Prognostic value of diastolic function parameters in significant aortic regurgitation: the role of the left atrial strain.

BACKGROUND: The management of patients with asymptomatic significant aortic regurgitation (sAR) is often challenging and appropriate timing of aortic valve surgery remains controversial. Prognostic value of diastolic parameters has been demonstrated in several cardiac diseases. The aim of this study was to analyze the prognostic significance of the diastolic function evaluated by echocardiography, in asymptomatic patients with sAR. METHODS: A total of 126 patients with asymptomatic sAR evaluated in the Heart Valve Clinic were retrospective included. Conventional echocardiographic systolic and diastolic function parameters were assessed. Left atrial (LA) auto-strain analysis was performed in a sub-group of 57 patients. A combined end-point of hospital admission due to heart failure, cardiovascular mortality, or aortic valve surgery was defined. RESULTS: During a median follow-up of 34.1 (interquartile range 16.5-48.1) months, 25 (19.8%) patients reached the combined end-point. Univariate analysis showed that LV volumes, LV ejection fraction (LVEF), LV-GLS, E wave, E/e' ratio, LA volume and LA reservoir strain (LASr) were significant predictors of events. Multivariate analysis that tested all classical echocardiographic variables statistically significant in the univariate model showed that LVEDV (HR = 1.02; 95% CI 1.01-1.03; p < 0.001) and E/e' ratio (HR = 1.12; 95% CI 1.03-123; p = 0.01) were significant predictors of events. Kaplan-Meier curve, stratified by median value of LASr, showed that lower LASr values (less than median of 34%) were associated with higher rates of events (p = 0.013). CONCLUSION: In this population of asymptomatic patients with sAR and normal LV systolic function, baseline diastolic parameters were prognostic markers of cardiovascular events; among them, LASr played a significant predictor role.

Impact of right ventricular systolic function in patients with significant tricuspid regurgitation. A cardiac magnetic resonance study.

BACKGROUND: Right ventricle (RV) dilatation and dysfunction are established criteria for intervention in severe tricuspid regurgitation (TR); however thresholds to support intervention are lacking. New measures of RV function such as RV shortening (RVS) and effective RV ejection fraction (eRVEF) may be earlier markers of RV dysfunction. PURPOSE: to compare the prognostic impact of different parameters of RV function and to describe cut-off values of RV size/function and TR severity of poor prognosis. METHODS: Consecutive patients evaluated in the Heart Valve Clinic with significant TR (severe, massive or torrential TR) undergoing a CMR study were included. In addition to parameters of biventricular volume and function, RVS and eRVEF were assessed. A combined endpoint of hospital admission due to right heart failure and cardiovascular mortality was defined. RESULTS: 75 patients were included (age 75 ± 8 years, female 75%). During a median follow-up of 3 years (IQR: 1.4-3.9 years), 39% experienced the endpoint. Cut-off values of worse prognosis were: RVS ≥ -14%, eRVEF ≤34%, RVEF ≤58%, RV-EDV ≥100 ml/m2, TR regurgitant fraction (TRF) ≥40% and TR volume ≥ 42 ml. RVS and eRVEF identified higher rates of RV dysfunction than RVEF. After adjustment for age and LVEF, both eRVEF ≤34% (HR: 5.29 [2.25-12.4]) and RVS ≥ -14% (HR: 3.46 [1.13-9.17]) were significantly associated with outcomes. Among all parameters of RV function, eRVEF was the strongest predictor of outcomes, incremental to RVEF (ΔC-statistic 0.139 [0.040-0.237], p = 0.005). Patients with eRVEF ≤34% and RV-EDV ≥100 ml/m2 or eRVEF ≤34% and TRF ≥40% had the worst prognosis (p < 0.01 for both). CONCLUSION: RVS and eRVEF identify higher rates of RV dysfunction beyond RVEF. Among all measures, eRVEF held the strongest association with outcomes, incremental to RVEF.

Prognostic implications of cardiac magnetic resonance feature tracking derived multidirectional strain in patients with chronic aortic regurgitation.

