Outcomes of Upgrading to LBBP in CRT Nonresponders: A Prospective, Multicenter, Nonrandomized, Case-Control Study.

BACKGROUND: Cardiac resynchronization therapy (CRT) nonresponders account for nearly 30% of CRT candidates. Left-bundle branch pacing (LBBP) is an alternative to CRT. OBJECTIVES: This study aimed to evaluate the feasibility, clinical efficacy, and outcomes of upgrading to LBBP in CRT nonresponders, using propensity-score matching (PSM) analysis. METHODS: CRT nonresponders were defined as those with an implantable CRT-pacemaker or CRT-defibrillator for more than 12 months who remained nonresponsive (a decrease in left ventricular end-systolic volume of <15% or a left ventricular ejection fraction [LVEF] absolute increase of <5%) after optimal medical therapy and device optimization compared with baseline. In total, 145 CRT nonresponders were prospectively enrolled and randomly divided into 2 groups: upgraded to LBBP (n = 48), and continuing biventricular pacing (BVP) (control; n = 97). PSM was performed at a 1:1 ratio, and clinical evaluation and echocardiographic assessments were compared at baseline and follow-up in paired cohorts. The primary composite endpoint for clinical outcomes (heart failure-related rehospitalization events, all-cause death, or heart transplantation) was analyzed. RESULTS: Successful upgrading to LBBP was achieved in 48/49 patients (97.96%), with a significant decrease in QRS duration (P < 0.001). In the paired LBBP group, LVEF significantly increased (baseline: 29.75% ± 7.79%; 6 months: 37.78% ± 9.25% [P < 0.001]; 12 months: 38.84% ± 12.13% [P < 0.001]) with 21/44 patients (47.73%) classified as echocardiographically responsive, whereas in the BVP control group, no significant improvement was observed (29.55% ± 6.74% vs 29.22% ± 8.10%; P = 0.840). In a multivariate logistic regression model, LV end-diastolic volume and baseline LBBB QRS morphology were independent predictors of echocardiographic response after upgrading to LBBP. At a median 24 months, the primary composite endpoint was significantly lower in the LBBP group (HR: 0.31; 95% CI: 0.14-0.72; log-rank P = 0.007). CONCLUSIONS: Upgrading to LBBP is feasible and effective in achieving significant heart function improvement and better clinical outcomes in CRT nonresponders, making it a reasonable and promising pacing strategy. (LBBP in CRT Non-Response patients; ChiCTR1900028131).

Cardiac resynchronization therapy from an iliac approach in a patient without superior access: a case report.

Background: Cardiac resynchronization therapy (CRT) has been shown to benefit patients with heart failure and left bundle branch block (LBBB). However, CRT implantation is challenging when the superior venous access is not feasible. Case summary: A 50-year-old man with a history of dilated cardiomyopathy and complete LBBB was referred to our hospital for CRT management. Angiography showed that the left and right brachiocephalic veins were occluded. Cardiac resynchronization therapy was finally implanted via the iliac vein. Follow-up echocardiography showed improved cardiac function, and the pacing system was functioning properly. Discussion: The iliac vein access is feasible for CRT implantation with good stability, which can be a viable alternative to avoid unnecessary risk associated with thoracotomy and epicardial lead placement.

A cross-sectional study on the association between dietary inflammatory index and hyperuricemia based on NHANES 2005-2018.

Background: Hyperuricemia is a common condition that can lead to gout and other related diseases. It has been suggested that Inflammatory factors play important role in the development and progression of hyperuricemia. The dietary inflammatory index (DII) enables the assessment of the inflammatory potential of an individual's diet. This study aimed to investigate the association between DII and hyperuricemia. Methods: This study was performed based on a cross-sectional dataset from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Participants aged 18 years and above with dietary intake and serum uric acid level information were included. DII scores were calculated using dietary intake data, based on which participants were categorized into tertiles. Multivariable logistic regression analysis was adopted to investigate the association between DII and hyperuricemia. Results: Among a total of 31,781 participants in the analysis, 5,491 had hyperuricemia. After adjusting confounding factors, the odds of hyperuricemia are significantly higher in the second (OR 1.17, 95% CI 1.07-1.29) and third tertiles (OR 1.31, 95% CI 1.19-1.44) relative to the first one. Conclusion: This study suggested that diet with higher inflammatory potential, as measured by DII, is associated with increased hyperuricemia risk. These findings indicated that dietary modification may be a potential approach for hyperuricemia's prevention and control.

