Fully digital data processing during cardiovascular implantable electronic device follow-up in a high-volume tertiary center

Background Increasing numbers of patients with cardiovascular implantable electronic devices (CIEDs) and limited follow-up capacities highlight unmet challenges in clinical electrophysiology. Integrated software (MediConnect®) enabling fully digital processing of device interrogation data has been commercially developed to facilitate follow-up visits. We sought to assess feasibility of fully digital data processing (FDDP) during ambulatory device follow-up in a high-volume tertiary hospital to provide guidance for future users of FDDP software. Methods A total of 391 patients (mean age, 70 years) presenting to the outpatient department for routine device follow-up were analyzed (pacemaker, 44%; implantable cardioverter defibrillator, 39%; cardiac resynchronization therapy device, 16%). Results Quality of data transfer and follow-up duration were compared between digital (n = 265) and manual processing of device data (n = 126). Digital data import was successful, complete and correct in 82% of cases when early software versions were used. When using the most recent software version the rate of successful digital data import increased to 100%. Software-based import of interrogation data was complete and without failure in 97% of cases. The mean duration of a follow-up visit did not differ between the two groups (digital 18.7 min vs. manual data transfer 18.2 min). Conclusions FDDP software was successfully implemented into the ambulatory follow-up of patients with implanted pacemakers and defibrillators. Digital data import into electronic patient management software was feasible and supported the physician’s workflow. The total duration of follow-up visits comprising technical device interrogation and clinical actions was not affected in the present tertiary center outpatient cohort

Postcardiac injury syndrome after cardiac implantable electronic device implantation

Background!#!Postcardiac injury syndrome (PCIS) is an inflammatory complication that derives from injury to the epicardium, myocardium, or endocardium. It occurs after trauma, myocardial infarction, percutaneous coronary intervention, cardiac surgery, intracardiac ablation, and implantation of cardiac implantable electronic device (CIED). In this study we assessed the incidence of PCIS after CIED implantation and its possible risk factors.!##!Material and methods!#!All patients who received CIED implantation at Heidelberg University Hospital between 2000 and 2014 were evaluated (n = 4989 patients). Clinical data including age, sex, underlying cardiac disease, type of implanted CIED, location of electrode implantation, clinical symptoms, time of symptom onset of PCIS, therapy, and outcome were extracted and analyzed.!##!Results!#!We identified 19 cases of PCIS in 4989 patients, yielding an incidence of 0.38%. The age of patients with PCIS ranged from 39 to 86 years. Dilated cardiomyopathy (DCM) as underlying cardiac disease and right atrial (RA) lead implantation had a significant association with occurrence of PCIS (p = 0.045 in DCM and p < 0.001 in RA lead implantation). Dyspnea, chest pain, dry cough, and fever were the most frequently reported symptoms in patients with PCIS. Pericardial and pleura effusion as well as elevated C‑reactive protein (CRP), increased erythrocyte sedimentation rate (ESR), and leukocytosis were the most common findings.!##!Conclusion!#!To the best of our knowledge, this is the largest cohort evaluating the incidence of PCIS after CIED implantation. The data show that PCIS is a rare complication after CIED implantation and occurs more frequently in patients with DCM and those with RA lead implantation. Although rare and mostly benign, PCIS can lead to potentially lethal complications and physicians must be aware of its symptoms

Cryoballoon pulmonary vein isolation-mediated rise of sinus rate in patients with paroxysmal atrial fibrillation

Background!#!Modulation of the cardiac autonomic nervous system by pulmonary vein isolation (PVI) influences the sinoatrial nodal rate. Little is known about the causes, maintenance and prognostic value of this phenomenon. We set out to explore the effects of cryoballoon PVI (cryo-PVI) on sinus rate and its significance for clinical outcome.!##!Methods and results!#!We evaluated 110 patients with paroxysmal atrial fibrillation (AF), who underwent PVI using a second-generation 28 mm cryoballoon by pre-, peri- and postprocedural heart rate acquisition and analysis of clinical outcome. Ninety-one patients could be included in postinterventional follow-up, indicating that cryo-PVI resulted in a significant rise of sinus rate by 16.5% (+ 9.8 ± 0.9 beats/min, p < 0.001) 1 day post procedure compared to preprocedural acquisition. This effect was more pronounced in patients with initial sinus bradycardia (< 60 beats/min.) compared to patients with faster heart rate. Increase of rate was primarily driven by ablation of the right superior pulmonary vein and for a subset of patients, in whom this could be assessed, persisted ≥ 1 year after the procedure. AF recurrence was neither predicted by the magnitude of the initial rate, nor by the extent of rate change, but postprocedural sinus bradycardia was associated with higher recurrence of AF in the year post PVI.!##!Conclusions!#!Cryo-PVI causes a significant rise of sinus rate that is more pronounced in subjects with previous sinus bradycardia. Patient follow-up indicates persistence of this effect and suggests an increased risk of AF recurrence in patients with postprocedural bradycardia

Inhibition of Cardiac Kir Current (IK1) by Protein Kinase C Critically Depends on PKCβ and Kir2.2.

