High-Fidelity 3D Stray Magnetic Field Mapping of Smartphones to Address Safety Considerations with Active Implantable Electronic Medical Devices.

Case reports indicate that magnets in smartphones could be a source of electromagnetic interference (EMI) for active implantable medical devices (AIMD), which could lead to device malfunction, compromising patient safety. Recognizing this challenge, we implemented a high-fidelity 3D magnetic field mapping (spatial resolution 1 mm) setup using a three-axis Hall probe and teslameter, controlled by a robot (COSI Measure). With this setup, we examined the stray magnetic field of an iPhone 13 Pro, iPhone 12, and MagSafe charger to identify sources of magnetic fields for the accurate risk assessment of potential interferences with AIMDs. Our measurements revealed that the stray fields of the annular array of magnets, the wide-angle camera, and the speaker of the smartphones exceeded the 1 mT limit defined by ISO 14117:2019. Our data-driven safety recommendation is that an iPhone 13 Pro should be kept at least 25 mm away from an AIMD to protect it from unwanted EMI interactions. Our study addresses safety concerns due to potential device-device interactions between smartphones and AIMDs and will help to define data-driven safety guidelines. We encourage vendors of electronic consumer products (ECP) to provide information on the magnetic fields of their products and advocate for the inclusion of smartphones in the risk assessment of EMI with AIMDs.

Acute left ventricular insufficiency in a Burkitt Lymphoma patient with myocardial involvement and extensive local tumor cell lysis: a case report.

BACKGROUND: Burkitt lymphoma (BL) is a rare disease with the sporadic variant accounting for less than 1% of adult non-Hodgkin lymphomas. BL usually presents with an abdominal bulk, but extranodal disease affecting the bone marrow and central nervous system is common. Cardiac manifestations, however, are exceedingly rare, with less than 30 cases reported in the literature. CASE PRESENTATION: We report on a 54-year-old male patient with a six week-long history of paranasal sinus swelling, fatigue and dyspnea on exertion. Stage IV sporadic BL with extensive lymphonodal and cardiovascular involvement was diagnosed. Manifestations included supra- and infradiaphragmatic lymphadenopathy as well as infiltration of the aortic root, the pericardium, the right atrium and the right ventricle. EBV-reactivation was detected, which is uncommon in the sporadic subtype. After initial full-dose chemotherapy with very good BL control, the patient developed acute, but fully reversible cardiac insufficiency. Myocardial lymphoma involvement receded completely during the following two therapy cycles, while cardiac function periodically deteriorated shortly after chemotherapy administration and quickly recovered thereafter. Interestingly, the decline in cardiac function lessened with decreasing myocardial lymphoma manifestation. Once the cardiovascular BL infiltration was resolved, cardiac function remained stable throughout further treatment. Following seven cycles of chemotherapy and mediastinal radiation, the patient is now in continued complete remission. CONCLUSIONS: Although rare, cardiac involvement in BL can quickly become life-threatening due to rapid lymphoma doubling time and should therefore be considered at initial diagnosis. This case suggests an association between myocardial infiltration, chemotherapy associated tumor cell lysis and transient deterioration of cardiac function until the damage caused by the underlying lymphoma could be restored. While additional studies are needed to further elucidate the mechanisms of acute cardiac insufficiency due to lymphoma lysis in the infiltrated structures, prompt BL control and full recovery of the patient supports courageous treatment start despite extensive cardiovascular involvement.

P-wave detection performance of the BioMonitor III, Confirm Rx and Reveal Linq implantable loop recorders.

