The differentiation between hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) is challenging due to similar myocardial hypertrophic phenotype. The purpose of this study is to evaluate the feasibility of cardiovascular magnetic resonance feature tracking (CMR-FT) and late gadolinium enhancement (LGE) to distinguish between HCM and HHD and the potential relationship between myocardial strain and cardiac functional parameters.One hundred and seventy subjects  underwent 3.0 T CMR, including steady-state free precession cines and LGE images. Global and segmental  analyses of myocardial radial, circumferential, longitudinal strain, and left ventricular (LV) torsion, as well as global and 16 segments of LGE were assessed. The multivariate analysis was used to predict the diagnostic ability by combining comprehensive myocardial strain parameters and LGE.P < 0.001). A similar trend was also seen in the corresponding strain rate. As for segmental strain analysis, basal radial strain (BRS), basal circumferential strain (BCS), basal longitudinal strain (BLS), mid-radial strain (MRS), and mid-circumferential strain (MCS) were higher in the HCM group than in the HHD group . The receiver operating characteristic (ROC) results showed that the area under the curve (AUC) of LGE in the mid-interventricular septum (mIVS) was the highest among global and segmental LGE analyses. On the multivariate regression analysis, a combined model of LGE (mIVS) with GRS obtained the highest AUC value, which was 0.835 with 88.89% sensitivity and 70.18% specificity, respectively. In addition, for patients with HCM, GRS, GCS, and global longitudinal strain had correlations with LV ejection fraction (LVEF), maximum interventricular septum thickness (IVST max), and left ventricular mass index (LVMi). Torsion was mildly associated with LVEF.Global radial strain (GRS), global circumferential strain (GCS), and LV torsion were significantly higher in the HCM group than in the HHD group  achieved the highest diagnostic value. Hypertrophic cardiomyopathy (HCM) is the most common genetically transmitted cardiomyopathy . HCM is Cardiovascular magnetic resonance (CMR) is the gold standard for evaluation of cardiac morphology, function, and tissue characterization. The presence of late gadolinium enhancement (LGE) represents changes in fibrosis or myocardial scarring, which can significantly predict the prognosis of severe cardiac complications . A previCardiovascular magnetic resonance feature tracking (CMR-FT) technology allows for high-resolution evaluation of myocardial deformation and the determination of myocardial strain parameters with excellent consistency and reproducibility –10. It tLeft ventricular torsion obtained from CMR-FT can be used to evaluate the ability of rotation during left ventricular motion, which plays a crucial role in pumping blood out of the heart. As for patients with dilated cardiomyopathy, amplitude of torsion was lower than that in healthy subjects and it was associated with LVEF and clinical endpoints , 14. HowThe purpose of this study is to evaluate the feasibility of CMR-FT and LGE to distinguish between HCM and HHD and to investigate the potential relationship between CMR-FT strain and cardiac functional parameters.A systematic retrospective analysis was conducted in one hundred and seventy consecutive subjects who underwent CMR from September 2020 to November 2021. All the images exhibited diagnostic quality, enabling the assessment of myocardial strain and LGE. Three cohorts were recruited: (i) 68 healthy volunteers who were free of any history of medical conditions; (ii) 57 patients with HCM, which was defined as nondilated left ventricular hypertrophy with end-diastolic wall thickness ≥ 15 mm (or ≥ 13 mm whose first-degree relatives had diagnosis of HCM) according to current established CMR diagnostic criteria  by using a three-dimensional phase-sensitive inversion recovery (PSIR) sequence; the scanning parameters were as follows: TR/TE = 6.1/3.0 ms, FOV = 300 × 300 mm2, voxel = 1.8 × 1.68 × 8.0 mm, flip angle = 25°, and 8-mm slice thickness. The acquisitions of SSFP cines and PSIR were conducted in 2-chamber, 3-chamber, and 4-chamber long-axis planes, as well as a stack of contiguous short-axis slices, which encompassed the left ventricular from the atrioventricular ring to the apex.Cardiovascular MRI was performed with a 3.0-Tesla system  using a 32-channel phased-array abdomen coil. Cine images were performed by using a steady-state free precession (SSFP) sequence with a breath-hold and ECG trigger for cardiac morphologic and functional analyses. The scanning parameters were as follows: repetition time (TR)/echo time (TE) = 2.8/1.42 ms, field of view (FOV) = 300 × 300 mmAll the CMR studies were postprocessed using a commercially available workstation . LV endocardial and epicardial borders were delineated automatically with manual calibrations throughout the cardiac cycle by a radiologist (with 3 years of experience in MRI) who was blinded to clinical information. LVEF, cardiac output (CO), end-diastolic volume (EDV), end-systolic volume (ESV), interventricular septal thickness (IVST), and cardiac chamber dimensions were measured. LV mass was calculated as the total myocardium volume multiplied by myocardial gravity (1.05 g/ml) without including papillary muscles.Cardiovascular magnetic resonance feature tracking-derived strain and strain rate were used to evaluate myocardial deformation. Quantitative parameters included radial, circumferential, and longitudinal orientation . Radial Late gadolinium enhancement quantification was obtained with mean ± 5 SDs algorithm and expressed as a volumetric proportion of the total LV myocardium. Segmental analysis on LGE was assessed according to the American Heart Association 17-segment model by setting the anterior and inferior right ventricular insertion points . To invet-test between the two groups or by ANOVA test with post-hoc Bonferroni analysis among the three groups. Nonnormally distributed continuous variables were shown as medians with interquartile range and verified by the Mann–Whitney U test or the Kruskal–Wallis H test. The Pearson's or Spearman's correlation coefficients were calculated to investigate the potential correlations between myocardial strain and functional CMR parameters. The multivariate logistic regression analysis was calculated to test the diagnostic ability of CMR parameters for distinguishing the two diseases. The area under the curves (AUCs), specificity, sensitivity, and Youden's index were analyzed by the receiver operating characteristic (ROC) curve. DeLong's test was used to compare the AUCs for the pairwise groups. All the data were calculated by SPSS version 26.0.0  or MedCalc . P < 0.05 was considered as statistically significant.Categorical variables were assessed by the Fisher's exact test or the chi-squared test and expressed as numbers with percentage. Normally, distributed continuous variables were presented as mean ± SD and compared by the Student's P = 0.014), less male (P = 0.009), had smaller body surface area (P < 0.001), and lower incidence of hypertension (P < 0.001). There was no statistical difference between the HCM and HHD group in terms of prevalence of diabetes mellitus, dyslipidemia, and smoker .The study cohort consisted of 170 participants, including 57 patients with HCM (33.5%), 45 patients with HHD (26.5%), and 68 healthy volunteers (40%). Clinical characteristics and basic CMR parameters of the HCM, HHD, and healthy group are given in P < 0.001). Those with HCM also had a lower LV end-diastolic volume index (EDVi)  and lower LV end-systolic volume index (ESVi) . As for maximum interventricular septum thickness (IVST max), there were higher values in patients with HCM when compared with patients with HHD . The LV end-diastolic diameter (EDD) of patients with HCM was 45.75 ± 7.39 mm, which was lower than that in patients with HHD . There were no significant differences regarding CO, LVMi, and right ventricular EDD between the two groups of LVH.Compared with patients with HHD, patients with HCM had a higher ejection fraction , whereas comparisons of GLS showed no obvious difference . Similar trend could also be detected in corresponding strain rate.Global radial strain (GRS) and global circumferential strain (GCS) were significantly higher in the HCM group relative to the HHD group, as shown in P < 0.05). Mid-radial strain (MRS) and mid-circumferential strain (MCS) were also higher in patients with HCM relative to patients with HHD , but mid-longitudinal strain (MLS) had no significant difference between the two groups. None of the three apical strain results showed obvious differences between the HCM and HHD cohort. Torsion in the HCM group was higher than that in the HHD group .As for segmental strain analysis, the three basal parameters  were higher in the HCM group than in the HHD group . On segmental analysis, the differences in LGE values were predominantly localized around the interventricular septum , which corresponds to the mid-segment of the anterior, anteroseptal, and inferoseptal of IVS. It was also pronounced for mIVS (P < 0.001) (Late gadolinium enhancement was assessed in 170 participants and shown in < 0.001) , but theR = 0.597, P < 0.001; GCS, R = −0.618, P < 0.001). In addition, torsion was mildly associated with LVEF  (P < 0.001). In the healthy group, GRS, GCS, and torsion were only associated with LVEF .In patients with HCM, GRS, GCS, and GLS showed correlations with LVEF, IVST max, and LVMi . Especia= 0.002) . In patiP < 0.001), GCS , and corresponding strain rate could distinguish HCM from HHD. For segmental strain parameters, the AUCs of BRS, BCS, BLS, MRS, and MCS for discriminating between HCM and HHD were 0.781, 0.776, 0.644, 0.711, and 0.697, respectively . The torsion cutoff value of > 1.40 differentiated HCM from HHD with a sensitivity of 71.11% and a specificity of 75.44%. The AUC of LGE (mIVS) was 0.735, which was the highest in the global and other segmental LGE analyses . Overall, BRS showed the highest diagnostic performance and the value of the AUC was 0.781 . On the multivariate regression analysis, the combination model of LGE (mIVS) with GRS obtained the highest AUC value, which was 0.835 with 88.89% sensitivity and 70.18% specificity, respectively (P < 0.05)  .Several important outcomes were found in evaluating patients with HCM and HHD using FT parameters and LGE data. The main findings of this study were: (1) LV GRS, GCS, and torsion were significantly higher in patients with HCM compared with patients with HHD. The differences of radial and circumferential strain mainly existed in LV basal and midsegments; (2) There was no significant difference in GLS between the two groups, but it was distinguishable in the LV basal segment (BLS); (3) The difference of %LGE can be used to distinguish between the two diseases, especially in the mIVS; and (4) In the multivariate regression model, the combination of GRS and LGE (mIVS) achieved the highest diagnostic value in differentiation between HCM and HHD diseases.Cardiovascular magnetic resonance feature tracking has been used in the assessment of HCM and HHD, respectively, due to its ability to quantify cardiac movement in different directions during the cardiac cycle , 18. ThiLongitudinal strain refers to systolic shortening of LV wall relative to its length and it was proven to be a surrogate of subendocardial fibrotic changes in the late stage of HHD disease . Based oLeft ventricular torsion provides the difference in rotation angle between the base and apex . InvestiCardiovascular magnetic resonance has the advantage of tissue characterization, which provides valuable diagnostic information. LGE identifies areas with myocyte necrosis or myocardial fibrosis in clinical practice, which has been shown to be closely associated with segmental dysfunction –32. PrevThere were several limitations in this study. First, as only a small cohort of patients was included in this study, larger studies are required to validate our findings. Second, subgroup evaluation may be a promising direction to analyze the differences among diverse phenotypes of HCM and HHD, such as the classification of patients with HCM according to LV outflow tract gradients. Third, we only analyzed systolic strain parameters, which already offered diagnostic value. Diastolic dysfunction was not considered in this study and it might offer new insights to characterize the two diseases. Fourth, a prospective study with the inclusion of genetic findings may help us to better understand the interplay between the genotype and phenotype in these cohorts. Last, the predictive value of myocardial strain for adverse cardiovascular events was not studied due to lack of follow-up.Cardiovascular magnetic resonance feature tracking-derived myocardial strain parameters could provide valuable methods for differentiating HCM from HHD. LV strain and torsion were closely related to LVEF, IVST max, and LVMi. LGE (mIVS) has shown the ability of discriminating between HCM and HHD. The combination of LV GRS and LGE (mIVS) achieved the highest diagnostic value. CMR strain analysis may contribute to improve the diagnostic accuracy and facilitate treatment guidance in hypertrophied cardiac diseases.