The definitive diagnosis of myocarditis is made by endomyocardial biopsy, but it is an invasive method. Recent investigations have proposed that cardiac MRI parameters have both diagnostic and prognostic roles in assessing myocarditis. We aimed to evaluate the role of functional and feature-tracking (FT)-derived strain values in predicting major adverse cardiovascular events (MACE) in patients with acute myocarditis.We evaluated 133 patients with acute myocarditis (74.4% men) between January 2016 and February 2021. During a mean follow-up of 31 ± 16 months, sixteen patients (12.03%) experienced MACE: three deaths (2.3%), nine ICD implantations (6.76%), and five cardiac transplantations (3.8%). The left ventricular ejection fraction (LVEF), the LV end-diastolic volume index (EDVI), and the LV global longitudinal strain (GLS) were the strongest predictors of MACE. Each 1-unit decline in LVEF and LVGLS or 1-unit rise in LVEDVI resulted in a 5, 24, and 2% increase in MACE, respectively. LVEF ≤36.46% and LVGLS ≤9% indicated MACE with 75% sensitivity and 74.4 and 73.5% specificity, respectively.In a group of acute myocarditis patients with evidence of myocardial edema and late Gadolinium enhancement, LVEF and GLS were the strongest predictors of adverse cardiac events. Myocarditis is an inflammatory myocardial disorder diagnosed by clinical, imaging, histological, immunological, and immunohistochemical criteria. Myocardial involvement is typically due to systemic viral infections, consisting of systemic inflammatory diseases and toxins; nonetheless, various infectious and non-infectious causes can result in myocarditis , 2.It is difficult to ascertain the exact frequency of myocarditis due to the wide variety of clinical signs and symptoms. It is assumed that its incidence is 1–10 cases per 100 000 persons. Clinical history ranges from mild symptoms to findings of acute decompensation of heart failure. Feldman et al. classified myocarditis as follows: fulminant myocarditis, acute myocarditis, chronic active myocarditis, and chronic persistent myocarditis . EndomyoAlthough the cardiac condition of most patients with myocarditis improves over time, some patients progress to devastating consequences. Accordingly, finding measures to predict prognosis is of utmost importance. Various CMR studies have derived different results on the predictive role of CMR parameters in patients with myocarditis , 7.Strong evidence characterizes the role of echocardiographic strain especially global longitudinal strain (GLS) in evaluating different myocardial disorders , 9.Recent research has underscored the value of CMR-derived myocardial strain measurement in the assessment of different types of cardiomyopathies –12. EvalSome previous studies have shown a significant association between cardiac prognosis and decreased ventricular strain values in myocarditis and other cardiomyopathies , 14–16.In the present study, we aimed to evaluate the role of functional and FT-derived CMR strain values in predicting major adverse cardiovascular events (MACE) in patients with the diagnosis of acute myocarditis.We evaluated all CMR examinations with a final diagnosis of acute myocarditis between January 2016 and February 2021. Based on electronic reports, the selection criteria were among patients who had all these four criteria: (1) History of acute symptoms (including dyspnea and chest pain) within a few days before admission. (2) Increased troponin levels. (3) Normal coronary angiography (no coronary artery disease) or CT angiography results during hospitalization. (4) CMR images with evidence of myocardial edema as well as mid-wall and subepicardial LGE . We founMACE was defined as the incidence of cardiac death, an implantable cardioverter-defibrillator (ICD) implantation, or heart transplantation.All the patients were assessed for the possible existence of MACE during a follow-up time of 10–69 months (mean ± SD: 31 ± 16 mon). We extract the follow-up data from patients' electronic records and telephone calls.CMR was accomplished using a 1.5-Tesla scanner  with an 8-element cardiac-phased array receiver surface coil.All ECG-gated cine functional sequences were done during an end-expiratory breath-hold. Left ventricular (LV) 2, 3, and 4-chamber views, as well as a stack of contiguous short-axis with LV coverage from inflow to apex, were acquired with sequence parameters, including a field of view (FOV) of 300 mm, an imaging matrix of 156 × 192, a slice thickness of 8 mm, no interslice gaps for short-axis images, and repetition time/ echo time of 31/1.2 ms. LV volume and LV systolic function were analyzed by tracing end-diastolic and end-systolic endocardial borders on cine short-axis images.Myocardial inflammation was assessed utilizing the short tau inversion recovery (STIR) series as a ratio of myocardial-to-skeletal muscle signal intensity of more than 1.9 .LGE extent was determined visually by a 17-segment model; the presence and absence of LGE in each LV myocardial segment were scored as 1 and 0, respectively, and the sum of the scores (maximum: 17) was reported as the LGE-visual presence score (LGE-VPS) .Due to the retrospective nature of our study, the mapping technique was unavailable. Therefore, we selected the myocarditis patients according to the old LLC, including 2 of 3 positive findings of myocardial hyperemia, edema, and LGE .CMR images were analyzed offline utilizing the FT software CVI 42 , version 5.6.2 (634). All endocardial and epicardial borders were manually traced in the end-diastolic phase and then propagated to the whole cardiac cycle in short-axis stacks and 2-, 3-, and 4-chamber planes to identify 3D global longitudinal, circumferential, and radial strains . Additionally, 2D right ventricular GLS was extracted from the 4-chamber view and RVGCS and RVGRS from the short-axis view. Image brightness was adjusted to discriminate between the endocardium and the blood pool. Longitudinal strain depicts longitudinal myocardial fiber shortening from the base to the apex, while circumferential strain shows the percentage of myocardial shortening around the perimeter –F. On thAll patient's electronic medical records were evaluated for myocardial biopsy data.U test to compare the parameters between the 2 groups. Independent sample t-test was to compare CMR parameters between groups with LVEF≥ 40 and <40%. Significantly different variables were entered in the stepwise logistic regression analysis to find the significant variables in the regression model to reveal the occurrence of MACE. The receiver operating characteristic (ROC) analysis was utilized to find the cutoff values of CMR parameters for predicting MACE. The area under the curve (AUC), sensitivity, and specificity were reported. A cutoff value of 0.05 was considered to denote statistically significant results.The SPSS software, version 22.00, was utilized for analyses. Continuous variables were presented as the mean ± SD, while categorical variables were demonstrated as frequencies and percentages. Considering the sample size discrepancy between the MACE positive and MACE negative groups, we applied the Mann–Whitney The study population was composed of 133 patients, including 74.4% men, at a mean ± SD age of 37 ± 16 years diagnosed with myocarditis between January 2016 and February 2021. Sixteen out of the 133 patients (12.03%) experienced MACE during a mean ± SD follow-up of 31 ± 16 months: three deaths (2.3%), nine ICD implantations (6.76%), and five cardiac transplantations (3.8%). One patient (0.75%) underwent ICD implantation and heart transplantation.As we can evaluate the previous reports among patients with history of ICD implantation, seven out of nine patients had LVEF< 36%, and two out of nine patients had a history of recurrent VT that resulted in ICD implantation.U test revealed a significant difference in the following parameters in patients with and without MACE: biventricular EF and end-diastolic volume index (EDVI), left atrial (LA) volume, biventricular GLS, LVGCS, LVGRS, LV global longitudinal systolic strain rate and LV global circumferential diastolic strain rate (The Mann–Whitney ain rate .P = 0.01) and 1.017 and CI: 1.006–1.028 (P = 002), respectively. In other words, each 1-unit decrease in LVEF and increase in LVEDVI resulted in a 5 and 2% rise in the incidence of MACE, respectively.All significantly different variables were entered in the stepwise logistic regression analysis in the next step. Only LVEF and LVEDVI were meaningful in the model with an odds ratio of 0.946, confidence interval (CI): 0.904–0.989 (P < 0.001). That is to say, each 1% decrease in LVGLS resulted in a 24% increase in the incidence of MACE.The biventricular deformation parameters were entered in the stepwise logistic regression analysis. LVGLS was the meaningful variable with an odds ratio of 0.760 and CI:0.655–0.882 (P<0.001). Furthermore, a maximum LVGLS of 9% predicted MACE with 75% sensitivity and 73.5% specificity .The ROC curve was drawn upon to determine cutoff values . A maximBased on the patient's electronic medical records, myocardial biopsy data were found in 11 (8.2%) cases. In two patients, the specimen was inadequate. Nine patients had evidence in favor of active myocarditis . The mean value and SD of the CMR parameters are depicted in This retrospective cohort analysis reviewed the CMR findings of 133 patients with the diagnosis of acute myocarditis referred for CMR at the first presentation. We assessed the relationship between cardiac prognosis and functional and FT-derived strain parameters. A summary of our study results is as follows:The strongest predictors of MACE were LVEF and LVEDVI.The ROC analysis showed a sensitivity of 75% and a specificity of 74% for a maximum LVEF of 36.5% in the prediction of MACE. Each 1-unit decrease in LVEF resulted in a 5% increase in the incidence of MACE.Among deformation parameters, LVGLS was the most potent predictor of MACE. A maximum LVGLS of 9% could predict MACE with a sensitivity of 75% and a specificity of 74%. A 1% decline in LVGLS resulted in a 24% increase in the incidence of MACE.In our study population, the incidence rate of MACE was about 12%. In a prospective analysis of 539 unselected patients with 37 cases of myocarditis performed by Mordi et al. MACE occurred in 8.1% over a mean follow-up time of 2.2 years. .In the present investigation, we included LGE + patients with acute myocarditis and found that LV function played an essential role in predicting the outcome even in patients with morphologically altered myocarditis. Our results also showed that LVEF with a cutoff value of 36.5% was able to predict MACE. It is logical to assume that moderate LV systolic dysfunction is