INTRODUCTION: Rhythm interpretation of EGMs recorded by implantable loop recorders (ILRs) is facilitated in cases when p-waves are visible. The three most commonly used ILRs (BioMonitor III, Confirm RX and Reveal Linq) vary in size, electrode placement and filter algorithms. Therefore, p-wave visibility and amplitude on EGM may vary according to the implanted device. MATERIAL AND METHODS: Consecutive patients were included after ILR implantation. P-wave visibility and amplitude were evaluated in sinus rhythm on 30-s EGMs with standard resolution (25 mm/mV for Biotronik and St. Jude, 30 mm/mV for Medtronic) and after maximum magnification. Additionally, baseline characteristics and p-wave amplitude in lead II on the surface-ECG were documented. RESULTS: 148 patients with either BioMonitor III (n = 48), Confirm Rx (n = 51) or Reveal Linq (n = 49) ILRs were included. With standard resolution, p-waves were visible in 40 patients (83%) implanted with BioMonitor III, 36 patients (71%) with Confirm Rx and in 35 patients (71%) with Reveal Linq ILRs (p = 0.267). After maximum magnification, p-waves could not be identified in 6 patients with Confirm Rx ILR (12%) and 1 patient in both BioMonitor III and Reveal Linq ILR (2%; p = 0.051). The Biomonitor III showed higher p-wave amplitudes compared to the Confirm Rx (0.050 mV (0.040-0.070) vs. 0.030 mV (0.020-0.040); p < 0.001) and the Reveal Linq ILR (0.050 mV (0.040-0.070) vs. 0.030 mV (0.020-0.040); p < 0.001). CONCLUSION: P-wave amplitudes were higher in patients with Biomonitor III. This did not lead to higher p-wave visibility compared to the Confirm RX ILR or the Reveal Linq ILR.

Low-voltage shock impedance measurements: A false sense of security.

BACKGROUND: Implantable cardioverter defibrillators use low-voltage shock impedance measurements to monitor the lead integrity. However, previous case reports suggest that low-voltage shock impedance measurements may fail to detect insulation breaches that can cause life-threatening electrical short circuits. METHODS AND RESULTS: We report six cases of insulation breaches in transvenous defibrillation leads that were not obvious during standard interrogations and testing of the lead beforehand. In two cases, an electrical short circuit during commanded shock delivery for internal electrical cardioversion resulted in a total damage of the ICD generator. In one of these cases, commanded shock delivery induced ventricular fibrillation, which required external defibrillation. In two cases, a shock due to ventricular tachycardia was aborted as the shock impedance was less than 20 Ω. However, in both cases the tiny residual shock energy terminated the ventricular tachycardia. In contrast, in one case the residual energy of the aborted shock did not end ventricular fibrillation induced at defibrillator threshold testing. In one case, the ICD indicated an error code for a short circuit condition detected during an adequate shock delivery. CONCLUSIONS: This case series illustrates that low-voltage shock impedance measurements can fail to detect insulation breaches. These data suggest that in patients without a contraindication, traditional defibrillator threshold testing or high voltage synchronized shock at the time of device replacement should be considered.

Cardiac arrhythmias in patients with COVID-19: Lessons from 2300 telemetric monitoring days on the intensive care unit.

BACKGROUND: Patients with COVID-19 seem to be prone to the development of arrhythmias. The objective of this trial was to determine the characteristics, clinical significance and therapeutic consequences of these arrhythmias in COVID-19 patients requiring intensive care unit (ICU) treatment. METHODS AND RESULTS: A total of 113 consecutive patients (mean age 64.1 ± 14.3 years, 30 (26.5%) female) with positive PCR testing for SARS-CoV2 as well as radiographically confirmed pulmonary involvement admitted to the ICU from March to May 2020 were included and observed for a cumulative time of 2321 days. Fifty episodes of sustained atrial tachycardias, five episodes of sustained ventricular arrhythmias and thirty bradycardic events were documented. Sustained new onset atrial arrhythmias were associated with hemodynamic deterioration in 13 cases (35.1%). Patients with new onset atrial arrhythmias were older, showed higher levels of Hs-Troponin and NT-proBNP, and a more severe course of disease. The 5 ventricular arrhythmias (two ventricular tachycardias, two episodes of ventricular fibrillation, and one torsade de pointes tachycardia) were observed in 4 patients. All episodes could be terminated by immediate defibrillation/cardioversion. Five bradycardic events were associated with hemodynamic deterioration. Precipitating factors could be identified in 19 of 30 episodes (63.3%), no patient required cardiac pacing. Baseline characteristics were not significantly different between patients with or without bradycardic events. CONCLUSION: Relevant arrhythmias are common in severely ill ICU patients with COVID-19. They are associated with worse courses of disease and require specific treatment. This makes daily close monitoring of telemetric data mandatory in this patient group.

The force stability of tissue contact and lesion size index during radiofrequency ablation: An ex-vivo study.