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by KY2021-132. The patients/participants provided their written informed consent to participate in this study.SL and GW designed the study and wrote the manuscript. XW, YeL, and YZ postprocessed the images. XG, JC, and BX collected the data. ZW and YuL analyzed the data. JT and BY supervised the study. All the authors have read and approved the final version of the manuscript.This study was supported by the National Natural Science Foundation of China (Grant No. 82100529/XG) and the Fund of Key Laboratory of Myocardial Ischemia, Ministry of Education (KF201910/YL).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Over the last two decades, implantable continuous flow left ventricular assist devices (LVAD) have proven to be invaluable tools for the management of selected advanced heart failure patients, improving patient longevity and quality of life. The presence of concomitant valvular pathology, including that involving the tricuspid, mitral, and aortic valve, has important implications relating to the decision to move forward with LVAD implantation. Furthermore, the presence of concomitant valvular pathology often influences the surgical strategy for LVAD implantation. Concomitant valve repair or replacement is not uncommonly required in such circumstances, which increases surgical complexity and has demonstrated prognostic implications both short and longer term following LVAD implantation. Beyond the index operation, it is also well established that certain valvular pathologies may develop or worsen over time following LVAD support. The presence of pre-existing valvular pathology or that which develops following LVAD implant is of particular importance to the destination therapy LVAD patient population. As these patients are not expected to have the opportunity for heart transplantation in the future, optimization of LVAD support including ameliorating valvular disease is critical for the maximization of patient longevity and quality of life. As collective experience has grown over time, the ability of clinicians to effectively address concomitant valvular pathology in LVAD patients has improved in the pre-implant, implant, and post-implant phase, through both medical management and procedural optimization. Nevertheless, there remains uncertainty over many facets of concomitant valvular pathology in advanced heart failure patients, and the understanding of how to best approach these conditions in the LVAD patient population continues to evolve. Herein, we present a comprehensive review of the current state of the field relating to the pathophysiology and management of valvular disease in destination LVAD patients. Albeit the term “destination” appeared in the literature in the mid-nineties , destinaSince this initial FDA approval of implantable LVAD for DT, LVAD technology and strategies for managing LVAD patients have evolved considerably. Pre-existing native valvular heart disease as well as in-situ valvular prostheses were traditionally considered a contraindication to LVAD implantation . Due to In this review, we critically appraise the impact of valvular heart disease on LVAD patient outcomes and delineate the current state of the field regarding how concomitant valve disease is addressed both medically and surgically in this population. Furthermore, we review current concepts of development of de-novo valvular pathology post LVAD implantation and proposed preventative strategies.de novo AI.In a conventional arrangement, continuous-flow LVADs funnel left ventricular blood into the ascending aorta creating a transvalvular pressure gradient across the aortic valve. Theoretically, when the gradient is >0, the aortic valve remains persistently closed throughout the cardiac cycle altering not only physiological flow patterns within the aortic root, but also the distribution of mechanical stress on the proximal ascending aorta and aortic valve apparatus. The ensuing pathophysiological changes of leaflet deterioration, commissural fusion, and aortic sinus dilation may lead to worsening of pre-existing aortic insufficiency (AI) or lead to the development of de novo AI during log-term LVAD support, investigators reported a pooled incidence of significant AI of 25% (11%−42%) during a support period of 412 ± 281 days , diuretic therapy, and pump speed optimization with concomitant right heart catheterization  has offered a great degree of translational insight. Callington et al.  demonstrgenicity . More regenicity  also havMitral regurgitation (MR) affects up to 10% of the general population, making it the most common heart valve disorder . In patiConventional heart failure pharmacological treatments and cardiac resynchronization therapy have been shown to reduce the severity of MR through positive remodeling and reduction in the degree of ventricular dyssynchrony , 53. ProIn patients with end stage heart failure that has proven refractory to conventional heart failure therapies, approximately one third have at least moderate to severe MR . EffectiIn an INTERMACS analysis that examined all LVAD implantations between 2008 and 2014, 263/4930 adults with moderate to severe MR underwent a concomitant mitral valve procedure, of whom 96% received a mitral valve repair . ConsensData on long term outcomes in patients with residual MR is conflicting. A recent INTERMACS analysis of patients receiving implants between 2006 and 2017 revealed that 18.8% of patients had at least moderate MR at 3 months post LVAD implant . Incidenp = 0.09)  . This daPredicting which patients are likely to be left with residual MR is challenging. Those at increased risk appear to be younger, more likely to be female, non-Caucasian, with non-ischemic etiology of heart failure . They alPerioperative measures may reduce the risk of residual MR. Appropriate inflow cannula alignment, as determined by a combined assessment of anterior and lateral angulation was associated with greater improvement in MR severity at 1 month . Use of Mitral stenosis impairs left ventricular filling that leads to reduced flows in an LVAD supported patient. Therefore, mitral valve repair or replacement is recommended in patients with moderate or severe mitral stenosis of any cause. The presence of a prosthetic mitral valve is not a contraindication to LVAD implantation. Trans mitral flow typically improves following LVAD implantation, therefore the risk of thrombus formation is low. The 2019 European Association of Cardiothoracic Surgeons Expert Consensus recommend that ‘Exchange of a functional mitral mechanical or biological prosthesis at the time of long-term mechanical circulatory support device implantation is not recommended .Moderate or severe tricuspid regurgitation (TR) is seen in around 20% of patients with chronic heart failure, and around a third of patients presenting with acute heart failure . Its preRight ventricular remodeling is a common consequence of left ventricular systolic impairment and/or left sided valve dysfunction, because of pulmonary arterial hypertension. This causes tricuspid annular dilation and leaflet tethering, leading to functional TR. High right ventricular preload due to venous congestion also leads to volume loading of the right ventricle, increasing the degree of TR. A significant proportion of patients with chronic heart failure have cardiac implantable electronic devices and leads crossing into the right ventricle can also impair tricuspid valve closing. The right ventricle is sensitive to volume loading conditions, relief of venous congestion through effective diuresis can lead to favorable right ventricular remodeling and reduce the degree of TR . TargeteRight ventricular failure remains a common early complication following LVAD implantation, and is associated with prolonged intensive care stays and increased mortality . Right hTR typically improves in the first month following LVAD implantation, as the reduction in pulmonary artery pressures aids right ventricular remodeling. A EUROMACS registry study demonstrated that 65% of patients with moderate to severe TR pre implant have no to mild TR at 30 days post-implant . PatientDespite the natural improvement in tricuspid valve competence post-LVAD in the short-medium term, the presence of at least moderate TR appears to complicate the early post-operative course, with a higher need for mechanical right ventricular support, prolonged inotrope use and intensive care stay . WhetherConcerns regarding early right ventricular recovery likely explains why tricuspid valve repair is the most frequent concomitant valve intervention performed at the time of LVAD implantation . HoweverSingle center retrospective studies have suggested a reduction in rates of early right heart failure, improved postoperative outcomes, and reduced early rehospitalization in patients undergoing concomitant TV repair, without a clear survival benefit –100. A sLarger registry database analyses have consistently failed to show a benefit from concomitant tricuspid valve intervention. A stratified INTERMACS registry analysis of 8,263 patients revealed an increased risk of adverse events, including bleeding, arrhythmia and stroke, and higher mortality in patients with moderate to severe TR undergoing valve intervention . SimilarA prospective randomized controlled trial of tricuspid valve intervention (annuloplasty or replacement) vs no intervention was recently presented at the 2022 American Association of Thoracic Surgeons meeting  . The priThe durability of tricuspid valve repair at the time of LVAD implant is questionable, with between 21 and 37.8% of patients developing at least moderate TR at follow up , 106. ThThe European Association of Cardiothoracic Surgeons Expert Consensus on long term mechanical circulatory support recommend “Re-evaluation of patients with moderate to severe TR after treatment with diuretic therapy, if condition permits” (class 1C) and “In carefully selected patients, tricuspid valve repair for moderate to severe TR at the time of long-term mechanical circulatory support implantation may be considered” (Class IIb C) . This coSome degree of pathology involving multiple valves is commonly encountered in the advanced heart failure population undergoing LVAD implant. When there is significant pathology involving multiple valves, concomitant multiple valve intervention with LVAD implant may need to be considered. There is limited empirical data to guide clinicians in prognostication around LVAD implant with multiple concomitant valve intervention (summarized in There appears to be a signal for temporal reduction in mortality risk associated with concomitant valve procedures during index LVAD implantation. Earlier studies have reported 30-day mortality rates ~25% with combined aortic valve procedures, a nearly 5-fold increase relative to isolated implants . In contThe impact of valvular pathology on outcome measures in critically ill patients is well described . “SurgicID, PC, and JK performed literature review, manuscript preparation, and critical revision. MK, JP, CB, and CM performed critical revision. All authors approved of the final version of the manuscript prior to submission.