The association between paced left ventricular activation time and cardiac reverse remodeling in heart failure patients with left bundle branch block.

INTRODUCTION: The association between paced LVAT and cardiac structure and function at baseline, as well as whether longer LVAT is associated with worse cardiac reverse remodeling in patients with heart failure (HF) and left bundle branch block (LBBB) has not been well investigated. The purpose of this study is to investigate the association between paced LVAT and baseline echocardiographic parameters and cardiac reverse remodeling at follow-up. METHODS: Patients with HF and LBBB receiving successful left bundle branch pacing (LBBP) from June 2018 to April 2023 were enrolled and grouped based on paced LVAT. NT-proBNP and echocardiographic parameters were recorded during routine follow-up. The relationships between paced LVAT and echocardiographic parameters at baseline and follow-up were analyzed. RESULTS: Eighty-three patients were enrolled (48 males, aged 65 ± 9.8, mean LVEF 32.1 ± 7.5%, mean LVEDD 63.0 ± 8.5 mm, median NT-proBNP 1057[513-3158] pg/mL). The paced QRSd was significantly decreased (177 ± 17.9 vs. 134 ± 18.5, p < .001) and median paced LVAT was 80[72-88] ms. After a median follow-up of 12[9-29] months, LVEF increased to 52.1 ± 11.2%, LVEDD decreased to 52.6 ± 8.8 mm, and NT-proBNP decreased to 215[73-532]pg/mL. Patients were grouped based on paced LVAT: LVAT < 80 ms (n = 39); 80 ≤ LVAT < 90 ms (n = 24); LVAT ≥ 90 ms (n = 20). Patients with longer LVAT had larger LVEDD and lower LVEF (LVEDDbaseline: p < .001; LVEFbaseline: p = .001). The difference in LVEF6M was statistically significant among groups (p < .001) and patients with longer LVAT had lower LVEF6M, while the difference in LVEF1Y was not seen (p = .090). There was no significant correlation between ΔLVEF6M-baseline, ΔLVEF1Y-6M and LVAT respectively (ΔLVEF6M-baseline: p = .261, r = -.126; ΔLVEF1Y-6M: p = .085, r = .218). CONCLUSION: Long paced LVAT was associated with worse echocardiographic parameters at baseline, but did not affect the cardiac reverse remodeling in patients with HF and LBBB. Those with longer LVAT required longer time to recover.

A novel method combining gated SPECT and vectorcardiography to guide left ventricular lead placement to improve response to cardiac resynchronization therapy: A proof of concept study.

BACKGROUND: The segment of the latest mechanical contraction (LMC) does not always overlap with the site of the latest electrical activation (LEA). By integrating both mechanical and electrical dyssynchrony, this proof-of-concept study aimed to propose a new method for recommending left ventricular (LV) lead placements, with the goal of enhancing response to cardiac resynchronization therapy (CRT). METHODS: The LMC segment was determined by single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) phase analysis. The LEA site was detected by vectorcardiogram. The recommended segments for LV lead placement were as follows: (1) the LMC viable segments that overlapped with the LEA site; (2) the LMC viable segments adjacent to the LEA site; (3) If no segment met either of the above, the LV lateral wall was recommended. The response was defined as ≥15% reduction in left ventricular end-systolic volume (LVESV) 6-months after CRT. Patients with LV lead located in the recommended site were assigned to the recommended group, and those located in the non-recommended site were assigned to the non-recommended group. RESULTS: The cohort comprised of 76 patients, including 54 (71.1%) in the recommended group and 22 (28.9%) in the non-recommended group. Among the recommended group, 74.1% of the patients responded to CRT, while 36.4% in the non-recommended group were responders (P = .002). Compared to pacing at the non-recommended segments, pacing at the recommended segments showed an independent association with an increased response by univariate and multivariable analysis (odds ratio 5.00, 95% confidence interval 1.73-14.44, P = .003; odds ratio 7.33, 95% confidence interval 1.53-35.14, P = .013). Kaplan-Meier curves showed that pacing at the recommended LV lead position demonstrated a better long-term prognosis. CONCLUSION: Our findings indicate that pacing at the recommended segments, by integrating of mechanical and electrical dyssynchrony, is significantly associated with an improved CRT response and better long-term prognosis.

Prospective randomized comparison between upgraded '2C3L' vs. PVI approach for catheter ablation of persistent atrial fibrillation: PROMPT-AF trial design.

