[Increasing independence of a resident in training: lessons in disciplinary law]. / Toenemende zelfstandigheid van een aios.

Objective To explore how the disciplinary board allocates responsibility between the resident in training and the supervisor. Design Case law analysis. Method All published disciplinary judgments containing the term 'resident in training' from January 1, 2010, to April 1, 2020 on www.tuchtrecht.overheid.nl were analyzed. Results 116 law cases involving 128 complaints were examined. The disciplinary boards' considerations could be distinguished into four groups: situational characteristics, the resident's competence, the extent and quality of supervision, and information provision. Conclusion The disciplinary boards allocates responsibility between the resident in training and the supervisor in the context of the specific complaint and situation. It is therefore important that the general rules and regulations regarding supervision of residents are clearly outlined and documented, including their momentary alignment. In addition, the hospital has a general responsibility to inform patients about the implications of training residents while providing healthcare.

Neutrophil extracellular traps induced by chemotherapy inhibit tumor growth in murine models of colorectal cancer.

Neutrophil extracellular traps (NETs), a web-like structure of cytosolic and granule proteins assembled on decondensed chromatin, kill pathogens and cause tissue damage in diseases. Whether NETs can kill cancer cells is unexplored. Here, we report that a combination of glutaminase inhibitor CB-839 and 5-FU inhibited the growth of PIK3CA-mutant colorectal cancers (CRCs) in xenograft, syngeneic, and genetically engineered mouse models in part through NETs. Disruption of NETs by either DNase I treatment or depletion of neutrophils in CRCs attenuated the efficacy of the drug combination. Moreover, NETs were present in tumor biopsies from patients treated with the drug combination in a phase II clinical trial. Increased NET levels in tumors were associated with longer progression-free survival. Mechanistically, the drug combination induced the expression of IL-8 preferentially in PIK3CA-mutant CRCs to attract neutrophils into the tumors. Further, the drug combination increased the levels of ROS in neutrophils, thereby inducing NETs. Cathepsin G (CTSG), a serine protease localized in NETs, entered CRC cells through the RAGE cell surface protein. The internalized CTSG cleaved 14-3-3 proteins, released BAX, and triggered apoptosis in CRC cells. Thus, our studies illuminate a previously unrecognized mechanism by which chemotherapy-induced NETs kill cancer cells.

Unveiling immune checkpoint regulation: exploring the power of in vivo CRISPR screenings in cancer immunotherapy.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer immunotherapy by reinvigorating antitumor immune responses, but their efficacy remains limited in most patients. To address this challenge and optimize Immune check inhibitor treatment, understanding the underlying molecular intricacies involved is crucial. The emergence of CRISPR-Cas9 technology has empowered researchers to precisely investigate gene function and has introduced transformative shifts in identifying key genes for various physiological and pathological processes. CRISPR screenings, particularly in vivo CRISPR screenings, have become invaluable tools in deciphering molecular networks and signaling pathways governing suppressive immune checkpoint molecules. In this review, we provide a comprehensive overview of in vivo CRISPR screenings in cancer immunotherapy, exploring how this cutting-edge technology has unraveled potential novel therapeutic targets and combination strategies. We delve into the latest findings and advancements, shedding light on immune checkpoint regulation and offering exciting prospects for the development of innovative and effective treatments for cancer patients.

A Clinically Oriented antimicrobial Resistance surveillance Network (ACORN): pilot implementation in three countries in Southeast Asia, 2019-2020.

