities , and 3) a 1 V circulation at the time of CMR followed by a surgical or catheter intervention intended to convert them to a 1.5 V or 2 V circulation. LDAVC patients were those with endocardial cushion defects and RV hypoplasia and/or more than 50% of the common atrioventricular valve related to the LV. Patient demographics, clinical history, and CMR data were obtained from the medical record. The Boston Children’s Hospital Institutional Review Board approved this study and a waiver of informed consent.All available clinical records were reviewed. The surgical or catheter intervention intended to convert them to a 1.5 V or 2 V circulation was defined as a failure for any one of the following: (1) oxygen saturation < 90% at the time of most recent follow-up, (2) conversion from a 2 V circulation back to a 1.5 V or 1 V circulation, or from a 1.5 V circulation back to a 1 V circulation, or (3) death. Additional outcome measures included RV dysfunction at follow-up defined as a qualitative RV function grade of mild or worse on the most recent echocardiogram, and ASD flow direction on the most recent echocardiogram.CMR was performed on a 1.5 T scanner . The imaging protocol included (1) steady-state free precession cine imaging in an axial plane covering the thorax and in ventricular long- and short-axis planes; (2) a gadolinium-enhanced magnetic resonance angiogram; (3) phase velocity flow measurements in the ascending aorta, pulmonary valve, atrioventricular valves, and branch pulmonary arteries; and, in some patients, (4) LGE imaging in ventricular long- and short-axis planes 10–15 min after the administration of contrast.Ventricular volumes and flow measurements were calculated using commercially available software  as previously described .Over the study period, 15 patients with PA/IVS with a 1 V circulation met the inclusion criteria and underwent CMR prior to conversion to a 1.5 V or 2 V circulation  months, 4 of the 8 patients underwent a subsequent surgery (branch pulmonary artery plasty (n = 1); pulmonary valve replacement, tricuspid valve plasty, and division of RV muscle bundles (n = 1); pulmonary valve replacement, tricuspid valve plasty, and creation of small atrial septal fenestration (n = 1); and tricuspid valve plasty and right atrial reduction (n = 1)), but all maintained a successful 1.5 V circulation. Also, 2 of the 8 patients underwent catheter interventions  and pulmonary valve balloon dilatation followed 6 months later by transcatheter pulmonary valve replacement (n = 1)).In the attempted 1.5 V group (n = 10), over a median post-surgical follow-up time of 40 months (18–75), there were 2 failures  months, 1 of the 4 patients underwent a subsequent surgical intervention .In the attempted 2 V group (n = 5), over a median post-surgical follow-up time of 60 months (1.4–95), there was 1 failure , 2 of the 12 successful 2 V patients underwent subsequent surgery. One patient underwent pacemaker placement 9 days after 2 V conversion surgery. The second patient underwent (1) ASD closure for patch dehiscence and cyanosis 7 days after surgery, (2) tricuspid valve repair for insufficiency 18 months after conversion surgery, and 3) tricuspid valve replacement with a Melody valve for stenosis, ASD creation, and RV muscle bundle resection 19 months after conversion surgery. Another 3 of the 12 patients underwent catheter interventions following conversion surgery (ASD device closure (n = 1), balloon dilatation of a pulmonary vein (n = 1), and balloon dilatation of the pulmonary valve (n = 1)).In the attempted 2 V surgical conversion group (n = 14), over a median post-surgical follow-up time of 39 months (0.5–116), there were 2 failures, both for oxygen saturation < 90%  (Table 2. In patients with a LDAVC, a larger RV:LV stroke volume ratio and a higher pre-operative CMR RV ejection fraction were associated with successful conversion to 2 V circulation, and a success was seen with an RV EDV as low as 22 ml/m2. These results may aid decision-making and serve as a stimulus for further study.This study is the first to report CMR descriptive data and findings associated with successful conversion from 1 V circulation to 1.5 V or 2 V circulation in patients with right heart hypoplasia. In patients with PA/IVS, a greater RV mass was associated with successful conversion to a 1.5 V circulation and none of the CMR parameters were significantly associated with successful conversion to a 2 V circulation. The presence of RV LGE was not associated with successful conversion. A successful 2 V conversion was seen with an RV EDV as low as 27 ml/mPatients with significant right heart hypoplasia often pose a management dilemma. A 1 V palliative approach incurs the morbidity and mortality risks of a Fontan circulation, and these risks tend to increase as patients age. Conversion to a 1.5 V or 2 V circulation may reduce these risks, particularly those that are related to elevated systemic venous pressure. Moreover, having a ventricle propel all or part of the systemic venous return to the pulmonary circulation may improve cardiovascular performance . HoweverManagement decisions in patients with right heart hypoplasia are often made by integrating multiple patient factors with a strong reliance on data from echocardiography and cardiac catheterization. For example, relevant echocardiographic measurements in unbalanced atrioventricular canals include the atrioventricular valve index , RV/LV i2 should not be considered for a 1.5 V or 2 V conversion. Moreover, in both the PA/IVS and LDAVC groups, some patients with moderately hypoplastic RVs were still able to achieve a successful 2 V conversion. This suggests that their RVs are relatively compliant and can adapt to an increase in inflow without a dramatic rise in filling pressure. Thus, an RV EDV as low as approximately 30 ml/m2 should not preclude an attempt at a 2 V conversion if other factors are favorable. Lastly, there were 4 patients with PA/IVS and an ejection fraction < 45% that were able to achieve a successful 1.5 V conversion. The impact of conversion on RV ejection fraction and the benefits of a 1.5 V circulation versus a Fontan circulation require further study.Despite its small sample size, our study was able to identify CMR parameters that were associated with a successful conversion from 1 V circulation to 1.5 V or 2 V circulation. In patients with a LDAVC, a larger RV:LV stroke volume ratio and a higher pre-operative CMR RV ejection fraction were linked with successful conversion to 2 V repair. Both of these findings make physiological sense as the RV is required to handle a greater volume of blood with the conversion procedure. Based on this data, we would strongly consider a 2 V conversion if the RV:LV stroke volume ratio is ≥ 0.4 and the RV EF is ≥ 55%. In patients with PA/IVS, a greater RV mass was associated with successful conversion to a 1.5 V circulation. Greater mass is likely advantageous because it allows the RV to maintain a higher mass:volume ratio in the setting of a volume increase. An insufficient mass to volume ratio leads to increased wall stress and afterload which may predispose the ventricle to systolic dysfunction. Our data suggest that patients with a RV mass less than approximately 10 g/mOur study has several important limitations. It had a relatively small sample size as PA/IVS and LDAVC are rare conditions and only a subset of patients with these diagnoses underwent a 1.5V or 2V conversion procedure. Moreover, our study design excluded patients who had a CMR study but did not undergo a conversion procedure, perhaps based on the CMR data itself. Both of these factors could have potentially decreased the power of the study to identify CMR parameters associated with a successful conversion. Moreover, all patients underwent their CMR studies and conversion procedures at a single institution thereby limiting the study’s generalizability. Lastly, this study did not have long-term follow-up on patients because many of the conversion surgery procedures were relatively recent. It is possible that over time additional patients may meet the criteria for failure.2 and in LDAVC patients with an RV EDV as low as 22 ml/m2. More studies that incorporate additional centers and subjects and with longer follow-up are needed to improve patient selection for conversion procedures and better define the role of CMR.This study identified multiple CMR parameters associated with successful conversion from 1 V circulation to 1.5 V or 2 V circulation in patients with PA/IVS and LDAVC. Moreover, it showed that successful 2 V conversions could be achieved in PA/IVS patients with an RV EDV as low as 27 ml/mAdditional file 1: Figure S1. 12-month-old male with pulmonary valve atresia and an intact ventricular septum status-post pulmonary valve perforation and dilation and placement of a ductus arteriosus stent at 3 days old. CMR cine images at end-diastole in the ventricular short-axis plane illustrating ventricular contours.Additional file 2: Figure S2. 5-year-old female with trisomy 21 and a left-dominant complete atrioventricular canal defect status-post pulmonary artery band placement at age 2 months and status-post a bidirectional Glenn shunt and over-sewing of the main pulmonary artery at age 11 months. CMR cine images at end-diastole in the ventricular short-axis plane illustrating ventricular contours.


