Efficacy of Balloon Expandable Extreme-Low Temperature Ventricular Epicardial Cryoablation: A Preclinical Proof of Concept Evaluation.

BACKGROUND: Current epicardial ablation technologies are limited by the inability to create adequate depth lesions and risk of collateral injury to extracardiac structures. OBJECTIVE: To evaluate the feasibility and efficacy of ventricular epicardial ablation with a novel balloon-expandable extreme-low temperature (XLT) cryoablation catheter with an embedded insulation pontoon for protection of extracardiac structures which has been specifically designed for epicardial ablation. METHODS: 10 healthy swine underwent surgical (6) and subxiphoid percutaneous (4) epicardial access respectively. A total of 3-6 sites were targeted in the right and left ventricular wall for different exposure durations. Ablation was performed with a large footprint (surgical) and smaller footprint (percutaneous) version of the HeartPad® (Corfigo Inc., Montclair, NJ) XLT system. The system consists of the balloon-expandable cryoablation catheter and a console. The console vaporizes liquid helium (-269˚C) and controls continuous delivery of extremely cold helium gas at high flow rates through a high-efficiency ablation element mounted on an expandable insulation pontoon to protect extracardiac structures. Ablation lesions were assessed by gross pathology and histological examination. RESULTS: A total of 42 epicardial lesions were created. The mean lesion depth increased progressively with the ablation time (surgical catheter: 11±2 mm at ≤30 seconds, 13±4 mm at 60 seconds, 15±3 mm at ≥120 seconds, P =0.001; percutaneous catheter: 10±2 mm at 30 seconds, 14±2 mm at 60 seconds, 16±2 mm at 120 seconds], P =0.001). Lesion geometry appeared unaffected by presence and thickness of epicardial fat. One episode of ventricular fibrillation occurred following ablation over the atrioventricular groove and 2 adjacent obtuse marginal arteries. CONCLUSION: Surgical or percutaneous epicardial ablation using the HeartPad® XLT cryoablation system is feasible and can efficiently produce deep ventricular lesions in different epicardial locations.

Prevalence and proportion by age and sex of chronic health conditions in a large healthcare system.

BACKGROUND: Disease prevalence and distribution by patient characteristics data are needed to guide "representative" patient enrollment in clinical trials and assess relevance of results to patient populations. Our objective was to describe disease prevalence, and age/sex distribution of patients with common chronic conditions from a large population sample. METHODS: A cross-sectional study of all members of Clalit Health Services, alive on January 1, 2020. Included were 26 chronic diseases, and 21 types of malignancies regarded as active by being diagnosed between January 1, 2018- to January 1, 2020, or by prescription of oncologic treatment medications January 1, 2018 and January 1, 2020. RESULTS: Data from 4,627,183 individuals, 2,274,349 males and 2,352,834 females from newborn to 110 years. Obesity (19%), hypertension (13%), diabetes mellitus (9%), esophagitis-gastritis (5.5%), thyroid disease (5.3%), asthma (5.1%), ischemic heart disease (4.5%), depression (4.5%), osteoporosis (3.8%), and atopic dermatitis (3.6%) were the ten most prevalent conditions. Proportions of age groups varied between conditions (67% of hypertensives were ≥65 years old, 24% ≥80 years; 73% with ischemic heart disease were ≥65 years, 29% ≥80 years; 59% of diabetics were ≥65 years, 17% ≥80 years; 42% of atrial fibrillation patients were ≥80 years; 40% of heart failure patients were ≥80 years). Proportions of males and females for most conditions paralleled prevalence except proportions of women increased after age 80 for cardiovascular diseases, and for diabetes after age 75. The five most frequent active cancers were breast, prostate, colon/rectal, lymphoma and melanoma. The prevalence of cancers increased with age beginning in the middle-aged groups and peaking at very old ages. Women had lower prevalence of lung cancers and accounted for lower percentages of patients with lung cancers (45 vs 55%) but similar percentages for women and men were seen in the patients with colon and rectal cancer (50.4 vs. 49.6% in women) and lymphoma (50.7 vs. 49.3% in women). CONCLUSIONS: Prevalence of medical conditions and distributions differ by age and sex. This information serves as an example and resource for data needed to describe a "representative" clinical population.

Glucose-Lowering Drugs with Proven Cardiovascular Benefit Following Acute Coronary Syndrome in Patients with Type 2 Diabetes: Treatment Gaps and Outcomes.