Background: Case-based surveillance of antimicrobial resistance (AMR) provides more actionable data than isolate- or sample-based surveillance. We developed A Clinically Oriented antimicrobial Resistance surveillance Network (ACORN) as a lightweight but comprehensive platform, in which we combine clinical data collection with diagnostic stewardship, microbiological data collection and visualisation of the linked clinical-microbiology dataset. Data are compatible with WHO GLASS surveillance and can be stratified by syndrome and other metadata. Summary metrics can be visualised and fed back directly for clinical decision-making and to inform local treatment guidelines and national policy. Methods: An ACORN pilot was implemented in three hospitals in Southeast Asia (1 paediatric, 2 general) to collect clinical and microbiological data from patients with community- or hospital-acquired pneumonia, sepsis, or meningitis. The implementation package included tools to capture site and laboratory capacity information, guidelines on diagnostic stewardship, and a web-based data visualisation and analysis platform. Results: Between December 2019 and October 2020, 2294 patients were enrolled with 2464 discrete infection episodes (1786 community-acquired, 518 healthcare-associated and 160 hospital-acquired). Overall, 28-day mortality was 8.7%. Third generation cephalosporin resistance was identified in 54.2% (39/72) of E. coli and 38.7% (12/31) of K. pneumoniae isolates . Almost a quarter of S. aureus isolates were methicillin resistant (23.0%, 14/61). 290/2464 episodes could be linked to a pathogen, highlighting the level of enrolment required to achieve an acceptable volume of isolate data. However, the combination with clinical metadata allowed for more nuanced interpretation and immediate feedback of results. Conclusions: ACORN was technically feasible to implement and acceptable at site level. With minor changes from lessons learned during the pilot ACORN is now being scaled up and implemented in 15 hospitals in 9 low- and middle-income countries to generate sufficient case-based data to determine incidence, outcomes, and susceptibility of target pathogens among patients with infectious syndromes.

Evaluation of SARS-CoV-2 Antibodies and the Impact of COVID-19 on the HIV Care Continuum, Economic Security, Risky Health Behaviors, and Mental Health Among HIV-Infected Individuals in Vietnam.

Coronavirus disease 2019 (COVID-19) and associated social responses may uniquely affect people living with HIV (PLHIV). SARS-CoV-2 antibody testing and a cross-sectional survey on COVID-19's socio-behavioral impacts were conducted among a large PLHIV cohort in Hanoi, Vietnam. We examined anonymous antibody test results for 1243 PLHIV (99.8%) from whom plasma was obtained and completed surveys were collected in June/July 2020, just after the end of the first COVID-19 outbreak and nationwide lockdown. Three participants (0.2%) tested positive for anti-SARS-CoV-2 IgG antibodies. HIV treatment was generally maintained without antiretroviral therapy interruption, but COVID-19 had substantial impacts on economic security and risky health behaviors among PLHIV, which may have amplified psychological stress. These findings highlight the need for continuous monitoring of COVID-19's impacts on PLHIV and for efforts to mitigate these impacts.

Clinical utility of rhythm control by electrical cardioversion to assess the association between self-reported symptoms and rhythm status in patients with persistent atrial fibrillation.

BACKGROUND: The best strategy to assess the association between symptoms and rhythm status (symptom-rhythm correlation) in patients with atrial fibrillation (AF) remains unclear. We aimed to determine the clinical utility of rhythm control by electrical cardioversion (ECV) to assess symptom-rhythm correlation in patients with persistent AF. METHODS: We used ECV to examine symptom-rhythm correlation in 81 persistent AF patients. According to current clinical practice, the presence of self-reported symptoms before ECV and at the first outpatient clinic follow-up visit (within 1-month) was assessed to determine the prevalence of a symptom-rhythm correlation (defined as self-reported symptoms present during AF and absent in sinus rhythm or absent in AF and yet relief during sinus rhythm). In addition, we evaluated symptom patterns around ECV. RESULTS: Only in 18 patients (22%), a symptom-rhythm correlation could be documented. Twenty-eight patients (35%) did not show any symptom-rhythm correlation and 35 patients (43%) had an unevaluable symptom-rhythm correlation as these patients were in symptomatic AF both at baseline and at the first outpatient AF clinic follow-up visit. Importantly, self-reported symptom patterns around ECV were intra-individually variable in 10 patients (12%) without symptom-rhythm correlation (of which 9 patients (11%) had AF recurrence) and in 2 patients (2%) with an unevaluable symptom-rhythm correlation. CONCLUSIONS: In patients with persistent AF, symptom assessment around rhythm control by ECV, once before ECV and once within 1-month follow-up, rarely identifies a symptom-rhythm correlation and often suggests changes in symptom pattern. Better strategies are needed to assess symptom-rhythm correlation in patients with persistent AF.

