Super Response Research Articles

A predictive model of super response to cardiac resynchronization therapy in short-term period.

The left bundle branch block, nonischemic heart failure (HF) and female gender are the most powerful predictors of a super response to cardiac resynchronization therapy (CRT). It is important to identify super responders who can derive most benefits from CRT. We aimed to establish a predicting model that could be used for prognosis of a super response to CRT in short-term period. Patients with QRS ≥ 130ms, New York Heart Association (NYHA) II-III class of HF, left ventricle ejection fraction (LVEF) ≤ 35% and indications for CRT were included in the study. Before and 6month after CRT the electrocardiography, echocardiography and cardiac scintigraphy were performed. The study's primary endpoint was the NYHA class improvement ≥ 1 and left ventricle end systolic volume decrease > 30% or LVEF improvement > 15% after 6month CRT. Based on collected data, we developed a predictive model regarding a super response to CRT. Of 49 (100.0%) patients, 32 (65.3%) had a super response to CRT. Patients with a super response were likelier to have a lower cardiac index (p = 0.007), higher rates of interventricular delay (IVD) (p = 0.003), phase standard deviation of left ventricle anterior wall (PSD LVAW) (p = 0.009) and ∆QRS (p = 0.02). Only IVD and PSD LVAW were independently associated with a super response to CRT in univariate and multivariate logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.812 (sensitivity 90.62%; specificity 70.59%). Our predictive model is able to distinguish patients with a super response to CRT.

Impact of DCM-Causing Genetic Background on Long-Term Response to Cardiac Resynchronization Therapy

BackgroundPatients with nonischemic dilated cardiomyopathy (DCM), severe left ventricular (LV) dysfunction, and complete left bundle branch block benefit from cardiac resynchronization therapy (CRT). However, a large heterogeneity of response to CRT is described. Several predictors of response to CRT have been identified, but the role of the underlying genetic background is still poorly explored. ObjectivesIn the present study, the authors sought to define differences in LV remodeling and outcome prediction after CRT when stratifying patients according to the presence or absence of DCM-causing genetic background. MethodsFrom our center, 74 patients with DCM subjected to CRT and available genetic testing were retrospectively enrolled. Carriers of causative monogenic variants in validated DCM-causing genes, and/or with documented family history of DCM, were classified as affected by genetically determined disease (GEN+DCM) (n = 25). Alternatively, by idiopathic dilated cardiomyopathy (idDCM) (n = 49). The primary outcome was long-term LV remodeling and prevalence of super response to CRT (evaluated at 24-48 months after CRT); the secondary outcome was heart failure–related death/heart transplant/LV assist device. ResultsGEN+DCM and idDCM patients were homogeneous at baseline with the exception of QRS duration, longer in idDCM. The median follow-up was 55 months. Long-term LV reverse remodeling and the prevalence of super response were significantly higher in the idDCM group (27% in idDCM vs 5% in GEN+DCM; P = 0.025). The heart failure–related death/heart transplant/LV assist device outcome occurred more frequently in patients with GEN+DCM (53% vs 24% in idDCM; P = 0.028). ConclusionsGenotyping contributes to the risk stratification of patients with DCM undergoing CRT implantation in terms of LV remodeling and outcomes.

Comparison between super-responders and non-super-responders in psoriasis under adalimumab treatment: a real-life cohort study on the effectiveness and drug survival over one-year

Background Data on the characteristics and treatment outcomes of super-responders and non-super-responders in psoriasis under adalimumab treatment are limited. Methods A retrospective analysis from psoriatic patients treated with adalimumab was compared to characterize super-responders vs non-super-responders’ groups, identify factors associated with super response, and assess treatment outcomes after switching. Results 15 out of 70 (21.4%) patients were categorized as super-responder. The proportion of patients achieving a PASI 100 response was significantly higher in super-responders than non-super-responders at weeks 12, 24, and 52. Female sex and Charlson Co-morbidity Index were significantly associated with super-responders. A high level of high-density lipoprotein was independently associated with PASI 90 response at weeks 24 and 52. Additionally, nearly 35%–43% of non-super-responders switching to interleukin-17A (IL-17A) inhibitors may achieve a PASI 100 response at week 12. In contrast, all super-responders switching to IL-17A inhibitors achieved a PASI 100 response at week 4. Conclusions Super-responders treated with adalimumab have a higher rate of being female and fewer comorbidities. And super-responders have better PASI responses than non-super-responders, whether the patients were treated with adalimumab or switched to IL-17A inhibitors.

Long-term efficacy of left bundle branch pacing and biventricular pacing in patients with heart failure complicated with left bundle branch block.

