Comparison of Postoperative Outcomes between Leadless and Conventional Transvenous Pacemakers Implantation: An Up-to-Date Meta-analysis.

Background: Leadless cardiac pacemakers (LCPs) are emerging as viable alternatives to conventional transvenous pacemakers (TVPs). This study aimed to systematically compare the postoperative outcomes of LCPs and TVPs based on available published studies. Methods: We conducted a systematic review and meta-analysis of literature comparing outcomes from LCP and TVP implantations. Data analysis was performed using Stata/MP 17.0. The evaluated endpoints included pericardial effusion or perforation, puncture site events, infective endocarditis, lead or device dislodgement, pocket-related complications, tricuspid regurgitation or dysfunction, any infection, increased right ventricle (RV) pacing threshold, embolism, and thrombosis. Aggregated odds ratios (OR) and 95% confidence intervals (CI) were determined. Sensitivity analyses were conducted for heterogeneity if I2 was >50% or p < 0.01, otherwise, the random-effects model was chosen. Publication bias was analyzed if the number studies exceeded ten. Results: The meta-analysis included 24 observational studies with 78,938 patients, comprising 24,191 with LCP implantation and 54,747 with TVP implantation. The results indicated a significantly lower incidence of lead or device dislodgment (OR = 3.32, 95% CI: 1.91-5.77, p < 0.01), infective endocarditis (OR = 3.62, 95% CI: 3.10-4.24, p < 0.01), and infection (OR = 3.93, 95% CI: 1.67-9.24, p < 0.01) in the LCP group compared to the TVP group. In contrast, incidences of puncture site complications (OR = 0.24, 95% CI: 0.19-0.32, p < 0.01) and pericardial effusion or perforation (OR = 0.33, 95% CI: 0.28-0.39, p < 0.01) were significantly higher in the LCP group. Conclusions: Compared with TVP, LCP implantation is associated with a lower risk of infective endocarditis, lead or device dislodgment, infections, and pocket-related complications. However, LCP implantation carries a higher risk of puncture site complications and pericardial effusion or perforation. These findings underscore the need for careful consideration of patient-specific factors when choosing between LCP and TVP implantation. The PROSPERO Registration: https://www.crd.york.ac.uk/prospero/ (CRD42023453145).

Fungal Leadless Pacemaker Endocarditis Managed by Percutaneous Vacuum-Assisted Evacuation of Vegetation, Pacemaker Extraction, and Replacement.

Leadless cardiac pacemakers (LCPs) mitigate the risks of traditional transvenous devices such as lead fracture and infection. Two LCPs are clinically available, using either a helix or tined active fixation approach. There are rare reports of LCP infection-all involving the tined device. We report the first pathologically confirmed fungal endocarditis involving a helix-based LCP. This was successfully managed by catheter-based mechanical vacuum evacuation of the vegetation, followed by device extraction and replacement.

Risk factors and incidence of new-onset heart failure with conventional pacemaker implant: A nationwide study.

Background: Studies have shown that the risk of new-onset heart failure (HF) is higher postimplantation for patients receiving right ventricular pacing. Objective: This study aimed to investigate incidence, risk factors, and implications for long-term prognosis of new-onset HF in patients after pacemaker implantation. Methods: Patients without pre-existing HF who received a pacemaker in Sweden during the period of 2005 to 2020 were identified via the nationwide Pacemaker Registry. Data were crossmatched with the population registry and national disease registries. The primary outcome was new-onset HF within 5 years, and a risk score for this was developed and validated. Results: In all, 65,579 patients met the inclusion criteria (10,351 single-chamber ventricular and 55,228 dual-chamber pacemakers). A total of 13,792 (21.0%) patients were diagnosed with HF within 5 years postimplantation. Of these, 6244 (45.3%) were hospitalized for HF. Patients with new-onset HF were more likely to die within 5 years (41.2% vs 19.7%, P < .0001). Risk factors for new-onset HF included increasing age, male sex, hypertension, diabetes, atrial fibrillation, chronic lung and kidney disease, ischemic heart disease, and atrioventricular block. In a combined score using these variables, patients in the highest risk-score quartile had a hazard ratio of 5.36 (95% CI 4.91-5.86, P < .001) and an absolute risk of 32% for developing HF. Conclusion: Pacemaker therapy is associated with >20% risk of new-onset HF within 5 years, and we identified 9 risk factors associated with the diagnosis of new-onset HF. The proposed score based on these variables can be used to identify patients at high risk for new-onset HF.