Real-world evidence for the use of subcutaneous implantable cardioverter-defibrillators in China: A single-center experience.

BACKGROUND: Subcutaneous implantable cardioverter-defibrillators (S-ICDs) have been shown to be non-inferior to transvenous ICDs in the prevention of sudden cardiac death (SCD), but there is still a lack of evidence from clinical trials in China. We investigated whether S­ICD implantation in the Chinese population is safe and feasible and should be promoted in the future. METHODS: Consecutive patients undergoing S­ICD implantation at our center were enrolled in this retrospective study. Data were collected within the median follow-up period of 554 days. Data concerning patient selection, implantation procedures, complications, and episodes of shock were analyzed. RESULTS: In total, 70.2% of all 47 patients (median age = 39 years) were included for secondary prevention of SCD with different etiologies. Vector screening showed that 98% of patients were with > 1 appropriate vector in all postures. An intraoperative defibrillation test was not performed on six patients because of the high risk of disease deterioration, while all episodes of ventricular fibrillation induced post implantation were terminated by one shock. As expected, no severe complications (e.g., infection and device-related complications) were observed, except for one case of delayed healing of the incision. Overall, 15 patients (31.9%) experienced appropriate shocks (AS) with all episodes terminated by one shock. Two patients (4.3%) experienced inappropriate shocks (IAS) due to noise oversensing, resulting in a high Kaplan-Meier IAS-free rate of 95.7%. CONCLUSION: Based on appropriate patient selection and standardized implantation procedures, this real-world study confirmed the safety and efficacy of S­ICD in Chinese patients, indicating that it may help to promote the prevention of SCD in China.

Electrical Resynchronization and Clinical Outcomes During Long-Term Follow-Up in Intraventricular Conduction Delay Patients Applied Left Bundle Branch Pacing-Optimized Cardiac Resynchronization Therapy.

BACKGROUND: Left bundle branch-optimized cardiac resynchronization therapy (LOT-CRT) has shown encouraging results for QRS duration reduction and heart function improvement. However, the feasibility and efficacy of LOT-CRT have not been well established in intraventricular conduction delay patients. This study aims to assess and compare the efficacy and clinical outcome of CRT based on left bundle branch pacing, combined with coronary sinus left ventricular pacing (LOT-CRT) with CRT via biventricular pacing (BiV-CRT) in intraventricular conduction delay patients indicated for CRT. METHODS: Consecutive patients with intraventricular conduction delay and CRT indications were assigned nonrandomized to LOT-CRT (n=30) or BiV-CRT (n=55). Addition of the left bundle branch pacing (or coronary venous) lead was at the discretion of the implanting physician guided by suboptimal paced QRS complex and on clinical grounds. Echocardiographic parameters and clinical characteristics were accessed at baseline and during 2-years' follow-up. RESULTS: Success rate for LOT-CRT and BiV-CRT was 96.8% and 96.4%. LOT-CRT had greater reduction of QRS duration compared with BiV-CRT (42.7±17.4 ms versus 21.9±21.5 ms; P<0.001). Higher left ventricular ejection fraction was also achieved in LOT-CRT than BiV-CRT at 6-month (36.7±9.8% versus 30.5±6.4%; P<0.05), 12-month (34.8±7.6% versus 30.3±6.2%; P<0.05), 18-month (36.3±7.9% versus 28.1±6.6%; P<0.005), and 24-month follow-up (37±9.5% versus 30.5±7%; P<0.05). Adverse clinical outcomes including heart failure rehospitalization and mortality were lower in LOT-CRT group for 24 months follow-up (hazard ratio, 0.33; P=0.035). CONCLUSIONS: LOT-CRT improves ventricular electrical synchrony and may provide greater clinical outcomes as compared with BiV-CRT in intraventricular conduction delay patients. These findings need further evaluation in future randomized controlled trials.

Trimetazidine Affects Mitochondrial Calcium Uniporter Expression to Restore Ischemic Heart Function via Reactive Oxygen Species/NFκB Pathway Inhibition.

