Fecal calprotectin: A novel predictor of ulcerated esophageal injury after atrial fibrillation catheter ablation.

BACKGROUND: Atrial esophageal fistula (AEF) is a lethal complication that can occur post atrial fibrillation (AF) ablation. Esophageal injury (EI) is likely to be the initial lesion leading to AEF. Endoscopic examination is the gold standard for a diagnosis of EI but extensive endoscopic screening is invasive and costly. This study was conducted to determine whether fecal calprotectin (Fcal), a marker of inflammation throughout the intestinal tract, may be associated with the existence of esophageal injury. METHODS: This diagnostic study was conducted in a cohort of 166 patients with symptomatic AF undergoing radiofrequency catheter ablation from May 2020 to June 2021. Fcal tests were performed 1-7 days after ablation. All patients underwent endoscopic ultrasonography 1 or 2 days after ablation. RESULTS: The levels of Fcal were significantly different between the EI and non-EI groups (404.9 µg/g (IQR 129.6-723.6) vs. 40.4 µg/g (IQR 15.0-246.2), p < .001). Analysis of ROC curves revealed that a Fcal level of 125 µg/g might be the optimal cut-off value for a diagnosis of EI, giving a 78.8% sensitivity and a 65.4% specificity. The negative predictive value of Fcal was 100% for ulcerated EI. CONCLUSIONS: The level of Fcal is associated with EI post AF catheter ablation. 125 µg/g might be the optimal cut-off value for a diagnosis of EI. Negative Fcal could predict the absence of ulcerated EI, which could be considered a precursor to AEF.

Respiratory control minimizes diaphragmatic contraction and dry cough during pulsed-field ablation of atrial fibrillation.

AIMS: Pulsed-field ablation (PFA) is a promising new ablation modality to treat atrial fibrillation. However, PFA can cause varying degrees of diaphragmatic contraction and dry cough, especially under conscious sedation. This prospective study presents a method to minimize the impact of PFA on diaphragmatic contraction and dry cough during the procedure. METHODS AND RESULTS: Twenty-eight patients underwent PFA for pulmonary vein (PV) and superior vena cava isolation under conscious sedation. Each patient received two groups of ablations in each vein: the control group allowed PFA application during any phase of respiratory cycle, while the test group used respiratory control, delivering PFA energy only at the end of expiration. A rating score system was developed to assess diaphragmatic contraction and dry cough. A total of 1401 control ablations and 4317 test ablations were performed. The test group had significantly lower scores for diaphragmatic contraction (P < 0.01) and dry cough (P < 0.001) in all PVs compared to the control group. The average relative reductions in scores for all PVs were 33-47% for diaphragmatic contraction and 67-83% for dry cough. The percentage of ablations with scores ≧2 for diaphragmatic contraction decreased significantly from 18.5-28.0% in the control group to 0.4-2.6% in the test group (P < 0.001). For dry cough, the percentage decreased from 11.9-43.7% in the control group to 0.7-2.1% in the test group. CONCLUSION: Pulsed-field ablation application at the end of expiration can reduce the severity of diaphragmatic contraction and eliminate moderate and severe dry cough during PV isolation performed under conscious sedation.

Intracardiac echocardiography is a safe and effective alternative to transesophageal echocardiography for left atrial appendage thrombus evaluation at the time of atrial fibrillation ablation: The ICE-TEE study.

