VTI/S′VTI) describes systolic–diastolic coupling. We evaluated these parameters in 69 healthy subjects and found that PSD correlated negatively with GWE  and E′VTI/S′VTI , but positively with GWW  and IVRT . GWE correlated negatively with GWW  and IVRT , but positively with E′VTI/S′VTI . In addition, E′VTI/S′VTI was negatively correlated with GWW  and IVRT . These associations remained significant after adjustment for sex, age and LV mass index of the subjects. In conclusion, there is an interaction between measures of LV asynchrony, myocardial work, diastolic function and its systolic–diastolic coupling in middle-aged healthy subjects. The clinical value of these interactions requires further investigation.In echocardiography, peak strain dispersion (PSD) is the standard deviation of the time to peak longitudinal strain for each left ventricular (LV) segment during systole. It assesses the coordination and synchrony of LV segment contractility. Global work efficiency (GWE) and global wasted work (GWW) quantify LV myocardial work and, if impaired, the coupling between LV systolic contraction and early relaxation. Isovolumetric relaxation (IVRT) measures the duration of initial LV relaxation, while the ratio of early diastolic recoil to systolic excursion (E′ As assessed by speckle-tracking echocardiography (STE), global longitudinal peak systolic strain (GLPSS) can detect early myocardial systolic dysfunction even when the left ventricular ejection fraction (LVEF) remains normal . STE hasPeak strain dispersion (PSD) represents the standard deviation of the time-to-peak longitudinal strain for each left ventricular (LV) segment over the entire cardiac cycle . It evalLV pressure–strain loops are used to assess the myocardium by several parameters. Global work efficiency (GWE) and global wasted work (GWW) are two commonly used examples ,13,14,15Abnormal GWW and GWE have been reported in cardiac patients ,17,18,19Afterload is the pressure the LV must exert to eject blood during contraction. Changes in afterload affect stroke volume and end-systolic and end-diastolic volumes and pressures. The LV isovolumetric relaxation time (IVRT) is the first LV diastolic parameter that afterload may modify ,22,23. BVTI) reflects the total upward movement of LV segments toward the apex. In contrast, the velocity integral of the early diastole (E′VTI) quantifies the total downward movement during the early LV filling. The E′VTI/S′VTI ratio is considered an index of LV systolic–diastolic coupling.Tissue Doppler measures tissue velocities of LV segments in different places, for example, at the level of septal and lateral parts of the mitral annulus during systole and diastole. The velocity time integral for the systolic part (S′LV compliance reflects how easily this ventricle stretches in response to blood filling during early diastole. The nadir of early diastolic tissue Doppler velocity (E′) represents the velocity at which the mitral annulus moves downward during early diastole and how the mitral annulus relaxes. The peak value of the early diastolic mitral valve flow velocity (E) by pulsed-wave Doppler shows the early filling of the LV by blood from the left atrium. The E/E′ ratio is an approximation of the LV filling pressure and thus LV compliance.The Frank–Starling principle states that the extent to which ventricles are stretched with blood during diastole is related to the force of contraction during systole . In otheVTI/S′VTI combines systole and early diastole beyond IVRT. Mutual associations among these parameters are uncertain. To address this issue, we designed this study to investigate peak strain dispersion in relation to myocardial work indices, IVRT and systolic–diastolic performance in a group of healthy people.PSD and GWE are mainly associated with LV systole. GWW can include both LV systole and early diastole. IVRT represents early diastole, while E′No known acute or chronic illness—participants were required to have no documented history of acute or chronic illness;Absence of signs and symptoms of acute disease—individuals were assessed for any physical signs or complaints related to underlying disease;No chronic medication use, except for oral hormonal contraception in women of reproductive age;Smokers were allowed to participate in the study;Occasional use of nonsteroid anti-inflammatory drugs for occasional pain relief  was allowed, except for 48 h before ECG and echocardiography.For the study, we used a set of rules for participants’ screening, selection and enrollment. To identify healthy participants, we used the following criteria:Brachial blood pressure;Standard 12-lead ECG recordings were obtained to assess the presence of sinus rhythm and to detect any abnormal findings;Transthoracic 2D echocardiography using a GE Vivid E95 platform. All potential participants underwent a comprehensive clinical evaluation consisting of the following components:Only good-quality images and cine loops were accepted to accurately measure left ventricular longitudinal strain and myocardial work (MW) during postprocessing. In addition, the following technical requirements were mandatory for all healthy participants: no myocardial contractile abnormalities or clinically significant valvular disease. Participants were not eligible if they had valvular disease with more than mild regurgitation or stenosis. Anthropometric measurements  were all made according to standard protocol. Sixty-nine healthy adult volunteers fulfilled all enrollment criteria. All presented sinus rhythm and normal findings on ECG. Brachial blood pressure was acquired by an oscillometric method  in the supine position (mean of three measurements) after 10 min of rest and was <130/80 mmHg.The University Ethics Committee approved the study protocol. Informed consent was obtained from all participants. The Declaration of Helsinki was followed in the study .Transthoracic echocardiography using a commercially available ultrasound system  was performed at rest with the subjects in the left lateral recumbent position. All procedures were performed using standard views according to the recommendations of the American Society of Echocardiography . DigitalVTI) and the early diastolic signal to measure early diastolic excursion (E′VTI). These values were then used to calculate average S′ and E′ velocities, E/E′ ratio and E′VTI/S′VTI ratio [The peak value of the mitral valve early diastolic flow velocity (E) was measured with pulsed-wave Doppler. Tissue Doppler was used to obtain the septal and lateral mitral annular systolic (S′) and early diastolic velocities (E′). Velocity time integrals were measured by tracing the systolic signal to measure mitral annulus systolic excursion . Automatic function imaging was used to automatically track each endocardial and epicardial boundary in the three apical dynamic images, and the region of interest (ROI) was adjusted by correcting the endocardial border or width, if necessary. Peak systolic longitudinal strain was estimated in 6 segments per one view, giving 18 values per patient. The peak strain dispersion (PSD), a synchronization marker of the myocardial contraction in the left ventricle, was calculated. Global longitudinal peak systolic strain (GLPSS) was achieved by averaging over 18 segmental peak systolic longitudinal strain values. Brachial artery pressure was measured before the echocardiographic examination, and GLPSS were used to quantify global LV myocardial work efficiency through the noninvasive LV pressure–strain analysis ,18,19,28For this study, only one cardiologist (A.M.) experienced in clinical echocardiography acquired all echocardiographic images and cine loops, and performed all postprocessing analyses using EchoPAC. We have tested his intrarater variability for tissue Doppler, GLPSS, MW and other measures, and the observed variability was in the range 3–6%, demonstrating the consistency of the measurements performed.p < 0.05.Continuous data had a normal distribution ; results are summarized as mean and standard deviation (SD) . NumbersSixty-nine healthy subjects were examined . Essential clinical and echocardiographic characteristics are presented in The Interrelations between Descriptors of Strain Dispersion, Myocardial Work, Isovolumetric Relaxation and Systolic–Diastolic CouplingVTI/S′VTI correlations. PSD correlated negatively with GWE and E′VTI/S′VTI but positively with GWW and IVRT. GWE correlated negatively with GWW (nearly linearly) and IVRT but positively with E′VTI/S′VTI. Negative correlations were found between E′VTI/S′VTI and GWW or IVRT.VTI/S′VTI are additionally shown in Mutual associations between PSD, GWW, GWE, IVRT and E′p = 0.0611). The associations between IVRT and GWW were still insignificant for the Pearson correlation.Irrespective of participants’ sex, age and LVMI, most reciprocal associations remained statistically significant, as did the Pearson correlation .. There VTI/S′VTI) are interrelated in middle-aged healthy subjects. Specifically, worse systolic function (higher PSD and GWW but lower GWE) is associated with longer IVRT and lower E′VTI/S′VTI. It may imply an impaired early diastolic function and ventricular–arterial coupling.The study found that indices of mechanical dispersion (PSD), myocardial work (GWE and GWW), isovolumetric relaxation (IVRT) and systolic–diastolic coupling (E′VTI/S′VTI), increased GWW and longer IVRT. GWE and GWW are inversely correlated, which is not surprising. The wasted myocardial work increases due to worsened work efficiency. Looking further ahead, longer IVRT translates into an impaired ability of the LV to relax and prepare to be filled with blood from the left atrium. Interestingly, worse GWE and E′VTI/S′VTI are associated with longer IVRT. Finally, E′VTI/S′VTI is impaired when PSD, GWW and IVR increase. Except for the association of IVRT with GWE and GWW, all the associations studied are independent of sex, age and LVMI of healthy subjects.Higher PSD represents increased heterogeneity of LV contraction and is associated with worse GWE, systolic–diastolic coupling  influences global LV performance. E′a et al.  with theVTI/S′VTI worsens when both systolic and diastolic function decline . Notably, these associations were still significant after adjustment for sex, age and LVMI of the subjects.We show that E′Assessing mechanical dispersion, myocardial work, isovolumetric relaxation and systolic–diastolic coupling can provide complementary information on the global and regional LV function and performance in healthy subjects. All of these parameters have demonstrated clinical value ,38,39,40It is important to mention the study’s limitations, which must be addressed in future research. First, it is a medium-sized study conducted only on healthy middle-aged people. Therefore, the results may not apply to other age groups. Second, extrapolating our findings to patients with different diseases, risk factors, conditions and complications may not be justified. Third, this was an observational physiological study. It takes more than observed correlations between different parameters to explain all the physiological mechanisms behind them. We are aware that correlations do not imply causation. A final limitation relates to speckle tracking echocardiography (STE) for analyzing PSD and myocardial work indices.PSD and GWE or GWW are derived from STE and are based on identifying LV deformation in the longitudinal direction. STE is mainly used to quantify LV systolic function. For GLPSS, the relative change in myocardial length from end-diastole to end-systole is assessed. Any problems in obtaining good quality STE automatically carry over to measurements of PSD and myocardial work indices. Some examples are imperfect tracking of myocardial motion in areas of low echogenicity. This can lead to inaccurate strain measurements in these areas.Another limiting factor for STE is the dependence on the imaging plane. The myocardium is not a homogeneous structure, and strains can vary in different regions of the myocardium. For STE, and thus PSD, GWE and GWW, strain measurements are typically made in the apical four-, two- and three-chamber views. Although three planes are commonly used, they are not equivalent to real three-dimensional signal acquisition and strain. Some mathematical approximations are introduced that may affect the final results. Also, any inaccuracies in the plane images will affect the final measurement.Occasionally, it is not possible to obtain good quality images in all three planes—this is often the case in patients with complex cardiac anatomy, obesity, narrow intercostal spaces or atypical heart position in the chest. Other limiting factors associated with STE are more technical, such as the frame rate of the acquired signal, the signal-to-noise ratio, angle dependence and intervendor variability. These factors can limit the accuracy and reproducibility of STE and, therefore, PSD and myocardial work analysis.Unfortunately, strain measurements are not standardized across different software platforms, which may lead to inconsistent results and interpretation. In our study, we used the same echocardiographic system and performed all measurements using the same postprocessing platform. However, differences between echo system vendors may limit the applicability and generalizability of STE-based findings.Despite these limitations, STE is a valuable tool for assessing LV function. The technology continues to improve, and PSD and myocardial work are good examples of this progress. Furthermore, many clinical studies have provided evidence for their practical usefulness in all these measures.We provide new insights into the relationships between mechanical dispersion, myocardial work, isovolumetric relaxation and systolic–diastolic coupling in healthy subjects. These parameters reflect different LV function and performance aspects, such as LV synchrony, efficiency, diastolic relaxation and systolic–diastolic interaction.Investigation of these relationships may be helpful to understand better the physiology and clinical findings of various cardiac diseases that affect LV function and performance, such as ischemic heart disease, heart failure, cardiomyopathies, valvular heart disease, diabetes, obesity, hypertension or atrial fibrillation. Studying these relationships can also help assess the effects of any drug that directly or indirectly affects the myocardium and cardiac function. Such drugs include typical cardiac medications for hypertension or heart failure and other drugs such as chemotherapy with cardiotoxic effects or antipsychotic/antidepressant treatment with cardiac side effects.VTI/S′VTI.The relationships described can also be studied in patients undergoing cardiac surgery, before and after implantation of cardiac devices, treatment of valvular heart disease and nonpharmacological interventions. Many treatment modalities have an impact on LV function and performance. For example, interventions that correct regional wall motion abnormalities may also improve myocardial work efficiency and reduce wasted work. Implanted cardiac devices optimizing LV synchrony may also improve IVRT and E′Nonpharmacological interventions that modify lifestyle or risk factors, such as dietary intervention and increasing physical activity, may also have beneficial effects on PSD, myocardial work, diastolic function, etc. Therefore, these parameters may serve as noninvasive and inexpensive echocardiographic biomarkers to monitor the response and outcome of various therapeutic modalities in patients with impaired LV function and performance.Overall, there is interaction between measures of LV asynchrony, myocardial work, diastolic function and its systolic–diastolic coupling in middle-aged healthy individuals. These parameters provide complementary information on global and regional LV function and performance. How these interactions change in different clinical conditions and whether any treatment can modify them is unknown and deserves further study.


