Burden of cardiac arrhythmias in patients with acute myocardial infarction and their impact on hospitalization outcomes: insights from China acute myocardial infarction (CAMI) registry.

BACKGROUND: The coexistence of cardiac arrhythmias in patients with acute myocardial infarction (AMI) usually exhibits poor prognosis. However, there are few contemporary data available on the burden of cardiac arrhythmias in AMI patients and their impact on in-hospital outcomes. METHODS: The present study analyzed data from the China Acute Myocardial Infarction (CAMI) registry involving 23,825 consecutive AMI patients admitted to 108 hospitals from January 2013 to February 2018. Cardiac arrhythmias were defined as the presence of bradyarrhythmias, sustained atrial tachyarrhythmias, and sustained ventricular tachyarrhythmias that occurred during hospitalization. In-hospital outcome was defined as a composite of all-cause mortality, cardiogenic shock, re-infarction, stroke, or heart failure. RESULTS: Cardiac arrhythmia was presented in 1991 (8.35%) AMI patients, including 3.4% ventricular tachyarrhythmias, 2.44% bradyarrhythmias, 1.78% atrial tachyarrhythmias, and 0.73% ≥2 kinds of arrhythmias. Patients with arrhythmias were more common with ST-segment elevation myocardial infarction (83.3% vs. 75.5%, P < 0.001), fibrinolysis (12.8% vs. 8.0%, P < 0.001), and previous heart failure (3.7% vs. 1.5%, P < 0.001). The incidences of in-hospital outcomes were 77.0%, 50.7%, 43.5%, and 41.4%, respectively, in patients with ≥ 2 kinds of arrhythmias, ventricular tachyarrhythmias, bradyarrhythmias, and atrial tachyarrhythmias, and were significantly higher in all patients with arrhythmias than those without arrhythmias (48.9% vs. 12.5%, P < 0.001). The presence of any kinds of arrhythmia was independently associated with an increased risk of hospitalization outcome (≥ 2 kinds of arrhythmias, OR 26.83, 95%CI 18.51-38.90; ventricular tachyarrhythmias, OR 8.56, 95%CI 7.34-9.98; bradyarrhythmias, OR 5.82, 95%CI 4.87-6.95; atrial tachyarrhythmias, OR4.15, 95%CI 3.38-5.10), and in-hospital mortality (≥ 2 kinds of arrhythmias, OR 24.44, 95%CI 17.03-35.07; ventricular tachyarrhythmias, OR 13.61, 95%CI 10.87-17.05; bradyarrhythmias, OR 7.85, 95%CI 6.0-10.26; atrial tachyarrhythmias, OR 4.28, 95%CI 2.98-6.16). CONCLUSION: Cardiac arrhythmia commonly occurred in patients with AMI might be ventricular tachyarrhythmias, followed by bradyarrhythmias, atrial tachyarrhythmias, and ≥ 2 kinds of arrhythmias. The presence of any arrhythmias could impact poor hospitalization outcomes. REGISTRATION: Clinical Trial Registration: Identifier: NCT01874691.

CMR feature tracking-based left atrial mechanics predicts response to cardiac resynchronization therapy and adverse outcomes.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an established therapy for advanced heart failure (HF) with prolonged QRS duration. However, 30% of patients have shown no benefit from the treatment. OBJECTIVE: This study aimed to examine the value of left atrial (LA) mechanics by cardiac magnetic resonance (CMR) to predict response to CRT and clinical outcomes. METHODS: A total of 163 CRT recipients with preimplantation CMR examination were retrospectively recruited. CMR feature tracking was used to evaluate LA size and function. The end points include (1) improvement of at least 5% in left ventricular ejection fraction combined with a reduction of at least 1 New York Heart Association functional class at 6-month follow-up and (2) any all-cause death or HF hospitalization during follow-up. RESULTS: Overall, 82 (50.3%) were CRT responders. CRT nonresponders had larger LA and worse LA reservoir and booster pump function than did responders (P < .001 for all). LA structural (maximum volume index < 47 mL/m2) and functional (booster pump strain > 8.5%) criteria were incremental to traditional indicators in detecting CRT response (χ2, 40.83 vs 9.98; P < .001). During follow-up (median 41 months), survival free from death or HF hospitalization increased with the number of positive LA criteria (log-rank, P < .001). After adjustment for clinical confounders, the absence of the 2 criteria remained associated with a considerably increased risk of death or HF hospitalization (adjusted hazard ratio 6.2; 95% confidence interval 2.15-17.88; P = .001). CONCLUSION: The preprocedure LA mechanics evaluated using CMR may be useful to predict response to CRT and improve risk stratification in CRT recipients.

