Closed-loop Stimulation Algorithm Research Articles

P396 OUR CERTIFIED SYNCOPE UNIT EXPERIENCE; FROM DIAGNOSTIC APPROPRIATENESS TO DEVICE IMPLANTS, FROM PATIENT EDUCATION TO THE IMPACT OF THE COVID–19 PANDEMIC. REPORT ON TWO “DIFFICULT” YEARS

Syncope is a frequent medical problem with an incidence of about 6.2/1000 people/year, with important impact on the patients quality of life and often difficult to diagnose and manage; in this regard, the Syncope Units certified by the Italian Group for the study of syncope were created. The following describes our experience over the last 30 months characterized by significant difficulties due to the COVID–19 pandemic. Our Syncope Unit, included in the OU of Cardiology, includes 3 doctors, 3 cardiology technicians, 2 nurses; the activity is three times a week in terms of clinic and HUTT (Head up tilt test). In 2019, 54 HUTTs were performed on patients with an average age of 67 years 50% male, with indication of vasovagal syncope (VVS) for 78% of cases, presyncope and other indications for the remaining 21%, requested by other services. The HUTT was positive for cardioinhibitory and sinus–carotid syncope with indication for Pacemaker implantation (with closed loop stimulation algorithm – CLS) for 22% of cases. In 12% of patients, an ECG–Loop recorder (ILR) was indicated, but 42% of these refused this procedure. In 2020, 32 HUTTs were performed, the same average age, with 86% indication of VVS syncope. The indication for a pacemaker implant was 15% as well as for an ILR implant. 33 to 38% of patients were educated, providing dedicated material, on the prevention of syncope. About 4% of patients refused to undergo the HUTT after the explanation of its performing modalities. The first 6 months of 2021 showed a similar trend to that of 2019. The data show a good appropriateness of the indications to the HUTT and a subsequent PM implantation rate similar to the data available in the literature. The device with CLS has shown benefits in reducing syncopal recurrences at 6 months by over 25%; only 3% of the ILRs were followed by PM implantation. The HUTT, despite of low sensitivity and specificity, is confirmed as a valid VVS characterization tool but sometimes the patient frightened by its performing methods. The COVID–19 pandemic significantly impacted our activity, related to the outpatient in office activities stop and to the shift of operators in COVID areas. We had a 40% reduction in visits and HUTTs performed with consequent missed and/or delayed diagnoses.

Cardiac Pacing in Cardioinhibitory Reflex Syncope: Clinical Use of Closed-loop Stimulation.

Cardiac pacing has been studied extensively in patients with reflex syncope over the past two decades. The heterogeneity of the forms and clinical manifestations of reflex syncope explain the controversial results of older randomised clinical trials. New evidence from recent trials has changed medical practice, now leading to clear indications for pacing in patients with asystolic syncope documented during carotid sinus massage, implantable cardiac monitoring or tilt testing. Given that recent trials in reflex syncope have been performed using the closed-loop stimulation algorithm, the authors will briefly discuss this pacing mode, review hypotheses about the mechanisms underlying its activation during syncope and provide practical instructions for programming and troubleshooting.

Heart rate distribution in paced and non-paced patients with severe recurrent reflex syncope and tilt-induced asystole: Findings from the BIOSync CLS study

BackgroundUndiagnosed sinus or atrioventricular node dysfunction may bias estimation of the real efficacy of cardiac pacing in preventing vasovagal reflex syncope. We assessed this hypothesis in the BIOSync CLS trial which showed that dual-chamber pacing with closed loop stimulation (CLS) remarkably reduced recurrences of syncope. Methods and resultsIn the study patients aged 40 years or older with ≥2 episodes of loss of consciousness in the last year and an asystolic response to Tilt-Table test were randomized to pacing ON (DDD-CLS mode) or pacing OFF (ODO mode). We utilized the available pacemaker diagnostic data in a total of 103 patients (52 pacing ON, 51 pacing OFF) to generate cumulative distribution charts for heart rate (HR) and percentage of pacing. At 12 months, we did not find evidence of suspected sinus or atrioventricular node dysfunction. Beats were similarly distributed between groups (p = 0.96), with an average HR of 76 ± 8 bpm (pacing ON) versus 77 ± 7 bpm (pacing OFF). In the active group, the median percentage of atrial and ventricular pacing was 47% and 0%, respectively. Intolerance to high pacing rates was reported in only one patient (1.6%) and was easily resolved by reprogramming the maximum CLS pacing rate. ConclusionsWe did not find evidence of suspected sinus or atrioventricular node dysfunction in the BIOSync CLS patients. The benefit of pacing should be ascribed to pacing prevention of pure vasovagal episodes. CLS algorithm modulated pacing rates over a wide frequency range, consistently competing with sinus node.