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Among the measures of CT and echocardiography, TEV and RV/LV ratio were significantly associated with impending shock. In backward stepwise logistic regression, TEV, age and respiratory rate remained independent associated with impending shock .Total embolic burden assessed by CT-based quantification serves as a useful index for stressed cardiopulmonary circulation condition and can provide insights into RV dysfunction and the prediction of impending shock.Detailed descriptions of acute pulmonary emboli (PE) morphology, total embolic volume (TEV), and their effects upon patients’ clinical presentation and prognosis remain largely unexplored. We studied 201 subjects with acute PE to the emergency department of a single medical center from April 2009 to December 2014. Patient hemodynamics, Troponin I and D-dimer levels, echocardiography, and the 30-day, 90-day and long-term mortality were obtained. Contrast-enhanced computed tomography (CT) of pulmonary structures and 3-dimensional measures of embolic burden were performed. The results showed a linear association between the greater TEV and each of the following 4 variables (increasing incidence of right ventricular (RV) dysfunction, higher systolic pulmonary artery pressure (sPAP), greater RV diameter, and RV/left ventricular (LV) ratio (all  Once a diagnosis of acute PE has been successfully established, patient risk stratification and prognostication are essential for guiding subsequent clinical management. The recent clinical guidelines published by the American Heart Association (AHA) and the European Society of Cardiology (ESC)3 stratify patients based on massive, submassive, and low-risk PE categories or the Pulmonary Embolism Severity Index (PESI)4, respectively. Both incorporate key prognostic indicators such as the level of hemodynamic stability, myocardial injury, and right ventricular dysfunction.Acute pulmonary embolism (PE) is a major public health concern and a potentially fatal disease. In the United States, the average incidence is about 0.1% per year, and more than 100,000 people die from acute PE annually5. This has revolutionized the diagnostic approach and serves as the first-line imaging diagnostic tool for acute PE clinically6.Rapid and accurate diagnosis is critical for managing patients presenting with acute PE, and over the last twenty years, multidetector computed tomography (MDCT) with high spatial resolution (1–2 mm) has become highly capable of detecting emboli within the main branches of the pulmonary arteries7, but studies have not shown any significant correlation between clot burden, as measured using current two-dimensional (2D) methods, and adverse clinical outcomes9. In contrast, some studies have shown a correlation between a patient’s clot location and burden, as measured using either 2D methods or the Mastora or Qanadli scores, and their clinical condition11. Praveen et al. also found that a higher clot burden was associated with right heart strain and adverse clinical events12. Previously, measuring clot burden using three-dimensional (3D) methods was impractical because it requires a large amount of manpower during daily clinical practice. It is also debated that the role of clot burden as an indicator of short-term prognosis13. Recently, however, a 3D-based computed tomography (3D CT) method was developed, and it has been widely applied to oncology patient images for precise tumor measurement15. As a result of the advancement of computer science and software, this 3D CT method has become more accurate and less demanding. Therefore, we aimed to assess the association between clot volume burden estimated using this 3D CT method and the Qanadli score, biomarkers, and clinical outcomes, including impending shock  and short-term mortality.Interestingly, as the most commonly used diagnostic test for acute PE, MDCT can provide detailed information on embolic location and burden, neither of which is considered in the above guidelines to be a prognostic marker. Tuzovic et al. found that central and multilobar clots were correlated with right ventricle (RV) dysfunctionThe mean age of the patient population was 66.8 ± 17 years, and it included 122 females (60.7%) and 79 males (39.3%). Their characteristics are shown in Table 3, and the embolic volume in the right and left pulmonary arterial tree was 5.26 ± 5.96 cm3 and 3.17 ± 4.33 cm3 .We used multivariate logistic regression analysis to evaluate the relationship between RV dysfunction and several clinical and radiologic factors . The TEV was expressed as unit of 10cmit Table . TEV wasp < 0.001; Fig. 3 and weaker when TEV was > 10 cm3  and the RV/LV ratio  were significantly correlated with impending shock (Table p = 0.58). Multivariate logistic regression analysis with backward selection was used to identify the factors related to impending shock. In addition, since the patients with cancer had poorer outcomes in our study , age , and respiratory rate  were significantly related to impending shock , 13.9% (28 cases), 24.4% (49 cases) and 29.9% 60 cases), respectively, and these were not significantly correlated to TEV or the Qanadli score. The leading cause of death was cancer , SpO16. However, it has played a limited role in prognostication. In the current clinical guidelines issued by the AHA and ESC, a high RV/LV ratio is one of the CT factors associated with poor prognosis3. A meta-analysis showed that a RV/LV ratio > 1.0 on CT was associated with a 2.5-fold increased risk for all-cause mortality 17. In our study, we also found that an increased RV/LV ratio was significantly associated with an increased risk for impending shock. Conversely, TEV may be an important predictor for stratifying acute PE patients who are referred to the emergency department. Increases in sPAP were correlated with increasing TEV quartiles , changes in cardiac morphology and function are minor. To our knowledge, no other studies prove the relationship between cardiac function and precise embolic burden, and we offer this perspective to clarify the relationship.For echo-based RV dysfunction Table , Q2 .Compared to the Qanadli score, TEV not only more accurately assesses 3D emboli burden but is also better correlated with RV dilatation and echo-based RV dysfunction. Increasing TEV and Qanadli score can both indicate a larger clot burden in the pulmonary arterial circulation, which can lead to pressure overload and RV dilatation. Recently, a small study with fifty-eight patients with acute pulmonary embolism showed that quantitative volumetric measures of TEV was positive correlation with RV/LV ratio21, whereas several more recent studies with a large number of subjects have failed to show a significant association between the Qanadli score and short-term survival23. This may be due to improvements in the early diagnosis and treatment of patients with shock and cardiac arrest from acute PE, which has increased their overall survival rate. Recently, Stein et al. investigated the mortality of PE patients in the United States and showed that, from 1999 to 2017, the mortality of all high-risk patients decreased from 72.7 to 49.8%24. A decreasing mortality rate for acute PE makes demonstrating a significant correlation between radiologic markers and mortality more difficult. This could explain why, despite 79.3% of our patients having a high-risk sPESI score, TEV was not significantly associated with short-term mortality. In contrast, cancer, which is a major risk factor for PE and is used in calculating the sPESI score, was the leading cause of death in our patients  death, additional factors such as hemodynamic status, clinical condition, RV dysfunction, and troponin I levels are important and need to be explored24.In this study, there was no significant association between TEV and 30- and 90-day mortality rates, but this was not unexpected. There are only two small studies published before 2010 that have shown a significant association between semiquantitative clot burden assessment and short-term survival27 using deep learning with realistic data augmentation showed good results in PA segmentation compared to semi-automatic quantification ground truths. Liu el al demonstrated the good correlation between deep leaning convolutional neural network full quantitative embolic burden and the Quanadli, Mastora scores in acute pulmonary emblism, but no further investigation into laboratory data and echocardiographic findings28. Future large cohort studies compares quantitative embolic burden among different semi-automatic and AI softwares may help to improve clinical efficiency by generating 3D volumetric results before radiologist interpretation and reducing possible manual operator errors.Our study has some limitations. First, it is a retrospective study with an exclusively Asian population from a single medical center, which may represent a selection bias and limit generalizability. Second, our 3D CT volumetric method is semiautomatic, still requires manual adjustments and doesn’t compared to other vendor-independent softwares. Recently, a fewstudies used artificial intelligence (AI) for training the data augmentation and fully automatic quantification of embolic burden. Roman et al.In conclusion, our study demonstrated that a 3D CT method for quantifying acute pulmonary embolism provides results that are significantly linked to clinical condition, laboratory data, RV dysfunction, and impending shock. 