His-Bundle Pacing for Pulmonary Hypertension With Bradycardia in Congenital Heart Disease: A Case Report.

Bradycardia, atrial tachyarrhythmia, heart failure, residual shunts, and pulmonary hypertension (PH) are significant problems after congenital heart disease surgery. We performed His-bundle pacing (HBP) for drug-resistant PH with bradycardia in a woman post-total anomalous pulmonary venous return repair complicated by bradycardia, hypertension, PH, residual atrial shunts, and heart failure. Significant improvement in PH post-HBP was achieved without exacerbation of left ventricular function. We successfully closed the atrial shunts 12 months after HBP.

Conduction Disturbances and Outcome After Surgical Aortic Valve Replacement in Patients With Bicuspid and Tricuspid Aortic Stenosis.

BACKGROUND: This study aimed to compare the incidence and prognostic implications of new-onset conduction disturbances after surgical aortic valve replacement (SAVR) in patients with bicuspid aortic valve (BAV) aortic stenosis (AS) versus patients with tricuspid aortic valve (TAV) AS (ie, BAV-AS and TAV-AS, respectively). Additionally, the study included stratification of BAV patients according to subtype. METHODS: In this cohort study, the incidence of postoperative third-degree atrioventricular (AV) block with subsequent permanent pacemaker requirement and new-onset left bundle-branch block (LBBB) was investigated in 1147 consecutive patients without preoperative conduction disorder who underwent isolated SAVR (with or without ascending aortic surgery) between January 1, 2005, and December 31, 2022. The groups were stratified by aortic valve morphology (BAV, n=589; TAV, n=558). The outcomes of interests were new-onset third-degree AV block or new-onset LBBB during the index hospitalization. The impact of new-onset postoperative conduction disturbances on survival was investigated in BAV-AS and TAV-AS patients during a median follow-up of 8.2 years. BAV morphology was further categorized according to the Sievers and Schmidtke classification system (possible in 307 BAV-AS patients) to explore association between BAV subtypes and new-onset conduction disturbances after SAVR. RESULTS: The overall incidence of third-degree AV block and new-onset LBBB after SAVR was 4.5% and 7.8%, respectively. BAV-AS patients had a higher incidence of both new-onset third-degree AV block (6.5% versus 2.5%; P=0.001) and new-onset LBBB (9.7% versus 5.7%; P=0.013) compared with TAV-AS patients. New-onset LBBB was associated with an increased all-cause mortality during follow-up (adjusted hazard ratio, 1.60 [95% CI, 1.12-2.30]; P=0.011), whereas new-onset third-degree AV block was not associated with worse prognosis. Subgroup analysis of the BAV cohort revealed that BAV-AS patients with fusion of the right- and non-coronary cusps had the highest risk of new-onset third-degree AV block (adjusted odds ratio [aOR], 8.33 [95% CI, 3.31-20.97]; P<0.001, with TAV as reference group) and new-onset LBBB (aOR, 4.03 [95% CI, 1.84-8.82]; P<0.001, with TAV as reference group), whereas no significant association was observed for the other BAV subtypes. CONCLUSIONS: New-onset LBBB after SAVR is associated with increased all-cause mortality during follow-up, and is more frequent complication in BAV AS patients compared with TAV-AS patients. BAV-AS patients with fusion of the right- and non-coronary cusps have an increased risk for conduction disturbances after SAVR. This should be taken into consideration when managing these patients.

The effect of extracellular potassium concentration on the oscillation frequency of the pacemaker nucleus in the weakly electric fish Apteronotus leptorhynchus.

The weakly electric brown ghost knifefish (Apteronotus leptorhynchus) exhibits a pronounced sexual dimorphism in its electric behavior-males discharge at higher frequencies than females, with little overlap between the sexes. The frequency of these electric organ discharges is controlled by the frequency of the synchronized oscillations of the medullary pacemaker nucleus. Previous studies have suggested that sex-specific differences in the morphology and gene expression pattern of the astrocytic syncytium that envelopes the pacemaking neural network cause differences in its capacity to buffer the extracellular concentration of K+. This change in the K+ buffering capacity affects the K+ equilibrium potential of the neurons constituting the neural network, which in turn modulates the frequency of the pacemaker nucleus. In the present study, we have tested a critical element of this hypothesis by examining whether, and how, changes in the extracellular K+ concentration influence the frequency of the pacemaker nucleus oscillations. By using an in vitro preparation of the pacemaker nucleus, the results of this investigation demonstrate that exposure of this nucleus to acutely increased/decreased concentrations of K+ in the perfusate (while maintaining osmolarity) leads to concentration-dependent increases/decreases in the frequency of the synchronized oscillations generated by the pacemaker nucleus.