ABSTRACT: Studies have demonstrated the roles of trimetazidine beyond being an antianginal agent in ischemic heart disease (IHD) treatment associated with mechanisms of calcium regulation. Our recent studies revealed that mitochondrial calcium uniporter (MCU, the pore-forming unit responsible for mitochondrial calcium entrance) inhibition provided cardioprotective effects for failing hearts. Because trimetazidine and MCU are associated with calcium homeostasis, we hypothesized that trimetazidine may affect MCU to restore the failing heart function. In the present study, we tested this hypothesis in the context of cardiac ischemia in vivo and in vitro. The IHD model was established in male C57BL/6 mice followed by trimetazidine administration intraperitoneally at 20 mg/kg q.o.d for 8 weeks. In vitro studies were performed in a hypoxia model using primary rat neonate cardiomyocytes. The mice survival outcomes and heart function, pathohistologic, and biological changes were analyzed. The results demonstrated that trimetazidine treatment resulted in longer life spans and heart function improvement accompanied by restoration of mitochondrial calcium levels and increase in ATP production via MCU down-regulation. Studies in vitro further showed that trimetazidine treatment and MCU inhibition decreased reactive oxygen species (ROS) production, inhibited the NFκB pathway, and protected the cardiomyocytes from hypoxic injury, and vice versa. Thus, the present study unveils a unique mechanism in which trimetazidine is involved in ameliorating the ischemic failing heart via MCU down-regulation and the following mitochondrial calcium homeostasis restoration, ROS reduction, and cardiomyocyte protection through NFκB pathway inhibition. This mechanism provides a novel explanation for the treatment effects of trimetazidine on IHD.

Current of injury is an indicator of lead depth and performance during left bundle branch pacing lead implantation.

BACKGROUND: Monitoring of lead depth is crucial to achieve left bundle branch pacing (LBBP) with a low capture threshold and avoid septal perforation, but lacks informative approach. OBJECTIVE: We aimed to prospectively assess the predictive value of current of injury on the occurrence of inadequate left bundle branch (LBB) capture threshold and acute septal perforation. METHODS: Consecutive patients who received LBBP were enrolled. ST-segment elevation ≥ 25% of intrinsic R-wave amplitude on the unipolar intracardiac electrogram was defined as a sign of distinct current of injury. An LBB capture threshold of <1.5 V/0.5 ms was considered acceptable. RESULTS: LBBP was attempted 513 times in 212 patients. The LBB capture threshold was more likely to improve to an acceptable level after 10 minutes in leads with initial (33 of 47 vs 0 of 8, with vs without) and residual (29 of 33 vs 4 of 14, with vs without) current of injury recorded on the tip electrode (P < .0001). Lead perforation during the procedure has occurred in 11 patients who had no current of injury noted on the tip electrode. The ratio of current of injury recorded on the tip electrode to that on the ring electrode was correlated to the lead depth determined by sheath angiography (Spearman correlation coefficient -0.624; P < .0001), and microperforation is highly possible when the ratio is decreased to <1 (sensitivity 100%; specificity 96.6%). CONCLUSION: Current of injury is a useful tool in forecasting LBBP lead depth and septal perforation, and it could facilitate the decision-making process when the initial LBB capture threshold is undesirable.

Evaluation of electrophysiological characteristics and ventricular synchrony: An intrapatient-controlled study during His-Purkinje conduction system pacing versus right ventricular pacing.

OBJECTIVES TO BACKGROUND: To compare electromechanical ventricular synchrony when pacing from different sites, including right ventricular apex pacing (RVAP), right ventricular septum pacing (RVSP), His bundle pacing (HBP), left bundle branch pacing (LBBP), and RVSP during unipolar pacing from the ring electrode of LBBP lead (RVSPring ) in each patient and evaluate the correlations between electrophysiological characteristics and ventricular synchrony. METHODS: Twenty patients with complete atrioventricular block indicated for dual-chamber pacemaker implantation were included in the study. Unipolar pacing at different sites, including RVAP, RVSP, HBP, LBBP, and RVSPring , was successively performed in each patient. The pacing characteristics and echocardiogram parameters were collected and compared among intrinsic rhythm and pacing at different sites. RESULTS: Similar to HBP (114.84 ± 18.67 ms), narrower paced QRSd was found in LBBP (116.15 ± 11.60 ms) as compared to RVSPring (135.11 ± 13.68 ms), RVSP (141.65 ± 14.26 ms), and RVAP (160.15 ± 19.35 ms) (p < .001). LBBP showed comparable pacing parameters to RVAP or RVSP and was significantly better than HBP, with maintained cardiac function. TS-12-SD was significantly improved in LBBP (41.80 ± 20.97 ms) than RVAP (69.70 ± 32.42 ms, p = .003) and RVSP (63.30.56 ± 32.53 ms, p = .018) but similar to HBP (51.50 ± 25.67 ms, p = .283) or RVSPring (57.80 ± 25.65 ms, p = .198). Among these pacing strategies, negative values of interventricular mechanical delay (IVMD) were only identified in LBBP (-19.25 ± 18.43 ms), significantly different from RVAP (35.00 ± 30.72 ms), RVSP (22.85 ± 22.05 ms), HBP (5.20 ± 18.64 ms), and RVSPring (16.00 ± 26.76 ms (all p < .05). Using Pearson's analysis, Sti-LVAT was positively correlated with QRS duration, IVMD, TS-12-SD, LVEDV, and LVESV, while a negative relationship could be observed for left ventricular ejection fraction. CONCLUSIONS: His-Purkinje conduction system pacing (HPCSP) achieved better electrical and mechanical synchrony than conventional RV pacing. For interventricular synchrony, only LBBP initiated earlier LV activation than RV, in accordance with the right bundle branch block (RBBB) pattern of paced QRS during LBBP. Sti-LVAT might be a good parameter correlating with LV systolic function and mechanical synchrony.