The extent of the hemodynamic benefit from AV-synchronous pacing in patients with sinus rhythm and AV block is not completely understood. Thus, we systematically investigated the association of an array of echocardiographic and epidemiological parameters with the change in cardiac output depending on the stimulation mode (AV-synchronous or AV-asynchronous pacing).Patients in sinus rhythm after previous dual chamber pacemaker implantation underwent a thorough basic echocardiographic assessment of diastolic and systolic left ventricular function, and atrial function . Then, stroke volume was measured with AV-synchronous (DDD) and AV-asynchronous (VVI) pacing. Each patient represented their own control, and the sequence of stroke volume measurements was randomized.P < 0.001]. No echo parameter under investigation was associated with the extent of stroke volume increase in a linear regression model. Of all epidemiological variables, a history of acute myocardial infarction (AMI) was associated with an attenuated stroke volume gain in a univariate and a multivariate regression model that adjusted for confounders. A- and S-wave velocities were reduced in the AMI group.In this prospective single-center study , we recruited 40 individuals. The stroke volume was higher in all patients when applying AV-synchronous DDD pacing [median increase 12.8 ml (16.9%), In our cohort of patients, each subject benefited from AV-synchronous DDD pacing. No single echo parameter could predict the amount of stroke volume increase. The beneficial effect of AV-synchronous pacing on stroke volume was attenuated after prior acute myocardial infarction.ClinicalTrials.gov identifier (NCT number): NCT04068233.  However, it is still unclear which patient groups are most likely to receive hemodynamic benefit from AV-synchrony or to develop pacemaker syndrome , 2. This2.2.1.In this prospective, randomized, single-center, single-cohort interventional trial, we recruited patients to undergo a single echocardiographic examination with different pacing modes according to our protocol. Each patient represented their own control. We collected baseline variables . No further follow-up was performed, as participants finished the study immediately after the echo examination or after any ongoing adverse event was resolved. Approval of the study protocol by the local ethics committee of the Province of Upper Austria was sought and granted . The study was prospectively registered with ClinicalTrials.gov and was assigned the unique identifier NCT04068233. Subjects above the age of 18, who were scheduled for a routine device follow-up at our outpatient department, were eligible for inclusion if they were implanted with a dual chamber pacemaker system for at least six weeks and were able and willing to give informed consent. The time interval of six weeks was chosen to allow the tissue-leads interface to mature and the device parameters to stabilize after initial implantation. Patients had to be in sinus rhythm on the day of recruitment and the day of the echo examination. Upon initial device interrogation, the ventricular pacing rate had to exceed 90% due to AV-block. Moreover, the technical parameters of the pacemaker system had to be within normal ranges . Patients were excluded if they were not in sinus rhythm or exhibited intrinsic ventricular activation on the day of the echo examination. Further exclusion criteria were relevant anatomical shunts on the atrial, ventricular, or pulmonary level, moderate or severe heart valve dysfunction (stenosis or regurgitation), presence of other medical devices that might have interacted with the pacemaker system, and pregnancy or breastfeeding in women. The exact location of the right ventricular (RV) lead was determined by analyzing the most recently available chest x-ray . RV lead position was classified as “mid/high septal”, “inferior septal”, “apical”, or “right ventricular outflow tract (RVOT)”.2.2.per se is heart rate dependent. The secondary endpoints were defined as the association between baseline echo parameters of (1) left ventricular systolic function and (2) left and right atrial function, as well as (3) epidemiological variables and the change of stroke volume with different pacing modes [AV-synchronous (DDD) vs. AV-asynchronous (VVI)].The primary endpoint was defined as the association between baseline echo parameters of left ventricular diastolic function and the change of stroke volume with different pacing modes [AV-synchronous (DDD) vs. AV-asynchronous (VVI)]. The echo parameters collected in this study are summarized in 2.3.r), the conduit phase (LAScd), and the contraction phase (LASct) of the left atrium . If the pacing mode was changed, measurements started after one minute at the earliest to allow for hemodynamic adaptation. All echo examinations were performed with continuous ECG tracings and stored digitally (at least five continuous beats). One-dimensional echo parameters were averaged over three consecutive beats. Global longitudinal strain measurements were performed using a dedicated speckle tracking software . Left ventricular global longitudinal peak systolic strain (GLPSS) was assessed as described previously from the apical four-, two-, and three-chamber view , 14. Peat atrium .2.3.1.In a first step, the AV interval was optimized by visually assessing the PW-Doppler tracing at the tips of the mitral valve leaflets. In each individual, we aimed at an AV interval that promoted ventricular pacing without (1) truncation of the A-wave or (2) E- and A-wave fusion at the baseline sinus rate. The programmed AV-delay was kept constant during the entire investigation.2.3.2.Parameters of left ventricular diastolic and systolic function as well as right and left atrial function were assessed applying a DDD pacing mode. Thereby, the intervention rate was set to 40 beats per minute to ensure atrial sensing and AV-synchronous ventricular pacing. Diastolic dysfunction was graded according to current guideline recommendations (grade I–III) . For tec2.3.3.Left ventricular stroke volume was measured with two different pacing modes: in (1) DDD mode with an intervention rate set to 40 beats per minute and in (2) VVI mode with the intervention rate approximately set to the intrinsic sinus rate. With the first setting, atrial sensing and AV-synchronous ventricular pacing were ensured, whereas with the second setting AV-asynchronous ventricular pacing was achieved for comparison. The sequence of pacing modes (VVI after DDD or vice versa) was randomized among the study subjects by coin tossing to account for a possible time trend bias. For echocardiographic assessment of the stroke volume, the left ventricular outflow tract (LVOT) diameter was measured in the parasternal long axis during mid-systole. A round shape of the outflow tract was assumed. Then, the LVOT volume time integral (VTI) was measured during systole with both pacing modes. The extent of mitral regurgitation was visually assessed with each pacing mode. In addition, the systolic and diastolic blood pressure were taken at the earliest one minute after changing the pacing mode