Geisinger Wyoming Valley Medical Center

Conduction system pacing (CSP) has emerged as a more physiological alternative to right ventricular pacing and is also being used in selected cases for cardiac resynchronization therapy. His bundle pacing was first introduced over two decades ago and its use has risen over the last five years with the advent of tools which have facilitated implantation. Left bundle branch area pacing is more recent but its adoption is growing fast due to a wider target area and excellent electrical parameters. Nevertheless, as with any intervention, proper technique is a prerequisite for safe and effective delivery of therapy. This document aims to standardize the procedure and to provide a framework for physicians who wish to start CSP implantation, or who wish to improve their technique.

OBJECTIVES: His bundle pacing (HBP) can potentially correct left bundle branch block (LBBB). We aimed to assess the efficacy of HBP to correct LBBB and long-term clinical outcomes with HBP in patients with heart failure (HF). METHODS: This is an observational study of patients with HF with typical LBBB who were indicated for pacing therapy and were consecutively enrolled from one centre. Permanent HBP leads were implanted if the LBBB correction threshold was <3.5V/0.5 ms or 3.0 V/1.0 ms. Pacing parameters, left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV) and New York Heart Association (NYHA) Class were assessed during follow-up. RESULTS: In 74 enrolled patients (69.6±9.2 years and 43 men), LBBB correction was acutely achieved in 72 (97.3%) patients, and 56 (75.7%) patients received permanent HBP (pHBP) while 18 patients did not receive permanent HBP (non-permanent HBP), due to no LBBB correction (n=2), high LBBB correction thresholds (n=10) and fixation failure (n=6). The median follow-up period of pHBP was 37.1 (range 15.0-48.7) months. Thirty patients with pHBP had completed 3-year follow-up, with LVEF increased from baseline 32.4±8.9% to 55.9±10.7% (p<0.001), LVESV decreased from a baseline of 137.9±64.1 mL to 52.4±32.6 mL (p<0.001) and NYHA Class improvement from baseline 2.73±0.58 to 1.03±0.18 (p<0.001). LBBB correction threshold remained stable with acute threshold of 2.13±1.19 V/0.5 ms to 2.29±0.92 V/0.5 ms at 3-year follow-up (p>0.05). CONCLUSIONS: pHBP improved LVEF, LVESV and NYHA Class in patients with HF with typical LBBB.

Aims: Permanent cardiac pacing of the His-bundle restores and retains normal electrical activation of the ventricles. Data on His-bundle pacing (HBP) are largely limited to small single-centre reports, and clinical benefits and risks have not been systematically examined. We sought to systematically examine published studies of patients undergoing permanent HBP and quantify the benefits and risks of the therapy. Methods and results: PubMed, Embase, and Cochrane Library were searched for full-text articles on permanent HBP. Clinical outcomes of interest included implant success rate, procedural and lead complications, pacing thresholds, QRS duration, and ejection fraction at follow-up, and mortality. Data were extracted and summarized. Where possible, meta-analysis of aggregate data was performed. Out of 2876 articles, 26 met the inclusion criteria representing 1438 patients with an implant attempt. Average age of patients was 73 years and 62.1% were implanted due to atrioventricular block. Overall average implant success rate was 84.8% and was higher with use of catheter-delivered systems (92.1%; P < 0.001). Average pacing thresholds were 1.71 V at implant and 1.79 V at >3 months follow-up; although, pulse widths varied at testing. Average left ventricular ejection fractions (LVEFs) were 42.8% at baseline and 49.5% at follow-up. There were 43 complications observed in 907 patients across the 17 studies that reported safety information. Conclusion: Among 26 articles of permanent HBP, the implant success rate averaged 84.8% and LVEF improved by an average of 5.9% during follow-up. Specific reporting of our clinical outcomes of interest varied widely, highlighting the need for uniform reporting in future HBP trials.