Comparisons of long-term clinical outcomes with left bundle branch pacing, left ventricular septal pacing, and biventricular pacing for cardiac resynchronization therapy.

BACKGROUND: Left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP) are referred to as left bundle branch area pacing. OBJECTIVE: This study investigated whether long-term clinical outcomes differ in patients undergoing LBBP, LVSP, and biventricular pacing (BiVP) for cardiac resynchronization therapy (CRT). METHODS: Consecutive patients with reduced left ventricular ejection fraction (LVEF <50%) undergoing CRT were prospectively enrolled if they underwent successful LBBP, LVSP, or BiVP. The primary composite end point was all-cause mortality or heart failure hospitalization. Secondary end points included all-cause mortality, heart failure hospitalization, and echocardiographic measures of reverse remodeling. RESULTS: A total of 259 patients (68 LBBP, 38 LVSP, and 153 BiVP) were observed for a mean duration of 28.8 ± 15.8 months. LBBP was associated with a significantly reduced risk of the primary end point by 78% compared with both BiVP (7.4% vs 41.2%; adjusted hazard ratio [aHR], 0.22 [0.08-0.57]; P = .002) and LVSP (7.4% vs 47.4%; aHR, 0.22 [0.08-0.63]; P = .004]. The adjusted risk of all-cause mortality was significantly higher in LVSP than in BiVP (31.6% vs 7.2%; aHR, 3.19 [1.38-7.39]; P = .007) but comparable between LBBP and BiVP (2.9% vs 7.2%; aHR, 0.33 [0.07-1.52], P = .155). Propensity score adjustment also obtained similar results. LBBP showed a higher rate of echocardiographic response (ΔLVEF ≥10%: 60.0% vs 36.2% vs 16.1%; P < .001) than BiVP or LVSP. CONCLUSION: LBBP yielded long-term clinical outcomes superior to those of BiVP and LVSP. The role of LVSP for CRT needs to be reevaluated because of its high mortality risk.

Comparison of clinical outcomes between transthoracic echocardiography- and X-ray-guided left bundle branch pacing for bradycardia: A randomized controlled trial.

INTRODUCTION: Left bundle branch pacing (LBBP) is a physiological pacing modality. However, the long procedure and fluoroscopy time of LBBP is still a problem. This study aims to compare the clinical outcomes between transthoracic echocardiography (TTE)- and X-ray-guided LBBP. METHODS: This is a single-center, prospective, randomized controlled study. Consecutive patients who underwent LBBP in our team from June 2022 to November 2022 were enrolled. Procedure and fluoroscopy time, pacing parameters, electrophysiological and echocardiographic characteristics, as well as complications were recorded at implantation and during follow-up. RESULTS: In this study, 60 patients were enrolled and divided into two groups: 30 patients were allocated to the X-ray group and the remaining 30 to the TTE group. There was no significant difference in the success rate between the two groups (86.7% vs. 76.7%, p = .317). The procedure time of TTE group was comparable to that of the X-ray group (9.0 vs. 12.0 min, p = .063). However, the fluoroscopy time in the TTE group was significantly lower than that of the X-ray group (2.5 vs. 5.0 min, p = .002). There were no statistically significant differences in pacing parameters, electrophysiological and echocardiographic characteristics, or complications between the two groups at implantation and during follow-up. CONCLUSION: TTE-guided LBBP is a feasible and safe method. Compared with X-ray, TTE showed a comparable success rate and procedure time, but it could significantly reduce the fluoroscopy time of LBBP.

A noninvasive multianalytical approach establishment for risk assessment and gastric cancer screening.

Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (CTTA) in cfDNA from large asymptomatic screening participants in a high-risk area of GC. The methylation and mutation candidates were validated simultaneously using one plasma from patients at various gastric lesion stages by multiplex profiling with Mutation Capsule Plus (MCP). Helicobacter pylori specific antibodies were detected with a recomLine assay. Integrated models were constructed and validated by the combination of multianalytical biomarkers. A total of 146 and 120 novel methylation markers were found in CpG islands and promoter regions across the genome with CTTA. The methylation markers together with the candidate mutations were validated with MCP and used to establish a 133-methylation-marker panel for risk assessment of suspicious precancerous lesions and GC cases and a 49-methylation-marker panel as well as a 144-amplicon-mutation panel for GC detection. An integrated model comprising both methylation and specific antibody panels performed better for risk assessment than a traditional model (AUC, 0.83 and 0.63, P < .001). A second model for GC detection integrating methylation and mutation panels also outperformed the traditional model (AUC, 0.82 and 0.68, P = .005). Our study established methylation, mutation and H. pylori-specific antibody panels and constructed two integrated models for risk assessment and GC screening. Our findings provide new insights for a more precise GC screening strategy in the future.