3D CT measurements of clot burden may thus become a useful and feasible method for acute PE risk stratification and prognostication.This retrospective study was approved, and all methods were performed in accordance with the relevant guidelines and regulations by the institutional review board of Mackay Memorial Hospital (no. 19MMHIS293e), Taipei, Taiwan. From April 2009 to December 2014, 1134 patients with either a clinical or a radiologic diagnosis of acute PE were evaluated. The medical records and images for all cases were reviewed by two radiologists (W.H. and C.Y.), and all images have been anonymous. A total of 201 patients were included in the final analysis after the following exclusion criteria had been applied: (1) no CT angiography for PE ; (2) no thin-slice (≤ 3 mm) image reconstruction; (3) poor imaging quality; (4) radiologic evidence of chronic PE; (5) no significant emboli detected in the CT images; (6) thromboemboli in non-pulmonary vascular locations ; or (7) no echocardiography results; (8) echocardiography performed more than 7 days after admission  and cardiac biomarkers  were recorded. The simplified Pulmonary Embolism Severity Index (sPESI)29 was calculated. To evaluate the effect of embolic volume on RV function, we collected the following echocardiographic data: estimated systolic pulmonary artery pressure (sPAP); RV and left ventricle (LV) diameter; and presence of RV dysfunction. RV dysfunction was diagnosed if the echocardiogram showed any of the following morphological remodeling features: (1) morphological segmental RV abnormality  with RV diameter ≤ 30 mm; (2) RV/LV diameter ratio > 1; or (3) RV diameter > 30 mm32. To evaluate clinical prognosis, we recorded the presence of shock (defined as requiring vasopressors) at emergency-department presentation or during the course of hospitalization, 30- and 90-day mortality, and the leading cause of mortality.Patient characteristics , their clinical presentation data  or a 64-slice  MDCT scanner. The standard CTPA for PE was performed according to the following scan and reconstruction protocols: scans were acquired within a single breath-hold and obtained with a detector width of 16 × 0.672 mm or 64 × 0.5 mm, a tube voltage of 120 kVp, automatic exposure control (AEC) for the tube current, a 0.5 s gantry rotation time, and a 2 mm reconstructed slice thickness. The injection rate of the contrast medium, which was 80 mL of intravenous iohexol (Omnipaque-300) or iopromide (Ultravist-300), was 2.5–3 mL/s. Scans were performed using a bolus-tracking technique and initiated when the contrast medium was first seen in the pulmonary trunk after injection. The scan covered the region from the lung apex to the lowest hemi-diaphragm.All CTPA images were reviewed by a radiologist (W.H.) with eight years of experience in chest CT. Any indeterminate image interpretation was resolved after discussion and review with a senior radiologist (C.Y.) with 18 years of experience in chest CT. For each case, the PE was identified and defined as an intraluminal central filling defect with partial or complete occlusion of the pulmonary artery. Cases with poor imaging quality  were excluded.10 was used for semiquantitative calculation of clot burden. Using the Qanadli score, the arterial tree of each lung was divided into 10 segmental arteries . The presence of an embolus in a segmental artery was scored 1 point and the proximal arterial level was scored points equal to the sum of the distal segmental arteries. To indicate the severity of the embolus obstruction, the following weighting factor was used: 2 for total occlusion, 1 for partial occlusion, and 0 for no thrombus observed. The maximal Qanadli score for one patient was therefore 40.The Qanadli scoreA 3D-based CT method was used for absolute quantitative evaluation of the total embolic volume (TEV). CTPA images were transferred to a dedicated workstation  and the embolic volume was measured semiautomatically. Filling defects were visually identified within the arterial tree , and the boundaries of the filling defects were defined semi-automatically by the workstation using 3D segmentation method known as Draw smart ROI Figure A and visTo evaluate clinical prognosis, we prespecified and recorded the clinical presentation of shock (defined as requiring vasopressors) at emergency-department presentation as the primary endpoint. We further assessed 30- day and 90-day, 1-year and 2-year all-cause mortality and rehospitalization during subsequent follow-up.http://www.r-project.org/). Quartiles were used to display the pattern of increasing TEV and its effects on cardiac echo, CT, Qanadli score, and lab data findings. A multivariate logistic regression model with backward stepwise selection was used to evaluate the factors affecting RV dysfunction and shock. The correlations between the different image modalities—CT  and cardiac echography —and impending shock were evaluated using odds ratios (OR). Receiver operating curve (ROC) analysis was used to compare the ability of TEV and Qanadli scores to predict RV dysfunction. The threshold for statistical significance was p < 0.05.Statistical analysis was performed using R  blinded to the initial results. The intraclass correlation coefficient was used for analysis.Study approval was obtained from the Mackay Memorial Hospital Institutional Review Board (IRB no. 19MMHIS293e). This 3D CT image was reconstructed from de-identified data and the informed consent was waived during Mackay Memorial Hospital Institutional Review Board review.


Graphical AbstractThe aim was to assess the late cardiotoxic effects in young adults treated for various cancer types in childhood using echocardiography and 24‐h ECG Holter monitoring. The development of new drugs and therapeutic procedures has improved the prognosis and quality of life of patients. Nevertheless, cardiotoxic medication, mainly anthracyclines, still play a key role in cancer treatment in children.22.1One hundred and six adult subjects were initially enrolled into the study. All subjects gave written informed consent before enrollment and the study was approved by the institutional ethic committee .Subsequently, eight patients were excluded, one for cardiac transplantation before final enrollment and seven for unsatisfactory quality of echocardiographic images. The final number of 98 subjects were included in the analysis. All were young adults, mean age 24.2 years, who underwent treatment for various types of cancer in childhood in the Department of Children's Oncology at Brno University Hospital in Brno, Czech Republic between 1978 and 2013.2.2S′), peak early diastolic (E′), and late diastolic (A′) velocities were measured from the lateral and septal part of the mitral annulus  was then connected, and patients were asked to have standard daily regimen. The following day the Holter device was disconnected and the record was checked for significant or inappropriate tachy‐ or bradycardia, supraventricular and ventricular arrhythmias, and conduction disturbances. Echocardiography was performed on the Vivid 9 , using parasternal and apical views. The heart dimensions were measured and the left ventricular ejection fraction was calculated according to Simpson's rule. Valve morphology and flow characteristics were also assessed for exclusion of significant valve disease. Tissue Doppler parameters were obtained from the apical four‐chamber view, the peak systolic . All control subjects underwent the same echocardiographic examination as the study patients and values were compared mutually. Patients in the study group were also divided into groups with and without anthracycline administration and according to the indexed anthracycline dose (mg/m2) below and above the median (200 mg/m2). The echocardiographic parameters and frequency of arrhythmias were assessed among the described groups above.The control group comprised 57 healthy age‐matched volunteers  and controls. In a subgroup analysis, the CCSs were further divided according to the use of anthracyclines in their medical history into groups with and without anthracycline therapy, and the abovementioned variables were again compared by the Student's t‐test; further, the number of supraventricular and ventricular premature beats, as recorded by Holter ECG, was compared using the Mann–Whitney U test. The value of α = 0.05 was used as the level of statistical significance throughout the analysis.Continuous variables  generally followed a Gaussian distribution as assessed by the Kolmogorov–Smirnov test and visual inspection of histograms, and were compared by the Student's 32.Radiotherapy underwent 63 (64%) of the CCS. The most frequent diagnoses were Hodgkin lymphoma , acute lymphoblastic leukemia , and the non‐Hodgkin lymphomas  The mean time since cessation of the therapy was 12.1 years. The complete characteristics of the study group are presented in Table p for both <0.001), tricuspid annulus , peak systolic velocity from the tricuspid annulus , and TAPSE . Comparison of echocardiographic parameters between CCS and controls are presented in Table 2) and above median dose did not show any significant differences in arrhythmia occurrence or echocardiographic parameters  who were treated by anthracyclines. The mean anthracycline dose was 195 mg/m42).A recent study by Sofia et al.2), however the median time since last administration of anthracyclines was also shorter (9.8 vs 12.1 years). The CCS had a significantly lower LVEF and global circumferential strain on CMR and the indexed myocardial mass and mass/volume ratio in the patient group were decreased as well. The LV extracellular volume was also higher in CCS.In contrast, right ventricular EF did not show significant differences against controls. Tissue Doppler echocardiography demonstrated lower peak diastolic velocities from the lateral and septal part of the mitral annulus. The assessment of right ventricular function was described in another paper,S′ velocity, TAPSE, and RV free wall strain were significantly lower in the CCS group. This is in concordance with our results, however the time difference since cancer therapy to follow‐up examination was lower in our group. The findings described above may implicate that the impairment of cardiac function worsens with time, from subtle changes detectable by CMR of 3D‐RT echocardiography to a decrease of tissue Doppler velocities. The occurrence of arrhythmias in CCS was described in a large study by Armstrong et al.p < 0.001). The authors also proved negative cumulative effects of anthracyclines and radiotherapy, mainly in the occurrence of coronary artery disease. The worsening influence of the combination of radio‐ and chemotherapy was also significant in the incidence of valve diseases, heart failure, and arrhythmias. In our cohort, there were 46 (47%) subjects who received both chemo‐ and radiotherapy, but we did not find any significant difference in tissue Doppler parameters or arrhythmia occurrence between subgroups with or without the administration of anthracyclines.The long‐term side effects including late cardiotoxicity in CCS have been increasingly studied during recent years, reflecting the growing number of adult CCS. The increased cardiovascular morbidity and mortality in patients treated by anthracyclines have also been well described in many studies.Clinical perspectives: Based on the abovementioned results, we suggest the late cardiotoxic effects gradually worsen with time, affecting first the left ventricular diastolic function with simultaneous impairment of the right ventricular systolic parameters. The cardiotoxic effects may be potentiated by concomitant use of radiotherapy. Furthermore, long‐term follow‐up in adulthood is needed and regular echocardiographic controls are still the first‐choice method, with the addition of other methods such as cardiac MRI and ECG Holter monitoring in relevant cases.Study limitations: Our study was only single‐center with a limited number of subjects and the follow‐up period was relatively shorter in comparison with other studies. However, we have been continuing to enroll subjects and further follow‐up is planned. In addition, the 24‐h ECG Holter monitoring is relatively short to detect all potential arrhythmias, however it is easier for patients to undergo.In conclusion, current therapeutic protocols in children's cancer diseases, including chemo‐ and radiotherapy, cause initially subclinical impairment of cardiac function, measurable by tissue Doppler imaging.The authors declare no conflict of interest or industrial funding or relationship.All authors contributed to this manuscript: VK, RP, TK, and VB (V.Bajciova) prepared the conception and design of the study, and data analysis, LO and VB (V.Bednarova) contributed on drafts of the manuscript, JM did the statistical analysis and wrote statistical section of the manuscript. VK completed the final article and RP and TK revised it. All authors read and approved this manuscript and declare they have no conflict of interest.The study was approved by Ethics committee of St. Anne's University Hospital, Brno, Czech Republic, Reg. No. 15V/2018. All subjects gave their informed consent before enrollment into study according to Declaration of Helsinki.