Background Cardiac resynchronization therapy (CRT) is an established therapy for patients with cardiomyopathy, left bundle branch block, and heart failure. His bundle pacing (HBP) may also improve clinical outcomes by narrowing QRS duration. The QRS narrowing by HBP may not always be optimal. The aim of the study was to determine if CRT could be optimized by sequential HBP followed by left ventricular (LV) pacing (His-Optimized CRT [HOT-CRT]) to maximize electrical resynchronization. Methods We attempted permanent HBP in 27 patients (left bundle branch block 17, intraventricular conduction defect 5, and right ventricular pacing 5) referred for CRT in addition to LV lead. HBP was followed by LV pacing at a delay equal to His-ventricular interval. QRS duration at baseline, during HBP, biventricular pacing, and HOT-CRT was measured. Echocardiographic parameters and New York Heart Association functional class were assessed at baseline and during follow-up. Results HOT-CRT was successful in 25 of 27 patients (age 72±15 years, men 23, ischemic 21). QRS duration at baseline was 183±27 ms and significantly narrowed to 162±17 ms with biventricular pacing ( P=0.003), to 151±24 ms during HBP ( P<0.0001), and further to 120±16 ms during HOT-CRT ( P<0.0001). During a mean follow-up of 14±10 months, LV ejection fraction improved from 24±7% to 38±10% ( P<0.0001), and New York Heart Association functional class changed from 3.3 to 2.04. Twenty-one of 25 patients (84%) were clinical responders while 23 of 25 (92%) showed echocardiographic response. Conclusions In this feasibility cohort, HOT-CRT resulted in improved electrical resynchronization. HOT-CRT may improve clinical and echocardiographic outcomes in advanced heart failure patients requiring CRT.

Background Cardiac resynchronization therapy utilizing biventricular pacing is an effective therapy for patients with left ventricular (LV) systolic dysfunction, left bundle branch block, and heart failure. Benefits of biventricular pacing may be limited in patients with right bundle branch block (RBBB). Permanent His bundle pacing (HBP) has recently been reported as an option for cardiac resynchronization therapy. The aim of the study was to assess the feasibility and outcomes of HBP in patients with RBBB and heart failure. Methods HBP was attempted as a primary or rescue (failed LV lead implant) strategy in patients with reduced LV ejection fraction, RBBB, QRS duration ≥120 ms, and New York Heart Association class II to IV heart failure. Implant characteristics, New York Heart Association functional class, and echocardiographic data were assessed in follow-up. Results Mean age was 72±10 years, female 15%, with an average LV ejection fraction of 31±10%. HBP was successful in 37 of 39 patients (95%) with narrowing of RBBB in 78% cases. His capture and bundle branch block correction thresholds were 1.1±0.6 V and 1.4±0.7 V at 1 ms, respectively. During a mean follow-up of 15±23 months, there was a significant narrowing of QRS from 158±24 to 127±17 ms ( P=0.0001), increase in LV ejection fraction from 31±10% to 39±13% ( P=0.004), and improvement in New York Heart Association functional class from 2.8±0.6 to 2±0.7 ( P=0.0001) with HBP. Increase in capture threshold occurred in 3 patients. Conclusions Permanent HBP was associated with significant narrowing of QRS duration and improvement in LV function in patients with RBBB and reduced LV ejection fraction. Permanent HBP is a promising option for cardiac resynchronization therapy in patients with RBBB and reduced LV ejection fraction.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in rheumatoid arthritis (RA) patients. This study is the first to report the association of hydroxychloroquine (an antirheumatic medication that has been associated with decreased risk of diabetes, a less atherogenic lipid profile, and antithrombotic properties) with CVD in RA. METHODS AND RESULTS: A retrospective incident RA cohort from January 1, 2001, to October 31, 2013, excluding patients with CVD prior to RA diagnosis, was constructed. Patients were categorized as hydroxychloroquine users versus nonusers and were allowed to contribute time to either group according to hydroxychloroquine exposure. The primary outcome was adjudicated incident CVD defined as a composite of coronary artery disease, stroke, transient ischemic attack, sudden cardiac death, and peripheral artery disease with arterial revascularization procedure. The secondary outcome was a composite of incident coronary artery disease, stroke, and transient ischemic attack. Cox time-varying regression models were used to estimate the association between hydroxychloroquine exposure and development of CVD, after adjusting for propensity score and relevant confounders, including demographics, CVD-related comorbidities, RA severity, and activity indicators and medications. We included 1266 RA patients, 547 hydroxychloroquine users, and 719 nonusers. During the observation period, 102 CVD events occurred, 3 in hydroxychloroquine users and 99 in nonusers. The fully adjusted Cox model showed a hazard ratio of 0.28 (95% CI 0.12-0.63, P=0.002) for incident CVD and 0.30 (95% CI 0.13-0.68, P=0.004) for incident composite coronary artery disease, stroke, and transient ischemic attack for hydroxychloroquine users versus nonusers, respectively. CONCLUSION: In this hypothesis-generating study, hydroxychloroquine use was associated with a 72% decrease in the risk of incident CVD in RA patients. If these preliminary results are confirmed in larger studies, our findings may be used as a rationale for a randomized study of hydroxychloroquine use for primary prevention of CVD in RA or nonrheumatic high-risk patients.

