Assessment of biventricular function by three-dimensional speckle tracking echocardiography in adolescents and young adults with human immunodeficiency virus infection. a pilot study.

Background. The purpose of the study was to assess biventricular parameters of wall deformation with three-dimensional speckle tracking echocardiography (3DSTE) in adolescents and young adults with human immunodeficiency virus infection (HIV) on antiretroviral therapy in order to detect a possible subclinical myocardial dysfunction. Methods. Twenty-one patients aged 12 to 39years with HIV, 21 normal controls of the same age and sex, and 21 patients with idiopathic non-ischemic dilated cardiomyopathy (DCM) were studied with 3DSTE. All HIV patients were stable in terms of HIV infection, with no history of heart disease or other chronic systemic disease except HIV infection, and were on highly active antiretroviral therapy (HAART) with good immunological control. Standard echocardiographic measures of LV-RV function were assessed. 3D LV global longitudinal strain (GLS), circumferential strain, radial strain and LV twist (TW) were calculated. Global area strain (GAS) was calculated by 3DSTE as percentage variation in surface area defined by the longitudinal and circumferential strain vectors. 3D right ventricular (RV) global and free-wall longitudinal strain were obtained. Results. LV GLS and GAS were lower in HIV patients compared to normal controls (p=0.002, and p=0.01, respectively). There were no significant differences in LV ejection fractions between the groups. There was a weak positive correlation between LV GLS and age (r=0.215, p=0.034) and a weak negative correlation between LV GLS and nadir-CD4 T-cells count (r=0.198, p=0.043). DCM patients had more marked and widespread reduction in LV GLS and GAS compared to controls (p<0.001), whereas in HIV patients LV strain impairment (p<0.05) was more localized in basal and apical regions. RV free-wall longitudinal strain was significantly reduced in HIV patients when compared with the control group (p=0.03). No patient had pulmonary systolic pressure higher than 35mmHg. Conclusions. Three-dimensional speckle tracking echocardiography may help to identify HIV patients at high cardiovascular risk allowing early detection of biventricular dysfunction in the presence of normal LV ejection fraction and in the absence of pulmonary hypertension. LV strain impairment in HIV patients is less prominent and widespread compared to DCM patients

The structure and function of Alzheimer's gamma secretase enzyme complex

The production and accumulation of the beta amyloid protein (Aβ) is a key event in the cascade of oxidative and inflammatory processes that characterizes Alzheimer’s disease (AD). A multi-subunit enzyme complex, referred to as gamma (γ) secretase, plays a pivotal role in the generation of Aβ from its parent molecule, the amyloid precursor protein (APP). Four core components (presenilin, nicastrin, aph-1, and pen-2) interact in a high-molecular-weight complex to perform intramembrane proteolysis on a number of membrane-bound proteins, including APP and Notch. Inhibitors and modulators of this enzyme have been assessed for their therapeutic benefit in AD. However, although these agents reduce Aβ levels, the majority have been shown to have severe side effects in pre-clinical animal studies, most likely due to the enzymes role in processing other proteins involved in normal cellular function. Current research is directed at understanding this enzyme and, in particular, at elucidating the roles that each of the core proteins plays in its function. In addition, a number of interacting proteins that are not components of γ-secretase also appear to play important roles in modulating enzyme activity. This review will discuss the structural and functional complexity of the γ-secretase enzyme and the effects of inhibiting its activity

Early, mid and long term echocardiographic results of percutaneous closure in simple and complex patent foramen ovale.