the strongest predictor of adverse cardiac events.Our analysis of the correlation between strain parameters and adverse cardiac events revealed that LVGLS with a cutoff value of 9% was the strongest deformation parameter to predict mortality, ICD implantation, and heart transplantation within the follow-up. Similarly, in a study by Garcia-Ropero et al. FT-derived LVGLS was an independent predictor of prognosis and disease severity among patients with acute myocarditis . In anotIt is assumed that GLS represents the function of longitudinally oriented subendocardial myocardial fibers , while GInterestingly, we found that each 1% decrease in absolute LVGLS value caused a 24% increase in the incidence of MACE. It confirms the meaningful role of minor LV longitudinal strain alterations in demonstrating hard cardiac events in patients with acute myocarditis. We believe that FT-CMR strain measurement will play a more prominent role in the management of patients with myocarditis in the future.We divided the study population into two groups according to LVEF> or <40%. All global strain values, EF and LVEDVI, differed between the two groups. We noticed no difference in the LGE extent between the patients with and without MACE or LVEF> or <40%. This research investigated myocarditis patients with edema and LGE in the acute phase MRI, which may represent underlying inflammation to a great extent and not precisely reflect the fibrosis. Thus, we suppose that the initial LGE extent probably is not a potent predictor for adverse outcomes.A dearth of follow-up information forced us to select only hard events  as outcomes, making these prognostic factors more invaluable. Functional and FT strain parameters can be calculated without prescribing a gadolinium contrast agent or requiring a unique cardiac sequence. In addition, they can select patients with acute myocarditis who need intense follow-up visits.Based on electronic medical records, we found eleven patients with cardiac biopsy results consisting of nine with evidence in favor of acute myocarditis. Interestingly, seven out of nine patients had MACE during follow-up. It may refer to selecting patients with a more acute nature of the disease for myocardial biopsy, but prospective studies focusing on the role of cardiac tissue sampling are required.In this research, we encountered some limitations. Firstly, we had no access to prognosis in a minority of patients, prompting their exclusion from the study and reducing the sample size. Future larger-scale multicentric investigations could address this drawback. Secondly, a lack of imaging data in a significant number of the studied patients precluded us from employing novel mapping methods. Additionally, we reported a relatively higher incidence of MACE. We think it is somehow related to referral bias; Many low-risk young myocarditis patients do not refer for cardiac MRI. In our study, almost all events happened during the first 3 months after the acute event suggesting more severe cases. Further prospective studies are required to determine the exact incidence of MACE. Additionally, due to the retrospective design of our study, we could only access the limited data regarding the patient's history and risk profile, and for many other cardiac complications, we did not have a clear recording; therefore, we had to omit them from the study. Furthermore, we suppose that different experts' functional measurements, including strain values, and reporting the interobserver variability may improve the results' reliability. Last but not least, we included only patients with acute myocarditis; however, we suppose that a detailed CMR evaluation of other myocarditis categories and investigation of the prognostic role of measured parameters in each group will be of great value.The present study evaluated the role of functional and deformation parameters in predicting outcomes in patients with acute myocarditis. LVEF and LVEDVI had a significant role in indicating cardiac mortality, heart transplantation, and ICD implantation. In addition, LVGLS had a strong association with MACE among deformation parameters.The raw data supporting the conclusions of this article will be made available by the authors without undue reservation.The studies involving human participants were reviewed and approved by Rajaie Cardiovascular Medicine and Research Center. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.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.


Patients treated with anthracyclines and trastuzumab are at increased risk of developing heart failure. Early diagnosis and treatment may prevent irreversible left ventricular (LV) dysfunction. This study investigates whether subclinical deterioration of global longitudinal strain (GLS) is a more reliable early predictor for LV dysfunction than three-dimensional (3D) LV ejection fraction (LVEF).Adult patients receiving anthracyclines and trastuzumab for breast cancer who had serial echocardiographic follow-up were included in this retrospective study. The primary endpoint was the necessity to temporarily pause chemo- or immunotherapy due to declining LVEF (decline in 3D LVEF of > 10 percentage points to < 53%). Linear mixed-effects models were used to assess the longitudinal evolution of 3D LVEF and GLS over time.p < 0.001). A decrease in GLS significantly predicted a lower LVEF on the subsequent echocardiogram . Conversely, prior LVEF did not significantly predict GLS on the subsequent echocardiogram . Nine patients reached the primary endpoint. On average, patients who reached the primary endpoint had a relative decrease of 15% GLS at day 205 and an absolute 10% decrease of LVEF to LVEF < 53% at day 235.Fifty-one women were included, mean age 54 (50.5–57.6) years, with a total of 216 follow-up echocardiograms (mean follow-up 1.1 ± 0.45 years). GLS and 3D LVEF were significantly correlated  contains supplementary material, which is available to authorized users. Myocardial strain imaging using global longitudinal strain (GLS) is able to identify subclinical left ventricular (LV) dysfunction earlier than three-dimensional LV ejection fraction measurement in women undergoing treatment for breast cancer with anthracyclines followed by trastuzumab.It remains to be established whether the use of GLS to guide early cardioprotective therapy results in improved clinical outcomes and which patients are at highest risk of developing cardiotoxicity.Cardio-oncology is an emerging field of interest in cardiology that focuses on the detection, monitoring and treatment of cardiovascular disease occurring as a side-effect of chemotherapy and radiotherapy. Cardiological assessment before starting potentially cardiotoxic cancer treatment is essential and should be continued throughout the oncological treatments, since left ventricular (LV) dysfunction can occur at any time.The cardiotoxicity of anthracyclines is well-recognised, dose-related and irreversible . TrastuzA recent consensus paper from the European Society of Cardiology proposed a definition of chemotherapy-related cardiotoxicity as an LVEF decrease of > 10 percentage points from baseline to a value < 53% on repeat confirmatory echocardiographic imaging . NeverthGlobal longitudinal strain (GLS) has been found to be a useful marker to detect subclinical myocardial dysfunction , 6. An eThe primary objective of our study is to assess whether subclinical deterioration of GLS is a more reliable early predictor for LV dysfunction than 3D LVEF and can predict 3D LVEF decline later on. Furthermore, we will examine which baseline factors are associated with a high risk of cardiotoxicity in a cohort of women with breast cancer treated with anthracyclines followed by trastuzumab.Adult patients receiving anthracyclines and/or trastuzumab for breast cancer at Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands, from 2014 to 2017 and who had undergone echocardiography at baseline and every 3 months thereafter were identified. Exclusion criteria were an LVEF < 50% prior to chemotherapy or pregnancy. 2D echocardiographic image quality should be at least reasonable to allow reliable 3D LVEF assessment. Therefore, patients with moderate or poor image quality were excluded.A retrospective chart review was conducted to collect chemotherapy regimens, treatment interruption data, baseline characteristics such as age, blood pressure, previous medical history and use of cardiovascular medications, and outcome data. The Cardiotoxicity Risk Score (CRS) proposed by the Mayo Clinic was calculated from baseline characteristics to estimate the a priori risk of developing cardiotoxicity .LV function was measured by 2D (Simpson’s method) and 3D LVEF and myocardial strain analysis was done using 2D speckle-tracking imaging according to the recommendations of the European Society of Echocardiography , 11. EchThe study was approved by the Medical Research Ethics Committee of the Rotterdam Hospital area. Due to the retrospective nature of the study design no informed consent was required. The study was conducted according to the principles of the 1975 Declaration of Helsinki.The endpoint of this study was the necessity to temporarily pause chemotherapy due to declining LVEF. Criteria for pausing treatment were: a decline in 3D LVEF of > 10 percentage points and a 3D LVEF of < 53% . SecondaContinuous data are presented as mean ± standard deviation (Gaussian distribution) or median and interquartile range (IQR) (non-Gaussian distribution). Categorical data are presented as frequencies (percentage).Linear mixed-effects models were used to assess the longitudinal evolution of 3D LVEF and GLS and the absolute and relative percentage change of these outcomes compared to baseline over time. These models included random intercepts and slopes over time to capture the correlation of the repeated measurements in each patient. Natural splines with one knot were used to allow for flexibility of the subject-specific trajectories over time. Patients were censored at the time trastuzumab was paused.Survival probabilities were estimated and visualised by the Kaplan-Meier method. Univariable Cox proportional hazard models were used to explore determinants associated with the endpoint.The dropout of some patients is caused by LVEF itself, as this was the criterion for pausing treatment. Sensitivity analysis was performed, whereby the dynamic longitudinal evolution of GLS and 3D LVEF was inserted into a Cox model predicting dropout under the joint modelling framework. Modelling these entities together alleviates possible bias due to values that are missing not at random. The current value parameterisation was investigated .In total, 51 females with a mean age at baseline