A 56-year-old man with no significant past medical history presented with exertional shortness of breath. Echocardiogram, cardiac magnetic resonance, and computed tomography showed mitral stenosis and a left atrial thrombus. Left atrial thrombus formation is a well-known complication of severe mitral stenosis that can lead to systemic thromboembolism. The patient underwent mitral valve replacement, left atrial thrombus resection, and left atrial appendage closure that resulted in significant improvement in breathing. A 56-year-old man with no significant past medical history presented with exertional shortness of breath. On examination, vital signs were stable, and a mid-diastolic rumbling murmur was appreciated on auscultation. Electrocardiogram showed normal sinus rhythm with P mitrale. An echocardiogram (echo) showed a preserved ejection fraction, severe mitral stenosis, and a dilated left atrium with a large thrombus (5 × 3.8 cm). Cardiac magnetic resonance confirmed the echo findings with features consistent with a thrombus. Preoperative cardiac computed tomography showed that the thrombus originated from the left atrial appendage , Video 13Left atrial thrombus formation is a well-known complication of severe mitral stenosis that can lead to systemic thromboembolism. It occurs secondary to the significant blood stasis in the dilated left atrium. To decrease the risk of thromboembolic complications, anticoagulation is recommended in patients with mitral stenosis complicated by atrial fibrillation. Moreover, in patients with significant mitral stenosis in sinus rhythm, long-term anticoagulation should be considered when the echo shows dense spontaneous echocardiographic contrast or an enlarged left atrium. A recent multicenter randomized study showed that vitamin K antagonist (VKA) therapy led to lower cardiovascular events compared with rivaroxaban therapy in patients with rheumatic heart disease-associated atrial fibrillation. Hence, VKA therapy is the recommended anticoagulation strategy in this population.


This cohort study investigates associations between left ventricular (LV) ejection fraction, LV end-systolic dimension index, and LV end-systolic volume index and risk of death in Japanese and Taiwanese individuals with chronic aortic regurgitation. Are ultrasonography indexes of left ventricular ejection fraction (LVEF), LV end-systolic dimension index (LVESDi), and LV end-systolic volume index (LVESVi) associated with excess risk of death among Asian adults with hemodynamically significant chronic aortic regurgitation?2 or greater, and 46 mL/m2 or greater, respectively, for both all-cause and cardiovascular death.In this multicenter cohort study of 1259 Japanese and Taiwanese adults, LVEF, LVESDi, and LVESVi were associated with all-cause and cardiovascular death. The cutoffs of LVEF, LVESDi, and LVESVi were 53% or less, 22 mm/mThe findings suggest that use of the aforementioned LV cutoffs to guide early surgical timing may be associated with improved overall outcomes in Asian patients with aortic regurgitation. Chronic hemodynamically significant aortic regurgitation (AR) is associated with excess risk of death, yet data for Asian patients are lacking, and whether Asian patients can abide by Western guidelines as to when aortic valve surgery should be performed is unknown.To assess AR presentation and cutoffs of left ventricular ejection fraction (LVEF), LV end-systolic dimension index (LVESDi), and LV end-systolic volume index (LVESVi) that are associated with risk of death in Asian patients with AR.This retrospective cohort study included consecutive patients with chronic, moderately severe to severe AR from 3 tertiary referral centers (2 in Japan and 1 in Taiwan) from June 11, 2008, through November 19, 2020, with follow-up through November 11, 2021.Aortic regurgitation severity, graded by a comprehensive integrated approach.The primary outcome was the association between volume-derived LVEF, LVESDi, and LVESVi and all-cause death (ACD). The secondary outcome was the association of these LV indexes with cardiovascular death (CVD). Clinical and echocardiographic data were analyzed retrospectively. A de novo disk-summation method was used to derive LV volumes and volume-derived LVEF.2; LVEF, 55% (11%); LVESDi, 24.7 (5.7) mm/m2; LVESVi, 50.1 (28.0) mL/m2; and indexed mid–ascending aorta size, 24.7 (5.5) mm/m2. Aortic valve surgery occurred in 483 patients (38%); 240 patients (19%) died during follow-up. Overall mean (SD) 8-year survival was 74% (2%). Separate multivariate models adjusted for covariates demonstrated independent associations of LVEF, LVESDi, and LVESVi with ACD  and CVD . In the total cohort, spline curves showed that mortality started to increase for an LVEF of 53% or less, LVESDi of 22 mm/m2 or greater, and LVESVi of 46 mL/m2 or greater for both ACD and CVD. Early surgery was beneficial in 3 strata of LVESDi  and 2 strata of LVESVi (<46 and ≥46 mL/m2).Of 1259 patients , 515 (41%) were Japanese and 744 (59%) were Taiwanese. The median follow-up was 4.1 years . The mean (SD) body surface area was 1.67 (0.21) mThis multicenter cohort study of Asian patients with hemodynamically significant AR found cutoff values of LVEF, LVESDi, and LVESVi that were associated with increased risk of death. These findings suggest that Western guidelines seem applicable in Asian patients and, most importantly, that indexed LV parameters with a lower cutoff could be used in discriminating patients with excess mortality risk. First, patients with Asian ancestry were underrepresented in most AR studies.10 Second, the cutoffs of absolute LV size—an LV end-systolic dimension (LVESD) of 50 mm and an LV end-diastolic dimension (LVEDD) of 65 mm—may fall short since Asian individuals tend to have a smaller body surface area than White individuals. Also, sociocultural factors may be associated with different outcomes in patients with AR.11 Some of us recently found that interethnic  differences exist in patients with AR.12 Therefore, there is a pressing need to explore the contemporary profile of Asian patients with AR and compare it with results found among Western patients.Whether current AR treatment guidelines, which largely focus on left ventricular (LV) chamber size,14 and have a compulsory health insurance system,15 wherein most medical expenses are covered by the government and there is ready access to medical care. In this Asian cohort with hemodynamically significant AR, we sought to (1) identify LV parameters and the cutoffs associated with risk of death; (2) explore interethnic differences, including between Asian and Western individuals and Japanese and Taiwanese individuals; and (3) explore the outcomes of aortic valve surgery.Japan and Taiwan are among the countries that have above-average life expectancySTROBE) reporting guideline. All cases were reviewed de novo to determine eligibility. Exclusion criteria included no research authorization, more than mild mitral stenosis or regurgitation or aortic stenosis, prior mitral or aortic valve surgery, complex cyanotic congenital heart disease, carcinoid heart disease, and acute AR .In this cohort study, between June 11, 2008, and November 19, 2020, all consecutive patients aged 18 years or older with chronic moderately severe to severe AR assessed by transthoracic echocardiography (TTE) were retrospectively identified from the electronic echocardiographic database of 3 university-affiliated hospitals   functional class, and comorbid conditions, independently and prospectively recorded by treating physicians, were abstracted from electronic or paper medical records. Asymptomatic patients were those without typical symptoms . The Charlson Comorbidity Index (CCI) was computed. Ischemic heart disease was defined as prior myocardial infarction, coronary artery bypass graft, coronary artery disease, or history of ischemic cardiomyopathy.16 Left ventricular volumes were derived from the biplane disk-summation method or single plane if biplane was not feasible. Left ventricular filling pressure was represented by the ratio of peak mitral inflow velocity to early diastolic mitral annular velocity. For diagnosis of AR severity, an integrated, comprehensive approach was used, including quantitative  and semiquantitative measurements  according to guidelines.17 Images stored for PISA quantification were not routinely obtained in Taiwan before 2020. To ensure consistency of AR severity diagnosis, 20 randomly selected cases from the Japanese cohort were