AIMS: Atrioventricular node ablation (AVNA) and right ventricular pacing (RVP) are effective therapies for patients with atrial fibrillation (AF) and rapid ventricular rates. His bundle pacing (HBP) is a physiologic alternative to RVP. The aim of our study is to assess the feasibility and safety of HBP in patients undergoing AVNA and its effect on left ventricular (LV) function. METHODS AND RESULTS: Permanent HBP is the preferred form of ventricular pacing at our institute. Atrioventricular node ablation and HBP were performed in patients with AF and difficulty in rate control. His bundle pacing implant characteristics and thresholds were recorded. Fluoroscopic relationship of AVNA site to HBP lead electrodes was documented. Left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) functional class at baseline and during follow-up were assessed. Forty-two patients underwent HBP and AVNA: age 74 ± 11 years; men 45%; HTN 64%; DM 19%; CAD 36%; permanent AF 40%; cardiomyopathy 55%. His bundle pacing was successful in 40 of 42 patients (95%). Successful AVNA site was at or below the ring electrode in 22 (no acute change in HBP threshold); above the ring electrode in 13 and left side in 2 pts (acute increase in HBP threshold in 7 of 15 pts). Final HBP threshold at implant was 1 ± 0.8 V@1 ms and increased to 1.6 ± 1.2 V@1 ms during a mean follow-up of 19 ± 14 months. Left ventricular ejection fraction increased from 43 ± 13% to 50 ± 11% (P = 0.01). New York Heart Association functional status improved from 2.5 ± 0.5 to 1.9 ± 0.5 (P = 0.04). CONCLUSION: Atrioventricular node ablation and HBP were successful in 95% of patients. His bundle pacing lead characteristics remained relatively stable. Left ventricular ejection fraction improved significantly during follow-up. His bundle pacing is feasible, safe and effective in pts undergoing AVNA.

AIMS: Vernakalant is a novel, relatively atrial-selective antiarrhythmic agent for conversion of atrial fibrillation (AF) to sinus rhythm. This study examined the safety and efficacy of vernakalant in converting atrial flutter (AFL) to sinus rhythm. METHODS AND RESULTS: This was a phase 2/3, randomized, double-blind, placebo-controlled trial. Adults with AFL received either a 10 min infusion of 3.0 mg/kg vernakalant (n = 39) or placebo (n = 15). If AFL or AF persisted at the end of a 15 min observation period, a second 10 min infusion of 2.0 mg/kg vernakalant or placebo was administered. The primary efficacy outcome was the proportion of patients who had treatment-induced conversion of AFL to sinus rhythm for a minimum duration of 1 min within 90 min after the start of the first infusion. No patient in the placebo group met the primary outcome. Only one patient receiving vernakalant (1 of 39, 3%) converted to sinus rhythm. A reduced mean absolute ventricular response rate occurred within 50 min in patients receiving vernakalant (mean change from baseline -8.2 b.p.m.) vs. patients receiving placebo (-0.2 b.p.m.) (P = 0.037). A post-hoc analysis revealed that vernakalant increased AFL cycle length by an average of 55 ms, whereas the AFL cycle length was unchanged in the placebo group (P < 0.001). There was no occurrence of 1 : 1 atrio-ventricular conduction. Dysgeusia and sneezing were the most common treatment-related adverse events, consistent with previous reports. CONCLUSION: Vernakalant did not restore sinus rhythm in patients with AFL. Vernakalant modestly slowed AFL and ventricular response rates, and was well tolerated.

