First-in-human noninvasive left ventricular ultrasound pacing: A potential screening tool for cardiac resynchronization therapy.

Background: A screening tool to predict response to cardiac resynchronization therapy (CRT) could improve patient selection and outcomes. Objective: The purpose of this study was to investigate the feasibility and safety of noninvasive CRT via transcutaneous ultrasonic left ventricular (LV) pacing applied as a screening test before CRT implants. Methods: P-wave-triggered ultrasound stimuli were delivered during bolus dosing of an echocardiographic contrast agent to simulate CRT noninvasively. Ultrasound pacing was delivered at a variety of LV locations with a range of atrioventricular delays to achieve fusion with intrinsic ventricular activation. Three-dimensional cardiac activation maps were acquired via the Medtronic CardioInsight 252-electrode mapping vest during baseline, ultrasound pacing, and after CRT implantation. A separate control group received only the CRT implants. Results: Ultrasound pacing was achieved in 10 patients with a mean of 81.2 ± 50.8 ultrasound paced beats per patient and up to 20 consecutive beats of ultrasound pacing. QRS width at baseline (168.2 ± 17.8 ms) decreased significantly to 117.3 ± 21.5 ms (P <.001) in the best ultrasound paced beat and to 125.8 ± 13.3 ms (P <.001) in the best CRT beat. Electrical activation patterns were similar between CRT pacing and ultrasound pacing with stimulation from the same area of the LV. Troponin results were similar between the ultrasound pacing and the control groups (P = .96), confirming safety. Conclusion: Noninvasive ultrasound pacing before CRT is safe and feasible, and it estimates the degree of electrical resynchronization achievable with CRT. Further study of this promising technique to guide CRT patient selection is warranted.

Machine learning for multidimensional response and survival after cardiac resynchronization therapy using features from cardiac magnetic resonance.

Background: Cardiac resynchronization therapy (CRT) response is complex, and better approaches are required to predict survival and need for advanced therapies. Objective: The objective was to use machine learning to characterize multidimensional CRT response and its relationship with long-term survival. Methods: Associations of 39 baseline features (including cardiac magnetic resonance [CMR] findings and clinical parameters such as glomerular filtration rate [GFR]) with a multidimensional CRT response vector (consisting of post-CRT left ventricular end-systolic volume index [LVESVI] fractional change, post-CRT B-type natriuretic peptide, and change in peak VO2) were evaluated. Machine learning generated response clusters, and cross-validation assessed associations of clusters with 4-year survival. Results: Among 200 patients (median age 67.4 years, 27.0% women) with CRT and CMR, associations with more than 1 response parameter were noted for the CMR CURE-SVD dyssynchrony parameter (associated with post-CRT brain natriuretic peptide [BNP] and LVESVI fractional change) and GFR (associated with peak VO2 and post-CRT BNP). Machine learning defined 3 response clusters: cluster 1 (n = 123, 90.2% survival [best]), cluster 2 (n = 45, 60.0% survival [intermediate]), and cluster 3 (n = 32, 34.4% survival [worst]). Adding the 6-month response cluster to baseline features improved the area under the receiver operating characteristic curve for 4-year survival from 0.78 to 0.86 (P = .02). A web-based application was developed for cluster determination in future patients. Conclusion: Machine learning characterizes distinct CRT response clusters influenced by CMR features, kidney function, and other factors. These clusters have a strong and additive influence on long-term survival relative to baseline features.

Pulsed Field Ablation: a Novel Therapeutic Tool for Catheter-Based Treatment of Atrial Fibrillation.

PURPOSE OF REVIEW: With catheter ablation of atrial fibrillation becoming increasingly common, the field of electrophysiology is searching for tools to improve procedural efficacy and safety. This review focuses on a novel ablation tool, pulsed field ablation, which promises to push the needle forward. Pulsed field ablation uses high-frequency electrical pulses to ablate cardiac tissue. RECENT FINDINGS: A number of pre-clinical and clinical studies have shown pulsed field ablation offers an efficient means of ablating cardiac tissue with minimal risk of collateral injury. Pulsed field ablation provides a non-thermal means of cardiac tissue ablation with minimal risk of injury to adjacent structures. Future studies will define the optimal current delivery, number of lesions needed to achieve the desired tissue effect, and how best to integrate pulsed field ablation catheters into 3-dimensional mapping systems.

Atrial Fibrillation and Objective Sleep Quality by Slow Wave Sleep.