reviewed by L.T.Y. to calculate AR vena contracta; the intraclass correlation coefficient was 0.945.In patients with multiple TTEs, the first eligible result was used as the baseline for analysis. Transthoracic echocardiography was performed by trained sonographers using commercially available echocardiography systems and reviewed de novo by cardiologists with level-3 echocardiography training. Chamber quantification was performed based on guideline suggestions.18 in the following order: (1) symptoms , (2) LV ejection fraction (LVEF) of 50% or less, (3) LVESD greater than 50 mm or indexed LVESD (LVESDi) greater than 25 mm/m2, (4) surgery for aortic dilatation or aneurysms (no patients had AR of moderate or lower severity), and (5) LVEDD greater than 65 mm. Surgery status was ascertained from medical records and telephone interview, if necessary.Surgical indications were stratified based on both 2017 European Society of Cardiology and 2014 American College of Cardiology guidelinesOur primary end point was all-cause death (ACD). The secondary end point was cardiovascular death (CVD). The association between aortic valve surgery and ACD and CVD was also analyzed. Observation time was between either (1) baseline TTE and death or last follow-up  or (2) baseline TTE and death, time of aortic valve surgery, or last follow-up . Mortality status, date of death, and cause of death were retrieved from medical records, mailed questionnaires, and for Taiwanese patients, the National Health Insurance Research Database. In Taiwan, the National Health Insurance program is a government-run, single-payer insurance plan that delivers universal coverage (99.5% of whole population) for all citizens and was linkable to national databases such as registries of deaths.t test or Wilcoxon rank sum test as appropriate based on normality of data distribution. Categorical data, presented as counts and percentages, were compared using the χ2 test. Survival was estimated using the Kaplan-Meier method and compared using the log-rank statistic. The primary and secondary end points of mortality were analyzed using the Cox proportional hazards regression model, in which variables with clinical and pathophysiological relevance plus univariate P < .05 were chosen for multivariable analyses; aortic valve surgery was analyzed as a time-dependent variable. Penalized smoothing splines were used to illustrate the risk of mortality over the range of the LV parameters. A landmark analysis19 was used to assess whether early aortic valve surgery was associated with better survival. After 6 months, surviving patients were further divided into 2 groups—those with and without aortic valve surgery within 6 months. Then, the results were plotted according to 3 LVESDi strata . To evaluate survival differences between Japanese and Taiwanese patients, the inverse probability of treatment weighting method was used to control confounding as previously described.20 All statistical analyses were performed using JMP, version 16 ; SAS, version 9.4 (SAS Institute); and R, version 4.1.2 . Two-sided P < .05 was considered statistically significant.Continuous variables, expressed as mean (SD) or median (IQR) according to data distribution, were compared using the Student 2; LVEF, 55% (11%); LVESDi, 24.7 (5.7) mm/m2; LVESVi, 50.1 (28.0) mL/m2; and indexed mid–ascending aorta size, 24.7 (5.5) mm/m2. As compared with Taiwanese patients, Japanese patients had similar prevalence of bicuspid aortic valves, were less symptomatic, and had a smaller body surface area, lower CCI score, greater proportion of female patients, greater proportion who had undergone aortic valve surgery, larger LV size (both absolute and indexed LV dimensions and volumes), lower LVEF , lower LV filling pressure, smaller AR vena contracta, and greater pressure half time , of whom 515 (41%) were Japanese and 744 (59%) were Taiwanese . The meaalf time . In thisP < .001) .The distribution of surgical procedures is shown in  < .001) A but les < .001) ; also, J < .001) . However < .001) . At the P = .002; LVESDi: HR, 1.04; 95% CI, 1.01-1.06; P < .002; LVESVi: HR per 10 mL/m2, 1.11; 95% CI, 1.05-1.17; P < .001) were independently associated with ACD during medical surveillance , with a maximum of 13 years, during which 240 patients (19%) died . Results of univariate analysis are shown in eTables 2 and 3 in eillance . In JapaDuring total follow-up in Taiwanese patients, all 3 LV indexes  were independently associated with ACD (n = 192) . In JapaP < .001; LVESDi: HR, 1.05; 95% CI, 1.01-1.09; P = .01; LVESVi per 10 mL/m2: HR, 1.15; 95% CI, 1.06-1.24; P < .001) were associated with CVD during medical surveillance (eTable 4 in Multivariable factors associated with CVD (n = 74) are shown in eTables 4 and 5 in P < .001 for Japanese vs Taiwanese patients). Taiwanese patients had greater risk of death, both with age and sex adjustment  and without  (both P < .001) (P < .001)  8-year survival in the entire cohort was 74% (2%); in Japanese patients, 84% (3%); and in Taiwanese patients, 69% (2%). Mean (SD) 10-year survival in the entire cohort was 69% (2%); in Japanese patients, 84% (3%); and in Taiwanese patients, 64% (2%) ( < .001) B. The inP = .03). In multivariable analysis, aortic valve surgery was not associated with CVD in the entire cohort (eTable 5 in 2) in the entire cohort, patients who underwent aortic valve surgery within 6 months had better survival than those who did not undergo aortic valve surgery within 6 months   C. Aortic2 for LVESDi, and 48 mL/m2 for LVESVi. The corresponding cutoffs for CVD were 52%, 23 mm/m2, and 46 mL/m2, respectively , LVESDi and LVESVi were associated with ACD during medical surveillance. However, LVEF was not  compared with prior versions .3 These guideline changes were based on recent studies conducted in Western individuals. So far, no evidence has shown that these results hold true in Asian individuals, who compose 60% of the global population but for whom data on AR are scarce. A recent study by some of us12 and the current study   (2),21 possibly due to intercountry variations of indexed LV volumes26 and because Asian individuals were at a later stage of AR natural history   was simi8 mL/m2)  was slig27 may be less vulnerable to AR-related LV remodeling. These observations could potentially be explained by earlier surgery at asymptomatic status, higher aortic valve surgery incidence, uncollected confounders , diet, culture, low prevalence of obesity, and educational level.28Compared with Taiwanese individuals, Japanese individuals had better survival despite larger indexed LV size , suggest2),22 yet the mean (SD) 8-year post-aortic valve surgery survival was similar   than the US cohort  and lower prevalence of aortic valve surgery in Asian individuals, the postsurgical survival was similar to that among Western individuals  who is experienced in AR assessment with relevant publications30 reviewed all echocardiograms de novo to discern AR severity. Also, compared with a US cohort,22 the indexed LV dimensions from Taiwanese individuals were larger and diastolic blood pressure and absolute LV size were similar, supporting the presence of hemodynamically significant AR. Given the relatively low mortality among Japanese individuals, there was insufficient power for finding LV cutoffs for death and for multivariable analysis, especially for CVD. Finally, prospective studies are needed to confirm benefits of early surgical timing using the LV cutoffs found herein. Future studies on usefulness of cardiac magnetic resonance imaging and global longitudinal strain in Asian patients with AR are also of interest.This study has limitations. It was a retrospective observational study from tertiary referral centers with the potential for selection bias. However, both Japan and Taiwan had compulsory health insuranceIn this large, multicenter, contemporary cohort study of Asian patients with hemodynamically significant AR, the cutoffs of LVEF, LVESDi, and LVESVi values associated with increased risks of death were similar to what have been reported for the Western population. Asian individuals were at a later stage of AR natural history with a larger indexed LV and lower rates of aortic valve surgery yet had similar postsurgical survival compared with Western individuals. These findings suggest that current guidelines seem applicable to Asian individuals with AR and that earlier surgical timing using indexed LV size as guidance may be associated with improvements in overall outcomes.


