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.

Cycle length statistics during human atrial fibrillation reveal refractory properties of the underlying substrate: a combined in silico and clinical test of concept study.

AIMS: The treatment of atrial fibrillation beyond pulmonary vein isolation has remained an unsolved challenge. Targeting regions identified by different substrate mapping approaches for ablation resulted in ambiguous outcomes. With the effective refractory period being a fundamental prerequisite for the maintenance of fibrillatory conduction, this study aims at estimating the effective refractory period with clinically available measurements. METHODS AND RESULTS: A set of 240 simulations in a spherical model of the left atrium with varying model initialization, combination of cellular refractory properties, and size of a region of lowered effective refractory period was implemented to analyse the capabilities and limitations of cycle length mapping. The minimum observed cycle length and the 25% quantile were compared to the underlying effective refractory period. The density of phase singularities was used as a measure for the complexity of the excitation pattern. Finally, we employed the method in a clinical test of concept including five patients. Areas of lowered effective refractory period could be distinguished from their surroundings in simulated scenarios with successfully induced multi-wavelet re-entry. Larger areas and higher gradients in effective refractory period as well as complex activation patterns favour the method. The 25% quantile of cycle lengths in patients with persistent atrial fibrillation was found to range from 85 to 190 ms. CONCLUSION: Cycle length mapping is capable of highlighting regions of pathologic refractory properties. In combination with complementary substrate mapping approaches, the method fosters confidence to enhance the treatment of atrial fibrillation beyond pulmonary vein isolation particularly in patients with complex activation patterns.

Safety and Feasibility of a Nocturnal Heart Rate Elevation-Exploration of a Novel Treatment Concept.

BACKGROUND: Diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF) are associated with myocardial fibrosis and concentric left ventricular hypertrophy (LVH). In a preclinical model of LVH, we demonstrated that a moderate increase in heart rate can reduce interstitial fibrosis and improve LV compliance. We therefore hypothesized that moderately elevated heart rates can be used to beneficially modify the myocardial substrate in patients with diastolic dysfunction and HFpEF. As a preliminary step to test this hypothesis, we evaluated if patients can tolerate this novel pacemaker-based treatment approach without adverse effects. METHODS AND RESULTS: A pacemaker-mediated increase in heart rate to 100 beats/min for 5 hours at night was tested over 4 weeks in 10 patients with diastolic dysfunction. The patients underwent a physical examination, biomarker collection, 6-minute walk test, heart failure questionnaire, and echocardiography before and after the pacing intervention. None of the patients reported any symptoms at night. No arrhythmias were induced. Eight patients completed the protocol. Three patients experienced unanticipated daytime pacing from an interfering pacemaker function. There were no detrimental changes in biomarkers or LV systolic function. CONCLUSIONS: Nocturnal pacing at a rate of 100 beats/min appears to be safe and well tolerated in this small exploratory patient cohort.

Honing in on optimal ventricular pacing sites: an argument for his bundle pacing.

OPINION STATEMENT: Frequent ventricular pacing is often or completely unavoidable in patients with high-grade or complete heart block. Over time, patients with high-burden RV pacing are at risk for developing symptomatic cardiomyopathy due to pacing-induced ventricular dyssynchrony. Growing awareness of this concern has generated interest in alternative pacing sites like the septum and outflow tract, the thinking being that these sites will more closely mimic His-Purkinje-mediated ventricular activation. Numerous studies have met with mixed results likely due to the fact that-to quote Marvin Gaye-there ain't nothing like the real thing. Herein lies the advantage of His bundle pacing (HBP), as it is the only pacing modality capable of physiological ventricular activation. HBP has been demonstrated to be safe and reliable in various forms of AV block with minimal drawbacks, namely modestly higher pacing thresholds when compared with other RV sites. Additionally, HBP is a truly physiologic alternative to biventricular pacing to effect cardiac resynchronization therapy (CRT), a concept supported by small observational and prospective studies. In our view, His bundle pacing should be considered in nearly all patients requiring ventricular pacing.

