Ventricular assist devices have become a valuable tool in the treatment of heart failure in children. The use of ventricular assist devices has decreased mortality in children with end-stage heart failure awaiting transplant. It is not uncommon for children with end-stage heart failure associated with cardiomyopathy or congenital heart disease to have significant systemic semilunar and atrioventricular valve regurgitation, which can impact the efficiency and efficacy of hemodynamic support provided by a ventricular assist device. Therefore, implanting clinicians should carefully assess for valve abnormalities that may need repair and impact device selection and cannulation strategy to effectively support this diverse population. The purpose of this review is to provide an overview of this important and relevant topic and to discuss strategies for managing these patients. VADs that are used for long-term support in children, which in the United States currently include the EXCOR Pediatric device  and the HeartMate 3 device , can serve as a bridge to heart transplant or, in rare cases, as a bridge to recovery in children with end-stage heart failure. The majority of children undergoing heart transplantation either have cardiomyopathy or end-stage congenital heart disease (CHD) that results in severe systolic and/or diastolic ventricular dysfunction and over the past two decades, the presence of VAD support in children eventually undergoing heart transplantation has doubled . Althoug2.The affected heart valve, type of valve lesion , type of VAD, and VAD cannulation sites influence the impact of valvular heart disease on the efficiency of VAD support. In the following discussion of each abovementioned factors, we will use the scenario of a VAD supporting the systemic circulation in a biventricular heart. This discussion can be extended to the scenario of a VAD-supported pulmonary circulation as well as a VAD-supported single ventricle heart.de novo AI after VAD implantation have higher localized wall shear stress on the aortic valve leaflet tips as compared to VAD patients who did not develop AI . In the most common situation of the VAD inflow cannula placed in the left ventricle and the VAD outflow connected to the aorta, aortic valve insufficiency (AI) would lead to the recirculation of VAD flow and thus loss of systemic cardiac output , 7 Figu. The extvelop AI .Since the AI is often continuous with continuous-flow VADs, even “mild to moderate” continuous AI can be deleterious . Becauseas long as the aortic valve is competent. The same cannulation strategy can also be successful in the setting of heart failure with preserved systolic function, a competent mitral valve, and a mildly insufficient aortic valve. In this scenario, VAD recirculation would be prevented by the competent mitral valve and the LV with normal systolic function should be able to eject the regurgitant volume from the mildly insufficient aortic valve. Certainly, this arrangement would not be tolerated if the left ventricular systolic function was decreased as left ventricular dilation would result in subsequent MR and impact right ventricle function.In the scenario of the VAD inflow cannula placed in the left atrium, mitral valve insufficiency (MR) may be well tolerated Mitral valve stenosis can limit the efficiency of VAD output if the inflow cannula is positioned in the left ventricle and significant gradients (mean > 10 mmHg) have been recommended as a reason to intervene on the mitral valve in adult patients . If the The type of VAD can also influence the clinical impact of mitral valve regurgitation. The EXCOR Pediatric VAD is a paracorporeal, pulsatile device and is used in infants and small children , 25. The3.There is a paucity of data on valve dysfunction and concomitant valve procedures performed at the time of VAD implant in pediatrics. One series of 45 patients with Fontan circulation supported with VAD reported severe atrioventricular valve regurgitation in 43%, mild aortic insufficiency in 28%, and moderate aortic insufficiency in 8% of patients . The pre4.Diagnosis of valvular heart disease in pediatric patients considered for VAD support or after the initiation of VAD support is usually diagnosed by transthoracic echocardiography . Transesde novo or progressive AI after VAD implantation because of the increased transvalvular gradient caused by enhanced pressurization of the aorta (In patients who develop he aorta , the comhe aorta , 34. Furhe aorta .5.In general, surgical intervention for regurgitant heart valves are either repair or replacement. A multitude of techniques have been developed for mitral valve repair and several options exist for mitral valve replacement in older children –38. Tech5.1.There is a dearth of literature describing mitral valve procedures in pediatric patients undergoing VAD implantation. The adult-focused literature, on the other hand, has demonstrated that significant, functional MR is common in patients undergoing VAD implantation , 39, 40,On the other hand, in children being considered for pulsatile flow VAD implantation, those with moderate or greater regurgitation should undergo mitral valve repair. In children with hypertrophic or restrictive cardiomyopathy and with a continuous flow device, mitral valve replacement may not be appropriate for the smaller hearts, for whom an atrial location for the inflow cannula or complete excision of the obstructing systemic atrioventricular valve is indicated. While complex and elegant repair techniques have been developed for regurgitant mitral valves , these oventricular side of the mitral valve apparatus. The remainder of the VAD procedure is undertaken. The edge-to-edge technique adds little cardiopulmonary bypass time and does not require a separate access incision to visualize the mitral valve. It is, however, a view of the mitral valve that surgeons are not particularly familiar with, which leads many surgeons to be uncomfortable about employing this technique.The edge-to-edge technique of mitral valve repair was introduced in the late 1990s by Alfieri and colleagues . The orivia a trans-septal incision, while on cardiopulmonary bypass, and without arresting the heart (Annuloplasty repair techniques for mitral valve repair are popular as adjuncts to complex mitral valve repair in the setting of degenerative MR in adults. In the setting of VAD implantation, annuloplasty is typically performed he heart . Unlike 5.2.Multiple single center studies have demonstrated that AI post LVAD implantation in adult patients can lead to poor clinical outcomes and ongoing heart failure , 48, 49.The insufficient aortic valve in the pediatric patient undergoing VAD implantation can be repaired with a central coaptation stitch . In thisAnother strategy to eliminate aortic valve insufficiency in pediatric VAD patients is complete valve closure. In this technique, if the leaflets are durable enough to hold sutures, then suturing them together can be more expedient than replacement. In infants with especially thin aortic leaflets, valve closure can be accomplished by excising the leaflets and suturing a patch to the annulus to accomplish a partition between the left ventricle aorta . An impo5.3.Tricuspid regurgitation can be the result of primary annular dilation as well as leaflet and subvalvar apparatus abnormalities. In the setting of a biventricular circulation with a VAD supporting a failing, systemic left ventricle, a leftward septal shift can induce tricuspid regurgitation, which can be prevented by titrating VAD speed gradually under echocardiographic monitoring of septal position and tricuspid valve function . Tricuspde novo tricuspid regurgitation that is associated with increased mortality after LVAD implantation is a surrogate marker of right ventricle dysfunction and poor right heart cardiac output. Tricuspid valve repair may be beneficial in instances where there is primary morphological abnormalities of the valve and adequate or recoverable right ventricle function. However, it is not as evident if tricuspid valve repair in the setting of functional tricuspid regurgitation and a dysfunctional right ventricle would provide any benefit. Further, it has been reported that tricuspid valve repair for at least moderate tricuspid regurgitation does not confer any survival benefit after LVAD implantation in adults, possibly due to a significant recurrence of tricuspid regurgitation (de novo or preexisting tricuspid regurgitation on outcomes in pediatric VAD patients are lacking. Nonetheless, most pediatric heart surgeons are familiar with tricuspid valve repair techniques, and thus we feel that it is reasonable to repair an insufficient tricuspid valve in pediatric patients with depressed right ventricle function. In smaller children, a suture annuloplasty at the commissures is usually sufficient, while in larger children, an annuloplasty ring can be implanted.However, significant tricuspid regurgitation that persists or develops after LVAD implantation in adult patients is associated with increased mortality , 59. OnePulmonary valve insufficiency can occur in pediatric patients with congenital heart disease who had prior transannular patch or right ventricle to pulmonary artery conduit placement. These patients would need replacement with a valved conduit or bioprosthetic valve in the setting of a right-sided VAD placement should there be significant native or conduit valve insufficiency.6.The patient was a 9-day-old, 2.7 kg female born at full term who presented with tachypnea, retractions, and cyanosis. An echocardiogram in clinic was notable for poor left ventricle function and she was immediately admitted to the intensive care unit. She was intubated for respiratory distress and started on empiric antibiotics. She was then transferred to our center for further care. Echocardiogram upon transfer demonstrated severely reduced left ventricle systolic function, mildly depressed right ventricle systolic function, and no semilunar or atrioventricular valve insufficiency. She was then evaluated and listed for heart transplantation. Five days after admission, the patient developed hemodynamic instability despite increased inotrope infusions and thus underwent urgent cannulation for venoarterial extracorporeal membrane oxygenation followed by balloon atrial septostomy for additional decompression of the left heart. She was then transitioned to a Berlin Heart EXCOR VAD two weeks later. Echocardiogram prior to VAD implantation demonstrated the presence of a nonrestrictive atrial septal defect with left to right shunting, severely depressed left ventricle systolic function, left ventricle dilation, mild mitral insufficiency, moderate and continuous AI , mildly 7.Durable VADs have improved the outcomes of children with end-stage heart failure. The efficacy of VAD therapy in children is affected by valvular heart disease. Clinicians treating pediatric VAD patients need to understand how valvular heart disease can impact the efficacy of VAD support in the varying scenarios of cannulation arrangement, type and location of the valvular heart disease, and type of device. Knowledge of the different surgical techniques to address an insufficient semilunar or atrioventricular valve in the pediatric VAD patient is also important in maximizing the efficacy of VAD therapy while minimizing the risk of surgery and preserving ventricular function. Much of the evidence guiding the current management of pediatric VAD patients with valvular heart disease is taken from the published experience in adult VAD patients and therefore future investigation should specifically study this area to provide pediatric-relevant practice guidelines.