of 54 ± 12 years were included in the study. After review of the echocardiograms, one patient was excluded due to inadequate quality of the echocardiographic imaging.Baseline characteristics and echocardiographic characteristics at baseline are presented in Table S1 . In total, 12 (26%) patients had cardiac medications at baseline. During a mean follow-up duration of 1.1 ± 0.45 years, 5 patients died, yielding a Kaplan-Meier survival estimate of 70.5 ± 13.9% at 5 years. None of the deaths were related to a cardiovascular event. None of the patients showed signs of clinical heart failure or any cardiac event during follow-up.In total, 216 follow-up 3D LVEF measurements were available  and 215 GLS measurements .p < 0.001], whereas later in the follow-up period this decrease stagnated , as estimated by a linear mixed model adjusted for baseline 3D LVEF. An effects plot of the modelled longitudinal evolution of 3D LVEF is presented in Fig. Initially, 3D LVEF decreased significantly over time [ß −14.7, 95% confidence interval (CI) −20.1 to −9.3, p < 0.001), whereas later in the follow-up period this decrease stagnated , as estimated by a linear mixed model adjusted for baseline GLS. An effects plot is shown in Fig. GLS initially decreased over time . Additionally, age and hypertension were not associated with different starting points and slopes over time.n = 1) or because the length of the therapy was considered adequate (n = 2).In none of the patients were anthracyclines paused for cardiac reasons. In 9 (18%) patients trastuzumab was paused due to a decline in 3D LVEF without clinical symptoms, on average for the duration of 36 days. This resulted in a freedom to pause trastuzumab of 59.4% ± 14.9% at 2 years (Kaplan-Meier estimate). The measurements of 3D LVEF and GLS in these 9 patients are shown in Fig. S3 . All patients with subclinical LV dysfunction were started on cardioprotective medication: 8 patients on angiotensin-receptor inhibitors and 1 patient on a beta-blocker. In all patients the decline in LVEF was transient. In 3 patients the oncologists chose not the restart the trastuzumab due to other side-effects  and hypertension  were not associated with pausing trastuzumab. No attempts at multivariable modelling were conducted due to the limited number of events.CRS was not associated with a pause in trastuzumab treatment [hazard ratio (HR) 0.90, 95% CI 0.47–1.74, p < 0.001). A decrease in GLS significantly predicts a lower LVEF on the following echocardiogram  . Conversely, prior LVEF does not significantly predict GLS on the following echocardiogram , suggesting that a decrease in GLS precedes an LVEF decline and not vice versa.GLS and 3D LVED were significantly correlated  subclinical LV dysfunction can be detected on average 30 days earlier by a GLS decrease than by a 3D LVEF decline; (2) no baseline characteristics, such as age, hypertension and CRS, could be identified as predictors for cardiotoxicity; (3) in our cohort none of the patients reached a clinical endpoint and LV dysfunction was reversible after pausing trastuzumab.GLS is an established preclinical marker of cardiac dysfunction . It is wIn contrast to other studies, we were not able to demonstrate with our advanced statistical model that parameters such as increasing age, hypertension, 3D LVEF at baseline or CRS are clinical predictors for the development of cardiotoxicity , 16. ThiIn our study, once subclinical 3D LVEF deterioration occurred, trastuzumab was paused and heart failure therapy was initiated empirically on an individualised basis by the treating cardiologist. Whether initiation of cardioprotective medications improves the outcome in patients with subclinical cardiac dysfunction is not entirely clear. A study by Boekhout et al. did not support the hypothesis that concomitant use of candesartan protects against a decrease in LVEF during or shortly after trastuzumab treatment in breast cancer patients . In the An ongoing larger randomised controlled trial with angiotensin-receptor inhibitors and beta-blockers in patients receiving anthracycline and trastuzumab and evaluated with strain measurements is still awaited . The SUCWhile the clinical consequence of subclinical cardiotoxicity remains uncertain, interrupting cancer therapy might have deleterious effects with regard to cancer outcome. Two studies aimed to determine whether trastuzumab may be continued despite a subclinical LVEF decline. One small but interesting prospective study suggested that, in patients administered ACE inhibitors and beta-blockers, trastuzumab may be continued safely despite mild cardiotoxicity . HoweverThe SAFE-HEaRt trial studied LVEF during trastuzumab treatment in patients with an LVEF of 40%–49% prior to trastuzumab initiation . They weWhile follow-up was relatively long, with multiple echocardiograms per patient, cardiotoxicity can occur in a later stage of life. Therefore, observations might change in either direction during a longer follow-up period. The study was limited by its retrospective nature and relatively small sample size. The latter may also explain the relatively weak correlation of GLS and 3D LVEF, although the correlation was found to be significant, as expected. Larger-scale studies are necessary particularly to identify the clinical risk factors for cardiotoxicity, thereby identifying the high-risk patients who need intensified cardiac follow-up. Although GLS is a very promising early detector of subclinical LV dysfunction, it does have some limitations. Currently, there are different echocardiography machines and software packages with potential intervendor variability of strain measurements . NeverthMyocardial strain imaging using GLS is able to identify subclinical LV dysfunction earlier than 3D LVEF measurement in women undergoing treatment with anthracyclines followed by trastuzumab for breast cancer. After pausing trastuzumab and starting cardioprotective therapy, this LV dysfunction is potentially reversible. It remains to be established whether the use of GLS to guide early cardioprotective therapy results in improved clinical outcomes and which patients are at highest risk of developing cardiotoxicity.Fig. S1Fig. S2Fig. S3Fig. S4n = 51. Fig. S2 Kaplan Meier curve of longitudinal evolution of global longitudinal strain over time in patients who did not reach the endpoint. n = 51. Fig. S3 Relative change in global longitudinal strain and absolute change in left ventricular ejection fraction compared to baseline in the 9 patients that reached the primary endpoint. Fig. S4 3D plot of prior global longitudinal strain (x‑axis) predicting left ventricular ejection fraction (y‑axis) on the following echocardiogram adjusted for time (z‑axis). Both an increase in time and worsening prior global longitudinal strain are associated with lower left ventricular ejection fraction. n = 51Table 1. Baseline characteristics. Fig. S1 Kaplan Meier curve of longitudinal evolution of global longitudinal strain stratified to CRS scores of 5 and 7.


Trimethylamine N-oxide (TMAO)-related metabolites are associated with the pathogenesis of atherosclerotic cardiovascular disease (ASCVD) and are known to disrupt lipid metabolism. The aims of this study were to evaluate the associations between TMAO-related metabolites and blood lipids and determine how lowering the lipid profile via rosuvastatin therapy influences TMAO-related metabolites.A total of 112 patients with suspected ASCVD were enrolled in this study. The levels of plasma TMAO-related metabolites, including TMAO, choline, carnitine, betaine, and γ-butyrobetaine (GBB), were analyzed by stable isotope dilution liquid chromatography-tandem mass spectrometry (LC/MS/MS) before and after rosuvastatin therapy in all patients. Statistical methods were used to detect the associations between TMAO-related metabolites and blood lipids and determine how rosuvastatin therapy alters the levels of these metabolites.r = 0.303, P < 0.05). Furthermore, significant negative correlations were found between TMAO and high-density lipoprotein cholesterol (HDL-c) and between betaine and low-density lipoprotein cholesterol (LDL-c) . Compared to baseline, significantly lower TMAO levels and higher carnitine, betaine and GBB levels were observed after rosuvastatin therapy, while the lipids decreased significantly (P < 0.05). The significant correlation between TMAO and TG or between betaine and LDL-c disappeared after rosuvastatin therapy . However, a significantly positive association between carnitine and TC and a negative association between carnitine and LDL-c or between betaine and TG were found after adjustment for sex, age, body mass index (BMI) and lipids (P < 0.05).A significant positive correlation was found between TMAO and triglycerides (TG) (This study suggests that TMAO-related metabolites are significantly associated with blood lipids, although some of them are changed postrosuvastatin therapy. Lower TMAO and higher TMAO precursors were observed after rosuvastatin therapy compared to baseline. This study indicates that elevated TMAO precursors after rosuvastatin therapy and their potential impact on ASCVD should be considered in the clinic.The online version contains supplementary material available at 10.1186/s12944-022-01673-3. Trimethylamine N-oxide (TMAO) is an oxidative product of trimethylamine (TMA), which is generated from choline, choline-containing substances, L-carnitine, γ-butyrobetaine (GBB) and betaine by the gut microbiota –3. TMAO http://clinicaltrials.gov/ (No.02305862). Patients with suspected ASCVD who were willing to receive coronary angiography and carotid magnetic resonance imaging (MRI) were consecutively recruited from Beijing Tiantan Hospital between January 2013 and December 2016. The demographic characteristics, personal history and diagnosis were based on personal statements, clinical records, current drug usages, and auxiliary examinations in the hospital. The exclusion criteria were age < 18 years, stent implantation, uncontrolled hypertension, acute myocardial infarction, malignant tumor, heart failure, active infections, severe liver or kidney dysfunction, stroke, diabetes mellitus (DM), familial hyperlipidemia, and antibiotic usage. A total of 135 patients were recruited in this study, including 35 patients who received irregular statin therapy for less than 1 month and had a clearance period of at least 2 weeks. A total of 121 patients received rosuvastatin therapy because of hyperlipidemia, ASCVD, and/or other proper purposes. All patients were initially administered 20 mg rosuvastatin per night, and 4 of these patients were adjusted to 10 mg because of impaired liver function during the follow-up time. No patients suspended usage