New-generation miniaturized insertable cardiac monitor with a long sensing vector: Insertion procedure, sensing performance, and home monitoring transmission success in a real-world population.

Background: Insertable cardiac monitors (ICMs) require an invasive procedure and are used for purely diagnostic purposes. Therefore, simplicity of the insertion procedure, low complication rate, long-term patient acceptance, sensing quality, and reliable remote monitoring are of great importance. Objective: To evaluate a novel ICM (BIOMONITOR III) regarding all these aspects. Methods: BIOMONITOR III has a miniaturized profile, long sensing vector (≈70 mm), a fast insertion tool for pocket formation and ICM placement in 1 step, and daily automatic Home Monitoring (HM) function. We evaluated the insertion procedure, complication rate, patient acceptance, sensing quality, and HM performance in 653 patients with BIOMONITOR III inserted for any ICM indication within 2 ongoing studies involving 51 sites in 11 countries. Results: The median time from skin incision to wound closure was 4.0 minutes (interquartile range, 2.3-6.2 minutes). Median follow-up period was 274 days (interquartile range, 175-342 days). Serious adverse device-related events occurred in 6 patients (0.9%). No deep infections were reported in 334 patients without antibiotic prophylaxis. The wearing comfort was good or excellent in ≈95%. The mean R-wave amplitude (0.73 mV) and HM transmission rate (≈94% of days) were stable over 1.5 years. R-wave amplitudes were larger (mean 0.80 vs 0.62 mV, P < .001) and noise burden was lower (median 3.7 vs 14.5 minutes/day, P < .001) for ICM insertions parallel to the heart's long axis (54.2%) vs parasternal (41.3%). A gross visibility of P waves was 95.1%. Conclusion: The study demonstrated fast insertion times, low complication rate, high patient acceptance, and favorable long-term sensing and HM performance of the ICM.

Impact of lockdown during COVID-19 pandemic on physical activity and arrhythmia burden in heart failure patients.

BACKGROUND: Restricted outdoor activity during COVID-19 related lockdown may accelerate heart failure (HF) progression and thereby increase cardiac arrhythmias. We analyzed the impact of March/April 2020 lockdown on physical activity and arrhythmia burden in HF patients treated with cardiac resynchronization therapy (CRT) devices with daily, automatic remote monitoring (RM) function. METHODS: The study cohort included 405 HF patients enrolled in Observation of Clinical Routine Care for Heart Failure Patients Implanted with BIOTRONIK CRT Devices (BIO|STREAM.HF) registry in 16 countries, who had left ventricular ejection fraction (LVEF) ≤40% (mean 28.2 ± 6.6%) and NYHA class II/III/IV (47.9%/49.6%/2.5%) before CRT pacemaker/defibrillator implantation. The analyzed RM data comprised physical activity detected by accelerometer, mean heart rate and nocturnal rate, PP variability, percentage of biventricular pacing, atrial high rate episode (AHRE) burden, ventricular extrasystoles and tachyarrhythmias, defibrillator shocks, and number of implant interrogations (i.e., follow-ups). Intraindividual differences in RM parameters before (4-week period) versus during (4-week period) lockdown were tested for statistical significance and independent predictors were identified. RESULTS: There was a significant relative change in activity (mean -6.5%, p < .001), AHRE burden (+17%, p = .013), and follow-up rate (-75%, p < .001) during lockdown, with no significant changes in other RM parameters. Activity decreased by ≥8 min/day in 46.5% of patients; predictors were higher LVEF, lower NYHA class, no defibrillator indication, and more activity before lockdown. AHRE burden increased by ≥17 min/day in 4.7% of patients; predictors were history of atrial fibrillation, higher LVEF, higher body mass index, and activity decrease during lockdown. CONCLUSION: Unfavorable changes in physical activity, AHRE burden, and follow-up rate were observed during lockdown, but not in ventricular arrhythmia.

Preventive or Deferred Ablation of Ventricular Tachycardia in Patients With Ischemic Cardiomyopathy and Implantable Defibrillator (BERLIN VT): A Multicenter Randomized Trial.