Risk factors of pacing dependence and cardiac dysfunction in patients with permanent pacemaker implantation.

AIMS: Right ventricular pacing (RVP) dependence could impair left ventricular ejection fraction (LVEF). This study aimed to illuminate the relationship between RVP proportion and LVEF, as well as disclosing independent predictors of RVP dependence. METHODS AND RESULTS: Patients indicated for permanent pacemaker implantation were included (2016-2020). The ventricular pacing lead was placed in right ventricular apex or septum. Pacing mode programming followed universal standard. Electrocardiographic, echocardiographic, and serological parameters were collected. RVP dependence was defined according to its influence on LVEF. This study was of case-control design. Included patients were matched by potentially confounding factors through propensity score matching. A total of 1183 patients were included, and the mean duration of follow-up was 24 months. Percentage of RVP < 80% hardly influenced LVEF; however, LVEF tended to decrease with higher RVP proportion. High degree/complete atrioventricular block (AVB) [odds ratio (OR) = 5.71, 95% confidence interval (CI): 3.66-8.85], atrial fibrillation (AF) (OR = 2.04, 95% CI: 1.47-2.82), percutaneous coronary intervention (PCI) (OR = 2.89, 95% CI: 1.24-6.76), maximum heart rate (HRmax ) < 110 b.p.m. (OR = 2.74, 95% CI: 1.58-4.76), QRS duration > 120 ms (OR = 2.46, 95% CI: 1.42-4.27), QTc interval > 470 ms (OR = 2.01, 95% CI: 1.33-3.05), and pulmonary artery systolic pressure (PASP) > 40 mmHg (OR = 1.93, 95% CI: 1.46-2.56) were proved to predict RVP dependence. CONCLUSIONS: High RVP percentage (>80%) indicating RVP dependence significantly correlates with poor prognosis of cardiac function. High degree/complete AVB, AF, ischaemic aetiology, PCI history, HRmax  < 110 b.p.m., QRS duration > 120 ms, QTc interval > 470 ms, and PASP > 40 mmHg were verified as independent risk factors of RVP dependence.

Cardiac resynchronization therapy via left bundle branch pacing vs. optimized biventricular pacing with adaptive algorithm in heart failure with left bundle branch block: a prospective, multi-centre, observational study.