Mechanisms of Heart Block after Transcatheter Aortic Valve Replacement - Cardiac Anatomy, Clinical Predictors and Mechanical Factors that Contribute to Permanent Pacemaker Implantation.

Transcatheter aortic valve replacement (TAVR) has emerged as a valuable, minimally invasive treatment option in patients with symptomatic severe aortic stenosis at prohibitive or increased risk for conventional surgical replacement. Consequently, patients undergoing TAVR are prone to peri-procedural complications including cardiac conduction disturbances, which is the focus of this review. Atrioventricular conduction disturbances and arrhythmias before, during or after TAVR remain a matter of concern for this high-risk group of patients, as they have important consequences on hospital duration, short- and long-term medical management and finally on decisions of device-based treatment strategies (pacemaker or defibrillator implantation). We discuss the mechanisms of atrioventricular disturbances and characterise predisposing factors. Using validated clinical predictors, we discuss strategies to minimise the likelihood of creating permanent high-grade heart block, and identify factors to expedite the decision to implant a permanent pacemaker when the latter is unavoidable. We also discuss optimal pacing strategies to mitigate the possibility of pacing-induced cardiomyopathy.

Performance of a previously validated CT colonography computer-aided detection system in a new patient population.

OBJECTIVE: A computer-aided detection (CAD) system with high sensitivity in the detection of adenomatous polyps in varied CT colonography (CTC) data sets increases the utility of CAD in the clinical setting. The purpose of this study was to evaluate the standalone performance of an existing CAD system with a new set of CTC data from screening patients at an institution and geographic location different from those at which the CAD system was trained. MATERIALS AND METHODS: CTC data were collected from the records of 104 patients undergoing screening for colorectal neoplasia. Most of the patients were at average risk, had CTC findings suggestive of polyps, and underwent colonoscopy. Patients underwent cathartic bowel preparation, were given an oral contrast agent, and underwent imaging in the prone and supine positions. The patients had 86 adenomas confirmed at same-day optical colonoscopy; 47 of these tumors were 10 mm in diameter or larger, and 39 measured 6-9 mm. The CTC data were analyzed with an existing CAD system for colonography that was trained with previously acquired data. In a previous non-polyp-enriched screening cohort, the standalone performance of the CAD system was 93.3% (28/30) sensitivity for adenomatous polyps 10 mm or larger, 51.1% (47/92) sensitivity for adenomas 6-9 mm, and a mean false-positive rate of 8.6 per patient. Sensitivity comparisons were made with findings in the previous study. RESULTS: The CAD system had per-polyp sensitivities of 91.5% (43/47; 95% CI, 78.7-97.2%; p = 1.0) for adenomas 10 mm or larger and 82.1% (32/39; 65.9-91.9%; p = 0.0009) for adenomas 6-9 mm. The per-patient sensitivities were 97.6% (40/41; 85.6-99.9%; p = 0.6) for patients with adenomas 10 mm or larger and 82.4% (28/34; 64.8-92.6%; p = 0.047) for patients with adenomas 6-9 mm. The mean and median false-positive rates were 9.6 +/- 9.6 and 7.0 per patient, respectively. Common reasons for CAD misses (false-negative findings) were the presence of adherent contrast medium, flat adenomas, and adenomas located on or adjacent to normal colonic folds. In a random sample, 72.5% (29/40) of false-positive findings were attributable to folds or residual feces. CONCLUSION: The CAD system evaluated has a high level of performance in the detection of adenomatous polyps with CTC data from a polyp-enriched cohort different from that used to train the system.

CT colonography with computer-aided detection as a second reader: observer performance study.