INTRODUCTION: Several single-center short-term studies have demonstrated the feasibility, safety, and positive clinical outcomes of permanent His bundle pacing (HBP). We performed a retrospective study to evaluate long-term technical and safety performances of HBP in a large population of pacemaker patients from two different centers. METHODS AND RESULTS: The analysis includes 844 patients (345 female, mean age = 75 ± 9 years) who underwent successful permanent HBP for pacemaker indications from 2004 to 2016. The main endpoints were long term electrical performances including pacing threshold, sensing, impedance, and freedom from pacing related complications. The pacing indication was AV Block in 348 (41.2%) patients, sinus node disease in 147 (17.4%), any bradycardia indication in patients with atrial fibrillation in 335 (39.7%) patients and need for cardiac resynchronization therapy in 14 (1.7%) patients. Mean pacing capture thresholds and sensed R waves were 1.6 V and 5.8 mV, respectively at implant and 2.0 V and 6.1 mV at chronic follow-up. During the median follow up of 3 years (interquartile range = 1-6 years), HBP was free of any complication in 91.6% of patients. In the first 368 patients, HBP was achieved using a deflectable curve delivery system, while in 476 using the fixed curve sheath. A significant difference was found in the thresholds (2.4 ± 1.0 V and 1.7 ± 1.1 V, P < .001, respectively) and complications (11.9% and 4.2%, P < .001, respectively) between the two groups. CONCLUSIONS: Permanent HBP was safe and effective during long-term follow-up. The fixed curved delivery sheath offered significantly better electrical parameters and reliability over time. The results of this multicenter study are consistent with recent studies.

We randomized 103 patients (68 arteriovenous [AV] fistulas, 35 polytetrafluoroethylene [PTFE] grafts; mean follow-up 197 days) to monthly measurement of access flow (QAT), monthly measurement of static venous pressure (VPS), or no monthly monitoring (control patients) to determine whether access thrombosis would decrease. Patients with access flow <750 cc/min or with static venous pressure > or =0.5 were referred for angiography and angioplasty of stenotic lesions > or =50%. Six of sixty-two (9.7%) of monthly monitored patients (MM) developed access thrombosis vs. 9 of 41 (22%) of control patients (p<0.05). Fewer MM patients developed thrombosis in AV fistulas (2.4% [2 of 42] vs. 15.4% [4 of 26] control patients; p<0.05). Monthly monitored patients had fewer thrombotic episodes than control patients (19 vs. 125 per 100 patient-years; p<0.01). Thrombosis rates were lowest in patients receiving monthly access flow measurement (5.9 [QAT] vs. 30.3 per 100 patient-years [VPS]; p<0.05). In conclusion, intervention based on monthly access flow measurement or static venous pressure decreased hemodialysis access thrombosis. Measurement of access flow tended to result in lower thrombosis rates than after static venous pressure. We believe that monthly access flow measurement will ensure the lowest incidence of thrombosis and decrease the cost of access maintenance.