Long-term intermittent versus short continuous heart rhythm monitoring for the detection of atrial fibrillation recurrences after catheter ablation.

BACKGROUND: The utility of long-term intermittent heart rhythm monitoring after atrial fibrillation (AF) ablation remains unclear. Therefore, we compared the efficacy and usability of long-term intermittent (AliveCor Kardia® (ACK)) versus short continuous (Holter) heart rhythm monitoring for the detection of AF recurrences after AF ablation and evaluated ACK accuracy to detect AF. METHODS: Patients were provided with Holter (for ≥24 h) simultaneously with an ACK (4 weeks) used three times a day and in case of symptoms. The primary endpoint was the difference in proportion of patients diagnosed with recurrent AF by ACK as compared to Holter monitoring. Secondary endpoints were the usability (System Usability Scale and a four-item questionnaire) of ACK and Holter monitoring; and the accuracy of the ACK algorithm for AF detection. RESULTS: Out of 126 post-ablation patients, 115 (91.3%; 35 females, median age 64.0 [58.0-68.0] years) transmitted overall 7838 ACK ECG recordings. ACK and Holter monitoring detected 29 (25.2%) and 17 (14.8%) patients with AF recurrences, respectively (p < 0.001). More than 2 weeks of ACK monitoring did not have additional diagnostic yield for detection of AF recurrences. Patients graded ACK higher than Holter monitoring and found ACK more convenient in daily usage than Holter (p < 0.001). Sensitivity and specificity of ACK for AF detection were 95.3% and 97.5%, respectively. CONCLUSIONS: Long-term intermittent monitoring by ACK more effectively detects AF recurrences after AF ablation and has a higher patients' usability than short continuous Holter monitoring. ACK showed a high accuracy to detect AF.

The "sex gap" in COVID-19 trials: a scoping review.

BACKGROUND: Many studies investigate the role of pharmacological treatments on disease course in Corona Virus Disease 2019 (COVID-19). Sex disparities in genetics, immunological responses, and hormonal mechanisms may underlie the substantially higher fatality rates reported in male COVID-19 patients. To optimise care for COVID-19 patients, prophylactic and therapeutic studies should include sex-specific design and analyses. Therefore, in this scoping review, we investigated whether studies on pharmacological treatment in COVID-19 were performed based on a priori sex-specific design or post-hoc sex-specific analyses. METHODS: We systematically searched PubMed, EMBASE, UpToDate, clinical trial.org, and MedRxiv for studies on pharmacological treatment for COVID-19 until June 6th, 2020. We included case series, randomized controlled trials, and observational studies in humans (≥18 years) investigating antiviral, antimalarial, and immune system modulating drugs. Data were collected on 1) the proportion of included females, 2) whether sex stratification was performed (a priori by design or post-hoc), and 3) whether effect modification by sex was investigated. FINDINGS: 30 studies were eligible for inclusion, investigating remdesivir (n = 2), lopinavir/ritonavir (n = 5), favipiravir (n = 1), umifenovir (n = 1), hydroxychloroquine/chloroquine (n = 8), convalescent plasma (n = 6), interleukin-6 (IL-6) pathway inhibitors (n = 5), interleukin-1 (IL-1) pathway inhibitors (n = 1) and corticosteroids (n = 3). Only one study stratified its data based on sex in a post-hoc analysis, whereas none did a priori by design. None of the studies investigated effect modification by sex. A quarter of the studies included twice as many males as females. INTERPRETATION: Analyses assessing potential interference of sex with (side-)effects of pharmacological therapy for COVID-19 are rarely reported. Considering sex differences in case-fatality rates and genetic, immunological, and hormonal mechanisms, studies should include sex-specific analyses in their design to optimise COVID-19 care. FUNDING: None.

An adaptive solution to the chemical master equation using quantized tensor trains with sliding windows.

