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Aims: Outcomes in pulmonary hypertension (PH) are related to right ventricular (RV) function and remodelling. We hypothesized that changes in RV function and especially area strain (AS) could provide incremental prognostic information compared to the use of baseline data only. We therefore aimed to assess RV function changes between baseline and 6-month follow-up and evaluate their prognostic value for PH patients using 3D echocardiography., Methods and Results: Ninety-five PH patients underwent a prospective longitudinal study including ESC/ERS guidelines prognostic assessment and 3D RV echocardiographic imaging at baseline and 6-month follow-up. Semi-automatic software tracked the RV along the cycle, and its output was post-processed to extract 3D deformation patterns. Over a median follow-up of 24.8 (22.1-25.7) months, 21 patients died from PH or were transplanted. Improvements in RV global AS were associated with stable or improving clinical condition as well as survival free from transplant (P < 0.001). The 3D deformation patterns confirmed that the most significant regional changes occurred within the septum. RV global AS change over 6-month by +3.5% identifies patients with a 3.7-fold increased risk of death or transplant. On multivariate COX analysis, changes in WHO class, BNP, and RV global AS were independent predictors of outcomes. Besides, the combination of these three parameters was of special interest to identify high-risk patients [HR 11.5 (1.55-86.06)]., Conclusion: Changes in RV function and especially changes in 3D RV AS are of prognostic importance. Our study underlines that assessing such changes from baseline to follow-up is of additional prognostic value for PH patients., Clinical Trial Registration: http://clinicaltrials.gov/ct2/show/NCT02799979., Competing Interests: Conflict of interest: None declared., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: Pulmonary embolism (PE) is a common life-threatening disease, with mortality related to right ventricular (RV) dysfunction., Aims: To investigate the value of 3D global and regional RV strain in patients with acute PE and at 1 month, as compared to a control population., Methods and Results: We conducted a longitudinal case-control prospective study, including 24 consecutive intermediate-risk PE patients. All patients underwent 2D and 3D transthoracic echocardiography within 12 hours of PE diagnosis and 1 month after hospital discharge. A control group was recruited, consisting of healthy volunteers matched on age and sex with PE patients. 3D RV echocardiographic sequences were analyzed by commercial RV-specific software and output meshes were post-processed to extract regional deformation. 3D echocardiographic 1-month follow-up was available in 18 patients. During acute PE, area strain was substantially altered in the RV free wall and within the trabecular septum. PE patients initially had RV dysfunction as assessed by 2D and 3D parameters. At follow-up, 2D parameters were restored compared to the control group, contrary to 3D RV area and circumferential strains. The McConnell's sign was identified in 83% of patients and was associated with reduced apical and global RV area strain., Conclusions: Our 3D RV strain study demonstrates an incomplete recovery of 3D strain parameters 1 month after an episode of intermediate-risk acute PE despite restored 2D parameters. Further studies are required to assess the prognostic role and implications of this residual RV strain impairment after PE., (© 2021 Wiley Periodicals LLC.)