using an appropriately sized blood pressure cuff. All device parameters were restored to original settings at the end of the examination.2.4.U test or Kruskal–Wallis test in the case of more than two groups. A χ2 test was used for discrete data. Linear regression models were fitted to assess the impact of echo parameters on the change of left ventricular stroke volume. Clinically significant effect modifiers were accounted for by applying a multivariate regression model. As this was a hypothesis-generating study, no adjustment for multiple testing was done. Lower p-values indicate a stronger trend of association. All calculations were performed with the software package Intercooled STATA .Continuous data are described as median, interquartile range (from the 25th to the 75th percentile). Discrete data are given as counts and percentages. Continuous variables were compared between groups using a two-sample Mann–Whitney 3.3.1.Between January 2019 and February 2020, we recruited 40 patients who met the predefined inclusion and exclusion criteria. The primary indication for device therapy was a complete AV-block in 31 patients (77.5%), a second-degree AV-block in 6 patients (15.0%), and a sick sinus syndrome in three patients (7.5%). Study participants received their first device a median of 5.3 years ago . RV leads were implanted at a high/mid septal position in 27 (67.5%), at an inferior septal location in one (2.5%), apically in 11 (27.5%), and in the RVOT in one (2.5%) subject. All eligible patients underwent and completed the study and were in sinus rhythm on the day of the echo examination. Two subjects reported palpitations during pacing in the VVI mode. No other adverse events or severe adverse advents occurred during the study. Baseline heart rates ranged between 41 and 92 beats per minute. For further details, see 3.2.p-value for difference <0.001). In all subjects, the stroke volume was higher with DDD mode than VVI mode stimulation. The median increase with AV-synchronous DDD pacing was 12.8 ml /71 (64–87), DDD: 144 (132–158)/76 (66–84), p-values for systolic and diastolic values were 0.042 and 0.163, respectively].The median heart rate at the time of the echo examination was 67 beats per minute. The median programmed optimized AV-delay was 98 ms . All echo examinations were performed by a single investigator (HB). Image quality was judged to be good in 11 (28%), fair in 19 (48%), and poor in 10 (25%) subjects. All echo parameters could be assessed, except for tricuspid regurgitation velocity in three subjects and pulmonary vein flow signals in one study participant see . Accordi3.3.p = 0.187) or the RV lead localization (p = 0.412) were not associated with the relative stroke volume increase with AV-synchronous DDD pacing.Applying linear regression models, no firm associations could be detected between primary and secondary endpoint echo parameters and the extent of relative stroke volume increase with AV-synchronous DDD pacing compared with VVI mode see . When lo3.4.p = 0.055), have lower systolic and diastolic blood pressure at baseline , and take spironolactone , whereas no difference was observed for other baseline parameters. A-wave and S-wave velocities, both primary endpoint echo parameters used to assess diastolic LV function, were lower in the AMI group, whereas no differences were found for the other echo parameters. The A-wave velocity was median 77.4 cm/s (IQR: 49.0–90.2) in the AMI group and 96.5 cm/s (IQR: 77.6–109.0) in the group without AMI (p = 0.056). S-wave velocities were 45.8 cm/s (IQR: 40.4–54.1) and 60.4 cm/s (IQR: 52.9–68.2), respectively (p = 0.036). Although average blood pressure values were lower in the AMI group than in patients without previous myocardial infarction, there was a trend toward a steeper increase with DDD pacing - as opposed to VVI pacing. The rise in diastolic blood pressure with DDD pacing was markedly more pronounced in the AMI group .Because of the association between AMI status and stroke volume increase, we further examined differences in baseline characteristics and echocardiographic data as a function of AMI status see . AMI was4.4.1.In our cohort of patients in sinus rhythm, each subject benefited from DDD pacing in terms of stroke volume increase (median: 12.8 ml/16.9%). We also observed a higher blood pressure and a trend towards less severe mitral regurgitation with AV-synchronous DDD pacing. None of the 26 single echo parameters studied could adequately predict the magnitude of stroke volume increase. However, patients with a history of AMI were found to benefit less compared with the other study participants. The AMI group comprised six individuals, four of whom were diabetics. AMI patients had on average lower baseline blood pressure values. In addition, the A- and S-wave velocities were reduced in patients after AMI compared with the rest of the study cohort.4.2.The wide range of stroke volume increase with AV-synchronous DDD pacing compared with AV-asynchronous VVI pacing in our study (increase of 0.1%–58.9%) was also observed in a trial by Masuyama et al. that investigated the same study question in 1986 (increase of 3%–73%) . The autAs optimally timed atrial contraction may increase the cardiac output by up to 30% , we opti4.3.As expected from a physiological point of view, the increase in stroke volume with AV-synchronous pacing tended to increase blood pressure. The rise in diastolic blood pressure with DDD pacing was especially pronounced in the AMI group. We hypothesize that this effect was caused due to higher arterial stiffness in this group (more diabetics and probably a higher atherosclerotic burden after AMI), even with relatively small rises in stroke volume. Reducing mitral regurgitation with AV-synchronous pacing is a well-known phenomenon observed as a trend in our data . However4.4.This study was a single-center study with all the limitations inherent in such. Because of strict inclusion and exclusion criteria and the complex echocardiographic examination protocol, only 40 participants could be included, which limited the statistical power. The volume status may have been a confounding factor that was not assessed during the echocardiographic examination. In addition, the number of patients with heart failure with reduced ejection fraction  was low . Hence, our findings must be interpreted with caution in this subgroup. As this was a hypothesis-generating study, larger multi-center trials with larger sample sizes will be necessary to corroborate our findings.5.In our cohort of patients in sinus rhythm, each subject benefited from AV-synchronous DDD pacing in terms of stroke volume increase. No single echo parameter under investigation could sufficiently predict the amount of stroke volume response. However, we could show that the beneficial effect, while still present, was attenuated after a prior acute myocardial infarction. In patients after an AMI, A- and S-wave velocities were found to be reduced. These results may form the basis for further studies to determine which patients are best suited for a leadless pacemaker in the presence of complete AV block.