INTRODUCTION: Radiofrequency (RF) ablation is a commonly used tool in the invasive electrophysiology laboratory to treat a variety of rhythm disorders. Reliable creation of transmural ablation lesions is crucial for long-term success. Lesion size index (LSI) is a multiparametric index that incorporates time, power, contact force (CF), and impedance data recorded during RF ablation in a weighted formula and has been shown to predict the extent of myocardial tissue lesions. Whether the force stability of contact influences lesion size in LSI-guided ablations is unknown. OBJECTIVES: The aim of this study was to analyze the influence of the force stability of contact on lesion size during LSI-guided ablations in an ex-vivo model. METHODS AND RESULTS: A total of 267 RF lesions (n = 6 hearts) were created on porcine myocardial slabs by using an open-tip irrigated ablation catheter with the following settings: 35 W with either intermittent (varied between 0 and up to 20 g), variable (10 to 20 g), or constant tissue contact (15 g) in a perpendicular or parallel fashion (applied manually) up to a target LSI of either 5 or 6. Subsequently, lesion width and depth were determined. Lesion width was mainly influenced by catheter tip orientation and LSI, whereas lesion depth was mainly influenced by LSI alone. The force stability of catheter contact had no relevant impact on lesion width or depth. CONCLUSION: The force stability of catheter contact has only little effect on lesion depth or width in LSI-guided catheter ablation while the catheter orientation primarily affects lesion width.

Quantitative evaluation of different high-density 3D mapping modes for atrial and ventricular substrate assessment of cardiac arrhythmias with the HD grid catheter.

BACKGROUND: Atrial and ventricular arrhythmias significantly contribute to morbidity and mortality of patients with cardiac disease. Ablation of these arrhythmias has shown to improve clinical outcomes, yet targeted ablation strategies rely on proper mapping capabilities. In the present study, we compare different modes of high-resolution mapping in clinically relevant arrhythmias using HD grid. METHODS AND RESULTS: Using the Advisor™ HD Grid Mapping Catheter in either the standard, the wave (bipolar along spline and bipolar orthogonal) or the wave diagonal setting, low-voltage areas were determined. Low-voltage was defined as local electrograms with an amplitude <0.5 mV (bipolar; atria/ventricle) or <4 mV (unipolar; ventricle). Ultra high-density mapping in 47 patients with ventricular tachycardia, ventricular premature beats, atrial fibrillation and atrial tachycardia provided reliable information for the understanding of the arrhythmia mechanism resulting in safe ablation procedures. Regions of low voltage were significantly decreased by 14 ± 2% and 31 ± 3% with wave and wave diagonal settings as compared to standard settings, respectively. CONCLUSION: Substrate mapping and risk stratification relies on proper low voltage discrimination. Even though the Advisor™ HD Grid Mapping Catheter was safely used in all cases, the extent of low voltage areas was mapping-mode dependent.

Cardiac Implantable Electronic Device Interrogation at Forensic Autopsy: An Underestimated Resource?

BACKGROUND: Postmortem interrogations of cardiac implantable electronic devices (CIEDs), recommended at autopsy in suspected cases of sudden cardiac death, are rarely performed, and data on systematic postmortem CIED analysis in the forensic pathology are missing. The aim of the study was to determine whether nonselective postmortem CIED interrogations and data analysis are useful to the forensic pathologist to determine the cause, mechanism, and time of death and to detect potential CIED-related safety issues. METHODS: From February 2012 to April 2017, all autopsy subjects in the department of forensic medicine at the University Hospital Charité who had a CIED underwent device removal and interrogation. Over the study period, 5368 autopsies were performed. One hundred fifty subjects had in total 151 CIEDs, including 109 pacemakers, 35 defibrillators, and 7 implantable loop recorders. RESULTS: In 40 cases (26.7%) time of death and in 51 cases (34.0%) cause of death could not be determined by forensic autopsy. Of these, CIED interrogation facilitated the determination of time of death in 70.0% of the cases and clarified the cause of death in 60.8%. Device concerns were identified in 9 cases (6.0%), including 3 hardware, 4 programming, and 2 algorithm issues. One CIED was submitted to the manufacturer for a detailed technical analysis. CONCLUSIONS: Our data demonstrate the necessity of systematic postmortem CIED interrogation in forensic medicine to determine the cause and timing of death more accurately. In addition, CIED analysis is an important tool to detect potential CIED-related safety issues.

Correlation of P-wave properties with the size of left atrial low voltage areas in patients with atrial fibrillation.