BACKGROUND: In randomized studies, the strategy of pulmonary vein antral isolation (PVI) plus linear ablation has failed to increase success rates for persistent atrial fibrillation (PeAF) ablation when compared with PVI alone. Peri-mitral reentry related atrial tachycardia due to incomplete linear block is an important cause of clinical failures of a first ablation procedure. Ethanol infusion (EI) into the vein of Marshall (EI-VOM) has been demonstrated to facilitate a durable mitral isthmus linear lesion. OBJECTIVE: This trial is designed to compare arrhythmia-free survival between PVI and an ablation strategy termed upgraded '2C3L' for the ablation of PeAF. STUDY DESIGN: The PROMPT-AF study (clinicaltrials.gov 04497376) is a prospective, multicenter, open-label, randomized trial using a 1:1 parallel-control approach. Patients (n = 498) undergoing their first catheter ablation of PeAF will be randomized to either the upgraded '2C3L' arm or PVI arm in a 1:1 fashion. The upgraded '2C3L' technique is a fixed ablation approach consisting of EI-VOM, bilateral circumferential PVI, and 3 linear ablation lesion sets across the mitral isthmus, left atrial roof, and cavotricuspid isthmus. The follow-up duration is 12 months. The primary end point is freedom from atrial arrhythmias of >30 seconds, without antiarrhythmic drugs, in 12 months after the index ablation procedure (excluding a blanking period of 3 months). CONCLUSIONS: The PROMPT-AF study will evaluate the efficacy of the fixed '2C3L' approach in conjunction with EI-VOM, compared with PVI alone, in patients with PeAF undergoing de novo ablation.

Clinical use conditions of lead deployment and simulated lead fracture rate in left bundle branch area pacing.

INTRODUCTION: Left bundle branch area pacing (LBBAP) is achieved by advancing the lead tip deep in the septum. Most LBBAP implants are performed using the Medtronic SelectSecure™ MRI SecureScan™ Model 3830 featuring a unique 4 Fr fixed helix lumenless design. Details of lead use conditions and long-term reliability have not been reported. This study was designed to quantify the mechanical use conditions for the 3830 lead during and after LBBAP implant, and to evaluate reliability using bench testing and simulation. METHODS: Fifty bradycardia patients with implantation of the 3830 lead for LBBAP were enrolled. Use conditions of lead deployment at implantation were collected and computed tomography (CT) scans were performed at 3-month follow-up. Curvature amplitude along the pacing lead was determined with CT images. Fatigue bending was performed using accelerated testing in a more severe environment than routine clinical use conditions. Conductor fracture rate in a simulated patient population was estimated based on clinical use conditions and fatigue test results. RESULTS: The number of attempts to place the 3830 lead for LBBAP was 2.1 ± 1.3 (range: 1-7) with 13 ± 6 lead rotations at the final attempt. Extreme implant conditions were simulated in bench testing with 5 applications of 20 turns followed by up to 400 million bending cycles. Reliability modeling predicted a 10-year fracture rate of 0.02%. CONCLUSIONS: LBBAP implants require more lead rotations than standard pacing implants and result in unique lead bending. Application of simulated LBBAP use conditions to the 3830 lead in an accelerated in-vitro model does not produce excess conductor fractures. IMAGE-LBBP Study ID of ClinicalTrial.GOV: NCT04119323.

A method using deep learning to discover new predictors from left-ventricular mechanical dyssynchrony for CRT response.

BACKGROUND: Studies have shown that the conventional parameters characterizing left ventricular mechanical dyssynchrony (LVMD) measured on gated SPECT myocardial perfusion imaging (MPI) have their own statistical limitations in predicting cardiac resynchronization therapy (CRT) response. The purpose of this study is to discover new predictors from the polarmaps of LVMD by deep learning to help select heart failure patients with a high likelihood of response to CRT. METHODS: One hundred and fifty-seven patients who underwent rest gated SPECT MPI were enrolled in this study. CRT response was defined as an increase in left ventricular ejection fraction (LVEF) > 5% at 6 [Formula: see text] 1 month follow up. The autoencoder (AE) technique, an unsupervised deep learning method, was applied to the polarmaps of LVMD to extract new predictors characterizing LVMD. Pearson correlation analysis was used to explain the relationships between new predictors and existing clinical parameters. Patients from the IAEA VISION-CRT trial were used for an external validation. Heatmaps were used to interpret the AE-extracted feature. RESULTS: Complete data were obtained in 130 patients, and 68.5% of them were classified as CRT responders. After variable selection by feature importance ranking and correlation analysis, one AE-extracted LVMD predictor was included in the statistical analysis. This new AE-extracted LVMD predictor showed statistical significance in the univariate (OR 2.00, P = .026) and multivariate (OR 1.11, P = .021) analyses, respectively. Moreover, the new AE-extracted LVMD predictor not only had incremental value over PBW and significant clinical variables, including QRS duration and left ventricular end-systolic volume (AUC 0.74 vs 0.72, LH 7.33, P = .007), but also showed encouraging predictive value in the 165 patients from the IAEA VISION-CRT trial (P < .1). The heatmaps for calculation of the AE-extracted predictor showed higher weights on the anterior, lateral, and inferior myocardial walls, which are recommended as LV pacing sites in clinical practice. CONCLUSIONS: AE techniques have significant value in the discovery of new clinical predictors. The new AE-extracted LVMD predictor extracted from the baseline gated SPECT MPI has the potential to improve the prediction of CRT response.