BACKGROUND: Self-reported poor sleep quality has been suggested in patients with AF. Slow wave sleep (SWS) is considered the most restorative sleep stage and represents an important objective measure of sleep quality. The aim of this study was to compare quantity of SWS between patients with and without AF. METHODS AND RESULTS: We included patients with and without a documented history of AF by reviewing clinically indicated polysomnography data from a single sleep center. Patients on medications with potential influence on sleep architecture were excluded. Logistic regression was performed to determine the association between AF and SWS time (low vs. high) adjusting for age, gender, body mass index, and sleep apnea. In a 2:1 case-control set-up, a total of 205 subjects (139 with AF, 66 without AF) were included. Mean age was 62 (SD: 14.3) years and 59% were men. Patients with AF had lower SWS time (11.1 vs. 16.6 min, p=0.02). In multivariable analysis, prevalent AF was associated with low SWS independent of sleep apnea and other potential confounders (OR 2.5 [1.3, 5.0], p=0.006). Limiting the analysis to patients whose total sleep time was greater than 4 hours (by excluding N=31) resulted in more robust results (OR 3.9 [1.7, 9.7]. p=0.002). CONCLUSION: AF is associated with more impaired sleep quality as indicated by lower quantity of SWS. More studies are needed to explore the mechanistic interactions between AF and sleep.

Recurrent Atrial Fibrillation After Catheter Ablation: Considerations For Repeat Ablation And Strategies To Optimize Success.

Recurrent AF after catheter ablation occurs in at least 20 to 40% of patients. Repeat ablation is primarily considered for those with symptomatic AF recurrences (often drug-refactory) occurring at least 3 months or more post-ablation. Pulmonary vein reconnection is almost universally encountered, and repeat isolation of electrically connected pulmonary veins should be the primary ablation strategy. Beyond repeat PVI and possible ablation of non-PV triggers, there is little to no evidence that additional substrate modification improves outcomes. In addition to repeat ablation, it is critical to address and treat comorbid conditions which increase arrhythmia risk post-ablation. Specifically, obesity, hypertension, and sleep-disordered breathing should be targeted and modified to increase the likelihood of success.

Effectiveness of integrating delayed computed tomography angiography imaging for left atrial appendage thrombus exclusion into the care of patients undergoing ablation of atrial fibrillation.

BACKGROUND: Computed tomography angiography (CTA) can identify and rule out left atrial appendage (LAA) thrombus when delayed imaging is also performed. OBJECTIVE: In patients referred for CTA to evaluate pulmonary vein anatomy before the ablation of atrial fibrillation (AF) or left atrial flutter (LAFL), we sought to determine the effectiveness of a novel clinical protocol for integrating results of CTA delayed LAA imaging into preprocedure care. METHODS: After making delayed imaging of the LAA part of our routine preablation CTA protocol, we integrated early reporting of preablation CTA LAA imaging results into clinical practice as part of a formal protocol in June 2013. We then analyzed the effectiveness of this protocol by evaluating 320 AF/LAFL ablation patients with CTA imaging during the time period 2012-2014. RESULTS: In CTA patients with delayed LAA imaging, the sensitivity and negative predictive values for LAA thrombus using intracardiac echocardiography or transesophageal echocardiography (TEE) as the reference standard were both 100%. Intracardiac echocardiography during ablation confirmed the absence of thrombus in patients with negative CTA or negative TEE results. No patients with either negative CTA results or equivocal CTA results combined with negative TEE results had strokes or transient ischemic attacks. Overall, the need for TEE procedures decreased from 57.5% to 24.0% during the 3-year period because of the CTA protocol. CONCLUSION: Clinical integration of CTA delayed LAA imaging into the care of patients having catheter ablation of AF or LAFL is feasible, safe, and effective. Such a protocol could be used broadly to improve patient care.

Catheter Ablation of Arrhythmia During Pregnancy.

Cardiac arrhythmia as a complication of pregnancy can be problematic to maternal health and fetal life and development. Catheter ablation of tachyarrhythmias during pregnancy has been successfully performed in selected patients with limited experience. Techniques to limit maternal and fetal radiation exposure, including intracardiac echo and electroanatomic mapping systems, are particularly important in this setting. Specific accommodations are necessary in the care of the gravid patient during catheter ablation.

Major complications and mortality within 30 days of an electrophysiological procedure at an academic medical center: implications for developing national standards.