Global, regional, and national burdens of atrial fibrillation/flutter from 1990 to 2019: An age-period-cohort analysis using the Global Burden of Disease 2019 study.

Background: Atrial fibrillation/flutter (AF/AFL) significantly impacts countries with varying income levels. We aimed to present worldwide estimates of its burden from 1990 to 2019 using data from the Global Burden of Disease (GBD) study. Methods: We derived cause-specific AF/AFL mortality and disability-adjusted life-year (DALY) estimates from the GBD 2019 study data. We used an age-period-cohort (APC) model to predict annual changes in mortality (net drifts), annual percentage changes from 50-55 to 90-95 years (local drifts), and period and cohort relative risks (period and cohort effects) between 1990 and 2019 by sex and sociodemographic index (SDI) quintiles. This allowed us to determine the impacts of age, period, and cohort on mortality and DALY trends and the inequities and treatment gaps in AF/AFL management. Results: Based on GBD data, our estimates showed that 59.7 million cases of AF/AFL occurred worldwide in 2019, while the number of AF/AFL deaths rose from 117 000 to 315 000 (61.5% women). All-age mortality and DALYs increased considerably from 1990 to 2019, and there was an increase in age risk and a shift in death and DALYs toward the older (>80) population. Although the global net drift mortality of AF/AFL decreased overall (-0.16%; 95% confidence interval (CI) = -0.20, 0.12 per year), we observed an opposite trend in the low-middle SDI (0.53%; 95% CI = 0.44, 0.63) and low SDI regions (0.32%; 95% CI = 0.18, 0.45). Compared with net drift among men (-0.08%; 95% CI = -0.14, -0.02), women had a greater downward trend or smaller upward trend of AF/AFL (-0.21%; 95% CI = -0.26, -0.16) in mortality in middle- and low-middle-SDI countries (P < 0.001). Uzbekistan had the largest net drift of mortality (4.21%; 95% CI = 3.51, 4.9) and DALYs (2.16%; 95% CI = 2.05, 2.27) among all countries. High body mass index, high blood pressure, smoking, and alcohol consumption were more prevalent in developed countries; nevertheless, lead exposure was more prominent in developing countries and regions. Conclusions: The burden of AF/AFL in 2019 and its temporal evolution from 1990 to 2019 differed significantly across SDI quintiles, sexes, geographic locations, and countries, necessitating the prioritisation of health policies based on risk-differentiated, cost-effective AF/AFL management.

Early left bundle branch pacing in heart failure with mildly reduced ejection fraction and left bundle branch block.

BACKGROUND: Left bundle branch pacing (LBBP) achieves resynchrony and improves cardiac function in heart failure (HF) patients with reduced ejection fraction (EF) by correcting left bundle branch block (LBBB). Few data on the efficacy of early LBBP in HF with mildly reduced EF (HFmrEF) and LBBB have been reported. OBJECTIVE: The purpose of this study was to explore the efficacy of early LBBP in patients with HFmrEF and LBBB. METHODS: Consecutive patients with HFmrEF (left ventricular EF [LVEF] 35%-50%) and LBBB were prospectively enrolled to receive LBBP (Early-LBBP group) plus guideline-directed medical therapy (GDMT) or GDMT alone (GDMT group). Study outcomes included changes in LVEF, LV end-diastolic diameter (LVEDD), New York Heart Association (NYHA) functional classification, and N-terminal pro-brain natriuretic peptide (NT-proBNP), and clinical events (HF rehospitalization or syncope). Subgroup analysis compared efficacy of LBBP between patients with LBBB only without comorbidities or late gadolinium enhancement (LGE) (LBBB-Only group) and patients with either comorbidities or LGE (LBBB-Combined group). RESULTS: Fifty-four patients were enrolled and analyzed (37 Early-LBBP group; 15 GDMT group). LBBP achieved greater improvement in LVEF (+14.75% ± 7.37% vs -2.42% ± 2.84%; P <.001), reduction of LVEDD (-7.51 ± 5.40 mm vs -0.87 ± 4.36 mm; P <.001) and NYHA classification (-0.84 ± 0.76 vs -0.13 ± 0.74; P = .004), and similar reduction of NT-proBNP (-408.83 ± 920.29 pg/mL vs -229.05 ± 1579.17 pg/mL; P = .610) at 6 months. Early LBBP showed significantly reduced clinical events (0.0% vs 40.0%; P <.001) after 20.68 ± 13.55 months of follow-up. Subgroup analysis showed patients in the LBBB-Only group benefited more from LBBP with regard to LVEF improvement and LVEDD reduction than the LBBB-Combined group. CONCLUSION: Early LBBP with GDMT demonstrated greater improvement of cardiac function and reduced clinical events than GDMT alone in patients with HFmrEF and LBBB.