Pacemaker implantation involves intraoperative testing of ventricular sensing using a device called a pacing system analyzer (PSA). The value obtained is expected to correspond to those taken by the pacemaker after its implantation. This study determined the latency period for sensing intracardiac electrogram (EGM) by the right ventricular (RV) lead.Patients without significant heart disease and underlying intrinsic atrioventricular (AV) conduction underwent Medtronic or Abbott dual‐chamber pacemaker implantation with the RV lead positioned on the mid‐septum. Real‐time sensing data were obtained through PSA and after pacemaker implantation to evaluate latency as the time interval Q‐VS between the onset of QRS on surface electrocardiogram and the sensed EGM by the RV lead.p < 0.001). RBBB patients had longer sensing latency compared with narrow QRS patients, either through PSA or through pacemaker (p < 0.001). The sensing latency of Medtronic recipients was longer than those of Abbott in narrow‐QRS (p < 0.05), but not in RBBB.Of 157 patients, 105 had narrow QRS (<120 ms) and 52 had wide QRS of complete right bundle branch block (RBBB). Both narrow‐QRS and RBBB patients had longer sensing latency through PSA  than through pacemaker  through PSA than through pacemaker, (2) in RBBB than in narrow‐QRS, and (3) in Medtronic pacemakers compared with Abbott pacemakers. Knowledge of sensing latency helps the optimization of the AV delay. The pacemaker recognizes the heart's own intrinsic signal through the implanted right ventricular (RV) lead by analyzing the local intracardiac electrogram (EGM). Once the RV lead is in place, intraoperative measurements include the determination of the sensing threshold using an external or inbuilt programmer pacing system analyzer (PSA) unit.The different methods of recording the electrical activity of the heart, i.e. ECG and EGM, raise the question as to whether the two signals coincide in time, in the knowledge that any signal should be expected to be displayed after a certain gap of time because of propagation and processing delays. In this context, clinical interest has grown substantially in the field of cardiac resynchronization therapy (CRT) with several investigators reporting differences in timing between the QRS on the ECG before the sensed EGM on the left ventricular lead.Still, basic knowledge regarding timing relationships between QRS and acquired EGM from the RV lead is lacking. In this work, the RV lead sensing latency refers to the gap of time by which the ventricular sensed EGM gets delayed relative to the QRS on ECG. It was the specific aim of our study to determine the RV lead sensing latency in patients without significant heart disease and intrinsic atrioventricular (AV) conduction, undergoing dual‐chamber pacemaker implantation of different manufacturers . Furthermore, we clarified by intra‐individual comparisons whether the intraoperatively RV electrical delay data through PSA correspond to those obtained through the implanted pacemaker.22.1We studied 157 patients  without evidence of significant heart disease who underwent common dual‐chamber pacemaker implantation for standard indication following written, informed consent. Patients were considered for inclusion in the study if they were hemodynamically stable and asymptomatic during operation and had intrinsic AV conduction of more than 40 beats per minute because of sinus bradycardia or 2:1 AV block with constant PR intervals. Eligible patients did not have a history of organic heart disease or heart failure and had normal left ventricular dimension and systolic ejection fraction ≥50%, as assessed by two‐dimensional echocardiography. Patients were excluded if they had: reversible causes for AV block, atrial or ventricular arrhythmia, acute coronary syndrome and/or unstable angina, severe pulmonary disease, or renal insufficiency; if they needed sympathomimetic drugs or atropine or temporary pacing during operation, as those undergoing pulse generator change or lead revision.according to their baseline QRS duration on 12‐lead ECG before pacemaker implantation.The patient population was divided into two groups: narrow QRS (<120 ms) or wide QRS (≥120 ms) 2.22 or Abbott 2088TC, tip electrode surface area 6.9 mm2, both of 58 cm length with tip to ring spacing 10 mm), was used for RV mid‐septal placement. The optimal RV lead position was confirmed by combined fluoroscopy views and characteristic paced ECG criteria.All patients underwent their first, Medtronic, or Abbott, transvenous dual‐chamber pacemaker implantation under continuous ECG monitoring through an external surface 12‐lead ECG polygraph . Standard implant techniques were used with local anesthesia. The electrode leads were introduced via the cephalic and/or the subclavian vein, and the pulse generator was placed in a subpectoral pocket. Pacemaker devices included the Medtronic models Adapta™ and Attesta MRI™, and the Abbott models Victory™, Endurity™, Assurity MRI™, and Ensura MRI™. The same bipolar steroid‐eluting active fixation RV pacing lead of the same brand  were configured to display in real‐time simultaneous ECG lead II, markers, and RV EGM. The standard programmer's ECG cables and lead wires of Medtronic and Abbott manufacturers , connected the programmers to skin electrodes for ECG. The use of a PSA unit (Medtronic module 2290 and Abbott model EX3100) of the same pacemaker brand served for EGM, peak‐to‐peak R‐wave amplitude, and maximum voltage deflection/time (slew rate) measurements. Note that in order to obtain optimal results, each pacemaker manufacturer supplies PSAs with band‐pass filters that match the filters used in their pacemaker systems.2.4A 12‐lead intrinsic rhythm baseline ECG was recorded before implantation at a paper speed of 50 mm/s with 10 mV/cm gain. The QRS duration was measured as the interval from the first onset of QRS in any lead until the latest offset in any lead. Wide QRS morphology was classified according to World Health Organization criteria.2.5p < 0.05. Statistical analysis was performed using the SPSS Statistical Software Package .Results of patient characteristics are presented as mean ± standard deviation or as percentages. Appropriate parametric or non‐parametric statistical tests (Student's t‐test or Wilcoxon signed ranks test for paired data and Student's t‐test or Mann–Whitney U test for unpaired data) were used for continuous variables and chi‐square tests for categorical variables, with the level of significance 33.1p < 0.05) and had a higher heart rate (p < 0.05) compared to RBBB patients. As expected, the RBBB patients had significantly longer QRS duration (p < 0.001). Overall, more Medtronic than Abbott pacemakers were implanted , but both normal QRS and RBBB patient groups included similar proportions of implanted pacemaker manufacturers . No complications occurred during the implantation procedures.The baseline characteristics of the study patients are summarized in Table 3.2p = 0.46). Overall, there were no differences between narrow QRS vs. RBBB patients in R wave amplitude and slew rate through the PSA , and in R wave amplitude through the pacemaker . There were also no differences in R wave amplitude or slew rate between the two pacemaker manufacturers when the study patients were considered as a whole group or were analyzed as separate groups of narrow QRS patients vs. RBBB patients All the patients had an R wave amplitude of 9.9 ± 3.7 mV and a slew rate of 2.74 ± 0.94 V/s through the PSA, and a similar R wave of 10.3 ± 3.4 mV through the pacemaker (3.3p < 0.0001]). Both narrow QRS and RBBB patients had similarly longer mean Q‐VS through PSA  than those values obtained through pacemaker  (p < 0.0001). Overall, RBBB patients had significantly longer Q‐VS than patients with narrow QRS when assessed either through the PSA or through the pacemaker (p < 0.001).Data on the Q‐VS results are presented in Table p < 0.001). All 81 Medtronic patients with narrow QRS showed shorter Q‐VS through pacemaker than through PSA. Abbott's longer Q‐VS through PSA of 14.7 ± 9.8 (range 0–42 ms) did not change significantly from that obtained through pacemaker of 13.1 ± 10.2 ms, (range 0–37 ms). On 2 of Abbott 24 occasions (8%), the Q‐VS through pacemaker was slightly longer than that through PSA . For RBBB patients, similarly, Medtronicʼs Q‐VS through PSA of 87.9 ± 18.9 ms (range 37–122 ms) was greater as compared to those obtained through pacemaker of 33.8 ± 15.1 ms, (range 6–60 ms) (p < 0.001), with all patients showing shorter Q‐VS through the pacemaker. Abbottʼs Q‐VS through PSA of 29.7 ± 14.2 ms (range 2–52 ms) did not differ from that obtained through pacemaker of 26.1 ± 13 ms, (range 2–56 ms) (p = 0.4), but on 8 of 18 occasions (44%), the Q‐VS through the pacemaker was slightly longer than that obtained through PSA . Overall, Medtronic's Q‐VS was longer when compared with that of Abbott in narrow QRS patients through both PSA and pacemaker (p < 0.001); RBBB patients had longer Medtronic Q‐VS through PSA, but not through pacemaker .The Q‐VS data according to the manufacturer are shown in Figure 4Proper sensing evokes order and meaning to most effective and qualitative pacing and is an essential precondition to promote intrinsic ventricular activity and avoid adverse ventricular pacing.During implant, clinicians usually take the device's proper sensing function for granted if the intrinsic EGM signal received by the electrode and transmitted to the PSA sensing circuit has sufficient amplitude and slew rate, whereas often do not take any notice of the signal propagation delay. Of course, as little as possible RV lead sensing latency is desired so as not to confound proper pacemaker operation. Our observation that the QRS consistently preceded the EGM obtained by either PSA or pacemaker concurs with the earlier manifestation of spontaneous activity on ECG.Focusing on the PSA application of both manufacturers, the EGM signal travels a similar fixed distance in the length of about 4.2 m (PSA cables of approximately 3.7 m and implanted electrode of 0.58 cm) to the terminal unit to be recorded. It is interesting that although for ECG recording the intrinsic ventricular event needs to cover an overall similar cable distance to the skin surface, the PSAs of both manufacturers needed more time for EGM processing to output “VS”. An unexpected finding was also the much shorter RV lead sensing latency of Abbott compared to Medtronic in both patient groups. The notable differences among the patient groups and manufacturers may be explained by differences in QRS waveform and different methods in R point recognition. In any case, these new observations demonstrated substantial RV lead sensing latency which should be taken into consideration for the management of pacemaker programming.Contrary to the wide‐held view that the implanted pacemaker replicates similar data to those obtained