Cardiac resynchronization therapy for patients with heart failure and nonspecific intraventricular conduction delay.

The efficacy of cardiac resynchronization therapy (CRT) in heart failure patients with left bundle branch block (LBBB) is well established with Class I or IIa recommendation according to 2021 ESC Guidelines on cardiac pacing and CRT, whereas non-LBBB morphology is less recommended. There is insufficient evidence that proves patients with NICD could benefit from CRT. As patients with NICD are characterized by heterogeneity, the effect of CRT on these patients is still controversial. Although the proportion of NICD in the population is lower than that of LBBB patients, it is still worth investigating the effects of CRT on patients with NICD in an era of His-Purkinje conduction system pacing (HPCSP).

Cardiovascular imaging in conduction system pacing: What does the clinician need?

Permanent pacemakers are used for symptomatic bradycardia and biventricular pacing (BVP)-cardiac resynchronization therapy (BVP-CRT) is established for heart failure (HF) patients traditionally. According to guidelines, patients' selection for CRT is based on QRS duration (QRSd) and morphology by surface electrocardiogram (ECG). Cardiovascular imaging techniques evaluate cardiac structure and function as well as identify pathophysiological substrate changes including the presence of scar. Cardiovascular imaging helps by improving the selection of candidates, guiding left ventricular (LV) lead placement, and optimization devices during the follow-up. Conduction system pacing (CSP) includes His bundle pacing (HBP) and left bundle branch pacing (LBBP) which is screwed into the interventricular septum. CSP maintains and restores ventricular synchrony in patients with native narrow QRSd and left bundle branch block (LBBB), respectively. LBBP is more feasible than HBP due to a wider target area. This review highlights the role of multimodality cardiovascular imaging including fluoroscopy, echocardiography, cardiac magnetic resonance (CMR), myocardial scintigraphy, and computed tomography (CT) in the pre-procedure assessment for CSP, better selection for CSP candidates, the guidance of CSP lead implantation, and the optimization of devices programming after the procedure. We also compare the different characteristics of multimodality imaging and discuss their potential roles in future CSP implantation.

Differentiating left bundle branch pacing and left ventricular septal pacing: An algorithm based on intracardiac electrophysiology.

BACKGROUND: Left bundle branch pacing (LBBP) is a new near-physiological pacing modality. Distinguishing left ventricular septal only pacing (LVSP) from nonselective LBBP still needs clarification. This prospective study sought to establish a differentiation algorithm to confirm LBBP. METHODS AND RESULTS: LBBP was attempted in consecutive patients. If direct LBB capture (LBBP) could not be confirmed, LVSP was considered to have been achieved. Intracardiac left ventricular (LV) activation sequence and activation time were analyzed using coronary sinus (CS) electrogram mapping. Electrophysiological parameters including S-CSmax, S-CSmin, LV lateral wall activation time, ΔLV, and LBB potential were compared between LBBP and LVSP. Stimulated LV activation time (S-LVAT) and stimulated QRS duration (S-QRSd) were also compared between the two groups. Multivariate logistic regression analysis was used to develop a prediction algorithm for LBBP. Of the 43 prospectively enrolled patients, 27 underwent LBBP and 16 underwent LVSP. All LBBP patients showed identical LV activation sequences to their intrinsic rhythm while no LVSP patients maintained their intrinsic sequence. S-CSmax, ΔLV, LV lateral wall activation time, and S-LVAT during LBBP were significantly shorter than those during LVSP. Combining LBB potential with S-LVAT had the largest area under the curve (AUC) of 0.985 for confirming LBBP with a sensitivity of 95.2% and a specificity of 93.7%. CONCLUSIONS: Compared with LVSP, LBBP preserves a normal LV activation sequence and better electrical synchrony. A combination of LBB potential with S-LVAT can be an effective and practical model to distinguish LBBP from LVSP during implantation in patients with normal LBB activation.