Emission and influences of non-road mobile sources on air quality in China, 2000-2019.

Non-road mobile sources (NRMS) are potential important contributors to air pollution in China. However, their extreme impact on air quality had been seldom studied. In this study, the emission inventory of NRMS in mainland China during 2000-2019 was established. Then, the validated WRF-CAMx-PSAT model was applied to simulate the contribution to the atmospheric PM2.5, NO3-, and NOx. Results showed that emissions increased rapidly since 2000 and reached a peak in 2014-2015, with an annual average change rate (AACR) of 8.7-10.0%; after then, the emissions were relatively stable (AACR, -1.4-1.5%). The modeling results indicated that NRMS has become a crucial contributor to the air quality in China: from 2000 to 2019, the contribution to PM2.5, NOx, and NO3- significantly increased by 131.1%, 43.9%, and 61.7%; and for NOx, the contribution ratio in 2019 reached 24.1%. Further analysis showed that the reduction (-0.8% and -0.5%) of the NOx and NO3- contribution ratios was much lower than that (-4.8%) of NOx emissions from 2015 to 2019, implying that the control of NRMS lagged behind the national overall pollution control level. The contribution ratio of agricultural machinery (AM) and construction machinery (CM) to PM2.5, NOx, NO3- in 2019 was 2.6%, 11.3%, 8.3% and 2.5%, 12.6%, 6.8%, respectively. Although the contribution was much lower, the contribution ratio of civil aircraft had the fastest growth (202-447%). Moreover, an interesting phenomenon was that AM and CM had opposite contribution sensitivity characteristics for air pollutants: CM had a higher Contribution Sensitivity Index (CSI) for primary pollutants (e.g., NOx), ∼1.1 times that of AM; while AM had a higher CSI for secondary pollutants (e.g., NO3-), ∼1.5 times that of CM. This work can provide a deeper understanding for the environmental impact of NRMS emissions and for the control strategy formulation of NRMS.

Device-evaluated autonomic nervous function for predicting ventricular arrhythmias and all-cause mortality in patients who underwent cardiac resynchronization therapy-defibrillator.

Introduction: Autonomic nervous system (ANS) function quantified by heart rate variability (HRV) was associated with long-term prognosis, but it was rarely used in the evaluation of patients with heart failure, especially those with cardiac resynchronization therapy-defibrillator (CRT-D) implantation. This study aimed to describe the changes in ANS function among patients who underwent CRT-D with remote home monitoring function, and explore predictive value of HRV for ventricular tachyarrhythmias (VTAs) and all-cause mortality. Method: Patients who underwent CRT-D implantation were included. Device-measured all-day HR, night-time HR, and HRV (measured by the standard deviation of the atrial-atrial sensed intervals) were used to quantify ANS function. Multivariate Cox proportional hazards models were fitted to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of VTAs or all-cause mortality in relation to ANS function at baseline and 6 months post-implantation. The cutoff value was determined using restrictive cubic splines. Multivariable logistic regression was further established to determine factors influencing postoperative HRV. Results: A total of 170 patients treated with CRT-D were eligible for analysis. During a median follow-up period of 50.8 months, 61 patients died and 69 patients experienced at least one spontaneous episode of VTAs. At 6 months after CRT implantation, 114 patients showed improvement in HRV, increasing from 66.4 ± 19.4 ms to 76.7 ± 21.2 ms. The postoperative HRV was associated with both all-cause mortality (HRs: 0.983; 95% CI: 0.968 to 0.998, p = 0.012) and VTAs (HRs: 0.973; 95% CI: 0.954 to 0.993, p = 0.008), and the relative risk would significantly increase when the postoperative HRV lower than 75 ms. After adjusting for basic ANS function and possible influencing factors, patients without diabetes (p = 0.018) and with higher daily physical activity (p = 0.041) could maintain higher postoperative HRV after CRT implantation. Conclusion: More than two-thirds of heart failure patients showed improvement in ANS function following CRT treatment. However, patients with diabetes and low daily physical activity levels have difficulty maintaining a higher postoperative HRV, which is associated with a worse clinical outcome.