Cardiac inwardly rectifying Kir current (IK1) mediates terminal repolarisation and is critical for the stabilization of the diastolic membrane potential. Its predominant molecular basis in mammalian ventricle is heterotetrameric assembly of Kir2.1 and Kir2.2 channel subunits. It has been shown that PKC inhibition of IK1 promotes focal ventricular ectopy. However, the underlying molecular mechanism has not been fully elucidated to date.In the Xenopus oocyte expression system, we observed a pronounced PKC-induced inhibition of Kir2.2 but not Kir2.1 currents. The PKC regulation of Kir2.2 could be reproduced by an activator of conventional PKC isoforms and antagonized by pharmacological inhibition of PKCβ. In isolated ventricular cardiomyocytes (rat, mouse), pharmacological activation of conventional PKC isoforms induced a pronounced inhibition of IK1. The PKC effect in rat ventricular cardiomyocytes was markedly attenuated following co-application of a small molecule inhibitor of PKCβ. Underlining the critical role of PKCβ, the PKC-induced inhibition of IK1 was absent in homozygous PKCβ knockout-mice. After heterologous expression of Kir2.1-Kir2.2 concatemers in Xenopus oocytes, heteromeric Kir2.1/Kir2.2 currents were also inhibited following activation of PKC.We conclude that inhibition of cardiac IK1 by PKC critically depends on the PKCβ isoform and Kir2.2 subunits. This regulation represents a potential novel target for the antiarrhythmic therapy of focal ventricular arrhythmias

The functional PKC consensus sites S64 and T353 are lacking in Kir2.1 channels.

<p>(A) Alignment of the amino acid sequence of Kir2.1 and Kir2.2. Interestingly, in Kir2.1 channels, the PKC consensus sites S64 and T353 which have been shown to be functionally relevant are lacking. (B) Schematic picture of a Kir2.2 channel subunit with the suggested locations of the PKC phosphorylation sites.</p

Heteromeric Kir2.1/Kir2.2 channels are inhibited by protein kinase C.

<p>Heteromeric Kir2.1/Kir2.2 channels were expressed as concatemers according to Preisig-Müller <i>et al</i>. (2002) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156181#pone.0156181.ref003" target="_blank">3</a>]. (A-C) A representative experiment and corresponding IV-curves. (D) Summary data of relative currents upon activation of PKC by thymeleatoxin (TMTX; 100 nmol/l) compared to measurements of Kir2.1/Kir2.2 heteromeric channels under control conditions. * indicates statistical significance.</p

Effects of different protein kinase C activators on Kir2.1 and Kir2.2 currents indicate a pronounced inhibitory regulation of Kir2.2 by conventional PKC isoforms with a predominant role of PKCβ.

<p>Representative recordings of Kir2.1 currents before and after superfusion with PMA (1 μmol/l) for 30 minutes (A-B). Corresponding IV-curves (C). Typical recording of Kir2.2 currents under control conditions (D), after superfusion with PMA (1 μmol/l) for 30 minutes (E) and corresponding IV-curves (F). (G) Summary data of the experiments with different PKC activators is shown for Kir2.1. (H) Summary data of the experiments with different PKC activators and co-applied PKCβ inhibitor is shown for Kir2.2. * indicates statistically significant difference to control experiments. These data point to a pronounced inhibitory regulation of Kir2.2 currents by PKC that predominantly depends on conventional PKC isoforms with a crucial role of PKCβ. In contrast, the moderate inhibition of Kir2.1 channels by PMA is likely to be independent of PKC signalling pathways. Protocol: holding potential -80 mV; test pulses from -120 mV to +40 mV in 10 mV-increments (400 ms).</p

Application of a small-molecule PKCβ inhibitor abolishes the inhibitory effect of thymeleatoxin on I_K1 in rat ventricular cardiomyocytes.

<p>Whole-cell patch-clamp experiments with isolated rat ventricular cardiomyocytes were performed using thymeleatoxin (TMTX 100 nmol/l) as PKC activator. A typical experiment is displayed in panels (A–C). Panel (D) shows the time course of effect. BaCl₂, applied at the end of the observation period induced only a slight further current inhibition, i.e. about 84% of barium-sensitive currents had been inhibited by TMTX before. Currents remained nearly unaltered when the PKCβ inhibitor (3 μmol/l) was co-applied with TMTX (E). Subsequent application of BaCl₂ to the bath at the end of the observation period lead to a fast block of inward currents. (F) Summary data of all experiments in rat ventricular cardiomyocytes. Protocol: holding potential -80 mV; test pulses from -130 mV to -80 mV in 10 mV-increments (200 ms). * indicates statistical significance.</p