Background. The interpretation of residual shunts after implantation of different devices for patent foramen ovale (PFO) with different morphologies after cerebrovascular events due to paradoxical embolism is controversial. Methods. Transcatheter PFO closure was performed in 123 patients with a history of ≥1 paradoxical embolism using three different devices: Amplatzer (n=46), Figulla Occlutech (n=41) and Atriasept Cardia (n=36). PFO was a simple flap (S-PFO) in 59 patients and complex (C-PFO) in 64 patients. Complex PFO included isolated aneurysmal septum, long tunnel–type, presence of a small additional atrial septal defect, septum primum deviation, and prominent Eustachian valve. All patients were studied with contrast-enhanced transesophageal echocardiography (TEE) before interventional procedure and thereafter at 1 and 6 months and every 6 to 12 months in case of incomplete closure. Definite closure was confirmed in at least two consecutive studies. Results. The diameter of the occluder varied according to the size of the atrial septum and the size of PFO at the TEE examination prior to implantation. The closure rate between simple and complex PFO concerning all implanted occluders was significantly different (p=0.03). Devices of 25 mm or less had a better occlusion rate. The difference between the closure rate of S-PFO and C-PFO concerning each device type was significant (Amplatzer, p<0.01; Figulla, p<0.01; Atriasept, p<0.05). In two patients thrombi were detected in the six month TEE controls and in two patients the implantation of an adjunctive device was necessary for residual shunt. The mean follow up period was 3.1 years (median 2.3 years) with a re-event-rate of 0.6% per year. Overall, no relation to residual PFO shunting or thrombus formation was seen. There were no peri-interventional major complications. Conclusions. The PFO closure rate is dependent on septal anatomy more than occluder size and type. An adjunctive device may be necessary in selected cases

Assessment of biventricular function by three-dimensional speckle tracking echocardiography in secondary mitral regurgitation after repair with the mitraclip system

Background. The goal of this study was to determine the changes of left (LV) and right (RV) ventricular function with three-dimensional speckle-tracking echocardiography (3DSTE) after percutaneous mitral valve repair with the MitraClip system in high-risk surgical patients with moderate-to-severe or severe secondary mitral regurgitation (MR). Methods. Thirty-two patients with MR undergoing MitraClip were prospectively included. Patients underwent two-dimensional and three-dimensional transthoracic echocardiography before clip implantation and after 6-month follow-up. LV and RV longitudinal strains were obtained by two-dimensional speckle-tracking echocardiography (2DSTE) and 3DSTE. LV circumferential, radial, and area strains were calculated by 3DSTE. Data analysis was performed offline. Results. At 6-month follow-up a significant improvement was shown in LV 2D global longitudinal strain (p&lt;0.005), 3D global longitudinal strain (p=0.0002), and 3D area strain (p=0.0003). Overall, a significant improvement was also shown in 3D RV ejection fraction (p&lt;0.05) and 3D RV free-wall longitudinal strain (p&lt;0.05). A poor increase in LV strains after clip implantation (p=ns) occurred in patients with pronounced pre-existing RV dysfunction. The areas under the ROC curve (AUC) for LV-RV 3DSTE parameters showed high discriminative values (0.87-0.91) in predicting unfavorable outcome with persistent symptoms (NYHA&gt;II) after the procedure. Conclusions. 3DSTE analysis showed overall LV-RV strain improvement after clip implantation as well as lower post-procedural LV strain values in patients with worse pre-existing RV function. These findings could help in guiding MR treatment strategies suggesting different therapies in the presence of marked RV impairment or viceversa anticipating the procedure in case of evolving RV dysfunction

Biatrial function before and after percutaneous closure of atrial septum in patients with and without paroxysmal atrial fibrillation. a two-dimensional and three-dimensional speckle tracking echocardiographic study

We aimed to analyze atrial function by two-dimensional (2DSTE) and three-dimensional (3DSTE) speckle-tracking echocardiography in patients with atrial septal devices and paroxysmal atrial fibrillation (PAF). One hundred sixteen patients and a subgroup of 22 patients who developed PAF after device insertion were studied. Left (LA) and right atrial (RA) peak longitudinal strain (PS) and standard deviations(SDs) of times to peak strain (TPS) were calculated using 2DSTE. LA-RA emptying fraction (EF) and expansion index (EI) were determined using 3DSTE. By multivariate analysis, pre-closure 3D-RA-EI, LA-TPS, and 3D-LA-EI were independently associated with PAF. ROC analysis showed better diagnostic accuracy of the combination of pre-closure TPS and 3D-EI for detecting PAF than the other indices. Patients with atrial septal devices have pre-existent left and right atrial dilatation and dysfunction as assessed by 2DSTE and 3DSTE that appear sensitive for the stratification of PAF risk in this population

assessment of light-chain amyloidosis using 3D speckle tracking echocardiography: Differentiation from other forms of myocardial hypertrophy