during the follow-up. All patients were given a recommended light diet before sampling and after discharge and monitored half-monthly at the outpatient department or by telephone interviews. Finally, 112 patients with complete follow-up data after 3 months of follow-up constituted the study cohort. The study flowchart is displayed in Fig. This is a prospective study based on a registered clinical trial at m/z 85.0 → 65.9 amu, d9-choline at m/z 113.2 → 68.9 amu, d9-carnitine at m/z 162.0 → 102.8 amu, d11-betaine at m/z 118.0 → 59.0 amu and d9- GBB at m/z 146.1 → 87 amu. Different concentrations of TMAO, carnitine, choline, betaine and GBB standards and a fixed amount of internal standards were added to 4% bovine serum albumin to generate the calibration curves for the quantification of blood TMAO-related metabolites. The standard curve coefficient of determination (R2) reached 0.999, and the accuracy across a span of different concentrations all reached 95%. After protein precipitation, the supernatant was recovered after centrifugation at 20000 g at 4 °C for 10 minutes. Then, 70 μL of the supernatant was absorbed into vials for loading, and the injection volume by the autosampler was 3 μl. The detections were performed on an API 5500Q-TRAP mass spectrometer . Analytes were monitored in positive MRM MS mode by using the following characteristic precursor-production ion transitions: TMAO at m/z 75.7 → 59.0 amu, choline at m/z 104.0 → 59.8 amu, carnitine at m/z 162.0 → 85.0 amu, betaine at m/z 118 → 57.7 amu and GBB at m/z 155.1 → 87.0 amu. All stable iso-labeled internal standards used in this study were purchased from Cambridge Isotope Laboratories, Inc. . Lipid parameters, including TG, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), LDL-c, apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB), were measured by a biochemistry autoanalyzer  in the clinical laboratory center of Beijing Tiantan Hospital. Hyperlipidemia was defined as TC ≥ 6.22 mmol/L, LDL-c ≥ 4.14 mmol/L, TG ≥ 2.26 mmol/L or HDL-C < 1.04 mmol/L, which was based on the criteria recommended by the U.S. Adult Treatment Panel III.Fasting venous blood samples were collected using EDTA-containing pyrogen-free tubes after admission and immediately centrifuged at 4 °C and 3000 rpm for 10 min to obtain plasma samples. Then, the plasma samples were stored at − 80 °C until analyses. The TMAO, choline, carnitine, betaine and GBB levels were measured by stable isotope dilution liquid chromatography-tandem mass spectrometry (LC/MS/MS) according to previous methods . BrieflyP value < 0.05 was considered statistically significant.Categorical variables were compared by the chi square test and expressed as frequencies (n) and percentages (%). Normality of continuous variables was evaluated using a one-sample Shapiro–Wilk test. Student’s t test was performed to compare the differences between groups, or the Mann–Whitney test was used when variables were not normally distributed. A paired test was used to compare the differences in lipids and TMAO-related metabolites before and after rosuvastatin therapy. All data are expressed as the mean ± standard deviation (SD). Pearson analyses were performed to evaluate the correlations between TMAO-related metabolites and lipids, and Spearman analyses were performed when variables were not normally distributed. Partial correlation analyses were performed to explore the correlations between TMAO-related metabolites and lipids by adjusting for sex, age, body mass index (BMI) and estimated glomerular filtration rate (eGFR). Multivariate analyses were performed using a linear regression model to identify the associations between TMAO-related metabolites and lipids and investigate the effect of rosuvastatin therapy on TMAO-related metabolites. The variables included in the multivariate analyses were sex, age, BMI, eGFR, TG, TC, LDL-c, HDL-c, ApoA1 and ApoB. The statistical analyses were performed using SPSS version 17.0 . A P < 0.05) and had lower rates of smoking  and drinking  than male patients (Supplementary Table SP < 0.05).In this study, female patients with suspected ASCVD were older , and betaine was negatively correlated with BMI  (Supplementary Table SP < 0.05), and the differences in other TMAO-related metabolites between the two patient groups were not significant (P > 0.05). Further analyses found that patients with hyper-TG or hypo-HDL-c had higher TMAO levels than patients without hyper-TG or hypo-HDL-c , respectively. Patients with hyper-LDL-c had lower betaine levels than patients without hyper-LDL-c .First, we found that TMAO was positively correlated with patient age and BMI and negatively correlated with eGFR , and betaine was negatively correlated with LDL-c . The correlations mentioned above still existed after partial correlation analyses adjusting for sex, age, BMI and eGFR (Table P < 0.05), and betaine was also significantly associated with TC after multivariate linear regression analyses (P < 0.05).In univariate analyses (Supplementary Table SFR Table  or multiP < 0.05). Moreover, lower TMAO levels and higher carnitine, betaine and GBB levels were observed compared to baseline . The changes in TMAO-related metabolites were still significant after adjustment for sex, age, BMI and eGFR by multivariate analyses (Table P < 0.05). Compared with patients in the low-TMAO group (Supplementary Table SP < 0.05).Rosuvastatin therapy significantly decreased TG, TC, LDL-c and ApoB levels but increased HDL-c and ApoA1 levels , but correlations between TMAO and ApoB and between carnitine and LDL-c or ApoB were found to be significantly negative . Further partial correlation analyses adjusting for sex, age, BMI and eGFR indicated that (Table P < 0.05), and betaine was negatively correlated with TG (P < 0.05). After adjustment for the personal characteristics and lipids mentioned above, the negative association between carnitine and LDL-c or between betaine and TG was still significant (Supplementary Tables SP < 0.05), and a significantly positive association was also found between carnitine and TC (Supplementary Table SP < 0.05).In addition, . Table S1. Baseline characteristics of patients without prior statin therapy (Group 1) and patients who received irregular statin therapy for less than one month (Group 2). Table S2. Baseline characteristics of males and females. Table S3. Correlations between the TMAO-related metabolites and personal characteristics (n = 112). Table S4. Correlations among the TMAO-related metabolites before statin therapy. Table S5. Partial correlation analyses for the associations among the TMAO-related metabolites before statin therapy. Table S6. Comparisons of the TMAO-related metabolites between different types of hyperlipidemia. Table S7. Correlations between the TMAO-related metabolites and blood lipids before rosuvastatin therapy (n = 112). Table S8. Multivariate linear regression analyses for the associations between TMAO and blood lipids before rosuvastatin therapy. Table S9. Multivariate linear regression analyses for the associations between betaine and blood lipids before rosuvastatin therapy. Table S10. The changes of TMAO-related metabolites after rosuvastatin therapy (n = 112). Table S11. The changes of TMAO-related metabolites between low-TMAO and high-TMAO groups after rosuvastatin therapy. Table S12. Correlations between the TMAO-related metabolites and blood lipids after rosuvastatin therapy (n = 112). Table S13. Multivariate linear regression analyses for the associations between carnitine and blood lipids after rosuvastatin therapy. Table S14. Multivariate linear regression analyses for the associations between betaine and blood lipids after rosuvastatin therapy.


Transthoracic echocardiography is commonly used to identify structural and functional cardiac abnormalities that can be prevalent in childhood chronic kidney failure (KF). Left ventricular mass (LVM) increase is most frequently reported and may persist post-kidney transplant especially with hypertension and obesity. While systolic dysfunction is infrequently seen in childhood chronic KF, systolic strain identified by speckle tracking echocardiography has been frequently identified in dialysis and it can also persist post-transplant. Echocardiogram association with long-term outcomes has not been studied in childhood KF but there are many adult studies demonstrating associations between increased LVM, systolic dysfunction, strain, diastolic dysfunction, and cardiovascular events and mortality. There has been limited study of interventions to improve echocardiogram status. In childhood, improved blood pressure has been associated with better LVM, and conversion from hemodialysis to hemodiafiltration has been associated with better diastolic and systolic function. Whether long-term cardiac outcomes are also improved with these interventions is unclear. Echocardiography is a well-established technique, and regular use in childhood chronic KF seems justified. A case can be made to extend screening to include speckle tracking echocardiography and intradialytic studies in high-risk populations. Further longitudinal studies including these newer echocardiogram modalities, interventions, and long-term outcomes would help clarify recommendations for optimal use as a screening tool. The mortality rate for children with chronic kidney failure (KF) is at least 30 times higher than their age-matched healthy peers . CardiovPrevention of cardiovascular (CV) events in chronic KF is a major challenge as CVD is often silent and a significant proportion of CV mortality is from sudden cardiac death . A key fThrough this review, we provide a refresher of the natural history of CVD in chronic KF and associated structural and functional cardiac changes that can be identified with echocardiography. We then summarise established and new echocardiographic techniques, and finally we review the evidence for use of echocardiogram as a screening tool in the pediatric dialysis and transplant population. Studies of children with CKD are not included in this review.Chronic KF has been associated with all types of structural cardiac disease including myocardial fibrosis and hypertrophy , arterioHypertension is the most common CV risk factor present in children with chronic KF, with uncontrolled hypertension evident in 51% of children after 1 year of dialysis  and in 2Dyslipidaemia, another pro-atherogenic state, has been reported in 45% of the pediatric transplant population . An incrChronic KF is a complex state of persistent low-grade inflammation . Pro infElevated serum calcium, phosphorus, and parathyroid hormone (PTH) are all independently linked to increased risk of coronary artery calcification  and