153 hemodialysis accesses (56 fistulas and 97 PTFE grafts) were followed from placement to see if elective intervention prolonged access survival. The mean follow-up was 772 days (minimum 14 days, maximum 2755 days). Patients who expired, were transplanted or transferred were excluded. The groups of fistulas and grafts were subdivided into those whose first intervention was an episode of clotting versus those whose first intervention was an elective revision (either surgical repair or angioplasty of an area of stenosis within the access or run-off). These groups were compared to see whether electively revising an access prior to clotting would change the ultimate longevity of the access when compared to repairing the access after clotting. PTFE grafts with an initial elective intervention had an improved survival compared to grafts that clotted first (1023 days vs 689 days, p = 0.01). The electively revised grafts had fewer subsequent clotting episodes (1.1 clots per patient year vs 3.6, p = 0.02) and fewer interventions (1.8 interventions per patient year vs 3.7, p = 0.06). In fistulas, an initial elective revision increased access longevity when compared to repair after the fistula clotted (999 days vs 358 days, p = 0.005). Clotting episodes were decreased in those electively revised (0.5 clots per patient year vs 4.8, p = 0.014). Total interventions per patient year were also lower in those electively revised (1.2 vs 5.3, p = 0.028). In conclusion, elective correction of abnormalities in PTFE grafts and in AV fistulas prolongs access life when compared to repair after an initial episode of clotting. Elective revision also decreased the subsequent number of clotting episodes per patient year and the total number of interventions (revisions and declottings) per patient year in both grafts and fistulas.

Conduction system pacing (CSP) has emerged as a more physiological alternative to right ventricular pacing and is also being used in selected cases for cardiac resynchronization therapy. His bundle pacing was first introduced over two decades ago and its use has risen over the last years with the advent of tools which have facilitated implantation. Left bundle branch area pacing is more recent but its adoption is growing fast due to a wider target area and excellent electrical parameters. Nevertheless, as with any intervention, proper technique is a prerequisite for safe and effective delivery of therapy. This document aims to standardize the procedure and to provide a framework for physicians who wish to start CSP implantation, or who wish to improve their technique. A synopsis is provided in this print edition of EP-Europace. The full document may be consulted online, and a 'Key Messages' App can be downloaded from the EHRA website.

Lung cancer remains one of the leading causes of cancer-related deaths worldwide, emphasizing the need for improved diagnostic and treatment approaches. In recent years, the emergence of artificial intelligence (AI) has sparked considerable interest in its potential role in lung cancer. This review aims to provide an overview of the current state of AI applications in lung cancer screening, diagnosis, and treatment. AI algorithms like machine learning, deep learning, and radiomics have shown remarkable capabilities in the detection and characterization of lung nodules, thereby aiding in accurate lung cancer screening and diagnosis. These systems can analyze various imaging modalities, such as low-dose CT scans, PET-CT imaging, and even chest radiographs, accurately identifying suspicious nodules and facilitating timely intervention. AI models have exhibited promise in utilizing biomarkers and tumor markers as supplementary screening tools, effectively enhancing the specificity and accuracy of early detection. These models can accurately distinguish between benign and malignant lung nodules, assisting radiologists in making more accurate and informed diagnostic decisions. Additionally, AI algorithms hold the potential to integrate multiple imaging modalities and clinical data, providing a more comprehensive diagnostic assessment. By utilizing high-quality data, including patient demographics, clinical history, and genetic profiles, AI models can predict treatment responses and guide the selection of optimal therapies. Notably, these models have shown considerable success in predicting the likelihood of response and recurrence following targeted therapies and optimizing radiation therapy for lung cancer patients. Implementing these AI tools in clinical practice can aid in the early diagnosis and timely management of lung cancer and potentially improve outcomes, including the mortality and morbidity of the patients.