To cope with an extremely large or even infinite state space when solving the chemical master equation in biological problems, a potent strategy is to restrict to a finite state projection (FSP) and represent the transition matrix and probability vector in quantized tensor train (QTT) format, leading to savings in storage while retaining accuracy. In an earlier adaptive FSP-QTT algorithm, the multidimensional state space was downsized and kept in the form of a hyper rectangle that was updated when needed by selectively doubling some of its side dimensions. However, this could result in a much larger state space than necessary, with the effect of hampering both the execution time and stepping scheme. In this work, we improve the algorithm by enabling sliding windows that can dynamically slide, shrink or expand, with updates driven by a number of stochastic simulation algorithm trajectories. The ensuing state space is a considerably reduced hyper rectangle containing only the most probable states at each time step. Three numerical experiments of varying difficulty are performed to compare our approach with the original adaptive FSP-QTT algorithm.

Safety of in-hospital insertable cardiac monitor procedures performed outside the traditional settings: results from the Reveal LINQ in-office 2 international study.

BACKGROUND: Historically, the majority of insertable cardiac monitor (ICM) procedures were performed in the cardiac catheterization (cath) lab, electrophysiology (EP) lab, or operating room (OR). The miniaturization of ICMs allows the procedure to be relocated within the hospital without compromising patient safety. We sought to estimate the rate of untoward events associated with procedures performed within the hospital but outside the traditional settings and to characterize resource utilization, procedure time intervals, and physician experience. METHODS: The Reveal LINQ in-Office 2 (RIO 2) International study was a single arm, multicenter, prospective study. Patients indicated for an ICM and willing to undergo device insertion outside the cath/EP lab or OR were eligible and followed for 90 days after insertion. RESULTS: A total of 191 patients (45.5% female aged 63.8 ± 26.9 years) underwent successful Reveal LINQ ICM insertion at 17 centers in Europe, Canada and Australia. The median total visit duration was 106 min (interquartile range [IQR]: 55-61). Patient preparation and patient education accounted for 10 min (IQR: 5-20) and 10 min (IQR: 8-15) of total visit duration, respectively. Preparation and education occurred in the procedure room for 90.6 and 60.2% of patients, respectively. There were no untoward events (0.0, 95% CI: 0.0-2.1%) though four patients presented with procedure-related adverse events that did not require invasive intervention. Physicians rated procedure location as convenient or very convenient. CONCLUSIONS: The Reveal LINQ™ ICM insertion can be safely and efficiently performed in the hospital outside the cath/EP lab or OR. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02412488 ; registered on April 9, 2015.

Deficiency of AtGFAT1 activity impairs growth, pollen germination and tolerance to tunicamycin in Arabidopsis.

The hexosamine biosynthetic pathway (HBP) plays essential roles in growth and development in plants. However, insight into the biological function of glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1), mediating the first regulatory step of the HBP, remains unclear in plants. Here, we report the molecular characterization of Arabidopsis AtGFAT1 gene. AtGFAT1 was highly expressed in mature pollen grains, but its expression was not detectable in the rest of the organs. Pollen grains bearing the gfat1-2 knockout allele displayed defects in a polar deposition of pectin and callose in the pollen cell wall, leading to no genetic transmission of the gfat1-2 allele through the male gametophyte. AtGFAT1 overexpression increased glucosamine (GlcN) content and enhanced resistance to tunicamycin (Tm) treatment, while RNAi-mediated suppression reduced GlcN content and resistance to Tm treatment. However, the decrease in Tm resistance by RNAi suppression of AtGFAT1 was recovered by a GlcN supplement. The exogenous GlcN supplement also rescued gfat1-2/gaft1-2 mutant plants, which were otherwise not viable. The gfat1-2/gfat1-2 plants stopped growing at the germination stage on GlcN-free medium, but GlcN supplement allowed wild-type growth of gfat1-2/gfat1-2 plants. In addition, reactive oxygen species production, cell death and a decrease in protein N-glycosylation were observed in gfat1-2/gaft1-2 mutant plants grown on GlcN-free medium, whereas these aberrant defects were not detectable on GlcN-sufficient medium. Taken together, these results show that the reduction of protein N-glycosylation was at least partially responsible for many aberrant phenotypes in growth and development as well as the response to Tm treatment caused by AtGFAT1 deficiency in Arabidopsis.