Background: Real-world data on the implementation and prognostic impact of glucose-lowering drugs with proven cardiovascular benefits in patients with type 2 diabetes (T2D) following acute coronary syndrome (ACS) are limited. We investigated the utilization and treatment patterns of sodium-glucose contrasporter-2 inhibitors (SGLT2Is) and glucagon-like peptide-1 recepto-agonists (GLP1RAs) in patients with T2D experiencing ACS and analyzed their association with mortality and major adverse cardiovascular events (MACEs) including recurrent ACS, acute revascularization, heart failure, or ischemic stroke. Methods: We carried out a retrospective analysis of 9756 patients with T2D from a nationwide healthcare organization in Israel who were hospitalized with ACS between 01/2019 and 01/2022. Drug prescriptions were estimated pre-hospitalization, 90 days, and 1 year following hospitalization. The association between SGLT2I and/or GLP1RA treatment with MACE and mortality was investigated using a time-dependent Cox regression analysis with multivariable adjustment. Results: The prescription rates (pre-hospitalization, 90 days, and 1 year post-hospitalization) of GLP1RAs were 13%, 13.2%, and 18%, and those of SGLT2Is were 23.9%, 33.6%, and 42.7%, respectively. At 1 year, 13.9% of patients were prescribed both treatments. The use of SGLT2Is and/or GLP1RAs was higher in younger age groups and increased from 2019 to 2021 (38.1% to 59.2%). The adjusted hazard ratio for the association of pre- or post-hospitalization SGLT2I and/or GLP1RA treatment with mortality and MACE was 0.724 (0.654-0.801) and 0.974 (0.909-1.043), respectively. Conclusions: In the real-world practice of treating patients with T2D experiencing ACS, the implementation of SGLT2Is, particularly GLP1RAs, was suboptimal when prescribed both early and 1 year following hospitalization, emphasizing the need to improve medical care. Treatment with SGLT2Is and/or GLP1RAs was associated with a favorable impact on mortality but not MACE.

Vascular Access Complications Following Catheter Ablation of Ventricular Arrhythmias: Impact of Vascular Closure Devices.

BACKGROUND: Vascular access-site complications are the most frequent complications of percutaneous catheter ablation (CA) of ventricular arrhythmias (VAs). Whether arterial/venous vascular closure devices (VCDs) prevent vascular complications is unknown. OBJECTIVE: We investigated the benefit of VCDs in patients undergoing CA of VAs. METHODS: Consecutive CA of VAs were included (2018-2022). Vascular accesses were obtained with ultrasound guidance. At the discretion of the operator, arterial and/or venous VCDs were used. Cases were divided into 3 groups: no use of VCDs for any of the arterial/venous accesses (manual compression - MC), use of VCDs for some but not the all of the accesses (Partial-VCDs), use of VCDs for all of the accesses (Complete-VCDs). Vascular complications were defined minor if they didn't require intervention or major if they required intervention. RESULTS: A total of 1,016 procedures were performed in 872 patients (62±13 years, BMI 30±6 kg/m2, 27% female) during the study period. Femoral arterial access was obtained in 887 procedures (875 single access - 7.4±1.5 Fr size, 12 two accesses - 7.3±3 Fr and 6.9±1.8 Fr). Femoral venous access was obtained in 1,014 procedures (unilateral in 17%, bilateral in 83%, mean N. 2.6±0.7, 8.4±1.3 Fr). Hemostasis was achieved with MC in 192 (19%) procedures, Partial-VCD in 275 (27%), and Complete-VCD in 549 (54%). A vascular complication occurred in 52 (5.1%) procedures, including a minor hematoma in 3.9% and/or a major complication in 1.7%. The rate of vascular complications was 6.8% (5.2% minor and 1.6% major) in the MC group, 7.6% (5.1% minor and 3.3% major) in the Partial-VCD group, and 3.3% (2.9% minor and 0.9% major, P=0.014 for comparison) in the Complete-VCD group. At multivariable analysis, Complete-VCD remained independently associated with lower risk of vascular complications (odds ratio 0.69, 95% confidence interval 0.48 to 0.96, P=0.036). CONCLUSIONS: In patients undergoing CA of VAs, Complete-VCD is associated with lower rates of vascular-related complications compared to MC or Partial-VCD.

Efficacy, adherence and persistence of various glucagon-like peptide-1 agonists: nationwide real-life data.