Recurrence rate and predictors in non-ischemic reversible bradyarrhythmias.

Objective: Non-ischemic symptomatic reversible bradyarrhythmia is a poorly characterized yet common clinical challenge. This study aimed to assess the incidence and predictors of recurrence and the need for permanent cardiac pacing in patients with non-ischemic symptomatic reversible bradyarrhythmia. Methods: This prospective single-center study enrolled 124 consecutive adult patients with non-ischemic symptomatic reversible bradyarrhythmia who were followed up for up to 24 months after conservative management during index hospitalization. The primary endpoint was a recurrence of bradyarrhythmia requiring permanent cardiac pacing. The secondary endpoint was a composite of recurrence requiring permanent pacing, readmission, or death. Univariate and multivariate analyses were conducted to determine the predictors of the endpoints. Results: Sinus node and atrioventricular node diseases were seen in 66.1% and 33.9% of patients, respectively. The most common causes of bradyarrhythmia were negative chronotropic drugs (58.1%) and hyperkalemia (55.6%). Permanent pacing was required in 21.8% of patients after a recurrence. Advanced atrioventricular block at presentation (HR: 6.10, 95% CI: 2.45-15.20, p < 0.001) and bifascicular block at discharge (HR: 3.63, 95% CI: 1.58-8.33, p = 0.002) during index hospitalization were significant independent predictors of recurrence requiring cardiac pacing. Conclusion: Non-ischemic symptomatic reversible bradyarrhythmia is associated with a high risk of recurrence. Permanent cardiac pacing should be considered during index hospitalization in patients with advanced atrioventricular block and/or bifascicular block.

Feasibility, safety and clinical impact of a less-invasive totally-endovascular (LITE) technique for transfemoral TAVI: A 1000 patients single-centre experience.

Background: Trans-femoral (TF) represents the main access for TAVI. Although there are various technical strategies to conduct TF-TAVI (pacing modality, secondary arterial access, primary access puncture etc.), the optimal technique is not recognized. Aims: In the present study, we assessed the impact of systematic use of LITE-TAVI in terms of feasibility, safety, and main access complication management using VARC-3 outcomes definitions. Methods: At our institution, a less-invasive totally-endovascular (LITE) technique for TF-TAVI has been developed since 2017. Key aspects are: precise TAVI access puncture using angiographic-guidewire ultrasound guidance; radial/ulnar approach as the default "secondary access"; non-invasive pacing (by guidewire stimulation or definitive pacemaker external programmer). Results: 1022 consecutive TF-TAVI patients (55 % women, mean age: 80 years, mean EuroSCORE II 6.1 %, mean STS-PROM 4.3 %, mean STS/ACC TVT TAVR mortality score 3.4 %) were approached using the LITE technique. Technical success was achieved in 993 (97.2 %) patients. Access-related major vascular complications occurred in 12 (1.2 %) and VARC-3 ≥ type 2 bleedings in 12 (1.2 %) patients. At 30-day, all-cause death occurred in 17 (1.7 %) patients. This figure resulted significantly lower than expected on the bases of the mortality predicted not only by EuroSCORE II (6.1 %, p < 0.001) and STS-PROM score (4.3 %; p < 0.001), but also by STS/ACC TVT TAVR mortality score (3.4 %; p = 0.01). Conclusions: Systematic use of LITE-TAVI is feasible and is associated with an extremely low rate of access-related bleeding and vascular complications which may drive to outcome improvement.

Machine learning for pacemaker implantation prediction after TAVI using multimodal imaging data.

Pacemaker implantation (PMI) after transcatheter aortic valve implantation (TAVI) is a common complication. While computed tomography (CT) scan data are known predictors of PMI, no machine learning (ML) model integrating CT with clinical, ECG, and transthoracic echocardiography (TTE) data has been proposed. This study investigates the contribution of ML methods to predict PMI after TAVI, with a focus on the role of CT imaging data. A retrospective analysis was conducted on a cohort of 520 patients who underwent TAVI. Recursive feature elimination with SHAP values was used to select key variables from clinical, ECG, TTE, and CT data. Six ML models, including Support Vector Machines (SVM), were trained using these selected variables. The model's performance was evaluated using AUC-ROC, F1 score, and accuracy metrics. The PMI rate was 18.8%. The best-performing model achieved an AUC-ROC of 92.1% ± 4.7, an F1 score of 71.8% ± 9.9, and an accuracy of 87.9% ± 4.7 using 22 variables, 9 of which were CT-based. Membranous septum measurements and their dynamic variations were critical predictors. Our ML model provides robust PMI predictions, enabling personalized risk assessments. The model is implemented online for broad clinical use.