BACKGROUND: Intracardiac echocardiography (ICE) technology has been increasingly accepted as an integral part of atrial fibrillation (AF) ablation procedures. It is still unknown whether ICE can routinely replace transesophageal echocardiography (TEE) for routine thrombus screening in non-selective AF patients. OBJECTIVE: To assess whether ICE can routinely replace TEE in screening for left atrial (LA)/left atrial appendage (LAA) thrombus in general patients undergoing catheter ablation for AF. METHODS: A total of 2003 consecutive patients undergoing AF ablation were included. 1155 patients (ICE group) received intra-procedural ICE examination for LA/LAA thrombus screening, while 848 patients (TEE group) received pre-procedure TEE examination. The incidence of thrombus, peri-procedure complications, and hospital efficiency were assessed. RESULTS: The LA and LAA were adequately visualized in all patients. Five patients in the ICE group and 15 patients in the TEE group were found to have LAA thrombus. The incidence of major periprocedural thrombo-embolic events was comparable between two groups (0.2% vs. 0.1%, p = .76), none were due to undetected LA/LAA thrombus. Other major periprocedural complications occurred at similar rates in both groups, while post-procedure fever was less common in the ICE group (12.7% vs. 17.4%, p < .001). Procedure times and hospital length of stay were both shorter in the ICE group (142 min [87-197 min] vs. 150 min [95-205 min], and 3[2-4] day vs. 4[3-5] day, respectively, both p < .001). CONCLUSIONS: ICE can replace TEE for atrial thrombus screening in AF patients undergoing ablation without increased complications. An "ICE replacing TEE" workflow can also reduce the incidence of postoperative fever and improve hospital efficiency.

Catheter ablation for persistent atrial fibrillation with left ventricular systolic dysfunction: Who is the best candidate?

BACKGROUND: Tachycardia-induced cardiomyopathy is poorly recognized pre-ablation. It remains unclear of better patient selection and timing for catheter ablation in persistent atrial fibrillation (PerAF) with heart failure (HF). METHODS: Consecutive patients with PerAF and left ventricular ejection fraction (LVEF) <50% referred for AF ablation were retrospectively included. The impact of LV size, heart rate (HR), and LVEF pre-ablation were analyzed for assessing LV systolic function recovery, defined as LVEF increase of ≥20% or to a value ≥55% after ablation. RESULTS: A total of 120 patients (2017-2020) were included. After 19 ±14 months post ablation, LVEF improvement was similar in patients with normal or dilated LV (18.3 ± 9.4% vs. 16.1 ± 10.8%, P = .25), rapid or controlled HR (19.5 ± 10% vs. 16.1 ± 10%, P = .09), but higher in HFrEF (HF with reduced EF) than HFmrEF (HF with midrange EF) (21.6 ± 10.3% vs. 14.9 ± 9.3%, P < .01). There was more LV systolic function recovery in those with normal to moderate LV dilation (80%, odds ratio [OR] 15.22, P < .01), HR ≥80 bpm (79%, OR 5.38, P < .01) and HFmrEF (80%, OR 4.03, P < .01). The overall AF freedom was similar between normal and dilated LV (59% vs. 62%, P = .95), rapid and controlled HR (67% vs. 56%, P = .18), and HFmrEF and HFrEF (65% vs. 50%, P = .19). CONCLUSION: Catheter ablation is effective independent of LV dilation, rate control or HFrEF. Patients with normal to moderate LV dilation, resting HR ≥80 bpm and HFmrEF may be candidates for early PerAF ablation to achieve LVEF normalization.

Adjunctive percutaneous ablation targeting epicardial arrhythmogenic structures in patients of atrial fibrillation with recurrence after multiple procedures.

INTRODUCTION: Repeat ablation strategy for atrial fibrillation (AF) recurrence after multiple ablation procedures is known to be challenging. This study evaluated the insights of adjunctive ablation for epicardial arrhythmogenic substrates in those patients via a percutaneous epicardial approach. METHODS AND RESULTS: Thirty-five consecutive patients with AF/atrial tachycardia (AT) recurrence, who had two or more prior ablation procedures, were enrolled from September 2016 to December 2018. In addition to a standard endocardial approach, epicardial mapping and ablation were performed via a percutaneous subxiphoid access in the electrophysiology lab. Adjunctive epicardial ablations for left lateral ridge (LLR) were performed in 31 of 35 patients (88.6%) for efficient transmural lesions with pacing capture loss. Marshall Bundle (MB) potentials were documented on epicardial LLR in three patients and abolished by direct epicardial ablation. Bachmann's bundle (BB) was ablated as an epicardial conduction gap in four patients with a refractory anterior wall line. Two epicardial AT/AF triggers were detected followed by successful termination with epicardial ablation. No periprocedural complications occurred. About 23 of 35 patients (65.7%) remained free from AF/AT after 23.2 ± 9 months of the procedure. CONCLUSIONS: Patients with multiple failed prior AF procedures refractory to antiarrhythmic therapy might warrant a percutaneous epicardial mapping and ablation strategy, with adjunctive therapy for targeting LLR/MB, BB, and underlying epicardial triggers in addition to a standard endocardial approach.