To investigate the difference of right ventricular (RV) structural and functional alteration in patients with diabetes mellitus (DM) with preserved left ventricular ejection fraction (LVEF), and the ventricular interdependence in these patients, using cardiac MR (CMR) feature tracking.From December 2016 to February 2022, 148 clinically diagnosed patients with DM who underwent cardiac MR (CMR) in our hospital were consecutively recruited. Fifty-four healthy individuals were included as normal controls. Biventricular strains, including left/right ventricular global longitudinal strain (LV-/RVGLS), left/right ventricular global circumferential strain (LV-/RVGCS), left/right ventricular global radial strain (LV-/RVGRS) were evaluated, and compared between patients with DM and healthy controls. Multiple linear regression and mediation analyses were used to evaluate DM's direct and indirect effects on RV strains.No differences were found in age , sex , and body surface area (BSA)  between DM and normal controls. Patients with DM had decreased RVGLS , RVGCS , and no decrease was found in RVGRS  in patients with DM compared with normal controls. The difference in RVGLS between normal controls and patients with DM was totally mediated by LVGLS . The difference in RVGCS between normal controls and DM was partly mediated by the LVGLS  and LVGCS .In the patients with DM and preserved LVEF, the difference in RVGLS between DM and normal controls was totally mediated by LVGLS. Although there were partly mediating effects of LVGLS and LVGCS, the decrease in RVGCS might be directly affected by the DM. Cardiovascular disease is one of the most important diabetes-related complications –3. RubleDue to the high temporal and soft tissue resolution, CMR imaging is considered the gold standard for assessing myocardial structure and function . Novel CThe Institutional Review Board approved this study, and informed consent was waived due to the retrospective nature of this investigation. From December 2016 to February 2022, clinically diagnosed patients with DM who underwent cardiac MR in our hospital were consecutively recruited. The inclusion criteria were:1) DM diagnosed according to the guidelines of the American Diabetes Association  or patiePatient's demographic characteristics, clinical history, cardiovascular risk factors, and laboratory test results were recorded through Hospital Information System and Laboratory Information Management System.◦; field of view, 250 mm × 300 mm; slice thickness, 8 mm; and the number of frames, 25 per cardiac cycle. The parameters for the MAGNETOM Skyra scanner were: temporal resolution, 39.34 ms; repetition time/ echo time 2.8/1.2 ms; flip angle, 38◦; slice thickness, 8 mm; the field of view, 360 mm × 300 mm; matrix size, 256 × 166; and the number of frames, 25 per cardiac cycle.Cardiac MR scanning was performed using a whole-body 3.0 T Siemens MAGNETOM Trio Tim system or a MAGNETOM Skyra scanner . The balanced steady-state free precession cine images were obtained in standard short- and long-axis views at end-expiratory breath-hold. The parameters for the Siemens MAGNETOM Trio Tim system were: temporal resolution,40.35 ms; repetition time/echo time, 3.4/1.3 ms; matrix, 208 × 139; flip angle, 50All the CMR images were independently analyzed by two radiologists with more than three years of experience in CMR diagnosis using commercial software . To calculate bi-ventricular functional parameters, including RV-/LV end-systolic volume (RV/LV ESV), RV/LV end-diastolic volume (RV/LV EDV), myocardial mass, and RV/LV ejection fraction (RV/LVEF), ventricular epi- and endocardial borders were traced in contiguous short-axis images on end-systole and end-diastole. RV/LV EDV, RV/LV ESV, and myocardial mass were standardized by body surface area (BSA). The RV/LV remodeling index (RV/LVRI) were calculated as the myocardial mass divided by the EDV. To analyze the biventricular feature tracking parameters, additional left ventricular four- and two-chamber longitudinal views and right ventricular four-chamber longitudinal views were tracked with the end-diastole set as the reference point. 3D LV strain parameters , LV global radial strain (LVGRS), and LV global circumferential strain (LVGCS)) and 2D RV strain parameters , RV global radial strain (RVGRS), and RV global circumferential strain (RVGCS)) were automatically generated after these contours tracing performed Fig. .Fig. 1IlTo determine intra- and inter-observer variability of biventricular CMR-FT parameters, 40 random subjects were measured twice by a radiologist at a 2-week interval. Another investigator reanalyzed the measurement results of the software (cvi42). The twice measurement results of the first investigators were used to assess intra-observer variability. The measurement results of the two investigators were used to assess inter-observer variability.2 test or Fisher’s exact test. Relationships between RV strain and LV geometric parameters and strains  were estimated with Pearson’s or Spearman’s correlation coefficient analysis, as appropriate.Continuous variables were expressed as mean ± standard deviation (SD) or median and interquartile range. The difference between normal controls and patients with DM was tested with the Mann–Whitney U test or independent t-test. Categorical variables were expressed as frequency and percentage, and differences between groups were compared using the χMultivariate linear regression models adjusting for statistically significant parameters in univariate analysis (p < 0.05) and traditional clinical risk factors  were constructed to determine the independent effects of DM on the biventricular strains. Multicollinearity was assessed by the variance inflation factor (VIF > 10). Mediation analyses with bootstrap method were performed to assess whether ventricular interdependence statistically mediated the RV strain difference between diabetes and normal controls . LV straThe final analysis included 148 patients with DM and preserved LVEF and 54 normal controls. The mean age of patients with DM was 56.98 ± 10.98 years, and 91 (61.5%) had hypertension. No differences were found in age , sex , and BSA  between DM and normal controls. The demographic and clinical characteristics of the research subjects are summarized in Table Table The comparison of biventricular strain between the DM and normal controls is shown in Fig. RVGLS were significantly correlated with LVEF , LVEDVI , LVESVI , LVRI , LVMI , LVGLS , LVGCS , and LVGRS . RVGCS were significantly correlated with LVEF , LVEDVI , LVESVI , LVMI , LVGLS , LVGCS , and LVGRS . RVGRS were significantly correlated with LVEF , LVEDVI , LVESVI , LVGCS , LVGLS , and LVGRS . No significant correlation was found between RVGRS and LVMI  or LVRI  , DM was the independent impactor of LVGLS , p = 0.008), LVGCS , p = 0.009), RVGLS , p = 0.036), RVGCS , < 0.001), but have no impact on LVRI , p = 0.328), LVMI , p = 0.635). (Fig. .196, p =Direct and indirect effects of DM on RV strains with mediators LVGLS and LVGCS are displayed in Table Intra- and inter-observer variabilities of biventricular strain are shown in Table The present study investigated the RV structure and function difference between DM individuals with preserved LVEF and normal controls using CMR tissue-tracking techniques. Notwithstanding, ventricular interdependence via the septum cannot be ignored in the study of right ventricular dysfunction. We further explored the differences in RV function between DM and normal populations with LV strain as mediators. Our data revealed that RVGLS, RVGCS, LVGLS, and LVGCS were decreased in patients with DM compared with normal controls, and DM was an independent influence on the aforementioned biventricular strain. However, the difference in RVGLS between DM and normal controls was totally mediated by LVGLS. LVGLS and LVGCS partially mediated the difference in RVGCS between DM and normal controls.Cardiovascular disease is a common complication in patients with diabetes , 21. A lDiabetes is a systemic disease, and it is reasonable to believe that the right ventricle suffers a parallel injury. As a convenient imaging modality, most of the findings of structural and functional alterations in the RV are based on the results of ultrasound studies. The narrow acoustic window, dependence on operator interpretation, and tracking errors due to the low signal-to-noise ratio limit the use of 2D-STE. The thinner wall of the RV increases the difficulty of assessment accurately and reproducibility of 2D-STE. Longitudinal strain based on 2D speckle tracking echocardiography is promoted as an approximate of RV myocardial work . SeveralVentricular interdependence via the septum and limited pericardial flexibility is another possible mechanism for RV dysfunction in DC. It is theorized that LV contraction might be the primary source for RV-developed pressure, and about 20–40% of RV systolic pressure resulted from LV contraction . The sepTaken together, left ventricular strain impairment in DM is associated with RV function is well known. Whether the impact of DM on RV strains decrease is mediated by LV strains alteration remains uncertain. RV free-wall GLS decrease was totally mediated by LVGLS, whereas RVGCS impairment was partially mediated by LV function in diabetic patients with preserved LVEF. Our results were inconsistent with the study of Pauline et al. . A possiDespite the meaningful results, several limitations of the current study cannot be ignored. Firstly, it was a single-center, retrospective study, and there might be potential selection bias. Secondly, we included diabetic patients with preserved LVEF, and the generalizability of our findings to other populations can be questioned, and whether biventricular function maintains the same interactions in DM with heart failure is worth to be further explored. Thirdly, the characteristics of retrospective studies limited our ability to consider the duration of diabetes diagnosis, it is crucial for future studies to investigate whether this variable has an impact on the changes in biventricular structure and function. Finally, the clinical outcomes, including heart failure, other cardiovascular complications, or cardiovascular death, were not available in the present study. There are available data elucidating the prognostic value of right ventricular strain , 39.RVGLS and RVGCS decreased in patients with DM and preserved LVEF. Abnormal diabetic metabolism could mediate reduced RVGLS mainly by impairing LVGLS in patients with preserved LVEF. Despite the partly mediating effect of LVGLS and LVGCS, the difference in RVGCS might be directly affected by the DM.