intra‐operatively through the PSA, it had been a pleasure to note much smaller sensing latency through the pacemaker. Specifically, we found through pacemaker mean Q‐VS values of 18.2 ms in Narrow‐QRS patients and 31.2 ms in RBBB patients within a wide range of values to a maximum of 50 ms and 60 ms, respectively. Of note, unlike Medtronic, Abbott showed in 8% of normal QRS patients, and in 44% of RBBB patients, slightly longer Q‐VS through the pacemaker as compared through PSA. The decrease of sensing latency by the implanted pacemaker compared to the PSA measurements was particularly impressive in Medtronic pacemakers of both patient groups, though still longer than in Abbott pacemakers. Possible explanations for the differences seen between Medtronic and Abbott devices include different manufacturing and engineering methods involving possibly different raw materials in lead and generator construction as well as different QRS recognition sensing methods and device band‐pass filters.4.1Though adjustment of the AV timing cycles intends to ensure optimal mechanical coordination between atrial and ventricular contractions, whether the atrium is sensed or paced, often, it is left programmed in an empirical way or to a predefined manufacture's setting value. Practically, the AV delay starts with an atrial event and allows a precisely timed interval to occur during which the pacemaker seeks activity on the ventricular channel to terminate it. With the sensing latency, the sensed AV interval becomes more prolonged and the ventricular channel waits for more time to alert for potential incoming ventricular activity. After termination of the paced programmed AV delay, the delivered ventricular pulse will not capture the ventricle if it lands on a late conducted intrinsic ventricular beat. The coincidence of a heart's intrinsic beat and a pacemaker spike will result in unnecessary and confusing fusion/pseudofusion which, in addition, may be counted and annotated as a ventricular‐paced event.Reduction of unnecessary ventricular pacing is recommended to be exercised in pacing populations with intact, low‐degree, or intermittent atrioventricular conduction.In point of fact, programming a longer AV delay, at least to the value of RV lead electrical delay, may add to the prevention of unnecessary ventricular pacing. This setting is possible since pacemaker manufacturers enable the extension of the AV delay usually in successive steps of 10 ms interval increments. Our findings of wide range RV lead sensing latency interpatient variability suggest possible clinical relevance and individualized AV delay programming, whereby much longer AV interval extensions may be needed particularly in patients with intrinsic RBBB.4.2Several limitations should be mentioned. First, our Q‐VS data relating to the RV lead placement in the mid‐septal position may not be extrapolated to other RV pacing sites. In addition, other pacemaker manufacturers may provide different RV lead sensing latency results either through PSA or through the implanted pacemaker. Also, there is a question as to whether comparable results might be related to other pacing populations with underlying cardiac disease.5The QRS on ECG does not coincide in time with the EGM signal from the RV lead, reflecting an appreciable RV lead electrical delay either through PSA or through the implanted pacemaker. Sensing EGM through PSA incorporates distinctly longer electrical delay compared with the pacemaker generator. RBBB patients exhibit longer RV lead sensing latency than patients with narrow QRS, as do Medtronic devices compared with Abbott devices. By remembering RV lead sensing latency, the extension of the AV delay to the value of RV lead electrical delay contributes to the avoidance of unnecessary ventricular stimuli.Authors declare no conflict of interests for this article.


Amongst automated functional analyses, GLS was the only independent predictor of MACE in multivariate analyses . Considering high agreement of automated GLS and equally high accuracy for risk prediction compared to the reference standard of manual analyses, automation may improve efficiency and aid in clinical routine implementation.Feasibility of automated volume-derived cardiac functional evaluation has successfully been demonstrated using cardiovascular magnetic resonance (CMR) imaging. Notwithstanding, strain assessment has proven incremental value for cardiovascular risk stratification. Since introduction of deformation imaging to clinical practice has been complicated by time-consuming post-processing, we sought to investigate automation respectively. CMR data (n = 1095 patients) from two prospectively recruited acute myocardial infarction (AMI) populations with ST-elevation (STEMI) (AIDA STEMI n = 759) and non-STEMI (TATORT-NSTEMI n = 336) were analysed fully automated and manually on conventional cine sequences. LV function assessment included global longitudinal, circumferential, and radial strains (GLS/GCS/GRS). Agreements were assessed between automated and manual strain assessments. The former were assessed for major adverse cardiac event (MACE) prediction within 12 months following AMI. Manually and automated derived GLS showed the best and excellent agreement with an intraclass correlation coefficient (ICC) of 0.81. Agreement was good for GCS and poor for GRS. Amongst automated analyses, GLS (HR 1.12, 95% CI 1.08–1.16, Trial registration: ClinicalTrials.gov, NCT00712101 and NCT01612312. Therefore, precise risk stratification is a cornerstone in clinical practice to evaluate adequate treatment strategies ranging from drug therapy4 to implantable cardioverter-defibrillator (ICD) implantation6. To date, the treatment decision broadly relies on left ventricular ejection fraction (LVEF) assessment, although data has demonstrated superiority of deformation imaging for risk stratification8.Cardiovascular disease, amongst which acute myocardial infarction (AMI) constitutes a major fraction9 as well as post-processing of routinely acquired cine sequences10. Although the latter allows reliable deformation imaging without alterations to the CMR protocol and offers incremental value for risk assessment7, clinical implementation has been complicated by costly and time-consuming post-processing. Meanwhile, artificial intelligence (AI) based volumetric post-processing has been introduced for automated analyses of CMR cine sequences and demonstrated non-inferiority for major adverse cardiac event (MACE) prediction compared to manual analyses11. With the novel availability of AI based deformation imaging, the present project aimed first to assess the reproducibility of automated deformation imaging compared to the reference standard of manual analyses and second to evaluate its value for MACE prediction12 in a large prospectively recruited population of ST-elevation myocardial infarction (STEMI) and non-STEMI patients.Cardiovascular magnetic resonance (CMR) imaging enables precise myocardial deformation assessments including dedicated sequences13 and TATORT-NSTEMI 14 trials. Both studies were approved by the respective ethics committees and the lead ethical institution at the University of Leipzig. The study was conducted according to the principles of the Helsinki Declaration and all research was performed in accordance with relevant guidelines/regulations All patients gave written informed consent before participation.The patient population of this CMR substudy consisted of patients from two previously published open-label, multicentre trials which included patients referred for CMR imaging following AMI: namely the AIDA STEMI 15 and patients with missing data or data of insufficient quality for manual postprocessing were excluded. This resulted in a dataset of 1095 patients  or rather n = 1077 long axis (LAX) cine sequences for GLS as well as n = 1048 short axis (SAX) datasets for GCS and GRS assessment. The clinical endpoint of the study was defined as the occurrence of major adverse cardiac events (MACE) within 12 months. These included, in order of study priority, all-cause mortality, reoccurrence of an AMI and congestive heart failure. If more than one MACE occurred, then only one was included based on the priority order.The flow-chart for the CMR substudy is shown in Fig. 16.CMR cine sequences were acquired using clinical 1.5 or 3 Tesla scanners. The standardised imaging protocol included steady-state free precession imaging  for the acquisition of 2 and 4 chamber views (CV) LAX as well as SAX cine sequencesManual strain analyses were performed by an experienced investigator using feature-tracking post-processing software . Manual analyses comprised global longitudinal strain (GLS) derived from 2 and 4 CV long axis cine sequences as well as global circumferential and radial strain (GCS/GRS) averaged from basal, midventricular, and apical locations of a short axis (SAX) cine sequence. Slice selection was performed based on the following criteria: The apical slice was required to have the blood pool present during the entire cardiac cycle. The basal slice must not include the LV outflow tract in any frame. The midventricular slice was chosen in between the apical and basal slice in the presence of the papillary muscles. GLS and GCS were obtained endocardially whilst GRS values were analysed for the myocardium after also placing an epicardial contour. Manually analysed strain values were used as the reference standard to evaluate reproducibility of automated AI derived strain values.Automated analyses were performed using commercially available dedicated post-processing software . Prior to the fully automated strain assessment, epi- and endocardial borders of the LV were traced by the algorithm for LAX Fig. 18. Non-parametric correlation was assessed using the Spearman’s rank correlation coefficient. The coefficient of variation (CoV) was calculated by taking the standard deviation of the difference and dividing it by the mean19. Bland–Altman plots were used to visualise the difference between the data sets and their outliers20, the bias was calculated as the difference between the means of each method. Furthermore, 95% limits of agreement (LOA) were calculated as the mean difference ± 1.96 SD of the mean difference. Univariate Cox regression analyses were used to calculate hazard ratio (HR) and are reported with corresponding confidence intervals (CI) of 95%. Multivariate analyses included univariate significant variables, excluding manual strain values due to high correlation between manual and automated strain values. Kaplan–Meier curves were applied for clinical end point assessment with the cut-off point defined as the median of each variable. Diagnostic accuracy is shown by the area under the curve (AUC) calculated from receiver operating characteristics (ROC). Manual and automated AUC were compared using the method proposed by DeLong et al.21. All p-values