BACKGROUND: Catheter ablation for ventricular tachycardia (VT) reduces the recurrence of VT in patients with implantable cardioverter-defibrillators (ICDs). The appropriate timing of VT ablation and its effects on mortality and heart failure progression remain a matter of debate. In patients with life-threatening arrhythmias necessitating ICD implantation, we compared outcomes of preventive VT ablation (undertaken before ICD implantation to prevent ICD shocks for VT) and deferred ablation after 3 ICD shocks for VT. METHODS: The BERLIN VT study (Preventive Ablation of Ventricular Tachycardia in Patients With Myocardial Infarction) was a prospective, open, parallel, randomized trial performed at 26 centers. Patients with stable ischemic cardiomyopathy, a left ventricular ejection fraction between 30% and 50%, and documented VT were randomly assigned 1:1 to a preventive or deferred ablation strategy. The primary outcome was a composite of all-cause death and unplanned hospitalization for either symptomatic ventricular arrhythmia or worsening heart failure. Secondary outcomes included sustained ventricular tachyarrhythmia and appropriate ICD therapy. We hypothesized that preventive ablation strategy would be superior to deferred ablation strategy in the intention-to-treat population. RESULTS: During a mean follow-up of 396±284 days, the primary end point occurred in 25 (32.9%) of 76 patients in the preventive ablation group and 23 (27.7%) of 83 patients in the deferred ablation group (hazard ratio, 1.09 [95% CI, 0.62-1.92]; P=0.77). On the basis of prespecified criteria for interim analyses, the study was terminated early for futility. In the preventive versus deferred ablation group, 6 versus 2 patients died (7.9% versus 2.4%; P=0.18), 8 versus 2 patients were admitted for worsening heart failure (10.4% versus 2.3%; P=0.062), and 15 versus 21 patients were hospitalized for symptomatic ventricular arrhythmia (19.5% versus 25.3%; P=0.27). Among secondary outcomes, the proportions of patients with sustained ventricular tachyarrhythmia (39.7% versus 48.2%; P=0.050) and appropriate ICD therapy (34.2% versus 47.0%; P=0.020) were numerically reduced in the preventive ablation group. CONCLUSIONS: Preventive VT ablation before ICD implantation did not reduce mortality or hospitalization for arrhythmia or worsening heart failure during 1 year of follow-up compared with the deferred ablation strategy. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02501005.

Rationale and design of BERLIN VT study: a multicenter randomised trial comparing preventive versus deferred ablation of ventricular tachycardia.

INTRODUCTION: Catheter ablation (CA) has shown to effectively reduce the burden of ventricular tachycardia in patients with implanted cardioverter-defibrillator (ICD). However, in patients with ICD implantation for secondary prevention of ventricular tachycardia (VT), the appropriate time point of CA and its effect on mortality and heart failure progression remains a matter of debate. METHODS AND ANALYSIS: We present the design of the ongoing preventive aB lation of vE ntriculartachyca R dia in patients with myocardia LIN farction (BERLIN VT) study that aims to prospectively enrol 208 patients with a stable ischaemic cardiomyopathy, a left ventricular ejection fraction of 30% to 50% and documented ventricular tachycardia. Patients will be 1:1 randomised to undergo CA at the time of ICD implantation or CA after the third appropriate ICD shock for ventricular tachycardia. ICD implantation will be performed in all patients. The primary endpoint is defined as the time to first event comprising all-cause mortality and unplanned hospital admission for congestive heart failure or for symptomatic VT/ventricular fibrillation. The patients will be followed until study termination according to the event driven design. Completion of enrolment is expected for mid of 2019. ETHICS AND DISSEMINATION: The study had been approved by the "Ethik-kommission der Landesärztekammer Hamburg" as well as the local institutional review boards for each of the participation sites. The results of the trial will be published in peer-reviewed journals TRIAL REGISTRATION NUMBER: NCT02501005.

Silent cerebral lesions and cognitive function after pulmonary vein isolation with an irrigated gold-tip catheter: REDUCE-TE Pilot study.

