echocardiographic-histological-examination-cardiac-morphology

Echocardiographic and Histological Examination of Cardiac Morphology in the Mouse

An increasing number of genetically modified mouse models has become available in recent years. Moreover, the number of pharmacological studies performed ...

CNRS, INSERM, iBV

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.

Imaging in pulmonary hypertension: Focus on the role of echocardiography.

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.

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

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.

Speckle-tracking imaging in patients with Eisenmenger syndrome.

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.

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

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.

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

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.

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

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.

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.

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.

Article	Year
Imaging in pulmonary hypertension: Focus on the role of echocardiography. Archives of cardiovascular diseases\| PubMed ID: 24746538	2014
B blood group: A strong risk factor for venous thromboembolism recurrence. Thrombosis research\| PubMed ID: 25981188	2015
Speckle-tracking imaging in patients with Eisenmenger syndrome. Archives of cardiovascular diseases\| PubMed ID: 26868160	2016
Inducible Conditional Vascular-Specific Overexpression of Peroxisome Proliferator-Activated Receptor Beta/Delta Leads to Rapid Cardiac Hypertrophy. PPAR research\| PubMed ID: 27057154	2016
Dnmt2/Trdmt1 as Mediator of RNA Polymerase II Transcriptional Activity in Cardiac Growth. PloS one\| PubMed ID: 27270731	2016
Early detection of cardiac involvement in sarcoidosis with 2-dimensional speckle-tracking echocardiography. International journal of cardiology\| PubMed ID: 27836307	2017
Cardiac remodelling amongst adults with various aetiologies of pulmonary arterial hypertension including Eisenmenger syndrome-implications on survival and the role of right ventricular trans... European heart journal cardiovascular Imaging\| PubMed ID: 28011668	2016
Three-dimensional right-ventricular regional deformation and survival in pulmonary hypertension. European heart journal cardiovascular Imaging\| PubMed ID: 28637308	2017
Symptomatic double aortic arch in an adult patient. Acta cardiologica\| PubMed ID: 28705108	2017

Delphine Baudouy

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