Kidney transplantation (KTX) markedly improves prognosis in pediatric patients with end-stage kidney failure. Still, these patients have an increased risk of developing cardiovascular disease due to multiple risk factors. Three-dimensional (3D) echocardiography allows detailed assessment of the heart and may unveil distinct functional and morphological changes in this patient population that would be undetectable by conventional methods. Accordingly, our aim was to examine left- (LV) and right ventricular (RV) morphology and mechanics in pediatric KTX patients using 3D echocardiography.n = 74) with median age 20 (14–26) years at study enrollment , were compared to 74 age and gender-matched controls. Detailed patient history was obtained. After conventional echocardiographic protocol, 3D loops were acquired and measured using commercially available software and the ReVISION Method. We measured LV and RV end-diastolic volumes indexed to body surface area (EDVi), ejection fraction (EF), and 3D LV and RV global longitudinal (GLS) and circumferential strains (GCS).Pediatric KTX recipients  and RVEDVi  were significantly higher in KTX patients. LVEF was comparable between the two groups , however, LVGLS was significantly lower , while LVGCS did not differ . RVEF  and RVGLS  were significantly lower, however, RVGCS was comparable between the two groups . In patients requiring dialysis prior to KTX  RVGCS showed correlation with the length of dialysis .Both LVEDVi (67 ± 17 vs. 61 ± 9 ml/mPediatric KTX patients demonstrate changes in both LV and RV morphology and mechanics. Moreover, the length of dialysis correlated with the contraction pattern of the right ventricle. Survival statistics among pediatric transplant recipients have had a significant improvement in recent decades due to the advancements in surgical care, the progress in post-KTX immunosuppressive management and infection control, and the improvement in cardiovascular care , 2.Following infections as the most frequent etiology, cardiovascular disease (CVD) is the second most common cause of death for pediatric ESKD patients . Albeit Hence, to prevent later cardiovascular events, the early detection of cardiovascular dysfunction is essential . Often mNovel imaging techniques, such as left ventricular (LV) speckle-tracking echocardiography-derived global longitudinal (GLS) and circumferential strain (GCS) have the ability to detect subclinical functional deterioration, even when conventional functional parameters, such as ejection fraction (EF), are still preserved , 12. SpeThree-dimensional (3D) echocardiography allows an even more detailed assessment of the heart and may unveil even subtle functional and morphological changes of the chambers. This technique provides a more precise quantification of ventricular volumes and EF while being highly reproducible and shows good agreement with the gold-standard cardiac magnetic resonance imaging-derived values . MoreoveAccordingly, our aim was to examine LV- and RV morphology and mechanics in childhood kidney transplantation patients using 3D echocardiography.2.2.1.Initially, 86 KTX patients transplanted in childhood were enrolled between December 2016 and October 2018 in this cross-sectional study. The post-transplant care of the patients is performed by the 1st Department of Pediatrics of Semmelweis University, prospectively referring them to the Heart and Vascular Center of Semmelweis University for an echocardiographic examination. During this visit blood samples were also taken and detailed medical history and demographic data were obtained. We reviewed the etiology of the KTX patients’ primary kidney disease, their history of dialysis, graft source and medication from electronic medical records. Glomerular filtration rate (eGFR) was calculated according to the Schwartz formula or the CKiD U25 formula when analysing patients up to 25 years of age.n = 9) and an established diagnosis of significant cardiac disease . The final study population consisted of 74 KTX patients  transplanted in childhood (age at KTX: 10 ± 4 years). An age- and gender-matched healthy population served as controls (CTR) .Inclusion criteria consisted of having a functioning allograft , and no history of cardiac disease. Exclusion criteria were poor echocardiography image quality  or a Phillips Epiq 7G  ultrasound system. A standard acquisition protocol consisting of loops from parasternal, apical, and subxiphoid views was used according to current guidelines . LV wall2.3.Beyond the routine echocardiographic protocol, ECG-gated full-volume 3D data sets reconstructed from four or six cardiac cycles optimized for the right or left ventricle were obtained for offline analysis. Image quality was verified at the bedside to avoid “stitching” and “dropout” artefacts of the 3D data. Further measurements were performed on a separate workstation using dedicated software . The software detects the endocardial surface of the left- and right ventricles, and following manual correction, it traces its motion throughout the cardiac cycle. We determined the end-diastolic volume index (EDVi), end-systolic volume index (ESVi), and stroke volume index (SVi) normalized to BSA, and to characterize global LV and RV functions, EFs were also assessed. By tracing the end-diastolic epicardial contour we measured LV mass index (LVMi) normalized to BSA. The dedicated 3D LV analysis software also enables 3D speckle-tracking analysis, therefore, LVGLS and LVGCS were also calculated. The software automatically measures LV twist and torsion using basal and apical short axis deformation, and systolic dyssynchrony index (SDI) as the standard deviation of the time takes to reach minimum systolic volume for each LV segment.2.4.Our custom 3D RV deformation analysis was previously described in detail , 18. AllThe analysis begins with the reorientation of the 3D RV mesh. A local coordinate system is defined for each mesh series, where the basis vectors correspond to the longitudinal, radial and anteroposterior directions.Second, the wall motions of the 3D RV model are decomposed in a vertex-based manner . This decomposition step transforms the original mesh series into several series of meshes, each corresponding to a decomposition type .In the final step, by the decomposition of the model's motion along the three anatomically relevant axes, we can measure the volume change of the right ventricle attributable to the specific direction separately. To assess GCS, we create 15 equidistant circumferential contours on the first mesh of each series and calculate their positions at later time instants. For GLS, 45 longitudes are generated by connecting the apex, the predefined vertices of the base, and vertices in equidistant latitude to the latter. The pulmonary and tricuspid annular planes are excluded from this part of the analysis. Our software calculates 3D RV GCS and GLS by averaging the length changes of each circumferential contour or longitude referenced to their end-diastolic length. Global area strain (GAS) is also calculated by the relative change of the endocardial surface between end-diastole and end-systole. The software also allows the measurement of segmental strain values, therefore, longitudinal, circumferential and area strains of the septum and the free wall were also calculated.2.5.t-test or Mann–Whitney U test for continuous variables and the chi-square or Fisher's exact test for categorical variables according to normality. Correlations between variables were evaluated by Pearson's rank correlation test or non-parametric Spearman correlation. p-values < 0.05 were considered to be statistically significant.We performed statistical analysis using STATISTICA version 13.4 . The normal distribution of our variables was verified using the Shapiro–Wilk test. Data are presented as mean ± standard deviation (SD), median (interquartile ranges), or percentage, as appropriate. Groups were compared with the unpaired Student's Intra- and interobserver variability of the most relevant parameters were also assessed. The operator of the first