However, the optimal metrics and image acquisition timing required to quantify the disease burden remain uncertain.Various parameters derived from technetium-99m pyrophosphate  and cardiac PYP activity (CPA). We also calculated the SUVmax ratios of myocardial SUVmax/blood pool SUVmax, myocardial SUVmax/bone SUVmax, and the SUVmax retention index. We assessed the correlations between uptake parameters and the four functional parameters associated with prognosis, namely left ventricular ejection fraction, global longitudinal strain, myocardial extracellular volume, and troponin T. CPV and CPA correlated more closely than the SUVmax ratios with the four prognostic factors. Significant correlations between volumetric parameters and prognostic factors were equivalent between 1 and 3 hours.We retrospectively evaluated 99mTc-PYP SPECT/CT than SUVmax ratios and the performance was equivalent between 1 and 3 hours.The disease burden of ATTR-CM was quantified more accurately by volumetric evaluation of The online version contains supplementary material available at 10.1007/s12350-023-03353-w. ATTR-CM can be non-invasively diagnosed in patients without light-chain cardiac amyloidosis using bone scintigraphy with technetium-99m pyrophosphate (99mTc-PYP), 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), or 99mTc-hydroxymethylenediphosphonate.5 Recently, bone scintigraphy has been actively investigated not only for diagnosis, but also for assessments of cardiac function, disease burden, prognosis, and response to therapy.19Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure (HF) resulting from the myocardial deposition of misfolded protein fibrils.99mTc-PYP scintigraphic images using three-dimensional single-photon emission computed tomography (SPECT) are useful for assessing the ATTR-CM disease burden and prognosis.14 Accurate quantitation also enables interval monitoring of disease progression and responses to treatment. However, an optimal method has not been established. Uptake parameters such as the standardized uptake value (SUV), the SUV ratio , as well as volumetric parameters have been investigated using images acquired at various timing. Most studies have investigated 99mTc-PYP SPECT images acquired 3 hours after radiotracer injection to minimize the influence of relatively high blood pool activity at 1 hour.11 Blood pool activity is particularly important for patients without ATTR-CM because it can result in false-positive diagnoses. However, the optimal method for diagnosis, including cohorts without ATTR-CM, is not necessarily the same as that for assessing disease burden.14 This should be determined based on cohorts with ATTR-CM.20 Moreover, images acquired at 1 hour after radiotracer injection have a unique feature that is lacking in images acquired at 3 hours; myocardial abnormal uptake on bone scintigraphic images peaks at 1 hour, then slowly declines.20Various quantitative parameters derived from 99mTc-PYP volumetric parameters or SUVmax ratios are more effective for quantifying ATTR-CM disease burden at 1 and 3 hours after radiotracer injection.The aim of this study was to define whether 99mTc-PYP SPECT/CT at Kanazawa University Hospital between September 2019 and February 2023 and diagnosed with ATTR-CM from endomyocardial biopsies (EMBs) and/or TTR gene tests. The diagnostic criteria for ATTR-CM were based on one or more of the following: (1) EMB positive for ATTR and (2) having a documented TTR genetic mutation and evidence of cardiomyopathy without apparent plasma cell dyscrasia (serum and urine immunofixation and serum-free light-chain assays). When patients had undergone multiple 99mTc-PYP tests during follow-up, only one was included in the present study. The ethics committee at Kanazawa University approved this study and waived the requirement for written informed consent because the study retrospectively selected patient data.We retrospectively evaluated patients who were assessed by 99mTc-PYP. Thorax planar images were acquired for 2 min at 1 and 3 hours later using a hybrid SPECT/CT system  with a low-energy high-resolution collimator. The acquisition time of 2 minutes was acceptable for 750,000 counts in Japanese patients. Before November 2021, SPECT/CT images of the thorax were acquired only 1 hour after radiotracer injection. Thereafter, SPECT/CT images were acquired at both 1 and 3 hours after injection. The SPECT/CT parameters comprised step-and-shoot acquisition with body-contour non-circular orbit, 120 steps at 15 s/each with a total acquisition time of 20 minutes, and zoom 1.0.Patients were injected intravenously with ~ 740 MBq (20 mCi) of Images were reconstructed to a 128 × 128 matrix using a dedicated iterative algorithm (xSPECT QUANT) with 72 iterations and 1 subset, and a 10-mm Gaussian filter. A low-dose, free-breathing, and non-contrast CT image was acquired for attenuation correction and anatomical localization using the following parameters: 130 kV, 50 mAs with care dose, pitch 1.5, rotation time .6 s, collimation 16 × 1.2. The CT-based attenuation and scatter corrections were performed automatically.99mTc-PYP activity in an aortic blood pool using SUVmax. A spherical volume of interest  was positioned in the center of the ascending aorta at the level of the pulmonary artery bifurcation on fused SPECT/CT images.21 A polygonal VOI was manually placed to include uptake by the left and right ventricles, but not adjacent ribs and the sternum.10 Total volumes of voxels in the myocardial regions with 99mTc-PYP uptake > 1.2, 1.4, and 1.6 × the SUVmax of the aortic blood pool were automatically evaluated using xSPECT Quant and defined as cardiac PYP volumes .10 We visually confirmed that the abnormal uptake areas were in the myocardial regions. The threshold values of 1.2, 1.4, and 1.6 were based on our previous study.10 We also defined cardiac PYP activity (CPA) as CPV × , using SUVmean in myocardial regions with uptake > 1.2, 1.4, and 1.6 × aortic blood pool SUVmax .9 CPA reflects the volume and intensity of abnormal uptake. We used SUVmean, which reflects the average uptake in the abnormal uptake areas, to evaluate CPA.22Figure 21 If T12 was not intact, the spherical VOI was placed at the nearest normal vertebral body. We then determined the soft-tissue SUVmax by positioning a spherical VOI at the paraspinal muscle near T12. Myocardial SUVmax/aortic blood pool SUVmax,23 myocardial SUVmax/vertebral SUVmax,24 and SUVmax retention index16 =  × paraspinal muscle SUVmax were calculated and we referred to them as SUVmax ratios.We also evaluated SUVmax within the entire left and right ventricular myocardium. We determined bone SUVmax by placing a spherical VOI at the center of an intact thoracic vertebral body .5 The H/CL ratio was calculated as the fraction of the average counts in a circular region of interest (ROI) drawn over the heart of a planar image to that in the contralateral lung ROI of the identical size. The visual grading score was determined by comparing myocardial uptake to rib uptake .We also evaluated the heart to contralateral lung (H/CL) ratio and the visual grading score.We acquired CMR images using a 3.0-T MRI scanner . Native and postcontrast T1 maps were acquired using a modified look-locker technique (with a 5-3-3 beat scheme), under the following parameters: repetition time, shortest; echo time, shortest; flip angle, 20°; slice thickness, 10 mm; matrix, 160 × 160; field of view, 30 cm. Postcontrast T1 maps were scanned 7−10 minutes after 10 mL (1.0 mol/L) of Gadovist  was injected. The myocardial extracellular volume (ECV) was calculated as the ratio of changes in myocardial to blood relaxation rates and adjusted to the fractional blood volume of distribution (1—hematocrit). The T1 values were quantified on ROI from the myocardium  and the blood (left ventricular blood pool) on both native and contrast T1 maps. The largest possible ROIs were manually drawn, avoiding regions of misregistration (cross-hatched areas) between images at each inversion time. We then applied a copy-and-paste technique to place the same shape ROIs at the exact location on native and postcontrast T1 maps. Thereafter, we calculated the ECV using the average value of each ROI.Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were assessed by echocardiography. High-sensitivity cardiac troponin T values, hematocrit (Ht), and estimated glomerular filtration rates (eGFR) were measured by blood examination.25 GLS,27 ECV,28 and troponin T25).We assessed the performance of quantifying disease burden. We evaluated correlations between uptake parameters  and functional parameters associated with prognosis .Continuous variables summarized as means ± standard deviation (SD) were compared using Student’s t-tests. Uptake parameters were compared between 1 and 3 hours using Student’s t-tests for paired comparisons. Categorical variables were summarized as numbers (%). Visual grading scores were compared between 1 and 3 hours using Wilcoxon signed-rank test. Correlations between parameters were assessed using Pearson correlation coefficients . Interobserver variability was assessed using an intraclass correlation coefficient (ICC) and Bland-Altman analysis. Values with 99mTc-PYP injection. Thirteen of them were also assessed by SPECT/CT at 3 hours because we changed the imaging protocol in November 2021, and they included patients who had been diagnosed with hereditary ATTR-CM and treated with tafamidis  was excellent at .990, and the interobserver variability was low , whereas SUVmax ratios did not significantly correlate with GLS. Myocardial SUVmax/vertebral SUVmax and the SUVmax retention index did not significantly correlate with ECV and troponin T. Myocardial SUVmax did not significantly correlate with any of the prognostic factors . The H/CL ratio and visual grading score did not correlate with LVEF, GLS, and troponin T.Both CPV1.4 and CPA1.4 significantly correlated with the four prognostic factors , excluding right ventricular activity. The CPV1.4 and CPV1.4LV similarly correlated with the four prognostic factors  than CPV1.2 and CPA1.2 (r2 = .37−.62).Table 99mTc-PYP injection. At 3 hours, neither CPV1.2 nor CPA1.2 significantly correlated with troponin T, whereas CPV1.4, CPV1.6, CPA1.4, and CPA1.6 correlated significantly and comparably with the four prognostic factors.Table 99mTc-PYP SPECT/CT, CPV and CPA quantified the ATTR-CM disease burden more accurately than SUVmax and SUVmax ratios. The performance of the volumetric parameters was equivalent between 1 and 3 hours after injecting 99mTc-PYP.This study has two important messages. The volumetric parameters derived from 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) are more effective than SUVmax as prognostic predictors in cancer.22 Volumetric parameters were more effective than the H/CL ratio, which is valuable and widely applied, but has inherent limitations due to being based on two-dimensional images. The H/CL ratio did not correlate with LVEF, GLS, and troponin T  and a more effective prognostic factor than all other echocardiographic parameters, including LVEF, in patients with HF and reduced LVEF.26 Impaired GLS is similarly a high risk factor for cardiovascular morbidity and mortality in patients with HF and preserved LVEF.27 Furthermore, the ECV determined by CMR has been validated for measuring the amyloid burden and it is an independent predictor of prognosis (HR: 1.155 per 3% increase).28 Bone scintigraphy can be an alternative modality for patients who cannot undergo contrast-enhanced CMR. High-sensitivity cardiac troponin T is used to assess prognosis in patients with ATTRwt-CM.25We found here that CPV and CPA significantly correlated with the four prognostic factors, LVEF, GLS, ECV, and troponin T. Therefore, CPV and CPA should play objective and important roles in prognostic evaluation. An echocardiographic LVEF reduced to < 50% predicts mortality in patients with wild type ATTR-CM (ATTRwt-CM).99mTc-PYP scintigraphy is a useful modality for evaluating prognosis. A volumetric parameter on 99mTc-PYP SPECT/CT images acquired 3 hours after injection and ECV correlated .7 Even CPV and CPA derived from 99mTc-PYP SPECT without CT significantly correlated with LVEF and CMR parameters, and had prognostic value and low interobserver variability.9 However, studies without CT did not correct attenuation or scatter. They acquired images only after 3 hours and applied filtered back projection. A multicenter study found that even the two-dimensional H/CL ratio of 99mTc-PYP scintigraphy can deliver prognostic information.30Other studies similarly support the notion that 99mTc-PYP uptake quantified by SUVmax was significantly higher at 1 hour than at 3 hours .12 The diagnostic ability of 99mTc-PYP three-dimensional SPECT is comparable between 1 and 3 hours.35 Delayed acquisition has been reported as a cause of false-negative diagnoses of ATTR-CM.36 Oncological 18F-FDG PET image acquisition at 1 hour is popular and delayed acquisition is optional. The expert consensus recommendation for image acquisition timing using 99mTc-PYP was 1 hour in 2019.5 This consensus was revised to recommend image acquisition at 2 or 3 hours with 1 hour as optional. The main reason for this was to avoid false-positive diagnoses caused by excessive blood pool activity.37 The blood pool activity is particularly important in patients without ATTR-CM. However, the optimal method for diagnosis, including cohorts without ATTR-CM, is not necessarily the same as that for assessing disease burden,14 which should be assessed based on cohorts with ATTR-CM.20The present findings supported the notion that the time-efficient acquisition of nt Table . Thus, l99mTc-PYP uptake,33 which we identified in some of our patients with EMB-proven ATTR-CM . However, some patients with ATTR-CM have focal or absent 10 That finding and those of images acquired at 1 and 3 hours herein Supplementary file2 (PPTX 301 kb)Below is the link to the electronic supplementary material.