Initial orthostatic hypotension among patients with unexplained syncope: An overlooked diagnosis?

BACKGROUND: Initial orthostatic hypotension (IOH) is a clinical syndrome of transient orthostatic hypotension that is defined as a drop in blood pressure of >40 mm Hg systolic and/or >20 mm Hg diastolic within 15 s after standing, accompanied by symptoms of cerebral hypoperfusion, but without sustained orthostatic hypotension (blood pressure decrease >20/10 mm Hg after 1-3 min of standing). As the etiology of syncope remains unknown in a large proportion of patients, we hypothesized that IOH is highly prevalent among patients with unexplained syncope. METHODS: We studied 250 consecutive outpatients with unexplained syncope that were evaluated in the syncope-unit of our tertiary referral hospital. We measured hemodynamic changes in response to active standing using a beat-to-beat blood pressure measurement device, first after lying supine for >5 min and then after squatting for 30 s. RESULTS: 11.2% of the patients were diagnosed with syncope due to IOH, with a mean fall in blood pressure of 47.4 ±â€¯12.5/29.0 ±â€¯10.7 mm Hg within 15 s after standing up. Therefore, IOH was the second commonest cause of syncope in our cohort. 46.2% of the patients diagnosed with syncope due to IOH used antihypertensive drugs, mostly betablockers (41.6%) and/or tamsulosin (24.9%). The squatting-to-standing-test in addition to the lying-to-standing-test resulted in only 3 additional patients diagnosed with syncope due to IOH. CONCLUSIONS: IOH is highly prevalent among patients with previously unexplained syncope. Therefore, beat-to-beat blood pressure measurement should be considered in patients with unexplained syncope.

External electrical cardioversion in patients with cardiac implantable electronic devices: Is it safe and is immediate device interrogation necessary?

BACKGROUND: Atrial tachyarrhythmias are common in patients with cardiac implantable electronic devices (CIEDs). Restoration of sinus rhythm by external electrical cardioversion (eECV) is frequently used to alleviate symptoms and to ensure optimal device function. OBJECTIVES: To evaluate the safety of eECV in patients with contemporary CIEDs and to assess the need for immediate device interrogation after eECV. METHODS: We conducted a retrospective observational study of 229 patients (27.9% female, age 69 ± 10 years) with a CIED (104 pacemakers, 69 implantable cardioverter defibrillators, and 56 biventricular devices) who underwent eECV between 2008 and 2016 in two centers. Data from device interrogation before eECV, immediately afterwards, and at first follow-up (FU) after eECV were collected. CIED-related complications and adverse events during and after eECV were recorded. RESULTS: No significant differences between right atrial (RA) and right ventricular (RV) sensing or threshold values before eECV, immediately afterwards, or at FU were observed. A small yet significant decrease was observed in RA and RV impedance immediately after eECV (484 Ω vs 462 Ω, P < 0.001 and 536 Ω vs 514 Ω, P < 0.001, respectively). The RV impedance did not recover to the baseline value (538 Ω vs 527 Ω, P  =  0.02). The impedance changes were without clinical consequences. No changes in left ventricular lead threshold or impedance values were measured. No CIED-related complications or adverse events were documented following eECV. CONCLUSION: eECV in patients with contemporary CIEDs is safe. There seems to be no need for immediate device interrogation after eECV.

Current perspective: Osimertinib-induced QT prolongation: new drugs with new side-effects need careful patient monitoring.