Hypertrophic cardiomyopathy (HCM) is a genetic myocardial disease of the sarcomere protein. The age of diagnosis of HCM tends to be between the second to third decades of life. However, the recent occurrence of HCM in the fifth and sixth decades of life has been seen in an increasing number of cases. In all cases, a transthoracic echocardiogram (TTE) is considered the gold standard of imaging. Here, we present a case of a 54-year-old Caucasian male who presented to the emergency department (ED) with dyspnea while on vacation. An electrocardiogram (ECG) taken at the time did not suggest any abnormalities. After returning home, a stress test conducted indicated left anterior descending (LAD) artery stenosis. Following treatment, symptoms improved temporarily but eventually came back. Repeat ECGs and TTEs done over the next two years indicated grade II diastolic dysfunction and mild left ventricular hypertrophy, which led to changes in the medication regime. Nevertheless, his condition progressively deteriorated over time. Repeat appearances to the ED led to the utilization of magnetic resonance imaging (MRI) to assess cardiac morphology function and velocity flow. The results were consistent with HCM. This case presents a unique obstacle for the diagnosis of adult-onset HCM. The change made to his medication regimen seemingly aggravated the patients’ condition. This case highlights the need for further imaging, beyond the gold standard, in adult males with repeated complaints of dyspnea on exertion (DOE). Hypertrophic cardiomyopathy (HCM) or hypertrophic obstructive cardiomyopathy (HOCM) is a genetic myocardial disease involving the sarcomere protein . MutatioThe diagnosis of HCM is confirmed with the presence of a left ventricular wall thickness of ≥15 mm that is otherwise unexplained by abnormal loading conditions  [Some patients develop an abnormal diastolic function, and complications can include increased left ventricular pressures that impair ventricular filling, which may further exacerbate obstruction . DiastolA 54-year-old Caucasian active male with past medical history of irritable bowel syndrome, hyperlipidemia, coronary artery disease, hypertension, obstructive sleep apnea (OSA), tobacco use disorder, and restless leg syndrome presented to his primary care provider (PCP) for a routine annual physical exam in December 2019. The patient did not report any family history of HCM or congenital heart defects. No audible murmurs, palpable thrills, or peripheral edema were noted in the physical exam. At the time, the patient denied headaches, dizziness, palpitations, and chest pain. In addition, an ECG was performed, and results indicated a regular rate and sinus rhythm. Two weeks later . For this reason, the test was aborted after seven minutes and 26 seconds (maximum mets = 9.2). The results indicated reversible ischemia in the apical inferior aspect of the left ventricle with a normal ejection fraction. He was sent directly to the emergency department for evaluation and cardiac consultation. In the ER, IV heparin was initiated in preparation for angiographic imaging. Doppler TTE was performed at bedside along with right and left heart catheterization. While imaging was unable to be retrieved for visualization in this report, the interpreted results of both modalities were consistent with the diagnosis of acute heart failure with preserved ejection fraction (HFpEF). In addition, the angiographic findings included coronary artery disease with 75% stenosis of the proximal left anterior descending (LAD) artery. Left ventricular end diastolic pressure (LVEDP) was elevated (LVEDP = 27 mmHg). However, the ejection fraction was preserved (EF= 65%). Mitral valve structure was noted to be normal with trace regurgitation. The aortic valve was observed as a tri-leaflet that exhibited normal excursion without thickening, regurgitation, or stenosis. In addition, no wall motion abnormalities were detected. Percutaneous catheter intervention (PCI) was undertaken, and a drug-eluting stent was placed in the proximal LAD artery. Stenosis was reduced to 0%. At the time, the treatment regimen included atorvastatin 40 mg, metoprolol XL 25 mg, fenofibrate 160 mg, spironolactone 25 mg daily, lisinopril 40 mg daily, nitroglycerin 0.4 mg taken as needed, furosemide 40 mg, and diltiazem 180 mg daily.Initially, the patient reported a mild improvement in symptoms. However, by May 2021, he continued experiencing difficulty completing daily tasks, such as mowing the lawn or climbing stairs without dyspnea. A repeat ECG Figure .In January 2022, the patient’s PCP diagnosed him with SARS-CoV-2 infection. The patient was not vaccinated and received a five-day course of nirmatrelvir/ritonavir and prednisone. The patient did not report any adverse effects from the treatment. However, he noted that his cardiac symptoms worsened following recovery of SARS-CoV-2. By March 2022, he presented to his outpatient cardiologist for follow-up. At that time, he presented with progressive lightheadedness, chest pain, and dyspnea on exertion (DOE). An ECG and TTE were performed. The ECG Figure  results Due to the patient’s reported chronic symptoms and lack of access to proper imaging modalities, he was referred to a larger, academic institution. Within three weeks, he followed up and reported dyspnea on relatively minimal exertion, which was worsening over time, as well as intermittent left-sided heaviness in his chest. The heaviness was described as radiating to the shoulder and lasting for hours. These symptoms had progressively climaxed in severity since meeting with his home state cardiologist weeks previously. The patient noted that over time, the frequency of use of his oral nitroglycerin  had increased. Consistent with previous findings, a repeat TTE revealed the impression of Grade II left ventricular diastolic dysfunction with a hyperdynamic left ventricular systolic function. Moderate concentric left ventricular hypertrophy was noted with a normal function and size of the right ventricle. The pulmonary venous pattern showed a blunted systolic flow, and trace mitral and tricuspid valve regurgitation were noted. Due to the history of DOE, further workup was utilized to quantitate left ventricular and valvular function.A Philips Achieva® 1.5 Tesla magnetic resonance imaging (MRI) scanner was utilized for the cardiac morphology function and velocity flow. Findings showed moderate to severe asymmetric septal hypertrophy  measuring up to 1.9 cm in the basal septum consistent with HOCM. The results showed no segmental wall motion abnormalities of the left ventricle. Quantitative left ventricular functional values (end diastolic volume (EDV), end systolic volume (ESV), stroke volume, left ventricular ejection fraction (LVEF), cardiac output, cardiac index, and left ventricular mass) were all within the range for normal limits. Subtle “sand-like” mid-myocardial spots were noted in the thickened septum, which, although non-specific, may appear in HCM. Otherwise, there was no evidence of prior myocardial damage due to ischemia. The aortic valve was unrestricted, and the mitral valve appeared structurally normal (with mild to moderate regurgitation directed posteriorly). There was systolic anterior motion of the mitral valve, with near mitral septal contact resulting in a significant flow acceleration within the left ventricular outflow tract. In addition, there were findings of mild ectasia of the mid-ascending thoracic aorta (4.0 cm). The right ventricle size and systolic function were noted to be normal.Furosemide was discontinued, as it was seemingly associated with extreme fatigue and exacerbation of symptoms. After the diagnosis, ventriculomyotomy-myectomy was performed, and up to eight grams of septal tissue and an incidental growth was removed and sent for biopsy. Pathology of the same noted that the sample taken was non-malignant and was perceived as an incidental finding. Additional findings during surgery were consistent with HCM. The results of the procedure, in addition to symptoms and imaging, allowed for the definitive diagnosis of HCM over other diagnoses. As many mutations can be associated with HCM, further genetic investigation was offered. However, the patient opted to not proceed with genetic testing. The patient's self-reported symptoms improved rapidly within one month post-operation, and progress is currently being monitored by his PCP.HCM is the most common cause of sudden death in the young and has disproportionately been excluded from possible diagnosis in those past the age of 40 . HoweverHCM is a genetic disease with the possibility of fatal outcomes. Genetic mutations lead to increased production of cardiac muscle, resulting in LV hypertrophy and LV outlet tract obstruction . HCM priRegardless of the age of onset, there exists a persistent misunderstanding that HCM is not only grim and unrelenting but increasingly progressive throughout life due to such mutations . Recent Anecdotally, TTE is regarded as the gold standard for the diagnosis of HCM . HoweverThat being said, other findings should be considered. A benign growth  was noted during the septal myectomy. The patient had been aware of a cardiac growth for many years previous to 2019 with the understanding of its incidental nature and minor impact on his long-term health. While there was no clear explanation as to the histology of this growth in comparison to septal tissue, biopsy results confirmed non-malignant pathology. A previously reported case highlights the onset of a cardiac myxoma in a patient with COVID-19 [Our patient’s age and comorbidities, in addition to imaging, repeatedly signaled diastolic heart failure. After being treated for diastolic heart failure, symptoms did not improve, prompting further workup. Diagnosis in this case was dependent upon imaging results from cardiac MRI. While this modality has proven to be superior in the established literature, many providers and hospitals have limited access to such advanced imaging. The patient subsequently underwent surgical removal of his hypertrophic interventricular septum muscle. Only then did his symptoms significantly remit and his quality of life improved. This case elucidates the danger of repeatedly utilizing common imaging modalities in complex cases, such as this one. In addition, our case demonstrated the importance of taking multiple variables into consideration when analyzing for the onset and worsening of HCM in the adult population. Those discussed were the role of genetics, COVID-19, and benign cardiac growth in disease manifestation.It is possible that the misinterpretation and redundancy of repeat imaging prolonged accurate diagnosis. It is equally likely that the traditional TTE employed in this case, due to their two-dimensionality, did not sufficiently portray hypertrophy in order to provide sufficient evidence to suggest the diagnosis of HCM. In this case, a two-dimensional approach displayed limitations in capturing septal hypertrophy on multiple occasions. In addition, this case demonstrated an increased sensitivity and specificity of a three-dimensional approach, such as that provided by cardiac MRI. This report highlights the need for considering HCM in patients with DOE, chest pain, and dizziness between the ages of 40 and 70 and the necessity of cardiac MRI in patients with repeated occurrences of symptoms when TTE imaging does not reveal significant abnormalities.