The evolving picture of SARS-CoV-2 and COVID-19 in children: critical knowledge gaps.

<h3>Background</h3> The closed-loop stimulation (CLS) pacemaker algorithm is a system that permanently monitors the contractile state of the myocardium and converts the intrinsic information into rate regulation. The role that the CLS algorithm plays in the prevention of syncope recurrences still remains unclear. The aim of our prospective, randomised, single-blind, crossover study was to evaluate the effect of dual-chamber CLS in the prevention of syncope recurrence in patients with refractory vasovagal syncope (VVS) and a cardioinhibitory response to head-up tilt test (HUT) during a 36 months follow-up. <h3>Method sand results</h3> We studied 50 patients (mean age 53±5.1; 33 male) with the indication for permanent dual-chamber cardiac pacing for HUT-induced vasovagal cardioinhibitory syncope. They were randomised after 1 month of stabilisation period to CLS algorithm features programmed OFF or ON for 18 months each, using a crossover design. The number of syncopal and presyncopal episodes during active treatment was lower than those registered during no treatment (n syncopal episodes: 2 vs 15; p=0.007; n presincopal episodes: 5 vs 30; p = 0.004). Lead parameters remained stable over time, and there were no lead-related complications. <h3>Conclusions</h3> Based on these 36 months follow-up data, it is concluded that dual-chamber CLS is an effective algorithm for preventing syncope recurrences in healthy patients with tilt-induced vasovagal cardioinhibitory syncope.

Role of implantable loop recorders in patients with postural orthostatic tachycardia syndrome.

We previously reported on a subgroup of postural orthostatic tachycardia syndrome (POTS) patients who may also have features of neurocardiogenic syncope as well. In this subgroup of patients, we found syncope and presyncope were predominant clinical features. To understand the mechanism of syncope in this subgroup, we identified 39 patients who underwent loop recorder insertion. We reviewed charts of 450 patients who had POTS and syncope seen at the University of Toledo Medical Center from 2003 to 2017. Thirty-nine patients had at least four episodes of syncope in the last 6 months and were included for this study. All of these patients had a prior evaluation with a Holter and an event monitor which were inconclusive. Thirty-nine patients, 33 (85%) women, aged 20-46 years, were included in this study. All patients demonstrated prolonged asystole(>6 seconds) or severe bradycardia (heart rate<30beats/min) during their syncope on implantable loop recorder (IRL). Fifteen patients demonstrated an asystole of>10 seconds and also had prolonged and convulsive syncope. All patients had abrupt syncope without any warning sign. All patients underwent dual-chamber pacemaker implantation using a closed loop stimulation algorithm. Syncope were completely eliminated in all patients following pacemaker implantation; however, they continued to have orthostatic tachycardia. POTS patients with unusually frequent syncope should be considered for ILR implantation if other monitoring modalities like 48-hour Holter monitor or event recorder are inconclusive. ILR may identify a subgroup of POTS patients who may benefit from pacemaker implantations.

Pacing for Vasovagal Syncope.

Vasovagal syncope (VVS) is due to a common autonomic reflex involving the cardiovascular system. It is associated with bradycardia (cardioinhibitory response) and/or hypotension (vasodepressor response), likely mediated by parasympathetic activation and sympathetic inhibition. While generally a situational, isolated and/or self-limited event, for some, VVS is recurrent, unpredictable and debilitating. Conservative, non-pharmacological management may help, but no specific medical therapy has been proven widely effective. Permanent pacing may have specific benefit, but its value has been debated. The temporal causative association of bradycardia with syncope in those with VVS may help identify which patient could benefit from pacing but the timing and type of pacing in lieu of blood pressure changes may be critical. The mode, rate, pacing algorithm and time to initiate dual-chamber pacing preferentially with respect to the vasovagal reflex may be important to prevent or ameliorate the faint but completely convincing data are not yet available. Based on available data, DDD pacing with the closed loop stimulation algorithm appears a viable, if not the best, alternative presently to prevent recurrent VVS episodes. While several knowledge gaps remain, permanent pacing appears to have a role in managing select patients with VVS.