Background: Left ventricular systolic and diastolic functions are known prognosticators for cardiovascular morbidity. One of the significant risk factors for cardiovascular diseases is obesity. The objective of this study is to determine the effect of obesity on the systolic and diastolic functions of the left ventricle on the basis of echocardiographic indices.Methods: 75 obese and 75 averagely built subjects were studied. They had no other comorbidities. The indices of echocardiography of systolic and diastolic function were taken and assessed using recent recommendations from the European Association of Cardiovascular Imaging and the American Society of Echocardiography.Results: The volume indices of systolic and diastolic function (ejection diastolic volume (EDV) and ejection systolic volume (ESV)) and iso-volumetric relaxation time (IVRT) showed a significant increase in obese subjects (p<0.05); however, the relative thickness of the wall and internal diameter were comparable to non-obese subjects. The indices of contractility like ejection fraction, early diastolic filling velocity and late diastolic filling velocity (E/A) ratio, and mitral annular velocity were significantly lower in the obese subjects as compared to non-obese subjects. It was also found that left atrial diameter in systole and diastole had a moderate association  while mitral inflow E/A ratio had a negative association with body mass index (BMI) .Conclusions: Volumetric changes and ejection are significantly altered by increased BMI. More comprehensive studies in the future are recommended to assess the same. Obesity is a global health issue as it is constantly increasing in worldwide prevalence, from 4.6% in 1980 to 14.0% in 2019; while in India, its prevalence was reported to vary from 11.8% to 31.3% [According to research, it is a lone predictor of eventual heart failure estimating up to 11% of all cases in men and up to 14% in women and accounts for about 45% of the increased risk of coronary heart disease ,7. AdditAs it impairs the LV's capacity to pump blood and fill with blood, left ventricular diastolic dysfunction (LVDD) has been linked in cohort studies to an increased risk of developing heart failure with a median prevalence rate of 11.8% (range of 4.7%-13.3%) in older adults -15. HencA total of 150 apparently healthy subjects were selected for this study following approval from Institutional Ethical and Research Board, and informed written consent was obtained from all patients participating in the study.The patients were categorized using the convenient stratified sampling method into two groups namely, Group A - obese (case) group and Group B - non-obese (control) group. The sample size was estimated based on the previous study by Chadha DS et al. in 2010 and considering the standard mean difference of ejection fraction (EF) (0.4%), power (80%), alpha error (5%), and a dropout rate of 10% .Study populationPatients reporting for medical examination to the Datta Meghe Medical College, Nagpur, between August 2021 and May 2022 were screened.Inclusion criteriaPatients above the age of 18 years were included.Exclusion criteriaPregnant females; patients with medical conditions like hypertension, diabetes mellitus, or dyslipidemia; patients with previous history or clinical evidence of coronary artery disease, heart failure, or cardiac valve disease; patients with respiratory disease; patients with the presence of chronic or acute disease; patients taking drugs that could affect the heart; patients with abnormal EF, valvular disease, regional hypokinesia on echocardiography; and individuals involved in competitive sports are excluded.Operational definition2, with clear evidence of excessive subcutaneous adipose tissue on physical examination as per the WHO guidelines for the South Asian population. Obesity was defined as a BMI of >25 kg/m2): a normal weight (control) group had a BMI of <25 kg/m2, the overweight group had a BMI of 23-24.9 kg/m2, obesity group had a BMI greater than 25 kg/m2 [The participants in the study were further classified into three groups using physical examination by the primary investigator who is a trained clinician based on the BMI cut-off points  of 0.79, negative predictive value (NPV) of 0.74, and overall accuracy of 0.89, and it was performed using a standardized protocol by a trained sonographer who is blinded to the study .Conventional diastolic function assessment was performed using an apical view and the following parameters were assessed Tables  and 2Statistical analysisFor statistical analysis, SPSS V.22.0 software  was used. The results for categorical variables were presented as numbers and percentages. Continuous variables were presented as mean and standard deviation (SD). We evaluated the accuracy of our echocardiographic system in detecting LVDD based on its sensitivity, specificity, PPV, and NPV. Pearson’s correlation analysis was used to examine the associations between BMI and echocardiographic parameters of LVDD. To compare echocardiographic parameters among three groups of obese patients, variance analysis using one-way ANOVA was used for continuous variables, and post hoc analysis was carried out using Tukey’s HSD test. A P value of <0.05 was considered to indicate a statistically significant result.The measured demographic variables of left ventricular systolic and diastolic function in the case and control groups are displayed in Table Post hoc analysis among the three groups found no significant difference among echocardiographic parameters of the obesity and overweight groups (P>0.05) Table .Correlation of BMI and echocardiography parametersA Pearson bivariate correlation test was used to assess the echocardiographic parameters and BMI. The mitral inflow E/A ratio was shown to have a negative correlation with BMI , but no other metrics were found to be significantly correlated. Left atrial (LA) diameter showed a moderate relationship in both systole and diastole  . Our results are comparable to Wong CY et al. and Kossaify A et al. who showed an alteration in LV morphology ,22. HoweThe E/A ratio was much lower in obese participants due to an increased late diastolic filling and a mostly stable early diastolic filling velocity. This might be because obese people's LVs tend to relax unusually and depend more heavily on left atrial contraction for appropriate filling ,22.In their investigation, Garg et al. discovered that 35% of obese participants and 53% of overweight subjects both had diastolic dysfunction with normal EF . While tContrarily, Chakko et al. did not discover any significant variations in the values of E, but they did discover an increase in the values of A, which led to a decrease in the E/A ratio . Hassan The methods utilized to evaluate the LV systolic function may be the cause of this disparity. Newer echocardiographic techniques can detect subclinical LV functional alterations in a more sensitive way than older echocardiographic techniques, which include measurements like EF, fractional shortening, and circumferential fiber shortening ,30.Reduced mitral annular velocity (Sm), as it was shown in the obese group in our study, is suggestive of early LV systolic dysfunction. It is interesting to note that this discovery has only recently been made in Asian Indians after being previously noted in Caucasians ,32.Increased intravascular volume, activation of the sympathetic and renin-angiotensin-aldosterone systems, abnormal production of myocardial growth factors from abdominal and cardiac adipose tissue, and metabolic changes that increase arterial stiffness and peripheral vascular resistances all play a role in the pathophysiological mechanisms proposed to explain the relationship between obesity and LVH ,25. The Early post-mortem investigations in morbidly obese patients revealed that an increase in epicardial fat and LVH together caused excess heart weight . AccordiOur study's limitations include not taking into account how lipid-lowering medications can affect left ventricular diastolic function. Additionally, we have not considered the impact of the persistence of obesity and the comorbidities that are linked to it.Volumetric alterations and ejection percent varied considerably among patients with higher BMI compared to control participants. The level of obesity will determine how strongly the other echocardiographic indices were affected. We can therefore draw the conclusion that obesity should be taken into account as a risk factor for upcoming cardiovascular events. Our study has limitations as the length of obesity and left ventricular dysfunction did not show the association. To examine cardiovascular morbidities such as heart failure and overall mortality in healthy obese people with changes in cardiac morphology and function, longitudinal investigations are necessary. It is important to determine how weight loss affects cardiac morphology and function.