AIM: The management of type 2 diabetes mellitus has advanced in the last two decades since the introduction of glucagon-like peptide-1 receptor agonists (GLP-1RAs). However, multiple factors may interfere with achieving better glycaemic control. This study evaluated the differences between various GLP-1RAs in efficacy, adherence and persistence. MATERIALS AND METHODS: We conducted a retrospective cohort study using the electronic medical database from Clalit Health Services. Adults with type 2 diabetes mellitus who purchased any GLP-1RA between 2009 and 2021 were included. The Index Date was defined as the date of the first purchase of any GLP-1RA. We evaluated the adherence, persistence and glycaemic control after GLP-1RAs initiation. Baseline glycaemic and post-treatment glycaemic controls were analysed. RESULTS: In total, 70 654 patients were included. The mean age was 11.7 ± 60.4, and 51% were females. A significant reduction in glycated haemoglobin (HbA1c) was observed in all patients who received GLP-1RAs. However, the percentage of changes in the HbA1c was higher among weekly GLP-1RA than daily initiators (14.6% vs. 10.2%, p < 0.001). The proportion of subjects with any decrease in HbA1c was higher among the once-weekly compared with the daily dose (82.4% vs. 74.7%) and mainly patients initiated semaglutide or dulaglutide, with 16.0% and 14.7% reduction. The frequency of good adherence (the proportion of days covered ≥80%) was significantly higher among the weekly group odds ratio = 1.25 (95% confidence interval 1.21-1.28). Good adherence was reported in older age, female gender, Jewish ethnicity and high socio-economic status (p < 0.001). CONCLUSIONS: Weekly GLP-1RAs initiators were more adherent, persistent to therapy and achieved better glycaemic control. Epidemiological variables might play a role in achieving this goal.

Mortality during the SARS-CoV-2 Pandemic: A Comparative Analysis between Lombardy in Italy and Israel.

Background: This retrospective study contrasts the impact of the SARS-CoV-2 pandemic in Lombardy (Italy) and Israel, focusing on mortality, healthcare response, public health measures, and demographics. Methods: We analyzed SARS-CoV-2 data from Lombardy and Israel covering four viral waves. Data included infection rates, hospitalizations, and mortality. In Lombardy, healthcare data were collected from the administrative database of the Lombardy Welfare Directorate; in Israel, they were collected from Clalit Health Services and the Israeli Ministry of Health's COVID-19 database. Statistical analyses compared trends in infection rates, demographics, and mortality rates across the four viral waves by using logistic and linear regression models and adjusting for age, sex, and comorbidities. Results: Lombardy exhibited significantly higher SARS-CoV-2 infections and COVID-19 hospitalization rates during the first wave than Israel, with 71,558 cases over a population sample of ~10 million versus 5741 over a population sample of ~4.7 million in Israel. The majority of cases in Israel were managed at home, with 18 cases only (0.3%) requiring intensive care unit (ICU) hospitalization during the first wave, compared to 4104 (5.7%) cases in Lombardy. Israel's vaccination campaign began earlier, so that by the fourth wave, 439,545 (42.2%) people in Israel were fully vaccinated with three doses, compared to 214,542 (22.9%) in Lombardy. Mortality decreased over time in both sites, dropping from 103 cases (1.8%) to 1550 (0.1%) in Israel and from 13,372 (18.7%) to 4388 (0.3%) in Lombardy. Conclusions: Early public health interventions and vaccination were crucial in managing the SARS-CoV-2 impact.

Methodology and challenges for harmonization of nutritional data from seven historical studies.

BACKGROUND: Collection of detailed dietary data is labor intensive and expensive, harmonization of existing data sets has been proposed as an effective tool for research questions in which individual studies are underpowered. METHODS: In this paper, we describe the methodology used to retrospectively harmonize nutritional data from multiple sources, based on the individual participant data of all available studies, which collected nutritional data in Israel between 1963 and 2014. This collaboration was established in order to study the association of red and processed meat with colorectal cancer. Two types of nutritional questionnaires, the Food Frequency Questionnaires (FFQ) and the 24-h dietary recall (24HR recall), and different food composition tables, were used by the participating studies. The main exposure of interest included type of meat (total meat, red meat, and poultry) and level of processing. RESULTS: A total of 29,560 Israeli men and women were enrolled. In studies using FFQ,the weighted mean intakes of total, red, processed meat, and poultry were 95, 27, 37 and 58 gr/day and 92, 25, 10, and 66 gr/day in studies using 24HR recall, respectively.. Despite several methodological challenges, we successfully harmonized nutritional data from the different studies. CONCLUSIONS: This paper emphasizes the significance and feasibility of harmonization of previously collected nutritional data, offering an opportunity to examine associations between a range of dietary exposures and the outcome of interest, while minimizing costs and time in epidemiological studies.

Outcomes of Atrial Fibrillation Ablation in Heart Failure Subtypes.