Cardiac MRI Risk Stratification for Dilated Cardiomyopathy with Left Ventricular Ejection Fraction of 35% or Higher.

Background Studies over the past 15 years have demonstrated that a considerable number of patients with dilated cardiomyopathy (DCM) who died from sudden cardiac death (SCD) had a left ventricular (LV) ejection fraction (LVEF) of 35% or higher. Purpose To identify clinical and cardiac MRI risk factors for adverse events in patients with DCM and LVEF of 35% or higher. Materials and Methods In this retrospective study, consecutive patients with DCM and LVEF of 35% or higher who underwent cardiac MRI between January 2010 and December 2017 were included. The primary end point was a composite of SCD or aborted SCD. The secondary end point was a composite of all-cause mortality, heart transplant, or hospitalization for heart failure. The risk factors for the primary and secondary end points were identified with multivariable Cox analysis. Results A total of 466 patients with DCM and LVEF of 35% or higher (mean age, 44 years ± 14 [SD]; 358 men) were included. During a mean follow-up of 79 months ± 30 (SD) (range, 7-143 months), 40 patients reached the primary end point and 61 reached the secondary end point. In the adjusted analysis, age (hazard ratio [HR], 1.03 per year [95% CI: 1.00, 1.05]; P = .04), family history of SCD (HR, 3.4 [95% CI: 1.3, 8.8]; P = .01), New York Heart Association (NYHA) class III or IV (HR vs NYHA class I or II, 2.1 [95% CI: 1.1, 3.9]; P = .02), and myocardial scar at late gadolinium enhancement (LGE) MRI greater than or equal to 7.1% of the LV mass (HR, 4.4 [95% CI: 2.4, 8.3]; P < .001) were associated with SCD or aborted SCD. For the composite secondary end point, LGE greater than or equal to 7.1% of the LV mass (HR vs LGE <7.1%, 2.0 [95% CI: 1.2, 3.4]; P = .01), left atrial maximum volume index, and reduced global longitudinal strain were independent predictors. Conclusion For patients with dilated cardiomyopathy and left ventricular (LV) ejection fraction of 35% or higher, cardiac MRI-defined myocardial scar greater than or equal to 7.1% of the LV mass was associated with sudden cardiac death (SCD) or aborted SCD. © RSNA, 2022 Online supplemental material is available for this article.

New-onset atrial fibrillation following left bundle branch area pacing vs. right ventricular pacing: a two-centre prospective cohort study.

AIMS: To investigate whether left bundle branch area pacing (LBBAP) can reduce the risk of new-onset atrial fibrillation (AF) compared with right ventricular pacing (RVP). METHODS AND RESULTS: Patients with indications for dual-chamber pacemaker implant and no history of AF were prospectively enrolled if they underwent successful LBBAP or RVP. The primary endpoint was time to the first occurrence of AF detected by pacemaker programming or surface electrocardiogram. Follow-up at clinic visit was performed and multivariate Cox regression models were applied to evaluate the effect of LBBAP on new-onset AF. The final analysis included 527 patients (mean age 65.3 ± 12.6, male 47.3%), with 257 in the LBBAP and 270 in the RVP groups. During a mean follow-up of 11.1 months, LBBAP resulted in significantly lower incidence of new-onset AF (7.4 vs. 17.0%, P < 0.001) and AF burden (3.7 ± 1.9 vs. 9.3 ± 2.2%, P < 0.001) than RVP. After adjusting for confounding factors, LBBAP demonstrated a lower hazard ratio for new-onset AF compared with RVP {hazard ratio (HR) [95% confidence interval (CI)]: 0.278 (0.156, 0.496), P < 0.001}. A significant interaction existed between pacing modalities and the percentage of ventricular pacing (VP%) (P for interaction = 0.020). In patients with VP ≥ 20%, LBBAP was associated with decreased risk of new-onset AF compared with RVP [HR (95% CI): 0.199 (0.105, 0.378), P < 0.001]. The effect of pacing modalities was not pronounced in patients with VP < 20% [HR (95% CI): 0.751 (0.309, 1.823), P = 0.316]. CONCLUSION: Left bundle branch area pacing demonstrated a reduced risk of new-onset AF compared with RVP. Patients with a high ventricular pacing burden might benefit from LBBAP.