Contemporary procedural guidelines for percutaneous left atrial appendage occlusions (LAAO) with the WATCHMAN device often require the utilization of pre-screening imaging, general anaesthesia, intubation, a dedicated intra-procedural echocardiographer, and overnight observation. For these reasons, LAAO with the WATCHMAN is not economically feasible for many hospital systems. Thus, we sought to evaluate a newstrategy for implantation that may provide a more minimalistic and less cumbersome approach to LAAO.We describe five cases utilizing single-operator left atrial appendage occlusion utilizing conscious sedation, transoesophageal echocardiography, lack of outpatient pre-imaging, and same-day expedited discharge (SOLO-CLOSE)—a novel single-operator procedural strategy for LAAO that safely foregoes the aforementioned procedural requirements and allows for same-day early discharge. All five patients were observed according to our newly devised SOLO-CLOSE protocol and were safely discharged home the same day. Follow-up transoesophageal echocardiography (TEE) at 45 days and 1 year revealed well-seated and well-anchored devices with no leaks (<5 mm) or device-related thrombi.The SOLO-CLOSE series is the first ever documented WATCHMAN strategy that utilizes a single-operator, TEE-guided, nurse-driven conscious sedation protocol that defers pre-screening imaging and allows for same-day discharge. The versatility of this technique allows proceduralists to comfortably achieve successful LAAO despite a wide range of risk profiles. This single-operator technique has potential to become a widely accepted universal approach for non-pharmacological cardioembolic stroke prophylaxis due to its efficacy, safety, simplicity, and presumable cost-effectiveness. Single-operator left atrial appendage occlusion utilizing conscious sedation, transoesophageal echocardiography, lack of outpatient pre-imaging, and same-day expedited discharge (SOLO-CLOSE) is an efficacious strategy for left atrial appendage occlusion that utilizes a single-operator and nurse-driven conscious sedation protocol that allows for safe and cost-effective outcomes.SOLO-CLOSE has potential to become a widely accepted approach for non-pharmacological cardioembolic stroke prophylaxis for structural heart centres around the world.1 Despite device enhancements, procedural methodology has not followed suit and remains unchanged. Contemporary approaches of LAAO with the WATCHMAN are not economically feasible for many hospital systems as they frequently require the use of pre-screening imaging, general anaesthesia, intubation, an intra-procedural echocardiographer, and overnight inpatient admission. Similar to the transcatheter aortic valve replacement evolution, we demonstrate a previously undescribed strategy for percutaneous LAAO with WATCHMAN FLX using a single-operator and nurse-driven conscious sedation protocol that defers pre-screening imaging and allows for early same-day discharge. We refer to this minimalist LAAO approach as single-operator left atrial appendage occlusion utilizing conscious sedation, transoesophageal echocardiography, lack of outpatient pre-imaging, and same-day expedited discharge (SOLO-CLOSE). We describe five SOLO-CLOSE cases and discuss why it is an appealing percutaneous LAAO strategy for structural heart programmes around the world.Percutaneous left atrial appendage occlusion (LAAO) with the WATCHMAN FLX device is a non-pharmacologic alternative for cardioembolic stroke prophylaxis in patients with atrial fibrillation. In the USA, LAAO is generally performed under general anaesthesia and pre-procedural echocardiographic guidance. The newest iteration—WATCHMAN FLX—has improved ease of deployment, manoeuvrability, and recapturability. Additionally, it met the primary effectiveness end point with a left atrial appendage closure incidence of 100.0% at both 45 days and 1 year.Table 1. We describe the typical procedural methodology. The right femoral vein is chosen as the primary point of access. A procedural oxygen mask with an orifice that allows for the insertion of a transoesophageal echocardiography (TEE) probe while delivering high-flow oxygen is applied to the patient. Nurse-driven conscious sedation protocol is then initiated. A covered TEE probe is then inserted via the perforated orifice to allow for sterile manipulation during the procedure by the operator. Upon completion of anatomical assessment of the left atrial appendage (LAA), the probe is then secured in the bicaval view using wheel-lock mechanisms, towels, and clips. X-plane echocardiography is initiated simultaneously. Thereafter, a standard 12-French sheath is inserted into the right femoral vein under ultrasound guidance. Through this sheath, a 0.035 guide wire is inserted into the superior vena cava, and over this wire, an 8.5-French pre-shaped Baylis VersaCross sheath is introduced. We then exchange out for the Baylis radiofrequency wire and perform a typical inferoposterior trans-septal puncture and advance the Baylis wire into the left atrium followed by the VersaCross sheath. The femoral venous 12-French and VersaCross sheaths are removed over the Baylis wire, and a standard WATCHMAN delivery sheath  is then inserted in sheathless fashion into the left atrium (LA). A 5-French pigtail catheter is then inserted into the WATCHMAN delivery sheath and manipulated into the LAA. In the right anterior oblique caudal projection with concomitant TEE, angiography of the appendage is performed. Based on this and the intra-procedural imaging, the size of the WATCHMAN FLX device is determined. The selected device is then prepared per manufacturer’s recommendations, appropriately deaired, and then positioned using fluoroscopy and the 135-degree view on TEE. We then unsheathe the device slowly and, using the FLX ball technique, ensure that the position of the device is appropriate before releasing the shoulders of the device. We then perform our usual post-deployment assessment including a tug test, and then once position, anchor, size, and seal criteria (PASS) are assessed and met, the device is finally released. All equipment is then removed, and a modified figure-of-eight suture is used for haemostasis. Transoesophageal echocardiography is performed again prior to procedural completion to ensure no pericardial effusion is seen, the device is assessed once more for stability and final position, and lastly, the inter-atrial septum is evaluated for the shunt and its haemodynamic effects to assess for the need for closure. The patient is monitored over the next 4–6 h to determine candidacy of same-day discharge. Table 2 summarizes our criteria for early discharge. Transoesophageal echocardiography is performed immediately prior to discharge. Patients are provided with an emergency department card as well as our structural heart office number in case any complication(s) arise(s). A follow-up phone call is done the next day, and if needed, a clinic visit is scheduled; otherwise, the patient follows up at 45 days for clinical evaluation and repeat TEE.The novelty of the SOLO-CLOSE strategy lays in its requirement of only a single operator to complete the LAAO. Patients with non-valvular atrial fibrillation who wish to undergo the WATCHMAN procedure and are screened appropriately may qualify for the SOLO-CLOSE protocol. Specific deferral criteria are summarized in Figure 1).An 81-year-old female with history of paroxysmal atrial fibrillation on warfarin , transient ischaemic attack, and hypertension developed gastrointestinal haemorrhage related to ulcerations and elevated international normalized ratio. Due to her frailty, the structural heart team elected a SOLO-CLOSE approach. Low-dose intravenous (IV) dexmedetomidine was initiated prior to the procedure with boluses of IV fentanyl and midazolam available as needed. Using the SOLO-CLOSE technique, a WATCHMAN FLX 20-mm device was successfully deployed and released .A 73-year-old male with history of hypertension, non-obstructive coronary artery disease, and paroxysmal atrial fibrillation  presented for LAAO evaluation due to episodes of rectal bleeding. Due to a history of post-anaesthesia confusion, the patient was deemed appropriate for SOLO-CLOSE. Intravenous propofol bolus was administered and a SOLO-CLOSE technique ensued. Small aliquots of propofol, fentanyl, and midazolam were used as needed. Intra-procedural appendage measurements were appropriate for a WATCHMAN FLX 24-mm device, which was deployed and released with no complication .An 81-year-old male with history of diabetes mellitus, gastric ulcers, transient ischaemic attack, chronic diastolic heart failure, non-obstructive coronary artery disease, chronic hypotension, recurrent falls, and long-standing persistent atrial fibrillation  presented for LAAO. Due to co-morbidities, a SOLO-CLOSE approach was elected. Intravenous fentanyl and midazolam were used for sedation. Based on intra-procedural measurements, it was determined that a WATCHMAN FLX 27 mm would be appropriate; this was ultimately deployed without complication .A 90-year-old female with history of chronic diastolic heart failure, hypertension, hyperlipidaemia, colon cancer status post-colectomy, and permanent atrial fibrillation  on dabigatran with recurrent gastrointestinal bleeds presented for LAAO. The SOLO-CLOSE approach was elected. Low-dose IV dexmedetomidine was initiated prior to the procedure with boluses of IV fentanyl and midazolam available as needed. A WATCHMAN FLX 27 mm was deployed without difficulty .A 71-year-old female with history of end-stage renal disease, prior haemorrhagic stroke, hypertension, diabetes mellitus, hyperlipidaemia, chronic diastolic heart failure, and long-standing persistent atrial fibrillation  presented for LAAO. Due to co-morbidities, the SOLO-CLOSE methodologic was utilized. Low-dose IV dexmedetomidine was initiated prior to the procedure with boluses of midazolam available as needed. Oral hydromorphone was administered pre- and post-procedurally. Transoesophageal echocardiography determined that a WATCHMAN FLX 27 mm would be appropriate; this was ultimately deployed without complication (Table 2). They were subsequently safely discharged home on antiplatelet therapy per standard guidelines. Forty-five-day follow-up TEE revealed well-seated and well-anchored devices, with no peri-device leaks (<5mm) or any device-related thrombi .All five patients were observed according to protocol , thus theoretically also improving efficiency and reducing costs. Despite perceived advantages of ICE, there are clear topics of concern: the need for a second venous access, the possibility of a second trans-septal puncture, an increase in thrombotic risk with an additional intra-cardiac device, the need for catheter manipulations in the pulmonary artery/left atrium (perforation risk), non-standard imaging planes, and the lack of standardized criteria for procedural guidance, device assessment, and release. Additionally, ICE imaging requires a greater capital investment in terms of the console, imaging software, and disposable imaging catheters. When considering the aforementioned issues, the use of ICE for LAAO may in fact paradoxically have a negative effect on procedural efficiency and economics.Contemporary proceduralists are invoking an alternative method of simplifying LAAO by utilizing intra-cardiac echocardiography (ICE).Table 2). Prior to discharge, our patients are provided with an emergency contact card linked to our emergency department and structural heart clinic which patients may utilize should any post-procedural complications arise. Otherwise, a follow-up nurse phone call is made the following day and a clinical visit is scheduled only if needed. All patients then undergo follow-up with TEE at 45 days and 1 year per standard protocol. As many transcatheter procedures were also once deemed complex procedures requiring overnight admission , we anticipate that LAAO will similarly also evolve and follow suit. Successful evolution requires large-scale studies to develop and validate clearly delineated criteria for same-day discharge candidacy, similar to that which we have attempted at our institution (Table 2). Recent and ongoing studies reveal no difference in safety or efficacy of LAAO between same-day and next-day discharge patients.13–16 Furthermore, this approach has potential to significantly reduce resource utilization and costs while improving patient and provider satisfaction.Lastly, a cornerstone to the SOLO-CLOSE strategy is same-day discharge. Our criteria for qualifying for same-day discharge included an uncomplicated procedure, use of vascular haemostasis devices, a minimum of 4 h of an uneventful observation period, baseline oxygenation and ambulation status, completion of a limited pre-discharge TTE demonstrating no peri-device leakage, and patient agreement to next-day follow-up if needed (17As with any procedure, single operators utilizing SOLO-CLOSE should be trained and equipped to identify and manage any potential procedural complications which include but are not limited to respiratory depression and cardiac tamponade. Conscious sedation should be monitored by the proceduralist and nursing personnel that are appropriately trained in managing supplemental oxygen delivery and providing appropriate antidotes. Further, LAAO often requires the operator to perform a posterior and inferior transeptal puncture to have a coaxial trajectory to the main body of the LAA. Although rare, this may lead to accidental puncture of the muscular portion of the septum which can lead to a delayed tamponade or effusion. In many such instances, single operators have the immediate ability to alter their own imaging to evaluate the pericardial space and expeditiously guide therapeutic pericardiocentesis.The SOLO-CLOSE protocol has not been studied extensively and is our group’s attempt at evolving the methodology of LAAO. Due to its inherent learning curve, procedure times for the SOLO-CLOSE may initially be prolonged but are expected to significantly improve with proficiency and will allow for synchronization between device manipulation and echocardiographic intra-procedural imaging. We anticipate that the SOLO-CLOSE methodology will significantly reduce healthcare costs. However, large-scale prospective observational studies are needed to further assess the efficacy and safety of this approach.Our series is the first documented WATCHMAN strategy that utilizes a single-operator, TEE-guided, nurse-driven conscious sedation protocol that defers pre-screening imaging and prioritizes same-day discharge. The versatility and ubiquitous applicability of this technique allows proceduralists to comfortably achieve successful LAAO despite a wide range of risk profiles. We believe SOLO-CLOSE has potential to become a widely accepted approach for non-pharmacological cardioembolic stroke prophylaxis due to its efficacy, safety, simplicity, and potential for cost-effectiveness.