An increasing number of tyrosine kinase inhibitors (TKIs) are available for the treatment of non-small cell lung cancer (NSCLC). QT prolongation is one of the known, but relatively rare, adverse events of several TKIs (e.g. osimertinib, crizotinib, ceritinib). Screening for QT prolongation in (high risk) patients is advised for these TKIs. When a QT prolongation develops, the physician is challenged with the question whether to (permanently) discontinue the TKI. In this perspective, we report on a patient who developed a grade III QT prolongation during osimertinib (a third-generation epidermal growth factor receptor [EGFR]-TKI) treatment. On discontinuation of osimertinib, she developed a symptomatic disease flare, not responding to subsequent systemic treatment. The main aim of this perspective is to describe the management of QT prolongation in stage IV EGFR driver mutation NSCLC patients. We also discuss the ethical question of how to weigh the risk of a disease flare due to therapy cessation against the risk of sudden cardiac death. A family history of sudden death and a prolonged QT interval might indicate a familiar long QT syndrome. We have summarised the current monitoring advice for TKIs used in the treatment of lung cancer and the most common drug-TKI interactions to consider and to optimise TKI treatment in lung cancer patients.

Cost comparison of two implantable cardiac monitors in two different settings: Reveal XT in a catheterization laboratory vs. Reveal LINQ in a procedure room.

AIMS: Implantable cardiac monitors (ICMs) are used for long-term heart rhythm monitoring, e.g. to diagnose unexplained syncope or for detection of suspected atrial and ventricular arrhythmias. The newest ICM, Reveal LINQ™ (Medtronic Inc.), is miniaturized and inserted with a specific insertion tool kit. The procedure is therefore minimally invasive and can be moved from catheterization laboratory (cath lab) to a less resource intensive setting. This study aims to assess the change in procedure costs when performed outside the cath lab. METHODS AND RESULTS: A bottom-up costing methodology was used. Data were collected from interviews with physicians, cath lab managers, and financial controllers. Hospitals in the Netherlands, France, and the UK were included in this study. The cost comparison of a Reveal XT implantation in a cath lab setting vs. a Reveal LINQ insertion outside a cath lab resulted in an estimated reduction of €662 for the UK, €682 for the Netherlands, and €781 for France. These cost savings were primarily realized through fewer staff, less equipment, and overhead costs. The net effect on savings depends on the price differential between these two technologies. The patient care pathway can be improved due to the possibility to move the procedure out of the cath lab. CONCLUSION: Inserting the miniaturized version of the ICM is simpler and faster, and the procedure can take place outside the cath lab in a less resource intensive environment. Hospitals save resources when the higher price of the Reveal LINQ does not outweigh these savings.

Adenosine testing after second-generation cryoballoon ablation (ATSCA) study improves clinical success rate for atrial fibrillation.

AIMS: Adenosine administration after pulmonary vein (PV) isolation using radiofrequency, laser, and cryoablation can cause acute recovery of conduction to the PVs and predict atrial fibrillation (AF) recurrence. This study evaluates whether ablation of dormant potentials post-adenosine administration following second-generation cryoballoon (CB-2G) ablation may improve the success rate for AF. METHODS AND RESULTS: In 45 of 90 patients after a waiting period of 30 min, a bolus 15-21 mg of adenosine was administered followed by rapid saline flush. The response was assessed for each PV using a circular octapolar catheter. If needed, further ablation using a cryoballoon and/or cryocatheter was performed until no reconduction was observed after repeat adenosine administration. The remaining 45 patients did not receive adenosine after the procedure. Acute PV isolation was achieved in 352 of 358 PVs (98.3%) of 86 of 90 patients (95.6%) using CB-2G. The adenosine group showed dormant reconduction in 5 of 45 patients (11%), 8 of 179 PVs (4.5%), including 1 left superior pulmonary vein, 3 left inferior pulmonary vein, 1 right superior pulmonary vein, and 3 right inferior pulmonary vein. The success rate for adenosine and without adenosine group was 84 and 79%, respectively, after a mean follow-up of 397 ± 47 and 349 ± 66 days, without any AF recurrence in patients in whom adenosine-induced dormant conduction was ablated. CONCLUSION: Adenosine testing after second-generation cryoballoon ablation study showed that reablation of initially isolated PVs increases the clinical success rate for AF.

Failure to reach the optimal temperature during cryoablation due to refrigerant cylinder problem.