A retrospective study was undertaken to see if screening ultrasounds and elective surgical revision could decrease access failure. Two hundred fifty-three accesses [177 gortex grafts, 76 arteriovenous (AV) fistulas] were studied with duplex imaging. Patients were subdivided by access type, flow, percent stenosis, and whether they were surgically revised. Data was examined to determine access failure within 6 months. Ten of 76 fistulas clotted (13.1%), while 53 of 177 grafts clotted (29.9%) (p = 0.005). In Gortex grafts, stenosis (p < 0.05) and decreased flow (p = 0.005) correlated with clotting. In unrevised grafts with flow < or = 801 ml/min, 13 of 14 (92.8%) clotted, whereas of those with flow > or = 1603 ml/min only, 10 of 38 (26.3%) clotted (chi-square = 24.74; p < 0.0001). Only 1 of 18 (5.6%) revised grafts with flow < or = 1300 ml/min clotted, while 29 of 69 (42%) unrevised grafts clotted (p = 0.004). We were unable to demonstrate decreased clotting in fistulae with revisions. In conclusion, screening duplex scanning was able to select groups with a higher risk of access failure over the subsequent 6 months. Elective revision with correction of areas of stenosis in grafts with flows < or = 1300 ml/min significantly decreased the incidence of clotting.

Background Persistent atrial fibrillation may lead to a higher probability of inappropriate shocks in heart failure patients with an implantable cardioverter‐defibrillator ( ICD ). The aim of this study was to evaluate the impact of His‐Purkinje conduction system pacing combined with atrioventricular node ablation in improving heart function and preventing inappropriate shock therapy in these patients. Methods and Results A total of 86 consecutive patients with persistent atrial fibrillation and heart failure who had indications for ICD implantation were enrolled from January 2010 to March 2018. His‐Purkinje conduction system pacing with ICD and atrioventricular node ablation was attempted in 55 patients, and the remaining patients underwent ICD implantation only. Left ventricular (LV) ejection fraction, LV end‐systolic volume, New York Heart Association ( NYHA ) classification, shock therapies, and drug therapy were assessed during follow‐up. Overall, 31 patients received ICD implantation with optimal drug therapy (group 1). atrioventricular node ablation combined with His‐Purkinje conduction system pacing was successfully achieved in 52 patients (group 2). During follow‐up, patients in group 2 had lower incidence of inappropriate shock (15.6% versus 0%, P &lt;0.01) and adverse events ( P =0.011). Meanwhile, improvement in LV ejection fraction and reduction in LV end‐systolic volume were significantly higher in group 2 than in group 1 (15% versus 3%, P &lt;0.001; and 40 versus 2 mL, P &lt;0.01, respectively). NYHA functional class improved in both groups from a baseline 2.57±0.68 to 1.73±0.74 in group 1 and 2.73±0.59 to 1.42±0.53 in group 2 ( P &lt;0.01). Conclusions His‐Purkinje conduction system pacing combined with atrioventricular node ablation is feasible and safe with a high success rate in persistent atrial fibrillation patients with heart failure and ICD indication. It can significantly reduce the incidence of inappropriate shocks and improve LV function.

OBJECTIVES/HYPOTHESIS: Surgery for goiter embodies a unique challenge. Our objective is to provide a comprehensive analysis of cervical and substernal goiter data in two paired articles. This second article focuses on surgical management. The following null hypotheses regarding goiter excision have been tested: 1) there are no goiter-associated risk factors for difficult intubation; 2) there are no predictive risk factors for recurrent laryngeal nerve injury (RLN) or postoperative hypocalcemia; 3) there is no difference in RLN injury with neural monitoring versus without. STUDY DESIGN: A retrospective review of 200 consecutive thyroidectomies meeting inclusion/exclusion criteria for cervical or substernal goiter. RESULTS: Temporary RLN paralysis occurred in 1.8% of nerves at risk and was significantly lower with recurrent laryngeal nerve monitoring than without. Permanent hypoparathyroidism occurred in 3% overall. Bilateral cervical goiter emerged as a definitive risk factor for difficult intubation (P = .05, univariate), recurrent laryngeal nerve injury (P = .002), and postoperative hypocalcemia (P = .001). Female patients (P = .04) or patients with positive family history (P = .01) were more likely to need repeat surgery. There were no cases of tracheomalacia, and sternotomy was required in 1%. CONCLUSIONS: In this series of patients with extensive goiter, primary and revision surgery were associated with low rate of complications. Surgical complications were associated with bilateral and large goiters suggesting increased caution in these patients.