Longer pulmonary transit time (PTT) is closely associated with hemodynamic abnormalities. However, the implications on heart failure (HF) risk have not been investigated broadly in patients with diverse cardiac conditions. In this study we examined the long-term risk of HF hospitalization associated with longer PTT in a large prospective cohort with a broad spectrum of cardiac conditions.All subjects were prospectively recruited to undergo cardiac magnetic resonance (CMR). The dynamic images of first-pass perfusion were acquired to assess peak-to-peak pulmonary transit time (PTT) which was subsequently normalized to RR interval duration. The risk of HF was examined using Cox proportional hazards models adjusted for baseline confounding risk factors.Among 506 consecutively consented patients undergoing clinical cardiac MR with diverse cardiac conditions, the mean age was 63 ± 14 years and 373 (73%) were male. After a mean follow up duration of 4.5 ± 3.0 years, 70 (14%) patients developed hospitalized HF and of these 6 died. A normalized PTT ≥ 8.2 was associated with a significantly increased adjusted HF hazard ratio of 3.69 . The HF hazard ratio was 1.26  for each 1 unit increase in PTT which was higher among those preserved  compared to those with reduced left ventricular ejection fraction (< 50%) . PTT remained a significant risk factor of hospitalized HF after additional adjustment for N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) or left ventricular global longitudinal strain with additionally demonstrated incremental model improvement through likelihood ratio testing.Our findings support the role of PTT in assessing HF risk among patients with broad spectrum of cardiac conditions with reduced as well as preserved ejection fraction. Longer PTT duration is an incremental risk factor for HF when baseline global longitudinal strain and NT-proBNP are taken into consideration. There is an extensive body of work examining the central circulation time spanning nearly a century using a predominantly invasive approach in the classic literature –7 and no2; claustrophobia; pacemaker/defibrillator implantation or other metallic hazards and significant atrial or ventricular arrhythmia. Patients referred for stress testing were not recruited for this study. All participants who consented to participate completed a questionnaire for demographic information and past medical history at time of enrollment (baseline) along with a CMR exam . Clinical charts were reviewed to confirm cardiovascular history in all subjects. The primary outcome of interest was hospitalized heart failure after their CMR examination and was identified from electronic medical records shared by a healthcare system consisting of 6 hospitals on Long Island, NY. Vital statistics were confirmed using the National Death Index in addition to medical records.The study protocol was approved by the St. Francis Hospital Institutional Review Board. Participants were recruited prospectively and written informed consent was obtained from all. Most of the participants were recruited from those who were referred for clinical cardiovascular magnetic resonance (CMR). The exclusions were the same for all participants, including impaired renal function with glomerular filtration rate (GFR) less than 45 ml/min/1.73 mA blood sample was collected for N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) before CMR for most of the study subjects. NT-proBNP was measured using an electrochemiluminescence immunoassay .2. To determine transit time, dynamic images at rest were acquired every cardiac cycle over at least 50 and up to 100 cardiac cycles in a sagittal plane where the main pulmonary artery and left atrium were well defined and additionally in a coronal view where the ascending aorta was well visualized during the infusion of 0.01 mmol/kg gadopentetate dimeglumine  at 6 ml/s followed with a 15 ml saline flush. An ECG gated saturation recovery SSFP sequence was used with a typical field of view 500 mm, an inversion time of 90 ms, TE 0.92 ms, imaging acquisition window 160 ms per slice, slice thickness 15 mm and flip angle 50 degrees. Parallel imaging was applied with an acceleration factor of 2.All participants underwent CMR on a 1.5 T scanner  with an 8-element phased array surface coil. Cardiac volumes and systolic function were assessed using balanced steady-state free-precession (SSFP) cine imaging with retrospective ECG gating. Images were acquired during breath-hold in a stack of short axis planes (8 mm thickness with 2 mm gap) and 3 long axis planes  with the following parameters: echo time (TE) 1.3 ms, repetition time (TR) 3.1 ms, flip angle 70° and average in-plane resolution 1.3 × 1.3 mmA phase-sensitive inversion recovery sequence for late gadolinium enhancement (LGE) was performed 10 to 15 min after the administration of 0.15 mmol/kg of gadopentetate dimeglumine on a stack of left ventricular (LV) diastolic short-axis slices with the following parameters: TE, 3.17 ms; flip angle, 25 degrees; voxel size, 1.9 × 1.4 mm; slice thickness, 8 mm; and field of view, 360 × 290 mm. A scout acquisition with increasing inversion time values was performed on a mid-ventricular short-axis slice to determine the inversion time that allowed for optimal nulling of normal myocardium before the LGE images were obtained.Left and right ventricular volumes, ejection fractions (EF) and myocardial mass were assessed from cine CMR images using QMASS software . Left atrial volume was assessed using the biplane area-length method. LGE reading was provided by experienced imaging cardiologists following the clinical guideline . CMR meat-tests, Wilcoxon’s rank-sum test, and χ2 tests as appropriate.Continuous variables were shown as mean ± SD for those variables with normal distribution, and median ± interquartile range (IQR) for those variables that were not normally distributed. Categorical variables were reported as frequency and percentage. PTT normalized by RR interval duration and measured during CMR at baseline was our primary exposure of interest, and time-to-first post-CMR heart failure hospitalization was our primary outcome of interest. The optimal cut point for PTT predicting heart failure hospitalization was determined by maximizing Youden’s Index applied to the receiving operator characteristic (ROC) analysis of a logistic regression model. Youden’s index defines the maximum potential effectiveness of a biomarker by combining sensitivity and specificity for all potential cut points . We compKaplan Meier curves were produced to examine the association between dichotomous PTT with heart failure admission over time, as well as stratified by LVEF ± 50% . Hazard Several post hoc sensitivity analyses were conducted to assess the incremental benefit of improving model fit/predictability of PTT over traditional measurements of heart failure and cardiac function. Among variables consisting of left and right ventricular systolic and diastolic volumes, stroke volumes, masses, left atrial volume, fibrosis evaluated by LGE, LV global longitudinal strain, and separately BNP / NT-proBNP, we used principal component analysis to generate combinations of variables to test PTT against. We added PTT to reduced models containing these aforementioned variables in order to (1) estimate the association between PTT and hospitalized heart failure through additional adjustment for these variables and (2) assess the incremental improved model fit using the likelihood ratio test (LRT)  and contThere were 506 consecutive subjects included in the analysis. The mean age was 63 ± 14 years and 373 (73%) were male. The mean LVEF was 49 ± 12% and there were 209 (41%) subjects with LVEF < 50%. Among diverse cardiac conditions identified by CMR the top three findings were dilated cardiomyopathy, myocardial infarction, and valvular heart disease , left and right ventricular chamber sizes as well as left atrial size were larger, stroke volume smaller and EF lower. The prevalence of infarct scar by LGE was higher. In contrast, the prevalence of non-infarct LGE was slightly lower although it was common in both groups  was associated with reduced survival during follow up compared to those with PTT < 8.2  in the fully adjusted model . This was also true for a model with variables selected through the use of principal component analysis, whereby after adjusting for age, gender, LV end diastolic volume index, RV end systolic volume index, LA volume index, LV global longitudinal strain, and presence of LGE, PTT remained a significant risk factor for hospitalized heart failure with HR 1.15  per 1 unit increase and HR 1.92  for PTT ≥ 8.2 vs. PTT < 8.2.In this prospective study, we demonstrated that longer PTT duration is an independent predictor of hospitalized heart failure in a large clinical cohort with a broad spectrum of cardiac conditions. Among those with longer PTT, there is significantly increased hazard of heart failure hospitalization with the greater hazard among those with LVEF ≥ 50%. We also demonstrated the incremental benefit of using PTT in models predicting hospitalized heart failure after considering not only traditional risk factors such as cardiac volume and function but also LV global longitudinal strain and NT-proBNP.There is extensive literature examining the relationship of PTT with cardiomegaly, systolic dysfunction, pulmonary hypertension and heart failure due to reduced LVEF –17. PTT There have been a number of small studies that reported outcome risk associated with longer PTT duration among patients with pulmonary hypertension  and thosTechnically, PTT can be easily incorporated into routine clinical CMR examination, as the sequence of first pass perfusion is commercially available and the contrast needed is trivial. In our study we only used gadolinium contrast at 0.01 mmol/kg, a small fraction (5–6%) of the dose for late gadolinium enhancement imaging, which provides the signal intensity or image quality adequate for PTT evaluation. In addition, the time-intensity curve to calculate PTT is easily accessible using commercial software and does not require a proprietary program. Therefore, to incorporate PTT evaluation to routine clinical CMR study is feasible. We used sagittal views which are copied from the standard sagittal localizer available for all clinical CMR scans to alleviate the need for acquisition planning.We acknowledge several limitations of our study. PTT is typically assessed between any representative structures of right and left circulation. The common approach is between right and left ventricle or between pulmonary artery and ascending aorta. In our study, we have chosen the main pulmonary artery and left atrium as the anatomic landmarks as they are perhaps the most appropriate chambers to mark the beginning and the end of the pulmonary circulation. Therefore, the absolute PTT value may differ from published results but the relative risk should remain unaltered. When calculating PTT, we used the peak-to-peak approach although there are several alternatives such as full width half maximum or the centroids of the time-intensity curve. Evidently, there are merits and limitations for each method. Nevertheless, we believe peak-to-peak evaluation remains the simplest and can be processed using any commercial software thereby making PTT evaluation clinically accessible. Besides technical differences, the clinical implications of PTT derived from different methods may also vary. As shown in our study, PTT calculated using full width half maximum did not seem to be associated with heart failure risk. To minimize contrast usage, we have kept the contrast dose very low with which we are able to produce adequate signal intensity for PTT analysis. However, larger dose may produce greater contrast signal and aid the post processing. Our cohort consisted of patients referred for clinical CMR with diverse cardiac conditions and levels of function thereby making the observation more generalizable comparing to studies that focus on specific cardiac conditions and types of heart failure. However, we are limited on subgroups analyses as each sub-cohort is relatively small. Lastly, this is a single center study. Future investigations with multicenter designs are warranted.To conclude, longer PTT duration can predict long-term risk of heart failure admission independent of LVEF in patients with broad spectrum of cardiac conditions. We also demonstrated the incremental benefit of using PTT in models predicting hospitalized heart failure after considering not only traditional risk factors such as cardiac volume and function but also LV global longitudinal strain and NT-proBNP. Our findings underscore the value of cardiopulmonary circulation evaluation in the heart failure risk assessment.