AIMS: The purpose of our study was to evaluate the feasibility and efficacy of cardiac resynchronization therapy (CRT) via left bundle branch pacing (LBBP-CRT) compared with optimized biventricular pacing (BVP) with adaptive algorithm (BVP-aCRT) in heart failure with reduced left ventricular ejection fraction ≤35% (HFrEF) and left bundle branch block (LBBB). METHODS AND RESULTS: One hundred patients with HFrEF and LBBB undergoing CRT were prospectively enrolled in a non-randomized fashion and divided into two groups (LBBP-CRT, n = 49; BVP-aCRT, n = 51) in four centres. Implant characteristics and echocardiographic parameters were accessed at baseline and during 6-month and 1-year follow-up. The success rate for LBBP-CRT and BVP-aCRT was 98.00% and 91.07%. Fused LBBP had the greatest reduced QRS duration compared to BVP-aCRT (126.54 ± 11.67 vs. 102.61 ± 9.66 ms, P < 0.001). Higher absolute left ventricular ejection fraction (LVEF) and △LVEF was also achieved in LBBP-CRT than BVP-aCRT at 6-month (47.58 ± 12.02% vs. 41.24 ± 10.56%, P = 0.008; 18.52 ± 13.19% vs. 12.89 ± 9.73%, P = 0.020) and 1-year follow-up (49.10 ± 10.43% vs. 43.62 ± 11.33%, P = 0.021; 20.90 ± 11.80% vs. 15.20 ± 9.98%, P = 0.015, P = 0.015). There was no significant difference in response rate between two groups while higher super-response rate was observed in LBBP-CRT as compared to BVP-aCRT at 6 months (53.06% vs. 36.59%, P = 0.016) and 12 months (61.22% vs. 39.22%, P = 0.028) during follow-up. The pacing threshold was lower in LBBP-CRT at implant and during 1-year follow-up (both P < 0.001). Procedure-related complications and adverse clinical outcomes including heart failure hospitalization and mortality were not significantly different in two groups. CONCLUSIONS: The feasibility and efficacy of LBBP-CRT demonstrated better electromechanical resynchronization and higher clinical and echocardiographic response, especially higher super-response than BVP-aCRT in HFrEF with LBBB.

Comparison of different insulin resistance surrogates to predict hyperuricemia among U.S. non-diabetic adults.

Purpose: Although it has been well-acknowledged that insulin resistance (IR) plays a critical role in the development of hyperuricemia (HU), specific relationship between IR and HU in non-diabetic patients remains rarely studied, and there is still no large-scale research regarding this issue. This study aims to explore the association between triglyceride glucose (TyG), TyG with body mass index (TyG-BMI), the ratio of triglycerides divided by high-density lipoprotein cholesterol (TG/HDL-C), metabolic score for insulin resistance (METS-IR), and the risk of HU in non-diabetic patients in The United States of America. Patients and methods: Data from the National Health and Nutrition Examination Survey (NHANES) enrolling a representative population aged ≥18-year-old were included to calculate these four indexes. Logistic regression analysis was applied to describe their associations and calculate odds ratios (OR) while the Receiver Operating Characteristic curve was utilized to assess the prediction ability of these four indexes. Results: A total of 7,743 people (3,806 males and 3,937 females, mean age: 45.17 ± 17.10 years old) were included in this study, among whom 32.18% suffered from HU. After adjustment for sex, age, ethnicity, education background, smoking status, drinking status, systolic blood pressure (SBP), diastolic blood pressure (DBP), metabolic equivalent values (METs), total cholesterol, low-density lipoprotein cholesterol, and estimated glomerular filtration rate, it showed that all four indexes were closely related to HU. Compared with the lowest quartile, OR of the highest quartile of these four indicators for HU were as following respectively: TyG: 5.61 (95% CI: 4.29-7.32); TyG-BMI: 7.15 (95% CI: 5.56-9.20); TG/HDL-C: 4.42 (95% CI: 3.49-5.60); METS-IR: 7.84 (95% CI: 6.07-10.13). TyG, TyG-BMI, TG/HDL-C and METS-IR had moderate discrimination ability for HU, with an AUC value of 0.66 (95% CI: 0.65-0.68), 0.67 (95% CI: 0.65-0.68), 0.68 (95% CI: 0.67-0.69) and 0.68 (95% CI: 0.66-0.69) respectively. Each index showed better prediction ability for HU risk in females than in males. Conclusion: It was found that the risk of HU was positively associated with the elevation of TyG, TyG-BMI, TG/HDL-C and METS-IR in a large-scale population of U.S., and TyG-BMI and METS-IR have a better ability to identify HU in both genders.

Prevalence and Related Risk Factors Associated with Coronary Heart Disease (CHD) Among Middle-Aged and Elderly Patients with Vision Impairment (VI).