Background. Cardiac amyloidosis (CA) is an infiltrative disease primarily caused by extracellular tissue deposition of amyloid fibrils in the myocardial interstitium. Over half of affected patients show cardiac involvement at diagnosis, and this condition is the most important prognostic factor in the natural progression of the disease. The aim of the present study was to examine left ventricular (LV) rotational mechanics in biopsy-proven CA by three-dimensional speckle-tracking echocardiography (3DSTE). Methods. Ten patients (67.9±10.3 years) with CA, 10 patients (68.6±11.7 years) with systemic arterial hypertension (HTN), 10 patients (59.9±13.8 years) with hypertrophic cardiomyopathy (HCM), and 10 age-matched normal controls were studied by conventional echocardiography and 3DSTE. LV longitudinal strain and systolic and diastolic strain rate were obtained in the basal, mid and apical segments of septal and lateral walls in apical 4-chamber view. Circumferential and radial strain and averaged LV rotation and rotational velocities from the base and apex were also determined. Results. LV longitudinal and circumferential strain were reduced in CA patients compared to controls (-14.6% vs -19.7%, p =.005, and -16.9% vs -27.1%, p =.013, respectively) with the most prominent impairment at the basal segments. Peak basal rotation (-5.1±1.4 vs -6.8±2.2degree, p =.001), peak apical rotation (8.7±3.1 vs 10.8±3.4degree, p <.05), and peak untwisting rate (64.3±11 vs 79.3±14degree/s, p =.02) were significantly lower compared to controls. Significant impairment of peak basal rotation was shown in CA patients compared to HTN (p<.05) and HCM patients (p<.01). Comparison of ROC curves for detecting CA showed that the AUC using basal rotation was significantly larger than the other echocardiographic parameters used for diagnosing CA (AUC 0.95, 95% CI 0.87-0.98). Conclusions. Different aspects of LV rotational mechanics are shown in CA, with significant basal hyporotation being the most frequent pattern. This pattern could identify early cardiac involvement and help to differentiate patients with CA from patients with other causes of increased LV wall thickness

Echocardiographic findings in simple and complex patent foramen ovale before and after transcatheter closure

Aims. Percutaneous closure of patent foramen ovale (PFO) in cryptogenic cerebrovascular events is an alternative to medical therapy. The interpretation of residual shunts after implantation of different devices for PFO with different morphologies is controversial. Methods and results. Transcatheter PFO closure was performed in 123 patients with a history of ≥1 paradoxical embolism using three different devices: Amplatzer (n=46), Figulla Occlutech (n=41) and Atriasept Cardia (n=36). Fifty-six patients presented with simple PFO and 67 patients had complex morphologies. All patients were studied with contrast-enhanced transesophageal echocardiography (TEE) before interventional procedure and thereafter at 1 and 6 months and every 6 to 12 months in case of incomplete closure. Definite closure was confirmed in at least two consecutive TEE studies. Various PFO morphologies were identified by TEE before device implantation. The device size to PFO diameter ratio was significantly increased in patients with complex PFO compared to those patients with a simple PFO morphology (p<0.05). The difference between the closure rate of S-PFO and C-PFO concerning each device type was significant (Amplatzer p=0.0027, Figulla p=0.0043, Atriasept p<0.01). The mean follow up period was 3.4 years (median 2.7 years) with a cerebrovascular re-event-rate of 2.4% per year. In three patients thrombi were detected in the six month TEE controls and resolved after medical therapy. In three other patients the implantation of an adjunctive device was necessary for residual shunt. Conclusion. In our series of patients the closure rate was dependent on PFO morphology more than occluder size and type. An adjunctive device was implanted in selected cases

