Objectives To determine whether dual-chamber rate-adaptive Closed Loop Stimulation (CLS) could prevent recurrence of Vasovagal Syncope (VVS).

Background During VVS, an increase in myocardial contractility associated with a reduction of ventricular filling produces an increase in baroreceptor afferent flow and a consequent decrease in the heart rate. The CLS algorithm is a form of rate-adaptive pacing, which responds to myocardial contraction dynamics, by measuring variations in right ventricular intracardiac impedance: during an incipient VVS it could increase paced heart rate and avoid bradycardia, arterial hypotension and syncope.

Methods Fifty patients (27 males, mean age 59 ± 18 year) with severe and recurrent vasovagal syncope and positive Head Up Tilt Test (HUTT) with cardioinhibition, received a CLS pacemaker (INOS2, Biotronik GmbH Co., Germany). The primary end point was recurrence of two VVSs during a minimum of 1 year of follow-up. Randomization between DDD-CLS and DDI mode (40 bpm) pacing was performed only during the first stage of the study (first year): 9/26 randomized to DDI mode (control group) and 17/26 in DDD-CLS mode. All the 24 patients recruited in the second stage of the study (second year) were programmed in DDD-CLS mode.

Results Of the nine patients randomized to the DDI mode, seven had recurrences of syncope during the first year. At the end of the first year the nine patients were reprogrammed to the CLS mode and no syncope occurred after reprogramming. The 41 patients programmed to CLS had a mean follow-up of 19 ± 4 months: none reported VVS, only four (10%) reported occasional presyncope and their quality of life greatly improved. Positive HUTT at the end of the first year failed to predict the clinical response to CLS pacing.

Conclusions The study demonstrates the effectiveness of CLS pacing in preventing cardioinhibitory VVS. A possible placebo effect of pacemaker implantation occurred in 22% of patients.

Closed loop stimulation in prevention of vasovagal syncope. Inotropy controlled pacing in vasovagal syncope (INVASY): a multicentre randomized, single blind, controlled study

Biventricular pacing improves cardiac function and prevents further left atrial remodeling in patients with symptomatic atrial fibrillation after atrioventricular node ablation.

Aim The benefit of cardiac pacing in patients with severe recurrent reflex syncope and asystole induced by tilt testing has not been established. The usefulness of tilt-table test to select candidates for cardiac pacing is controversial. Methods and results We randomly assigned patients aged 40 years or older who had at least two episodes of unpredictable severe reflex syncope during the last year and a tilt-induced syncope with an asystolic pause longer than 3 s, to receive either an active (pacing ON; 63 patients) or an inactive (pacing OFF; 64 patients) dual-chamber pacemaker with closed loop stimulation (CLS). The primary endpoint was the time to first recurrence of syncope. Patients and independent outcome assessors were blinded to the assigned treatment. After a median follow-up of 11.2 months, syncope occurred in significantly fewer patients in the pacing group than in the control group [10 (16%) vs. 34 (53%); hazard ratio, 0.23; P = 0.00005]. The estimated syncope recurrence rate at 1 year was 19% (pacing) and 53% (control) and at 2 years, 22% (pacing) and 68% (control). A combined endpoint of syncope or presyncope occurred in significantly fewer patients in the pacing group [23 (37%) vs. 40 (63%); hazard ratio, 0.44; P = 0.002]. Minor device-related adverse events were reported in five patients (4%). Conclusion In patients aged 40 years or older, affected by severe recurrent reflex syncope and tilt-induced asystole, dual-chamber pacemaker with CLS is highly effective in reducing the recurrences of syncope. Our findings support the inclusion of tilt testing as a useful method to select candidates for cardiac pacing. Study registration ClinicalTrials.gov identifier NCT02324920, Eudamed number CIV-05-013546.

Cardiac pacing in severe recurrent reflex syncope and tilt-induced asystole.