OBJECTIVE: Speckle-tracking echocardiography (STE) deformation parameters detect latent LV dysfunction in chronic aortic regurgitation (AR) and are associated with outcomes. The aim of the study was to evaluate cardiac magnetic resonance (CMR) feature tracking (FT) deformation parameters in asymptomatic patients with AR and implications in outcomes. METHODS: Fifty-five patients with AR and 54 controls were included. Conventional functional CMR parameters, aortic regurgitant volume, and fraction were assessed. CMR-FT analysis was performed with a dedicated software. Clinical data was obtained from hospital records. A combined endpoint included all-cause mortality, cardiovascular mortality, aortic valve surgery, or cardiovascular hospital admission due to heart failure. RESULTS: Left ventricular (LV) mechanics is impaired in patients with significant AR. Significant differences were noted in global longitudinal strain (GLS) between controls and AR patients (- 19.1 ± 2.9% vs - 16.5 ± 3.2%, p < 0.001) and among AR severity groups (- 18.3 ± 3.1% vs - 16.2 ± 1.6% vs - 15 ± 3.5%; p = 0.02 for AR grades I-II, III, and IV). In univariate and multivariate analyses, circumferential strain (GCS) and global radial strain (GRS) but not GLS were associated with and increased risk of the end point with a HR of 1.26 (p = 0.016, 1.04-1.52) per 1% worsening for GCS and 0.90 (p = 0.012, 0.83-0.98) per 1% worsening for GRS. CONCLUSIONS: CMR-FT myocardial deformation parameters are impaired in patients with AR not meeting surgical criteria. GLS decreases early in the course of the disease and is a marker of AR severity while GCS and GRS worsen later but predict a bad prognosis, mainly the need of aortic valve surgery. KEY POINTS: • CMR feature tracking LV mechanic parameters may be reduced in significant chronic AR with normal EF. • LV mechanics, mainly global longitudinal strain, worsens as AR severity increases. • LV mechanics, specially global radial and circumferential strain, is associated with a worse prognosis in AR patients.

The tva(A) Gene from Brachyspira hyodysenteriae Confers Decreased Susceptibility to Pleuromutilins and Streptogramin A in Escherichia coli.

The tva(A) gene suspected to confer resistance to pleuromutilins in Brachyspira hyodysenteriae was tested for functionality in Escherichia coli AG100A and Staphylococcus aureus RN4220. Expression of the cloned tva(A) gene conferred decreased susceptibility to pleuromutilin (P) and streptogramin A (SA) antibiotics in E. coli and had a minor effect in S. aureus The finding provides evidence of the direct association of tva(A) with the PSA resistance phenotype.

VLA-4 mediated adhesion of melanoma cells on the blood-brain barrier is the critical cue for melanoma cell intercalation and barrier disruption.

Melanoma is the most aggressive skin cancer in humans. One severe complication is the formation of brain metastasis, which requires extravasation of melanoma cells across the tight blood-brain barrier (BBB). Previously, VLA-4 has been assigned a role for the adhesive interaction of melanoma cells with non-BBB endothelial cells. However, the role of melanoma VLA-4 for breaching the BBB remained unknown. In this study, we used a mouse in vitro BBB model and imaged the shear resistant arrest of melanoma cells on the BBB. Similar to effector T cells, inflammatory conditions of the BBB increased the arrest of melanoma cells followed by a unique post-arrest behavior lacking immediate crawling. However, over time, melanoma cells intercalated into the BBB and compromised its barrier properties. Most importantly, antibody ablation of VLA-4 abrogated melanoma shear resistant arrest on and intercalation into the BBB and protected the BBB from barrier breakdown. A tissue microarray established from human brain metastasis revealed that indeed a majority of 92% of all human melanoma brain metastases stained VLA-4 positive. We propose VLA-4 as a target for the inhibition of brain metastasis formation in the context of personalized medicine identifying metastasizing VLA-4 positive melanoma.

Geometrical and functional cardiac changes after cardiac surgery: a phisiopatological explanation based on speckle tracking.