Chronic graft failure and cumulative rejection history in pediatric heart transplant recipients (PHTR) are associated with myocardial fibrosis on endomyocardial biopsy (EMB). Cardiovascular magnetic resonance imaging (CMR) is a validated, non-invasive method to detect myocardial fibrosis via the presence of late gadolinium enhancement (LGE). In adult heart transplant recipients, LGE is associated with increased risk of future adverse clinical events including hospitalization and death. We describe the prevalence, pattern, and extent of LGE on CMR in a cohort of PHTR and its associations with recipient and graft characteristics.This was a retrospective study of consecutive PHTR who underwent CMR over a 6-year period at a single center. Two independent reviewers assessed the presence and distribution of left ventricular (LV) LGE using the American Heart Association (AHA) 17-segment model. LGE quantification was performed on studies with visible fibrosis (LGE+). Patient demographics, clinical history, and CMR-derived volumetry and ejection fractions were obtained.2, p = 0.011) and decreased LV ejection fraction (LVEF) . There were no significant differences in history of moderate/severe rejection (p = 0.196) or cardiac allograft vasculopathy (CAV) (p = 0.709).Eighty-one CMR studies were performed on 59 unique PHTR. Mean age at CMR was 14.8 ± 6.2 years; mean time since transplant was 7.3 ± 5.0 years. The CMR indication was routine surveillance  in 63% (51/81) of studies. LGE was present in 36% (29/81) of PHTR. In these LGE + studies, patterns included inferoseptal in 76% of LGE + studies (22/29), lateral wall in 41% (12/29), and diffuse, involving > 4 AHA segments, in 21% (6/29). The mean LV LGE burden as a percentage of myocardial mass was 18.0 ± 9.0%. When reviewing only the initial CMR per PHTR (n = 59), LGE + patients were older , with greater time since transplant . These patients demonstrated higher LV end-systolic volume index (LVESVI) (34.7 ± 11.7 vs. 28.7 ± 6.1 ml/mLV LGE was present in approximately one third of PHTR, more commonly in older patients with longer time since transplantation. Grafts with LGE have lower LVEF. CMR-derived LGE may aid in surveillance of chronic graft failure in PHTR. The overall median survival for pediatric heart transplant recipients (PHTR) has improved over time and is now reaching 20 years . The expAssessment for late-gadolinium enhancement (LGE) on CMR is a validated method to detect focal myocardial fibrosis , which hAmong adult heart transplant recipients, the presence and extent of LGE are associated with increased risk of future adverse clinical events including hospitalization and death –11. In tThis study is a cross-sectional, retrospective cohort study of PHTR who underwent comprehensive structure-function CMR with LGE at a single center from 2015 to 2021. The Institutional Review Board (IRB) approved this Health Insurance Portability and Accountability Act (HIPAA)-compliant study. PHTR were included with clinician ordered CMR and excluded if LGE sequences were incomplete or the quality was inadequate for analysis. Although all patients were followed at a pediatric center, age was not an exclusion criterion. We used all observations available for this study, which included multiple CMR studies for some patients.2). In addition, 2D cine balanced steady-state free-precession (bSSFP) images were obtained in the 2-chamber, 3-chamber and 4-chamber, and short axis orientations , LV mass index (LVMI), and LV/RV ejection fraction (EF) was performed at the time of completion of the CMR report using 2D bSSFP short-axis stack using dedicated commercially available software . Ventricular volumes and LV mass were indexed to body surface area.Two reviewers (LG and NH), determined the presence of LV LGE by visual identification of areas of relatively increased signal intensity on delayed-contrast enhanced images by consensus review. Orthogonal planes were used to confirm the presence of LGE. The reviewers assessed the distribution of LV LGE by the American Heart Association (AHA) 17-segment model and further classified the pattern as infarct-typical, with subendocardial involvement, or infarct-atypical, as described by Braggion-Santos et al. . In addiFor studies with LV LGE by qualitative assessment, two reviewers (AAL and NH) quantified the LGE burden by consensus review. Commercially available post-processing software  was used. The reviewers selected 4–7 slices from base to apex in the short axis plane in which the myocardium was well visualized. Then, they manually traced LV epicardial and endocardial borders. The reviewers placed regions of interest in an area of healthy myocardium and an area of hyperenhanced tissue. Next, the LGE burden was quantified using the full-width half-maximum method. The LV borders were inspected again and adjusted, if necessary, to completely exclude the blood pool. LGE burden was recorded as a percentage of LV myocardium by mass  was noted from clinical notes or CMR indication at the time the study was ordered. Patients were classified as having history of moderate to severe rejection if there was acute cellular rejection (ACR) ≥ 2R or antibody mediated rejection (AMR) ≥ 2 per International Society of Heart and Lung Transplantation criteria at any point since the most recent transplantation , 20. TheWe performed separate univariate analyses on the entire dataset of CMR studies as well as the set of initial CMR studies per PHTR, excluding follow-up studies. To test for significance, we used a t-test for continuous variables and Chi-squared test for categorical variables . We performed ordinary least squares regression analysis for presence of LGE with robust standard errors. We performed a Bland-Altman analysis to evaluate the agreement between LGE mass percentage values obtained by two blinded observers on 19% (5/27) of the LGE + cohort.During the study period, 81 CMR studies were performed on 59 unique PHTR. Reviewing the data for all CMR studies (n = 81), mean age at CMR was 14.8 ± 6.2 years with an average time since transplantation of 7.3 ± 5.0. Congenital heart disease was the most common indication for transplantation in this cohort 53% (43/81), followed by cardiomyopathy 35% (28/81), and re-transplantation 12% (10/81). A documented history of moderate/severe AMR or ACR prior to CMR was present in 29% (23/80) of all CMR studies, while a history of CAV was present in 11% (9/81). Specifically, there were 4 CMR studies of patients with CAV 1, two with CAV 2, and three with CAV 3. The indication for CMR was routine surveillance  in 63% of the studies (51/81). In the remaining 37% (30/81), a clinical concern was present. Clinical concerns, which were not mutually exclusive, included history of recent, significant rejection (n = 9) or CAV (n = 10), changes in catheterization-derived hemodynamic parameters (n = 4), changes in echocardiographic parameters (n = 3), LGE on prior CMR (n = 3), or unexplained cardiac symptoms (n = 2). The mean CMR-derived volumetric and functional parameters for all studies (n = 81) and initial studies (n = 59) are given in Table LV LGE was present in 36% of all CMR 29/81) and 32% (19/59) of initial CMR per PHTR. Among LGE + scans, the mean number of AHA segments involved was 2.5 ± 2.7  were used for analysis. The mean LV LGE mass percentage was 18.0 ± 9.0% (range 4.1–37.0%) in the LGE + studies. A subset of 5 LGE + patients had repeat LGE quantification performed by a single reviewer to evaluate reproducibility of quantification results. A Bland-Altman analysis revealed no significant mean bias between the two observers for LV LGE mass percentage (− 0.01 ± 7.2% LGE); however, the 95% limits of agreement were wide (− 14.6 to 14.6% LGE).When reviewing the initial CMR per PHTR (n = 59), LGE + PHTR were found to be older , with a longer time since transplant  . Notably, there were no significant differences in history of moderate or severe rejection, history of any CAV, or hypertension diagnosis between LGE + and LGE- groups. There were six initial studies of patients with CAV, of which 3 had LGE, each in an infarct-atypical pattern. There were no significant group differences in PCWP, right atrial pressure, or histologic rejection grade by cardiac catheterization with EMB.By regression analysis Table , older a2, p = 0.011) and lower LV EF . There was no difference in RVEDVI, RVESVI, or RV EF based on the presence of ventricular (LV and/or RV) LGE.The presence of LV LGE was associated with increased LV end-systolic volume index  and death –11. The Scrutiny of observed patterns of LGE may provide clues about the etiology of these myocardial injuries. LGE patterns in adult heart transplant recipients have traditionally been classified as infarct-typical or infarct-atypical. To date, the best evidence tying an LGE pattern to a specific disease process affecting heart transplant recipients involves CAV. In multiple adult studies, the infarct-typical, subendocardial pattern of LGE was associated with CAV, while infarct-atypical LGE was not , 18, 24.The LV LGE patterns we observed could be classified into three distinct, non-mutually exclusive categories. Inferoseptal (posterior RV insertion point) enhancement was the most common, followed by lateral LV wall. Diffuse enhancement (involving four or more AHA segments) was the least common. Inferoseptal enhancement was frequently found in isolation, without extensive LGE involvement elsewhere in the LV myocardium. Lateral wall enhancement was generally subepicardial and infarct-atypical. Notably, the inferoseptal enhancement observed was remote from the RV-aspect of the mid-septal region typically accessed for endomyocardial biopsy, involvement of other septal segments was rare Fig. . As suchFor patients with LV LGE by qualitative assessment, the average LGE burden by subsequent quantiative analysis was 18% of LV mass. This LV LGE burden is marginally higher than the means (3–12.2%) previously reported among adult heart transplant recipients . Soslow We identified three primary difficulties with LGE quantification: First, the LGE mass calculation is very sensitive to small adjustments to the manual regions of interest selected for healthy and hyperenhanced myocardium in children. This is a well-described source of variability in quantification even in adults . Second,Future inquiry should include longitudinal studies of PHTR undergoing serial CMR studies, with correlation to interval events. Any identified associations between graft disease processes and specific LGE patterns would aid in the early and non-invasive identification of patients requiring increased monitoring or treatment. Specifically, future study should include consideration of a multi-center study of PHTR undergoing CMR.This study’s retrospective, single-center design and sample size limits generalizability to other PHTR cohorts. Specifically, there is selection-bias in the PHTR who were referred for CMR, which was prompted by a clinical concern in some cases. The sample size limits this study’s power to assess differences in clinical history between LGE + and LGE- patients. Longitudinal clinical outcomes were not assessed. Quantification of LV LGE mass percentage was not highly reproducible for the reasons discussed above. Because only one patient had RV LGE on initial CMR, this study was underpowered to assess differences in RV volume index and RV EF based specifically on the presence of RV LGE.CMR-derived LGE was noted in a third of PHTR. Older PHTR and those with greater time since transplantation were more likely to have LGE, with age being an important predictor of LGE independent of time since transplant. Grafts with LGE had lower mean LV EF. LGE may be an important finding in surveillance for graft failure and further investigation is needed to determine its association with clinical outcomes.


Assessing regional wall motion abnormalities (RWMA) in the myocardium may provide early diagnosis and treat chronic remodeling in STEMI patients. We assessed RWMA in 217 subjects with anterior STEMI admitted to Era University Hospital in Lucknow, UP, India. Besides abnormalities in the LAD territory, sub-sets of patients exhibited diffuse regional myocardial dysfunction. Interestingly, variations in serum electrolytes, specifically sodium and potassium, significantly affected the distribution and frequency of RWMA. Notably, RWMA occurred in the basal septum, apical septum, apex, and lateral wall in the anterior STEMI group. Additionally, the rate of regional dysfunction varied with serum urea and creatinine levels. This suggests that anterior STEMI can manifest myocardial abnormalities beyond the LAD territory. These findings indicate that ST-segment elevation might not be specific, possibly influenced by electrolyte changes affecting cardiac rhythm. Therefore, diagnosing and correcting region-specific wall motion abnormalities and electrolyte imbalances may improve outcomes in STEMI patients. DiagnIn addition, it is essential to note that the cardiac action potential differs from the surface electrocardiogram, which represents the heart's total electrical activity recorded from the body surface . Action Given the significant variation in the cell-types in the myocardium across different heart regions , 19, it 2.2.1.In the present study, we have assessed the incidence of RWMA in 217 anterior STEMI subjects admitted to the Era's Lucknow Medical College & Hospital, Era University by ECG, 2D-ECHO, and correlated with the serum sodium, potassium, urea, and creatinine Refer to .2.2.ST-elevation (STE) is the primary immediately available marker for detecting complete coronary artery occlusion without collateral circulation, indicating a significant region of injured myocardium at risk of irreversible infarction, necessitating urgent reperfusion therapy. Patients with acute chest pain were assessed based on ECG criteria for ST-elevation myocardial infarction (STEMI), as defined by the American College of Cardiology, American Heart Association, European Society of Cardiology, and the World Heart Federation