However, evaluating the IV fluid ‘dose–response’ curve of the heart is elusive. Two patients were studied in the emergency department with a wireless, wearable Doppler ultrasound system. Change in the common carotid arterial and internal jugular Doppler spectrograms were simultaneously obtained as surrogates of left ventricular stroke volume (SV) and central venous pressure (CVP), respectively. Both patients initially had low CVP jugular venous Doppler spectrograms. With preload augmentation, only one patient had arterial Doppler measures indicative of significant SV augmentation . The other patient manifested diminishing arterial response, suggesting depressed SV  with evidence of ventricular asynchrony. In this  The prescription of intravenous (IV) fluid is a clinical decision most often triggered by signs and symptoms of organ hypoperfusion and guided by traditional vital signs , 2. Howe∆) led to significantly less IV fluid administered and improved patient-centered outcomes [In early sepsis and septic shock, a clinically significant proportion of patients receiving IV fluids do not exhibit SV augmentation and, as resuscitation progresses, more than 90% of patients cease having the anticipated SV-enhancing effect of a crystalloid infusion –8. Imporshort communication, we describe two patients receiving preload augmentation in an emergency department (ED) while monitored by the wearable Doppler; clinical and physiological implications are considered within the framework of a ‘Doppler Starling curve’.We have described a novel, wearable Doppler ultrasound that measures and displays common carotid artery and internal jugular Doppler spectrograms –16. ThesWritten and informed consent was obtained for both patients for publication of this report and accompanying images; the study was approved by the Peoria Institutional Review Board. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. Both patients were recruited from a community emergency department and were deemed in need of IV fluid resuscitation by the treating clinician who was blinded to the results of the wearable ultrasound. The choice for preload augmentation was at the discretion of the treating clinician.The ultrasound patch  is a wearable, wireless, FDA-cleared, continuous-wave 4 MHz ultrasound. Adhesive straps fix the transducer angle relative to the direction of carotid blood flow . The wea∆) and % change in VTI (VTIc∆). The number of cardiac cycles averaged before and during preload augmentation was dictated by the coefficient of variation of each particular measure to ensure change could be detected with statistical confidence [∆ [∆ and +18% VTIc∆ [The Doppler spectrograms were analyzed for the absolute and % change in ccFT  assessment. The 250 mL RFC was administered at a rate of 100 mL/min while the patient remained in semi-Fowler , 36. ThiA 72-year-old man presented to the emergency department with altered mental status, back pain, hypotension, leukocytosis, acute kidney injury and a working diagnosis of sepsis due to lumbar osteomyelitis versus ascending urinary tract infection. He had a known history of tricuspid and mitral band valvuloplasties and diminished left ventricular ejection fraction (LVEF) of 40% consequent to chronic hypertension and ethanol use. His outpatient medications were lisinopril, furosemide and carvedilol. The patient’s intake vital signs were a heart rate of 83 beats per minute, blood pressure of 69/52 mmHg, afebrile with normal respiratory rate and oxygen saturation. His ECG showed a possible ectopic atrial rhythm with incomplete left bundle block pattern. In the emergency department, a PLR was performed prior to IV fluids and the results presented in Table Patient 1 was treated with broad spectrum antibiotics and required norepinephrine infusion to maintain a mean arterial pressure above 60 mmHg. He was transferred to the intensive care unit where trans-thoracic echocardiography showed abnormal septal motion with systolic and diastolic flattening consistent with right ventricular (RV) pressure and volume overload, dilated RV size and reduced RV systolic function with RV hypertrophy. The patient had no significant valvular abnormalities, indeterminate left ventricular (LV) diastolic function, and a left ventricular ejection fraction (LVEF) of 50% while on norepinephrine.A 54-year-old woman presented with shortness of breath and acute hypercapnic and hypoxemic respiratory failure secondary to sepsis from an infected sacral ulcer versus urinary source. She had history of traumatic quadriplegia with chronic sacral wounds complicated by osteomyelitis, indwelling suprapubic catheter, active cigarette smoker, COPD on home oxygen, diastolic dysfunction with congestive heart failure, obstructive sleep apnea and type II diabetes mellitus. She was febrile on presentation with a heart rate of 75 beats per minute, blood pressure 87/51 mmHg, respiratory rate 25 breaths per minute and 93% on 6 L nasal cannula. In the ED she received broad spectrum antibiotics. The patient had a Doppler assessment performed for the first 250 mL of each of the two liters received in the ED. Given her hypotension, the first and second liters were given in rapid succession  and inferior vena cava (IVC) with normal RV systolic function and no valvular abnormalities; the LVEF was 60–65% with normal diastolic function.dynamic fluid intolerance [The baseline, low power, non-pulsatile, high velocity venous Doppler spectrograms observed in both patients strongly suggested jugular vein collapse, indicating low CVP  , 37, 38.olerance .Fig. 4ThRecognizing a state of dynamic fluid intolerance is important clinically because many of these patients might receive physiologically unhelpful preload based upon markers of right heart filling. For example, a CVP of less than 5 mmHg was observed in 25% of fluid unresponsive patients , while iThat the arterial Doppler response of patient 1 implied falling SV during the PLR deserves some elaboration, albeit speculative. Given the results of his trans-thoracic echocardiogram (TTE) performed within hours after his assessment by the wearable Doppler ultrasound, both diastolic and systolic ventricular interdependence likely contributed to impaired LV output. That is, with RV volume overload noted on the TTE, RV diastolic filling during the PLR diminished LV preload via cross-ventricular diastolic stiffening . Furthershort communication is the small, clinical sample size, though this report is not meant to change local clinical practice or protocols. Our objective is to highlight bedside physiology with a novel and potentially helpful clinical biosensor. In both patients neither CVP nor SV was measured, so the data from the wearable Doppler are inferences. Nevertheless, data supporting ccFT∆ as a surrogate for SV∆ have good clinical evidence [∆ correlates strongly with SV∆ in the largest-known Doppler data set making this comparison [∆ for detecting significant SV∆ mirrored that in our healthy volunteer studies [The primary limitation of this evidence  and we hmparison . Further studies . Neverth studies , 50.short communication, we described the clinical application of a novel, wearable, Doppler biosensor in two patients deemed to need IV fluids by clinical examination. Simultaneous venous and arterial Doppler spectrograms are plotted using a novel framework best characterized as a “Doppler Starling curve”. Both patients initially demonstrated venous Doppler waveforms consistent with low CVP, which increased during preload augmentation. However, only patient 2 exhibited simultaneously acquired arterial Doppler changes indicative of rising stroke volume. By contrast, patient 1 displayed dynamic fluid intolerance; evidence from large, randomized controlled trials suggests that this phenotype may be managed by withholding additional IV fluids, ostensibly preventing downstream complication and cost.In this


The study aimed to investigate the alterations of myocardial deformation responding to long-standing pressure overload and the effects of focal myocardial fibrosis using feature-tracking cardiac magnetic resonance (FT-CMR) in patients with resistant hypertension (RH).Consecutive RH patients were prospectively recruited and underwent CMR at a single institution. FT-CMR analyses based on cine images were applied to measure left ventricular (LV) peak systolic global longitudinal (GLS), radial (GRS), and circumferential strain (GCS). Functional and morphological CMR variables, and late gadolinium enhancement (LGE) imaging were also obtained.p < 0.001) with the intake of 5 ± 1 antihypertensive drugs. RH patients showed increased LV mass index , decreased GLS  and GRS , and GCS was reduced by trend . Twenty-one (42%) RH patients demonstrated a LV focal myocardial fibrosis (LGE +). LGE + RH patients had higher LV mass index  and attenuated GRS  compared to LGE − RH patients, whereas GLS (p = 0.146) and GCS (p = 0.961) were similar.A total of 50 RH patients  and 18 normotensive controls  were studied. RH patients had a higher average systolic blood pressure than controls (166 ± 21 mmHg vs. 116 ± 8 mmHg, Attenuation of LV GLS and GRS, and GCS decline by tendency, might be adaptative changes responding to chronic pressure overload. There is a high incidence of focal myocardial fibrosis in RH patients, which is associated with reduced LV GRS.Feature-tracking CMR-derived myocardial strain offers insights into the influence of long-standing pressure overload and of a myocardial fibrotic process on cardiac deformation in patients with resistant hypertension.Variations of left ventricular strain are attributable to the degree of myocardial impairment in resistant hypertensive patients.• Focal myocardial fibrosis of the left ventricle is associated with attenuated global radial strain.• Feature-tracking CMR provides additional information on the attenuation of myocardial deformation responding to long-standing high blood pressure.