The mediation function of resting heart rate in how physical activity improves all-cause mortality: Continuous and automatic measurement via cardiac implantable electronic devices.

Background: Physical activity (PA) and resting heart rate (RHR) are connected with all-cause mortality. Moreover, there was an inverse correlation between PA and RHR. However, the causal relationship between PA, RHR, and long-term mortality has been rarely evaluated and quantified, particularly the mediation effect of RHR in the association between PA and all-cause mortality. Objective: To describe the relationship between PA and RHR when consistently measured via cardiac implantable electronic devices (CIED) and further explore the mediation effect of PA on all-cause mortality through RHR. Materials and methods: Patients who underwent CIED implantation and received remote home monitoring services were included. During the first 30-60 days after CIED implantation, daily PA and RHR were continuously measured and automatically transmitted by CIED. The primary endpoint was all-cause mortality. The multiple linear regression model was used to confirm the relationship between PA and RHR. The predictive values of both PA and RHR for all-cause mortality were assessed by multivariable Cox proportional hazards models. The causal mediation model was further established to verify and quantify the mediation effect of RHR in the association between PA and all-cause mortality. Results: A total of 730 patients with CIED were included. The mean daily PA and RHR were 10.7 ± 5.7% and 61.3 ± 9.1 bpm, respectively. During a mean follow-up period of 55.8 months, 187 (26.5%) death was observed. A negative linear relationship between PA and RHR was demonstrated in the multiple regression model (ß = -0.260; 95% CI: -0.377 to -0.143, p < 0.001). Multivariable Cox proportional hazards analysis showed that both lower levels of PA (HR = 0.907; 95% CI: 0.878-0.936, p < 0.001) and higher RHR (HR = 1.016; 95% CI: 1.001-1.032, P = 0.031) were independent risk factors of all-cause mortality. Causal mediation analysis further confirmed and quantified the mediation function of RHR in the process of PA improving all-cause mortality (mediation proportion = 3.9%; 95% CI: 0.2-10.0%, p = 0.036). Conclusion: The effects of the higher level of PA on improving life prognosis may be partially mediated through RHR among patients with CIED. It indicates that changes in the autonomic nervous function during postoperative rehabilitation exercises should get more attention.

DNA methylation alternation in Stanford- A acute aortic dissection.

BACKGROUND: Acute aortic dissection (AAD) is a life-threatening cardiovascular disease. Recent studies have shown that DNA methylation may be associated with the pathological mechanism of AAD, but the panorama of DNA methylation needs to be explored. METHODS: DNA methylation patterns were screened using Infinium Human Methylation 450 K BeadChip in the aortic tissues from 4 patients with Stanford-A AAD and 4 controls. Gene enrichment was analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO). DNA methylation levels of candidate genes were determined by pyrosequencing in the replication cohort including 16 patients with AAD and 7 controls. Protein expression level of candidate gene was assessed by Western blot. RESULTS: A total of 589 differentially methylated positions including 315 hypomethylated and 274 hypermethylated positions were found in AAD group. KEGG analysis demonstrated that differentially methylated position-associated genes were enriched in MAPK signaling pathway, TNF signaling pathway and apoptosis pathway, et al. GO analysis demonstrated that differentially methylated position-associated genes were enriched in protein binding, angiogenesis and heart development et al. The differential DNA methylation in five key genes, including Fas, ANGPT2, DUSP6, FARP1 and CARD6, was authenticated in the independent replication cohort. The protein expression level of the Fas was increased by 1.78 times, indicating the possible role of DNA methylation in regulation of gene expression. CONCLUSION: DNA methylation was markedly changed in the aortic tissues of Stanford-A AAD and associated with gene dysregulation, involved in AAD progression.

Randomized Trial of Left Bundle Branch vs Biventricular Pacing for Cardiac Resynchronization Therapy.