BACKGROUND: Left atrial low voltage areas (LVA) are associated with increased recurrence rates of atrial fibrillation (AF) after catheter ablation and can be a potential ablation target during the procedure. Therefore, noninvasive prediction of the presence and the distribution of LVA may help physicians to predict ablation outcomes and to guide antiarrhythmic management. MATERIAL AND METHODS: Seventy-three consecutive patients with atrial fibrillation undergoing first time left atrial ablation for paroxysmal or persistent AF were enrolled. P-wave properties (amplitude and duration) were measured in all limb and precordial leads in pre-interventional sinus rhythm surface ECGs and correlated with total LVA size. LVA were detected via high density low voltage maps of the left atrium in sinus rhythm. LVA were then manually encircled, their total size was calculated and given as a percentage of the total LA surface area. RESULTS: A significant, inverse correlation with LVA size was shown for P-wave amplitude for leads I, II, aVR, aVF, V1, V4, V5 and V6. Additionally, a significant positive correlation between LVA size and P-wave duration was shown for leads V1, V2 and V3. As the strongest correlation was shown for the amplitude in lead I (R = -0.578), this lead was used to find a potential cutoff for LVA prediction. The best cut-off for a P-wave amplitude in lead I to predict severe scarring (defined as LVA size >35%, according to UTAH stadium IV) was 0.062 mV with an area-under-the receiver-operating-characteristic curve of 0.935, a sensitivity of 85% and a specificity of 88%. CONCLUSIONS: P-wave duration and amplitude show significant correlations with LVA size and may be used as a noninvasive tool to predict severe scarring. Amplitudes in lead I smaller than 0.062 mV were found to be predictive of LVA >35%.

Zinc Inhibits Phosphate-Induced Vascular Calcification through TNFAIP3-Mediated Suppression of NF-κB.

Background The high cardiovascular morbidity and mortality of patients with CKD may result in large part from medial vascular calcification, a process promoted by hyperphosphatemia and involving osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Reduced serum zinc levels have frequently been observed in patients with CKD, but the functional relevance of this remains unclear.Methods We performed experiments in primary human aortic VSMCs; klotho-hypomorphic (kl/kl), subtotal nephrectomy, and cholecalciferol-overload mouse calcification models; and serum samples from patients with CKD.Results In cultured VSMCs, treatment with zinc sulfate (ZnSO4) blunted phosphate-induced calcification, osteo-/chondrogenic signaling, and NF-κB activation. ZnSO4 increased the abundance of zinc-finger protein TNF-α-induced protein 3 (TNFAIP3, also known as A20), a suppressor of the NF-κB pathway, by zinc-sensing receptor ZnR/GPR39-dependent upregulation of TNFAIP3 gene expression. Silencing of TNFAIP3 in VSMCs blunted the anticalcific effects of ZnSO4 under high phosphate conditions. kl/kl mice showed reduced plasma zinc levels, and ZnSO4 supplementation strongly blunted vascular calcification and aortic osteoinduction and upregulated aortic Tnfaip3 expression. ZnSO4 ameliorated vascular calcification in mice with chronic renal failure and mice with cholecalciferol overload. In patients with CKD, serum zinc concentrations inversely correlated with serum calcification propensity. Finally, ZnSO4 ameliorated the osteoinductive effects of uremic serum in VSMCs.Conclusions Zinc supplementation ameliorates phosphate-induced osteo-/chondrogenic transdifferentiation of VSMCs and vascular calcification through an active cellular mechanism resulting from GPR39-dependent induction of TNFAIP3 and subsequent suppression of the NF-κB pathway. Zinc supplementation may be a simple treatment to reduce the burden of vascular calcification in CKD.

Pushing the limits: establishing an ultra-low framerate and antiscatter grid-less radiation protocol for left atrial ablations.

Aims: Despite the use of 3D mapping systems and new developments of non-fluoroscopic options, most centres still rely at least in part on fluoroscopy for catheter visualization during catheter ablations. The purpose of this study was to assess the feasibility of using an ultra-low frame rate and antiscatter grid-less radiation protocol during complex left atrial ablations to minimize radiation exposure for the patient and staff. Methods and results: A total of 150 consecutive patients undergoing left atrial ablations in our hospital were included in the analysis. The procedures were performed between January 2015 and November 2016. Of the included patients 75 (50%) underwent ablation before and 75 (50%) after the ultra-low frame rate (reduced from 4 to 2 FPS) and antiscatter grid-less radiation protocol was established. Procedures performed after the dose reduction protocol was established showed a 64% reduction of the dose area product (630.28 ± 550.96 vs. 226.44 ± 277.44 µGym2, P < 0.001), while fluoroscopy duration (14.22 ± 4.47 vs. 13.62 ± 7.11 min, P = 0.066) and procedural duration (1:48 ± 0:28 vs. 1:53 ± 0:34 min, P = 0.525) were not prolonged. Acute procedural success was achieved in all procedures. Two complications occurred before and one complication after the protocol was established. During four procedures, operators decided to re-introduce the antiscatter grid. This was due to impaired visibility in morbidly obese patients (n = 2) or technically difficult transseptal puncture (n = 2). Conclusion: The use of an ultra low framerate and antiscatter grid-less radiation protocol effectively reduced radiation dose for complex left atrial ablation procedures and lead to very low average patient doses. Reduced image quality did not impair procedural and fluoroscopy duration or acute procedural success.