PURPOSE: To investigate the prevalence and related risk factors associated with coronary heart disease (CHD) among middle-aged and elderly patients with vision impairment (VI). PATIENTS AND METHODS: The study was conducted with 1355 visually impaired adults over 45 years old, recruited from a Rehabilitation Hospital in China. Visual impairment is diagnosed by a doctor according to guidelines. Data were analyzed using multiple correspondence and logistic regression analysis. This research represents an important step towards the development of empirically based practical suggestions for decision-makers and health professionals that support visually impaired middle-aged and elderly people to participate in physical exercise and weight management when needed. RESULTS: Of the 1335 middle-aged and elderly adults (mean age ± SD, 63.56 ± 7.74 years; 45.6% male) with VI, a total of 154 (11.5%) developed CHD. In all people with VI, age (OR 1.47; 95% CI 1.16-2.02), hypertension (OR 2.14; 95% CI 1.46-3.14), diabetes (OR 3.79; 95% CI 2.29-6.27), blindness (OR 1.68; 95% CI 1.16-2.43), moderate activity (OR 0.86; 95% CI 0.69-0.98), and HR <60 beats/min (OR 1.43; 95% CI 1.08-2.48) are significantly related to CHD. Statistical analysis based on age grouping indicated that fasting plasma glucose, hypertension, diabetes, blindness, heart rate (<60 beats/min), and moderate activity were shown to have a strong association with development of CHD in age group <65 years (p < 0.05). CONCLUSION: Compared with historical data, poorer vision degree, resting heart rate below 60 beats a minute and low physical activity level are emerging as new and increasing threats to CHD in middle-aged and elderly VI population. Interventions to enhance physical functioning and risk screening may be effective in the prevention of CHD in VI population.

Procedure-Related Complications of Left Bundle Branch Pacing: A Single-Center Experience.

Background: Although left bundle branch pacing (LBBP) has emerged as a novel physiological pacing strategy with a low and stable threshold, its safety has not been well-documented. In the present study, we included all the patients with procedure-related complications at our centre to estimate these LBBP cases with unique complications. Methods: We enrolled 612 consecutive patients who received the procedure in Zhongshan Hospital, Fudan University, between January 2018 and July 2020. Regular follow-ups were conducted (at 1, 3, and 6 months in the first year and every 6-12 months from the second year), and the clinical data of the patients with complications were collected and analyzed. Results: With a mean follow-up period of 12.32 ± 5.21 months, procedure-related complications were observed in 10 patients (1.63%) that included two postoperative septum perforations (2/612, 0.33%), two postoperative lead dislodgements (2/612, 0.33%), four intraoperative septum injuries (4/612, 0.65%), and two intraoperative lead fractures (2/612, 0.33%). Pacing parameters were stable during follow-up, and no major complications were observed after lead repositioning in the cases of septum perforation and lead dislodgement. Conclusion: The incidence of procedure-related complications for LBBP, namely postoperative septum perforation, postoperative lead dislodgement, intraoperative septum injury, and intraoperative lead fracture, were low. No adverse clinical outcomes were demonstrated after successful repositioning of the lead and appropriate treatment.

Protective effects of cardiac resynchronization therapy in a canine model with experimental heart failure by improving mitochondrial function: a mitochondrial proteomics study.

PURPOSE: Cardiac resynchronization therapy (CRT) is well acknowledged as an effective treatment for dyssynchronous heart failure. However, the molecular mechanism is unclear to date. Mitochondrial dysfunction and impaired energetic metabolism are two important mechanisms that lead to heart failure. Therefore, we aim to screen the changes of mitochondria-associated proteins and signaling pathways involved in heart failure and CRT treatment. METHODS: A total of 24 beagle dogs were randomly assigned into control (CON), heart failure (HF), or CRT group. Myocardial mitochondria from the free wall of left ventricle was extracted for isobaric tags for relative and absolute quantitation (iTRAQ) labeling coupled with two-dimensional liquid chromatography tandem mass spectrometry analysis (2DLC-MS/MS). RESULTS: A total of 2190 proteins were identified, among which 234 proteins were differentially expressed in HF compared with CON group, 151 proteins were differentially expressed in CRT compared with HF group. A total of 192 of the 234 differentially expressed proteins in HF group were changed oppositely by CRT treatment, and 128 of the 151 CRT-induced differentially expressed proteins showed opposite trend of expression to HF/CON. Gene Ontology analysis of the 128 proteins revealed that 16 were localized in mitochondria, 17 were associated with calcium signaling, and 7 could be secreted extracellularly for cell-to-cell signaling. Calpain-1 (CAPN1), which is localized to mitochondria and related to calcium signaling, was upregulated in HF and downregulated after CRT treatment. CRT treatment also improved mitochondrial morphology and function and reduced collagen areas of both interstitial and perivascular fibrosis. CONCLUSIONS: CRT treatment significantly improved cardiac function, reduced myocardial fibrosis, and enhanced mitochondrial function in the failing heart through CAPN1 downregulation.

The feasibility and safety of left bundle branch pacing vs. right ventricular pacing after mid-long-term follow-up: a single-centre experience.