committee. STE is considered significant when the J point of at least 2 contiguous leads measures ≥2 mm (0.2 mV) in men or ≥1.5 mm (0.15 mV) in women, in leads V2–V3 and/or ≥1 mm (0.1 mV) in other contiguous chest or limb leads . Recipro2.2.1.All subjects were between the ages of 30 and 95. Subjects with anterior STEMI, i.e., the occurrence of ≥1 and stenosis of ≥50% in ≥1 of 15 coronary segments were selected for the study.2.2.2.Individuals with stenosis <50%, septicemia, acute and chronic kidney disease, cerebrovascular accident, presence of malignancy, and pregnant women were excluded from the study.2.3.ECG recordings and analysis were performed following the American College of Cardiology, American Heart Association, European Society of Cardiology, and the World Heart Federation committee criteria using GE MAC, 2000 12 lead machine. The rate of ECG acquisition was set at 25 mm/sec with the voltage set at 10 mm/millivolt. The standard 12 lead ECG was a 10-second strip. The bottom line was a full rhythm strip spanning the whole 10 s of the ECG - other leads spanned only about 2.5 s.2.4.Two-dimensional echo and doppler analyses were performed using PHILIPS Epic 7C system. ECHO images were acquired using parasternal long axis view, parasternal short axis view, apical four-chamber view, apical two-chamber view, and apical five-chamber view. Regional wall motion was recorded using 16 – Segment model, recommended by the American Society of Cardiology. Ejection fraction (EF) and segmental wall motion tracing were analyzed in PSLAX M-Mode of LV dimensions from mid-ventricular papillary muscle level. Stroke volume (SV) is calculated as the difference between end-diastolic volume (EDV) and end-systolic volume (ESV). LVEF is calculated using the formula LVEF: (SV/EDV)×100. For assessing longitudinal contraction, Simmons method was adopted to trace the LV endocardial border in both the apical four-chamber and two-chamber views in end-systole and end-diastole.2.5.Serum - Sodium (Na+) and Potassium (K+) concentrations were quantitatively measured using commercial kits (VITROS). Na+ Slides and K+ Slides (Potentiometric Micro Slide Kit); Serum-urea and – creatinine were quantitatively measured by VITROS - urea slides and creatinine slides (Colorimetric Micro Slide Kit) as described by the manufacturer.3.3.1.p > 0.05, ns)  . The stuAmong the 217 STEMI subjects, 92% exhibited regional wall motion abnormalities (RWMA) at multiple sites, including the basal septum (25%), mid septum (11%), apical septum (20%), LAD territory (28%), inferior wall (23%), posterior wall (12%), and anterior wall (1.8%), regardless of the ejection fraction (EF). Variable degrees of RWMA with multiple overlapping zones were identified in STEMI patients with normal EF . Analysi3.2.The serum sodium level is an independent clinical variable for identifying HF with preserved ejection fraction (HFpEF) –24. In o3.3.Both reduced  and increased  serum potassium levels are associated with cardiac arrhythmia , 26. In 3.4.We found a poor correlation between serum urea and EF . NonetheAmong males with low urea levels, significant RWMA was found at the apical septum (18%), lateral wall (13%), and basal septum (10%), with lower frequency in the LAD territory . In cont3.5.Interestingly, males with normal creatinine levels exhibit prominent RWMA at the apical septum, apex, lateral wall, and LAD territory, while males with high creatinine levels display predominant but insignificant abnormalities in the LAD territory. Females with both high and normal serum creatinine levels do not show any significant or prominent areas with RWMA . No dire4.ECG patterns/scores have been used to classify STEMI subjects . HoweverElectrolyte imbalances are common in STEMI subjects , 32, andSerum urea and creatinine levels have the potential to predict kidney dysfunction in coronary patients . HoweverIn this study, we observed variations in serum electrolytes, such as sodium and potassium, resulting in differences in the distribution and frequency of regional abnormalities among STEMI subjects . This su4.1.This study emphasizes improved diagnostic methods for STEMI patients, using sensitive echocardiography to assess myocardial health. Widespread myocardial dysfunction is observed, particularly in the LAD territory. Monitoring and correcting electrolyte imbalances are crucial. Combining electrolyte correction with traditional PCI interventions expedites patient recovery. Personalized care based on RMWA and electrolyte correction may significantly improve outcomes.4.2.This study offers valuable insights but comes with several limitations. Firstly, being a cross-sectional study, unable to establish causal relationships. To investigate these associations, we need longitudinal studies with a larger patient cohort. Secondly, it focuses on a specific ethnic population, and require more diverse and extensive samples for generalizing. Furthermore, the specific mechanisms behind the associations between electrolytes, myocardial abnormalities, and STEMI remain unclear in this study.


Severe acute respiratory distress syndrome in children, or PARDS, carries a high risk of morbidity and mortality that is not fully explained by PARDS severity alone. Right ventricular (RV) dysfunction can be an insidious and often under-recognized complication of severe PARDS that may contribute to its untoward outcomes. Indeed, recent evidence suggest significantly worse outcomes in children who develop RV failure in their course of PARDS. However, in this narrative review, we highlight the dearth of evidence regarding the incidence of and risk factors for PARDS-associated RV dysfunction. While we wish to draw attention to the absence of available evidence that would inform recommendations around surveillance and treatment of RV dysfunction during severe PARDS, we leverage available evidence to glean insights into potentially helpful surveillance strategies and therapeutic approaches. Acute respiratory distress syndrome (ARDS) in children, or pediatric ARDS (PARDS), is a common but severe manifestation of a host of insults to the respiratory system of a child that carries a significant risk of morbidity and mortality . As in aIn our experience, right ventricular (RV) dysfunction and eventual failure is an important, and often occult, driver of multiorgan failure in the setting of PARDS. Though RV dysfunction is a well-known phenomenon described in adult ARDS literature, evidenced by various reviews on the topic in recent years , there i2/FIO2 ratio. The Consensus Conference also recognized that use of arterial oxygen sampling is not homogeneous across pediatric intensive care units (PICU) and thus incorporated oxyhemoglobin data from pulse oximetry into the determination of PARDS severity when PaO2 data are unavailable. The PALICC experts simplified the radiological criteria for PARDS to any radiographic evidence of alveolar disease rather than “bilateral opacifications” on chest imaging as recommended in the Berlin criteria. Unique to the PALICC definition, PARDS could be described in specific pediatric populations with pre-existing comorbidities such as chronic lung disease and cyanotic heart disease.Though operational definitions for ARDS have existed for adults for decades , their vIO2) ratios became standard management of ARDS in adults following the first ARDS Network trial in 2000  to less than 15 cmH2O, and preserving functional residual capacity (FRC) by preventing atelectasis  and higher PEEP/Flectasis . Howeverlectasis . Moreovelectasis , 13. Howlectasis  that maylectasis , 15.In utero, high PVR facilitates the redirection of systemic and placental venous return away from the lung through either the ductus arteriosus or the foramen ovale for eventual ejection to the systemic circulation. As the morphologic RV (assuming situs solitus with levocardia and D-looped ventricles) is conditioned by elevated PVR in utero, RV and left ventricle (LV) wall thicknesses are nearly identical at birth  than neonates through elevations in heart rate, contractility, and stretch to accommodate the increased RVEDV. Moreover, extrapolating from canine models of acute afterload changes to the ventricles, LV contractility may contribute 20%–40% of RV output in older children through ventricular tethering .Given the limited contractile reserve of the RV in an older child, acute increases in RVEDV are initially tolerated through modest dilation of the relatively compliant RV wall. As greater stress is placed on the RV myocardium through increasing afterload and/or preload and myofibrils are stretched further, myosin-actin interactions are reduced and systolic function becomes embarrassed (extreme of the Frank–Starling relationship). The reduction in RV contractility is thus unable to respond to the increased preload by raising, or even maintaining, stroke volume. The ensuing acute RV dilation can cause a precipitous compression of the LV through ventricular interdependence. In combination with diminished pulmonary venous return due to limited RV output and reduced pulmonary blood flow, LV compression can result in an embarrassment to systemic cardiac output—a process termed acute cor pulmonale (ACP). The combination of increased RV wall stress and decreased systemic cardiac output can result in coronary ischemia that further reduces RV systolic function that can culminate in cardiac arrest.During PARDS, the developing heart of a neonate or young infant is rather suddenly exposed to a potentially toxic cardiorespiratory milieu. Intrathoracic positioning intrinsically subjects the right atrium and RV to transpulmonary pressures changes. During positive pressure ventilation with high mean airway pressures, right atrial filling is limited due to a reduction in transmural pressure, which may decrease RV preload (though this effect may be diminished as lung compliance worsens). While positive pressure ventilation generally reduces transmural pressures across both ventricles (which would be expected to reduce ventricular afterload and metabolic demand), increases in PVR observed during PARDS can overwhelm the modest reduction in RV afterload and stress the RV myocardium. As PARDS severity worsens, PVR rises due to hypoxia-/hypercarbia-mediated vasoconstriction, reduction in recruited alveolar units, and higher mean airway pressures generated in an effort to sustain systemic oxygenation. These stressors to the RV are not easily correctable. The RV of an older child generally has the capacity to handle acute increases in RVEDP and RVEDV by mounting an increase in RV contractility and moderate dilatation . As discTo the credit of the PALICC investigators, the RV is mentioned as a potential culprit worthy of interrogation in the setting of “suspected cardiac dysfunction” during PARDS . UnfortuWhile a general gestalt exists amongst pediatric cardiologists and intensive care providers, an objective, operational definition of pediatric RV dysfunction or failure remains elusive for a number of important reasons. First, there is not a consensus among pediatric cardiologists regarding whether RV dysfunction should be categorized according to systolic dysfunction, diastolic dysfunction, or both. Second, while most pediatric cardiologists and pediatric intensive care providers would agree that a battery of biomarkers and echocardiographic data are essential to diagnosing RV dysfunction at the bedside, the precise assays and ultrasonic readouts required for diagnosis continue to be debated. Moreover, many echocardiographic measures commonly employed to determine RV function in adults remain unvalidated in children and are rarely performed by pediatric sonographers.Early and persistent RV hypertension and dysfunction have been associated with higher mortality in children with ARDS , 25. How2/FIO2 ratio <150 mmHg, PaCO2 ≥48 mmHg, and driving pressure ≥18 cmH2O , and inspiratory pulse pressure variation (reverse pulsus paradoxus) on invasive arterial pressure monitoring that is unresponsive to volume expansion. Children with RV dysfunction commonly develop acute hepatomegaly that can result in abdominal distention and worsening respiratory system compliance from thoraco-abdominal competition. Anasarca that is unrelated to fluid overload manifests due to a persistently elevated CVP that leads to elevated hydrostatic pressures in peripheral microvascular beds. Similarly, high CVP may reduce lymphatic drainage into the subclavian veins that can result in pleural effusions and ascites. Feeding intolerance manifest as a reduction in intestinal perfusion pressure and due to the peritoneal space occupation by severe hepatomegaly. Elevated plasma levels of brain-type natriuretic peptide (BNP) or N-terminal pro-BNP are sensitive but nonspecific markers