Aims: Right ventricular (RV) function assessment is crucial in congenital heart disease patients, especially in atrial septal defect (ASD) and repaired Tetralogy of Fallot (TOF) patients with pulmonary regurgitation (PR). In this study, we aimed to analyse both 3D RV shape and deformation to better characterize RV function in ASD and TOF-PR., Methods and Results: We prospectively included 110 patients (≥16 years old) into this case-control study: 27 ASD patients, 28 with TOF, and 55 sex- and age-matched healthy controls. Endocardial tracking was performed on 3D transthoracic RV echocardiographic sequences and output RV meshes were post-processed to extract local curvature and deformation. Differences in shape and deformation patterns between subgroups were quantified both globally and locally. Curvature highlights differences in RV shape between controls and patients while ASD and TOF-PR patients are similar. Conversely, strain highlights differences between controls and TOF-PR patients while ASD and controls are similar [global area strain: -31.5 ± 5.8% (controls), -34.1 ± 7.9% (ASD), -24.8 ± 5.7% (TOF-PR), P < 0.001, similar significance for longitudinal and circumferential strains]. The regional and local analysis highlighted differences in particular in the RV free wall and the apical septum., Conclusion: Chronic RV volume loading results in similar RV shape remodelling in both ASD and TOF patients while strain analysis demonstrated that RV strain is only reduced in the TOF group. This suggests a fundamentally different RV remodelling process between both conditions., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Association between Hydroxychloroquine (HCQ) and Azithromycin (AZT) is under evaluation for patients with lower respiratory tract infection (LRTI) caused by the Severe Acute Respiratory Syndrome (SARS-CoV-2). Both drugs have a known torsadogenic potential, but sparse data are available concerning QT prolongation induced by this association. Our objective was to assess for COVID-19 LRTI variations of QT interval under HCQ/AZT in patients hospitalized, and to compare manual versus automated QT measurements. Before therapy initiation, a baseline 12 lead-ECG was electronically sent to our cardiology department for automated and manual QT analysis (Bazett and Fridericia's correction), repeated 2 days after initiation. According to our institutional protocol (Pasteur University Hospital), HCQ/AZT was initiated only if baseline QTc ≤ 480ms and potassium level> 4.0 mmol/L. From March 24 th to April 20 th 2020, 73 patients were included (mean age 62 ± 14 years, male 67%). Two patients out of 73 (2.7%) were not eligible for drug initiation (QTc ≥ 500 ms). Baseline average automated QTc was 415 ± 29 ms and lengthened to 438 ± 40 ms after 48 hours of combined therapy. The treatment had to be stopped because of significant QTc prolongation in two out of 71 patients (2.8%). No drug-induced life-threatening arrhythmia, nor death was observed. Automated QTc measurements revealed accurate in comparison with manual QTc measurements. In this specific population of inpatients with COVID-19 LRTI, HCQ/AZT could not be initiated or had to be interrupted in less than 6% of the cases., (© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.)

[This corrects the article DOI: 10.1155/2016/7631085.].

This case illustrates the evolution of right ventricular (RV) 3-dimensional (3D) area strain during pregnancy in a patient with repaired Tetralogy of Fallot. The report highlights impairment in RV function with pregnancy, suggesting the importance of prepregnancy RV systolic function assessment, especially using 3D echocardiography., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Two-dimensional transesophageal echocardiography (2DTEE) is currently validated for left atrial appendage (LAA) thrombus assessment but has some limitations., Aims: To evaluate the performance and interest of systematic real time three-dimensional transesophageal echocardiography (3DTEE) for LAA thrombus assessment, when performed after 2DTEE., Methods and Results: Consecutive patients undergoing TEE were prospectively included. LAA was first evaluated using 2DTEE, and patients were classified as "2D-NT" if no thrombus was found, "2D-T" in case of clear thrombus, or "2D-EQ" if equivocal. Then, 3DTEE of the LAA was performed and patients were similarly classified as "3D-NT," "3D-T," or "3D-EQ." Additional LAA CT scan was only performed if LAA thrombus was not clearly ruled out or confirmed by TEE. Additional value of 3DTEE after 2DTEE LAA evaluation was then assessed. We included 104 patients undergoing TEE. Agreement between 2DTEE and 3DTEE was very good for thrombus diagnosis (k = 0.936), but moderate for vacant LAA (k = 0.562) due to more frequent 2D-EQ than 3D-EQ (11.5% vs 2.9%; P = .016). 3DTEE allowed to refine the LAA status in 11 of 12 (91.7%) 2D-EQ patients: 10 3D-NT, 1 3D-T, and 1 3D-EQ. Coupling 3DTEE to 2DTEE permitted a definite LAA diagnosis in 103 of 104 (99%) vs 92 of 104 (88.5%) patients when 2DTEE was used alone (P = .002). Nine (8.7%) LAA thrombi were diagnosed, and 3 CT scan were performed., Conclusion: 3DTEE of the LAA is more effective for thrombus assessment than 2DTEE. 3DTEE should be particularly considered in case of equivocal 2DTEE, as it allows to reach a definite LAA diagnosis in almost all of the patients., (© 2018, Wiley Periodicals, Inc.)