Intraprocedural endpoints to predict durable pulmonary vein isolation: a randomized trial of four post-ablation techniques.

AIMS: The optimal procedural endpoint to achieve permanent pulmonary vein isolation (PVI) during ablation of atrial fibrillation (AF) remains unknown. We aimed to compare the impact of prolonged waiting periods and adenosine triphosphate (ATP) testing after PVI on long-term freedom from AF. METHODS AND RESULTS: In total, 538 patients (median age 61 years, 62% male) undergoing first-time radiofrequency ablation for paroxysmal AF were randomized into four groups: Group 1 [PVI (no testing), n = 121], Group 2 (PVI + 30min waiting phase, n = 151), Group 3 (PVI+ATP, n = 131), and Group 4 (PVI + 30min+ATP, n = 135). The primary endpoint was freedom from AF. Repeat mapping to assess for late pulmonary vein (PV) reconnection was performed in patients who remained AF-free for >3 years (n = 46) and in those who had repeat ablation for AF recurrence (n = 82). During initial procedure, acute PV reconnection was observed in 33%, 26%, and 42% of patients in Groups 2, 3, and 4, respectively. At 36 months, no significant differences in freedom from AF recurrence were observed among all four groups (55%, 61%, 50%, and 62% for Groups 1, 2, 3, and 4, respectively; P = 0.258). Late PV reconnection was commonly observed, with a similar incidence between patients with and without AF recurrence (74% vs. 83%; P = 0.224). CONCLUSION: Although PVI remains the cornerstone for AF ablation, intraprocedural techniques to assess for PV reconnection did not improve long-term success. Patients without AF recurrence after 3 years exhibited similarly high rates of PV reconnection as those that underwent repeat ablation for AF recurrence. The therapeutic mechanisms of AF ablation may not be solely predicated upon durable PVI.

Risk of esophageal thermal injury during catheter ablation for atrial fibrillation guided by different ablation index.

BACKGROUND: During ablation for atrial fibrillation (AF), energy delivery toward the left atrial posterior wall may cause esophageal injury (EI). Ablation index (AI) was introduced to estimate ablation lesion size, however, the impact of AI technology on the risk of EI has not been explored. METHOD: From March 2019 to December 2019, 60 patients with paroxysmal AF undergoing first-time ablation were prospectively enrolled. The first 30 consecutive patients were ablated with the AI target value of 400 (AI-400 group), and the later 30 consecutive patients were ablated with the AI target value of 350 at the posterior wall (AI-350 group). Endoscopic ultrasonography was used to evaluate EI postablation. EI was classified as a category 1 (erythema or erosion) or a category 2 (hematoma or ulceration). RESULTS: Compared with the AI-400 group (59.9 ± 8.4 years; male, 60%), the AI-350 group (59.1 ± 9.9 years; male, 50%) had a lower incidence of EI (3.3% vs 26.7%, P = .03). There was no significant difference in the percentage of first-pass PVI between the AI-400 group and the AI-350 group (left PVI: 80% vs 73.4%, P = .54; right PVI: 80% vs 60%, P = .1). Neither ablation time nor fluoroscopy time was significantly different between the AI-400 group and the AI-350 group. CONCLUSIONS: AF ablation guide by AI target value of 350 may reduce esophageal thermal injury and has a similar efficiency on the acute success rate of first-pass PVI compared with an AI target value of 400 at the posterior wall.