caroAnaemia is a frequent complication of dialysis and reduced GFR and has been associated with LVH and diastolic dysfunction in several pediatric studies , 25, 26.Dialysis is perhaps the most significant risk factor for CVD. Pre-emptive transplantation and reduced cumulative time on dialysis have been associated with improved survival , 28. A mDialysis patients are at risk of pressure and volume overloaded cardiovascular states, both of which have been associated with increasing LV mass, hypertrophy, and functional changes including impaired ventricular relaxation (diastolic dysfunction) and ventricular contraction (systolic dysfunction). There is significant interdependence of hypertension and volume overload, although control of volume state may be the most important factor in reducing LV mass . The geoTrans-thoracic echocardiography is the most widely used diagnostic modality available for structural and functional cardiac assessment. Conventional modes of echocardiography use two-dimensional (2D) assessments of structure and motion to assess myocardial wall thickness, wall mass, chamber size, and systolic function. Accurate assessment requires gating with an electrocardiogram to determine timing of systole and diastole. Integration of Doppler measures allows evaluation of pressure, velocity, valvular function, and diastolic/systolic function (including tissue Doppler imaging TDI). Newer methods such as strain imaging and three-dimensional (3D) echocardiography may provide more accurate assessments and early detection of sub-clinical systolic dysfunction . Overall2-D echocardiography is the most commonly used modality and provides cross-sectional views for basic assessment of cardiac structure and function. Left ventricular ejection fraction (LVEF) is calculated by the biplane Simpson’s method using the formula (left ventricular end-diastolic volume − end-systolic volume)/end-diastolic volume in 2 planes  . SystoliMotion-mode or M-mode is a time gated view of structures along a single ultrasound line. It is generally used as a complementary tool in assessment of ventricular wall thickness, chamber dimension, and abnormal valvular movement. Measurements can be acquired in circumferential (short-axis) or longitudinal (long-axis) planes. Linear measurement of left ventricular end diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) are used to calculate fractional shortening (FS) as a measure of LV systolic function ((LVEDD − LVESD / LVEDD) × 100) . However3-D echocardiography obviates the need for geometric assumptions and provides more accurate measurements of ventricular volume and function than 2DE . It is, E/A ratio, with impaired ventricular relaxation and diastolic dysfunction often defined by E/A < 1. Continuous wave, pulsed wave (PWD), and colour Doppler are the main modalities utilised. Limitations with Doppler studies include underestimation of the gradient if the sound beam is not exactly parallel to jet. In addition, fast heart rates can make assessment of A and E waves difficult. Finally, volume status can influence some parameters , thus standardisation of scanning in relation to dialysis schedules is important.Doppler echocardiography allows assessment of velocity and direction of blood flow to provide precise hemodynamic evaluation of the heart. Doppler velocity data is used to derive pressure data using the Bernouilli equations to estimate systemic and pulmonary pressures. Data across valves is useful to gauge valvular function and ventricular diastolic function. For LV diastolic function, velocities are measured at the level of the mitral valve, with the E wave representing early diastolic flow Fig. , and theE′), late diastole (A′), and systole (S′). Peak measurements are most commonly undertaken at the LV free wall myocardium just below the mitral valve annulus , medial wall just at the top of the ventricular septum , and at the right ventricular free wall just below the tricuspid valve annulus (RV). TDI assessment of mitral annular velocity (E′)  [E′ more than A′, and TDI E′/A′ is another measure of diastolic function. Conventional E to tissue Doppler E′ (E/E′) may be the most reliable and sensitive Doppler measure of diastolic dysfunction [S′), and to measure strain. There may be limitations of TDI due to discrepancies in the beam angle and limitations in plane of assessment , although inter and intra-observer reproducibility appears reasonable [Tissue Doppler imaging (TDI) measures myocardial velocities in specific locations. Typically, pulsed wave TDI is used. Measurements include velocity data during early diastole (E′) Fig.  is a val . As withfunction . TDI canasonable .Speckle tracking echocardiography (STE) tracks the motion of individual reflections within the myocardium to assess myocardial deformation and provides an assessment of strain  during systole or diastole. Strain is associated with myocardial hypertrophy and fibrosis in human and animal studies , 44. MicCEE has been recently approved for use in children in the USA. This technique uses intravenous microbubble contrast agents in conjunction with echocardiography, and is considered to improve resolution, with utility especially in obese patients . Clear r2DE in conjunction with exercise- or drug- (e.g. dobutamine) induced myocardial work can be used to detect coronary artery disease through detection of regional wall abnormalities. It is rarely clinically used in children but in research has been shown to demonstrate that children with chronic KF on dialysis have reduced contractile reserve during exercise and dobutamine stress , 50. TheThe cardiac work index (CWI) is a non-invasive assessment of strain and LV pressure. Strain data derived from STE is superimposed on population reference LV pressure measures at time of LV peak pressure, mitral valve opening, and closure. The derived LV pressure curve is then matched with the patient’s strain data to develop a pressure-strain loop. The area of the loop is the CWI . CWI canWall thickness, chamber size, and functional assessment should form part of each echocardiogram assessment and there are published recommendations to guide this , as wellZ-scores [Z-scores for LVM may be most accurate [Given the potential hemodynamic changes in chronic KF, echocardiogram standardisation can be a challenge . IdeallyZ-scores . Given baccurate . The mosAn increasing array of echocardiogram changes in chronic KF are now described. In many of these, associations with cardiac events and mortality have been reported in adult populations. Longer outcome studies in pediatrics are required. Detailed definitions of more commonly described markers in clinical and research use are provided in Table There are countless observational studies of prevalence and risk of echocardiogram changes in pediatric chronic KF. Many incorporate control populations to demonstrate significantly worse LVM, diastolic and systolic function , 58–61. LVM/LVH is the most commonly studied echocardiogram parameter, with some studies also assessing LVM influence on function, demonstrating a correlation with worse diastolic , 59, andGlobal LV systolic function as measured by conventional echo-based LVEF/FS is mostly preserved in childhood chronic KF , 75. DurE/A, E′/A′, or E/E′, although some define specific criteria for diastolic dysfunction [E/E′ ratio has been associated with mortality [LV diastolic function can be impaired in both dialysis and transplantation , 60, 80.function , 66. TDIfunction . Duratiofunction , 60, 75.function , 79; howfunction , 73, andfunction , and hypfunction  have beefunction , 73. In ortality . In HD, ortality . LAS hasortality .Right heart changes are infrequently reported in childhood chronic KF, although these are still an important part of standard echocardiogram assessment. Right heart geometry has been reported to change in adolescents on HD, especially in the presence of an arterio-venous fistula , with inAscending aortic dilatation appears to be somewhat of a novel finding for children (versus adults) with chronic KF , 84, 85,Guidelines that incorporate routine echocardiography assessment of chronic kidney failure patients are listed in Table While prevalence of echocardiogram abnormalities is significant across childhood dialysis and transplant populations, current pediatric recommendations for echocardiogram screening in chronic KF are limited. A key screening test principle is that screening followed by an intervention should reduce clinical events. Currently, there are no trials assessing whether echocardiogram triggered interventions improve CV events. Physiologic principles, longitudinal studies, and multivariable analyses, including adult studies and those assessing echocardiogram outcomes, do, however, suggest that some interventions could be of benefit. For example, improved volume state and blood pressure in children is associated with better LVM in PD and HD , 63. In One could argue that many echocardiogram abnormalities are associated with volume overload or hypertension, and that a screening echocardiogram should not be required to identify these states. Regular echocardiogram screening to identify subclinical and potentially reversible end-organ damage could be of benefit, however, to prompt an earlier change in management and a more complete evaluation of patient CV risk and therapy options. This could be individualised with screening further extended or increased in frequency according to local echocardiogram access or baseline suspected risk. For example, HD patients could be screened during dialysis or immediately post-dialysis to identify stunning or strain. Given that stunning has been associated in adults with irreversible systolic dysfunction and mortality by 12 months , and theMinimum recommended standards for pediatric echocardiography have been published by the American Society of Echocardiography , 53. TheGiven future lifelong exaggerated CV risks in childhood chronic KF, and the complexities of these risk states, it is our opinion that regular assessment of CV risk factors and subclinical CV health is warranted during dialysis, pre- and post-transplant. Annual echocardiography, even with minimum standard assessment, is well-placed to help screen overall cardiac health. Further extended screening using newer modalities such as STE could be considered dependent on baseline suspected or known CV risk status. Echocardiography is a well-established technique which does not involve risk or significant time commitment for patients, and also provides important functional data. Further long-term research and interventional studies would help further clarify the specific utility of echocardiogram screening in the childhood chronic KF population.