As most of us are aware, almost every facet of our society is becoming, for better or worse, progressively more technology-dependent. Technological advancement has made autonomous systems, also known as robots, an integral part of our life in several fields, including medicine. The application of robots in anesthesia could be classified into 3 types of robots. The first ones are pharmacological robots. These robots are based on closed-loop systems that allow better-individualized anesthetic drug titration for optimal homeostasis during general anesthesia and sedation. Recent evidence also demonstrates that autonomous systems could control hemodynamic parameters proficiently outperforming manual control in the operating room. The second type of robot is mechanical. They enable automated motorized reproduction of tasks requiring high manual dexterity level. Such robots have been advocated to be more accurate than humans and, thus, could be safer for the patient. The third type is a cognitive robot also known as decision support system. This type of robot is able to recognize crucial clinical situation that requires human intervention. When these events occur, the system notifies the attending clinician, describes relevant related clinical observations, proposes pertinent therapeutic options and, when allowed by the attending clinician, may even administer treatment. It seems that cognitive robots could increase patients' safety. Robots in anesthesia offer not only the possibility to free the attending clinicians from repetitive tasks but can also reduce mental workload allowing them to focus on tasks that require human intelligence such as analytical and clinical approach, lifesaving decision-making capacity, and interpersonal interaction. Nevertheless, further studies have yet to be done to test the combination of these 3 types of robots to maintain simultaneously the homeostasis of multiple biological variables and to test the safety of such combination on a large-scale population.

Autonomous Systems in Anesthesia: Where Do We Stand in 2020? A Narrative Review

Pre-clinical animal models are commonly used to evaluate the osteogenic potential of bone grafting materials in-vivo. Based on the histology analysis, the currently commercially available bone grafting materials show comparable results with respect to biocompatibility, incorporation and remodeling. In the present pilot study we introduce a methodology to compare calcium phosphate-based bone grafting materials from world-leading companies in clinical trials and analyze them by means of established histology and synchrotron radiation-based micro computed tomography (SRlCT). The results indicate that the morphology of the bony structures depends on the selected bone grafting material and that an arbitrarily selected histological slice can lead to misleading conclusions. Complementary lCT data can become the basis for the identification of a representative slice. The registration of the selected histological slice with its counterpart in the three-dimensional lCT dataset was performed both visually and automatically with well comparable results. This registration allows for the compilation of a joint histogram to identify anatomical features, which can neither be extracted from histology nor from lCT data on their own. Accordingly, lCT will become an integral part of studies on the efficacy of bone augmentation materials and beyond.

Combined use of micro computed tomography and histology to evaluate the regenerative capacity of bone grafting materials

OSSWALD, S., et al.: Closed-Loop Stimulation Using Intracardiac Impedance as a Sensor Principle: Correlation of Right Ventricular dP/dtmax and Intracardiac Impedance During Dobutamine Stress Test. Changes of the unipolar right ventricular impedance during the cardiac cycle are related to the changing content of blood (low impedance) and tissue (high impedance) around the tip of the pacing electrode. During myocardial contraction, the impedance continuously increases reaching its maximum in late systole. This impedance increase is thought to correlate with right ventricular contractility, and thus, with the inotropic state of the heart. In the new Inos2 DDDR pacemaker, integrated information from the changing ventricular impedance (VIMP) is used for closed-loop regulation of the rate response. The aim of this study was to analyze the effect of increasing dobutamine challenge on RV contractility and the measured impedance signals. In 12 patients (10 men, 68 ± 12 years) undergoing implantation of an Inos2 DDDR pacemaker (Biotronik), a right ventricular pigtail catheter was inserted for continuous measurements of RV-dP/dtmax and simultaneous VIMP signals during intrinsic and ventricular paced rhythm. Then, a stress test with a stepwise increase of intravenous dobutamine (5–20 μg/kg per min) was performed. To assess the relationship between RV contractility and measured sensor signals, normalized values of dP/dtmax and VIMP were compared by linear regression. There was a strong and highly significant correlation between dP/dtmax and VIMP for ventricular paced (r2= 0.93) and intrinsic rhythm (r2= 0.92), although the morphologies of the original impedance curves differed quite substantially between paced and intrinsic rhythm in the same patient. Furthermore, VIMP correlated well with sinus rate (r2= 0.82), although there were at least four patients with documented chronotropic incompetence. We conclude, that for intrinsic and ventricular paced rhythms sensor signals derived from right ventricular unipolar impedance curves closely correlate with dP/dtmax, and thus, with a surrogate of right ventricular contractility during dobutamine stress testing. Our results suggest that “inotropy-sensing” via measurement of intracardiac impedance is highly accurate and seems to be a promising sensor principle for physiological rate adaptation in a closed-loop pacing system.

Closed-loop stimulation using intracardiac impedance as a sensor principle: correlation of right ventricular dP/dtmax and intracardiac impedance during dobutamine stress test.

M. Lippert

Papers

Closed-loop stimulation using intracardiac impedance as a sensor principle: correlation of right ventricular dP/dtmax and intracardiac impedance during dobutamine stress test.