Esophageal contraction during cryoablation: A possible protective mechanism.

BACKGROUND: Contraction of the esophagus was observed during cryoablation for paroxysmal atrial fibrillation (PAF). The purpose of this study is to investigate the mechanism of esophageal contraction and the correlation between the contraction and esophageal thermal lesions. METHODS: This prospective study enrolled 64 patients with PAF undergoing second-generation cryoballoon (CB2) ablation for pulmonary vein isolation (PVI). During PVI for the left inferior pulmonary vein, contrast esophagography was performed before and during cryoablation. The sample population was divided into two groups: A (31 patients) and B (33 patients). Group A consisted of patients in whom the distal half of the CB was in proximity to the esophagus, while for group B the esophagus was away from the distal half of the CB. Esophageal contraction was recorded as a variation in the width of the esophageal lumen during PVI. Postablation esophageal endoscopy was done on all patients. RESULTS: The reduction in the width of the esophageal lumen in group A was greater than in group B during freezing (40.12 ± 23.24% vs 8.14 ± 10.35%, P < .001). Following endoscopy, no apparent esophageal lesion was detected in all patients. CONCLUSION: The extent of esophageal contraction is correlated with the positioning of the esophagus at the distal half of the CB. The findings of this study indicate that esophageal contraction during freezing may be a self-protective mechanism.

Impact of Anatomically Guided Ganglionated Plexus Ablation on Electrical Firing from Isolated Pulmonary Veins.

BACKGROUND: The mechanisms underlying atrial fibrillation (AF) initiation and pulmonary vein isolation (PVI) effectiveness remain unclear. Ganglionated plexus (GPs) have been implicated in AF initiation and maintenance. In this study, we evaluated the impact of GP ablation in patients with pulmonary vein (PV) firing after PVI. METHODS: Patients with drug-refractory paroxysmal AF undergoing radiofrequency catheter ablation therapy with PVI were screened. Among 840 cases over a 3.75-year period, 12 cases were identified with persistent PV firing (left = 4 and right = 8) after PVI was achieved and left atrial sinus rhythm restored. Adjacent GP ablation was performed anatomically and followed if necessary by additional PV ablation. RESULTS: In eight patients, PV firing was terminated during GP ablation outside of the circumferential ablation line. In one patient, additional PV ablation resulted in cessation of PV firing and in the remaining three patients, firing could not be terminated by GP ablation or additional PVI. CONCLUSION: GP ablation outside of wide antral circumferential line frequently results in the cessation of rapid firing from electrically isolated PVs. These observations suggest that interactions between left atrium and PV beyond electrical conduction warrant consideration in AF mechanisms.

Marked suppression of pulmonary vein firing after circumferential pulmonary vein isolation in patients with paroxysmal atrial fibrillation: is pulmonary vein firing an epiphenomenon?

INTRODUCTION: Rapid firing in pulmonary veins (PVs) is a leading cause of paroxysmal atrial fibrillation. We hypothesized that PV firing (PV-F) should continue after circumferential PV isolation (CPVI) because the PV tissue responsible for PV-F remains intact. METHODS AND RESULTS: In Group-1 (n = 92), isoproterenol (ISP) and adenosine triphosphate (ATP) were co-administered to provoke PV-F before and after CPVI. The site of rapid focal discharge that initiated atrial fibrillation (AF) defined PV-F versus non-PV-F. Additional 17 patients with PV-F induced by ISP+ATP before CPVI were enrolled into Group-2 and various pacing maneuvers were used in conjunction to ISP+ATP to provoke PV-F after CPVI. In Group-1, AF was induced in 47/81 (58.0%) and 16/88 (18.2%) patients before and after CPVI, respectively (P < 0.01). Before CPVI, 43/47 (91.5%) of the rapid firing originated from PV. After successful CPVI, 88/92 patients were in sinus rhythm and non-PV-F was induced in 14/88 patients. PV-F was induced in 2/88 patients, which was eliminated by ganglionated plexus ablation outside the CPVI line. In Group-2, various pacing maneuvers with ISP+ATP only induced PV-F in 1/17 patients after CPVI. CONCLUSION: Marked suppression of PV-F after CPVI strongly suggests that the real source of PV-F is located in the atrium. PV-F may be an epiphenomenon.