Left bundle branch pacing (LBBP) can physiologically correct complete left bundle branch block (CLBBB), and has become the best alternative to biventricular pacing (BiVP). To compare the efficacy of LBBP and BiVP in patients with heart failure (HF) complicated with CLBBB. This was a single-center retrospective study. Patients with HF complicated with CLBBB who underwent successful cardiac resynchronization therapy (CRT) in Wuhan Asian Heart Hospital from June 2018 to June 2023 were enrolled and divided into LBBP group and BiVP group according to the pacing method. The primary endpoints were the absolute increase of left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and echocardiographic response rate. Secondary endpoints were all-cause mortality, heart failure hospitalization (HFH), NT-proBNP, paced QRS duration, pacing threshold, and procedural duration. A total of 120 patients were enrolled in this study, including 60 patients in LBBP group and 60 patients in BiVP group. The median follow-up time was 37 ± 19 months. Compared with BiVP group, LBBP group had a more significant increase in absolute LVEF (ΔLVEF) (14.8 ± 9.9% vs. 10.7 ± 9.0%, P = 0.02), a more significant reduction in LVEDD (56.9 ± 10.9 mm vs. 61.1 ± 10.8 mm, P = 0.03), and a higher echocardiographic super response rate (65% vs. 45%, P = 0.02). There were no significant differences in all-cause mortality (1.7% vs. 10.0%, P = 0.11) and HFH (6.7% vs. 13.3%, P = 0.22). In terms of paced QRS duration (128.7 ± 14.1 ms vs. 137.5 ± 16.5 ms, P = 0.002), pacing threshold (0.72 ± 0.21 V/0.4 ms vs. 1.39 ± 0.51 V/0.4 ms, P < 0.001), procedural duration (134.1 ± 32.2 min vs. 147.7 ± 39.4 min, P = 0.04), the LBBP group was superior to the BiVP group. In nonischemic cardiomyopathy (NICM) patients with HF combined with CLBBB and LVEF ≤ 35%, LBBP is better than BiVP.

Outcomes of Antithymocyte Globulin and Cyclosporine for Severe Aplastic Anemia

Background: Aplastic anemia (AA) is mediated by T cell destruction of hematopoietic stem and progenitor cells causing pancytopenia and bone marrow hypoplasia. The current standard of care for severe aplastic anemia (SAA) is hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST) with antithymocyte globulin (ATG) plus cyclosporine (CsA) with or without eltrombopag (Epag), a thrombopoietin receptor agonist. HSCT is preferred for SAA in young adults as a curative option, but only a small proportion of patients have histocompatible siblings and mortality increases with age. The IST plus CsA combination with or without Epag has led to survival rates comparable with those observed with HSCT recipients. However, complete hematologic remission is rare with IST and there is a considerable risk of clonal complications, including PNH evolution and progression to MDS. The aim of this study was to evaluate outcomes of ATG plus CsA therapy in a large cohort of SAA patients. Methods: We retrospectively analyzed medical records of 156 patients with SAA, aged ≥2 years treated with ATG plus CsA with or without Epag at our institution between July 2000 and January 2023. Hematologic responses were evaluated at 3-, 6- and 12-months post therapy initiation. Super response (SR) was defined as hemoglobin ≥12 g/dL, platelet count ≥150x10 9/L and absolute neutrophil count (ANC) ≥1.0x10 9/L; complete response (CR) was defined as hemoglobin ≥10 g/dL, platelet count ≥100x10 9/L and ANC ≥1.0x10 9/L. Partial response (PR) was defined as not meeting the criteria for CR and SAA. Overall response encompassed SR, CR, and PR. Statistical analyses were performed with the use of Chi-squared test and Kaplan Meier method. Results: The median age at diagnosis was 52 (IQR 30-66) years, 47% were male, and 86% were Caucasian. Twenty three percent of the cohort had coexisting paroxysmal nocturnal hemoglobinuria. Most patients were treated with ATG plus CsA (92%), the remaining 8% additionally received Epag. Overall response rates were 70%, 67%, and 77% at 3-, 6- and 12-months post-treatment initiation, respectively. CR was achieved in 10%, 15%, and 18% at 3-, 6- and 12-months, respectively. SR was achieved in 16.3% of patients at 12 months, as shown in Figure 1. Patients who achieved SR were young with median age at diagnosis of 28 years, while those who achieved PR or no response had a median age of 54 and 56 years, respectively. Patients who responded to the ATG + CsA therapy had significantly higher baseline ANC (p=0.04), absolute reticulocyte count (ARC) (p&amp;lt;0.001) and absolute lymphocyte count (ALC) (p&amp;lt;0.001). Pre-treatment median values of ANC, ARC and ALC were higher for patients who achieved SR compared to the rest of responders. With a median follow up time of 4.5 years, the estimated median relapse free survival was 9.2 years (95% CI, 3.2 - not reached [NR]) (Figure 2). Of the entire cohort, 21 (13%) patients progressed to acute myeloid leukemia or myelodysplastic syndrome. At data cut off, a total of 66 patients had died; the estimated median OS was 11.6 years (95% CI, 8.4 - NR). In particular, 30 patients died within the first 12-months, 13 within 3-months of ATG initiation from treatment-related complications, 6 from pneumonia and the rest from unknown causes. Conclusion: The findings of our study demonstrate that ATG plus CsA is an effective and safe treatment option for patients with SAA, especially in the older patient population where HSCT-related toxicities can lead to high mortality. Those with higher baseline ALC, ANC and ARC were more likely to respond to therapy compared to those with lower counts. A small percentage of patients progressed to myeloid neoplasia. Mortality within the first 12-months was high, indicating the need for close monitoring to avoid treatment-related mortality.