Computed tomography imaging-identified location and electrocardiographic characteristics of left bundle branch area pacing in bradycardia patients.

INTRODUCTION: Left bundle branch area pacing (LBBAP) is a novel physiological pacing modality. The relationship between the pacing lead tip location and paced electrocardiographic (ECG) characteristics remains unclear. The objectives are to determine the lead tip location within the interventricular septum (IVS) and assess the location-based ECG QRS duration (QRSd) and left ventricular activation time (LVAT). METHODS: This multicenter study enrolled 50 consecutive bradycardia patients who met pacemaker therapy guidelines and received LBBAP implantation via the trans-ventricular septal approach. After at least 3 months postimplant, 12-lead ECGs and pacing parameters were obtained. Cardiac computed tomography (CT) imaging was performed to assess the LBBAP lead tip distance from the LV blood pool. RESULTS: Among the 50 patients, analyzable CT images were obtained in 42. In 23 of the 42 patients, the lead tips were within 2 mm to the LV blood pool (the LV subendocardial (LVSE) group), 13 between 2 and 4 mm (the Near-LVSE group), and the remaining 6 beyond 4 mm (the Mid-LV septal (Mid-LVS) group). No significant differences in paced QRSd were found among the three groups (LVSE, 107 ± 15 ms; Near-LVSE, 106 ± 13 ms; Mid-LVS, 104 ± 15 ms; p = .87). LVAT in the LVSE (64 ± 7 ms) was significantly shorter than in the Mid-LVS (72 ± 8 ms; p < .05), but not significantly different from that in the Near-LVSE (69 ± 8 ms; p > .05). CONCLUSION: In routine LBBAP practice, paced narrow QRSd and fast LVAT, indicative of physiological pacing, were consistently achieved for lead tip location in the LV subendocardial or near LV subendocardial region.

Predictive values of left ventricular mechanical dyssynchrony for CRT response in heart failure patients with different pathophysiology.

BACKGROUND: Cardiac resynchronization therapy (CRT) patients with different pathophysiology may influence mechanical dyssynchrony and get different ventricular resynchronization and clinical outcomes. METHODS: Ninety-two dilated cardiomyopathy (DCM) and fifty ischemic cardiomyopathy (ICM) patients with gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) were included in this retrospective study. Patients were classified based on the concordance between the left ventricular (LV) lead and the latest contraction or relaxation position. If the LV lead was located on or adjacent to both the latest contraction and relaxation position, the patient was categorized into the both match group; if the LV lead was located on or adjacent to the latest contraction or relaxation position, the patient was classified into the one match group; if the LV lead was located on or adjacent to neither the latest contraction nor relaxation position, the patient was categorized to the neither group. CRT response was defined as [Formula: see text] improvement of LV ejection fraction at the 6-month follow-up. Variables with P < .05 in the univariate analysis were included in the stepwise multivariate model. RESULTS: During the follow-up period, 58.7% (54 of 92) for DCM patients and 54% (27 of 50) for ICM patients were CRT responders. The univariate analysis and stepwise multivariate analysis showed that QRS duration, systolic phase bandwidth (PBW), diastolic PBW, diastolic phase histogram standard deviation (PSD), and left ventricular mechanical dyssynchrony (LVMD) concordance were independent predictors of CRT response in DCM patients; diabetes mellitus and left ventricular end-systolic volume were significantly associated with CRT response in ICM patients. The intra-group comparison revealed that the CRT response rate was significantly different in the both match group of DCM (N = 18, 94%) and ICM (N = 24, 62%) patients (P = .016). However, there was no significant difference between DCM and ICM in the one match and neither group. For the inter-group comparison, Kruskal-Wallis H-test revealed that CRT response was significantly different in all the groups of DCM patients (P < .001), but not in ICM patients (P = .383). CONCLUSIONS: Compared with ICM patients, systolic PBW, diastolic PBW and PSD have better predictive and prognostic values for the CRT response in DCM patients. Placing the LV lead in or adjacent to the latest contraction and relaxation position can improve the clinical outcomes of DCM patients, but it does not apply to ICM patients.

A pilot study to determine if left ventricular activation time is a useful parameter for left bundle branch capture: Validated by ventricular mechanical synchrony with SPECT imaging.

