Diverse QRS morphology reflecting variations in lead placement for left bundle branch area pacing.

AIMS: Left bundle branch area pacing (LBBAP) is a potential alternative to His bundle pacing. This study aimed to investigate the impact of different septal locations of pacing leads on the diversity of QRS morphology during non-selective LBBAP. METHODS AND RESULTS: Non-selective LBBAP and left ventricular septal pacing (LVSP) were achieved in 50 and 21 patients with atrioventricular block, respectively. The electrophysiological properties of LBBAP and their relationship with the lead location were investigated. QRS morphology and axis showed broad variations during LBBAP. Echocardiography demonstrated a widespread distribution of LBBAP leads in the septum. During non-selective LBBAP, the qR-wave in lead V1 indicated that the primary location for pacing lead was the inferior septum (93%). The non-selective LBBAP lead was deployed deeper than the LVSP lead in the inferior septum. The Qr-wave in lead V1 with the inferior axis in aVF suggested pacing lead placement in the anterior septum. The penetration depth of the non-selective LBBAP lead in the anterior septum was significantly shallower than that in the inferior septum (72 ± 11 and 87 ± 8%, respectively). In lead V6, the deep S-wave indicated the time lag between the R-wave peak and the latest ventricular activation in the coronary sinus trunk, with pacemaker leads deployed closer to the left ventricular apex. CONCLUSION: Different QRS morphologies and axes were linked to the location of the non-selective LBBAP lead in the septum. Various lead deployments are feasible for LBBAP, allowing diversity in the conduction system capture in patients with atrioventricular block.

Temporal and spatial pacemap parameters for identification of cardiac surfaces with critical sites for ventricular tachycardia.

INTRODUCTION: Multisurface pacemapping may help identify the surface of interest in scar-related ventricular tachycardia (VT). This study aimed to investigate the performance of pacemap parameters for detecting critical sites through multisurface mapping. METHODS AND RESULTS: In 26 patients who underwent scar-related VT ablation, pacemap parameters including a matching score, the difference between the longest and shortest stimulus-QRS intervals (Δs-QRS), and the distance between the good pacemap sites were measured. The parameters were compared between surfaces with and without critical sites and ablation outcomes. A total of 941 pacemap at 56 surfaces targeting 35 VTs were analyzed. A greater Δs-QRS (40 vs. 8 ms, p < .001) and longer distance between two good pacemap sites (24 vs. 13 mm, p < .001) were observed on the surfaces with critical sites. A similar trend was seen in multisurface pacemapping for the same VTs (52 vs. 18 ms in Δs-QRS, p = .021; 37 vs. 12 mm in distance, p = .019), although the best pacemap scores were comparable (94 vs. 87, p = .295). The Δs-QRS > 20 ms and the distance >19 mm showed high positive likelihood ratios (19.8 and 6.1, respectively) for discriminating the surface harboring the critical site. Ablation of VTs fulfilling these parameters was successful on the surfaces, but without the required multisurface ablation. CONCLUSION: Temporal (Δs-QRS) and spatial (distance) parameters for good pacemap match sites were excellent markers for detecting the surface harboring critical sites in scar-related VT. A multisurface pacemapping can successfully identify the surface of interest.

Fluoroscopic predictors of acceptable capture threshold during the implantation of the micra transcatheter pacing system.

INTRODUCTION: Few predictors of low capture threshold before the deployment of the Micra transcatheter pacing system (Micra TPS) have been determined. We aimed to identify fluoroscopic predictors of an acceptable capture threshold before Micra TPS deployment. METHODS: Sixty patients were successfully implanted with Micra TPS. Before deployment, gooseneck appearance of the catheter shaft was quantified using the angle between the tangent line of the shaft and the cup during diastole in the right anterior oblique (RAO) view. The direction of the device cup toward the ventricular septum was evaluated using the angle between the cup and the horizontal plane in the left anterior oblique (LAO) view. RESULTS: Of the 95 deployments we evaluated, 56 achieved an acceptable capture threshold of ≤2.0 V at 0.24 ms. In this acceptable threshold group, the deflection angle of the gooseneck shaft was significantly larger and the device cup was placed more horizontally with a lower elevation angle compared with those in the high threshold group. A deflection angle of ≥6° and an elevation angle of ≤30° were identified as the predictors of an acceptable capture threshold after deployment. An acceptable capture threshold was achieved in 24/31 (77.4%) patients in whom either angle criterion was satisfied at the first deployment. CONCLUSIONS: Diastolic gooseneck appearance of the delivery catheter in the RAO view or near-horizontal direction in the LAO view predicts an acceptable capture threshold after deployment. The shape of the delivery catheter before deployment should be evaluated using multiple fluoroscopic views to ensure successful implantation of Micra TPS.