The CardioMEMS system in the clinical management of end-stage heart failure patients: three case reports.

BACKGROUND: Recent clinical trials have shown that pulmonary artery pressure-guided therapy via the CardioMEMS™ system reduces the risk of recurrent hospitalizations in chronic heart failure (HF) patients. The CardioMEMS™ pressure sensor is percutaneously implanted in a branch of the pulmonary artery and allows telemetric pressure monitoring via a receiver. According to the most recent ESC guidelines, this technology has currently a class IIb indication in patients with class III New York Heart Association symptoms and a previous hospitalization for congestive heart failure within the last year, regardless of ejection fraction. Aim of this guided-therapy is multifold, including an early prediction of upcoming decompensation, optimization of patients' therapy and thereby avoidance of hospital admissions. In addition, it can be used during acute decompensation events as a novel tool to direct intra-hospital therapeutic interventions such as inotropes infusion or left ventricular (LV) assist device monitoring, with the aim of achieving an optimal volume status. CASE PRESENTATION: We present a case series of three end-stage HF patients with reduced ejection fraction (HFrEF) who received a CardioMEMS™ device as an aid in their clinical management. The CardioMEMS™ system enabled a closer non-invasive hemodynamic monitoring of these patients and guided the extent of therapeutic interventions. Patients were free from device- or system-related complications. In addition, no pressure-sensor failure was observed. Two patients received a 24-h infusion of the calcium sensitizer levosimendan. One patient showed a refractory acute decompensation and underwent LV assist device (LVAD) implantation as a bridge to cardiac transplantation. Switching a patient with recurrent hospitalizations to the Angiotensin Receptor Neprilysin Inhibitor (ARNI, Sacubitril-Valsartan) on top of the optimal heart failure-therapy improved its subjective condition and hemodynamics, avoiding further hospitalization. CONCLUSIONS: Our case series underlines the potential impact of CardioMEMS™ derived data in the daily clinical management of end-stage HF patients. The new concept to combine CardioMEMS™ in the setting of an outpatient levosimendan program as well as a bridge to LVAD-implantation/heart transplantation looks promising but needs further investigations.

Activation of Peroxisome Proliferator-Activated Receptor-δ as Novel Therapeutic Strategy to Prevent In-Stent Restenosis and Stent Thrombosis.

OBJECTIVE: Drug-eluting coronary stents reduce restenosis rate and late lumen loss compared with bare-metal stents; however, drug-eluting coronary stents may delay vascular healing and increase late stent thrombosis. The peroxisome proliferator-activated receptor-delta (PPARδ) exhibits actions that could favorably influence outcomes after drug-eluting coronary stents placement. APPROACH AND RESULTS: Here, we report that PPARδ ligand-coated stents strongly reduce the development of neointima and luminal narrowing in a rabbit model of experimental atherosclerosis. Inhibition of inflammatory gene expression and vascular smooth muscle cell (VSMC) proliferation and migration, prevention of thrombocyte activation and aggregation, and proproliferative effects on endothelial cells were identified as key mechanisms for the prevention of restenosis. Using normal and PPARδ-depleted VSMCs, we show that the observed effects of PPARδ ligand GW0742 on VSMCs and thrombocytes are PPARδ receptor dependent. PPARδ ligand treatment induces expression of pyruvate dehydrogenase kinase isozyme 4 and downregulates the glucose transporter 1 in VSMCs, thus impairing the ability of VSMCs to provide the increased energy demands required for growth factor-stimulated proliferation and migration. CONCLUSIONS: In contrast to commonly used drugs for stent coating, PPARδ ligands not only inhibit inflammatory response and proliferation of VSMCs but also prevent thrombocyte activation and support vessel re-endothelialization. Thus, pharmacological PPARδ activation could be a promising novel strategy to improve drug-eluting coronary stents outcomes.