Long-Term Follow-up of Hypereosinophilic Syndrome Patients Treated with Mepolizumab: A Nationwide Real-Life Study of 59 Patients

Background Mepolizumab, a humanized monoclonal antibody directed against IL-5, has proven efficacious for the treatment of FIP1L1 ∷ PDGFRA ( F/P)-negative Hypereosinophilic Syndrome (HES) in two randomized controlled trials with short term follow-up. However, both its efficacy and safety profiles on the long term are unknown. Methods All F/P-negative HES patient treated with mepolizumab in France from 2003 to 2022 in either GlaxoSmithKline-sponsored randomized trials (MHE100185 and HES200622) or long-term access programs (MHE100901 and MHE10417) were included. For each study visit, we retrospectively collected the following data: drug doses (and spacing), HES-disease status, absolute eosinophil counts (AEC), and doses of oral corticosteroids (OCS). Clinical remission (CR) was defined as the absence of symptoms related to HES. Complete hematological remission (CHR) was defined as an AEC &amp;lt; 0.5 x 10 9/L, and relapse by the occurrence of new or worsening of HES-related symptoms, irrespective of either AEC or increase of HES treatments. Relapse-free survival was modeled using a Kaplan-Meier method. We also assessed the rates of “super responses”, a new outcome measure defined as the combination of both CR, CHR and complete withdrawal of OCS at last follow-up. Results and discussion Data were available for 64 out of the 80 patients identified. All patients ultimately received 300mg subcutaneous mepolizumab, but 27 (45.8%) patients had initially been started on higher doses (700 or 750 mg intravenous). Five patients were excluded because of misdiagnoses despite initially high AEC and HES-mimicking presentation (IgG4-related disease (n=1), Castleman's disease (n=1), lymphoma (n=2) and STAT6 gain-of-function mutation (n=1)). Ultimately, the study population consisted of 59 patients (idiopathic HES, n=51; lymphocytic HES, n=8) with chronic HES sensitive to high-dose OCS yet who remained OCS-dependent on the long run (median [IQR] dose of OCS at baseline: 11 [9-20] mg/d). In median, patients had two organs involved, with gastro-intestinal, respiratory, and cutaneous manifestations being the most frequent symptoms. After a median follow-up of 4.5 [2.5-12.3] years, 11 patients (19%) relapsed, among whom five were clearly related to prior mepolizumab spacing to more than four weeks between injections (Figure 1). In details, most of the patients were in CR (n=55, 93%) and/or in CHR (n=56, 95%) at last follow-up, including 38 (64%) OCS-free patients who fulfilled criteria for super response. No baseline predictive factor for super response was evidenced. When focusing on the 21 (36%) patients with more than eight years of follow-up (median 14.4 [12.2-17.3] years), outcomes tended to be the same as those of the overall population. At last follow-up more than 70% of patients were able to space mepolizumab's infusions for more than four weeks (median time between two injections at last follow-up: 8 [4-11] months). Ultimately, four patients were able to discontinue mepolizumab without subsequent relapse with more than two years of follow-up. There was no new safety signal, and no patient withdrew mepolizumab due to a treatment-related adverse event. Conclusion Mepolizumab remains highly efficacious in the long-term (including in patients with more than 10 years of follow-up), enabling sustained disease remission despite tapering of OCS and spacing of injections. Very few cases of mepolizumab failure were identified, among which the leading cause was HES misdiagnosis.

180 Guselkumab clinical super response is associated with faster normalization of blood and skin pathology: data from Phase IIIb GUIDE trial

180 Guselkumab clinical super response is associated with faster normalization of blood and skin pathology: data from Phase IIIb GUIDE trial

PH-Responsive Hexa-Histidine Metal Assembly (HmA) with Enhanced Biocatalytic Cascades as the Vehicle for Glucose-Mediated Long-Acting Insulin Delivery.

Diabetes has been listed as one of the three major diseases that endanger human health. Accurately injecting insulin (Ins) depending on the level of blood glucose (LBG) is the standard treatment, especially controlling LBG in the long-term by a single injection. Herein, the pH-responsive hexa-histidine metal assembly (HmA) encapsulated with enzymes (GOx and CAT) and Ins (HmA@GCI) is engineered as the vehicle for glucose-mediated insulin delivery. HmA not only shows high proteins loading efficiency, but also well retained proteins activity and protect proteins from protease damage. Within HmA, the biocatalytic activities of enzymes and the efficiency of the cascade reaction between GOx and CAT are enhanced, leading to a super response to the change of LBG with insulin release and efficient clearance of harmful byproducts of GOx (H2 O2 ). In the treatment of diabetic mice, HmA@GCI reduces LBG to normal in half an hour and maintains for more than 5 days by a single subcutaneous injection, and nearly 24 days with four consecutive injections. During the test period, no symptoms of hypoglycemia and toxicity to tissues and organs are observed. These results indicate that HmA@GCI is a safe and long-acting hypoglycemic agent with prospective clinical application.