INTRODUCTION: Stroke is one of the most feared complications during catheter ablation of atrial fibrillation (AF). While symptomatic thromboembolic events are rare, magnetic resonance imaging (MRI) may identify asymptomatic (ie, silent) cerebral lesions (SCLs) following pulmonary vein isolation (PVI) procedures. METHODS AND RESULTS: The REDUCE-TE Pilot was a prospective multicenter, single-arm observational study investigating the incidence of SCL in patients with symptomatic paroxysmal AF undergoing PVI with a novel gold-tip, externally irrigated ablation catheter. After ablation, cerebral diffusion-weighted MRI and a postablation follow-up were performed at 1 to 3 days after the ablation procedure. A neurocognitive test was done before and after ablation. The primary study endpoint was the occurrence of one or more new SCLs. Secondary study endpoints included neurocognitive status, procedural success rate, and periprocedural complications including symptomatic thromboembolic events. A total of 104 patients were enrolled (69% male, mean age: 61.5 ± 9.7 years, mean CHA2 DS 2 -VASc score: 1.7 ± 1.2). Postprocedural MRI examination was performed in 97 patients, and in nine of them (9.3%; 95% CI: 4.3-16.9%) a total of 11 SCLs were detected. Univariate analyses did not reveal any significant predictor for new SCLs. Nonsignificant trends were observed for low activated clotting time during ablation and for international normalized ratio value outside the range of 2 to 3 at ablation. There was no evidence of significant deterioration of neurocognitive function after PVI. In four patients, a pericardial tamponade was noted but all patients fully recovered during follow-up. CONCLUSIONS: Ablation of AF using a novel gold-tip, externally irrigated ablation catheter, resulted in SCLs in approximately one out of 10 patients without a measurable effect on neurocognitive function.

A comparison of chronaxies for ventricular fibrillation induction, defibrillation, and cardiac stimulation: unexpected findings and their implications.

INTRODUCTION: A low-energy (

Intrathoracic far-field electrocardiogram allows continuous monitoring of ischemia after total coronary occlusion.

INTRODUCTION: Recording of intrathoracic far-field electrocardiograms (FF-ECG) via can and electrodes of implantable cardioverter-defibrillators (ICD) is a promising method for continuous monitoring of myocardial ischemia. We assessed the hypothesis that experimentally induced ischemia provokes segment changes in the FF-ECG that can be detected by the ICD. METHODS AND RESULTS: In seven pigs with an ICD implanted in the left pectoral region and electrodes placed in the right ventricle and the superior vena cava, we occluded all major coronary arteries in proximal and distal locations for 180 s each. Surface and FF-ECGs were compared for presence and time course of ischemic ST segment changes. Reliable detection of ischemia by ST segment analysis was possible in all (38/38) experiments. Maximum deviation from baseline was larger in FF-ECG (1.21 mV) than surface ECG leads (0.23 mV, P < 0.01) for all occlusion sites. Ischemia could be detected earlier (P < 0.05) in the FF-ECG, with a sensitivity of 100%, 93%, and 100% after occlusions in the left anterior descending, left circumflex, and right coronary arteries, respectively. CONCLUSION: Intrathoracic FF-ECG allows reliable and reproducible detection of experimentally induced ischemia originating from all major coronary arteries and therefore could be an interesting tool for clinicians in monitoring high risk patients.

Nitric oxide/cyclic guanosine monophosphate signaling in the central complex of the grasshopper brain inhibits singing behavior.

Grasshopper sound production, in the context of mate finding, courtship, and rivalry, is controlled by the central body complex in the protocerebrum. Stimulation of muscarinic acetylcholine receptors in the central complex has been demonstrated to stimulate specific singing in various grasshoppers including the species Chorthippus biguttulus. Sound production elicited by stimulation of muscarinic acetylcholine receptors in the central complex is inhibited by co-applications of various drugs activating the nitric oxide/cyclic guanosine monophosphate (cGMP) signaling pathway. The nitric oxide-donor sodium nitroprusside caused a reversible suppression of muscarine-stimulated sound production that could be blocked by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxaline-1-one (ODQ), which prevents the formation of cGMP by specifically inhibiting soluble guanylyl cyclase. Furthermore, injections of both the membrane-permeable cGMP analog 8-Br-cGMP and the specific inhibitor of the cGMP-degrading phosphodiesterase Zaprinast reversibly inhibited singing. To identify putative sources of nitric oxide, brains of Ch. biguttulus were subjected to both nitric oxide synthase immunocytochemistry and NADPH-diaphorase staining. Among other areas known to express nitric oxide synthase, both procedures consistently labeled peripheral layers in the upper division of the central body complex, suggesting that neurons supplying this neuropil contain nitric oxide synthase and may generate nitric oxide upon activation. Exposure of dissected brains to nitric oxide and 3-(5'hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) induced cGMP-associated immunoreactivity in both the upper and lower division. Therefore, both the morphological and pharmacological data presented in this study strongly suggest a contribution of the nitric oxide/cGMP signaling pathway to the central control of grasshopper sound production.