Does the extent of left atrial arrhythmogenic substrate depend on the electroanatomical mapping technique: impact of pulmonary vein mapping catheter vs. ablation catheter.

AIMS: In persistent atrial fibrillation (AF), left atrial low-voltage areas and complex fractionated atrial electrograms (CFAEs) have been thoroughly discussed as critical substrate points for AF perpetuation. Thus, in patients undergoing pulmonary vein isolation, these sites are often considered additional ablation targets. Currently, mapping techniques for these substrate indicators are still under discussion. The aim of this study was to evaluate the impact of different mapping catheters on the detection of low-voltage areas and CFAE. METHODS AND RESULTS: Two bipolar voltage maps and two CFAE left atrial maps were obtained each in 30 patients undergoing catheter ablation of AF using the following two different catheters: A four-pole ablation catheter (MAP, mapping and ablation catheter) (electrode size: tip: 4 mm, band: 1 mm; inter-electrode spacing: 0.5-5-2 mm) and a 10-pole circular pulmonary vein mapping catheter (CMC) (electrode size: 1 mm; inter-electrode spacing: 7-7-7 mm). Successively, low-voltage and CFAE area sizes were then compared between the two catheters. Areas with a bipolar voltage of <0.5 mV were significantly smaller when obtained with the CMC compared with the MAP (8.9 ± 8.9 vs. 17.4 ± 11.7 cm², P < 0.001). This was also significantly different for a bipolar voltage of <0.2 mV (2.3 ± 4.6 vs. 6.2 ± 9.6 cm², P < 0.001). Complex fractionated atrial electrogram area sizes were significantly larger when obtained with the CMC compared with the MAP group (14.6 ± 10.9 vs. 19.4 ± 9.4 cm², P = 0.011). CONCLUSION: Low-voltage and CFAE area size varies significantly between different mapping catheters. Mapping electrode settings have to be taken into consideration for the assessment of electroanatomical substrate of AF.

Safety and efficacy of applying a low-dose radiation fluoroscopy protocol in device implantations.

AIMS: For cardiac implantable electronic device (CIED) implantations, visualization of lead placement is necessary and fluoroscopy remains by far the most commonly used technique. With simple changes in the X-ray system settings, total radiation dose can be reduced significantly. The purpose of this study was to assess the safety and efficacy of various CIED implantations performed after implementation of a new dose reduction protocol (DRP). METHODS AND RESULTS: We conducted a retrospective chart review of 584 patients undergoing CIED implantation or revision in our hospital. Of these patients, 280 (48%) underwent the implantation prior to and 304 (52%) after the DRP introduction. The DRP included various changes for optimized image processing and exposure system settings to enable dose reduction, as well as a reduced frame rates (4 FPS for fluoroscopy and 7.5 FPS for cinematographic images). Of the 584 patients, 53 (9.1%) had a one-chamber pacemaker, 232 (39.7%) a two-chamber pacemaker, 133 (22.8%) a one-chamber ICD, 35 (6.0%) a two-chamber ICD, 82 (14.0%) a CRT (de novo) implantation, and 49 (8.3%) had an upgrade to a CRT device. DRP was associated with a 64% reduction of the dose-area product (1372 ± 2659 vs. 3792 ± 5025 cGcm2, P < 0.001), while fluoroscopy duration (13 ± 15 vs. 13 ± 15 min) and procedural duration (93 ± 52 vs. 92 ± 52 min.) did not significantly increase. Complication rates did not differ significantly between the two groups. CONCLUSION: The DRP proved to effectively reduce radiation dose for all types of CIED implantations. Fluoroscopy time, total procedure time, and the number of complications did not increase after introducing the DRP.

The effect of an ultra-low frame rate and antiscatter grid-less radiation protocol for cardiac device implantations.