SURPASS-ET: phase III study of ropeginterferon alfa-2b versus anagrelide as second-line therapy in essential thrombocythemia.

Patients diagnosed with high-risk essential thrombocythemia (ET) have limited treatment options to reduce the risk of thrombosis and lessen the progression of the disease by targeting the molecular source. Hydroxyurea is the recommended treatment, but many patients experience resistance or intolerance. Anagrelide is an approved second-line option for ET, but concerns of a higher frequency of disease transformation may affect its role as a suitable long-term option. Interferons have been evaluated in myeloproliferative neoplasms for over 30 years, but early formulations had safety and tolerability issues. SURPASS-ET (NCT04285086) is a phase III, open-label, multicenter, global, randomized, active-controlled trial that will evaluate the safety, efficacy, tolerability and pharmacokinetics of ropeginterferon alfa-2b compared with anagrelide as second-line therapy in high-risk ET.

Essential thrombocythemia (ET) is a condition characterized by having more platelets than normal. The high number of platelets increases the risk of a life-threatening blood clot and/or bleeding. Patients with ET and at a high risk for these events are usually treated first with hydroxyurea (HU), but some patients do not respond properly or may develop significant side effects. Anagrelide is an approved medication used in patients who do not respond to HU. Ropeginterferon alfa-2b is a disease-specific, long-acting interferon with a good safety profile approved in polycythemia vera, another type of myeloproliferative neoplasm. The SURPASS-ET clinical trial will evaluate the safety, efficacy, tolerability and pharmacokinetics of ropeginterferon alfa-2b compared with anagrelide in patients with ET who are resistant or cannot tolerate HU. Clinical Trial Registration: NCT04285086 (ClinicalTrials.gov).

Relation Between Reach Distance and Center of Pressure Distance for Multidirectional Reach in Hemiplegic Patients.

Background Sitting balance training is an important therapy used by physical and occupational therapists who work with hemiplegic patients. Objective This study compared reach distance (Rd) and center of pressure distance (COPd) for postural control during a multidirectional reaching task in 26 patients with hemiplegia. Method Following the evaluation of trunk function, we classified subjects according to their Chedoke-McMaster assessment stage: group A, stages 5 and 6; group B, stage <4. We used a functional reach apparatus with a body pressure distribution measurement system and a video camera to measure Rd and COPd. Subjects performed multidirectional reaching tasks in the forward/front direction and toward the nonparetic and paretic sides. Resuts Group A showed moderately strong to strong positive correlations between Rd and COPd in all directions, particularly in the forward/front direction. Group B showed lower correlations between Rd and COPd, particularly during tasks where reach was directed toward the paretic side. Conclusion These results suggest that differences in trunk function had an effect on Rd and COPd during multi-directional reaching task.

Left Atrial Reverse Remodeling Following the Modified Box Isolation with Centerline in Patients with Persistent Atrial Fibrillation.

Esophageal injury is a rare but serious complication of atrial fibrillation (AF) ablation. To minimize esophageal injury, our persistent AF (PerAF) protocol involves complete left atrial posterior wall (LAPW) and pulmonary vein (PV) isolation (box isolation), with a centerline away from the esophagus. However, there has been a concern that extensive LA isolation might deteriorate LA function. There has been a paucity of data on LA remodeling after box isolation. Therefore, we compared LA size pre- and post-box isolation with an LAPW centerline in patients with PerAF.Patients who underwent catheter ablation (CA) for PerAF between November 2016 and December 2018 were retrospectively evaluated.The LAPW, including all PVs, was completely isolated in 105 consecutive patients (75 men; mean age: 68 ± 10 years) with PerAF, including 58 patients with long-standing PerAF. During a follow-up of 660 ± 332 days, 76 patients (72%) were arrhythmia-free. The LA dimension (38 ± 6 mm versus 42 ± 7 mm; P < 0.0001) and volume index (38 ± 13 mL/m2 versus 47 ± 14 mL/m2; P < 0.0001) at 6 months post-ablation were significantly decreased in patients who maintained sinus rhythm compared to pre-ablation. In patients with recurrent AF/atrial tachycardia (AT), these parameters were also significantly decreased (P < 0.001, respectively).Box isolation with a posterior centerline has no esophageal complications and a high clinical success rate in patients with PerAF. Reverse remodeling could be achieved even when using extensive isolation of the PV and LAPW in patients with PerAF.

