Automatic optimization of cardiac resynchronization therapy using SonR-rationale and design of the clinical trial of the SonRtip lead and automatic AV-VV optimization algorithm in the paradym RF SonR CRT-D (RESPOND CRT) trial.

Although cardiac resynchronization therapy (CRT) is effective in most patients with heart failure (HF) and ventricular dyssynchrony, a significant minority of patients (approximately 30%) are non-responders. Optimal atrioventricular and interventricular delays often change over time and reprogramming these intervals might increase CRT effectiveness. The SonR algorithm automatically optimizes atrioventricular and interventricular intervals each week using an accelerometer to measure change in the SonR signal, which was shown previously to correlate with hemodynamic improvement (left ventricular [LV] dP/dtmax). The RESPOND CRT trial will evaluate the effectiveness and safety of the SonR optimization system in patients with HF New York Heart Association class III or ambulatory IV eligible for a CRT-D device. Enrolled patients will be randomized in a 2:1 ratio to either SonR CRT optimization or to a control arm employing echocardiographic optimization. All patients will be followed for at least 24 months in a double-blinded fashion. The primary effectiveness end point will be evaluated for non-inferiority, with a nested test of superiority, based on the proportion of responders (defined as alive, free from HF-related events, with improvements in New York Heart Association class or improvement in Kansas City Cardiomyopathy Questionnaire quality of life score) at 12 months. The required sample size is 876 patients. The two primary safety end points are acute and chronic SonR lead-related complication rates, respectively. Secondary end points include proportion of patients free from death or HF hospitalization, proportion of patients worsened, and lead electrical performance, assessed at 12 months. The RESPOND CRT trial will also examine associated reverse remodeling at 1 year

Contractility sensor-guided optimization of cardiac resynchronization therapy: results from the RESPOND-CRT trial

Aims Although cardiac resynchronization therapy (CRT) is effective in patients with systolic heart failure (HF) and a wide QRS interval, a substantial proportion of patients remain non-responsive. The SonR contractility sensor embedded in the right atrial lead enables individualized automatic optimization of the atrioventricular (AV) and interventricular (VV) timings. The RESPOND-CRT study investigated the safety and efficacy of the contractility sensor system in HF patients undergoing CRT. Methods and results RESPOND-CRT was a prospective, randomized, double-blinded, multicentre, non-inferiority trial. Patients were randomized (2:1, respectively) to receive weekly, automatic CRT optimization with SonR vs. an Echo-guided optimization of AV and VV timings. The primary efficacy endpoint was the rate of clinical responders (patients alive, without adjudicated HF-related events, with improvement in New York Heart Association class or quality of life), at 12 months. The study randomized 998 patients. Responder rates were 75.0% in the SonR arm and 70.4% in the Echo arm (mean difference, 4.6%; 95% CI, −1.4% to 10.6%; P < 0.001 for non-inferiority margin −10.0%) (Table 2). At an overall mean follow-up of 548 ± 190 days SonR was associated with a 35% risk reduction in HF hospitalization (hazard ratio, 0.65; 95% CI, 0.46–0.92; log-rank P = 0.01). Conclusion: Automatic AV and VV optimization using the contractility sensor was safe and as effective as Echo-guided AV and VV optimization in increasing response to CRT. ClinicalTrials.gov number NCT0153423

Contact force transmission at rough interfaces: numerical and experimental investigation

ICTAM 2000, Chicag

Contact force transmission at rough interfaces: numerical and experimental investigation

ICTAM 2000, Chicag

The effect of scale and criticality in rock slope stability

The apparent shear strength of rock discontinuities is considerably smaller than that of small scale samples. At the same time, the sliding behavior is characterized, in situ, by marked instabilities, with the typical features of Critical Phenomena. Contact mechanics permits to calculate normal and tangential forces at any point, and to follow the stick-slip transition for arbitrary loading histories. On the other hand, the above aspects are not captured by the classical theories, including those based on roughness indices. We argue that the multiscale topology of contact domains plays a fundamental role in determining the behavior of rock joints. In particular, experiments and numerical simulations show that these domains are lacunar sets with fractal dimension smaller than 2.0. This provides peculiar scaling of normal and tangential pressures at the interface, and the consequent size-dependence of the apparent friction coefficient. Moreover, we implement Renormalization Group to determine the critical point (e.g. the critical shear force) when rock sliding occurs. We show that the critical force is less than the one predicted by the classical Coulomb's theory, and that it depends on the specimen size and on the topology of the interface. The same reasoning can be extended to other phenomena, e.g., to the rupture of brittle materials