of RV wall stretch and, in the absence of frank renal failure, are commonly employed to evaluate for RV wall stress and right atrium/RV dilation . ClimbinUltrasonographic assessment, both by formal comprehensive echocardiography and by point-of-care ultrasound, is now one of the hallmark methods for diagnosing RV dysfunction in PARDS. In the PICU, transthoracic echocardiography (TTE) is most commonly employed because of its noninvasive approach and capability of being performed at the bedside by a sonographer without the express need for a cardiologist present. TTE also affords the ability for serial examination of the heart in concert with dynamic changes during the course of PARDS. However, adequate acoustic windows can be challenging to acquire during PARDS, and the retrosternal position of the RV may further complicate proper image acquisition. The American Society of Echocardiography recommends both qualitative and at least one quantitative assessment to determine RV systolic function in adults . Though Due to its complex geometry, singular measurements of linear dimensions are rarely sufficient functional readouts, and commonly used measures of LV function  are unreliable with two-dimensional sonography of the RV. Qualitatively, using an apical 2 or 4 chamber view, RV diameter can be grossly, though subjectively, compared to LV diameter. This assessment may be further quantified as the RV/LV end-systolic diameter ratio. In older children (average age ~8.5 years), normal RV/LV ratios have been reported to be <0.6 with values >1 being associated RV hypertension and adverse clinical outcomes . QualitaVTI) using continuous-wave doppler. When combined with an average CVP measured in the superior vena cava or right atrium, this peak velocity can provide a more objective measure of systolic pressures the RV is capable of mounting [RV systolic pressure = average right atrial pressure + 4*(VTI)2]. Longitudinal shortening can be measured quantitatively using tricuspid annular plane systolic excursion (TAPSE)  . TAPSE i (TAPSE) . There a (TAPSE) ; howeverFractional area change of the RV can also provide a quantitative measure of systolic function. In the apical view, the RV cavity is traced and measured in end-diastole and end-systole. A reduction of at least 1/3 of the area from diastole to systole suggests normal RV systolic function in adults . HoweverZ scores for children using two-dimensional speckle tracking echocardiography, which may prove helpful in quantifying RV systolic function during PARDS in the years to come. However, until RV strain measures are more consistently performed by pediatric cardiologists and reported strain values are more widely circulated in literature, the utility of employing RV strain values to diagnosis new or persistent RV systolic dysfunction during PARDS remains unknown.RV wall strain pattern has become a helpful adjunct to diagnose RV systolic dysfunction in adults , 41. A rP/dt), approximating the rate of rise in RV pressure during early systole reflective of RV systolic performance. Though each of these advanced imaging modalities may eventually prove useful  in diagnosing RV dysfunction in the setting of PARDS in the future, their availability and scope of use outside the management of congenital heart disease remain quite limited.In addition to changes in RV geometric dimensions or RV wall strain, various doppler measurements of RV performance may have utility in diagnosing RV systolic and/or diastolic dysfunction during PARDS. Tissue doppler imaging of the RV free wall at the level of the tricuspid annulus can be used to measure myocardial systolic peak velocity (s′), early diastolic velocity (e′), and late diastolic velocity (a′); together, these readouts provide valuable real-time information on RV myocardial contractility and relaxation. To corroborate RV s’ data and detail RV systolic function, sonographers may capture the isovolumetric acceleration of the basilar aspect of the RV free wall that can provide more specific information on RV longitudinal shortening. Myocardial performance index (Tei index), measured as the sum of the duration of the cardiac cycle in RV isovolumetric contraction and relaxation divided by the duration of RV ejection, may provide a sensitive readout suggestive of either RV systolic or diastolic dysfunction. Finally, in the presence of tricuspid insufficiency, changes in tricuspid regurgitation velocity can be measured and reported as a change in pressure over change in time  in an effort to preserve FRC  and drive oxyhemoglobin saturation above 90%. Caution is warranted here as prolonged exposure to high FIO2 may contribute to ventilator-induced lung injury, and exposure to high mean airway pressure without re-evaluation of RV performance may precipitate further RV decline. Permissive hypercapnia goals should be tightened, though a precise upper limit of PaCO2 is unclear at this time. Acidemia should be corrected either with judicious increases in minute ventilation (while limiting driving pressure) and/or with increased circulating levels of bicarbonate. There is insufficient evidence to support mode of ventilation  to accomplish these goals, regardless of RV function  in the setting of LV systolic failure, therapies that directly target PVR reduction are logical to prescribe in the setting of PARDS-related RV systolic dysfunction. The most commonly prescribed first-line treatment for increased PVR during PARDS is inhaled nitric oxide (iNO)  given itOrally administered systemic vasodilators, such as sildenafil (phosphodiesterase 5 inhibitor), ambrisentan (endothelin receptor antagonist), bosentan (endothelin receptor antagonist), and riociguat (stimulator of guanylate cyclase), are typically utilized in children with chronically elevated PVR from diseases such as bronchopulmonary dysplasia, congenital heart disease, or sickle cell anemia , 66. In 1 G-protein coupled receptors with variable activity on pulmonary arterial vasodilatation through β2-receptors  or dobutamine (1–20 μg/kg/min) are catecholamines used to promote inotropy through βeceptors , 67. TheCalcium is an important inotrope in an infant with RV dysfunction. Prior work has demonstrated that infants treated with intravenous calcium following cardiopulmonary bypass demonstrated significant improvements in cardiac output and mean systemic blood pressure compared to infants who did not receive calcium . SimilarMilrinone may be considered in a hemodynamically stable children RV dysfunction due to PARDS. Milrinone is a phosphodiesterase 3 inhibitor, promoting pulmonary and systemic vasodilation along with myocardial inotropy by decreasing the degradation of cyclic adenosine monophosphate within vascular smooth muscle and myocardium, respectively. However, milrinone should be used with caution. It may promote global pulmonary vasodilatation that could worsen the respiratory shunt fraction and exacerbate systemic hypoxemia. Moreover, the long half-life and renal clearance of milrinone may precipitously lead to refractory hypotension in a child developing impaired renal function . In a he1-receptors, norepinephrine raises the systemic diastolic pressure and thus may improve coronary perfusion. Norepinephrine also has mild activity on myocardial β1-receptors that can improve both RV contractility and the LV contribution to RV cardiac output. In addition, norepinephrine increases LV afterload that results in higher LV end-diastolic pressures to compete against the rightward-shifting interventricular septum during RV failure  . TypicalThe notion of preload dependence in a failing RV has merit, and increasing intravascular volume in an acutely hemodynamically unstable patient may be necessary. However, excess preload can worsen RV dilatation, resulting in septal bowing into the LV, tricuspid regurgitation with worsening venous congestion, and increased RV myocardial wall tension that compromises coronary perfusion pressure and may precipitate clinical decompensation , 76–78. The decision to deploy extracorporeal membrane oxygenation (ECMO) for severe PARDS refractory to lung-protective ventilation is often challenging and emotionally charged. The pediatric intensivist often has to guide a family through the complex risks and benefits of deploying ECMO for their child in a time-sensitive manner with limited information. When RV dysfunction develops in the setting of severe PARDS, complex treatment decisions can become substantially more intricate. Here we would like to discuss (1) the decision to use venovenous (VV) versus venoarterial (VA) ECMO as the initial cannulation strategy for PARDS complicated by RV dysfunction and (2) specific treatment decisions around RV dysfunction during VV ECMO.2 and restoring precapillary oxygenation may reduce PVR and improve RV systolic function , the primary etiology is an isolated elevation in cardiac output, and other potential diagnoses are ruled out or treated. Bunge et al.  reportedAlthough a precise definition for RV dysfunction in children has not been settled, it is clear that embarrassment of RV systolic and diastolic function in the setting of PARDS is associated with worse clinical outcomes. PARDS outcomes are usually not dictated by PARDS severity alone and appear to have a greater association with the development of multiorgan failure , 106. WeLW, JL, PP, and RR equally contributed to the conception of the manuscript. LW, LB, AM, PP, JL, and RR substantially contributed to the writing and revision of the manuscript and approve its final draft. All authors contributed to the article and approved the submitted version.RR is funded through the National Institutes of Health National Institute of General Medical Sciences grant 5K08 GM144788-02. This grant was used to cover the publication cost for this manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Previous studies have reported impairment in systolic and diastolic function in people with HIV (PWHIV). Our aim was to determine if echocardiographically measured left ventricular (LV) global longitudinal strain (GLS) is abnormal in asymptomatic PWHIV.n = 98, 89% male, median age 53 years) and HIV-negative people  without known cardiovascular disease were recruited from a single centre. All participants completed a health/lifestyle questionnaire, provided a fasting blood sample, and underwent a comprehensive echocardiogram for assessment of diastolic and systolic LV function, including measurement of GLS.A cross-sectional study of PWHIV (p = 0.14] or left ventricular ejection fractions . Following adjustment for covariates , the difference in GLS remained non-significant. There were no differences in LV diastolic function between the groups. Exposure to at least one mitochondrially toxic ART drug  was not associated with impairment of LV systolic function.All PWHIV were receiving antiretroviral therapy (ART) for a median of 12 years , the majority with good virological control (87% suppressed) and without immunological compromise . Compared with controls of similar age and gender, there was no difference in GLS [mean GLS −20.3% (SD 2.5%) vs. −21.0% (SD 2.5%), No clinically significant impairment of myocardial systolic function, as measured by LV GLS, was detected in this predominantly Caucasian male population of PWHIV on long-term ART, with no history of cardiovascular disease. The success of antiretroviral therapy (ART) has shifted the course of HIV to one of near-normal life expectancy, albeit with an increased prevalence of serious non-AIDS conditions, including cardiovascular disease. People with HIV (PWHIV) are at increased risk for atherosclerotic cardiac disease , 2, and The majority of echocardiographic studies examining left ventricular systolic function in PWHIV have been limited to evaluation of changes in left ventricular ejection fraction and ventricular volumes. The use of left ventricular global longitudinal strain (GLS) offers the possibility of identifying a subgroup of PWHIV who have not yet manifested clinical evidence of heart disease but are developing cardiac dysfunction not evident from measurement of LV ejection fraction. Identification of such individuals could allow early-targeted intervention to prevent further progression. The earlier studies in small patient groups included measurement of GLS in PWHIV , 26. MorThe primary objective of this study was to determine the potential value of screening for subclinical cardiac dysfunction in adults with HIV. We assessed cardiac function, as estimated primarily by GLS, detected in adults with well-controlled HIV on antiretroviral treatment compared with an HIV-negative control group of similar age, ethnicity, and sex. In addition, we examined the factors, including ART, that may contribute to cardiac dysfunction in PWHIV.via advertising. All participants with HIV were receiving ART. Individuals were excluded if they had a history of myocardial infarction, cardiac surgery, atrial fibrillation, significant arrhythmia or known valvular heart disease, in addition to newly diagnosed valvular heart disease detected during screening.This single centre study recruited PWHIV, aged between 30 and 70 years, when they attended the Infectious Diseases outpatient clinic for routine HIV care. A convenience sample of HIV-negative healthy volunteers of similar age (+/− 5 years) and sex was recruited The participants attended for a single research visit following an overnight fast. At this visit, transthoracic echocardiography was performed, medical history was taken , blood pressure was measured with Philips Suresigns VS3 after a 5 min rest, and blood was collected for markers of HIV control , renal function, glucose levels, and lipids . Hypertension was defined as a systolic blood pressure above 140 mmHg, diastolic blood pressure above 90 mmHg, or prescription of antihypertensive medication. The duration of known HIV infection and the duration of ART were determined as the time from first positive HIV serology or time of ART start to study visit, respectively. An undetectable HIV viral load was defined as <20 copies/ml.The participants completed a questionnaire concerning lifestyle factors such as smoking, drug use, diet, alcohol consumption, and usual exercise levels, as well as symptoms potentially related to heart failure.