Idiopathic Ventricular Arrhythmia Ablation Using Non-Fluoroscopic Catheter Visualization System.

A novel, sensor-based, electromagnetic, non-fluoroscopic catheter visualization (NFCV) system shows tracked catheters directly on pre-acquired fluoroscopy or cine loops. We aimed to evaluate the effectiveness of this system in the setting of catheter ablation for idiopathic premature ventricular contractions/ventricular tachycardia (i-PVC/VT).A total of 30 i-PVC/VT ablation procedures were performed using the NFCV system in conjunction with three-dimensional electroanatomic mapping system (3D-EMS) between January 2013 and April 2017. At the beginning of the procedure, cine loops of right and left anterior oblique views were obtained and replayed for subsequent mapping and ablation. Right ventriculography, aortography, or coronary angiography was performed, depending on the chamber of interest. We reviewed procedural parameters, comparing with the i-PVC/VT ablation procedure using conventional fluoroscopy (CvF) system (pre-, and post-NFCV implementation; 20 and 11 cases, respectively).I-PVC/VTs were successfully eliminated in 26 patients (87%) in the NFCV group and in 26 (84%) in the CvF group (P = 1.000). The procedure time in the NFCV group was comparable to that in the CvF group (119.8 versus 125.0 minutes, respectively, P = 0.868); the total fluoroscopy time was significantly shorter in the NFCV group (3.3 versus 16.6 minutes, P < 0.001). One patient in the CvF group experienced cardiac tamponade, requiring pericardial drainage. No major complications were encountered in the NFCV group.NFCV system, in conjunction with 3D-EMS, was safe and feasible for i-PVC/VT mapping and ablation. The system contributed to dramatically reduced fluoroscopy time, compared with CvF.

Oligosynaptic inhibition of group Ia afferents from brachioradialis to triceps brachii motor neurons in humans.

INTRODUCTION: This study examines effects of low-threshold afferents from the brachioradialis (BR) on excitability of triceps brachii (TB) motor neurons in humans. METHODS: We evaluated the effects using a post stimulus time histogram (PSTH) and electromyogram averaging (EMG-A) methods in 13 healthy human participants. Electrical conditioning stimulation to the radial nerve branch innervating BR with the intensity below the motor threshold was delivered. RESULTS: In the PSTH study, the stimulation produced a trough (inhibition) in 36/69 TB motor units for all the participants. A cutaneous stimulation never provoked such inhibition. The central latency of the inhibition was 1.5 ± 0.5 ms longer than that of the homonymous facilitation. In the EMG-A study, the stimulation produced inhibition in EMG-A of TB in all participants. The inhibition diminished with a tonic vibration stimulation to BR. DISCUSSION: These findings suggest that oligosynaptic inhibition mediated by group Ia afferents from BR to TB exists in humans. Muscle Nerve 57: 122-128, 2018.

Oligosynaptic inhibition mediated by group Ia afferents from flexor digitorum superficialis to wrist flexors in humans.