BACKGROUND: Despite growing attention to performance and quality measures, national standards for reporting of outcomes after all electrophysiology (EP) procedures have not yet been developed. We sought to characterize the incidence and timing of adverse events up to 30 days after EP procedures at a tertiary academic medical center. METHODS AND RESULTS: We prospectively followed all patients undergoing EP procedures between January 2010 and September 2012. All were followed for 30 days postprocedure either in clinic or by telephone. Major complications were defined as events related to the procedure that led to prolongation of hospital stay or readmission, required additional procedural intervention, or resulted in death or significant injury. These were further categorized as intraprocedure, postprocedure, or postdischarge events. Seven EP physicians collectively adjudicated whether complications were directly related to the procedure. A total of 3,213 procedures were performed. Major complications occurred in 2.2% of patients; 49% of these events occurred after discharge. Death occurred in 0.6% of patients; 73% of these deaths were found to be secondary to worsening of the patient's underlying comorbid conditions and unrelated to the procedure. CONCLUSIONS: When considering national standards for reporting outcomes of all EP procedures, continued follow-up after discharge is important. In our cohort, half of major complications occurring within 30 days occurred after discharge. In addition, three-quarters of deaths within 30 days were not directly related to the procedure and caution should be used in using all-cause mortality as an outcome measure for EP procedures.

Impact of mechanical activation, scar, and electrical timing on cardiac resynchronization therapy response and clinical outcomes.

OBJECTIVES: Using cardiac magnetic resonance (CMR), we sought to evaluate the relative influences of mechanical, electrical, and scar properties at the left ventricular lead position (LVLP) on cardiac resynchronization therapy (CRT) response and clinical events. BACKGROUND: CMR cine displacement encoding with stimulated echoes (DENSE) provides high-quality strain for overall dyssynchrony (circumferential uniformity ratio estimate [CURE] 0 to 1) and timing of onset of circumferential contraction at the LVLP. CMR DENSE, late gadolinium enhancement, and electrical timing together could improve upon other imaging modalities for evaluating the optimal LVLP. METHODS: Patients had complete CMR studies and echocardiography before CRT. CRT response was defined as a 15% reduction in left ventricular end-systolic volume. Electrical activation was assessed as the time from QRS onset to LVLP electrogram (QLV). Patients were then followed for clinical events. RESULTS: In 75 patients, multivariable logistic modeling accurately identified the 40 patients (53%) with CRT response (area under the curve: 0.95 [p < 0.0001]) based on CURE (odds ratio [OR]: 2.59/0.1 decrease), delayed circumferential contraction onset at LVLP (OR: 6.55), absent LVLP scar (OR: 14.9), and QLV (OR: 1.31/10 ms increase). The 33% of patients with CURE <0.70, absence of LVLP scar, and delayed LVLP contraction onset had a 100% response rate, whereas those with CURE ≥0.70 had a 0% CRT response rate and a 12-fold increased risk of death; the remaining patients had a mixed response profile. CONCLUSIONS: Mechanical, electrical, and scar properties at the LVLP together with CMR mechanical dyssynchrony are strongly associated with echocardiographic CRT response and clinical events after CRT. Modeling these findings holds promise for improving CRT outcomes.

Postprocedure mapping of cardiac resynchronization lead position using standard fluoroscopy systems: implications for the nonresponder with scar.

BACKGROUND: The relationship between cardiac resynchronization therapy (CRT), left ventricular (LV) lead position, scar, and regional mechanical function influences CRT response. OBJECTIVE: To determine LV lead position relative to LV structural characteristics in standard clinical practice, we developed and validated a practical yet mathematically rigorous method to register procedural fluoroscopic LV lead position with pre-CRT cardiac magnetic resonance (CMR). METHODS: After one-time calibration of the standard fluoroscopic suite, we identified the projected CMR LV lead position using three reference landmarks on both CMR and fluoroscopy. This predicted lead position was validated in a canine model by histology and in eight "validation group" patients based on postoperative computed tomography scans (n = 7) or CMR coronary sinus venography (n = 1). The methodology was applied in an additional eight patients with CRT nonresponse and infarction-related myocardial scar. RESULTS: The projected and actual lead positions were within 1.2 mm in the canine model. The median distance between projected and actual lead positions for the validation group (n = 8) and animal validation case was 11.3 mm (interquartile range 9.2-14.6 mm). In the application (nonresponder) group (n = 8), the lead mapped to the scar periphery in three patients, the core of the scar in one patient, and more than 3 cm from scar in four patients. CONCLUSIONS: This methodology projects procedural fluoroscopic LV lead position onto pre-CRT CMR using standard fluoroscopic equipment and a one-time calibration, enabling assessment of LV lead position with sufficient accuracy to identify the lead position relative to regional function and infarction-related scar in CRT nonresponders.