Pacemaker Implantation for Low-Grade Conduction Abnormalities After Balloon-Expandable Transcatheter Aortic Valve Implantation.

INTRODUCTION: A frequent complication after TAVI are postinterventional conduction abnormalities requiring permanent pacemaker implantation. In this study, we analyzed the characteristics of borderline conduction abnormalities leading to pacemaker implantation and the resulting ventricular pacing amounts. METHODS AND RESULTS: All patients who underwent balloon-expandable TAVI between 2014 and 2019 in our tertiary center were analyzed in a retrospective manner. One hundred and sixty-five patients of 1083 TAVI-patients developed postinterventional conduction abnormalities leading to pacemaker implantation. Of these 19 (11.5%) did not represent a clear indication for cardiac pacing according to current European guidelines. Patient characteristics, underlying conduction abnormalities, and the temporal change of ventricular pacing percentages at 24 h and 6 weeks after pacemaker implantation were analyzed. The dominating borderline conduction abnormalities leading to pacemaker implantation were new-onset persisting bundle-branch-blocks and new first-degree AV-blocks with progression of AV-delay. While pacemaker implantation was safe and without severe complications in all cases, only 6 of 19 patients had high pacing amounts (95%-100%) after 24 h while 11 patients had low to no pacing amounts (0%-5%). After 6 weeks, 8 patients showed decreasing pacing amounts, no patient had an increasing amount of ventricular pacing and all patients had an intrinsic ventricular rhythm > 30/min. CONCLUSION: In our cohort of 1038 TAVI patients, 19 patients underwent PMI for borderline CAs (11.5% of all PMI). Of these, only 2 patients had high pacing amounts after 6 weeks. The risk of complete persisting heart block in these patients is very low. Furthermore, algorithms to reduce ventricular pacing are highly effective to avoid ventricular pacing whenever reasonable.

Immune checkpoint inhibitor-associated sick sinus syndrome and cardiogenic shock.

Immune checkpoint inhibitors (ICI) represent a major advance in the treatment of cancer. Most studies of ICI have underestimated their cardiotoxicity; however, an increasing number of cases of cardiotoxicity are being reported. Herein we discussed a 67-year-old, male, Japanese patient who presented with cardiogenic shock accompanied by sick sinus syndrome 4 days into his second course of ipilimumab plus nivolumab combination therapy. A temporary transvenous pacemaker was subsequently placed, and a permanent pacemaker was implanted for persistent, symptomatic, intermittent bradycardia. The permanent implantation of the pacemaker improved his symptoms and allowed him to continue his ICI therapy.

Endocardial ablation of ganglionated plexus for the treatment of carotid sinus syndrome.

INTRODUCTION: Carotid sinus syndrome (CSS), characterized by exaggerated vagal responses leading to asystolic pauses with carotid sinus massage (CSM), often necessitates pacemaker implantation. This study investigates cardioneuroablation (CNA) as an alternative strategy for CSS. METHODS: Prospective study of consecutive patients referred for CNA due to CSS. All patients underwent CSM, atropine test and 24-h Holter monitoring before the procedure and at 6 months. The primary objective was the absence of any cardioinhibitory response to CSM following CNA. Secondary objectives included the combined endpoint of syncope and presyncope-free survival, pacemaker-free survival, differences in heart rate variation (HRV), as well as differences in the pre- and postprocedure atropine tests and in the SF-36 quality-of-life questionnaire. RESULTS: A total of 13 consecutive patients (84.6% male, mean age 63.8 ± 12.3 years) were included. CSM revealed a symptomatic asystolic pause in all patients before CNA (7.3 [5.6-10.5] s). After the procedure, all the patients had a negative CSM, and only one patient (7.7%) had a positive CSM at 6 months. After a median follow-up of 11.2 (10.6-16.3) months, syncope or presyncope-free survival was 84.6%, and none required pacemaker implantation. There was an improvement in the energy and health change items in the SF-36 questionnaire. There was a reduction in HR increase in the atropine test at 6 months (pre-CNA: 66% [52-84] vs. post-CNA 26.0% (19.8-29.3]; p = .008) and in HRV parameters. CONCLUSIONS: In this proof-of-efficacy study, performed in patients affected by asystolic CSS, CNA was effective in reducing the rate of cardioinhibitory responses, suggesting a potential efficacy in also reducing syncopal recurrences. Controlled trials are warranted to corroborate clinical findings.