BACKGROUND AND AIMS: Antiscatter grids improve image contrast by absorbing scattered x-ray beams, although by removing the antiscatter grid patient dose can be reduced as more x-ray beams reach the image receptor. Additionally, there is a trend toward ultra-low frame rates for radiation dose reduction during various electrophysiology procedures. As for most cardiac device implantations (CIED) image quality demands are usually modest, the purpose of this study was to assess the safety and efficacy of an ultra-low frame rate and scatter grid-less radiation protocol. METHODS/RESULTS: A total of 140 patients undergoing CIED implantation between 2014 and 2017 were included in the study. Seventy patients (50%) implanted after implementation of the antiscatter grid-less and ultra-low frame rate protocol were matched to controls before the dose-reduction protocol was established. Forty patients (28.6%) had a one-chamber pacemaker or one-chamber implantable cardioverter defibrillator (ICD) implantation/revision, 60 (42.9%) had a two-chamber pacemaker or two-chamber ICD implantation/revision, and 40 (28.6%) patients had a cardiac resynchronization therapy device implantation/revision. Removing the antiscatter-grid and lowering the frame rate led to a 73% reduction of the overall dose area product (1,206 ± 2,015 vs 324 ± 422 µGym, P < 0.001). Procedural duration (95 ± 51 minutes vs 82 ± 44 minutes, P  =  0.053) and rate of complications were not significantly different between the two groups. CONCLUSION: The use of an ultra-low frame rate and antiscatter grid-less radiation protocol significantly reduced radiation dose for implantation of CIED and led to very low average patient doses, while procedural duration and complication rates did not increase.

Performance of the New BioMonitor 2-AF Insertable Cardiac Monitoring System: Can Better be Worse?

BACKGROUND: Implantable loop recorders (ILR) are valuable tools for the investigation of patients with suspected arrhythmias. The BioMonitor 2-AF is a novel insertable ILR with enhanced atrial fibrillation (AF) detection algorithm and remote monitoring capability. OBJECTIVE: The objective of this first-in-human study with the BioMonitor 2-AF was to analyze course of P-wave sensing performance and R-wave amplitude, prevalence of false and correctly sensed and classified episodes, and effectiveness of remote monitoring. METHODS: All 19 patients who underwent ILR insertion were included in the BIOTRONIK Home Monitoring® system (BIOTRONIK GmbH, Berlin, Germany). Daily changes in P-wave and R-wave sensing were analyzed over 6 weeks. A breathing test (in- and expiration) was performed in two different body positions at baseline and during a 6-week in-house follow-up to investigate alterations of P-wave and R-wave sensing. RESULTS: R-wave amplitude and the high P-wave visibility (94.4%) remained unchanged during the follow-up period. In most patients both an increase and decrease of R-wave amplitude, and in some cases a complete R-wave vector change (31.6%), was documented during the "breathing test." Change of body position did not alter R-wave sensing amplitude mostly. "Breathing test" and change of body position had no effect on P-wave sensing performance. In 15.8% of the patients, misclassification of episodes as AF or high ventricular rates due to P-wave oversensing occurred. No ILR-related complication occurred. Automatic transmission via BIOTRONIK Home Monitoring® was successful 100% of the time. CONCLUSION: This study demonstrates that the BioMonitor 2-AF is a safe and effective tool for continuous cardiac monitoring.

Catheter ablation of atrial flutter: A survey focusing on post ablation oral anticoagulation management and ECG monitoring.

BACKGROUND: A considerable amount of patients with typical atrial flutter develop atrial fibrillation after cavotricuspid isthmus (CTI) ablation. No uniform recommendations are available to guide anticoagulation regimes or electrocardiogram (ECG) monitoring strategies after this procedure. METHODS: We conducted a web-based survey in electrophysiology (EP) centers in Germany, Switzerland, and Austria. Responses were received from 47 centers. The survey was designed to investigate variations in management of the following: ablation strategy, oral anticoagulation (OAC) management, and ECG monitoring after successful CTI ablation. RESULTS: More than 55% of the participating centers assume that at least every third patient will develop atrial fibrillation during follow-up. Despite this assumption, most EP experts (81%) would still stop OAC after CTI ablation even in patients with higher CHADS2-VA2SC-score, or even perform CTI in asymptomatic patients with the purpose to stop OAC (52%). Most experts agree that ECG monitoring is necessary during follow-up. A majority still rely on short-term monitoring tools like resting ECGs (7%) or Holter ECGs (43%), while continuous monitoring by implantable loop recorders (10%) are rarely used for postablation OAC management. CONCLUSION: A majority of the centers stop OAC in patients with higher CHADS2-VA2SC-score after CTI ablation. There is evidence that this practice might not be safe and lead to an increased number of ischemic strokes during follow-up. This reflects the need for prospective studies to allow for clear guidelines regarding these issues.

Embryonic cardiomyocytes can orchestrate various cell protective mechanisms to survive mitochondrial stress.