−2 BSA. Biplane disc summation method was used to calculate left atrial (LA) volumes in the four-chamber views, and these values were indexed by BSA as LA volume index (LAVI) in g m−2 BSA. The LV volumes were measured by biplane 2D Simpson's method, and LV ejection fraction was calculated using standard equations.Comprehensive transthoracic echocardiography was performed using a cardiac ultrasound system  by a single echocardiography-trained cardiologist. Two-dimensional data acquisitions were obtained from parasternal long-axis and short-axis views and the three standard apical views. For each view, three consecutive cardiac cycles were recorded. The LV diameters and the interventricular septal wall and posterior wall thickness were measured at end-diastole from M-mode recordings according to the guidelines of the American Society of Echocardiography , 31. LV The mitral valve inflow peak early filling velocity (MVE) and deceleration time (MVDT) of the early filling velocity were assessed by pulsed-wave Doppler in the apical four-chamber view. Tissue Doppler Imaging (TDI) was also performed in the apical four-chamber view. The early diastolic annular velocity (e') was measured by TDI recordings. For the assessment of global LV diastolic function, Tissue Doppler signals at the septal and lateral sides of the mitral annulus were acquired, and their mean values were calculated, providing early diastolic Tissue Doppler mean velocity (e' mean). The ratio of MVE to e' mean (MV E/e') was then calculated. Diastolic dysfunction was defined if 3 or more of e’, MV E/e’ ratio, LAVI, and peak tricuspid regurgitation (TR) velocity were abnormal.All data of speckle tracking were analysed offline using a dedicated automated software (Qlab). Three endocardial markers were placed in an end diastolic frame at apical 4-, 2-, and 3-chamber views for the 2D longitudinal speckle tracking analysis. The software automatically tracked the contour of endocardium to cover the myocardial thickness of the entire LV wall. Appropriate tracking was corroborated in real time and manually adjusted for the area of interest to ensure accurate tracking. The mean LV global GLS was calculated for the 18 segments  in relation to the strain magnitude at aortic valve closure. A single observer made LV GLS measurements. The coefficient of variation (CV) for repeated measures was <2%.For the sample size estimation, the published average GLS of −19.7% (CI −20.4 to −18.9) in healthy people without known cardiovascular disease  or HIV wχ2 or Fisher's exact test, Student's t-test, or Mann–Whitney U test, as appropriate.The participant demographics, echocardiography variables, and lifestyle factors were described using frequencies (%), mean , and median , depending on distribution. Unadjusted comparisons between individuals with and without HIV were made using a The primary outcome was the mean difference (SD) in LV GLS between individuals with and without HIV. Secondary outcome measures included differences in echocardiographic measures of LV systolic and diastolic function and right heart function.p-value less than 0.05 from the unadjusted analysis were included in a multivariable model, with the a priori specified variables of gender and systolic and diastolic blood pressure. Using a stepwise selection procedure, only variables that were significant at p < 0.05 were retained in the final model.To determine the factors that might impact the relationship between LV GLS and HIV, the participant demographic, lifestyle variables, and echocardiographic variables with a All analyses were performed using STATA, v17.0 .All participants provided written informed consent. The study was approved by the Alfred Hospital Ethics Committee (Project: #240/17).n = 100) and HIV-negative controls (n = 50) were recruited. Two PWHIV were subsequently excluded because they were found to have significant valvular disease on echocardiography; thus, 98 PWHIV were analysed. The participants with HIV were predominantly male [90 (91.8%)] with a median age of 53 years and Caucasian [82 (83.7%)], reflecting the demographic of PWHIV receiving HIV care at this centre.PWHIV  had low level viremia with a median HIV RNA of 35 (IQR: 27–35) copies/ml.PWHIV had a long median duration of HIV infection [13.9 years (IQR: 8.5–24 years)], were all on ART, largely with a suppressed viral load (87%), and had good immunological function  . Those wp < 0.001, p = 0.137]). One patient in the HIV group had LV GLS higher than −15 (LV GLS = −13.5), giving a prevalence of subclinical cardiac dysfunction, as estimated by GLS, of 0.68%.In univariate analyses, PWHIV had higher mean heart rates . PWHIV demonstrated less evidence of early systolic dysfunction with lower LV mass ; however, this was no longer significant after adjustment for covariates . There was no association between log10 CD8 cell count nor viral load with GLS in PWHIV.In PWHIV, there was a borderline significant correlation between GLS and logp = 0.027). PWHIV were less likely to have undertaken vigorous activity in the last week (p = 0.022) and were more likely to report shortness of breath that was limiting their usual activity (p = 0.019). There was no difference in the reported incidence of peripheral oedema, positional dyspnoea, or difficulty climbing stairs , had a longer duration of ART , and a median of 10.0 years  exposure to the older ART drugs. They had higher mean systolic (136 mmHg vs. 123 mmHg) and diastolic (85 mmHg vs. 78 mmHg) blood pressures, and a lower mean BMI  than those who had not  people had been exposed to older, mitochondrially toxic antiretrovirals  . PWHIV w had not . They weWhen comparing PWHIV who had or had not been exposed to older mitochondrial toxic antiretroviral therapy , we found no difference in mean GLS . Those ep = 0.018]. A similar association was found for LVEF . There was no alteration to the directionality of the results. When adjustment for the other factors significant on univariate analysis were included, the association between GLS and exposure to older ART became non-significant, whilst the association between LVEF and exposure to older ART remained borderline significant .Because there was a significant age difference between those PWHIV who had or had not been exposed to the older ART, multivariate regression was performed adjusting for age to determine if this was driving the differences in the echocardiography parameters detected. After adjustment, the association between GLS and PWHIV exposed to older ART was significant indicating that those exposed to older ART had significantly lower GLS [OR (95% CI) of 0.79 , We found no difference in mean GLS values between people with well-controlled HIV infection and controls, with all GLS values measured, except one in a person with HIV, within the normal range in adults . PWHIV hIn PWHIV in our study, there was also no difference in GLS between those who had received “older” mitochondrially toxic ART compared with those who had not, whilst left ventricular ejection fraction, left ventricular mass index, and systolic and diastolic blood pressure were higher in those who had received one of the older drugs. After adjustment for age only, GLS was significantly lower in those who were exposed to the more toxic ART drugs. Whilst there was a significant difference in diastolic function, as assessed by the ratio of early mitral inflow velocity and mitral annular early diastolic velocity (E/e'), and pulmonary pressures between those exposed to or not exposed to older mitochondrially toxic ART drugs, the values were still within the normal range for both groups. A large study of 662 men with HIV compared with 533 men without HIV from the Multicenter AIDS Cohort reported a lower LV mass in those currently receiving nucleoside reverse transcriptase (NRTI) containing ART, but they did not differentiate the older mitochondrial toxic ART and current exposure to less toxic NRTI .The difference in heart rate between groups may be explained by a difference in fitness level. People without HIV had a higher LV mass index despite a lower blood pressure, which would, along with a lower heart rate, be compatible with increased cardiovascular fitness. There were minor differences in reported levels of exercise and more PWHIV reported exertional symptoms, which in the absence of differences in LV function and clinical evidence of cardiac failure or respiratory disease, might represent a reduced level of fitness. All PWHIV were under regular medical review, and none had physical findings thought to be due to heart failure. As in the general population, cardiorespiratory fitness has been observed to decline with age in PWHIV unrelated to the duration of HIV or immunological parameters .Whilst previous echocardiographic studies have reported impairment in both systolic and diastolic function in PWHIV, there are a number of differences between the current study and previous reports. Several, but not all, studies contained no control group and referenced results against population data , 27, 28.Diastolic left ventricular dysfunction has been reported to occur in PWHIV regardless of receipt of ART . The parThere is only one retrospective study that has assessed changes in cardiac structure and function longitudinally over 5 years, and these were performed in patients referred for echocardiography, so potentially a biased group. Whilst LV GLS, mass, and volumes were associated with markers of HIV disease control early in the course of infection , the autThere are a number of study limitations to consider. This was a small cross-sectional study of virologically suppressed, predominantly Caucasian men with HIV and no history of pre-existing cardiovascular disease. Thus, the findings may not be generalisable to the greater population of PWHIV. In addition, it is likely that people with significantly elevated pulmonary pressures may have been excluded by our study inclusion criteria. Whilst the groups were well matched for age and gender, there were significant differences in some other parameters that may have contributed to the findings. The study is strengthened by a single cardiologist performing and analysing the echocardiograms on all participants, in a single centre.As the majority of studies have been cross-sectional, it is imperative to understand changes in cardiac structure and function over time. The impact of immediate initiation of ART at HIV diagnosis, level of immunodeficiency, and exposure to contemporary well-tolerated ART on parameters of ventricular function needs further characterisation but supports earlier diagnosis and treatment of HIV.In summary, in this cohort of PWHIV with good virological control after 12 years of ART, we found no difference in left ventricular GLS compared with controls, which was within the reference levels for the general population. Despite the observed increased risk of clinical heart failure, and an increased prevalence of systolic and diastolic dysfunction reported in some echocardiographic and cardiac magnetic resonance imaging studies in PWHIV, our study does not support routine screening of asymptomatic individuals with echocardiography in people with HIV and similar characteristics to those presented in this study.