OBJECTIVES: The objectives of this study were to: 1) determine the association between vasopressor dosing intensity during the first 6 hours and first 24 hours after the onset of septic shock and 30-day in-hospital mortality; 2) determine whether the effect of vasopressor dosing intensity varies by fluid resuscitation volume; and 3) determine whether the effect of vasopressor dosing intensity varies by dosing titration pattern. DESIGN: Multicenter prospective cohort study between September 2017 and February 2018. Vasopressor dosing intensity was defined as the total vasopressor dose infused across all vasopressors in norepinephrine equivalents. SETTING: Thirty-three hospital sites in the United States (n = 32) and Jordan (n = 1). PATIENTS: Consecutive adults requiring admission to the ICU with septic shock treated with greater than or equal to 1 vasopressor within 24 hours of shock onset. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of 1,639 patients screened, 616 were included. Norepinephrine (93%) was the most common vasopressor. Patients received a median of 3,400 mL (interquartile range, 1,851-5,338 mL) during the 24 hours after shock diagnosis. The median vasopressor dosing intensity during the first 24 hours of shock onset was 8.5 μg/min norepinephrine equivalents (3.4-18.1 μg/min norepinephrine equivalents). In the first 6 hours, increasing vasopressor dosing intensity was associated with increased odds ratio of 30-day in-hospital mortality, with the strength of association dependent on concomitant fluid administration. Over the entire 24 hour period, every 10 μg/min increase in vasopressor dosing intensity was associated with an increased risk of 30-day mortality (adjusted odds ratio, 1.33; 95% CI, 1.16-1.53), and this association did not vary with the amount of fluid administration. Compared to an early high/late low vasopressor dosing strategy, an early low/late high or sustained high vasopressor dosing strategy was associated with higher mortality. CONCLUSIONS: Increasing vasopressor dosing intensity during the first 24 hours after septic shock was associated with increased mortality. This association varied with the amount of early fluid administration and the timing of vasopressor titration.

PURPOSE: To evaluate the efficacy and toxicity of tirapazamine, a hypoxic cytotoxin, combined with conventional radiotherapy (RT) for advanced head and neck carcinomas. MATERIALS AND METHODS: From Oct. 1994 to Nov. 1996, 40 patients with stage III or IV carcinomas of the head and neck were enrolled in a Phase II trial to receive conventional RT (70 Gy in 7 weeks) with concurrent tirapazamine (159 mg/m2 intravenously, 3 times per week for 12 doses). One patient subsequently withdrew from the protocol treatment, and was excluded from analyses. Among the 39 cases, the primary sites were located in the oropharynx (n = 28), supraglottic larynx (n = 6), or hypopharynx (n = 5). Twenty-seven patients had T3 or T4, and 27 had N2 or N3 disease. RESULTS: Thirty-two (82%) patients received full 12 drug doses. Thirty-two patients (82%) received full 70 Gy of RT. The most frequent drug toxicities were muscle cramps (77%) and nausea/vomiting (62%), usually grade 1 or 2. Overall, 13 patients (33%) experienced grade 3 or 4 drug-related toxicities. No excessive RT-associated acute normal tissue reactions were observed. With a median follow-up of 13 months, the 1-year and 2-year local control rate was 64% and 59% respectively. CONCLUSION: The tirapazamine regimen was well tolerated with a compliance rate of 82%. The toxicity of RT with concurrent tirapazamine was acceptable in treating advanced head and neck carcinomas. The disease control trend was encouraging. Further clinical studies are warranted.