Effects of low-threshold afferents from the flexor digitorum superficialis (FDS) to the flexor carpi radialis (FCR), flexor carpi ulnaris (FCU) and extensor carpi ulnaris (ECU) motoneurons were examined using a post-stimulus time-histogram (PSTH) and electromyogram-averaging (EMG-A) methods in seven healthy human subjects. Electrical conditioning stimulation to the median nerve branch innervating FDS with the intensity immediately below the motor threshold was delivered. In the PSTH study, the stimulation produced a trough (inhibition) in 19/44 (43%) of FCR and 17/41 (41%) of FCU motor units. Remaining motor units received no facilitatory and inhibitory effects. The central latency of the inhibition was 1.1 ± 0.6 ms (mean ± SD) and 0.6 ± 0.4 ms longer than that of the homonymous monosynaptic Ia facilitation of FCR and FCU, respectively. In the EMG-A study, the stimulation produced a trough (inhibition) in EMG-A of FCR and FCU in all the seven subjects. Amount of the inhibition was 14.5 ± 3.8% (FCR) and 17.9 ± 2.5% (FCU). Since the inhibition diminished after withdrawal of tonic vibration stimuli to the FDS muscle belly, group Ia afferents should be responsible for the inhibition. The stimulation did not produce facilitatory or inhibitory effect on ECU motoneurons in both the PSTH and EMG-A studies. These findings suggest that group Ia afferents from FDS inhibit excitability of motoneurons supplying FCR and FCU through an oligo (di- or tri-) synaptic path in the spinal cord. The reflex arcs would function to prevent wrist flexion during hand grasping movements.

Performance of Leadless Pacemaker in Japanese Patients vs. Rest of the World　- Results From a Global Clinical Trial.

BACKGROUND: A global study designed to demonstrate the safety and efficacy of a transcatheter pacing system included 38 Japanese patients enrolled at 4 sites. Subgroup analysis to evaluate the performance of the leadless intracardiac transcatheter pacing system in Japanese patients was performed.Methods and Results:Safety and efficacy outcomes, patient and implant procedure characteristics, and patient and physician acceptability from the Japanese population were compared with those from outside Japan. Differences in patient characteristics, implant procedure characteristics and patient acceptability were observed. There were no major complications in Japanese patients and pacing thresholds remained low and stable throughout follow-up. There were no observable differences between Japanese patients and patients from outside Japan in the freedom from major complication rate at 12-months post-implant (100.0% vs. 95.7%, P=0.211) or physician acceptability. CONCLUSIONS: Although some differences in specific baseline characteristics, such as body size and pacing indication, and in implant procedure characteristics, including anticoagulation strategy and hospitalization period, were observed in the Japanese patients, transcatheter pacemaker performance was similar to that in the global trial. (Clinical Trial Registration: ClinicalTrials.gov ID NCT02004873.).

Facilitation from flexor digitorum superficialis to extensor carpi radialis in humans.

Effects of low-threshold afferents from the flexor digitorum superficialis (FDS) to the extensor carpi radialis (ECR) motoneurons were examined using a post-stimulus time-histogram (PSTH) and electromyogram-averaging (EMG-A) methods in eight healthy human subjects. In the PSTH study in five of the eight subjects, electrical conditioning stimuli (ES) to the median nerve branch innervating FDS with the intensity below the motor threshold induced excitatory effects (facilitation) in 39 out of 92 ECR motor units. In 11 ECR motor units, the central synaptic delay of the facilitation was -0.1 ± 0.3 ms longer than that of the homonymous facilitation of ECR. Mechanical conditioning stimuli (MS) to FDS with the intensity below the threshold of the tendon(T)-wave-induced facilitation in 51 out of 51 ECR motor units. With the EMG-A method, early and significant peaks were produced by ES and MS in all the eight subjects. The difference between latencies of the peaks by ES and MS was almost equivalent to that of the Hoffmann- and T-waves of FDS by ES and MS. The peak was diminished by tonic vibration stimuli to FDS. These findings suggest that a facilitation from FDS to ECR exists in humans and group Ia afferents mediate the facilitation through a monosynaptic path.

Biological Effects of Cloth Containing Specific Ore Powder in Patients with Pollen Allergy.