BACKGROUND: Left bundle branch pacing (LBBP) is the most rapidly growing conduction system pacing technique that is capable of correcting intrinsic left bundle branch block (LBBB). As such, it is potentially an optimal alternative to cardiac resynchronization therapy (CRT) with biventricular pacing (BiVP). OBJECTIVES: The authors sought to compare the efficacy of LBBP-CRT with BiVP-CRT in patients with heart failure and reduced left ventricular ejection fraction (LVEF). METHODS: This is a prospective, randomized trial of patients with nonischemic cardiomyopathy and LBBB with 6-month preplanned follow-up. Crossovers were allowed if LBBP or BiVP were unsuccessful. The primary endpoint was the difference in LVEF improvement between 2 groups. The secondary endpoints included changes in echocardiographic measurements, N-terminal pro-B-type natriuretic peptide (NT-proBNP), New York Heart Association functional class, 6-minute walk distance, QRS duration, and CRT response. RESULTS: The study included 40 consecutive patients (20 males, mean age 63.7 years, LVEF 29.7% ± 5.6%). Crossovers occurred in 10% of LBBP-CRT and 20% of BiVP-CRT. All patients completed follow-up. Intention-to-treat analysis showed significantly higher LVEF improvement at 6 months after LBBP-CRT than BiVP-CRT (mean difference: 5.6%; 95% CI: 0.3-10.9; P = 0.039). LBBP-CRT also appeared to have greater reductions in left ventricular end-systolic volume (-24.97 mL; 95% CI: -49.58 to -0.36 mL) and NT-proBNP (-1,071.80 pg/mL; 95% CI: -2,099.40 to -44.20 pg/mL), and comparable changes in New York Heart Association functional class, 6-minute walk distance, QRS duration, and rates of CRT response compared with BiVP-CRT. CONCLUSIONS: LBBP-CRT demonstrated greater LVEF improvement than BiVP-CRT in heart failure patients with nonischemic cardiomyopathy and LBBB. (Left Bundle Branch Pacing Versus Biventricular Pacing for Cardiac Resynchronization Therapy [LBBP-RESYNC]; NCT04110431).

His-bundle pacing vs biventricular pacing following atrioventricular nodal ablation in patients with atrial fibrillation and reduced ejection fraction: A multicenter, randomized, crossover study-The ALTERNATIVE-AF trial.

BACKGROUND: Atrioventricular nodal ablation (AVNA) combined with biventricular pacing (BVP) improves outcomes in patients with persistent atrial fibrillation (AF), adequate rate control, and reduced left ventricular ejection fraction (LVEF). His-bundle pacing (HBP) delivers physiological ventricular activation and is a promising alternative to BVP. OBJECTIVE: The purpose of this trial was to compare HBP with BVP following AVNA. METHODS: In this multicenter, prospective, randomized crossover trial, we recruited patients with persistent AF and reduced LVEF (≤40%). All patients underwent AVNA and received both HBP and BVP. Patients were randomized to either HBP or BVP for 9 months (phase 1), then were switched to the alternative pacing modality for the next 9 months (phase 2). The primary endpoint was change in LVEF. RESULTS: Fifty patients (age 64.3 ± 10.3 years; ventricular rate 93.1 ± 19.9 bpm; 72% male) were enrolled. Thirty-eight patients completed the 2 phases and were included in the crossover analysis. A significant improvement in LVEF was observed with HBP compared to BVP (phase 1: ΔLVEFHBP 21.3% and ΔLVEFBVP 16.7%; phase 2: ΔLVEFHBP 3.5% and ΔLVEFBVP -2.4%; Pgeneralizedadditivemodel = 0.015). Significant improvements in left ventricular end-diastolic diameter, New York Heart Association functional class, and B-type natriuretic peptide level were observed with both pacing modalities compared with baseline, whereas no significant differences were observed between HBP and BVP. CONCLUSION: HBP delivers a modest but significant improvement in LVEF in patients with persistent AF, impaired ventricular function, and narrow QRS duration post-AVNA compared with BVP. Larger long-term trials are required to confirm the additional improvements in function with HBP.

The initial experience of left bundle branch area pacing in patients with hypertrophic cardiomyopathy.

PURPOSE: Whether left bundle branch area pacing (LBBAP) could be achieved in patients with hypertrophic cardiomyopathy (HCM) requiring ventricular pacing remains unknown. The present study aimed to investigate the feasibility and effect of LBBAP in HCM. METHODS: Patients with HCM who underwent LBBAP were recruited from November 2018 to September 2021. Clinical characteristics, echocardiographic, and pacing parameters were prospectively collected at baseline and during follow-up. RESULTS: Eleven consecutive HCM patients who attempted LBBAP were included (mean age 64.0 ± 8.7 years, female 45.5%, mean interventricular septum 16.7 mm). The success rate of LBBAP was 36.4% (4/11) and the reason for failed LBBAP in other seven HCM patients was the inability to screw the lead into the deep septum or capture the left bundle branch. Patients with successful LBBAP had significantly narrower QRS duration than those with failed cases (118.0 ± 3.7 ms vs. 140.9 ± 9.4 ms, p = .01) while the capture thresholds, sensing amplitudes, and pacing impedances were similar. Successful cases presented with less positive late gadolinium enhancement (25.0% vs. 71.4%, p = .02) and thinner interventricular septum thickness (14.5 ± 1.0 mm vs. 18.0 ± 2.5 mm, p = .02) compared with failed cases. Pacing parameters remained stable and no procedure-related complications occurred during a mean follow-up of 8.9 ± 7.3 months. CONCLUSION: LBBAP may be successfully achieved in less than half of HCM patients due to thick interventricular septum and heavy burden of myocardial fibrosis. Pacing strategies should be cautiously considered in patients with HCM.