AIMS: The aim of this study is to prospectively assess the feasibility and safety of left bundle branch pacing (LBBP) when compared with right ventricular pacing (RVP) during mid-long-term follow-up in a large cohort. METHODS AND RESULTS: Patients (n = 554) indicated for pacemaker implantation were prospectively and consecutively enrolled and were non-randomized divided into LBBP group and RVP group. The levels of cTnT and N-terminal pro-B type natriuretic peptide were measured and compared within 2 days post-procedure between two groups. Implant characteristics, procedure-related complications, and clinical outcomes were also compared. Pacing thresholds, sensing, and impedance were assessed during procedure and follow-up. Left bundle branch pacing was feasible with a success rate of 94.8% with high incidence of LBB potential (89.9%), selective LBBP (57.8%), and left deviation of paced QRS axis (79.7%) with mean Sti-LVAT of 65.07 ± 8.58 ms. Paced QRS duration was significantly narrower in LBBP when compared with RVP (132.02 ± 7.93 vs. 177.68 ± 15.58 ms, P < 0.0001) and the pacing parameters remained stable in two groups during 18 months follow-up. cTnT elevation was more significant in LBBP when compared with RVP within 2 days post-procedure (baseline: 0.03 ± 0.03 vs. 0.02 ± 0.03 ng/mL, P = 0.002; 1 day post-procedure: 0.13 ± 0.09 vs. 0.04 ± 0.03 ng/mL, P < 0.001; 2 days post-procedure: 0.10 ± 0.08 vs. 0.03 ± 0.08 ng/mL, P < 0.001). The complications and cardiac outcomes were not significantly different between two groups. CONCLUSION: Left bundle branch pacing was feasible in bradycardia patients associated with stable pacing parameters during 18 months follow-up. Paced QRS duration was significantly narrower than that of RVP. Though cTnT elevation was more significant in LBBP within 2 days post-procedure, the complications, and cardiac outcomes were not significantly different between two groups.

Circulating metabolite profiles to predict response to cardiac resynchronization therapy.

BACKGROUND: Heart failure is associated with ventricular dyssynchrony and energetic inefficiency, which can be alleviated by cardiac resynchronization therapy (CRT) with approximately one-third of non-response rate. Thus far, there is no specific biomarker to predict the response to CRT in patients with heart failure. In this study, we assessed the role of the blood metabolomic profile in predicting the response to CRT. METHODS: A total of 105 dilated cardiomyopathy patients with severe heart failure who received CRT were included in our two-stage study. Baseline blood samples were collected prior to CRT implantation. The response to CRT was defined according to echocardiographic criteria. Metabolomic profiling of serum samples was carried out using ultrahigh performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry. RESULTS: Seventeen metabolites showed significant differences in their levels between responders and non-responders, and these metabolites were primarily involved in six pathways, including linoleic acid metabolism, Valine, leucine and isoleucine biosynthesis, phenylalanine metabolism, citrate cycle, tryptophan metabolism, and sphingolipid metabolism. A combination of isoleucine, tryptophan, and linoleic acid was identified as an ideal metabolite panel to distinguish responders from non-responders in the discovery set (n = 51 with an AUC of 0.981), and it was confirmed in the validation set (n = 54 with an AUC of 0.929). CONCLUSIONS: Mass spectrometry based serum metabolomics approach provided larger coverage of metabolome which can help distinguish CRT responders from non-responders. A combination of isoleucine, tryptophan, and linoleic acid may associate with significant prognostic values for CRT.

Patient-tailored SyncAV algorithm: A novel strategy to improve synchrony and acute hemodynamic response in heart failure patients treated by cardiac resynchronization therapy.