A convergence analysis for projected fast iterative soft-thresholding algorithm under radial sampling MRI.

Radial sampling is a fast magnetic resonance imaging technique. Further imaging acceleration can be achieved with undersampling but how to reconstruct a clear image with fast algorithm is still challenging. Previous work has shown the advantage of removing undersampling image artifacts using the tight-frame sparse reconstruction model. This model was further solved with a projected fast iterative soft-thresholding algorithm (pFISTA). However, the convergence of this algorithm under radial sampling has not been clearly set up. In this work, the authors derived a theoretical convergence condition for this algorithm. This condition was approximated by estimating the maximal eigenvalue of reconstruction operators through the power iteration. Based on the condition, an optimal step size was further suggested to allow the fastest convergence. Verifications were made on the prospective in vivo data of static brain imaging and dynamic contrast-enhanced liver imaging, demonstrating that the recommended parameter allowed fast convergence in radial MRI.

False Tendons in the Left Ventricle: Implications for Successful Ablation of Left Posterior Fascicular Tachycardias.

BACKGROUND: The anatomical substrate for left posterior fascicular ventricular tachycardia (LPF-VT) is still unclear. OBJECTIVES: The purpose of this study is to describe the endocavitary substrate of the re-entrant loop of LPF-VT. METHODS: A total of 26 consecutive patients with LPF-VT underwent an electrophysiology study and radiofrequency ablation. RESULTS: Intracardiac echocardiography imaging observed a 100% prevalence of false tendons (FTs) at the left posterior septal region in all patients, and 3 different types of FTs could be classified according to their location. In 22 patients, a P1 potential could be recorded via the multielectrode catheter from a FT. In 4 patients without a recorded P1 during LPF-VT, the earliest P2 potentials were recorded from a FT in 3 patients, and from a muscular connection between 2 posteromedial papillary muscles in 1 patient. Catheter ablation focused on the FTs with P1 or earliest P2 (in patients without P1) was successful in all 26 patients. After 19 ± 8.5 months of follow-up, no patients had recurrence of LPF-VT. CONCLUSIONS: FTs provide an electroanatomical substrate for LPF-VT and a "culprit FT" may be identified as the critical structure bridging the macro-re-entrant loop. Targeting the "culprit FT" is a novel anatomical ablation strategy that results in long-term arrhythmia-free survival.

Feasibility and safety of both His bundle pacing and left bundle branch area pacing in atrial fibrillation patients: intermediate term follow-up.

PURPOSE: His bundle pacing (HBP) improves heart failure (HF) in atrial fibrillation (AF) pacing-dependent patients with a potential for a progressively increased threshold. HBP with right ventricular pacing (RVP) as a backup is always the preferred choice; however, RVP may induce HF. His Purkinje system pacing (HPSP) includes HBP and left bundle branch area pacing (LBBAP). LBBAP maintains left ventricular synchrony but has not been proven to be safe over the long term. We assessed the feasibility and safety of both HBP and LBBAP in AF pacing-dependent patients and compared the parameters of both leads at baseline and at the 6-month follow-up. METHODS: A total of 16 AF patients in our center, who successfully attempted both HBP and LBBAP, were prospectively enrolled unless only one of these treatment statuses was attained. The electrocardiogram characteristics, leading parameters, echocardiography results, and clinical outcomes were assessed. RESULTS: Thirteen out of 16 patients achieved both HBP and LBBAP successfully in the same AF pacing-dependent patients. In symptomatic HF patients with preserved left ventricular ejection fraction (LVEF) (n = 10), the left ventricular end-diastolic diameter (LVEDD) was reduced from 51.8 ± 4.4 to 48.3 ± 3.1 mm (p = 0.01) with the use of diuretics, either reduced or stopped (n = 7). During the follow-up, one patient in the group without HF had an increased HBP threshold and developed HF symptoms. His HF symptoms disappeared when switched into LBBAP mode. Another patient in the group with HF got his LVEF elevated by HBP for 3 months by utilizing left bundle branch block(LBBB)correction and continued to increase when switched into LBBAP for another 3 months due to an increased HBP correction threshold. The average unipolar pacing threshold of LBBAP was lower than that of HBP. No perforation or dislodgement occurred in our study. CONCLUSION: Both HBP and LBBAP could be attempted successfully in the same AF patients when one of the two modes could be adopted and switched according to the clinical feasibility. Compared with HBP, LBBAP yielded better and more stable parameters but showed comparable effects during the 6-month follow-up.

