Acute effects of biventricular pacing on right ventricular function assessed by tissue Doppler imaging.

AIMS: The benefits of cardiac resynchronization therapy (CRT) on functional status, left ventricular (LV) remodelling and survival in patients with drug-refractory congestive heart failure (CHF), LV systolic dysfunction, and wide QRS have been demonstrated in randomized trials. However, the impact of CRT on right ventricular (RV) function, an independent prognostic factor in CHF remains questionable. This study examined the acute effects of various pacing modes on RV function in recipients of CRT systems. METHODS AND RESULTS: Echocardiographic examinations were performed in 15 patients (median age: 67 years, range 49-78), to compare RV function during atrial (AAI), RV and LV pacing, and biventricular (BiV) pacing, in random order. At baseline, the median LV ejection fraction was 20% (range 10-35) and the median LV end-diastolic diameter was 78 mm (range 62-85). Right ventricular function was impaired, with a median 36% fractional shortening of RV surfaces (7-59). Tissue Doppler systolic peak of velocity (Sa) recorded at the tricuspid annulus increased significantly from 9.9 cm/s (range 4.7-16.5) during AAI pacing, 10 cm/s (range 5.4-20.3) during RV pacing, and 11.7 cm/s (range 4.6-16.7) during LV pacing to 12.6 cm/s (range 6.6-19.1) during BiV pacing (P < 0.01). Trends toward improvements in other indices of RV function, particularly myocardial performance index and systolic excursion of the tricuspid annulus, were also observed. CONCLUSIONS: This short-term study showed a significant improvement in RV systolic function during BiV pacing compared with AAI, RV, or LV pacing in CRT recipients

Septal versus apical pacing sites in permanent right ventricular pacing: The multicentre prospective SEPTAL-PM study

International audienceBACKGROUND: The optimal right ventricular pacing site for patients requiring pacemaker implantation for permanent atrioventricular block is a matter of debate. Long-term right ventricular apical pacing has been associated with left ventricular ejection fraction impairment and heart failure. Right ventricular septal pacing has been proposed as an alternative. AIM: The aim of this randomized prospective multicentre trial was to compare left ventricular remodelling and outcomes between right ventricular apical and septal pacing after mid-term follow-up. METHODS: Patients requiring pacemaker implantation for high-degree atrioventricular block were enrolled and randomized in a 1:1 fashion to receive a right ventricular apical or septal lead. RESULTS: A total of 141 patients were included, 69 in the septal group and 72 in the apical group. Both groups exhibited similar left ventricular ejection fractions after 18 months of follow-up (septal 57.1±11.9% vs. apical 57.4±13.4%), and left ventricular ejection fraction variation was similar in the two groups at the end of follow-up (septal -1.5±13.2% vs. apical 0.3±13.3%). Additionally, left ventricular volume, quality of life and 6-minute walk distance were similar in the two groups. However, patients in the septal group were more likely to be asymptomatic, with a significantly lower concentration of N-terminal prohormone of brain natriuretic peptide. Lastly, lead position did not impact 18-month survival. CONCLUSION: Pacing from the right ventricular apex does not have any detrimental effect on left ventricular systolic function compared with septal pacing over an 18-month period

Luzerne références: Edition 2016-2018

Luzerne références. Edition 2016-201

SAR156497, an Exquisitely Selective Inhibitor of Aurora Kinases

The Aurora family of serine/threonine kinases is essential for mitosis. Their crucial role in cell cycle regulation and aberrant expression in a broad range of malignancies have been demonstrated and have prompted intensive search for small molecule Aurora inhibitors. Indeed, over 10 of them have reached the clinic as potential anticancer therapies. We report herein the discovery and optimization of a novel series of tricyclic molecules that has led to SAR156497, an exquisitely selective Aurora A, B, and C inhibitor with in vitro and in vivo efficacy. We also provide insights into its mode of binding to its target proteins, which could explain its selectivity