Comprehensive assessment of biventricular function and aortic stiffness in athletes with different forms of training by three-dimensional echocardiography and strain imaging

AimsPrevious studies have shown distinct models of cardiac adaptations to the training in master athletes and different effects of endurance and strength-training on cardiovascular function. We attempted to assess left-ventricular (LV) function, aortic (Ao) function, and right-ventricular (RV) function in athletes with different forms of training by using three-dimensional (3D) echocardiography, tissue Doppler imaging (TDI) and speckle-tracking imaging (STI).Methods and resultsWe examined 35 male marathon runners (endurance-trained athletes, ETA), 35 powerlifting athletes (strength-trained athletes, STA), 35 martial arts athletes (mixed-trained athletes, MTA), and 35 sedentary untrained healthy men (controls, CTR). Two-dimensional and three-dimensional echocardiography were performed for the assessment of LV and RV systolic/diastolic function. LV and RV longitudinal strain (LS) and LV torsion (LVtor) were determined using STI (EchoPAC BT11, GE-Ultrasound). Maximum velocity of systolic wall expansion peaks (AoSvel) was determined using TDI. ETA experienced LV eccentric hypertrophy with increased 3D LV end-diastolic volume and mass and significant increase in peak systolic apical rotation and LVtor. In all groups of athletes, RV-LS was reduced at rest and improved after exercise. AoSvel was significantly increased in ETA and MTA and significantly decreased in STA compared with CTR. There were good correlations between LV remodelling and aortic stiffness values. Multivariate analysis showed aortic wall velocities to be independently related to LV mass index.ConclusionIn strength-trained, endurance-trained, and mixed-trained athletes, ventricular and vascular response assessed by 3DE, TDI, and STI underlies different adaptations of LV, RV, and aortic indexes. © 2013 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013. For permissions please email: journals.permissions@oup. com

Three-dimensional speckle tracking echocardiographic evaluation of biventricular function in adolescents and young adults with human immunodeficiency virus infection acquired in early life

Objective: The pathogenesis of left ventricular (LV) dysfunction in HIV patients includes cardiac direct effects of HIV, the presence of autoantibodies, myocardial inflammatory response to viruses, other infections related to the immune status of patients and side effects associated with antiretroviral drugs or other drugs used for the management of HIV. The purpose of our study was to evaluate biventricular parameters of wall deformation with three-dimensional speckle tracking echocardiography (3DSTE) in HIV-infected patients on antiretroviral therapy in order to detect a possible subclinical myocardial dysfunction. Method: Eighteen patients aged 14 to 33years vertically infected with human immunodeficiency virus and 18 normal controls of the same age and sex were studied with 3DSTE. All patients were on HAART, stable in terms of HIV infection, with no history of heart disease or other chronic systemic disease except HIV infection. Standard echocardiographic measures of LV-RV function were assessed. LV global longitudinal strain (GLS), circumferential and radial strains were calculated. Global area strain (GAS) was calculated by 3DSTE as percentage variation in surface area defined by the longitudinal and circumferential strain vectors. Right ventricular (RV) 3D global and free-wall longitudinal strain were obtained. Results: LV GLS and GAS were lower in HIV patients compared to normal controls (p=0.021, and p=0.004, respectively). There were no significant differences in ejection fractions between the groups. There was a weak positive relationship between LV GLS and age (r=0.418, p=0.039) and a weak negative relationship between LV GLS and CD4 T-cell count (r=0.304, p=0.047). RV free-wall longitudinal strain was significantly reduced in HIV patients when compared with the control group (p=0.023). No patient had pulmonary systolic pressure higher than 35mmHg. Conclusion: Three-dimensional speckle tracking echocardiography is helpful in identifying HIV patients at high cardiovascular risk by allowing early detection of biventricular dysfunction in the absence of pulmonary hypertension