His bundle pacing versus left bundle branch pacing on ventricular function in atrial fibrillation patients referred for pacing: a prospective crossover comparison.

BACKGROUND: His bundle pacing (HBP) and left bundle branch pacing (LBBP) both provide physiologic pacing which maintain left ventricular synchrony. They both improve heart failure (HF) symptoms in atrial fibrillation (AF) patients. We aimed to assess the intra-patient comparison of ventricular function and remodeling as well as leads parameters corresponding to two pacing modalities in AF patients referred for pacing in intermediate term. METHODS: Uncontrolled tachycardia AF patients with both leads implantation successfully were randomized to either modality. Echocardiographic measurements, New York Heart Association (NYHA) classification, quality-of-life assessments and leads parameters were obtained at baseline and at each 6-month follow up. Left ventricular function including the left ventricular endo-systolic volume (LVESV), left ventricular ejection fraction (LVEF) and right ventricular (RV) function quantified by tricuspid annular plane systolic excursion (TAPSE) were all assessed. RESULTS: Consecutively twenty-eight patients implanted with both HBP and LBBP leads successfully were enrolled (69.1 ± 8.1 years, 53.6% male, LVEF 59.2% ± 13.7%). The LVESV was improved by both pacing modalities in all patients (n = 23) and the LVEF was improved in patients with baseline LVEF at less than 50% (n = 6). The TAPSE was improved by HBP but not LBBP (n = 23). CONCLUSION: In this crossover comparison between HBP and LBBP, LBBP was found to have an equivalent effect on LV function and remodeling but better and more stable parameters in AF patients with uncontrolled ventricular rates referred for atrioventricular node (AVN) ablation. HBP could be preferred in patients with reduced TAPSE at baseline rather than LBBP.

ICE-Derived Left Atrial and Left Ventricular Endocardial and Myocardial Speckle Tracking Strain Patterns in Atrial Fibrillation at the Time of Radiofrequency Ablation.

Objectives: Intracardiac echocardiography(ICE) has excellent imaging resolution and border recognition which increase strain measurement accuracy. We hypothesized that left atrial(LA) substrate and functional impairment can be detected by measuring LA strain deformation in patients with persistent and paroxysmal atrial fibrillation(AF), as compared to those with no AF. Strain deformation changes in LA and left ventricle(LV) can also be assessed post-ablation to determine its effect. Methods: ICE-derived speckle tracking strain(STS) was prospectively performed in 96 patients, including 62 patients with AF(31 persistent and 31 paroxysmal AF) pre-/post-ablation, and 34 patients with no AF. We measured major strain parameters including longitudinal segmental(endo/myocardial) "average peak overall strain of all segments"(PkAll), peak strain rate(SR),and different time-to-peak strain in LA and LV images. Results: At baseline, persistent AF patients had significantly lower(p<0.01) LA endocardial(4.3±2.5 vs. 20.3±8.9 and 25.5±12.9 %) and myocardial PkAll(4.4±2.6 vs. 15.7±7.2 and 20.9±9.2 %), endocardial(0.9±0.4 vs. 1.8±0.7 and 2.2±0.6 1/s) and myocardial peak SR(0.7±0.4 vs. 1.5±0.6 and 1.9±0.5 1/s), as compared to paroxysmal AF and no AF patients. After successful ablation, endo-/myocardial LA PkAll and peak SR were significantly improved, most dramatically in patients with persistent AF. LV endocardial/myocardial strain and SR also improved in AF patients post-ablation. Conclusion: LA longitudinal strain(%)/SR(1/s) parameters in AF patients are more abnormal than those with no AF, suggesting LA substrate/functional damage. AF ablation improved LA strains/SR but with values in paroxysmal > persistent AF suggesting background LA damage in persistent AF.

