Cardiac Electrical and Mechanical Synchrony Analysis of LBBP and RVP Utilizing Tissue Doppler Imaging Technology.

Background: Right ventricular pacing (RVP) therapy is the conventional approach for atrioventricular block despite its propensity to cause electrical and mechanical dyssynchrony. This dyssynchrony increases the risk of atrial fibrillation and heart failure, eventually leading to left ventricular dysfunction. Left bundle branch pacing (LBBP) has recently emerged as a novel physiological pacing method. This study utilizes conventional ultrasound cardiography (UCG), two-dimensional speckle tracking imaging (2D-STI), and tissue Doppler imaging (TDI) to investigate the disparities in electrical and mechanical cardiac synchrony between LBBP and RVP patients. Methods: The retrospective analysis includes data from patients who underwent LBBP (n=50) and RVP (n=50) in Zhangjiagang First People's Hospital between January 2019 and June 2020, meeting the stipulated inclusion criteria. The study compares pacing parameters, UCG metrics, cardiac electrical and mechanical synchrony, pacing success rates, and safety events both pre-operation and at 3, 6, 12, and 24 months post-operation. Results: Implantation success rates for both RVP and LBBP groups were 100%, with 92% and 100% pacing success rates, respectively [P = .001 RR (95% CI) : 2.5 (1.5, 3.5)]. The LBBP group exhibited significant advantages over the RVP group throughout the follow-up period. LBBP patients displayed shortened QRS duration, reduced pacing thresholds and impedance, improved sensory function, lower serum NT-proBNP levels, and an increased proportion of NYHA class I patients [P = .003 RR (95% CI) : 1.6 (1.1, 2.3)]. Furthermore, left ventricular ejection fraction increased significantly, while left ventricular diastolic and end-systolic diameters decreased in the LBBP group compared to the RVP group [P = .004 RR (95% CI) : 1.7 (1.3, 2.2)]. The LBBP group also demonstrated shorter ventricular systolic synchrony parameters, including Tls-Dif, PSD, Trs-SD, Tas-SD, Tas-post, Ts-SD, and Ts-DIf, compared to the RVP group [P = .005 RR (95% CI) : 1.5 (1.2, 2.0)]. Notably, no postoperative complications occurred in either group, such as electrode displacement, lead thrombus attachment, incision bleeding, pocket hemorrhage, or infection. However, the readmission rates for heart failure were 16% in the RVP group and 2% in the LBBP group. Conclusion: LBBP achieves physiological cardiac pacing, leading to significant improvements in serum NT-proBNP levels and cardiac function and enhanced ventricular contraction synchrony. Utilizing UCG, 2D-STI, and TDI for quantitative evaluation of cardiac electrical and mechanical synchrony proves to be a valuable clinical approach.

A novel homozygous variant in TRAPPC2L results in a neurodevelopmental disorder and disrupts TRAPP complex function.

BACKGROUND: Next-generation sequencing has facilitated the diagnosis of neurodevelopmental disorders with variable and non-specific clinical findings. Recently, a homozygous missense p.(Asp37Tyr) variant in TRAPPC2L, a core subunit of TRAPP complexes which function as tethering factors during membrane trafficking, was reported in two unrelated individuals with neurodevelopmental delay, post-infectious encephalopathy-associated developmental arrest, tetraplegia and accompanying rhabdomyolysis. METHODS: We performed whole genome sequencing on members of an Ashkenazi Jewish pedigree to identify the underlying genetic aetiology of global developmental delay/intellectual disability in three affected siblings. To assess the effect of the identified TRAPPC2L variant, we performed biochemical and cell biological functional studies on the TRAPPC2L protein. RESULTS: A rare homozygous predicted deleterious missense variant, p.(Ala2Gly), in TRAPPC2L was identified in the affected siblings and it segregated with the neurodevelopmental phenotype within the family. Using a yeast two-hybrid assay and in vitro binding, we demonstrate that the p.(Ala2Gly) variant, but not the p.(Asp37Tyr) variant, disrupted the interaction between TRAPPC2L and another core TRAPP protein, TRAPPC6a. Size exclusion chromatography suggested that this variant affects the assembly of TRAPP complexes. Employing two different membrane trafficking assays using fibroblasts from one of the affected siblings, we found a delay in traffic into and out of the Golgi. Similar to the p.(Asp37Tyr) variant, the p.(Ala2Gly) variant resulted in an increase in the levels of active RAB11. CONCLUSION: Our data fill in a gap in the knowledge of TRAPP architecture with TRAPPC2L interacting with TRAPPC6a, positioning it as a putative adaptor for other TRAPP subunits. Collectively, our findings support the pathogenicity of the TRAPPC2L p.(Ala2Gly) variant.

Enhanced electrochemiluminescent brightness and stability of porphyrins by supramolecular pinning and pinching for sensitive zinc detection.