Cardiac magnetic resonance (CMR) imaging is a well-set diagnostic technique for assessment of valvular heart diseases and is gaining ground in current clinical practice. It provides high-quality images without the administration of ionizing radiation and occasionally without the need of contrast agents. It offers the unique possibility of a comprehensive stand-alone assessment of the heart including biventricular function, left ventricle remodeling, myocardial fibrosis, and associated valvulopathies. CMR is the recognized reference for the quantification of ventricular volumes, mass, and function. A particular strength is the ability to quantify flow, especially with new techniques which allow accurate measurement of stenosis and regurgitation. Furthermore, tissue mapping enables the visualization and quantification of structural changes in the myocardium. In this way, CMR has the potential to yield important prognostic information predicting those patients who will progress to surgery and impact outcomes. In this review, the fundamentals of CMR in assessment of aortic valve diseases (AVD) are described, together with its strengths and weaknesses. This state-of-the-art review provides an updated overview of CMR potentials in all AVD issues, including valve anatomy, flow quantification, ventricular volumes and function, and tissue characterization. Aortic valve disease (AVD) affects approximately 0.9% of the general population , with a Although echocardiography still represents the first-line technique to assess the aortic valve, cardiovascular magnetic resonance (CMR) imaging is emerging as a method able to provide a comprehensive evaluation of many aspects of aortic valvulopathy.CMR is a non-invasive, multiplanar, and high-spatial-resolution imaging technique. It offers a robust alternative for assessing the severity of aortic stenosis (AS) , is supeThe aim of this review is to provide an updated overview of CMR in AVD. In this paper, we will first review the CMR sequences commonly used to assess patients with aortic valvulopathy. Then, we will discuss the role of CMR in AS and AR. Next, we will focus on the application of CMR in patients requiring transcatheter aortic valve prosthesis implantation (TAVI).The steady-state free precession (SSFP) pulse sequence is commonly used for the assessment of valve morphology and function ,7. ImageCine sequences enable visualization of post-stenotic and regurgitant blood flow. Qualitative analysis relies on the evaluation of signal void artifact, which results from intravoxel spin dephasing due to turbulent flow. Gradient echo imaging (GRE) , a formeQuantitative analysis of flow velocity can be performed using through-plane phase contrast (PC) velocity mapping . PC pulsCMR gives the possibility to characterize the anatomy of the thoracic aorta; aortic root dilatation is associated with functional AR, whereas post-stenotic remodeling occurs in AS, especially in bicuspid aortic valves. In patients scheduled for aortic valve intervention, it is fundamental to provide aortic measurements. One of the most used tools is contrast-enhanced MR angiography (CEMRA), which is usually non-ECG-triggered . Thus, iA three-dimensional (3D) self-navigated free-breathing high-resolution whole-heart CMR sequence with either end-systolic or diastolic gating  grants aFour-dimensional (4D) flow or time-resolved 3D phase-contrast CMR is applied for the synchronous evaluation of morphometry and flow parameters along the thoracic aorta. It holds the possibility to measure non-laminar flow in any direction in space during the cardiac cycle . VelocitCMR is the gold-standard imaging technique to evaluate LV volume, mass, and function . AccuratLate gadolinium contrast-enhanced (LGE) imaging is deemed to be the reference standard to quantify myocardial replacement fibrosis and scar. Standard LGE sequences obtained 10 to 15 min after contrast agent injection. Furthermore, inversion recovery gradient echo sequences are used, consisting of an inversion pulse to suppress normal myocardium and a T1-weighted GRE acquisition. In regions with higher gadolinium concentration, T1 time is shorter than in adjacent areas and shows high signal intensity on LGE images. Normal myocardial tissue will appear darker compared with the bright signal of the damaged myocardium where gadolinium washout is delayed . AnotherAS is the most common valvulopathy in developed countries with a prevalence constantly increasing due to rising life expectancy ,32. TranEven though less utilized in clinical practice, CMR offers several advantages in patients affected by AS, allowing a non-invasive, multiplanar, radiation-free, and high-resolution assessment of valvular anatomy and severity of stenosis, coupled with a thorough functional evaluation. Furthermore, compared to other modalities, CMR offers the unique asset of myocardial tissue characterization. In patient candidates for TAVI, as described later, CMR represents an alternative tool to CT for procedural planning in subjects with contraindications to contrast agents.In patients with non-diagnostic TTE due to poor acoustic windows, CMR can be used for aortic valve anatomy assessment and to determine the degree of stenosis. Assessment of AS severity by CMR utilizes two parameters: planimetry of the valve area A and peaThe latter, different from Doppler echocardiography, is time-consuming and tends to underestimate the transvalvular gradients secondary to intravoxel dephasing errors in presence of high-velocity flows . On the LV remodeling in the setting of AS starts as a compensatory process to maintain wall stress, but often it progresses to a maladaptive response characterized by myocyte hypertrophy, interstitial fibrosis, and apoptosis. Although LV reverse remodeling occurs after aortic valve replacement (AVR), the intervention is often performed late after irreversible maladaptive LV remodeling and fibrosis . Dweck aMyocardial fibrosis is a hallmark of severe AS and has an important prognostic role. Three main patterns have been described: endocardial fibrosis, microscars (mainly in the subendomyocardium), and diffuse interstitial fibrosis .Although the gold standard for assessing myocardial fibrosis is histology on endomyocardial biopsy, CMR is able to non-invasively assess the presence of both focal and diffuse fibrosis. Focal non-ischemic fibrosis, often identified as an area of mid-wall LGE D, is freSimilarly, diffuse fibrosis, identified with native T1 and ECV, is a relevant risk marker in patients with AS. Lee et al. showed that high native T1 value on non-contrast T1 mapping CMR is an independent predictor of adverse outcome in patients with significant AS . More reRecent guidelines suggest that CMR is indicated for AR evaluation when echocardiographic images are suboptimal, echo parameters are discordant, disagreement subsists between clinical assessment and echocardiographic grading, inadequate echocardiographic measurements of LV volumes and systolic function are obtained in patients with moderate/severe AR, and insufficient aorta evaluation by echocardiography is achieved in patients with bicuspid aortic valve .CMR assessment of AR is advisable due to the high degree of accuracy for measurement of LV volumes and function as well as aortic regurgitant volumes ,54. ThisCMR assessment of AR initiates from the visual inspection of the aortic valve, aortic root, LV, and LV outflow tract structure and function with SSFP A. Valve A preliminary evaluation of the severity of AR can be achieved by visualization of the signal void of the regurgitant jet on cine imaging A. A narrHowever, the most commonly used method to quantify AR is through-plane PC imaging A, which Regurgitant fraction and regurgitant volume are independent predictors of outcome in patients with AR. A regurgitant fraction of >33% and a regurgitant volume threshold of >42 mL have been shown to predict the likelihood of requiring surgery (mean follow-up of 2.6 years). No patients with a regurgitation fraction <26% progressed to surgery . MoreoveThe presence of holodiastolic retrograde flow (HRF) in the descending aorta can also be assessed easily by PC imaging. HRF on CMR was strongly and independently associated with heart failure, hospitalization, and cardiovascular death .Four-dimensional flow MRI is an emerging tool for the assessment of AR B. The adAccurate LV volumes with CMR are fundamental to clinically assess the impact of AR D. In a mR = 0.70, p < 0.001) [p = 0.001), implying the presence of expanded interstitial fibrosis [R = 0.79, p = 0.011) [p < 0.03 for both), despite a recovery in LV ejection fraction and a shrinkage of LV dimensions [Pressure and volume overload exerted on the LV by AR induce interstitial fibrosis, characterized by increased fibronectin and glucosamine deposit with altered collagen organization . Replace< 0.001) . Malahfj< 0.001) . Sparrowfibrosis . In anot= 0.011) . CMR-FT = 0.011) . Moreovemensions . In addiCT is the gold standard imaging tool to assess the feasibility of TAVI. CT provides accurate annular sizing, determination of risk of annular injury and coronary occlusion, and co-planar fluoroscopic angle pre-procedural prediction. Further benefits of cardiac CT have also been demonstrated in the follow-up of TAVI for assessment of post-procedural complications, including identification of leaflet thickening ,72.However, CT requires contrast agent administration that may be high-risk in allergic patients and in subjects with chronic renal insufficiency, who make up a vast percentage of patients undergoing TAVI. The use of ionizing radiation in CT was not considered particularly relevant for the population involved in the intervention in the past; however, now, it represents a non-negligible issue with the extended indications to younger subjects with lower perioperative risk .CMR may be a valid alternative to CT providing high-quality 3D multislice images without the administration of contrast agents and ionizing radiation. It offers the unique possibility of a one-stop-shop approach to not only assess the anatomical feasibility of TAVI, but to also provide a thorough analysis of the heart, including biventricular function, LV remodeling, myocardial fibrosis, and associated valvulopathies. Moreover, compared to CT, heart rate control is not a major concern because of the superior temporal resolution of CMR. Drawbacks of the use of CMR for TAVI include a longer study time, a greater patient collaboration, and underestimation of calcifications given that calcified tissue produces little signal.A complete evaluation with CMR of the aortic root, including assessment of annular size, aortic leaflet dimensions, and height of coronary artery ostia, is attainable and accurate when compared to cardiac CT ,74 Figu.In order to perform these measurements, a CMR protocol pre-TAVI should include two long axis cine images of the aortic root and a stack of cine images acquired orthogonally to the above two planes, covering the entire aortic root.Magnetic resonance imaging (MRI) can also be used to assess TAVI peripheral access route using CEMRA or, in patients allergic to contrast agents, a 3D-SSFP navigator-echo and ECG-gated  sequence for the thoracic aorta while a non-contrast-enhanced MR angiography can be used for aorto-iliac evaluation . HoweverThe identification of myocardial tissue characterization abnormalities with CMR allows prognostic stratification of patients before TAVI. Indeed, the presence of LGE in patients undergoing TAVI predicts higher cardiovascular disease related mortality .Moreover, CMR is a powerful tool for the screening of association between amyloidosis and AS, which occurs in one of eight patients evaluated for TAVI . Indeed,The recent study by Nitsche et al. demonstrated that although patients with AS and cardiac amyloidosis were older and had worse clinical presentation , they had similar outcomes to those with lone AS .However, there was a trend for higher mortality at 1 year in AS cardiac amyloidosis versus lone AS and other relevant clinical outcomes, including re-hospitalization for heart failure, functional class, and quality of life, which were not considered. Moreover, the study was limited to a 3-year follow-up, whereas cardiac amyloidosis may have an impact on longer-term outcomes .Although the diagnosis of cardiac amyloidosis in symptomatic patients with severe AS should not preclude the consideration for TAVI, its identification with CMR is of importance as it may lead to consideration for pharmacological treatment .In the post-intervention phase and follow-up, CMR can be valuable for the assessment of para-valvular aortic regurgitation, a condition associated with long-term mortality after TAVI . TTE is In the future, real-time CMR (RT-CMR) may be considered for guiding TAVI. Owing to an unlimited scan plane orientation and an unsurpassed soft-tissue contrast with simultaneous device visualization, RT-CMR could allow safe device navigation and offer optimal orientation for precise axial positioning. Non-contrast, radiation-free, and RT-CMR-guided TAVI has been successfully implanted in animals using dedicated conditional equipment , paving