The transjugular intrahepatic portosystemic shunt: Smaller stent diameters are required to optimize pressure response

The present treatment goal of the transjugular intrahepatic portosystemic shunt (TIPS) is a portosystemic pressure gradient of ≤12 mmHg or its reduction by >50%. This study relates the stent diameter to the reduction of the pressure gradient and attempts to predict the appropriate stent diameter necessary to reach the treatment goal. Pressure response, super response, and poor response were investigated in 208 de-novo TIPS patients and defined as post-TIPS gradients between >6 and 12 mmHg, ≤6 mmHg, or not reaching the goal (>12 mmHg, reduction <50%), respectively. Pressures were related to the smallest stent diameters measured by planimetry of the radiographic image. Responders (65%), super responders (26%), or poor responders (9%) had comparable stent diameters of 7.2 ± 1.0 mm, but different post-TIPS gradients (9.7 ± 1.9 mmHg, 4.5 ± 1.5 mmHg, and 14.2 ± 1.4 mmHg, p < 0.001), relative reduction of pre-TIPS gradients (51.7 ± 11.4%, 73.6 ± 11.1%, and 34.0 ± 9.1%, p < 0.001), and specific reduction per mm of stent diameter (7.5 ± 2.0%/mm, 10.1 ± 2.0%/mm, and 4.8 ± 1.4%/mm, p < 0.001). Prediction of the stent diameter required to reach response was not possible. Only two super responders had a stent diameter of <6 mm. Super and poor responders differed by the increase in the right atrial pressure (+5.0 mmHg vs. +3.1 mmHg, p = 0.026) and reduction in the portal vein pressure (−8.6 mmHg vs. −4.6 mmHg, p < 0.001). Most patients reached the treatment goal with stent diameters of <8 mm. Overtreatment (super response, gradient ≤6 mmHg) can be prevented by stent diameters as small as 6 mm. The individual response was not related to the stent diameter and not predictable. Cardiac dysfunction may play an important role by its effect on the right atrial (preload) and portal pressure (afterload).

CI-452766-4 LONG-TERM CLINICAL OUTCOMES OF LEFT BUNDLE BRANCH AREA PACING VERSUS BIVENTRICULAR PACING FOR HEART FAILURE TREATMENT: REAL-WORLD EXPERIENCE

Left bundle branch area pacing (LBBAP) has shown potential to be an alternative to biventricular pacing (BiVP) in patients with indications for cardiac resynchronization therapy (CRT). However, few studies focused on the long-term clinical outcomes of LBBAP versus BiVP. This prospective observational study aimed to compare long-term clinical outcomes and complications between LBBAP and BiVP. Consecutive patients with left ventricular ejection fraction (LVEF) <50% and CRT indications were enrolled and prospectively followed up at device clinic if they received successful LBBAP or BiVP from Jan. 2019 to Dec. 2020 at two centers. The primary endpoint was the composite outcomes of all-cause death or heart failure hospitalization (HFH). Secondary endpoints included the occurrence of death, or HFH, or malignant ventricular arrhythmias (VAs). The safety endpoints were device-related complications. Pacing parameters and cardiac function were routinely tracked. A total of 259 patients (mean age 63 ± 11 years, male 65.6%, LVEF 30.4% ± 6.9%) were enrolled, including 106 cases with LBBAP and 153 with BiVP. The paced QRS duration of LBBAP was significantly shorter than that of BiVP (137.3 ± 27.8 ms vs. 148.8 ± 22.1 ms, p<0.001). During the median follow-up of 27 months, LBBAP achieved a higher LVEF improvement from baseline (12.8 ± 12.3% vs. 9.81 ± 12.7%, p=0.043) and similar echo response or super response as compared with BiVP. The risk of the primary endpoint was significantly decreased by 42% in patients with LBBAP than those with BiVP [21.7% vs. 41.2%, adjusted hazard ratio (aHR) 0.58; 95% confidence interval (CI) 0.35–0.98; p=0.041], which was primarily driven by significantly reduced events of HFH after LBBAP treatment [16.0% vs. 36.6%, aHR (95%CI): 0.49 (0.28, 0.85), p=0.012]. The events of all-cause death or malignant VAs were comparable between two groups. Subgroup analysis revealed that patients with left bundle branch block (LBBB) benefited more from LBBAP [aHR (95%CI): 0.35 (0.17, 0.73), p=0.005] than those with non-LBBB or narrow QRS (p for interaction=0.005). The device-related complications were lower in the LBBAP than BiVP group (3.8% vs. 13.1%, p=0.005), mainly due to lead-related complications (1.9% vs. 11.1%, p<0.001). The long-term clinical outcomes of LBBAP for HF treatment might be superior to BiVP with reduced HFH events and lead-related complications in patients with indications for CRT.