provided are two-sided and were considered statistically significant below 0.05.Statistical analyses were performed using SPSS Statistics, v28,  and MedCalc Version 20.011 . Categorical variables are reported as absolute numbers with corresponding percentages and were compared using the Chi-Squared test. Continuous variables are reported as median with interquartile range and were compared using the Mann–Whitney-U test if independent or the Wilcoxon signed-rank test if dependent, respectively. Agreement of manual vs automated strain values are reported using the intraclass correlation coefficient (ICC) in a model of absolute agreement. An excellent agreement is considered at values greater than 0.74, values from 0.60 to 0.74 good, from 0.40 to 0.59 fair and anything less than 0.40 would have poor agreementp < 0.001), cardiovascular risk factors such as hypertension and diabetes mellitus were significantly more common in patients with MACE (p = 0.014 and p = 0.008 respectively). The Killip class on admission was significantly higher in patients with MACE (p < 0.001), so was the number of diseased vessels (p = 0.010). Both the thrombolysis in myocardial infarction (TIMI) flow grade before and after PCI were not significantly related to the increase of MACE occurrence (p ≥ 0.177).Baseline characteristics according to type of AMI as well as occurrence of MACE are reported in Table p < 0.001) as well as GRS . In contrast, GCS automated strain values were lower compared to manual analyses  Table Automated strain values were higher compared to manually derived GLS . GRS 3 slices and all slices showed lower correlation to manual GRS (r = 0.48 and 0.49 respectively).p < 0.001), hypertension (p = 0.016) and diabetes mellitus (p = 0.009) emerged statistically significantly associated to an increased risk of MACE. Other clinical factors such Killip class on admission (p < 0.001) and number of diseased vessels (p = 0.003) were also significantly associated with MACE occurrence Table p < 0.001) with GLS showing the highest HR of 1.12, 95% CI 1.08–1.16) Table p < 0.001) in multivariate analyses.In univariate cox regression, baseline characteristics such as age .Another multivariate model was built to compare manual LVEF and GLS to automated analyses . As appreciated from AUC statistics, automated analyses were non-inferior for risk prediction compared to the reference standard of manual assessment: GLS , GCS  and GRS  Table Dichotomization at the median of respective strain values was performed to assess risk stratification using Kaplan–Meier curves Fig. 7, GLS emerged as the best and only independent predictor for MACE amongst functional parameters. Second, GLS showed the best and excellent reproducibility compared to its manually assessed counterpart. Last, fully automated AI derived strains may help to implement deformation imaging within clinical routine by cutting down on post-processing times and costs. However, to date, fully-automated results will still need to be confirmed by a clinician who takes responsibility for the management of the patient.The present study investigated the clinical feasibility of novel AI-derived deformation imaging in a large population of prospectively recruited patients who underwent CMR imaging following AMI. Similar to previously published results on manual analyses7 in both ischemic and non-ischemic heart disease23. Indeed, previous studies have consistently shown that, amongst deformation imaging parameters, longitudinal strain has the highest power for MACE prediction25. In accordance, the present results demonstrate that automated derived GLS best predicted MACE with similar accuracy as appreciated from ROC analyses compared to the reference standard of manual analyses. Similar results for equally accurate risk prediction comparing automated and manual analyses were found for GCS and GRS, however, automated GLS emerged as an the only independent predictor of MACE amongst automated functional assessments which is in line with results shown for manual assessments7.Deformation imaging has shown improved risk prediction in comparison to volumetric analyses26. Unfortunately, its clinical availability is still limited due to the lack of standardised reference values caused by limited agreements between respective approaches for strain assessment and even limited agreements between different software vendors for a specific strain approach26. In the present study, especially longitudinal and circumferential strain values highly correlated with manually derived FT values. This is in line with previously shown high intra- and inter-observer reproducibility for FT GLS and GCS24. In contrast, absolute agreements comparing manual to automated strains showed higher variations with GLS being under- and GCS being overestimated by automation. Previous data from non-commercially available deep-learning algorithms have reported higher correlation values of GLS and GCS27 whilst a study based on echocardiography has reported similar reproducibility of manual and automated assessments for GLS28. Notwithstanding, GLS emerged as the parameter with the highest agreement and an absolute bias of below 1.5%. In contrast, GRS was found to be inflated in automation. This could be due to the difficulty of achieving the value of change of thickness of the radius, considering it is relatively small, which could introduce significant errors. It is generally considered a relatively unreliable measure29. In the present setting, the automated software did not directly provide the equivalent to manual strain measurements because the automated software derives strain values for the entire ventricle rather than a basal, midventricular and apical slice in manual analyses. The latter is done in manual analyses only to save time without compromising diagnostic accuracy10. In that regard, we tested reproducibility to manual analyses first comparing the exact value given by the automated analyses without any observer interference  as well as three manually selected slices from the automated analyses matching the same selection criteria chosen for manual assessment. Notwithstanding, when comparing reproducibility between manual and automated analyses based either on average strain values from all the slices or from the three manually selected slices, similar results were found. Besides, this also indicates that manual analyses based on basal, midventricular and apical SAX assessment represent overall myocardial function adequately.Strain values have been evaluated using different methods in previous studies30. This can be achieved by applying machine learning algorithms, which could improve patient care, is cost effective and could reduce mortality rates. Traditional clinical methods have been compared to AI methods in predicting coronary obstructive disease with AI displaying higher sensitivity31. It was also shown that machine learning could aid in risk prediction of patients with suspected coronary disease with the support of computed tomographic angiography parameters as opposed to using these parameters alone32.Using AI is progressing in the clinical field, especially regarding cardiovascular medicine33. Strain could be better at adverse event prediction than volumetric analysis (LVEF)33 but both should be taken into consideration in the clinical setting, as together they could act as a strong risk prediction tool. Using AI based automation software in determining strain shortens the post-processing period and may be implemented to the clinical routine to save time and costs. Indeed, it can be applied on bSSFP cine sequences while perfusion or LGE imaging within the CMR protocol is still being performed. However, results still need to be confirmed by the operator, considering outlier measurements occurred in the automated analysis with extreme values such as positive GLS or GCS and zero strain values. Additionally, the software might detect false borders and would calculate the strain based on those borders. Unfortunately, advances in AI based automated analyses do not address the issue of inter-vendor comparability as an ongoing issue delaying clinical implementation. Furthermore, methodological differences in strain assessment need to be taken into consideration representing26 a further obstacle to overcome for AI-based automated strain assessment. Future approaches in AI based risk evaluation in cardiovascular disease may be based on comprehensive cardiac analyses beyond functional evaluations including quantification of LGE and microvascular obstruction (MVO)11. Notwithstanding, in contrast to volumetric and strain analyses, the latter still requires manual interaction to differentiate LGE and MVO in infarcted areas. Consequently, for automated comprehensive cardiac functional analyses and tissue characterisation parallel to image acquisition, further developments are warranted. Such future developments combining myocardial shape and function have recently been described and may even further expand our options for fully AI based quantification of cardiac phenotypes with potentially even better prediction of clinical outcome and management of cardiac therapies34.Usually, volumetric analysis and late gadolinium enhancement are used for prediction of MACE but measuring strain has shown to have promising results in adverse event prediction7 and echocardiography if for image quality not all 3 views can be obtained35.The data collected for this study was obtained in multiple centres using different CMR vendors. However, the study protocol was the identical. For CMR image acquisition, patients need to be stable enough to undergo the process. Therefore, there might be a selection bias in the selection of the study cohort. Due to the dynamic formation of necrosis and beginning of cardiac remodelling post-AMI, measuring strain after a longer preceding myocardial infarct could lead to an improved prognostic value, however this is not evaluated in the study. The specifications of the algorithm used for the AI software and the deep learning methods are not disclosed by the manufacturer. Thus, the deep learning models could not be properly detailed. Only 2 and 4 CV were available for GLS assessment, nevertheless the progonostic value of GLS derived from 2/4 CV analyses has been demonstrated for MRIAI based automated GLS assessment shows similarly high diagnostic accuracy and excellent agreement compared to the reference standard of manually derived GLS. AI based automated strain assessment of GLS representing the most clinically relevant parameter may thus emerge to cut down on post-processing time and costs. If remaining issues such as low inter-vendor agreements between different software types and the absence of uniform reference values can be adequately addressed this technology may enable widespread adoption of CMR GLS measurements in clinical routine practice.Supplementary Information.