PURPOSE: To evaluate the effect of computer-aided detection (CAD) as second reader on radiologists' diagnostic performance in interpreting computed tomographic (CT) colonographic examinations by using a primary two-dimensional (2D) approach, with segmental, unblinded optical colonoscopy as the reference standard. MATERIALS AND METHODS: This HIPAA-compliant study was IRB-approved with written informed consent. Four board-certified radiologists analyzed 60 CT examinations with a commercially available review system. Two-dimensional transverse views were used for initial polyp detection, while three-dimensional (3D) endoluminal and 2D multiplanar views were available for problem solving. After initial review without CAD, the reader was shown CAD-identified polyp candidates. The readers were then allowed to add to or modify their original diagnoses. Polyp location, CT Colonography Reporting and Data System categorization, and reader confidence as to the likelihood of a candidate being a polyp were recorded before and after CAD reading. The area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, and specificity were estimated for CT examinations with and without CAD readings by using multireader multicase analysis. RESULTS: Use of CAD led to nonsignificant average reader AUC increases of 0.03, 0.03, and 0.04 for patients with adenomatous polyps 6 mm or larger, 6-9 mm, and 10 mm or larger, respectively (P > or = .25); likewise, CAD increased average reader sensitivity by 0.15, 0.16, and 0.14 for those respective groups, with a corresponding decrease in specificity of 0.14. These changes achieved significance for the 6 mm or larger group (P < .01), 6-9 mm group (P < .02), and for specificity (P < .01), but not for the 10 mm or larger group (P > .16). The average reading time was 5.1 minutes +/- 3.4 (standard deviation) without CAD. CAD added an average of 3.1 minutes +/- 4.3 (62%) to each reading (supine and prone positions combined); average total reading time, 8.2 minutes +/- 5.8. CONCLUSION: Use of CAD led to a significant increase in sensitivity for detecting polyps in the 6 mm or larger and 6-9 mm groups at the expense of a similar significant reduction in specificity.

Polyps: linear and volumetric measurement at CT colonography.

PURPOSE: To retrospectively determine which of several computed tomographic (CT) colonography-based polyp measurements is most compatible with the linear measurement at optical colonoscopy and which is best for assessing change in polyp size. MATERIALS AND METHODS: This HIPAA-compliant study had institutional review board approval; informed consent was obtained. Prone and supine CT colonography with same-day optical colonoscopy was performed in 216 patients (147 men and 69 women; age range, 46-79 years; mean age, 59.2 years) with 338 polyps detected at CT colonography. Polyp size was measured with three linear measurements and two volume measurements. One linear measurement and one volume measurement were performed by using automated segmentation; remaining measurements were performed manually. Compatibility with linear size at optical colonoscopy and measurement reproducibility were assessed three ways: variation from size measurement at optical colonoscopy, change between prone and supine scans, and variability between observers. Confidence analysis assessed the ability of each measurement to identify polyps with an optical colonoscopy measurement of 1 cm or greater. RESULTS: Two hundred fifty-one segmentable polyps were present on both supine and prone scans. Linear polyp diameter manually measured on a three-dimensional endoluminally viewed surface (L(M3D)) indicated with 95% confidence that a polyp measured as 0.8 cm or smaller was less than 1.0 cm at optical colonoscopy. Prone and supine polyp size difference was smallest for L(M3D) and the linear diameter computed from manual and automated volume measurements, with interquartile ranges smaller than or equal to 0.3, 0.2, and 0.5 cm, respectively. Interobserver and intraobserver variability was smallest for linear polyp diameter measurements on a two-dimensional display, with a mean percentage difference of 2.8% (95% Bland-Altman limits of agreement: -17.8%, 23.4%) and 5.0% (95% Bland-Altman limits of agreement: -28.3%, 38.3%), respectively. CONCLUSION: L(M3D) best approximated polyp size measurements at optical colonoscopy. Linear diameter calculated from automated volume measurements showed the smallest variation between supine and prone scans while avoiding observer variability and may be best for assessing polyp size changes with serial examinations.