OBJECTIVE: The custom-homebuilding company, Cosmic Garden Co. Ltd., located in Okayama City, Japan was established in 1997 and uses specific natural ore powder (SNOP) in wall materials and surveys customers in order to improve allergic symptoms. METHODS: To investigate the biological effects of SNOP, patients with a pollen allergy were recruited to stay in a room surrounded by cloth containing SNOP (CCSNOP), and their symptoms and various biological parameters were compared with those of individuals staying in a room surrounded by control non-woven cloth (NWC). Each stay lasted 60 min. Before and immediately after the stay, a questionnaire regarding allergic symptoms, as well as POMS (Profile of Mood Status) and blood sampling, was performed. Post-stay minus pre-stay values were calculated and compared between CCSNOP and NWC groups. RESULTS: Results indicated that some symptoms, such as nasal obstruction and lacrimation, improved, and POMS evaluation showed that patients were calmer following a stay in CCSNOP. Relative eosinophils, non-specific Ig E, epidermal growth factor, monocyte chemotactic protein-1, and tumor necrosis factor-α increased following a stay in CCSNOP. CONCLUSION: This ore powder improved allergic symptoms, and long-term monitoring involving 1 to 2 months may be necessary to fully explore the biological and physical effects of SNOP on allergic patients.

Clinical implications of provocation tests for coronary artery spasm: safety, arrhythmic complications, and prognostic impact: multicentre registry study of the Japanese Coronary Spasm Association.

AIMS: Provocation tests of coronary artery spasm are useful for the diagnosis of vasospastic angina (VSA). However, these tests are thought to have a potential risk of arrhythmic complications, including ventricular tachycardia (VT), ventricular fibrillation (VF), and brady-arrhythmias. We aimed to elucidate the safety and the clinical implications of the spasm provocation tests in the nationwide multicentre registry study by the Japanese Coronary Spasm Association. METHODS AND RESULTS: A total of 1244 VSA patients (M/F, 938/306; median 66 years) who underwent the spasm provocation tests were enrolled from 47 institutes. The primary endpoint was defined as major adverse cardiac events (MACEs). The provocation tests were performed with either acetylcholine (ACh, 57%) or ergonovine (40%). During the provocation tests, VT/VF and brady-arrhythmias developed at a rate of 3.2 and 2.7%, respectively. Overall incidence of arrhythmic complications was 6.8%, a comparable incidence of those during spontaneous angina attack (7.0%). Multivariable logistic regression analysis demonstrated that diffuse right coronary artery spasm (P < 0.01) and the use of ACh (P < 0.05) had a significant correlation with provocation-related VT/VF. During the median follow-up of 32 months, 69 patients (5.5%) reached the primary endpoint. The multivariable Cox proportional hazard model revealed that mixed (focal plus diffuse) type multivessel spasm had an important association with MACEs (adjusted hazard ratio, 2.84; 95% confidence interval, 1.34-6.03; P < 0.01), whereas provocation-related arrhythmias did not. CONCLUSION: The spasm provocation tests have an acceptable level of safety and the evaluation of spasm type may provide useful information for the risk prediction of VSA patients.

Effective Management of Polycythemia Vera With Ropeginterferon Alfa-2b Treatment.

Background: Polycythemia vera (PV) is a myeloproliferative neoplasm. Ropeginterferon alfa-2b is a new-generation polyethylene glycol-conjugated proline-interferon. It is approved for the treatment of PV at a starting dose of 100 µg (50 µg for patients receiving hydroxyurea (HU)) and dose titrations up to 500 µg by 50 µg increments. The study was aimed at assessing its efficacy and safety at a higher starting dose and simpler intra-patient dose escalation. Methods: Forty-nine patients with PV having HU intolerance from major hospitals in China were treated biweekly with an initial dose of 250 µg, followed by 350 µg and 500 µg thereafter if tolerated. Complete hematological response (CHR) was assessed every 12 weeks based on the European LeukemiaNet criteria. The primary endpoint was the CHR rate at week 24. The secondary endpoints included CHR rates at weeks 12, 36 and 52, changes of JAK2V617F allelic burden, time to first CHR, and safety assessments. Results: The CHR rates were 61.2%, 69.4% and 71.4% at weeks 24, 36, and 52, respectively. Mean allele burden of the driver mutation JAK2V617F declined from 58.5% at baseline to 30.1% at 52 weeks. Both CHR and JAK2V617F allele burden reduction showed consistent increases over the 52 weeks of the treatment. Twenty-nine patients (63.0%) achieved partial molecular response (PMR) and two achieved complete molecular response (CMR). The time to CHR was rapid and median time was 5.6 months according to central lab results. The CHRs were durable and median CHR duration time was not reached at week 52. Mean spleen index reduced from 55.6 cm2 at baseline to 50.2 cm2 at week 52. Adverse events (AEs) were mostly mild or moderate. Most common AEs were reversible alanine aminotransferase and aspartate aminotransferase increases, which were not associated with significant elevations in bilirubin levels or jaundice. There were no grade 4 or 5 AEs. Grade 3 AEs were reversible and manageable. Only one AE led to discontinuation. No incidence of thromboembolic events was observed. Conclusion: The 250-350-500 µg dosing regimen was well tolerated and effectively induced CHR and MR and managed spleen size increase. Our findings demonstrate that ropeginterferon alfa-2b at this dosing regimen can provide an effective management of PV and support using this dosing regimen as a treatment option.