Selective Interventricular Septal Radiofrequency Ablation in Patients With Hypertrophic Obstructive Cardiomyopathy: Who Can Benefit?

Introduction: Septal mass reduction is beneficial for hypertrophic obstructive cardiomyopathy (HOCM) patients with severe left ventricular outflow (LVOT) gradient and symptoms, with surgical myectomy or alcohol septal ablation (ASA) currently recommended in selected patients. Radiofrequency (RF) ablation of hypertrophied septum has been published as a novel method to alleviate LVOT obstruction in small populations. This study aims to investigate factors influencing clinical outcomes of radiofrequency septum ablation. Methods and Results: In this study, 20 patients with HOCM who underwent endocardial ablation were included. Echocardiography and cardiac MRI (CMR) data was collected and analyzed pre- and (or) post- procedure. Nineteen patients underwent ablation successfully, while ablation was aborted in one patient with prior RBBB due to transient complete atrioventricular block (AVB). After 6 months of follow-up, NYHA heart functional class improved from III (2 - 3) to II (1 - 2) (p < 0.001), and resting LVOT gradient was significantly reduced (87.6 ± 29.5 mmHg vs. 48.1 ± 29.7, p < 0.001). LVOT gradient reduction was significantly higher in patients with limited basal septal hypertrophy (60.9 ± 8.3 vs. 27.9 ± 7.1, p = 0.01), shorter anterior mitral leaflet (56.1 ± 6.4 vs. 20.4 ± 5.0, p < 0.01), and normally positioned papillary muscle (36.9 ± 7.1 vs. 75.0 ± 6.3, p < 0.05). Conclusions: Endocardial septal ablation appears to be a safe and effective procedure for alleviating LVOT gradient in patients with HOCM, especially in those with limited basal septal hypertrophy, shorter anterior mitral leaflet, and normal positioned papillary muscle.

Intracardiac ultrasound-guided left bundle branch pacing in a bradycardia patient.

Left bundle branch pacing was associated with narrower QRS in patients with pacemaker indications. LBBP guided by ICE improves the accuracy of LBBP, facilitates the lead localization, minimizes complications, and above all reduces radiation exposure time.

PV isolation guided by esophageal visualization with a tailored ablation strategy for the avoidance of esophageal thermal injury: a randomized trial.

PURPOSE: Radiofrequency ablation along the posterior wall of the left atrium may lead to atrioesophageal fistula due to esophageal thermal injury. The purpose of our study was to prospectively investigate whether ablation guided by soluble contrast esophageal visualization (SCEV) reduces injury during atrial fibrillation (AF) ablation. METHODS: Seventy-eight patients with paroxysmal AF undergoing circumferential pulmonary vein isolation (PVI) were randomized to a SCEV group (n = 39) and control group without visualization (n = 39). Cine imaging of the esophagus was performed during soluble contrast swallowing at the beginning of ablation, after adjacent ipsilateral PVI and at the end of the procedure. The ablation lesion set was modified to avoid radiofrequency delivery within the contrast esophagram boundaries. In the control group, a single final ingestion was performed at the end of the procedure. Esophageal injury was assessed by esophagogastroscopy within 24 h in all patients. RESULTS: In the control group, the ablation lesion crossed over the esophagus in 46.2% of patients, whereas in SCEV group, the ablation line violated the boundaries of the esophagus unavoidably in 15.4% of patients (confidence interval (CI); 1.61-13.98, p = 0.003). The incidence of esophageal injury was significantly lower in patients that underwent ablation with SCEV (5.1% vs. 20.5%, CI; 0.04-1.06, p = 0.042). Regardless of randomization group, patients who received ablation which overlapped the esophagus had a higher incidence of esophageal injury compared with those without overlap (37.5 vs. 1.9%, CI; 3.73-271.37, p = 0.000). CONCLUSIONS: Esophageal contrast visualization helps to reduce the potential for esophageal injury during paroxysmal AF ablation. This simple procedural adjunct has important implications to improve safety of paroxysmal AF ablation procedures globally.