Aims: Survival in pulmonary hypertension (PH) relates to right ventricular (RV) function. However, the RV unique anatomy and structure limit 2D analysis and its regional 3D function has not been studied yet. The aim of this study was to assess the implications of global and regional 3D RV deformation on clinical condition and survival in adults with PH and healthy controls., Methods and Results: We collected a prospective longitudinal cohort of 104 consecutive PH patients and 34 healthy controls between September 2014 and December 2015. Acquired 3D transthoracic RV echocardiographic sequences were analysed by semi-automatic software (TomTec 4D RV-Function 2.0). Output meshes were post-processed to extract regional motion and deformation. Global and regional statistics provided deformation patterns for each subgroup of subjects. RV lateral and inferior regions showed the highest deformation. In PH patients, RV global and regional motion and deformation [both circumferential, longitudinal, and area strain (AS)] were affected in all segments (P < 0.001 against healthy controls). Deformation patterns gradually worsened with the clinical condition. Over 6.7 [5.8-7.2] months follow-up, 16 (15.4%) patients died from cardio-pulmonary causes. Right atrial pressure, global RV AS, tricuspid annular plane systolic excursion, 3D RV ejection fraction, and end-diastolic volume were independent predictors of survival. Global RV AS  > -18% was the most powerful RV function parameter, identifying patients with a 48%-increased risk of death (AUC 0.83 [0.74-0.90], P < 0.001)., Conclusion: Right ventricular strain patterns gradually worsen in PH patients and provide independent prognostic information in this population.

Aims: Survival in pulmonary arterial hypertension (PAH) and Eisenmenger syndrome (ES) relates to right ventricular (RV) function. Little is known about differences of ventricular function between ES patients and those suffering from other PAH aetiologies. In this study, we compared global ventricular function assessed by speckle-tracking in adult patients with ES, other PAH aetiologies, or healthy controls; and assessed the relationship between ventricular function and survival., Methods and Results: We performed a prospective cohort study recruiting 83 adult PAH patients (43 ES and 40 other PAH aetiologies patients) and 37 controls between March 2011 and June 2015. Patients with complex congenital heart disease were excluded. Fifty-three patients (63.9%) were in NYHA functional class ≥III at baseline and 60 (72.3%) were on advanced therapies. Mean RV peak longitudinal strain was -16.3 ± 7% in ES, lower compared with healthy controls (P < 0.001) but similar to other PAH aetiologies (P = 0.6). Mean RV peak transverse strain was +26.1 ± 17% in ES, lower than in controls (P < 0.001) but higher than in other PAH aetiologies (P < 0.001). No difference was observed between ES and other PAH in LV circumferential and longitudinal strain. Over a median follow-up of 22.6 months (3.3-32.2), 22 (26.5%) patients died all from cardio-pulmonary causes. ES and RV peak transverse strain were independent predictors of survival. RV peak transverse strain ≤22% identified patients with a 14-fold increased risk of death., Conclusion: Right ventricular remodelling differs between adults with ES and other PAH aetiologies. ES and increased RV free wall transverse strain are associated with better survival., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions, please email: journals.permissions@oup.com.)

An increasing number of genetically modified mouse models has become available in recent years. Moreover, the number of pharmacological studies performed in mice is high. Phenotypic characterization of these mouse models also requires the examination of cardiac function and morphology. Echocardiography and magnetic resonance imaging (MRI) are commonly used approaches to characterize cardiac function and morphology in mice. Echocardiographic and MRI equipment specialized for use in small rodents is expensive and requires a dedicated space. This protocol describes cardiac measurements in mice using a clinical echocardiographic system with a 15 MHz human vascular probe. Measurements are performed on anesthetized adult mice. At least three image sequences are recorded and analyzed for each animal in M-mode in the parasternal short-axis view. Afterwards, cardiac histological examination is performed, and cardiomyocyte diameters are determined on hematoxylin-eosin- or wheat germ agglutinin (WGA)-stained paraffin sections. Vessel density is determined morphometrically after Pecam-1 immunostaining. The protocol has been applied successfully to pharmacological studies and different genetic animal models under baseline conditions, as well as after experimental myocardial infarction by the permanent ligation of the left anterior descending coronary artery (LAD). In our experience, echocardiographic investigation is limited to anesthetized animals and is feasible in adult mice weighing at least 25 g.