PO-02-013 EFFICACY OF LEFT BUNDLE BRANCH PACING IN PATIENTS WITH DIFFERENT LEFT BUNDLE BRANCH BLOCK MORPHOLOGIES

Left bundle branch pacing (LBBP) is a novel technique to deliver cardiac resynchronization therapy (CRT) by correcting intrinsic LBBB to achieve electrical and mechanical resynchrony. Whether the efficacy of LBBP is different across different LBBB morphologies has not been reported. To explore the efficacy of LBBP in patients with different LBBB morphologies. Consecutive patients who received LBBP due to either heart failure (HF) with LBBB or atrioventricular block accompanied with a LBBB pattern escape rhythm were recruited. The changes of QRS duration (ΔQRSd) and left ventricular activation time (ΔLVAT) were compared before and after LBBP. Relationships of ΔQRSd and ΔLVAT with cardiac function in HF patients were also explored. HF patients were followed up for at least 6 months. Electrical resynchrony and cardiac function were compared based on 4 major LBBB morphological criteria. Comparison 1: LBBB meeting Strauss criteria vs not; Comparison 2: presence of q wave in lead I and aVL vs not; Comparison 3: presence of QS vs rS morphology of QRS in lead V1; and Comparison 4: presence of S wave in lead V6 vs not. A total of 82 patients were enrolled from January 2018 to August 2022. In Comparison 1, 59 patients had LBBB meeting Strauss criteria vs 23 not meeting criteria. Patients with LBBB meeting Strauss criteria had greater reduction in QRSd (56.95±24.10ms vs 36.83±32.16ms, P<0.05) and LVAT (56.47±14.90ms vs 41.52±17.13ms, P<0.001). Forty-two HF patients met the Strauss criteria had greater LVEF improvement (19.92±6.89% vs 12.41±13.10%, P<0.05) compared to those not meeting the criteria. Comparison 4 included 61 patients without S wave in lead V6 and these patients exhibited better electrical synchrony after LBBP (ΔQRSd: -55.18±24.79ms vs -40.05±33.67ms, P<0.05; ΔLVAT: -55.74±14.70ms vs -41.67±18.55ms, P<0.05) than patients with S wave in V6. Among them, 51 patients without S wave in V6 had HF and showed greater LVEF improvements than those with S wave in V6 (ΔLVEF: 18.65±10.13% vs 6.61±7.78%, P<0.05). Correlation analyses showed significant associations between both ΔQRSd (R=0.55, P <0.001) and ΔLVAT (R=0.39, P <0.01) with LVEF improvement. In multivariate analysis, ΔQRSd>53 ms is an independent predictor of cardiac super response (LVEF improvement>15%). LBBB pattern meeting the Strauss criteria and absence of S wave in lead V6 can predict better electrical resynchrony and LVEF improvement by LBBP.

Netarsudil as an Adjunctive Therapy: Efficacy and Factors Contributing to a Favorable IOP-Lowering Effect.

The aim of the study is to assess netarsudil's intraocular pressure (IOP)-lowering potential when prescribed as an adjunctive agent, to examine the effect of baseline IOP on patients' response to netarsudil, and to explore patients' characteristics predictive of pronounced responses to netarsudil. This is a single-center, multiprovider retrospective cohort study set at Massachusetts Eye and Ear. Patients with a diagnosis of glaucoma or ocular hypertension on netarsudil and at least one other hypotensive agent for glaucoma who had at least one month of follow-up were included. Patients with additional procedures or glaucoma medication changes were excluded. The main outcome measures were IOP reduction, Kaplan-Meier survival analyses, netarsudil responder type, and complication rates. 236 eyes of 236 patients were included. The mean baseline IOP was 19.06 ± 4.6 mmHg on an average of 4 ocular hypotensive medications. 196 (83.1%) patients experienced IOP reduction at the first follow-up visit of 2.84 ± 0.30 mmHg at 55.66 ± 51.89 days. IOP reduction at the second visit among these patients was 3.01 ± 0.44 mmHg at 133.24 ± 77.63 days. After starting netarsudil, 59% had a sustained response (median duration of 315 days), 25% had a robust response (>20% IOP reduction for at least 80% of visits), and 10% had a super response (>20% and >10 mmHg IOP reduction). Netarsudil was effective as an adjunctive therapy across all baseline IOP categories with greater relative IOP reduction in higher baseline IOP groups. Netarsudil is an effective adjunctive glaucoma therapy. IOP reductions between 2 and 3 mmHg are typical, but a minority had more pronounced and sustained effects (>10 mmHg). Further analysis is needed to assess specific demographic and clinical factors predictive of these robust responses.