Factors Associated with Permanent Pacemaker Placement After Tricuspid Valve Operations.

BACKGROUND: Conduction abnormalities requiring permanent pacemaker (PPM) implantation are common after tricuspid valve operations, though incidence is variable. This study aims to investigate contemporary rates of and risk factors for PPM after tricuspid operations. METHODS: The Society of Thoracic Surgeons Adult Cardiac Surgery Database was used to identify patients with tricuspid repair or replacement from 2011 to 2020. Factors independently associated with risk of postoperative PPM during index hospital admission were examined using multivariable logistic regression with a complete case approach. Annualized hospital and surgeon volumes were calculated. RESULTS: We identified 71,937 patients undergoing tricuspid operations. Median patient age was 66 (53-74) years, 56% were female (n=40,590), and median ejection fraction was 56% (48%-60%). Tricuspid operations were concomitant in 87% (n=62,457), elective in 62% (n=44,393), and included repair in 86% (n=61,720). Overall postoperative incidence of PPM was 15% (n=10,857); 13% (n=8,304) after repair and 25% (n=2,553) after replacement; 4% (n=174) for isolated tricuspid repair and 24% (n=1,248) for isolated tricuspid replacement. Multivariable analysis showed baseline characteristics, endocarditis, concomitant operations, longer CPB time, tricuspid replacement, and lower hospital and surgeon tricuspid operative volumes were independently associated with greater risk for PPM. After adjustment, tricuspid replacement had 3.2 times greater PPM risk compared to tricuspid repair. CONCLUSIONS: Nationally, 15% of patients undergoing tricuspid operations required postoperative PPM implantation. PPM risk was increased with concomitant valve operations, tricuspid replacement, longer CPB time, and operations performed by less experienced surgeons and centers. Innovation is needed to decrease this significant morbidity.

Impact of burden and distribution of aortic valve calcification on the hemodynamic performance and procedural outcomes of a self-expanding, intra-annular transcatheter aortic valve system.

Aortic valve calcification (AVC) has been explored as a powerful predictor of procedural complications in patients undergoing transcatheter aortic valve implantation (TAVI). However, little evidence exists on its impact on intra-annular devices' performance. We aimed to investigate the impact of AVC burden and distribution pattern on the occurrence of paravalvular leak (PVL), conduction disturbances requiring permanent pacemaker implantation (PPI) and 30-day clinical outcomes in patients undergoing TAVI with a self-expanding, intra-annular device. According to AVC, 103 patients enrolled in a single medical centre from November 2019 to December 2022 were divided into tertiles. Valve Academic Research Consortium (VARC)-3 definitions were used to classify procedural complications and outcomes. Patients in the highest AVC tertile showed an increased occurrence of mild or more PVL and conduction disorders (p < 0.001 and p = 0.006). AVC tertiles (highest tertile) emerged as an independent predictor of PVL (OR 7.32, 95%CI 3.10-17.28, p < 0.001) and post-TAVI conduction disturbances (OR 3.73, 95%CI 1.31-10.60, p = 0.013) but not of PPI (OR 1.44, 95%CI 0.39-5.35, p = 0.579). Considering calcium distribution, ROC analyses revealed that annular AVC but not left ventricle outflow tract (LVOT) calcium burden significantly indicated the development of PVL (AUC 0.863, 0.77-0.93, p < 0.001) and conduction disorders/PPI (AUC 0.797, 0.70-0.89, p < 0.001 and 0.723, 0.58-0.86, p = 0.018, respectively). After adjustment for age and sex, the highest tertile remained an independent predictor of the 30-day composite outcome (death, myocardial infarction, stroke, major vascular complications, type 3/4 bleedings, acute kidney injury, PPI and ≥ moderate PVL) (OR 3.26; 95%CI 1.26-8.40, p = 0.014). A higher AVC is associated with an increased risk of PVL and conduction disturbances after TAVI with a self-expanding, intra-annular device. However, our findings suggest a minor role for LVOT calcification compared with annular AVC in the performance of this specific prosthesis.