Effects of closed-loop stimulation vs. DDD pacing on haemodynamic variations and occurrence of syncope induced by head-up tilt test in older patients with refractory cardioinhibitory vasovagal syncope: the Tilt test-Induced REsponse in Closed-loop Stimulation multicentre, prospective, single blind, randomized study.

Closed-loop stimulation (CLS) seemed promising in preventing the recurrence of vasovagal syncope (VVS) in patients with a cardioinhibitory response to head-up tilt test (HUTT) compared with conventional pacing. We hypothesized that the better results of this algorithm are due to its quick reaction in high-rate pacing delivered in the early phase of vasovagal reflex, which increase the cardiac output and the blood pressure preventing loss of consciousness. This prospective, randomized, single-blind, multicentre study was designed as an intra-patient comparison and enrolled 30 patients (age 62.2 ± 13.5 years, males 60.0%) with cardioinhibitory VVS, carrying a dual-chamber pacemaker incorporating CLS algorithm. Two HUTTs were performed one week apart: one during DDD-CLS 60-130/min pacing and the other during DDD 60/min pacing; patients were randomly and blindly assigned to two groups: in one the first HUTT was performed in DDD-CLS (n = 15), in the other in DDD (n = 15). Occurrence of syncope and haemodynamic variations induced by HUTT was recorded during the tests. Compared with DDD, DDD-CLS significantly reduced the occurrence of syncope induced by HUTT (30.0% vs. 76.7%; P < 0.001). In the patients who had syncope in both DDD and DDD-CLS mode, DDD-CLS significantly delayed the onset of syncope during HUTT (from 20.8 ± 3.9 to 24.8 ± 0.9 min; P = 0.032). The maximum fall in systolic blood pressure recorded during HUTT was significantly lower in DDD-CLS compared with DDD (43.2 ± 30.3 vs. 65.1 ± 25.8 mmHg; P = 0.004). In patients with cardioinhibitory VVS, CLS reduces the occurrence of syncope induced by HUTT, compared with DDD pacing. When CLS is not able to abort the vasovagal reflex, it seems to delay the onset of syncope.

The effect of dual-chamber closed-loop stimulation on syncope recurrence in healthy patients with tilt-induced vasovagal cardioinhibitory syncope: a prospective, randomised, single-blind, crossover study

BackgroundThe closed-loop stimulation (CLS) pacemaker algorithm is a system that permanently monitors the contractile state of the myocardium and converts the intrinsic information into rate regulation. The role that the...

Closed Loop Stimulation is Effective in Improving Heart Rate and Blood Pressure Response to Mental Stress: Report of a Single‐Chamber Pacemaker Study in Patients with Chronotropic Incompetent Atrial Fibrillation

Closed-loop stimulation (CLS) is a form of rate-adaptive pacing capable of providing an effective pacing rate profile not only during physical exercise but also during mental stress. To test its effectiveness, CLS and accelerometer sensor (AS) rate response were compared intraindividually during a mental stress test (MST). Thirty-six patients (mean age 78.9 ± 6.4 years) implanted with a pacemaker with the CLS algorithm (Cylos, Biotronik, Berlin, Germany) underwent MSTs in different pacing configurations: nonrate-adaptive mode (VVI), AS mode (VVIR), and CLS mode, respectively. A modified Stroop test was used in order to induce mental stress. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure, and pacing percentage burden were collected for 5 minutes before, during, and 5 minutes after the test. Mean peak-HR during MST was significantly higher in CLS configuration than in VVIR and VVI modes (92.8 ± 12.6 vs 78.9 ± 6.5 vs 77.8 ± 7.5; P ≤ 0.001). The average HR increase during MST was also higher in CLS configuration than in VVIR and VVI modes (22.7 ± 16.7 vs 8.2 ± 8.6 vs 6.6 ± 6.3; P ≤ 0.001). The percentage of pacing beats during MST was higher in CLS configuration than with the other two algorithms (48.4 ± 17.9 vs 27.4 ± 17.5 vs 25.8 ± 17.6; P ≤ 0.001). The average peak-SBP was significantly higher during MST in CLS mode than in VVIR and VVI configurations (172.6 ± 15.5 vs 156.7 ± 12.2 vs 145.5 ± 13.7; P ≤ 0.001). The mean SBP increase showed a similar behavior (51.8 ± 24.7 vs 18.4 ± 13.7 vs 16.4 ± 10.3; P ≤ 0.001). CLS algorithm in a single-chamber device is more effective than AS in detecting an hemodynamic demand due to an emotional stress and supplying a proper HR increase. These results are even more surprising compared to previous data in dual-chamber pacemakers, because they imply that CLS algorithm can provide an appropriate rate-modulation in patients with AF and chronotropic incompetence.