• The online version contains supplementary material available at 10.1007/s00330-023-09595-z. Among other cardiovascular risk factors hypertension remains a major cause of cardiovascular mortality worldwide . ResistaA recent work offers an overview of speckle-tracking echocardiography (STE) in assessing LV dysfunction in hypertension . The expTherefore, the main purpose of this study was to investigate the alterations of myocardial deformation responding to long-standing pressure overload and to elucidate the degree of myocardial impairment using FT-CMR. The secondary objective was to identify the potential effects of focal myocardial fibrosis in RH patients.The prospective study was approved by the local research ethics committee and complied with the Declaration of Helsinki. All participants gave written informed consent. This study recruited consecutive RH patients at a single institution and included 16 patients who were recruited in a previously publication . The ini2), (2) significant stenosis and prior stenting or dilatation of renal arteries, (3) myocardial infarction < 6 months before planned renal denervation, (4) diabetes mellitus type I, and (5) persisting atrial fibrillation ). Ten minutes after a bolus injection of 0.2 mmol/kg gadoteric acid  at a rate of 2.5 mL/s late gadolinium enhancement (LGE) images were acquired using an end-diastolic phase-sensitive inversion-recovery sequence in short-axis direction covering the entire heart and in 2-, 3-, and 4-chamber views.CMR was performed on a 1.5-T scanner equipped with a 5-channel cardiac-phased array receiver coil . Standard retrospectively gated, ECG-triggered steady-state free-precession cine images (25 phases per cardiac cycle) were acquired in short- and long-axis  views using a breath-hold technique with the following typical parameters: acquired voxel size 1.98 × 1.80 × 6 mm2 for men and > 61 g/m2 for women [CMR images were post-processed independently and blindly using a commercially available software . CMR parameters are given as the mean of two investigators and are indexed to body surface area (BSA). For LV volume and mass evaluation, the endo- and epicardial contours were delineated in systole and diastole in a stack of short-axis cine slices covering the whole LV with inclusion of the papillary muscles as part of the LV volume . For rigor women . Focal mor women , 15. LV t-test or Wilcoxon signed rank-test as appropriate. Categorical data are presented as absolute numbers (percentage) and were compared using χ2 test or Fischer’s exact test as appropriate. Multivariate linear regression analyses were conducted to identify the independent associations of clinical and CMR-derived parameters with strain. p < 0.05 was regarded as statistically significant.All statistical analyses were performed using SPSS  and GraphPad Prism (version 9.2.0). All continuous data were checked for normality using the D’Agostino-Pearson omnibus normality test. Numerical variables are presented as the mean ± SD. Differences of continuous data between the groups were performed using the independent samples p = 0.839) and age (p = 0.055) between RH patients and normotensive controls. RH patients had higher BSA (p = 0.004) and body mass index (BMI) (p < 0.001) than controls. Office systolic blood pressure (SBP) (166 ± 21 mmHg) and diastolic blood pressure (DBP) (91 ± 17 mmHg) were elevated in RH patients despite the intake of 5 ± 1 antihypertensive drugs. The mean of 24-h ABPM, SBP, and DBP of the patient group were 149 ± 18 mmHg and 84 ± 16 mmHg, respectively  and 18 normotensive controls  were eventually enrolled. A flowchart of the study is presented in Figure p = 0.276) and LV/LA volumes, but markedly increased LV mass index  compared to controls. In the patient group, 28 (56%) had LVH. No differences were observed between the groups regarding RV function and volumes. Feature-tracking analyses showed attenuated LV GLS  and GRS  in RH patients. LV GCS had a downward tendency   RH patients, a focal myocardial fibrosis (LGE +) of the LV was detected. A total of 7 ischemic and 14 non-ischemic LGE patterns were visualized as shown in Fig. p < 0.001), increased LV mass index was found in both LGE − (p = 0.004) and LGE + (p < 0.001) RH patients. The two RH subgroups and controls had similar cardiac functional and anatomical parameters. Compared to normotensive controls, LV GLS was decreased in LGE +  and LGE − RH patients , GRS was decreased in LGE + RH , but not in LGE − RH patients  (Table p = 0.101) and LGE + (p = 0.127) RH patients, but a trend for attenuation.LGE − and LGE + RH patients had significantly higher BMI and office SBP than controls   than LGE − RH patients. Age (p = 0.727) and BMI (p = 0.842) were similar. Office SBP  and DBP , ABPM SBP  and DBP  were similar. CMR revealed a higher LV mass index in LGE + RH patients with 85 ± 14 g/m2 than in LGE − RH patients with 73 ± 15 g/m2 (p = 0.007). Patients with LVH had a similar distribution between the LGE − and LGE + RH subgroups. No significant differences regarding cardiac function and volumes were observed (Table p = 0.048) compared to LGE − RH patients, whereas there were no differences in LV GLS  and GCS   Table . LGE + RR =  − 0.443, p = 0.001 and R = 0.466, p < 0.001, respectively), GRS , and GCS   and GRS . LVESVi and LVSVi were independently associated with LV GCS  , LVESVi was independently associated with LV GRS , and LVESVi and LVSVi were independently associated with LV GCS   and LV mass index in RH patients were associated with LV GLS  RH patients had significantly higher LV mass index and attenuated LV GLS and GRS in comparison to normotensive controls, whereas GCS was attenuated by trend; (2) 21 RH patients (42%) demonstrated a focal myocardial fibrosis (LGE +), predominantly localized in the basal inferior and inferolateral LV segments; (3) in the subgroup analysis, LGE + RH patients had a markedly reduced LV GLS compared to controls, attenuated GRS compared to LGE − RH patients and controls, and GCS was also attenuated by trend; and (4) LV mass index and stroke volume index were associated with multidirectional strain in RH patients.In this study, a decrease of LV GLS and GRS was observed in RH patients compared to normotensive controls, GCS did not differ statistically, but showed a decreasing trend. LV strain is sensitive to and influenced by afterload alteration , and itsThe alterations in radial and circumferential strain are more complex compared to longitudinal strain, especially with the progression of the given disease and the presence of LVH. Imbalzano et al detected reduced longitudinal strain by STE in hypertensive patients both with and without LVH, and those with LVH had reduced radial and increased circumferential strain . Wang etOf note, in the current study, there was a borderline difference of age between controls and RH patients; age-dependency may contribute to the compensation of age-related LV stiffness by radial strain . HoweverTaken together, our results support the notion that the attenuation of longitudinal and radial strain in RH patients might constitute a LV adaptation as a response to a long-standing pressure overload. The tendential decrease of circumferential strain might be explained with the subepicardial layer being affected to a lesser degree in this RH patient cohort.Recently, an observational study reported that 145 (18%) of 786 patients with essential hypertension had non-ischemic LGE; they were more likely to be men and had greater LV mass and decreased strain . Also, WMyocardial fibrosis is a common end point of many cellular and noncellular pathological processes in hypertension; the severity and duration of hypertension might be responsible for the development of cardiac remodeling , 27. In  − and LGE + RH patients, compatible with an early decrease of longitudinal systolic function. However, while LGE − RH patients showed similar radial strain compared to controls, a worsening radial strain emerged in LGE + RH patients.Our results showed that reduction in longitudinal strain was observed in both LGEGenerally, radial strain has been shown to have large ranges between studies and the variability of segmental strain remains rather high . NeverthEarlier echocardiographic studies have investigated the effects of myocardial fibrosis on LV deformation through identifying the association of plasma markers of myocardial fibrosis with strain alterations. Kang et al found increasing tissue inhibitor of matrix metalloproteinase (TIMP)-1 in hypertensive patients with normal LVEF correlated with attenuation of longitudinal strain, whereas circumferential and radial strain were not attenuated . PoulsenThe sample size in our study was small, which may have had an influence on the power to identify differences between study groups. However, all participants were recruited consecutively and prospectively according to the stringent selection criteria; future studies with larger populations are warranted to corroborate the consistency and reproducibility of our preliminary findings. Second, although some risk factors had been adjusted for multivariate regression analyses, several potential confounders, such as the dosages of antihypertensive drugs and sodium intake, may have an additional effect. Age-matching of controls and RH patients was not precise, but a multivariate analysis did not alter the results after adjustment for age. Another limitation is the lack of detailed information about the duration of hypertension. Nevertheless, all recruited patients were classified as RH according to the ESC guidelines and extensive diagnostics had been previously performed at our tertiary university medical center excluding secondary causes of hypertension. It can be assumed that hypertension has been developing over a long period of time during the aging process in the vast majority of the current elder cohort. Further, FT-CMR is performed mainly based on a block-matching algorithm, which requires a careful tuning of the search region and solving for displacements between short-distance regions . Thus, rOur study revealed that attenuation of LV global longitudinal and radial strain as well as the tendency of circumferential strain attenuation might be consecutive adaptations responding to long-standing pressure overload in RH patients, and global circumferential strain attenuation only by tendency might be attributable to a still partially preserved subepicardial layer. Further, focal myocardial fibrosis has a high incidence in RH patients, presents primarily with a non-ischemic LGE pattern predominantly localized in the basal inferior and inferolateral LV segments, and is associated with reduced global radial strain. Therefore, FT-CMR-derived myocardial strain offers insights into the influence of long-standing pressure overload and of a myocardial fibrotic process on cardiac deformation in RH.Supplementary file1 (PDF 168 KB)Below is the link to the electronic supplementary material.