BACKGROUND: Left bundle branch (LBB) pacing has emerged as a novel pacing modality. Left ventricular activation time (LVAT) was reported to be associated with the activation via LBB, but the value of LVAT for determining LBB pacing was unknown. We conducted a pilot study to determine if LVAT could define LBB capture by validating left ventricular (LV) mechanical synchrony. METHODS: We analyzed LVAT in 68 bradycardia-indicated patients who received LBB pacing. LVAT was measured from the stimulus to R-wave peak in lead V5 and V6. LV mechanical synchrony assessed by SPECT MPI was compared according to the value of LVAT and the presence of LBB potential. RESULTS: The mean LVAT was 75.4 ± 12.7 ms. LBB potential was recorded in 47 patients (69.1%). Patients with LVAT < 76 ms had better LV mechanical synchrony than those with LVAT ≥ 76 ms. Patients with LVAT < 76 ms or LBB potential had better mechanical synchrony than those with LVAT ≥ 76 ms and no potential. LVAT < 76 ms could predict the normal synchrony with a sensitivity of 88.9% and a specificity of 87.5%. CONCLUSION: A short LVAT indicated favorable mechanical synchrony in SPECT imaging. LVAT < 76 ms might be a practical parameter for defining LBB capture.

Left ventricular systolic and diastolic dyssynchrony to improve cardiac resynchronization therapy response in heart failure patients with dilated cardiomyopathy.

BACKGROUND: The systolic and diastolic dyssynchrony is physiologically related, but measure different left ventricular mechanisms. Left ventricular systolic mechanical dyssynchrony (systolic LVMD) has shown significant clinical values in improving cardiac resynchronization therapy (CRT) response in the heart failure patients with dilated cardiomyopathy (DCM). Our recent study demonstrated that LV diastolic dyssynchrony (diastolic LVMD) parameters have important prognostic values for DCM patients. However, there are a limited number of studies about the clinical value of diastolic LVMD for CRT. This study aims to explore the predictive values of both systolic LVMD and diastolic LVMD for CRT in DCM patients. METHODS: Eighty-four consecutive CRT patients with both DCM and complete left bundle branch block (CLBBB) who received gated resting SPECT MPI at baseline were included in the present study. The phase analysis technique was applied on resting gated short-axis SPECT MPI images to measure systolic LVMD and diastolic LVMD, characterized by phase standard deviation (PSD) and phase histogram bandwidth (PBW). CRT response was defined as ≥ 5% improvement of LVEF at 6-month follow-up. Variables with P < 0.10 in the univariate analysis were included in the multivariate cox analysis. RESULTS: During the follow-up period, 59.5% (50 of 84) patients were CRT responders. The univariate cox regression analysis showed that at baseline QRS duration, non-sustained ventricular tachycardia (NS-VT), systolic PSD, systolic PBW, diastolic PSD, diastolic PBW, scar burden and LV lead in the scarred myocardium were statistically significantly associated with CRT response. The multivariate cox regression analysis showed that QRS duration, NS-VT, systolic PSD, systolic PBW, diastolic PSD, and diastolic PBW were independent predictive factors for CRT response. Furthermore, the rate of CRT response was 94.4% (17 of 18) in patients whose LV lead was in the segments with both the first three late contraction and the first three late relaxation; by contrast, the rate of CRT response was only 6.7% (1 of 15, P < 0.000) in patients whose LV lead was in the segments with neither the first three late contraction nor the first three late relaxation. CONCLUSION: Both systolic LVMD and diastolic LVMD from gated SPECT MPI have important predictive values for CRT response in DCM patients. Pacing at LV segments with both late contraction and late relaxation has potential to increase the CRT response.

A new method to recommend left ventricular lead positions for improved CRT volumetric response and long-term prognosis.

