A Revised Definition of Left Bundle Branch Block Using Time to Notch in Lead I.

Importance: Current left bundle branch block (LBBB) criteria are based on animal experiments or mathematical models of cardiac tissue conduction and may misclassify patients. Improved criteria would impact referral decisions and device type for cardiac resynchronization therapy. Objective: To develop a simple new criterion for LBBB based on electrophysiological studies of human patients, and then to validate this criterion in an independent population. Design, Setting, and Participants: In this diagnostic study, the derivation cohort was from a single-center, prospective study of patients undergoing electrophysiological study from March 2016 through November 2019. The validation cohort was assembled by retrospectively reviewing medical records for patients from the same center who underwent transcatheter aortic valve replacement (TAVR) from October 2015 through May 2022. Exposures: Patients were classified as having LBBB or intraventricular conduction delay (IVCD) as assessed by intracardiac recording. Main Outcomes and Measures: Sensitivity and specificity of the electrocardiography (ECG) criteria assessed in patients with LBBB or IVCD. Results: A total of 75 patients (median [IQR] age, 63 [53-70.5] years; 21 [28.0%] female) with baseline LBBB on 12-lead ECG underwent intracardiac recording of the left ventricular septum: 48 demonstrated complete conduction block (CCB) and 27 demonstrated intact Purkinje activation (IPA). Analysis of surface ECGs revealed that late notches in the QRS complexes of lateral leads were associated with CCB (40 of 48 patients [83.3%] with CCB vs 13 of 27 patients [48.1%] with IPA had a notch or slur in lead I; P = .003). Receiver operating characteristic curves for all septal and lateral leads were constructed, and lead I displayed the best performance with a time to notch longer than 75 milliseconds. Used in conjunction with the criteria for LBBB from the American College of Cardiology/American Heart Association/Heart Rhythm Society, this criterion had a sensitivity of 71% (95% CI, 56%-83%) and specificity of 74% (95% CI, 54%-89%) in the derivation population, contrasting with a sensitivity of 96% (95% CI, 86%-99%) and specificity of 33% (95% CI, 17%-54%) for the Strauss criteria. In an independent validation cohort of 46 patients (median [IQR] age, 78.5 [70-84] years; 21 [45.7%] female) undergoing TAVR with interval development of new LBBB, the time-to-notch criterion demonstrated a sensitivity of 87% (95% CI, 74%-95%). In the subset of 10 patients with preprocedural IVCD, the criterion correctly distinguished IVCD from LBBB in all cases. Application of the Strauss criteria performed similarly in the validation cohort. Conclusions and Relevance: The findings suggest that time to notch longer than 75 milliseconds in lead I is a simple ECG criterion that, when used in conjunction with standard LBBB criteria, may improve specificity for identifying patients with LBBB from conduction block. This may help inform patient selection for cardiac resynchronization or conduction system pacing.

Treatment of Neurocardiogenic Syncope: From Conservative to Cutting-edge.

Neurocardiogenic syncope is the most frequent cause of syncope in the general population. Many years have been spent on determining an effective treatment for this condition. Conventional treatment usually follows a tiered approach for neurocardiogenic syncope, as follows: first, lifestyle modification, including increased fluid intake and the introduction of physical counterpressure maneuvers, is tried; then the use of targeted pharmacologic therapy, particularly agents that support blood pressure or that drive blood pressure is attempted; and, finally, pacemaker implantation in patients with a predominant cardioinhibitory component to their syncopal episodes is performed. More recently, autonomic modulation with cardiac ganglion ablation has emerged as a promising treatment modality for patients refractory to traditional approaches. In this review, we sought to summarize the existing therapies for neurocardiogenic syncope and explore the latest research on new modalities of treatment.

Quantitative Association Between Peripapillary Bruch's Membrane Shape and Intracranial Pressure.

Purpose: The purpose of this study was to determine if there is a quantitative relationship between chronic intracranial pressure (ICP) and peripapillary Bruch's membrane (pp-BM) shape and to determine whether change in pp-BM shape can be detected within 1 hour after ICP lowering by lumbar puncture (LP). Methods: In this study, 30° nasal-temporal optical coherence tomography B-scans were obtained within 1 hour before and after LP in 39 eyes from 20 patients (age = 23-86 years, 75% female, ICP [opening pressure] = 10-55 cm H2O). A total of 16 semi-landmarks defined pp-BM on each image. Geometric morphometric analysis identified principal components of shape in the image set. Generalized estimating equation models, accounting for within-subject correlation, were used to identify principal components that were associated with chronic ICP (comparing pre-LP images between eyes) and/or acute ICP changes (comparing pre- and post-LP images within eyes). The pp-BM width and anterior pp-BM location were calculated directly from each image and were studied in the same manner. Results: Principal component 1 scalar variable on pre-LP images was associated with ICP (P < 0.0005). Principal component 4 magnitude changed within eyes after LP (P = 0.003). For both principal components 1 and 4, lower ICP corresponded with a more posterior position of pp-BM. Chronic ICP was associated with both pp-BM width (6.81 µm/cm H2O; P = 0.002) and more anterior location of temporal and nasal pp-BM margins (3.41, 3.49 µm/cm H2O; P < 0.0005, 0.002). Conclusions: This study demonstrates a quantitative association between pp-BM shape and chronic ICP level. Changes in pp-BM shape are detectable within 1 hour of lowering ICP. pp-BM shape may be a useful marker for chronic ICP level and acute ICP changes. Further study is needed to determine how pp-BM shape changes relate to clinical markers of papilledema.

Loss of lung WWOX expression causes neutrophilic inflammation.

The tumor suppressor WW domain-containing oxidoreductase (WWOX) exhibits regulatory interactions with an array of transcription factors and signaling molecules that are positioned at the well-known crossroads between inflammation and cancer. WWOX is also subject to downregulation by genotoxic environmental exposures, making it of potential interest to the study of lung pathobiology. Knockdown of lung WWOX expression in mice was observed to cause neutrophil influx and was accompanied by a corresponding vascular leak and inflammatory cytokine production. In cultured human alveolar epithelial cells, loss of WWOX expression resulted in increased c-Jun- and IL-8-dependent neutrophil chemotaxis toward cell monolayers. WWOX was observed to directly interact with c-Jun in these cells, and its absence resulted in increased nuclear translocation of c-Jun. Finally, inhibition of the c-Jun-activating kinase JNK abrogated the lung neutrophil influx observed during WWOX knockdown in mice. Altogether, these observations represent a novel mechanism of pulmonary neutrophil influx that is highly relevant to the pathobiology and potential treatment of a number of different lung inflammatory conditions.