INTRODUCTION: Pulmonary vein (PV) isolation is considered as a key to atrial fibrillation (AF) treatment. Cryoballoon ablation is an effective therapy for PV isolation for AF with minimal side effects and was approved by the US Food and Drug Administration (FDA) several years ago. Successful isolation of PVs during cryoablation depends on the balloon temperature and helps in early identification of noneffective cryoballoon applications. A lower balloon temperature has been associated with long-term success in isolation of PVs. CASE PRESENTATION: At the start of the procedure, the cryoconsole displayed "low refrigerant level". After a few cycles of successful cryoballoon applications, for a fresh application for a new PV, the optimal temperature was not obtained in spite of obtaining good grade of occlusion and ostial positioning for right inferior pulmonary vein (RIPV). Later, immediately after changing the refrigerant cylinder, suitable temperature was obtained. We faced this situation thrice in a span of eight months. CONCLUSION: Low refrigerant level may cause nonoptimal temperature during cryoablation, which can be resolved by premature change of a gas cylinder.

Left ventricular lead placement in the latest activated region guided by coronary venous electroanatomic mapping.

AIM: Left ventricular (LV) lead placement in the latest activated region is an important determinant of response to cardiac resynchronization therapy (CRT). We investigated the feasibility of coronary venous electroanatomic mapping (EAM) to guide LV lead placement to the latest activated region. METHODS AND RESULTS: Twenty-five consecutive CRT candidates with left bundle-branch block underwent intra-procedural coronary venous EAM using EnSite NavX. A guidewire was used to map the coronary veins during intrinsic activation, and to test for phrenic nerve stimulation (PNS). The latest activated region, defined as the region with an electrical delay >75% of total QRS duration, was located anterolaterally in 18 (basal, n = 10; mid, n = 8) and inferolaterally in 6 (basal, n = 3; mid, n = 3). In one patient, identification of the latest activated region was impeded by limited coronary venous anatomy. In patients with >1 target vein (n = 12), the anatomically targeted inferolateral vein was rarely the vein with maximal electrical delay (n = 3). A concordant LV lead position was achieved in 18 of 25 patients. In six patients, this was hampered by PNS (n = 4), lead instability (n = 1), and coronary vein stenosis (n = 1). CONCLUSION: Coronary venous EAM can be used intraprocedurally to guide LV lead placement to the latest activated region free of PNS. This approach especially contributes to optimization of LV lead electrical delay in patients with multiple target veins. Conventional anatomical LV lead placement strategy does not target the vein with maximal electrical delay in many of these patients.

Different regions of latest electrical activation during left bundle-branch block and right ventricular pacing in cardiac resynchronization therapy patients determined by coronary venous electro-anatomic mapping.

AIM: Current targeted left ventricular (LV) lead placement strategy is directed at the latest activated region during intrinsic activation. However, cardiac resynchronization therapy (CRT) is most commonly applied by simultaneous LV and right ventricular (RV) pacing without contribution from intrinsic conduction. Therefore, targeting the LV lead to the latest activated region during RV pacing might be more appropriate. We investigated the difference in LV electrical activation sequence between left bundle-branch block (LBBB) and RV apex (RVA) pacing using coronary venous electro-anatomic mapping (EAM). METHODS AND RESULTS: Twenty consecutive CRT candidates with LBBB underwent intra-procedural coronary venous EAM during intrinsic activation and RVA pacing using EnSite NavX. Left ventricular lead placement was aimed at the latest activated region during LBBB according to current recommendations. In all patients, LBBB was associated with a circumferential LV activation pattern, whereas RVA pacing resulted in activation from the apex of the heart to the base. In 10 of 20 patients, RVA pacing shifted the latest activated region relative to LBBB. In 18 of 20 patients, the LV lead was successfully positioned in the latest activated region during LBBB. For the whole study population, LV lead electrical delay, expressed as percentage of QRS duration, was significantly shorter during RVA pacing than during LBBB (72 ± 13 vs. 82 ± 5%, P = 0.035). CONCLUSION: Right ventricular apex pacing alters LV electrical activation pattern in CRT patients with LBBB, and shifts the latest activated region in a significant proportion of these patients. These findings warrant reconsideration of the current practice of LV lead targeting for CRT.