The pathophysiological effects of chronic right ventricular pacing and the role of right ventricular lead position are not well understood. Therefore, we investigated the association between left ventricular contractile dyssynchrony and pacing-induced cardiomyopathy (PICM) in patients with chronic right ventricular pacing. Furthermore, we assessed the association between right ventricular lead location and left ventricular contractile dyssynchrony.This was a retrospective study using data from 153 pacemaker patients with normal (≥ 50%) pre-implant left ventricular ejection fraction (LVEF). Baseline and follow-up echocardiograms were analyzed, and PICM was defined as LVEF < 50% with ≥ 10% decrease in LVEF after pacemaker implantation. Relative index of contractile asymmetry (rICA), a novel strain rate-based method, was calculated to quantify left ventricular contractile dyssynchrony between opposing walls in the three apical views. Right ventricular lead position was categorized into anterior septum, posterior septum, free wall, and apex based on contrast-enhanced cardiac computed tomography.p < 0.001). Thirty-seven (24%) leads were implanted anterior septal, 11 (7.2%) posterior septal, 74 (48.4%) apical, and 31 (20.3%) free wall. Left ventricular anterior-inferior dyssynchrony was significantly different between the four pacing lead locations (p < 0.01) with the highest rICA observed in the posterior septal group (1.30 ± 0.37).Forty-seven (31%) developed PICM. Overall contractile dyssynchrony, measured by mean rICA, was higher in the PICM group compared with the non-PICM group . Left ventricular anterior-inferior dyssynchrony, assessed in the apical two-chamber view, was independently associated with PICM (PICM is significantly associated increased contractile dyssynchrony assessed by rICA. This study suggests that especially left ventricular dyssynchrony in the anterior-inferior direction is associated with PICM, and pacing the right ventricular posterior septum resulted in the highest degree of anterior-inferior dyssynchrony. Quantification of left ventricular dyssynchrony by rICA provides important insights to the potential pathophysiology of PICM and the impact of right ventricular lead position. Driven by the dyssynchronous activation of the myocardium, right ventricular (RV) pacing may have detrimental effects on left ventricular (LV) function resulting in pacing-induced cardiomyopathy (PICM) , 2. It hThe RV septum is a complex electroanatomical structure. Pacing from various RV septal regions may result in different activation patterns possibly with no advantage over non-septal pacing , 8. FurtSpeckle tracking echocardiography (STE) has over the years provided important information on myocardial function and mechanical dyssynchrony , 11. HowIn patients with chronic RV pacing, we investigated the association between LV contractile dyssynchrony and PICM. Furthermore, we assessed the association between RV lead location and LV contractile dyssynchrony.This was a retrospective cohort study including 153 patients who had been implanted with a dual chamber pacemaker at Aalborg University Hospital between March 2012 and May 2020 due to advanced atrioventricular (AV) block. Advanced AV block was defined as second-degree AV block Mobitz type II, 2:1 AV block, higher degree AV block with ≥ 2 consecutive P-waves not conducted and third-degree AV block. All patients had preserved LV ejection fraction (LVEF) (≥ 50%) prior to pacemaker implantation and a high pacing burden (RV pacing ≥ 40%). Patients were excluded if they were unable to attend a study follow-up visit  or unable or unwilling to provide informed written consent. Furthermore, patients with competing cause of decreased LVEF , device complications with replacement of the RV lead ≥ 3 months after implantation, or contraindications to iodinated contrast agents for cardiac computed tomography (CT) were excluded.Pre-implant characteristics were obtained by review of electronic medical records. RV pacing percentages were obtained from pacemaker interrogation reports. Participants attended a study-specific follow-up visit including transthoracic echocardiography for assessment of contractile myocardial activation and contrast-enhanced cardiac CT to confirm the RV lead position.The study was approved by the North Denmark Region (31-1521-103) and study participants signed an informed written consent form. The study was not considered as an interventional study after evaluation by the North Denmark Region Committee on Health Research Ethics and was therefore exempt from requiring formal ethical approval.-1. Analyses were subsequently performed offline using EchoPAC® software . Using transaortic continuous wave Doppler trace, the duration of systole was calculated as the time from QRS onset to aortic valve closure. LVEF was calculated using Simpson’s biplane method by two experienced physicians. PICM was defined as LVEF < 50% with ≥ 10% decrease in LVEF after pacemaker implantation.Pre-implant and follow-up echocardiograms were obtained and analyzed. ECG-gated transthoracic two-dimensional echocardiography was performed during RV pacing at study follow-up. Standard apical two-chamber (2CH), three-chamber (3CH), and four-chamber (4CH) images were acquired using a 2.5 MHz transducer. For each image, three consecutive paced cardiac cycles excluding ectopic beats were stored in a cine-loop format for offline analyses. Images for strain analyses were acquired at a high mean frame rate of 106 ± 18 sThe ICA method is described in detail in the method paper by Zaremba et al. . In shorWhile ICA is a measure of contractile dyssynchrony, negative systolic strain rate is related to myocardial contractility . To adjuFurthermore, rICA was calculated from echocardiograms performed in 10 healthy individuals with no history of cardiovascular disease and used as controls.n = 42). If no scan was available, a study-specific CT scan was performed at the follow-up visit (n = 111). The scans were performed using a second-generation dual source scanner . The scans were ECG-synchronised and performed during breath hold at the end of inspiration. Administration of contrast was timed for optimal visualisation of both the right and left ventricle.RV lead position was determined from cardiac CT. A contrast-enhanced CT scan was obtained for all patients. Some patients had a high-quality contrast-enhanced CT scan with clear visualisation of the RV lead tip available at study follow-up  analysis was applied to assess the predictive performance of rICA. Cutoff values were calculated corresponding to the Youden index. Modified Poisson regression with robust variance estimation was used to estimate relative risks (RR) between groups. Two-sided tests were applied and p = 0.3). There was a median pacing percentage of 96.5% (85.8–99.8) with no difference between the PICM and non-PICM group .During follow-up, 47 31%) developed PICM and an overall reduction in LVEF of 8% ± 10% was observed. Pre-implant characteristics at time of pacemaker implantation are shown in Table % developp < 0.001). Therefore, rICA 2CH was chosen for further analyses.The radar plot in Fig. ROC analysis of rICA 2CH for prediction of having PICM yielded an area under the curve (AUC) of 0.73 [95% confidence interval (CI) 0.65–0.82]. A cutpoint of rICA 2CH of 0.90 had a 70% sensitivity, a 72% specificity, a positive predictive value (PPV) of 52%, and a negative predictive value (NPV) of 84% for PICM. rICA 2CH ≥ 0.90 yielded a RR of 3.4 (95% CI 2.0-5.8) for having PICM. Changing the outcome to LVEF ≤ 40% yielded an AUC of 0.82 (95% CI 0.74–0.90). Looking at follow-up LVEF ≤ 40%, a 0.90 rICA 2CH cutpoint had a 90% sensitivity, a 66% specificity, a PPV of 29%, and a NPV of 98%. rICA 2CH ≥ 0.90 yielded an RR of 12.9 (95% CI 3.1–53.7) for having a follow-up LVEF ≤ 40%.p = 0.000 for each view). The linear regression slopes were not significantly different between the three apical views (p = 0.80). However, the regression slope for mean rICA was significantly steeper and the correlation higher compared jointly with the regression slopes for the three apical views (p = 0.003).Figure Determined by cardiac CT, the RV lead was implanted throughout the RV endocardium with 37 (24%) located on the anterior septum, 11 (7.2%) located on the posterior septum, 74 (48.4%) located in the apical region and 31 (20.3%) located on the free wall.Mean rICA was borderline significantly different between the four RV lead groups Table . In the The radar plot in Fig. In this study, using rICA for detailed assessment of LV dyssynchrony in chronically RV paced patients, we found: ① Both magnitude and location of LV dyssynchrony were significantly associated with PICM and reduction in LVEF. ② Anterior-inferior LV dyssynchrony assessed by rICA in the 2CH view was highly predictive of having PICM. ③ RV lead location was significantly associated with both magnitude and location of LV dyssynchrony with the highest degree of LV dyssynchrony observed in those paced from the posterior septum.This study supports that LV mechanical dyssynchrony is a driving factor in PICM , 15. It Different echocardiographic techniques to assess LV mechanical dyssynchrony have been developed over the years. Early on, methods like M-mode and pulsed Doppler have been used to assess wall motion delay or delay in RV an LV outflow as indicators of dyssynchrony . Later, Building on the initial experiences with ICA, we indexed ICA to the mean negative systolic strain rate in this study to make the assessment of LV contractile dyssynchrony independent of myocardial contractility. This yielded a more balanced parameter of dyssynchrony in a pacemaker population with heterogenous myocardial contractility. Using rICA, we comprehensively investigated both the degree and location of LV mechanical dyssynchrony, thus providing new insights to the pathophysiology of RV pacing.Generally, we found that pacing the anterior septum, apex and free wall resulted in similar activation patterns with rICA being lowest in the 2CH view and highest in the 3CH and 4CH view. In contrast, the posterior septum group showed consistently high rICA in all views. The differences in LV activation patterns between the RV lead positions may be explained by differences in recruitment of the specialized conduction system as well as the RV lead position relative to the LV. In this study, the apical and free wall groups were not further divided into anterior and posterior. However, looking at the distribution of the septal leads, most leads were located anteriorly. Thus, it is likely that the distribution is similar in the apical and free wall groups with the majority of the leads being implanted anteriorly. Therefore, those three categories may all primarily induce early anterior LV activation resulting in similar LV activation patterns. This is merely hypothetical and should be investigated in future studies.In a previous study, using the same RV lead categories, we found no significant association between RV lead position and risk of PICM . MeanwhiThe potential detrimental consequence of pacing the RV posterior region is in line with a study by Vančura et al., who investigated the acute effects of RV pacing from 18 different RV locations on invasive LV hemodynamic measures . They foThe vast majority of clinical studies searching for the optimal RV lead position, have applied a simplistic, often binary, categorization of RV lead locations. However, any categorical RV location may demonstrate large electroanatomical variations , 19. ConThis was a single-center retrospective study with a relatively small sample size limiting its power, especially when dividing the RV lead position into four categories for comparison. Also, as study inclusion was done after pacemaker implantation, there is a risk of selection bias. The study did not consider clinical endpoints which would have contributed to a more comprehensive evaluation of the consequences of RV pacing. Assessment of dyssynchrony was done in a follow-up echocardiogram after a median of 3.1 years of follow-up and baseline assessment of RV paced dyssynchrony was not available. Consequently, this study is not predictive of developing PICM but should be considered more descriptive when concluding on the effects of chronic RV pacing on LV mechanical dyssynchrony. However, a substudy of Protect-PACE, a randomized controlled trial comparing RV apical and non-apical pacing, demonstrated consistent levels of LV dyssynchrony with no significant changes during the 2-year study follow-up period . TherefoResults from this first study, applying rICA to assess LV mechanical dyssynchrony in chronically RV paced patients, revealed that PICM is significantly associated increased rICA. This study suggests that especially LV dyssynchrony in the anterior-inferior direction is associated with PICM and pacing the RV posterior septum resulted in the highest degree of anterior-inferior dyssynchrony. Quantification of LV dyssynchrony by rICA provides important insights to the pathophysiology of PICM and the impact of RV lead position.