Cross Talk Between p22phox and ATF4 in the Endothelial Unfolded Protein Response.

BACKGROUND: Cardiovascular diseases have been associated with stress in the endoplasmic reticulum (ER) and accumulation of unfolded proteins leading to the unfolded protein response (UPR). Reactive oxygen species (ROS) such as superoxide and H2O2 derived from NADPH oxidases have been implicated in the pathogenesis of cardiovascular diseases. ROS have also been associated with ER stress. The role NADPH oxidases in the UPR is, however, not completely resolved yet. AIM: In this study, we investigated the role of p22phox, an essential component of most NADPH oxidases, in the UPR of endothelial cells. RESULTS: Induction of ER stress increased p22phox expression at the transcriptional level. p22phox was identified as novel target of the UPR transcription factor ATF4 (activator of transcription factor 4) under ER stress conditions by promoter analyses and ChIP. Depletion of ATF4 and p22phox diminished the levels of superoxide and H2O2 under ER stress conditions. On the contrary, p22phox was instrumental in increasing eIF2α phosphorylation and subsequent ATF4 expression on induction of ER stress by chemicals, oxysterols, or severe hypoxia in vitro and in vivo, leading to increased expression of CHOP and activation of effector caspases. INNOVATION: p22phox is a novel target of ATF4 in response to ER stress, which can promote the PERK-ATF4 branch of the UPR in vitro and in vivo. CONCLUSION: p22phox-dependent NADPH oxidases are important mediators of ER stress driving the UPR.

Stabilization of p22phox by Hypoxia Promotes Pulmonary Hypertension.

AIMS: Hypoxia and reactive oxygen species (ROS) have been shown to play a role in the pathogenesis of pulmonary hypertension (PH), a potentially fatal disorder characterized by pulmonary vascular remodeling, elevated pulmonary arterial pressure, and right ventricular hypertrophy. However, how they are linked in the context of PH is not completely understood. We, therefore, investigated the role of the NADPH oxidase subunit p22phox in the response to hypoxia both in vitro and in vivo. RESULTS: We found that hypoxia decreased ubiquitinylation and proteasomal degradation of p22phox dependent on prolyl hydroxylases (PHDs) and the E3 ubiquitin ligase protein von Hippel Lindau (pVHL), which resulted in p22phox stabilization and accumulation. p22phox promoted vascular proliferation, migration, and angiogenesis under normoxia and hypoxia. Increased levels of p22phox were also detected in lungs and hearts from mice with hypoxia-induced PH. Mice harboring a point mutation (Y121H) in the p22phox gene, which resulted in decreased p22phox stability and subsequent loss of this protein, were protected against hypoxia-induced PH. Mechanistically, p22phox contributed to ROS generation under normoxia, hypoxia, and hypoxia/reoxygenation. p22phox increased the levels and activity of HIF1α, the major cellular regulator of hypoxia adaptation, under normoxia and hypoxia, possibly by decreasing the levels of the PHD cofactors ascorbate and iron(II), and it contributed to the downregulation of the tumor suppressor miR-140 by hypoxia. INNOVATION: These data identify p22phox as an important regulator of the hypoxia response both in vitro and in vivo. CONCLUSION: p22phox-dependent NADPH oxidases contribute to the pathophysiology of PH induced by hypoxia.