measurements (BL) and a second expert reader (ZL), both blinded to the study groups, repeated the measurements in a randomly chosen subset of 5–5 subjects from each group. We calculated Lin's concordance correlation coefficient and coefficient of variation.3.3.1.The baseline statistics of the KTX and CTR groups are presented in There was no significant difference regarding the age, gender, weight, BSA and heart rate of the two groups. However, the controls were significantly taller than the transplant patients. Furthermore, the KTX group presented with significantly higher systolic blood pressure, while the diastolic blood pressure did not differ.n = 64) received dialysis prior to transplant, 41% of whom (n = 26) was treated with hemodialysis. Preemptive transplant occurred in 14% (n = 10) of the patients. Their mean age at KTX was 10 ± 4 years, and 112 ± 82 months passed since the transplantation.In the KTX group, 86% (n = 14), polycystic kidney disease (n = 9), obstructive uropathy (n = 4), focal segmental glomerulosclerosis (n = 14), nephronophthisis (n = 8), chronic glomerulonephritis (n = 7), pyelo- or interstitial nephritis (n = 5), congenital disorders (n = 6), miscellaneous (n = 5) and unknown etiology (n = 2).The underlying primary kidney disease were as follows: kidney agenesis or dysplasia  did not differ between the transplant and control groups, while LV end-systolic diameter (LVIDs) was significantly lower in the transplant patients. However, both the interventricular septal thickness (IVSd) and the posterior wall thickness (PWd) were shown to be higher in the KTX group and the RWT was also higher in them.Both the transmitral E wave and A waves were significantly increased in the KTX patients, while the E/A ratio did not differ, and neither did the DT. The mitral lateral s’ and e’ were significantly lower in the transplanted group, on the other hand, the mitral lateral a’ did not show any difference. Accordingly, E/e’ was significantly higher in the KTX group.Neither the RV basal diameter, the TAPSE nor the PASP showed any difference between the transplanted and the control patients.Regarding atrial dimensions, LAVi and RAVi did not differ between the two groups.3.3.The 3D and LV speckle tracking data are shown in Both the LVEDVi and LVESVi were significantly increased in the transplant group . HoweverLVGLS was decreased in the transplant patients, while the LVGCS did not differ , 3. SDI RVEDVi and the RVESVi were both increased in the transplant group , althoug3.4.The data of the global and segmental 3D RV deformation measures are presented in 3D RVGLS was significantly reduced in the KTX patients, while the RVGCS did not differ between the groups , 3. The The septal longitudinal strain (SLS) did not show any difference, however, the septal circumferential (SCS) and area (SAS) strains were significantly reduced in the KTX group. The free wall circumferential (FWCS), longitudinal (FWLS) and area strains (FWAS) did not differ between the groups.3.5.As shown in A handful of meaningful laboratory parameters also showed correlation with the 3D echocardiographic parameters. These findings are presented in 3.6.The intra- and interreader variability analysis of our key 3D parameters demonstrated good agreement in the assessment of these measures .4.KTX is the treatment of choice in pediatric patients with ESKD, since it carries the best long-term prognosis in this population . NeverthOur findings that the transplanted children grew up to be shorter compared to their age- and gender-matched peers, are in unison with evidence that CKD in childhood impairs growth , 25, andIn accordance with previous studies, a large proportion of our KTX patients had treated, albeit existing hypertension . Its cliIn CKD and after KTX, LV hypertrophy is a common finding with conventional echocardiographic measures as well, and shows association with poor cardiovascular outcomes . AccordiLV hypertrophy is also commonly associated with diastolic dysfunction, which is also demonstrated in the KTX group by altered transmitral velocities and Tissue Doppler values –39.While conventional, linear measures of LV and RV dimensions were comparable between the two study groups, 3D LV and RV volumes were significantly higher in the KTX group, suggesting dilation of the ventricles. The steroid-receiving KTX subgroup also presented with increased LV and RV dimensions, suggesting the contribution of immunosuppressive therapy to the observed findings . In the Regarding RV function, TAPSE did not differ between KTX and controls, however, 3D RVEF, RVGLS and RVGAS were impaired along with comparable 3D RVGCS. Previous 2D speckle-tracking echocardiography studies enrolling adult patients demonstrated improvement of RV longitudinal deformation following KTX . AccordiAssessment of regional RV function may unveil further aspects of ventricular mechanics: in our study, transplant recipients had impaired 3D RV SCS and SAS, suggesting a more pronounced deterioration of septal movement components. Along with the impaired GLS in both ventricles, the septal predominance of this functional impairment indicate an origin of direct myocyte damage, rather than the effect of altered hemodynamic measures affecting the myocardium with the highest working load, i.e., the subendocardium and the interventricular septum. Interestingly, LV measures did not correlate with the length of pre-transplant dialysis, while RVGCS and regional strain measures showed a direct relationship with it—longer dialysis needs correlated with more impaired deformation. In a previous study enrolling adult ESKD patients, RVEF showed a relatively strong correlation with the duration of dialysis . Based oESKD is complicated by mineral bone disease that is characterized by abnormalities in calcium and phosphorus metabolism, as well as dysregulation of the FGF-23 and PTH hormonal axis , 50. As We found that magnesium levels are also directly correlated with a number of 3D biventricular parameters. Magnesium plays a key role in modulating neuronal excitation, intracardiac conduction, and myocardial contraction by various ion transporters, including potassium and calcium channels. It also participates in regulating vascular tone, atherogenesis and thrombosis, vascular calcification, and proliferation and migration of endothelial and vascular smooth muscle cells. Accordingly, magnesium has a considerable influence on the pathogenesis of CVD. As the kidney is the major regulator of magnesium homeostasis, kidney disorders can potentially lead to both magnesium depletion and overload, thus increasing the risk of CVD . The ser4.1.Our study has a number of limitations that should be acknowledged for adequate interpretation. Firstly, this is a single-centre, retrospective study with a limited number of cases—further multicentre expansion of the population would strengthen our findings. Secondly, the cross-sectional study design did not allow the assessment of the prognostic power of the 3D parameters. The ReVISION Method is currently not a commercially available software, however, it was previously validated against gold-standard cardiac magnetic resonance imaging. Despite discussing the possible role of FGF-23 in the ventricular remodeling, we did not measure its serum levels in our population. Lastly, cystatin C was not measured in our cohort, therefore, we calculated GFR using the form of CKiD U25 formula which does not implement this laboratory measure.4.2.Using three-dimensional speckle tracking echocardiography, we found distinct morphological and functional changes in both ventricles in pediatric kidney transplant patients. With the ReVISION Method we also measured the changes of right ventricular motion components, which were previously undescribed in this population. However, the pathophysiological background and clinical relevance of our RV strain findings are still unclear and require further research. Nevertheless, our data support the use of a comprehensive echocardiographic protocol applying advanced techniques in the care of kidney transplant patients.