INTRODUCTION: Several automatic algorithms have developed to optimize the timing cycle setting in cardiac resynchronization therapy (CRT). The present study aims to investigate whether the novel device-based SyncAV algorithm could elicit better synchrony and acute hemodynamic response. METHODS AND RESULTS: Thirty five patients undergoing CRT implantation were prospectively studied. The device was programmed to three biventricular (BiV) pacing modes sequentially after the procedure: QuickOpt algorithm (mode I), SyncAV algorithm with default 50 ms offset (mode II), and SyncAV algorithm with optimized offset minimizing QRS duration (QRSd) (mode III). After each setting, electrocardiographic and echocardiographic data were collected. As a result, QRSd was reduced from 172.8 ± 17.9 ms during intrinsic conduction to 153.1 ± 15.9 ms in mode I, further narrowed to 140.5 ± 16.7 ms in mode II, and reached shortest (134.8 ± 16.1 ms) in mode III (P < .01 for all). Besides, significantly shorter QT intervals were observed in mode I (453.2 ± 45.5 ms), mode II (443.9 ± 34.2 ms) and mode III (444.1 ± 28.7 ms), compared with native condition (472.5 ± 51.2 ms) (P < .01). All three BiV modes exhibited comparable Tp Te interval and Tp Te /QT ratio (P > .05). Mode I presented significantly higher aortic velocity time integral than intrinsic conduction (21.0 ± 6.4 cm vs 18.4 ± 5.5 cm; P < .01), which was even higher in mode II (22.0 ± 6.5 cm) and mode III (23.7 ± 6.5 cm). All three BiV modes significantly reduced standard deviation of time to peak contraction of 12-LV segments (Ts-SD) (Mode I: 55.2 ± 16.5 ms, Mode II: 50.2 ± 14.7 ms, Mode III: 45.4 ± 14.4 ms) compared with intrinsic conduction (66.3 ± 18.4 ms) (P < .01), with Mode III demonstrating the smallest (P < .01). CONCLUSION: SyncAV CRT ameliorated electrical and mechanical synchrony as well as acute hemodynamic response beyond conventional QuickOpt optimization. An additional individualized adjustment to the SyncAV offset added to its advantage.

The mechanical effects of CRT promoting autophagy via mitochondrial calcium uniporter down-regulation and mitochondrial dynamics alteration.

The mechanism of cardiac resynchronization therapy (CRT) remains unclear. In this study, mitochondria calcium uniporter (MCU), dynamin-related protein-1 (DNM1L/Drp1) and their relationship with autophagy in heart failure (HF) and CRT are investigated. Thirteen male beagle's dogs were divided into three groups (sham, HF, CRT). Animals received left bundle branch (LBB) ablation followed by either 8-week rapid atrial pacing or 4-week rapid atrial pacing and 4-week biventricular pacing. Cardiac function was evaluated by echocardiography. Differentially expressed genes (DEGs) were detected by microarray analysis. General morphological changes, mitochondrial ultrastructure, autophagosomes and mitophagosomes were investigated. The cardiomyocyte stretching was adopted to imitate the mechanical effect of CRT. Cells were divided into three groups (control, angiotensin-II and angiotensin-II + stretching). MCU, DNM1L/Drp1 and autophagy markers were detected by western blots or immunofluorescence. In the present study, CRT could correct cardiac dysfunction, decrease cardiomyocyte's size, alleviate cardiac fibrosis, promote the formation of autophagosome and mitigate mitochondrial injury. CRT significantly influenced gene expression profile, especially down-regulating MCU and up-regulating DNM1L/Drp1. Cell stretching reversed the angiotensin-II induced changes of MCU and DNM1L/Drp1 and partly restored autophagy. CRT's mechanical effects down-regulated MCU, up-regulated DNM1L/Drp1 and subsequently enhanced autophagy. Besides, the mechanical stretching prevented the angiotensin-II-induced cellular enlargement.

Whole-exome sequencing reveals a novel mutation of MT-ND5 gene in a mitochondrial cardiomyopathy pedigree: Patients who show biventricular hypertrophy, hyperlactacidemia, pulmonary hypertension, and decreased exercise tolerance.

OBJECTIVE: The aim of the present study was to determine whether pathogenic mutations were present in families with mitochondrial cardiomyopathy that presented during adolescence. METHODS: The proband was a 21-year-old man who presented clinically with palpitations, chest tightness, pulmonary hypertension, and limited exercise tolerance. Cardiac magnetic resonance imaging studies showed biventricular cardiac hypertrophy. We determine whether pathogenic mutations were present by whole-exome sequencing (WES) in families. RESULTS: Screening of the family using tandem mass spectrometry showed elevated lactic acid levels, glutaric aciduria, a mildly increased glutarylcarnitine-to-octanoylcarnitine ratio, and normal blood α-glucosidase, which was consistent with a respiratory chain complex 1 metabolic disorder. We identified a novel mutation of MT-ND5, c.1315A>G (p.Thr439Ala). Skeletal muscle biopsy histology showed predominantly ragged red fibers and few ragged blue fibers, which was consistent with mitochondrial myopathy. CONCLUSION: In the present study, we identified a novel mutation of MT-ND5, c.1315A>G (p.Thr439Ala), in a family pedigree using WES.