Heart Rate Changes during Acute Mental Stress with Closed Loop Stimulation: Report on Two Single‐Blinded, Pacemaker Studies

Mental stress affects hemodynamic properties of the heart in patients indicated for a pacemaker, therefore highlighting the need for a rate-adaptive sensor that responds to mental loads. One such sensor utilizes Closed Loop Stimulation (CLS), which translates right ventricular contractility into patient specific pacing rates. Clinical studies utilizing CLS [Emotional Response (ER) and Emotional Response 2 (ER2) studies] have been performed to confirm CLS provides appropriate heart rate response to acute mental stress. The objective of these studies was to compare heart rates during a mental stress test, with the patient's pacemaker programmed to a CLS pacing mode and an accelerometer pacing mode. Patients were implanted with a BIOTRONIK Protos/CLS pacemaker (Berlin, Germany) and subjected to mental stress testing. The stress test consisted of a relaxation period followed by a color-word test and an arithmetic challenge test. The ER2 study utilized a randomized study design, in which pacing mode testing order was randomized. Analysis included patients who exhibited at least 80% sensor-driven heart rates during stress testing. Results for both studies demonstrated that CLS provided a statistically significant higher increase in heart rate during testing compared with an accelerometer pacing mode. The studies also showed that CLS provided a statistically significant higher peak heart rate during testing compared with an accelerometer pacing mode. The ER and ER2 studies demonstrate that the CLS algorithm responds with an appropriate heart rate response to acute mental stress in patients exhibiting a high percentage of sensor-driven pacing.

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

To determine whether dual-chamber rate-adaptive Closed Loop Stimulation (CLS) could prevent recurrence of Vasovagal Syncope (VVS). 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. 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. 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. The study demonstrates the effectiveness of CLS pacing in preventing cardioinhibitory VVS. A possible placebo effect of pacemaker implantation occurred in 22% of patients.

ON THE CANCER-PRODUCING FACTOR IN TAR

Background The closed-loop stimulation (CLS) pacemaker algorithm is a system that permanently monitors the contractile state of the myocardium and converts the intrinsic information into rate regulation. The role that the CLS algorithm plays in the prevention of syncope recurrences still remains unclear. The aim of our prospective, randomised, single-blind, crossover study was to evaluate the effect of dual-chamber CLS in the prevention of syncope recurrence in patients with refractory vasovagal syncope (VVS) and a cardioinhibitory response to head-up tilt test (HUT) during a 36 months follow-up. Method sand results We studied 50 patients (mean age 53±5.1; 33 male) with the indication for permanent dual-chamber cardiac pacing for HUT-induced vasovagal cardioinhibitory syncope. They were randomised after 1 month of stabilisation period to CLS algorithm features programmed OFF or ON for 18 months each, using a crossover design. The number of syncopal and presyncopal episodes during active treatment was lower than those registered during no treatment (n syncopal episodes: 2 vs 15; p=0.007; n presincopal episodes: 5 vs 30; p = 0.004). Lead parameters remained stable over time, and there were no lead-related complications. Conclusions Based on these 36 months follow-up data, it is concluded that dual-chamber CLS is an effective algorithm for preventing syncope recurrences in healthy patients with tilt-induced vasovagal cardioinhibitory syncope.