BACKGROUND: Left bundle branch pacing (LBBP) is emerging as a novel option for physiological ventricular pacing. The impact of current of injury (COI) at left bundle branch (LBB) has not been previously evaluated. METHODS: Consecutive patients with QRS duration less than 120 milliseconds referred for LBBP in whom LBB potentials were recorded were included from August 2018 to March 2019. We recorded LBB COI during LBBP and assessed its impact on the pacing parameters and complications during implantation and at short term follow-up. RESULTS: A total of 115 patients with an identifiable LBB potential at implant were included. LBB COI was confirmed in 77 (67.0%) of these patients. Three types of LBB COI were observed. LBB was captured in all patients at a pacing threshold less than 1.5 V/0.5 ms in COI(+) patients, while present in only 29 patients without an LBB COI(-) (100% vs 76.3%; P < .001). There was no significant difference between COI(+) and COI(-) patients in LBB bundle capture threshold (0.64 ± 0.24 vs 0.74 ± 0.26 V/0.5 ms). Selective LBBP was more common in COI(+) group than COI(-) group (54.5% vs 0%; P < .001). Pacing parameters were stable and no lead perforation or dislodgements were observed during follow-up. CONCLUSIONS: LBB COI is commonly observed during LBBP in cases with an identifiable LBB potential and can be associated with a low LBB capture threshold and demonstrable selective capture of the LBB acutely and during follow-up. A COI does not preclude safe and stable LBBP pacing.

BACKGROUND: Left bundle branch area pacing (LBBAP) may be associated with greater improvement in left ventricular ejection fraction and reduction in death or heart failure hospitalization compared with biventricular pacing (BVP) in patients requiring cardiac resynchronization therapy. We sought to compare the occurrence of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and new-onset atrial fibrillation (AF) in patients undergoing BVP and LBBAP. METHODS: The I-CLAS study (International Collaborative LBBAP Study) included patients with left ventricular ejection fraction ≤35% who underwent BVP or LBBAP for cardiac resynchronization therapy between January 2018 and June 2022 at 15 centers. We performed propensity score–matched analysis of LBBAP and BVP in a 1:1 ratio. We assessed the incidence of VT/VF and new-onset AF among patients with no history of AF. Time to sustained VT/VF and time to new-onset AF was analyzed using the Cox proportional hazards survival model. RESULTS: Among 1778 patients undergoing cardiac resynchronization therapy (BVP, 981; LBBAP, 797), there were 1414 propensity score–matched patients (propensity score–matched BVP, 707; propensity score–matched LBBAP, 707). The occurrence of VT/VF was significantly lower with LBBAP compared with BVP (4.2% versus 9.3%; hazard ratio, 0.46 [95% CI, 0.29–0.74]; P &lt;0.001). The incidence of VT storm (&gt;3 episodes in 24 hours) was also significantly lower with LBBAP compared with BVP (0.8% versus 2.5%; P =0.013). Among 299 patients with cardiac resynchronization therapy pacemakers (BVP, 111; LBBAP, 188), VT/VF occurred in 8 patients in the BVP group versus none in the LBBAP group (7.2% versus 0%; P &lt;0.001). In 1194 patients with no history of VT/VF or antiarrhythmic therapy (BVP, 591; LBBAP, 603), the occurrence of VT/VF was significantly lower with LBBAP than with BVP (3.2% versus 7.3%; hazard ratio, 0.46 [95% CI, 0.26–0.81]; P =0.007). Among patients with no history of AF (n=890), the occurrence of new-onset AF &gt;30 s was significantly lower with LBBAP than with BVP (2.8% versus 6.6%; hazard ratio, 0.34 [95% CI, 0.16–0.73]; P =0.008). The incidence of AF lasting &gt;24 hours was also significantly lower with LBBAP than with BVP (0.7% versus 2.9%; P =0.015). CONCLUSIONS: LBBAP was associated with a lower incidence of sustained VT/VF and new-onset AF compared with BVP. This difference remained significant after adjustment for differences in baseline characteristics between patients with BVP and LBBAP. Physiological resynchronization by LBBAP may be associated with lower risk of arrhythmias compared with BVP.