Erdheim–Chester disease (ECD) is a rare multisystem histiocytosis, whose cardiovascular involvement has not been systematically characterized so far. We aimed to systematically  describe the features of cardiovascular involvement in a large cohort of ECD patients and to evaluate its impact on myocardial fibrosis extension and cardiac function.Among 54 patients with biopsy-proven ECD, 29 patients  underwent 1.5-T CMR using a standardized protocol for qualitative and quantitative assessment of disease localization, evaluation of atrial and ventricular function, and assessment of non-dense and dense myocardial fibrosis.The right atrioventricular (AV) groove was the most commonly affected cardiac site (76%) followed by the right atrial walls (63%), thoracic aorta (59%), and superior vena cava (38%). Right AV groove involvement, encasing the right ventricular artery, was associated with non-dense myocardial fibrosis in the infero-septal (20/26 patients) and the inferior (14/26 patients) mid-basal left ventricular (LV) wall. In two patients with right AV groove localization, LGE revealed myocardial infarction in the same myocardial segments. Three out of five patients with left AV groove involvement had non-dense LGE on the lateral LV mid-basal wall. Bulky right atrial pseudomass was associated with atrial dysfunction and superior and inferior vena cava stenosis.In ECD patients, AV groove localization is associated with LV wall fibrosis in the downstream coronary territories, suggesting hemodynamic alterations due to coronary encasement. Conversely, atrial pseudomass ECD localizations impact on atrial contractility causing atrial dysfunction and are associated with atrio-caval junction stenosis. Erdheim–Chester disease (ECD) is a rare systemic non-Langerhans cells histiocytosis of unknown etiology characterized by multiorgan xanthomatous infiltration by CD68 + , CD1a − foamy histiocytes . Its clinical presentation is heterogeneous, ranging from isolated bone involvement to multisystemic and sometimes life-threatening phenotypes . Bone pain due to skeletal infiltration is the most common clinical manifestation, occurring in approximately 95% of patients. Involvement of central nervous system (CNS) and of cardiovascular system are independent predictors of fatal outcome , 4. SpecCardiovascular involvement in ECD is poorly characterized for scarcity of data from systematic screenings with advanced imaging modalities. Available data are mainly derived from case reports , 6 or smCardiac magnetic resonance (CMR) is the imaging modality of choice for morphofunctional assessment of the cardiac chambers and for the identification of ECD involvement for its superior soft tissue resolution –15.The aim of the present study is to qualitatively and quantitatively characterize ECD cardiac involvement, and to investigate the impact of site and extension of ECD cardiac involvement on cardiac chamber volumes, function, and structural remodeling.This observational retrospective study includes 54 consecutive patients with biopsy-proven ECD referred to our Institution  between June 2009 and December 2021.In previous studies were included data on 25  and 1 ofIn the present study we included all patients with clinical suspicion of cardiac involvement at multimodality evaluation  who underwent CMR for disease confirmation and characterization before therapy start Fig. . Only 29CMR was performed with 1.5-T system  using a 32-element cardiac phased-array coil. T2-weighted short-tau inversion recovery (T2-STIR) sequences were acquired using a body coil. All images were acquired during breath-holding periods. CMR protocol included: multiplanar  2-D balanced turbo field echo (BTFE) images and axial and sagittal T2-STIR and proton density (PD) sequences covering the entire mediastinum; steady-state free precession (SSFP) cine, T2-STIR, black-blood PD, PD-fat-saturated (PD-fat-sat) sequences and 10-min post-contrast  three dimension inversion recovery T1w (3D-IR-T1w) images acquired in the short-axis, 2-chamber and 4-chamber long-axis cardiac views.In a subgroup of ten patients who underwent CMR after 2016 T1 mapping acquisition was performed. Both native and post-contrast T1 mapping were acquired in the same three short-axis planes  and in a single four chambers long-axis view, using a modified Look-Locker inversion recovery sequence with 5(3)3 and 4(1)3(1)2 sampling scheme, respectively.All CMRs were analyzed by a cardiac radiologist with 10 years of experience in cardiac imaging and revised by a senior cardiac radiologist with 17 years of experience using a dedicated cardiac analysis software .Left and right ventricle end-diastolic and end-systolic volumes , ejection fractions (EF) and myocardial mass were extracted from automatic segmentation of endocardial and epicardial contours in the end-diastolic and end-systolic short-axis cine-SSFP images, and manually corrected when necessary.Atrial ESV, EDV and EF were assessed by biplane area-length method after semiautomatic tracing of the endocardial contours in 2-chambers and 4-chambers long-axis views.2 placed in a chest wall muscle.Myocardial edema was assessed on T2-STIR images as areas characterized by relative hyperintensity at visual assessment and by the measurement of T2-ratio (positive ≥ 1.9). The SI of myocardium resulted from semiautomatic contouring of endocardial and epicardial left ventricular borders, while the SI of the reference skeletal muscle resulted from a manual ROI of at least 10 mmMyocardial fibrosis was assessed as Late Gadolinium enhancement (LGE) on 3D-IR-T1w images and classified as non-dense scar  and dense scar . Both non-dense and dense scar were quantified as percentage of LV wall mass. Additionally, LGE was classified according to the transmural pattern  and the segmental (AHA 16 segments model) involvement.Native T1 mapping and ECV values were obtained after outlining endocardial and epicardial edges on the short-axis slices , with an automatic offset of 10% from endocardial and epicardial borders to reduce partial volume effect. Local reference value were for native T1 ≤ 1045 ms, and for ECV < 27%.Site of cardiovascular involvement was firstly visually assessed on axial PD, BTFE and LGE images, and then quantified on the sequence showing the best image quality, by tracing contours slice-per-slice in order to cover the entire mass and compute the mass volume. Additionally, maximum mass thickness was manually measured on axial images.Pericardial effusion and pericardial thickening were visually identified and manually measured at the thickest point. Similarly, aortic wall infiltration was visually identified and manually measured at the thickest point.Vascular stenosis or dilatation at the level of ECD infiltration were assessed as vascular diameter change in comparison to a reference vascular diameter measured at a level without ECD infiltration.p ≤ 0.05 was considered statistically significant.Data analyses were performed using IBM SPSS for macOS version 28.0.1.0 . Data are reported as medians and interquartile ranges [IQRs] or frequencies and relative percentages. Mann–Whitney U test for unpaired samples was used to compare continuous variables. A value of Patients were mainly men (M:F = 23:6), with a median age of 61  years. All patients had skeletal involvement (Table Three out of 29 patients had chronic kidney failure and CMR was performed without contrast media. Cardiovascular involvement was found in 22 of 29 patients (76%). Detailed information about cardiovascular localization of ECD at CMR is reported in Table ECD cardiovascular localization at CMR was characterized by intermediate signal in PD images, mild hyperintensity in PD-fat-sat, and high signal intensity in T2-STIR and LGE images and were present in 22/29 patients (76%).Right AV groove localization  was present in all patients with cardiovascular involvement. Right atrial wall infiltration was found in 14 of 29 patients , and had always a pseudotumor appearance. Five patients (17%) had also left AV groove infiltration .Pericardial late enhancement was present in 16 patients  and was associated with pericardial effusion in 14 of them (median thickness: 10 mm [IQR 7–20] mm). In eight patients it had a circumferential distribution. Thoracic aorta was the most affected mediastinal vessel , with maximum wall thickness of 20 mm . In nine patients (31%), its involvement had the appearance of “coated aorta” . No patip < 0.001).The overall volume of ECD cardiovascular localizations was 32  mL and it correlated with the number of anatomical structures involved , as well as the end-diastolic LV wall mass . Myocardial T2-ratio was slightly increased in patients with ECD cardiac involvement compared to those without cardiac involvement , p < 0.001). This finding indicates a slight diffuse myocardial edema in the former group. All participants except one  had non-dense LGE (between + 3 and + 5 SD), with a median non-dense scar burden of 5.8 %. Non-dense fibrosis had a transmural pattern in most cases , mostly involving the infero-septal mid-basal wall , the inferior wall , and the lateral mid-basal wall  . However, right atrial EDV was significantly higher , and atrial ejection fraction was significantly lower . Of note, in the majority of patients  with a right atrial pseudomass volume > 20 mL a depressed right atrial EF (< 46%) was depicted, considering a normal range of 52.9 ± 6.7%  mL vs 5.95 [4.5–7] mL, (p = 0.04) .ECD is a rare multisystem histiocytosis associated with a poor prognosis, especially when the cardiovascular system