Whereas adult cardiomyocytes are highly susceptible to stress, cardiomyocytes in the prenatal heart appear to be rather resistant. To investigate how embryonic cardiomyocytes respond to metabolic stress in vivo, we utilized tissue mosaicism for mitochondrial dysfunction in 13.5dpc mouse hearts. The latter is based on inactivation of the X-linked gene encoding Holocytochrome c synthase (Hccs), which is essential for mitochondrial respiration. In heterozygous heart conditional Hccs knockout females (cHccs(+/-)) random X chromosomal inactivation results in a mosaic of healthy and HCCS deficient cells in the myocardium. Microarray RNA expression analyses identified genes involved in unfolded protein response (UPR) and programmed cell death as differentially expressed in cHccs(+/-) versus control embryonic hearts. Activation of the UPR is localized to HCCS deficient cardiomyocytes but does not involve ER stress pathways, suggesting that it is caused by defective mitochondria. Consistently, mitochondrial chaperones, such as HSP10 and HSP60, but not ER chaperones are induced in defective cells. Mitochondrial dysfunction can result in oxidative stress, but no evidence for excessive ROS (reactive oxygen species) production was observed in cHccs(+/-) hearts. Instead, the antioxidative proteins SOD2 and PRDX3 are induced, suggesting that ROS detoxification prevents oxidative damage in HCCS deficient cardiomyocytes. Mitochondrial dysfunction and unrestricted UPR can induce cell death, and we detected the initiation of upstream events of both intrinsic as well as extrinsic apoptosis in cHccs(+/-) hearts. Cell death is not executed, however, suggesting the activation of antiapoptotic mechanisms. Whereas most apoptosis inhibitors are either unchanged or downregulated in HCCS deficient cardiomyocytes, Bcl-2 and ARC (apoptosis repressor with caspase recruitment domain) are induced. Given that ARC can inhibit both apoptotic pathways as well as necrosis and attenuates UPR, we generated cHccs(+/-) embryos on an Arc knockout background (cHccs(+/-),Arc(-/-)). Surprisingly, the absence of ARC does not induce cell death in embryonic or postnatal HCCS deficient cardiomyocytes and adult cHccs(+/-),Arc(-/-) mice exhibit normal cardiac morphology and function. Taken together, our data demonstrate an impressive plasticity of embryonic cardiomyocytes to respond to metabolic stress, the loss of which might be involved in the high susceptibility of postnatal cardiomyocytes to cell death.

Class IA Phosphatidylinositol 3-Kinase Isoform p110α Mediates Vascular Remodeling.

OBJECTIVE: Neointima formation after vascular injury remains a significant problem in clinical cardiology, and current preventive strategies are suboptimal. Phosphatidylinositol 3'-kinase is a central downstream mediator of growth factor signaling, but the role of phosphatidylinositol 3'-kinase isoforms in vascular remodeling remains elusive. We sought to systematically characterize the precise role of catalytic class IA phosphatidylinositol 3'-kinase isoforms (p110α, p110ß, p110δ), which signal downstream of receptor tyrosine kinases, for vascular remodeling in vivo. APPROACH AND RESULTS: Western blot analyses revealed that all 3 isoforms are abundantly expressed in smooth muscle cells. To analyze their significance for receptor tyrosine kinases-dependent cellular responses, we used targeted gene knockdown and isoform-specific small molecule inhibitors of p110α (PIK-75), p110ß (TGX-221), and p110δ (IC-87114), respectively. We identified p110α to be crucial for receptor tyrosine kinases signaling, thus affecting proliferation, migration, and survival of rat, murine, and human smooth muscle cells, whereas p110ß and p110δ activities were dispensable. Surprisingly, p110δ exerted noncatalytic functions in smooth muscle cell proliferation, but had no effect on migration. Based on these results, we generated a mouse model of smooth muscle cell-specific p110α deficiency (sm-p110α(-/-)). Targeted deletion of p110α in sm-p110α(-/-) mice blunted growth factor-induced cellular responses and abolished neointima formation after balloon injury of the carotid artery in mice. In contrast, p110δ deficiency did not affect vascular remodeling in vivo. CONCLUSIONS: Receptor tyrosine kinases-induced phosphatidylinositol 3'-kinase signaling via the p110α isoform plays a central role for vascular remodeling in vivo. Thus, p110α represents a selective target for the prevention of neointima formation after vascular injury, whereas p110ß and p110δ expression and activity do not play a significant role.