Ultrasensitive electrochemiluminescence (ECL) detection can benefit substantially from the rational configuration of emitter-enhancer stereochemistry. Here, using zinc(II) meso-5,10,15,20-tetra(4-sulfonatophenyl)porphyrin (ZnTSPP) as a model, we demonstrate that both the ECL intensity and the photostability of this emitter were significantly improved when it was trapped in pyridyl-bridged ß-cyclodextrin dimer (Py(CD)2); a synthetic enhancer that is ECL inactive. Through NMR characterization, we confirmed that ZnTSPP formed a clam-like inclusion complex involving pinning and pinching forces from the biocompatible container Py(CD)2. Up to a threefold increase in the ECL brightness of ZnTSPP was witnessed when it was encapsulated in ß-CD. Absorption and emission spectroscopic data revealed that both the extended excitation lifetime and the restricted mobility of the guest contributed to the observed improvement in signal transduction within the host molecule. This bioinspired entrapment also led to a marked boost in ECL stability. With the aid of the newly identified coreactant H2O2, the hollow TSPP@Py(CD)2 system was employed to create a Zn2+-selective probe that was capable of sensitive and accurate zinc detection. The observed increase in ECL conversion and enhanced photophysical properties of this compact supramolecular assembly render it a novel template for enhancing ECL in analytical applications. Graphical abstract ᅟ.

The incidence and outcomes of delayed response to cardiac resynchronization therapy.

BACKGROUND: The incidence and clinical outcomes of delayed response to cardiac resynchronization therapy (CRT) have not been well clarified. We aimed to observe the incidence and prognosis of delayed response and to identify its possible mechanisms. METHODS: A total of 115 CRT patients were retrospectively analyzed in our study. Patients who met the enrollment criteria were divided into two groups: group A, conventional responders who showed response at 1-year follow-up, and group B, delayed responders who showed response after 1-year follow-up. CRT response was defined as an absolute increase of ≥10% in left ventricular ejection fraction. RESULTS: Fifty-two patients (61 ± 12 years, 37 male) experienced conventional response to CRT and 17 patients (63 ± 11 years, 10 male) experienced delayed response. The mean follow-up time was 5.2 ± 2.4 years. The incidence of delayed response was 14.8% (17/115). All-cause mortality and hospitalization rates for heart failure were similar for delayed and conventional responders. Multivariate logistic regression analysis revealed that scar burden > 35% was an independent predictor of CRT delayed response (odds ratio 8.794, P  =  0.038). CONCLUSIONS: A significant proportion of patients demonstrated delayed response to CRT. The delayed responders had a good prognosis that was similar to that of conventional responders. More scar burden might be related to the incidence of delayed response.

Cardiac electrical and mechanical synchrony of super-responders to cardiac resynchronization therapy.

BACKGROUND: Super-responders (SRs) to cardiac resynchronization therapy (CRT) regain near-normal or normal cardiac function. The extent of cardiac synchrony of SRs and whether continuous biventricular (BIV) pacing is needed remain unknown. The aim of this study was to evaluate the cardiac electrical and mechanical synchrony of SRs. METHODS: We retrospectively analyzed CRT recipients between 2008 and 2016 in 2 centers to identify SRs, whose left ventricular (LV) ejection fraction was increased to ≥50% at follow-up. Cardiac synchrony was evaluated in intrinsic and BIV-paced rhythms. Electrical synchrony was estimated by QRS duration and LV mechanical synchrony by single-photon emission computed tomography myocardial perfusion imaging. RESULTS: Seventeen SRs were included with LV ejection fraction increased from 33.0 ±â€Š4.6% to 59.3 ±â€Š6.3%. The intrinsic QRS duration after super-response was 148.8 ±â€Š30.0 ms, significantly shorter than baseline (174.8 ±â€Š11.9 ms, P = 0.004, t = -3.379) but longer than BIV-paced level (135.5 ±â€Š16.7 ms, P = 0.042, t = 2.211). Intrinsic LV mechanical synchrony significantly improved after super-response (phase standard deviation [PSD], 51.1 ±â€Š16.5° vs. 19.8 ±â€Š8.1°, P < 0.001, t = 5.726; phase histogram bandwidth (PHB), 171.7 ±â€Š64.2° vs. 60.5 ±â€Š22.9°, P < 0.001, t = 5.376) but was inferior to BIV-paced synchrony (PSD, 19.8 ±â€Š8.1° vs. 15.2 ±â€Š6.4°, P = 0.005, t = 3.414; PHB, 60.5 ±â€Š22.9° vs. 46.0 ±â€Š16.3°, P = 0.009, t = 3.136). CONCLUSIONS: SRs had significant improvements in cardiac electrical and LV mechanical synchrony. Since intrinsic synchrony of SRs was still inferior to BIV-paced rhythm, continued BIV pacing is needed to maintain longstanding and synchronized contraction.

Continuous Directional Water Delivery on the 3D-Printed Arrowhead Microstructure Array.

Unidirectional transport is attracting increasing attention in the field of microfluidics, because it does not require an external energy supply. However, most of the current self-driving structures are still plagued with persistent problems that restrict their practical applications. These include low transport velocity, short transport distance, and complex structure. This work reports the design of a new arrowhead microstructure array, on which liquid transport can reach speeds of 23 mm/s and the ratio of transport length to channel width (L/R) can reach up to approximately 40. This structure drives liquid through a unique arrow conformation, which can induce capillary force and arrest the reverse motion of the liquid simultaneously. By means of theory, simulation, and experiment, we have studied the mechanism of liquid transport on this structure. We provide a detailed discussion of the relationship between the velocity of liquid transport and the microstructural dimensions. The findings may inspire the design of novel, unidirectional, liquid-spreading surfaces.