Delphine Baudouy

Imaging in pulmonary hypertension: Focus on the role of echocardiography

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.

Early detection of cardiac involvement in sarcoidosis with 2-dimensional speckle-tracking echocardiography.

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.

Cardiac remodelling amongst adults with various aetiologies of pulmonary arterial hypertension including Eisenmenger syndrome—implications on survival and the role of right ventricular transverse strain

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.

Dnmt2/Trdmt1 as Mediator of RNA Polymerase II Transcriptional Activity in Cardiac Growth

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.

Three-dimensional right-ventricular regional deformation and survival in pulmonary hypertension

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.

Speckle-tracking imaging in patients with Eisenmenger syndrome

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.

B blood group: A strong risk factor for venous thromboembolism recurrence

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.

Inducible Conditional Vascular-Specific Overexpression of Peroxisome Proliferator-Activated Receptor Beta/Delta Leads to Rapid Cardiac Hypertrophy

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.

Transesophageal echocardiography for the assessment of left atrial appendage thrombus: Study of the additional value of systematic real time 3D imaging after regular 2D evaluation

Two‐dimensional transesophageal echocardiography (2DTEE) is currently validated for left atrial appendage (LAA) thrombus assessment but has some limitations.

Three-Dimensional speckle tracking of the right ventricle: implications on survival

Background: Survival in pulmonary hypertension (PH) relates to right ventricular (RV) function. However, the singular anatomy and structure of the right ventricle (RV) limit 2D analysis, and its regional 3D function has not been studied yet. Purpose: We examined the implications of regional 3D RV deformation on clinical condition and survival in adults with PH and healthy. Methods: We performed a prospective longitudinal cohort study recruiting 104 consecutive adult PH patients (58 female, 63±18 years)) and 34 healthy controls (43±14 years) between September 2014 and December 2015. Sixty-four patients (63.4%) were in NYHA functional class ≥III at baseline and 87 (83.7%) were on PH-targeted advanced therapies. 3D transthoracic RV echocardiographic sequences were acquired. Myocardial tracking was performed by a semi-automatic software. Output RV meshes included spatial correspondences. They were post-processed to extract local motion and deformation (area strain) and align the data temporally. Global and local statistics provided representative shape and deformation patterns for each subgroup of subjects. Results: The highest deformation was found in the RV lateral and inferior regions. In PH patients, RV global and regional motion as well as deformation (both area strain, circumferential and longitudinal strain) and global volume patterns were affected in all segments, as compared to healthy controls (p -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: RV shape and strain patterns are gradually deteriorated in PH patients and provide independent prognostic information in this population. Global RV area strain >-18% identifies high-risk PH patients.