OBJECTIVES: Using ECG-gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), we sought to develop and validate a new method to recommend left ventricular (LV) lead positions in order to improve volumetric response and long-term prognosis after cardiac resynchronization therapy (CRT). METHODS: Seventy-nine patients received gated SPECT MPI at baseline, and echocardiography at baseline and follow-up. The volumetric response referred to a reduction of ≥ 15% in LV end-systolic volume 6 months after CRT. After excluding apical, septal, and scarred segments, there were three levels of recommended segments: (1) the optimal recommendation: the latest contracting viable segment; (2) the 2nd recommendation: the late contracting viable segments whose contraction delays were within 10° of the optimal recommendation; and (3) the 3rd recommendation: the viable segments adjacent to the optimal recommendation when there was no late contracting viable segment. RESULTS: After excluding 11 patients whose LV lead was placed in apical or scarred segments, 75.6% of the patients concordant to recommended LV segments (n = 41) responded to CRT while 51.9% of those with non-recommended LV lead locations (n = 27) were responders (P = .043). Response rates were 76.9%, 76.9% , and 73.3% (P = .967), respectively, when LV lead was implanted in the optimal recommendation (n = 13), the 2nd recommendation (n = 13), and the 3rd recommendation (n = 15). LV leads placed at recommended segments reduced composite events of all-cause mortality or heart failure (HF) rehospitalization compared with pacing at non-recommended segments (log-rank χ2 = 5.623, P = .018). CONCLUSIONS: Pacing in the recommended LV lead segments identified on gated SPECT MPI was associated with improved volumetric response to CRT and long-term prognosis.

Comparative efficacy of image-guided techniques in cardiac resynchronization therapy: a meta-analysis.

BACKGROUND: Several studies have illustrated the use of echocardiography, magnetic resonance imaging, and nuclear imaging to optimize left ventricular (LV) lead placement to enhance the response of cardiac resynchronization therapy (CRT) in heart failure patients. We aimed to conduct a meta-analysis to determine the incremental efficacy of image-guided CRT over standard CRT. METHODS: We searched PubMed, Cochrane library, and EMBASE to identify relevant studies. The outcome measures of cardiac function and clinical outcomes were CRT response, concordance of the LV lead to the latest sites of contraction (concordance of LV), heart failure (HF) hospitalization, mortality rates, changes of left ventricular ejection fraction (LVEF), and left ventricular end-systolic volume (LVESV). RESULTS: The study population comprised 1075 patients from eight studies. 544 patients underwent image-guided CRT implantation and 531 underwent routine implantation without imaging guidance. The image-guided group had a significantly higher CRT response and more on-target LV lead placement than the control group (RR, 1.33 [95% CI, 1.21 to 1.47]; p < 0.01 and RR, 1.39 [95% CI, 1.01 to 1.92]; p < 0.05, respectively). The reduction of LVESV in the image-guided group was significantly greater than that in the control group (weighted mean difference, - 12.46 [95% CI, - 18.89 to - 6.03]; p < 0.01). The improvement in LVEF was significantly higher in the image-guided group (weighted mean difference, 3.25 [95% CI, 1.80 to 4.70]; p < 0.01). Pooled data demonstrated no significant difference in HF hospitalization and mortality rates between two groups (RR, 0.89 [95% CI, 0.16 to 5.08]; p = 0.90, RR, 0.69 [95% CI, 0.37 to 1.29]; p = 0.24, respectively). CONCLUSIONS: This meta-analysis indicates that image-guided CRT is correlated with improved CRT volumetric response and cardiac function in heart failure patients but not with lower hospitalization or mortality rate.

Efficacy of upgrading to left bundle branch pacing in patients with heart failure after right ventricular pacing.

BACKGROUND: Chronic right ventricular (RV) pacing is associated with an increased incidence of heart failure and mortality. Left bundle branch (LBB) pacing could produce near-physiological electrical activation and mechanical synchrony. We aimed to report the effects of upgrading to LBB pacing in heart failure patients after chronic RV pacing. METHODS: The indications included pacing-induced cardiomyopathy (PICM) in Group 1 and heart failure after RV pacing with left ventricular ejection fraction (LVEF) ≥ 50% in Group 2. LBB pacing was achieved by penetrating the pacing lead to the subendocardium of left-sided interventricular septum through the venous access. Left ventricular activation time (LVAT) was measured from the pacing stimulus to the ascending peak of lead V5 or V6. All patients underwent clinical and echocardiographic evaluations before and after upgrading. RESULTS: Totally 27 patients (13 in Group 1 and 14 in Group 2) were consecutively enrolled. The mean follow-up time after upgrade was 10.4 ± 6.1 months. Paced QRS duration was significantly shortened from 174.1 ± 15.8 milliseconds to 116.6 ± 11.7 milliseconds (p < .0001). The mean LVAT was 83.2 ± 11.7 milliseconds. LVEF increased from 40.3 ± 5.2% before upgrading to 48.1 ± 9.5% at follow-up in patients with PICM. Serum N-terminal probrain natriuretic peptide levels decreased and New York Heart Association classification improved in both groups. No upgrade-related complications were observed. CONCLUSIONS: Upgrading to LBB pacing was feasible and effective with improved cardiac function in heart failure patients with both reduced and preserved LVEF after RV pacing.