Conduction system pacing: Current status and prospects.

Conduction system pacing (CSP), including His bundle pacing (HBP) and left bundle branch area pacing (LBBAP), is the most physiological of all pacing modalities for ventricular capture and a potential alternative to right ventricular pacing. It induces electrical and mechanical dyssynchrony, resulting in left ventricular dysfunction, heart failure hospitalization, and atrial arrhythmia. CSP activates the normal conduction system and restores ventricular synchrony. In 2000, HBP was first performed as permanent ventricular pacing, which improved left ventricular systolic dysfunction. The feasibility of permanent HBP has already been demonstrated in patients with bradycardia, although a high capture threshold and limited efficacy for infra-Hisian conduction diseases remain critical issues. The LBBAP is an alternative pacing form that overcomes the limitations of the HBP. A lower capture threshold was obtained at implantation and preserved during the follow-up period in patients with LBBAP. Cardiac resynchronization therapy with HBP or LBBAP may provide better synchronization than the traditional biventricular pacing. Hybrid therapy utilizing HBP or LBBAP in combination with left ventricular pacing has been introduced to treat patients with heart failure. In this review, we have focused on the clinical implications, limitations, and a literature review on CSP.

Predictors of implantation failure in left bundle branch area pacing using a lumenless lead in patients with bradycardia.

Background: Left bundle branch area pacing (LBBAP) is a novel conduction system pacing technique. In this multicenter study, we aimed to evaluate the procedural success, safety, and preoperative predictors of procedural failure of LBBAP. Methods: LBBAP was attempted in 285 patients with pacemaker indications for bradyarrhythmia, which were mainly atrioventricular block (AVB) (68.1%) and sick sinus syndrome (26.7%). Procedural success and electrophysiological and echocardiographic parameters were evaluated. Results: LBBAP was successful in 247 (86.7%) patients. Left bundle branch (LBB) capture was confirmed in 54.7% of the population. The primary reasons for procedural failure were the inability of the pacemaker lead to penetrate deep into the septum (76.3%) and failure to achieve shortening of stimulus to left ventricular (LV) activation time in lead V6 (18.4%). Thickened interventricular septum (odds ratio [OR], 2.48; 95% confidence interval [CI], 1.15-5.35), severe tricuspid regurgitation (OR, 8.84; 95% CI, 1.22-64.06), and intraventricular conduction delay (OR, 8.16; 95% CI, 2.32-28.75) were preoperative predictors of procedural failure. The capture threshold and ventricular amplitude remained stable, and no major complications occurred throughout the 2-year follow-up. In patients with ventricular pacing burden >40%, the LV ejection fraction remained high regardless of LBB capture. Conclusions: Successful LBBAP was affected by abnormal cardiac anatomy and intraventricular conduction. LBBAP is feasible and safe as a primary strategy for patients with AVB, depending on ventricular pacing.

Supporters' experiences of sensory characteristics of children with profound intellectual and multiple disabilities in after-school daycare centres: A qualitative study.

AIM: To examine how supporters working at after-school daycare centres, who are involved in the lives of children with profound intellectual and multiple disabilities in the community, pay attention to the sensory characteristics of these children and provide support. DESIGN: A qualitative descriptive design. METHODS: Data were collected through semi-structured interviews with 20 supporters in after-school daycare centres. Interview transcripts were analysed via qualitative content analysis. RESULTS: The participants' years of involvement in supporting children with profound intellectual and multiple disabilities ranged from 0.5 to 40 years, with an average of 9.8 years. Data were classified into 68 subcategories, 11 categories and three themes: understanding sensory characteristics and devising support, systematic support and challenges supporting the children. Supporters dealt with physical complications and cooperated with other caregivers to understand and respond to children's sensory characteristics. Difficulties dealing with sensory characteristics, challenges due to the supporters' own characteristics and challenges with the facility's infrastructure were identified. The findings could guide sensory characteristics considerations and support systems in after-school daycare facilities for children with profound intellectual and multiple disabilities. Both support content and challenges in supporting these children were identified.