Association of time-varying changes in physical activity with cardiac death and all-cause mortality after ICD or CRT-D implantation.

OBJECTIVE: To evaluate the association of longitudinal changes in physical activity (PA) with long-term outcomes after implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D) implantation. METHODS: Patients with ICD/CRT-D implantation from SUMMIT registry were retrospectively analyzed. Accelerometer-derived PA changes over 12 months post implantation were obtained from the archived home monitoring data. The primary endpoints were cardiac death and all-cause mortality. The secondary endpoints were the first ventricular arrthymia (VA) and first appropriate ICD shock. RESULTS: In 705 patients, 446 (63.3%) patients showed improved PA over 12 months after implantation. During a mean 61.5-month follow-up duration, 99 cardiac deaths (14.0%) and 153 all-cause deaths (21.7%) occurred. Compared to reduced/unchanged PA, improved PA over 12 months could result in significantly reduced risks of cardiac death (improved PA ≤ 30 min: hazard ratio (HR) = 0.494, 95% CI: 0.288-0.848; > 30 min: HR = 0.390, 95% CI: 0.235-0.648) and all-cause mortality (improved PA ≤ 30 min: HR = 0.467, 95%CI: 0.299-0.728; > 30 min: HR = 0.451, 95% CI: 0.304-0.669). No differences in the VAs or ICD shocks were observed across different groups of PA changes. PA changes can predict the risks of cardiac death only in the low baseline PA group, but improved PA was associated with 56.7%, 57.4%, and 62.3% reduced risks of all-cause mortality in the low, moderate, and high baseline PA groups, respectively, than reduced/unchanged PA. CONCLUSIONS: Improved PA could protect aganist cardiac death and all-cause mortality, probably reflecting better clinical efficacy after ICD/CRT-D implantation. Low-intensity exercise training might be encouraged among patients with different baseline PA levels.

T1 Mapping and Extracellular Volume Fraction in Dilated Cardiomyopathy: A Prognosis Study.

OBJECTIVES: The aim of this study is to examine the prognostic value of T1 mapping and the extracellular volume (ECV) fraction in patients with dilated cardiomyopathy (DCM). BACKGROUND: Patients with DCM with functional left ventricular remodeling have poorer prognoses. Noninvasive assessment of myocardial fibrosis using T1 mapping and the ECV fraction may improve risk stratification of patients with DCM; however, this has not yet been systematically evaluated. METHODS: A total of 659 consecutive patients with DCM (498 men; 45 ± 15 years) who underwent cardiac magnetic resonance with T1 mapping and late gadolinium enhancement (LGE) imaging with a 1.5-T magnetic resonance scanner were enrolled in this study. Primary endpoints were cardiac-related death and heart transplantation. Secondary endpoints were hospitalization for heart failure, ventricular arrhythmias, and implantable cardioverter-defibrillator or cardiac resynchronization therapy implantation. Survival estimates were calculated by Kaplan-Meier curves with the log-rank test. RESULTS: During a mean follow-up of 66.3 ± 20.9 months, 122 and 205 patients with DCM reached the primary and secondary endpoints, respectively. The presence of LGE had an association with both of the primary and secondary endpoints observed in the patients with DCM (both P < 0.001). The maximum native T1 (HR: 1.04; 95% CI: 1.02-1.09) and maximum ECV fraction (HR: 1.14; 95% CI: 1.08-1.21) had associations with the primary endpoints in the patients with positive LGE (both P < 0.001), whereas the mean native T1 (HR: 1.13; 95% CI: 1.10-1.36) and mean ECV fraction (HR: 1.32; 95% CI: 1.12-1.53) had the best associations in the patients with negative LGE (all P < 0.001). CONCLUSIONS: T1 mapping and the ECV fraction had prognostic value in patients with DCM and were particularly important in patients with DCM without LGE. Using a combination of T1 mapping, ECV fraction, and LGE provided optimal risk stratification for patients with DCM.