Outcomes of leadless pacemaker implantation in the United States based on sex.

BACKGROUND: To determine differences in baseline characteristics and outcomes of leadless pacemaker implantation based on sex. METHODS: For the purpose of this study, data were extracted from the National Inpatient Sample database for years 2016-2020. The study group was then stratified based on sex. Baseline characteristics and in-hospital outcomes including complications were then analyzed in each group. Multivariable logistic regression models were created to analyze the association of sex with important outcomes of mortality, major complications (defined as pericardial effusion requiring intervention and any vascular complication), prolonged length of stay (defined as > 6 days), and increased cost of hospitalization (defined as median cost > 34,098$) after leadless pacemaker implantation. RESULTS: A total of 29,000 leadless pacemakers (n in women = 12,960, 44.7%) were implanted during our study period. Women were found to have an increased burden of co-morbidities as compared to men. In the adjusted analysis, the likelihood of mortality (aOR 1.27, 95% CI 1.14-1.43), major complications (aOR 1.07, 95% CI 0.98-1.18), prolonged length of stay (aOR 1.09, 95% CI 1.04-1.15), and increased hospitalization cost (aOR 1.14, 95% CI 1.08-1.20) were higher in women as compared to men after leadless pacemaker implantation. CONCLUSION: Important and significant differences exist in leadless pacemaker implantation in women as compared to men. These findings highlight the need for evaluating etiologies behind such differences with a goal of improving outcomes in all patients after leadless pacemaker implantation.

Taurolidine-containing solution for reducing cardiac implantable electronic device infection-early report from the European TauroPace™ registry.

INTRODUCTION: Infection is a significant complication of cardiac implantable electronic device (CIED) therapy. The European TauroPace™ Registry investigates the safety and efficacy of TauroPace™ (TP), an antimicrobial solution containing taurolidine, designed to prevent CIED infections. METHODS: This multicenter study included patients undergoing CIED procedures at participating centers where TP was used as a disinfectant for external hardware surfaces and an antiseptic for irrigating surgical sites. All patients eligible for CIED placement with adjunctive TP as the standard of care were included. Other aspects of CIED procedures adhered to current guidelines. Data on CIED-related infective endocarditis, CIED pocket infection, device and procedure-related complications, adverse events, and all-cause mortality were prospectively collected for 12 months. In cases of revision, the previous procedure was censored, and a new procedure was created. Binomial and Kaplan-Meier statistics were employed to analyze event rates. RESULTS: From January 2020 to November 2022, TP was used in 822 out of 1170 CIED procedures. Among patients who completed the 3-month follow-up, no CIED pocket infections were observed, and one case of CIED-related infective endocarditis was reported. In the 12-month follow-up cohort, two additional local pocket CIED infections were observed, resulting in a total of three major CIED infections within 1 year after the CIED placement procedure. The 3-month and 12-month major CIED infection rates were 0.125% and 0.51%, respectively. During the observation a complication rate of 4.4% was reported. No adverse events related to TP were observed. CONCLUSIONS: TP appears to be effective and safe in preventing CIED infections. CLINICALTRIALS: gov Identifier: NCT04735666.

Bilateral Pneumothorax After Unilateral Subclavian Vein Cannulation for Pacemaker Implantation: A Case Report.

Ipsilateral pneumothorax is a common complication of pacemaker implantation due to transvenous lead placement. We report a case of bilateral pneumothorax after unilateral subclavian vein cannulation for pacemaker implantation. An 85-year-old woman underwent dual-chamber pacemaker implantation for symptomatic atrioventricular block. The transvenous leads were inserted through the left subclavian vein under fluoroscopy and contrast venography, and bilateral pneumothorax was noted the day after implantation, although echocardiography and computed tomography showed no pericardial effusion or lead extrusion. A chest tube was placed in the left chest cavity, which was removed one week later without complications.

Embryo Development in a Stochastic Universe.

Despite the elucidation of the many processes by which a single eukaryotic cell develops into a complex mature organism, it is still puzzling to some biologists how it is that an unvarying, interconnected set of processes becomes coordinated and insulated from a stochastic universe. This article suggests that electromagnetic processes deriving from the chemistry of an organism may provide such coordination. Specifically, the author develops the pacemaker concept, the periodic, autonomous electrical signal to the entire embryo, the result of which, after each pulse, is to alter or enlarge the transcriptome to produce the next level of complexity and maturity of the organism.