Oral and intestinal microbial features in pregnant women with hypothyroidism and their correlations with pregnancy outcomes.

The purpose of this study was to explore the characteristics of oral and intestinal microbiota of pregnant women with hypothyroidism during pregnancy, and to find the correlations between the changes of flora and pregnancy outcome of pregnant women with hypothyroidism during pregnancy. In this study, oral and intestinal microbial composition was surveyed by using the 16S rRNA sequencing approach in 61 pregnant women (30 with hypothyroidism and 31 normal controls). Sequentially, we validated the differential microbial features by using the quantitative real-time PCR (qPCR) approach in 10 randomly selected pregnant women (5 with hypothyroidism and 5 normal controls). Furthermore, general clinical data and serological indices were added to the analysis to examine the links between oral and intestinal microbiota and pregnancy outcomes. The 16S rRNA results showed that the relative abundances of Gammaproteobacteria were higher in pregnant women in the hypothyroidism group than in those in the control group, whereas the levels of Firmicutes were higher in the control group than in the hypothyroidism group. The serum C-reactive protein level, the weight gain during pregnancy, and the incidence of fetal distress were higher in the hypothyroidism group than in the control group. The QPCR results also showed the same changes of the intestinal microbiota in the two groups. There were significant differences in the oral and intestinal microbiota between pregnant women with hypothyroidism and normal pregnant women. The changes of microbiota is one of the factors influencing the occurrence and development of hypothyroidism during pregnancy.

Differential intestinal and oral microbiota features associated with gestational diabetes and maternal inflammation.

Maternal microbiota is involved in many metabolic diseases. However, its role in the pathophysiology of gestational diabetes mellitus (GDM) remains unclear. In this case-control study, we performed a 16S rRNA sequencing-based microbial survey to compare the intestinal and oral microflora at third trimester during pregnancy between 30 GDM and 31 normal controls. Sequentially, a correlation-based network analysis was further performed to explore the interactions among microbiota, maternal and infant blood sugar, and inflammatory markers. Our results show that, compared with controls, the GDM cases showed significant differences in ß-diversity and increased Gammaproteobacteria and Hemophilus in intestinal microbiota. Furthermore, the GDM cases showed lower α-diversity, increased Selenomonas and Bifidobacterium, and decreased Fusobacteria and Leptotrichia in oral microbiota. The ROC curve showed the area under the curve to be equal to 0.70 and 0.66 when using oral Leptotrichia or gut Hemophilus, respectively, to predict GDM status. In addition, the components and topography of microbial cooccurrence and coexclusion network were quite distinct by GDM status. In summary, intestinal and oral microorganisms in pregnant women are closely related to the status of GDM in the third trimester of pregnancy. The changes of intestinal and oral microbial features may be noninvasive biomarkers for monitoring the health management of GDM pregnancy.

The efficacy of left bundle branch area pacing compared with biventricular pacing in patients with heart failure: A matched case-control study.

BACKGROUND: Left bundle branch area pacing (LBBAP) was reported to improve cardiac function by correcting complete left bundle branch block (CLBBB). Our study aimed to compare the efficacy of LBBAP and biventricular pacing (BIVP) in heart failure patients with CLBBB. METHODS: Ten patients prospectively underwent LBBAP (LBB-CRT group) and 30 patients received BIVP (BIV-CRT group) were matched using propensity score matching. LBBAP was achieved by the trans-interventricular septum method. Echocardiography, electrocardiogram, NYHA classification, and blood B-type natriuretic peptide concentration were evaluated at preimplantation and at 6-month follow up. CRT response was defined as at least 15% decrease in left ventricular end-systolic volume. RESULTS: In the LBB-CRT group, CLBBB were successfully corrected by LBBAP with no complications. QRS duration (QRSd) significantly decreased after implantation in both groups, and the decrease of QRSd in the LBB-CRT group was significantly greater than that in the BIV-CRT group (60.80 ± 20.09 vs. 33.00 ± 21.48 ms, p = .0009). The echocardiographic measurements including left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and left ventricular ejection fraction significantly improved after 6 months in both groups. The response rate was significantly higher in LBB-CRT group than BIV-CRT group (100.00% vs. 63.33%, p = .038). The percentage of patients in New York Heart Association classification Grades I and II was significantly higher in the LBB-CRT group compared with that in the BIV-CRT group (median 1.5 vs. 2.0, p = .029) at 6-month follow-up. CONCLUSIONS: It is effective and safe to correct CLBBB with LBBAP in heart failure patients. Compared with BIVP, LBBAP can better optimize electrical synchrony and improve cardiac function.