Cardiac surgery induces geometrical and functional changes, which are not clearly explained. Objective: to investigate the physiopathology of the heart after cardiac surgery using advanced techniques of echocardiography. Thirty patients undergoing cardiac surgery had echocardiographic study prior and after surgery. Left and right ventricular (RV) longitudinal displacement and strain were studied with speckle-tracking. Using longitudinal displacement, we defined a static longitudinal reference-point (sLRP) to which the other segments moved during systole. Transversal displacement and global function were determined by conventional-echo. Left and RV segments showed systolic longitudinal displacement towards the apex, which was the sLRP before surgery; and towards the medium segment of lateral RV-wall one week after surgery. The displacement of basal RV segment towards this sLRP was smaller, causing decreased TAPSE. Apical segments showed an inverse displacement towards the new sLRP, and septum displacement was decreased or inverted towards the lateral RV-wall, causing paradoxus septal motion. RV-wall longitudinal strain was reduced (- 23.1 ± 8.6 vs. - 14.6 ± 5.3;p < 0.001), RV transversal fractional shortening was increased (36.5 ± 10.5 vs. 41.7 ± 13; p = 0.011), and the RV fractional area change was unchanged (46.7 ± 9.5 vs. 47.8 ± 11.7; p = 0.625). The medium segment of RV lateral wall, in contact with sternotomy, remains static after surgery and acts as a new sLRP towards which the rest of segments move, explaining the reduction of TAPSE and paradoxus septal motion. The longitudinal strain of the lateral RV-wall gets impaired, but an increase of transversal motion maintains global RV function.

Area strain from 3D speckle-tracking echocardiography as an independent predictor of early symptoms or ventricular dysfunction in asymptomatic severe mitral regurgitation with preserved ejection fraction.

The indication for surgery in asymptomatic severe mitral regurgitation (SMR) with preserved left ventricular ejection fraction (LVEF) is controversial. We sought to study 3D myocardial mechanics in this population and test 3D-speckle tracking (3DST) parameters as possible predictors of events. 45 asymptomatic patients with SMR and LVEF >60 % and 20 control individuals without cardiac disease underwent 3DST echocardiography. MR group additionally underwent further clinical monitoring. Dyspnea, LVEF under 60 %, or admissions for heart failure were considered as events. When compared with control group, MR group showed lower percentage of global 3D strain, (35.4 ± 9.1 vs. 43.9 ± 10.6; p = 0.003), lower radial strain, lower area change rate and higher end-diastolic volume. In a follow-up time of 23.2 ± 14.5 months we found 15 events (33.3 %). When comparing the remaining patients with this new-onset HF group we found significant differences in longitudinal strain (-17.9 ± 3.3 vs. -15.8 ± 2.1; p = 0.036), area strain (AS) (-48.6 ± 4.6 vs. -43.7 ± 6.2; p = 0.006), circumferential strain (-35.8 ± 4.7 vs. -31.8 ± 6.1; p = 0.034), 3D LVEF (67.1 ± 4.6 vs. 63.0 ± 7.4; p = 0.034) and E/E' index (13.5 ± 3.9 vs. 19.3 ± 9.5; p = 0.006). In multivariate Cox regression AS alone was the only independent predictor. A cutoff value of AS greater than -41.6 % reached a hazard ratio of 4.41 (p = 0.004) for prediction of events. In asymptomatic patients with SMR and preserved ejection fraction, 3DST derived AS is a promising tool for predicting the development of heart failure. This finding may be useful for guiding the selection of patients for early mitral valve repair/replacement surgery even if they are asymptomatic.

Predictors of persistent pulmonary hypertension after mitral valve replacement.

Persistent pulmonary hypertension (P-PH) after mitral valve replacement (MVR) leads to an increased risk of morbidity and mortality. We sought to determine which factors were involved in its occurrence. Patients undergoing MVR for a 3-year period were collected in a retrospective way. We excluded those with an available follow-up shorter than 3 months. Sample size was 111 patients. PH was diagnosed if systolic pulmonary artery pressure (sPAP) estimated by Doppler echocardiography was >40 mmHg. Clinical, echocardiographic, and surgical factors were analyzed. P-PH was present in 42.3 % of patients after 12.6 months of mean follow-up. P-PH was more frequently observed in elderly and female patients, in those with severe degrees of PH before surgery, and significant tricuspid regurgitation (TR). On multivariable analysis, significant TR (OR 1.739; p = 0.01) and more severe degrees of PH before surgery (OR 1.761; p = 0.03) were significantly associated with the presence of P-PH after MVR. Surgical factors related to P-PH were prosthesis size and tricuspid annuloplasty: no need for the performing of tricuspid annuloplasty (OR 0.345; p = 0.025) and the implantation of a smaller prosthesis (OR 0.656; p = 0.004) were related to higher rates of P-PH after MVR. MVR was associated with high prevalence of P-PH after mid-term follow-up. Both PH and significant TR before surgery were associated with P-PH. Our data point out that MVR should be planned before the development of PH and greater TR. Smaller prosthetic size is also a risk factor for P-PH and bigger prostheses are desirable when possible.