A new dosing regimen of ropeginterferon alfa-2b is highly effective and tolerable: findings from a phase 2 study in Chinese patients with polycythemia vera.

Ropeginterferon alfa-2b represents a new-generation pegylated interferon-based therapy and is administered every 2-4 weeks. It is approved for polycythemia vera (PV) treatment in the United States and Europe with a starting dose of 100 µg (50 µg for patients receiving hydoxyurea) and intra-patient dose titrations up to 500 µg at 50 µg increments, which took approximately 20 or more weeks to reach a plateau dose level. This study aimed to assess ropeginterferon alfa-2b at an alternative dosing regimen with a higher starting dose and quicker intra-patient dose titrations, i.e., the 250-350-500 µg schema, in 49 Chinese patients with PV with resistance or intolerance to hydroxyurea. The primary endpoint of the complete hematologic response rate at treatment weak 24 was 61.2%, which was notably higher than 43.1% at 12 months with the approved dosing schema. The JAK2V617F allele burden decreased from baseline to week 24 (17.8% ± 18.0%), with one patient achieving a complete molecular response. Ropeginterferon alfa-2b was well-tolerated and most adverse events (AEs) were mild or moderate. Common AEs included alanine aminotransferase and aspartate aminotransferase increases mostly at grade 1 or 2 levels. Patients did not present with jaundice or significant bilirubin level increase. No grade 4 or 5 AEs occurred. Seven patients (14.3%) experienced reversible, drug-related grade 3 AEs. No AEs led to treatment discontinuation. Ropeginterferon alfa-2b at the 250-350-500 µg regimen is highly effective and well-tolerated and can help patients achieve greater and rapid complete hematologic and molecular responses.Clinical Trial Registration: This trial is registered at ClinicalTrials.gov (Identifier: NCT05485948) and in China (China National Medical Products Administration Registration Number: CTR20211664).

Worldwide survey on implantation of and outcomes for conduction system pacing with His bundle and left bundle branch area pacing leads.

BACKGROUND: Adoption and outcomes for conduction system pacing (CSP), which includes His bundle pacing (HBP) or left bundle branch area pacing (LBBAP), in real-world settings are incompletely understood. We sought to describe real-world adoption of CSP lead implantation and subsequent outcomes. METHODS: We performed an online cross-sectional survey on the implantation and outcomes associated with CSP, between November 15, 2020, and February 15, 2021. We described survey responses and reported HBP and LBBAP outcomes for bradycardia pacing and cardiac resynchronization CRT indications, separately. RESULTS: The analysis cohort included 140 institutions, located on 5 continents, who contributed data to the worldwide survey on CSP. Of these, 127 institutions (90.7%) reported experience implanting CSP leads. CSP and overall device implantation volumes were reported by 84 institutions. In 2019, the median proportion of device implants with CSP, HBP, and/or LBBAP leads attempted were 4.4% (interquartile range [IQR], 1.9-12.5%; range, 0.4-100%), 3.3% (IQR, 1.3-7.1%; range, 0.2-87.0%), and 2.5% (IQR, 0.5-24.0%; range, 0.1-55.6%), respectively. For bradycardia pacing indications, HBP leads, as compared to LBBAP leads, had higher reported implant threshold (median [IQR]: 1.5 V [1.3-2.0 V] vs 0.8 V [0.6-1.0 V], p = 0.0008) and lower ventricular sensing (median [IQR]: 4.0 mV [3.0-5.0 mV] vs. 10.0 mV [7.0-12.0 mV], p < 0.0001). CONCLUSION: In conclusion, CSP lead implantation has been broadly adopted but has yet to become the default approach at most surveyed institutions. As the indications and data for CSP continue to evolve, strategies to educate and promote CSP lead implantation at institutions without CSP lead implantation experience would be necessary.