Abstract 14258: Left Bundle Branch Pacing for Cardiac Resynchronization Therapy in Heart Failure: A Systematic Review and Meta-Analysis

Introduction: : Cardiac resynchronization therapy (CRT) using a biventricular pacemaker (BVP) reduced mortality and rehospitalizations in patients with symptomatic heart failure (HF) with a left ventricular ejection fraction (LVEF) of less than 35% and concomitant left bundle branch block. However, 10-30% of BVP patients fail to show a clinical or echocardiographic response. Recently left bundle branch pacing (LBBP) has been studied as a more physiological alternative to BVP. The aim of this study is to summarize the available evidence on LBBP. Hypothesis: LBBP is an effective and feasible alternative option for CRT. Methods: Unrestricted searches of the PubMed, EMBASE, and Cochrane databases from inception till June 1, 2022, for studies examining the role of LBBP for CRT in HF patients. Data were analyzed using Revman 5.3 software. Mean Difference (MD), Odds Ratio (OR), and 95% Confidence interval (CI) were calculated using the random-effects model. Results: A total of 8 observational studies (3 single-armed, and 5 comparative studies) examined 756 HF patients who underwent CRT (551 LBBP vs 205 BVP). LBBP was successful in 87% of patients. Compared to baseline, LBBP was associated with a reduction in QRS duration (MD -53.5, 95%CI -69.77, -37.24), an increase in LVEF (MD 17%, 95%CI 13.38, 20.6), and a reduction in NYHA class (MD -1.4, 95%CI -1.56, -1.05). Compared to BVP, LBBP was associated with a significant reduction in QRS duration (MD -22.68, 95%CI -31, -14.35), improvement in LVEF (MD 7.58, 95%CI 5.21, 9.95), and a decrease in NYHA class (MD -0.55, 95% CI -0.73, -0.37) during a mean follow-up of 9.2 months. The super response rate, which is defined as an increase in LVEF of more than 20% or LVEF at or above 50% after CRT, was higher in LBBP compared to BVP (OR 2.98, 95%CI 1.65, 5.32). Conclusions: LBBP is a feasible and effective alternative for CRT. LBBP was associated with better electrical ventricular synchrony than BVP which was also translated into better echocardiographic and clinical outcomes in the short term. Our findings need to be further validated in larger randomized controlled trials with a long-term follow-up.

A Stretchable Strain Sensor Based on CNTs/GR for Human Motion Monitoring

Flexible/stretchable strain sensors have attracted much attention due to their advantages for human-computer interaction, smart wearable and human monitoring. However, there are still great challenges on gaining super durability, quick response, and wide sensing range. This paper provides a simple process to obtain a sensor which is based on graphene (GR)/carbon nanotubes (CNTs) and Ecoflex hybrid, which demonstrates superb endurance (over 1000 cycles at 100% strain), remarkable sensitivity (strain over 125% sensitivity up to 20) and wide sensing range (175%). All results indicate that it is capable for human movement monitoring, such as finger and knee bending and pulse beat. Most importantly, it can be used as a warning function for the night cyclist’s ride. This research provides the feasibility of using this sensor for practical applications.

Relationship between left bundle branch block patterns and super-response to cardiac resynchronization therapy in patients with heart failure

Aim. To assess a relationship of left bundle branch block (LBBB) patterns defined by electrocardiography (ECG) and echocardiography with super-response (SR) to cardiac resynchronization therapy (CRT).Material and methods. Sixty patients (mean age, 54,5±10,4 years) were examined at baseline and during follow-up (10,6±3,6 months). Patients were divided into groups: group I (n=31) — decrease of left ventricular end-systolic volume (ESV) ≥30% (super-responders) and II group (n=29) — decrease of LV ESV &lt;30% (non-super-responders). Three strain-markers of LBBB assessed by tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) were used: early contraction of basal or midventricular segment in the septal wall and early stretching of basal or midventricular segment in the lateral wall (marker 1); early peak contraction of the septal wall occurred in the first 70% of the systolic ejection phase (marker 2, septal flash (SF)); early stretching wall that showed peak contraction after aortic valve closure (marker 3). The classical LBBB pattern was defined if all three strain-markers were present. The heterogeneous LBBB pattern was defined if two from three strain-markers were present.Results. At baseline, groups did not differ in main clinical characteristics, including QRS width and LBBB assessed by ECG. Mechanical abnormalities were found only in group I: SF (32,3% vs 0,0%; p=0,001) and apical rocking (19,4% vs 0,0%; p=0,024), as well as classic LBBB mechanical pattern (20,8% vs 0,0%; p=0,05). The complex of heterogeneous LBBB mechanical pattern (odds ratio (OR), 7,512; 95% CI, 1,434-39,632; р=0,025), interventricular mechanical delay (OR, 1,037; 95% CI, 1,005-1,071; р=0,017) and longitudinal strain of interventricular septum mid segment (OR, 0,726; 95% CI, 0,540-0,977; р=0,035) had an independent relationship with SR. According to the ROC analysis, the sensitivity and specificity of model in SR prediction were 77,3% and 91,3% (AUC=0,862; p&lt;0,001).Conclusion. SR is associated with both LBBB mechanical patterns assessed by STE and TDI. LBBB defined by ECG did not have significant association with SR to CRT.