Background/objectives: Cardiac sarcoidosis (CS) is associated with high morbidity and sudden death. The absence of specific symptoms and lack of diagnostic gold standard technique is challenging. New imaging methods could improve the diagnosis of CS. The aim of our study was to assess the role of left ventricular (LV) longitudinal and circumferential strain as estimated by 2D speckle-tracking imaging in patients with diagnosed sarcoidosis without cardiac involvement according to the current guidelines. We investigated the prevalence of LV strain impairment in this population and assessed its relationship with clinical outcomes, composite of mortality, heart failure, arrhythmia and/or secondarily development of CS and cardiac device implantation., Methods and Results: We performed a prospective case-control longitudinal study including 35 patients with diagnosed sarcoidosis and normal cardiac function as assessed by standard transthoracic echocardiography and 35 healthy age- and gender-matched controls. All patients underwent a comprehensive echocardiographic study. Mean age of patients was 47.9±14.8years old (22 women). Compared with controls, global LV longitudinal strain (LV GLS) was reduced in sarcoidosis patients: (-17.2±3.1 vs -21.3±1.5%, p<0.0001). Circumferential LV strain was preserved in patients compared to controls (-19.9±-4.3% vs -21.3±1.5%, p=0.12). Impaired LV GLS was significantly associated with clinical outcomes (HR 1.56; [1.16-2.11], p<0.01) on univariate analysis., Conclusion: Speckle-tracking echocardiography revealed decreased longitudinal LV strain in sarcoidosis patients that was associated with outcomes. LV GLS may represent an early marker of myocardial involvement in sarcoidosis patients that needs to be studied further., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Dnmt2/Trdmt1 is a methyltransferase, which has been shown to methylate tRNAs. Deficient mutants were reported to exhibit various, seemingly unrelated, defects in development and RNA-mediated epigenetic heredity. Here we report a role in a distinct developmental regulation effected by a noncoding RNA. We show that Dnmt2-deficiency in mice results in cardiac hypertrophy. Echocardiographic measurements revealed that cardiac function is preserved notwithstanding the increased dimensions of the organ due to cardiomyocyte enlargement. Mechanistically, activation of the P-TEFb complex, a critical step for cardiac growth, results from increased dissociation of the negatively regulating Rn7sk non-coding RNA component in Dnmt2-deficient cells. Our data suggest that Dnmt2 plays an unexpected role for regulation of cardiac growth by modulating activity of the P-TEFb complex.