PrePH had a higher amount of insertional point LGE (69%) and LGE patterns characteristic of non-vascular fibrosis (77%) compared to IpcPH  . Assessment of global LGE, native T1, and ECV burdens did not show a statistically significant difference between PrePH  and IpcPH  . Global native T1 and ECV were higher in patients (1050.9 ± 33.8 and 31.0 ± 4.1%) than controls (28.2 ± 3.7% and 1012.9 ± 29.4 ms) (p < 0.05). Cardiac MRI-based tissue characterization may augment understanding of cardiac involvement and become a tool to facilitate PH patient classification.Cardiac magnetic resonance imaging (MRI) is emerging as an alternative to right heart catheterization for the evaluation of pulmonary hypertension (PH) patients. The aim of this study was to compare cardiac MRI-derived left ventricle fibrosis indices between pre-capillary PH (PrePH) and isolated post-capillary PH (IpcPH) patients and assess their associations with measures of ventricle function. Global and segmental late gadolinium enhancement (LGE), longitudinal relaxation time (native T1) maps, and extracellular volume fraction (ECV) were compared among healthy controls , PH patients , and PH subgroups . Cardiac cine measured ejection fraction, end diastolic, and end systolic volumes and were assessed for correlations with fibrosis. LGE mural location was qualitatively assessed on a segmental basis for all subjects. PrePH patients had elevated  septal left ventricle native T1 values  compared to IpcPH patients  ( Cardiac MRI can characterize myocardial tissue abnormalities and has been used to evaluate diseases due or associated with left ventricle (LV) ,2 and/orPH is defined by an elevated mean pulmonary artery pressure (mPAP) at rest as measured by right heart catheterization (RHC). The exact mPAP value used to define PH has recently changed ; acute kidney injury; kidney or liver transplant within 8 weeks; any contraindication to MRI; pregnant or breastfeeding women; adults unable to consent; children; prisoners. Right heart catheterization: a fluid-filled catheter (Swan-Ganz) connected to an analog pressure recorder was used to obtain mPAP, systolic PAP, diastolic PAP, pulmonary capillary wedge pressure (PCWP), and right ventricular cardiac output (QP). PVR (in Wood Units (WU)) was calculated using the formula: PVRRHC = ΔP/QP, where ΔP is the trans-pulmonary pressure gradient (ΔP = mPAP − PCWP) and QP is the flow in the pulmonary artery measured by the Fick principle using the pulmonary artery oxygen saturation.The study was approved by the Institutional Review Board (IRB) and all subjects provided written informed consent. Patients with suspected PH who had undergone standard-of-care RHC were identified. Patients with a mPAP ≥ 25 mmHg at rest, or mPAP > 30 mmHg during exercise, were recruited to undergo a research cardiac MRI protocol within 28 days of the RHC procedure. The control group consisted of healthy age- and sex-matched volunteers without any cardiac disease. Venous blood hematocrit was measured at the time of scan. Enrollment began in August 2017 and ended in March 2020. Our exclusion criteria were: allergy to gadolinium-based contrast agents; severe kidney disease (estimated glomerular filtration rate < 30 mL/min/1.73 mPH patients were classified by MV (cardiologist 5 years) based on a review of their clinical courses, therapeutic histories, and hemodynamic measurements. Patients’ clinical courses and therapeutic histories were considered in addition to hemodynamic measurements, during classification, because invasive parameters are known to vary with a patient’s fluid and metabolic status and it has been suggested that hemodynamics should be interpreted in the context of the clinical picture . For theThe cardiac MRI protocol was performed by certified technicians using a 1.5T MRI system . A three-plane fast localization sequence was used to determine anatomic orientations for subsequent sequences, and four-chamber, two-chamber, and short-axis localizer views were obtained. The native T1 portion of the protocol consisted of multiplanar segmented balanced cine steady state free precession (bSSFP) and native T1 mapping (modified Look-Locker inversion recovery (MOLLI) technique). After contrast administration , LGE and MOLLI T1 mapping sequences were performed . The combined duration of the MRI sequences was 30 min.The bSSFP cine acquisition was performed in the two-, three-, four-chamber, and short-axis orientations. Data were acquired during breath-holds at end-expiration using retrospective electrocardiogram (ECG) gating. Cine sequence MRI parameters were as follows: field of view (FOV) read = 340 mm × 340 mm, spatial resolution = 1.8 mm × 1.8 mm × 6.0 mm, temporal resolution = 35.49 ms, flip angle = 80°, echo time/repetition time (TE/TR) = 1.16/35.49 ms.2, GRAPPA with an acceleration factor, R = 2. Imaging reconstruction included the auto-calculation of parametric LV T1 maps.The GRE bSSFP MOLLI acquisitions were collected pre- and post-contrast (delay = 10 min) with sequence parameters as follows: TE 1.33 ms, flip angle 35°, slice thickness 8.00 mm, pixel size = 1.0 × 1.0 mm2, GRAPPA with an acceleration factor, R = 2) a segmented 2D IR gradient recalled echo (turboFLASH) pulse sequence . Inversion times for each scan were carefully selected by identifying the TI that best nulls the normal myocardium signal (range: 260–340 ms)  , or global ECV and RHC measurements  .A group of 79 subjects was assessed. The initial patient cohort comprised of 25 control subjects , 29 PrePH , 19 IpcPH , and 6 CpcPH patients. CpcPH patients were excluded because of the distinct impairment of both ventricles making it impractical to test the relationships between MRI-based fibrosis measurements and ventricular function [Across all subjects, global LGE was associated with worse LV function. Global ECV and native T1 measurements, however, did not show any statistically significant associations. Statistically significant and moderate  correlatGiven the small number of CpcPH patients (n = 6), this cohort was excluded from inter-group comparisons.p = 0.45). Patients showed elevated global ECV and global native T1, compared to controls   . Segment < 0.05) .p = 0.756; 1056.2 ± 36.3 ms vs. 1042.4 ± 28.1 ms, p = 0.229) (p = 0.102), although the difference was not significant. A significantly higher LGE percent was found in the lateral wall  of IpcPH patients  when compared to the PrePH patients   . Global ctively) . Septal ctively) .p = 0.782) and the LGE mural extent determined by rater 1 vs. rater 2 (p = 1.000).Cohen’s Kappa showed fair  agreemenOur exploratory proof-of-concept study showed several differences and associations related to myocardial fibrosis in PH. Previous studies have reported associations between RV fibrosis  higher amount of LGE compared to PrePH patients. Discordance between ECV and LGE has been seen elsewhere. In a study by Treibel et al., LGE was found to correlate with collagen volume fraction whereas ECV did not . TreibelIf additional studies corroborate the differences observed in this work, a reduced need to rely on RHC for PH workups may result. Currently, there is a class Ic recommendation for the use RHC in patients with suspected PH and left heart or lung disease to assist in the differential diagnosis and support treatment decisions . FibrosiDisease progression or remission may have occurred during the time between RHC and cardiac MRI. Patients were therefore classified based on a consideration of RHC, volumetric, and clinical information. Another study did similar, and grossly considered  all PrePH, without reference to RHC values . Second,Cardiac MRI-based tissue characterization may augment understanding of cardiac involvement and become a tool to facilitate PH patient classification. Regional quantitative assessments of native T1 (and ECV) and qualitative assessments of LGE mural location appear to be the most promising parameters to assess in future studies.


In recent years, attention has shifted to the role of right ventricular (RV) dysfunction in prediction of clinical outcome among patients with septic shock. However, very few studies have correlated RV dysfunction with survival early in the course of sepsis. In the period from September 2021 to July 2022, we included a total number of 248 patients within 24 h of their presentation with sepsis. All patients were subjected to a comprehensive echocardiographic study to evaluate different parameters of RV function and LV systolic and diastolic functions. We aimed primarily to study the predictive value of RV dysfunction on 30-day all-cause mortality rates and ventilator-free days.isolated RV dysfunction. Patients with RV dysfunction had a significantly higher APACHE 2 (P < 0.001) score and 30-day all-cause mortality rates (P = 0.003) compared to those without RV dysfunction. A significant association was reported between 30-d mortality and dysfunction status (P = 0.025). Those with no dysfunction had lower mortality (14.1%) than in those with RV dysfunction only (33.3%), LV dysfunction only (20%), and RV + LV dysfunction (31.6%). No significant difference was observed in ventilator free days according to dysfunction status (P = 0.081). A multivariate logistic regression analysis showed that RV dysfunction was among the significant independent predictors for 30-day mortality , controlling for the effect of age and gender.Almost half of study population (48.4%) showed evidence of RV dysfunction (in isolation or with LV dysfunction), with 25.4% showing evidence of In a cohort of ICU patients with early sepsis, RV dysfunction is found to be common and predictive of 30-day mortality irrespective to the LV function. Sepsis or septic shock is a clinical syndrome characterized by augmented and dysregulated immune-inflammatory response to infection, that could culminate finally into what’s called “multi-organ dysfunction” . One of The ventricular interdependence is an interesting phenomenon in which the RV can keep pace with the LV for proper overall heart pump function. However, in sepsis, the RV affection in terms of decreased preload and increased afterload adversely affects the RV ability to be in concordance with the LV .Earlier and recent studies evaluating the RV function in patients with sepsis had several limitations including but not limited to the fact that they had no correlation with survival , 6, and primary clinical outcome) and ventilator free days . We included patients who met the following inclusion criteria:Age 20–70 years.Smokers and nonsmokers.Had a clinically suspected infection.Had two or more systemic inflammatory response syndrome criteria.Had either septic shock  or severe sepsis (defined in this study as serum lactate > 4 mmol/L) . This could be explained by the higher APACHE 2 score, the lower prevalence of isolated LV diastolic dysfunction in Michael et al.’s cohort.In contrast to Michael et al.  who did The current study is not without limitations. First, the observational nature of the study hinders any causal claims behind the link of RV dysfunction and survival in patients with sepsis. Second, we did not use RV strain as an assessment tool for RV function, but this could be relatively understood if we know that there is a gap of knowledge about the normative data from larger cohorts for RV strain that could be used as cutoffs to define RV dysfunction in those patients. Third, the vast majority of our patients presented earlier in the course of sepsis than late. We were expecting that ventilator-free days will be sewed to a higher value representing the whole length of hospital stay and follow-up period, as those patients were presenting earlier i.e., relatively healthier. That’s why we assigned it as a secondary outcome. And this was exactly the case when we were analyzing the data to generate the results. We found that the ventilator-free days value was non-normally distributed i.e., skewed to a higher value, and the maximum was the most frequentist (median 30 [range 0–30]), reflecting the relatively healthier patient effect. This prevented us from using it as a continuous variable of meaningful predictive ability or dichotomizing it into 2 categories, as it will yield non-comparable groups and non-valid statistical results. Finally, all our study patients are medical ICU ones, so our findings may not be extrapolatable to other categories of patients.In a cohort of ICU patients with early sepsis, RV dysfunction is found to be common and predictive of 30-day mortality irrespective to the LV function. Extreme caution should be exercised before using RV dysfunction improvement as a target for improving outcomes of those patients in general.