Left ventricular-only fusion pacing versus cardiac resynchronization therapy in heart failure patients: A randomized controlled trial.

BackgroundIt is unclear whether clinical benefits of cardiac resynchronization can be achieved by pacing only the left ventricle.HypothesisWe aimed to compare the effect of a novel adaptive left ventricular‐only fusion pacing (LVP) on ventricular function with conventional biventricular pacing (BVP) in cardiac resynchronization therapy (CRT) indicated patients.MethodsThis prospective, randomized, multicenter study enrolled CRT‐indicated patients with PR interval ≤ 200 ms who were randomized in the adaptive LVP group (using the AdaptivCRT™ algorithm with intentional non‐capture right ventricular pacing) or the echocardiography‐optimized BVP group. Cardiac function and echocardiography were evaluated at baseline and follow‐ups. CRT super response was defined as two‐fold or more increase of left ventricular ejection fraction (LVEF) or final LVEF >45%, and LV end‐systolic volume (LVESV) decrease >15%, and New York Heart Association (NYHA) class improved by at least one level.ResultsSixty‐three patients were enrolled in the study (LVP = 34 vs. BVP = 29). At 6‐month follow‐up, significant improvements in LVEF, LVESV, and NYHA class were observed in both groups. The CRT super response rate was significantly higher in patients with high‐percentage adaptive LV‐only pacing in LVP group (68.4%) than in BVP group (36.4%, p = .04).ConclusionsAdaptive LV‐only pacing was comparable to BVP in improving cardiac function and clinical condition in CRT‐indicated patients. This finding raises the possibility that an adaptive LVP algorithm with appropriate right ventricular sensing to fuse with intrinsic right ventricular activation in a two‐lead (right atrium and left ventricle) device may provide clinical benefit in a subset of CRT patients with intact atrioventricular conduction.

Role of sCD40L in the prediction of super-response to cardiac resynchronization therapy.

The aim of this paper is to analyze the role of the biomarkers Interleukin 6, Tumoral Necrosis Factor a, sCD40L, high sensitive Troponin T, high sensitive C-Reactive Protein and Galectin-3 in predicting super response (SR) to Cardiac Resynchronization Therapy (CRT), as they have not been studied in this field before. Clinical, electrocardiographic and echocardiographic data was obtained preimplant and after one year. SR was defined as reduction in LVESV = 30% at one year follow-up. Blood samples were extracted preimplant. Multivariate logistic regression and ROC curves were performed. 50 patients were included, 23 (46%) were SR. Characteristics related to SR were: female (35 vs. 11%, p?=?0.04), suffering from less ischemic cardiomyopathy (13 vs. 63%, p?<?0.0001) and lateral (0 vs. 18%, p?=?0.03), inferior (4 vs. 33%, p?=?0.01) and posterior infarction (0 vs. 22%, p?=?0.01); absence of mitral regurgitation (47% vs. 22%, p?=?0.04), wider QRS width (157.7?±?22.9 vs. 140.8?±?19.2ms, p?=?0.01), higher concentrations of sCD40L (6.9?±?5.1 vs. 4.4?±?3.3 ng/mL, p?=?0.02), and left ventricular lead more frequent in lateral medial position (69 vs. 26%, p?=?0.002). QRS width, lateral medial position of the lead and absence of mitral regurgitation were independent predictors of SR. sCD40L showed a moderate direct correla-tion with SR (r?=?0.39, p?=?0.02) and with the reduction of LVESV (r?=?0.44, p?=?0.02). sCD40L correlates significantly with SR to CRT. QRS width, absence of mitral regurgitation and lateral medial position of the lead are independent predictors of SR in this cohort.