Background: Adults with Eisenmenger syndrome have a survival advantage over those with idiopathic pulmonary arterial hypertension. Improved survival may result from preservation of right ventricular (RV) function., Aims: To assess left ventricular (LV) and RV remodelling in patients with Eisenmenger syndrome compared to a control population, using speckle-tracking imaging., Methods: Adults with Eisenmenger syndrome and healthy controls were enrolled into this prospective two-centre study. Patients with Eisenmenger syndrome with low acoustic windows, irregular heart rhythm or complex congenital heart disease were excluded. Clinical assessment, B-type natriuretic peptide (BNP), 6-minute walk test and echocardiography (including dedicated views to perform offline two-dimensional-speckle-tracking analysis) were performed on inclusion., Results: Our patient population (n=37; mean age 42.3 ± 17 years) was mostly composed of patients with ventricular septal defect (37.8%) or atrial septal defect (35.1%). Compared with the control population (n=30), patients with Eisenmenger syndrome had reduced global LV longitudinal strain (-17.4 ± 3.5 vs. -22.4 ± 2.3; P<0.001), RV free-wall longitudinal strain (-15.0 ± 4.7 vs. -29.9 ± 6.8; P<0.001) and RV transverse strain (25.8 ± 25.0 vs. 44.5 ± 15.1; P<0.001). Patients with Eisenmenger syndrome also more frequently presented a predominant apical longitudinal and transverse strain profile. Among patients with Eisenmenger syndrome, those with a post-tricuspid shunt presented with reduced global LV longitudinal strain but increased RV transverse strain, compared to patients with pre-tricuspid shunt., Conclusion: Patients with Eisenmenger syndrome had impaired longitudinal RV and LV strain, but present a relatively important apical deformation. RV and LV remodelling, as assessed by speckle-tracking imaging, differ between patients with pre- and post-tricuspid shunt., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Peroxisome proliferator-activated receptors are nuclear receptors which function as ligand-activated transcription factors. Among them, peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) is highly expressed in the heart and thought to have cardioprotective functions due to its beneficial effects in metabolic syndrome. As we already showed that PPARβ/δ activation resulted in an enhanced cardiac angiogenesis and growth without impairment of heart function, we were interested to determine the effects of a specific activation of PPARβ/δ in the vasculature on cardiac performance under normal and in chronic ischemic heart disease conditions. We analyzed the effects of a specific PPARβ/δ overexpression in endothelial cells on the heart using an inducible conditional vascular-specific mouse model. We demonstrate that vessel-specific overexpression of PPARβ/δ induces rapid cardiac angiogenesis and growth with an increase in cardiomyocyte size. Upon myocardial infarction, vascular overexpression of PPARβ/δ, despite the enhanced cardiac vessel formation, does not protect against chronic ischemic injury. Our results suggest that the proper balance of PPARβ/δ activation in the different cardiac cell types is required to obtain beneficial effects on the outcome in chronic ischemic heart disease.

Background: Non-O blood group patients are at higher risk of first episode of venous thromboembolism (VTE). However, only little is known about the risk of recurrence according to the blood group. In this study, we aimed to determine the impact of ABO blood group on VTE recurrence., Methods: We prospectively recruited 106 consecutive patients with a first documented episode of pulmonary embolism (PE). Patients were followed at least 12months after anticoagulation discontinuation. The main endpoint was recurrence of symptomatic VTE., Results: Data from 100 patients were analyzed. Median follow-up was 28months [24-34.8]. PE was unprovoked in 48 patients. Mean anticoagulation duration was 5.3±2.2months. The rate of VTE recurrence was 12.7 per 100 patient-years (30 recurrences). B blood group patients had a 2.7-fold increased risk of VTE recurrence (95%CI 1.1-6.2, p=0.03). On multivariate analysis, B blood group was the strongest independent predictor of VTE recurrence (Hazard Ratio (HR) 2.6, 95%CI 1.1-6.1, p=0.04). In contrast, A and AB blood groups were not associated with VTE recurrence. VTE recurrences were less frequent in O blood group compared to non-O patients (HR 0.5, 95%CI 0.2-1.1, p=0.09). O blood group women had a 5-fold decreased risk of VTE recurrence (HR 0.2, 95%CI 0.1-0.8, p=0.01)., Conclusions: Non-O blood groups, beyond being involved in the occurrence of a first VTE event, also contribute to VTE recurrence. B blood group is strongly associated with VTE recurrence, thus high-risk B blood group patients could benefit from long-term anticoagulation therapy after a first VTE event., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Patients with pulmonary hypertension must be evaluated using a multimodality approach to ensure a correct diagnosis and basal evaluation as well as a prognostic assessment. Beyond the assessment of pulmonary pressures, the echocardiographical examination allows the evaluation of right ventricular adaptation to elevated afterload. Numbers of variables are commonly used in the assessment of the pulmonary hypertension patient in order to detect changes in right heart geometry, right-to-left interaction and right ventricular dysfunction. Whereas an isolated change in one echocardiographical variable is not meaningful, multiple echocardiographical variable modifications together provide accurate information. In this review, we will link pulmonary hypertension pathophysiological changes with echocardiographical indices and describe the clinical implications of echocardiographical findings., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)