Systolic T1 mapping was associated with fewer myocardial segments being affected by artefact compared to diastolic T1 mapping [217/2472 (9%) vs 515/2472 (21%)]. Mean native T1 values were not significantly different when measured in systole and diastole  and mean post-contrast values showed similar good agreement . No clinically significant differences in ECV, native T1 and post-contrast T1 were identified between diastolic and systolic T1 maps in males versus females, or in patients with permanent atrial fibrillation versus sinus rhythm. A statistically significant improvement in R2 value was observed with systolic over diastolic T1 mapping in all analysed maps (n = 411)  and in subgroup analyses  . In conclusion, myocardial T1 mapping is associated with similar T1 and ECV values in systole and diastole. Furthermore, systolic acquisition is less prone to gating artefact in arrhythmia.Cardiovascular magnetic resonance T1-mapping enables myocardial tissue characterisation, and is capable of quantifying both intracellular and extracellular volume. T1-mapping is conventionally performed in diastole, however, we hypothesised that systolic readout would reduce variability due to a reduction in myocardial blood volume. This study investigated whether T1-mapping in systole alters T1 values compared to diastole and whether reproducibility alters in atrial fibrillation compared to sinus rhythm. We prospectively identified 103 consecutive patients recruited to the Mitral FINDER study who had T1 mapping in systole and diastole. These patients had moderate or severe mitral regurgitation and a high incidence of ventricular dilatation and atrial fibrillation. T1, ECV and goodness-of-fit (R Parametric T1 mapping values correlate favourably with histological fibrosis observed on myocardial biopsy2 and are markers of adverse myocardial remodelling. Parametric T1 mapping has incremental value in predicting outcomes, including arrhythmia and mortality. The technique has proven clinical utility in cardiac amyloidosis, iron deposition, Fabry disease, myocarditis, as well as potential clinical utility in the assessment of ischaemia and non-ischaemic cardiomyopathy, heart failure, congenital heart disease and suspected transplant rejection1.Cardiovascular magnetic resonance (CMR) is the primary non-invasive imaging modality for myocardial tissue characterisation, utilising a number of different imaging techniques. Myocardial T1 mapping is capable of quantifying both intracellular and extracellular myocardial changes based on T1 and extracellular volume (ECV) measurements3, myocardial thickness is also lowest at this time. Furthermore, the high prevalence of ectopy and arrhythmia (e.g. AF) in patients with cardiac disease, cause electrocardiogram (ECG) gating artefacts4 that adversely affect acquisition sequences such as the 3(3)3(3)5 scheme MOLLI, which requires a consistent R-R interval over its 11 cardiac cycle acquisition period5. T1 mapping in systole is feasible6 and may help to overcome these issues. This could potentially negate gender-related differences in ECV9 and myocardial blood volume, which is lowest in peak systole10.T1 mapping images are traditionally acquired in end-diastole. T1 relaxation times and ECV values are then calculated from the signal of the myocardium, carefully selected to exclude voxels at the endocardial order, thus minimising contamination from the blood due to partial volume effect. However, although myocardial motion is lowest in end-diastole 2 values; (iii) reduce the variation in ECV and T1 results related to patient gender and presence of AF.We therefore hypothesised that compared to diastolic T1 mapping, systolic T1 mapping will: (i) provide more reliable ECV values by measuring at a time when intramyocardial vascular space and capillary blood pool are smallest; (ii) reduce gating artefacts as reflected by higher RWe chose to examine this hypothesis in patients with moderate and severe mitral regurgitation (MR). This population has a high prevalence of atrial fibrillation (AF) and ventricular dilatation.11. In brief, mitral FINDER was a multicentre prospective study of adult patients (aged 18 and over) with primary degenerative MR, recruited from 3 regional tertiary cardiac centres. Mitral regurgitation was diagnosed and quantified by a multiparametric echocardiographic approach, as recommended by international guidelines13. For the present study, the pre-operative CMR studies of patients recruited for the mitral FINDER project at the Queen Elizabeth Hospital Birmingham were retrospectively assessed. Patients were included if native and post-contrast T1 values were acquired in diastole and systole.The present study is a planned sub-study of patients recruited to the Mitral FINDER project, for which the full study protocol has been previously publishedExclusion criteria included patients without T1 values acquired in both diastole and systole, non-degenerative MR aetiology, co-existing moderate or severe aortic valve disease, congenital disease, inherited or acquired cardiomyopathy, symptomatic coronary artery disease, uncontrolled AF (resting heart rate > 100/min), pregnancy, and those unable to undergo CMR. All included AF patients were in AF at the time of the scan (permanent AF).14 pre- and 15 min after the administration of gadolinium contrast, at the basal and mid left ventricular short axis level (3(3)3(3)5 scheme). Echo time (TE) was 1.01 ms for 4-chamber (4Ch) and 1.06 ms for short axis slices in both systole and diastole. The echo repetition time (TR) was 338 ms in systole and varied in diastole depending on the heart rate . Flip angle was 35° and voxel size was 2 × 2 × 8 mm3 and 1.8 × 1.8 × 8 mm3 for 4ch and short axis slices respectively. The first inversion time was 100 ms for all acquisitions, partial acceleration factor 2 (36 reference lines) and partial Fourier imaging factor 7/8. In systole, the minimum trigger delay was set to 0 ms, with a data acquisition at 257.5 ms. In diastole, the trigger delay was variable depending on the heart rate . There were 92 readouts per heartbeat. MOLLI T1-maps were acquired from vendor-provided product protocols  which provides pixel-based myocardial quantification and colour mapping with motion correction. T1 times and ECV were calculated offline using Circle cvi42® (Circle Cardiovascular Imaging Inc. Canada), in accordance with the European Society of Cardiology recommendations15. A 20% offset was used on endocardial and epicardial contours to avoid the blood-myocardial boundary. Extracellular volume was calculated using blood and myocardial T1 values pre- and post-contrast using the validated formula below:All patients underwent CMR at 1.5 T at University Hospital Birmingham  using an 18-channel phased-array coil with the participant supine. For myocardial characterisation, myocardial and blood pool relaxation times were measured using the modified Look-Locker inversion recovery (MOLLI) sequence2) values based on the difference between the measured and fitted inversion recovery signal curves of the 11 consecutive images acquired by the 3(3)3(3)5 scheme in the basal and mid-left ventricular level, pre- and post-contrast. Inversion recovery signal curves were generated based on the exponential model. Baseline LV parameters such as volume, mass and function were obtained using CMR.Haematocrit was measured at the same time as the CMR study. DICOM images were imported into in-house software  to create goodness-of-fit (R2) values of native and post-contrast T1 times at the basal and mid-left ventricular levels (n = 411) were analysed using paired Student’s T test. Categorical variables were compared using a chi squared test. A p value of < 0.05 was considered significant. All analyses were conducted using SPSS software version 23.0 .Normal and non-normally distributed continuous variables are expressed as mean ± standard deviation or median with interquartile range and were compared using Student’s T test or Mann–Whitney U test respectively. Linear regression  and conformed to the Helsinki Declaration. Subjects gave written informed consent to participate.2. Prior diagnoses included AF 20/103 (19%), diabetes 2/103 (2%) and hypertension 34/103 (33%). Patients had a mean New York Heart Association (NYHA) classification of 1.4 ± 0.6, median estimated glomerular filtration rate (eGFR) of 74 ml/min/1.73m2 (IQR: 63–86) and median NT-proBNP level of 203 ng/L (IQR: 108–596).Amongst 150 patients recruited to the mitral FINDER study, 103 patients underwent T1 mapping in systole and diastole and were included in this study. Baseline demographics are shown in Table 2), showed a significantly greater mean R2 value  with systolic imaging , shown in Fig. p = 0.061) and the same was true for mean post-contrast values —Table Examples of the difference between diastolic and systolic myocardial thickness are demonstrated in Fig. Intra and inter-observer variability when measuring T1 values in systole and diastole was tested in a random sample of 10 patients but differences were small and were not statistically significant  and systole . No significant differences in absolute ECV, native T1 and post-contrast T1 values were identified between diastolic versus systolic T1 maps in patients with permanent atrial fibrillation or sinus rhythm  had slightly higher ECV values than patients in sinus rhythm (n = 207), when imaged in both diastole  in all patients and subgroups . In this respect, systolic and diastolic R2 values showed strong correlation (r = 0.81) with less variability (SD = 0.8) between the methods than in the measurements themselves (SD = 1.4), explaining the statistical significance despite small mean differences. Our rationale for better R2 values with systolic imaging is that this is likely related to reduction in susceptibility to gating artefact. A typical example in a patient with atrial fibrillation is illustrated in Supplementary Video Even following the exclusion of a higher number of artefact-affected segments during diastolic T1 mapping, systolic imaging was less variable  were not performed.Different T1 mapping sequences have different susceptibilities to artefact/error, so these findings may not be applicable to all T1 mapping sequences. However, errors due to blood pool contamination are common to all sequences and it is likely that our findings are relevant to most or all of these sequences. Furthermore, the analysis may be impacted by low image signal-to-noise ratio, artefacts, varying slice locations and small dataset size.Myocardial T1 mapping is associated with similar T1 and ECV values in systole and diastole. Systolic acquisition is associated with reduced susceptibility to artefact and lower variability due to greater myocardium:blood volume ratio and less gating artefact.Supplementary Information 1.Supplementary Video 1.