Relationship between left bundle branch block mechanical patterns and super-response to cardiac resynchronization therapy in patients with congestive heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Background Left bundle branch block (LBBB) assessed by electrocardiography (ECG) is used in current clinical guidelines for patient selection to cardiac resynchronisation therapy (CRT). But percentage of non-responders among patients with congestive heart failure is high. Super-response (SR) to CRT was not enough described in clinical guidelines. We hypothesized that mechanical patterns of LBBB and parameters of mechanical dyssynchrony could be used as predictors of SR to CRT. Aim To assess a relationship of LBBB patterns defined by ECG and echocardiography with SR to CRT. Materials and methods 60 patients (mean age 54.5 ± 10.4 years) were examined at baseline and during follow-up: 10.6 ± 3.6 months. Patients were divided into groups: I group (n = 31) with decrease of left ventricular end-systolic volume (ESV) ≥30% (super-responders) and II group (n = 29) - decrease of LV ESV &amp;lt;30% (non-super-responders). Three strain-markers of LBBB assessed by Tissue Doppler Imaging (TDI) and Speckle Tracking Echocardiography (STE) were used: (1) early contraction of basal or midventricular segment in the septal wall and early stretching of basal or midventricular segment in the lateral wall (yellow arrows); (2) the early peak contraction of the septal wall occurred in the first 70% of the systolic ejection phase (blue arrow); (3) the early stretching wall that showed peak contraction after aortic valve closure (red arrows). The classic LBBB pattern was defined if all three strain-markers were present. The heterogeneous LBBB pattern was defined if two from three strain-markers were present. Results At baseline groups did not differ in main clinical characteristics, including QRS width and LBBB assessed by ECG. Mechanical abnormalities were found only in group I: SF (32.3% vs 0.0%; p = 0.001) and apical rocking (19.4% vs 0.0%; p = 0.024), as well as classic LBBB mechanical pattern (20.8% vs 0.0%; p = 0.05). The complex of heterogeneous LBBB mechanical pattern (HR 7.512; 95% CI 1.434 – 39.632; р=0.025), interventricular mechanical delay (HR 1.037; 95% CI 1.005 – 1.071; р=0.017) and longitudinal strain of interventricular septum mid segment (HR 0.726; 95% CI 0.540 – 0.977; р=0.035) had an independent relationship with SR. According to the ROC analysis the sensitivity and specificity of model in the prediction of SR were 77.3% and 91.3% (AUC = 0.862; p &amp;lt; 0.001). Conclusion SR is associated with both LBBB mechanical patterns assessed by STE and TDI. LBBB defined by ECG did not have significant association with SR to CRT. Abstract Figure.

Super response and selectivity to H2S at room temperature based on CuO nanomaterials prepared by seed-induced hydrothermal growth

Sea anemone-like CuO nanoarrays (SACNAs) are grown on alumina substrates with Ag–Pd interdigital electrodes by seed-induced hydrothermal method with different growth times. The SACNAs composed of CuO nanotentacles show excellent gas-sensing performance at room temperature of 25 °C mainly due to the diameter of nanotentacles close to the Debye length of CuO. Besides, CuO nanoarrays can maximize the adsorption of the gas molecules on the surface area, and further their diffusion between CuO nanotentacles based on the structure of the cross-linked clusters, which could be beneficial for gas-sensing performance. Moreover, the adequate point-to-point contacts between CuO nanotentacles build abundant effective electrical conducting paths for the sensing reactions. A high response up to 24.08 was achieved at as low as 5 ppb H2S with an ultra-low detection limit of 1.52 ppb. In contrast, there are negligible responses to other gases such as ethanol, methanol, acetone and so on, even at very high concentrations (200 ppm). The sensor based on SACNAs indicates a remarkable response to extremely low concentrations of H2S, as well as ultra-high selectivity, excellent repeatability, and long-term stability at 25 °C. The response of the sensor is affected by variations in operating temperature and humidity.

What can we learn from hyper-responders to cardiac resynchronisation therapy (CRT)? Characteristics and predictors of super response to CRT. An Algerian single centre experience

In some patients with dilated cardiomyopathy (DCM) and left bundle branch block (LBBB), cardiac resynchronisation therapy (CRT) has been shown to reverse almost completely left ventricular (LV) function. Determine the proportion of super responders among patients with DCM and attempt to determine their profile. Consecutive patients with DCM (LV ejection fraction (LVEF) < 35%, LV end-diastolic diameter > 60 mm) and LBBB implanted with a CRT were prospectively followed. Patients were considered super-responders if they fulfilled two criteria: class NYHA I/II and LVEF ≥ 50%. Among the 98 DCM patients, 19 (19.5%) were found to be super-responders following CRT (LVEF increased from 29.89 ± 4.44 to 53.37 ± 3.76%, P < 0.001). In the 79 (81%) remaining patients, there was a significant increase in LVEF from 26.49 ± 4.67 to 37.27 ± 7.20, P < 0.001). At baseline, there were no significant differences between super-responders and other patients, except that super-responders were female, had no hospitalisation for heart failure before implantation and no renal deficiency. Super responders had also less severe LVEF and lower pulmonary artery systolic pressure. CRT-P (OR: 5.47; 95% CI: 1.48–20.27; P = 0.007), lower left ventricular end-diastolic dimension (OR: 0.97; 95% CI: 0.95–0.0.99; P = 0.0002) and lower pulmonary artery systolic pressure (OR: 0.92; 95% CI: 0.87, 0.96; P < 0.001) were independent predictors of super-response to CRT (see Table 1 ). Among patients with DCM and LBBB, Patients in earlier phases of the cardiomyopathy, with a less altered ventricular geometry, seem to have a greater probability of becoming super-responders.