is involved . CardiovIn agreement with previous studies , 10, 11,The most important finding of our study is that, regardless of the amount of AV pseudomasses, coronary artery encasement, due to ECD localization, seems responsible for various degrees of myocardial fibrosis. This finding substantially differs from what had been previously reported in the English literature where absence of cardiac scars or presence of only patchy LGE with non-coronary distribution was associated with cardiac ECD involvement , 11. Thepostmortem case report by Vaideeswar et al. [The localization and the transmural distribution of myocardial non-dense LGE we found in our population suggest ischemia as the first etiological hypothesis. Extrinsic compression or direct infiltration of coronary artery walls by histiocytes may induce vascular stenosis and increase coronary wall stiffness, thus impacting on coronary hemodynamic and promoting extracellular matrix remodeling processes in their perfusion territories. This mechanism could explain the accumulation of regional interstitial fibrosis with coronary distribution, as observed in our study population. Interestingly, a r et al.  describer et al.  who docuIt could be speculated that the ischemic mechanism is intrinsically associated with the inflammatory process underlying myocardial fibrosis in ECD patients. Indeed, ECD lesions were demonstrated to be characterized by spontaneous production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) , responsOur findings are further corroborated by mapping results, which demonstrated diffuse alteration of native T1 values and diffuse expansion of ECV, in patients with ECD-related cardiac disease, with higher values in the posterior-septal and inferior walls in those with right peri-coronary infiltration.Myocardial fibrosis is a known prognostic CMR biomarker, being associated with the development of ventricular arrhythmias, cardiac remodeling, and heart failure , 29. HowIn-line with previous studies , 7, 11 bIn our study, we observed right atrial pseudomasses in 14 (48%) patients. This finding is in-line with previous data, in which it was reported with a frequency between 31 and 69% , 30–32. Bulky right atrium pseudomasses (median mass volume: 34 mL) were associated with vena cava stenosis. In only two patients we found superior vena cava stenosis in absence of right atrium involvement. Although only few cases are reported worldwide , 34, in We observed pericardial involvement and infiltration of thoracic aorta in 28% and 59% of our patients, respectively, in-line with previous reports , 30–32. Our study has some limitations. First, the sample size is relatively small. However, ECD is a very rare condition, and all our patients were studied homogeneously with the same imaging modality. Second, data about interobserver reliability lack. Nevertheless, all measurements were taken with a quantitative and semiquantitative approach to overcome subjectivity of visual interpretation, and were obtained in consensus by two readers with different experience. Finally, mapping data are available only in a subgroup of patients. Future studies aiming at assessing the reversibility of these findings after targeted and anti-inflammatory therapies  would be


There has been an increase in the reporting of cases of left ventricular noncompaction (LVNC) cardiomyopathy in medical literature due to advances in medical imaging. Patients with LVNC may be asymptomatic or may present with arrhythmias, heart failure, thromboembolism or sudden death. LVNC is typically diagnosed by echocardiography, although there are higher-resolution cardiac imaging techniques such as cardiac magnetic resonance imaging (MRI) to make the diagnosis. The objective of the study is to report on a series of 9 cases of LVNC cardiomyopathy seen at the University College Hospital, Ibadan. Cases of LVNC seen between September 1, 2015 and July 31, 2022 in our echocardiography service  is being reported.There were a total of 6 men and 3 women. Mean age at presentation was 52.89 ± 15.02 years. The most common mode of presentation was heart failure (6 patients). Hypertension was the most common comorbidity (6 patients). Three patients had an ejection fraction of less than 40% and the mean ratio of noncompacted to compacted segment at end-systole was 2.80 ± 0.48. The most common areas of trabecular localization were the LV lateral wall and the apex. Beta blockers were highly useful in the management of the patients.LVNC cardiomyopathy is not uncommon in our environment and a high index of suspicion is often required. Left ventricular noncompaction (LVNC) cardiomyopathy belongs to the group of unclassified cardiomyopathies according to the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases . It is cThere are limited reports of this condition in Africa. The first case in sub-Saharan Africa was reported in 2006 by Ker and Van De Maewe . ReportsThe aim of the present study was to report a predetermined series of LVNC seen at our cardiology unit between September 2015 and July 2022 and to estimate the prevalence.Multiple (> 3) left ventricular trabeculae;Deep inter-trabecular recesses;Doppler colour flow within the recesses and communicating with the left ventricular cavity andDouble-layered endocardial structure with the noncompacted to compacted segment ratio of more than 2 in end-systole.This is the report of a case series collected between September 1, 2015 and July 31, 2022. The study was conducted at the Cardiology Unit of the Department of Medicine, University College Hospital, Ibadan. The study adheres to all widely accepted ethical principles guiding human research. Ethical approval was obtained as part of the Ibadan Heart Failure Registry, and all patients gave informed verbal consent before recruitment. The diagnosis of LVNC was made in the presence of the following on echocardiography .MultipleA proforma was used for the collection of their socio-demographic information, clinical details, 12-lead ECG findings and echocardiography data. All echocardiography screening was performed according to the guidelines of the American Society of Echocardiography .We obtained the left ventricular (LV) septal and posterior wall thickness as well as the LV internal dimensions in diastole and systole. LV ejection fraction was obtained using the modified Simpsons biplane method . The rigDuring the study period, 14,949 patients had echocardiography procedures carried out in our laboratory and a total of nine patients met the case definition. Of these, 6 of them were male while 3 of them were females. Their ages ranged from 25 to 73 years, with the mean age being 52.89 ± 15.02 years. The clinical and electrocardiographic details of the patients are shown in Table On echocardiography, the mean ejection fraction (EF) was 49.18 ± 17.49%, with 3 of the patients having an EF less than 40%. Up to six patients had reduced fractional shortening < 29%). The mean ratio of noncompacted to compacted segments (NC/C) at end-systole was 2.80 ± 0.48 . It helps provide better visualization of the trabeculations, especially at the apical and anterolateral regions of the ventricle . However. Most of them use echocardiography, with the most popular being the one by Jenni et al. [Several diagnostic criteria have been put forward for the diagnosis of LVNC , 21, 29.i et al.  which waThe localization of the trabeculae is important in symptomatology. In patients with LVNC, the trabeculae are most commonly found in the apex and lateral walls , 9, 30. . Beta blockers were used in 5 of the patients to control heart failure, while 3 patients each received ACE inhibitors, loop diuretics and spironolactone. Amiodarone was used for rate control in two patients, while one of them received electrical rate control by cardioversion.Treatment of patients with LVNC varies depending on the mode of presentation, comorbidities and complications developed. Heart failure is managed with ACE inhibitors, beta blockers and diuretics, rhythm abnormalities are contained depending on the type of arrhythmia . The useThe mortality rate of patients with LVNC is about 35%. The most common causes of death in these patients are sudden cardiac death causing up to half of deaths, while heart failure causes about one-third of deaths . Sudden This study is the first report of LVNC case series in Nigeria. This study highlights that the disease is not uncommon in our environment and may be underreported due to poor imaging techniques or poor index of suspicion. It is possible some cases were missed during the recruitment process due to the fact that cardiac MRI is not available in our centre. This imaging technique would have been very useful in ensuring a higher sensitivity and better characterization of the condition.LVNC is not uncommon in sub-Saharan Africa and presents in various ways, ranging from heart failure to arrhythmias and thromboembolic phenomena. It occurs across all age groups and is more common in males. Because the presentation is similar to other cardiac diseases, a high index of suspicion is required. The first-line modality for diagnosis is two-dimensional trans-thoracic echocardiography, where numerous trabeculations are seen, most commonly at the apex of the left ventricle, with a noncompacted/compacted ratio at end-systole greater than 2.0. Other findings which may be seen on echocardiography in patients with LVNC include valvular defects and wall motion abnormalities. Treatment varies, depending on the mode of presentation and the existing comorbidities Fig. .Fig. 3A