LASr  was also lower in ALHIV and multivariate analysis showed that age  and infection duration  were independently associated with LASr. In the absence of cardiovascular risk factors, adults living with HIV display normal LV systolic function. Left atrial reservoir strain, is, however, decreased and suggests early diastolic dysfunction.Adults living with HIV (human immunodeficiency virus) infection (ALHIV) have high rates of cardiovascular events. New approaches are needed to detect subclinical cardiac dysfunction. We used conventional and speckle tracking echocardiography to investigate whether ALHIV display latent cardiac dysfunction. We analyzed 85 young subjects with HIV infection and free from cardiovascular risk factors (31 ± 4 years) and 80 matched healthy volunteers. We measured left ventricular (LV) layered global longitudinal strain, circumferential strain, peak longitudinal strain in the reservoir and contraction phases of the left atrium (LASr respectively LASct). In the HIV group, LV ejection fraction and s’ TDI (tissue doppler imaging) were slightly lower but still in the normal ranges. Layered longitudinal strain showed no significant difference, whereas circumferential global strain was significantly lower in the HIV group (−20.3 ± 3.9 vs. −22.3 ± 3.0,  In 2020, approximately 37 million adults were living with human immunodeficiency virus (HIV) infection, and 75% were receiving antiviral therapy. The development of targeted therapy protocols such as antiretroviral therapy (ART) and the increasing accessibility to treatment led to a steep decrease in mortality among adults living with HIV (ALHIV) .The effective suppression of viral replication significantly lowered the prevalence of acute opportunistic infections and oncologic complications, shifting the clinical spectrum of HIV infection towards chronic, more subtle conditions of the heart, liver and kidney. The relationship between HIV and cardiac disease was early documented and exceedingly studied. HIV infection is associated with an adverse metabolic and cardiovascular risk profile , and theDespite effective treatment, there is still evidence that the rate of acute cardiac events remains higher in ALHIV, beyond that explained by recognized risk factors ,5. Thus,Speckle tracking echocardiography has become a valuable clinical tool for the quantification of myocardial function . Global There have been relatively few studies addressing cardiac abnormalities detectable by speckle tracking echocardiography among adults infected with HIV in the modern era of antiretroviral therapy. Thus, we investigated using a multiparametric approach whether speckle tracking echocardiography-derived indices of both ventricles and the left atrium can detect early cardiac dysfunction in young patients with HIV infection, free from conventional risk factors.We prospectively recruited 85 patients  with acquired HIV infection between June 2020 and June 2021 from a single center. Inclusion criteria were (1) age between 18 and 45 years old; (2) presence of sinus rhythm and (3) ability to sign an informed consent. Exclusion criteria were (1) history of cardiomyopathy, coronary artery disease or valvular heart disease; (2) presence of diabetes mellitus; (3) history of arterial pressure above 140 mmHg or (4) echocardiographic images unsuitable for quantification. The control group was selected among 80 age- and gender-matched healthy volunteers with low risk of HIV infection and no history of any cardiovascular disease and with normal findings on clinical examination, electrocardiography and echocardiography.Blood pressure, heart rate and anthropometric information including age, weight and body surface area (BSA) were collected at the time of study. Available clinical data and laboratory results as well as the treatment protocols (for the study group) were obtained from the medical records of the patient.Written informed consent was obtained from each subject, and the study was approved by the ethics committee of our institution.Transthoracic echocardiographic images were recorded using a commercially available ultrasound system . Echocardiography was performed and analyzed offline by two experienced cardiologists (M.M. and O.M.). Subjects were examined at rest, positioned in the left lateral decubitus. A minimum of three cardiac cycles/image were acquired with a mean frame rate of 60 fps.All echocardiographic measurements were obtained in accordance with the current recommendations for chamber quantification . Left veDiastolic function was estimated by measuring the peak early (E) and late (A) transmitral diastolic peak flow velocities (m/s), the E/A ratio and E wave deceleration time (DTE). Peak systolic (s’), early diastolic (e’) and late diastolic (a’) mitral annular velocities were obtained by averaging the values recorded at the septal and lateral positions. To assess LV filling pressures, the E/e’ ratio was calculated.Left atrium volume was obtained from the four-chamber view at end-systole and end-diastole. The right atrium (RA) volume as well as RV end-diastolic area (EDA) and end-systolic area (ESA) and the fractional area change (FAC) were measured from the modified 4-chamber view. The RV function was estimated from tricuspid annular plane systolic excursion (TAPSE) measurements and the TDI systolic values of the free lateral wall. Pulmonary arterial systolic pressure (PASP) was estimated by Doppler echocardiography from the systolic right ventricular to the right atrial pressure gradient using the modified Bernoulli equation (4 times the peak tricuspid velocity-squared). In the presence of a nondilated inferior vena cava with >50% collapsibility, right atrial pressure was assumed to be 6 mmHg. When appropriate, parameters were indexed to BSA.Speckle tracking analysis was performed using EchoPAC version 204 software (GE Vingmed Ultrasound). For all LV, RV and LA measurements, zero strain was defined by the automatic R wave trigger on the ECG. The range ROI was changed if deemed necessary, and the tracking of each segment was visually assessed and rejected when not appropriate. Patients were excluded from the strain analysis if the regional tracking of one or more segments was suboptimal. Aortic valve closure was set on the pulsed wave doppler recording of the LV outflow track.A left ventricular 17-segment model was used. In summary, endocardial border was tracked in 2-, 3-, and 4-chamber views. Global longitudinal strain (GLS) for each layer  was provided automatically A. Peak lRV global longitudinal strain was obtained from the modified four-chamber view by tracing the endocardium border. For RV global LS, a six-segment model was used. RV free wall strain was calculated by averaging the segmental strain  C.LA strain was obtained using the dedicated tool for LA strain (EchoPac v 204). In summary, three anatomic landmarks were positioned manually  and LA strain during the contraction phase (LASct) were automatically provided D.Clinical and echocardiographic measurements are provided as mean ± standard deviation for continuous variables or as absolute number or percentage for categorical variables. Variables were checked to be normally distributed and to have equal variances. To compare data between the predefined study groups, the unpaired t-test was used. Significance was set at a two-tailed probability level of <0.05. Statistical analyses were performed using SPSS version 17.0 .There were no major differences in anthropometric characteristics between the groups . The meap < 0.01) (p = 0.06). LA end-systolic and end-diastolic volumes were also similar between the groups (p = 0.28 and p = 0.34). Eighteen (21%) HIV patients showed diastolic dysfunction grade I. A decrease in e’ and increase in the E/e’ ratio were observed in the HIV group (p < 0.01 for both).LV wall thickness and mass were higher in ALHIV ( < 0.01) , whereasp < 0.001).Right heart measurements were also similar between the groups  except fThe feasibility was 98% for LV strain, 89% for RV strain and 93% for LA strain.p = 0.06). GCS was significantly lower in ALHIV   .p = 0.04 and −25.9 ± 4.1 vs. −27.7 ± 3.8, p = 0.02, respectively). Using the univariate logistic regression analysis, parenteral infection , duration of HIV infection  and BMI  were independent predictors of RV global strain.RV global strain and free wall strain were significantly lower in ALHIV . Univariate logistic regression analysis demonstrated that age  and years of HIV infection  were independent predictors of LA strain. LAS during contraction showed no difference between the groups.The LA reservoir average was 38 ± 7% in the control group and significantly lower (34 ± 7%) in patients with HIV (The main findings of the present study can be summarized as follows: (a) Young patients with long-lasting HIV infection receiving ART show normal LV systolic function; (b) RV global and free wall LS were lower in ALHIV and (c) LA reservoir strain was significantly reduced among ALHIV.We prospectively included young patients with long-lasting HIV infection (mean duration of 17 ± 8 years). This allowed us to more accurately study the effect of HIV infection in subjects free from cardiovascular risk factors. Adults living with HIV showed a mild increase in LV wall thickness and subsequent LV mass compared with controls. The association between increased LV mass and high all-cause mortality was previously reported in HIV patients ,10. The During the past decade, GLS has consolidated its clinical value in assessing early LV impairment. In our study, endocardial, myocardial and epicardial GLS were similar between the groups, suggesting normal LV function in ALHIV. Our results are difficult to compare with previous studies as patient characteristics and patient numbers vary considerably. However, small studies using two- and three-dimensional strain measurements reported impaired LV deformation in ALHIV, regardless of the ART ,15. SimiRight ventricular global strain and free wall strain showed lower values in the HIV group compared with controls. While there is no clear pathophysiologic explanation, early studies also reported isolated RV dysfunction in people living with HIV independent from pulmonary hypertension ,22. MoreLeft atrial strain was shown to be a powerful predictor of cardiovascular events in subjects free from cardiac disease  as well Several studies have related antiretroviral therapy to the development of arterial hypertension ,30 or dyThe main limitation of this study was the small number of patients with HIV infection. Our population was highly selected, and we included only young asymptomatic subjects without cardiovascular risk factors. Moreover, as only treated patients were included, the role of antiretroviral therapy could not be assessed independent of HIV infection. Lastly, in the absence of complete data, we could not assess the impacts of viral load on cardiac function.Young asymptomatic adults with HIV infection and antiviral therapy present with normal left ventricular systolic function. The assessment of LA strain dynamics by speckle tracking echocardiography in HIV patients may be of particular interest in those with no evidence of LA enlargement.