Lead performance and clinical outcomes of patients with permanent His-Purkinje system pacing: a single-centre experience.

AIMS: His-Purkinje system (HPS) pacing, including His bundle (HB) and left bundle branch (LBB) pacing, has emerged as a highlighted topic in recent years. Comparisons in lead performance and clinical outcomes between HB and LBB pacing were seldom reported. We aimed to investigate the mid-long-term lead performance and clinical outcomes of permanent HPS pacing patients in our centre. METHODS AND RESULTS: Permanent HB pacing was implemented by placing the pacing lead helix at the HB area. Left bundle branch pacing was achieved by placing the lead helix in the left-side sub-endocardium of the interventricular septum. Pacing parameters, 12-lead ECG, echocardiography, and clinical outcomes were evaluated during follow-up. A total of 64 patients with HB pacing and 185 with LBB pacing were included. Left bundle branch pacing exhibited a slightly longer paced QRS duration than HB pacing (117.7 ± 11.0 vs. 113.7 ± 19.8 ms, P = 0.04). Immediate post-operation, LBB pacing had a significant higher R-wave amplitude (16.5 ± 7.5 vs. 4.3 ± 3.6 mV, P < 0.001) and lower capture threshold (0.5 ± 0.1 vs. 1.2 ± 0.8 V, P < 0.001) compared with HB pacing. During follow-up, an increase in capture threshold of >1.0 V from baseline was found in eight (12.5%) patients in the HB pacing group and none in LBB pacing. Paced QRS morphology changed from Qr to QS in lead V1 in seven patients (3.8%) with LBB pacing. Both HB and LBB pacing preserved cardiac function in patients with left ventricular ejection fraction (LVEF) over 50%. In patients with LVEF <50%, both HB and LBB pacing improved clinical outcomes during follow-up. CONCLUSION: His-Purkinje system pacing produced favourable electrical synchrony and improved cardiac function in patients with heart failure. Left bundle branch pacing showed superior pacing parameters over HB pacing. Lead micro-displacement with changes in paced QRS morphology posts a concern in LBB pacing.

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OBJECTIVES: To evaluate the response to cardiac resynchronization therapy (CRT) and the correlation between CRT and pulmonary artery hemodynamic parameters. METHODS: The patients with chronic heart failure indicator for CRT were enrolled. The left ventricular end-systolic volume (LVESV) was measured by echocardiography and New York Heart Association (NYHA) classification was evaluated between one week before and six months after CRT. Mean pulmonary artery pressure (mPAP), pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) were measured by right heart catheterization. Left ventricular reverse remodeling (LVRR) is defined as a decrease of 15% or more in LVESV at the 6th month after CRT; Clinical response is defined as a decrease of NYHA classification at or above grade 1 at the 6th month after CRT. Pulmonary hypertension (PH) was defined as mPAP≥25 mmHg. According to the response, patients were divided into 3 groups: group A (LVRR+clinical response), group B (no LVRR+clinical response) and group C (no LVRR+no clinical response). The changes of NYHA classification, echocardiographic and pulmonary hemodynamic parameters were observed in the 3 groups. The Kaplan-Meier survival curve was used to analyze the differences in all-cause mortality, combined end-point events of death or re-hospitalization due to heart failure among different groups. RESULTS: A total of 45 patients with CRT implantation [aged (63.27±9.55) years, 36 males] were included. The average follow-up period was (33.76±11.50) months. Thirty-one patients (68.89%) were in group A, 9 of whom with PH. Eight patients (17.78%) were in group B, 7 of whom with PH. Six patients were in group C, all with PH. Cardiac function including NYHA classification, echocardiographic and pulmonary hemodynamic parameters had been significantly improved in group A after CRT implantation (P<0.05). In group B, NYHA classification and pulmonary hemodynamic parameters were decreased significantly (P<0.05), but echocardiographic parameters did not change obviously (P>0.05). There were no significant changes in NYHA classification, echocardiographic and pulmonary hemodynamic parameters in group C (P>0.05). Compared with group C, group A and group B had lower all-cause mortality (P=0.005) and lower incidence of composite endpoint events (P=0.001). CONCLUSIONS: Patients with LVRR and clinical response after CRT have a good prognosis. Patients with clinical response but without LVRR have a better prognosis than those without clinical response and LVRR, which may be related to the decrease of pulmonary hemodynamic parameters such as mPAP and TPG.