BACKGROUND: Catheter ablation (CA) improves clinical outcomes in patients with atrial fibrillation (AF) and heart failure (HF) with reduced ejection fraction (HFrEF). We aimed to evaluate the impact of CA on clinical and quality-of-life outcomes across HF subtypes. METHODS: All patients undergoing AF ablation at a tertiary center were enrolled in a prospective registry and included in this study (2013-2021). The primary end point was AF recurrence. Secondary end points included AF-related hospitalizations and quality-of-life outcomes. Patients were categorized according to their HF status: no HF, HFrEF, HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). RESULTS: A total of 7020 patients were included (80% no HF, 8% HFrEF, 7% HFmrEF, and 5% HFpEF). Over 3 years, the cumulative incidence of AF recurrence after ablation was as follows: HFpEF (53%), HFmrEF (41%), HFrEF (41%), and no HF (34%); P<0.01. Multivariable Cox analyses confirmed these findings using no HF group as reference (HFpEF: hazard ratio, 1.47 [95% CI, 1.21-1.78]; HFmrEF: hazard ratio, 1.23 [95% CI, 1.04-1.45]; and HFrEF: hazard ratio, 1.17 [95% CI, 1.01-1.37]; P<0.05 for all). In all groups, CA resulted in a significant reduction of AF-related hospitalization (mean rate per 1 patient-years [before and after CA]; HFpEF [1.8 versus 0.3], HFmrEF [1.1 versus 0.2], HFrEF [1.1 versus 0.2], and no HF [1 versus 0.1]; P<0.01 for each comparison) and significant improvement in quality of life as measured by both the AF symptom severity score and the AF burden score (P<0.01 for the comparison between baseline and follow-up for each score when tested separately). CONCLUSIONS: AF recurrence rates after CA were higher in patients with HF compared with those without HF, with patients with HFpEF being at the highest risk of recurrence. Nonetheless, CA was associated with a significant reduction in AF symptoms, AF-related hospitalization, and HF symptoms in most patients irrespective of HF subtypes.

A historical cohort study with 27,754 individuals on the association between meat consumption and gastrointestinal tract and colorectal cancer incidence.

In order to explore the association between meat consumption and gastrointestinal/colorectal cancer (CRC) risk and to estimate the Israeli population attributable fraction (PAF), we conducted a collaborative historical cohort study using the individual participant data of seven nutritional studies from the past 6 decades. We included healthy adult men and women who underwent a nutritional interview. Dietary assessment data, using food-frequency or 24-h recall questionnaires, were harmonized. The study file was linked to the National Cancer and death registries. Among 27,754 participants, 1216 (4.4%) were diagnosed with gastrointestinal cancers and 839 (3.0%) with CRC by the end of 2016. Using meta-analysis methods applied to Cox proportional hazard models (adjusted for daily energy intake, sex, age, ethnic origin, education and smoking),100 g/day increments in beef, red meat and poultry consumption, and 50 g/day increment in processed meat consumption were associated with hazard ratios (HRs) and 95% confidence intervals of 1.46 (1.06-2.02), 1.15 (0.87-1.52), 1.06 (0.89-1.26), and 0.93 (0.76-1.12), respectively, for CRC. Similar results were obtained for gastrointestinal cancer, although red meat consumption reached statistical significance (HR = 1.27; 95%CI: 1.02-1.58). The PAFs associated with a reduction to a maximum of 50 g/day in the consumption of red meat were 2.7% (95%CI: -1.9 to 12.0) and 5.2% (0.3-13.9) for CRC and gastrointestinal cancers, respectively. Reduction of beef consumption to a maximum of 50 g/day will result in a CRC PAF reduction of 7.5% (0.7%-24.3%). While beef consumption was associated with gastrointestinal/CRC excess risk, poultry consumption was not. A substantial part of processed meat consumption in Israel is processed poultry, perhaps explaining the lack of association with CRC.

Left ventricular mass as a modulator of ventricular arrhythmia risk and sex differences after CRT for nonischemic cardiomyopathy and LBBB.

BACKGROUND: The risk of ventricular arrhythmias (VAs) after cardiac resynchronization therapy (CRT) has been associated with ischemic disease/scar, sex, and possibly left ventricular mass (LVM). OBJECTIVE: The purpose of this study was to evaluate sex differences and baseline/postimplant change in LVM on VA risk after CRT implantation in patients with nonischemic cardiomyopathy and left bundle branch block. METHODS: In patients meeting the criteria, baseline and follow-up echocardiographic images were obtained for LVM assessment. VA events were reported from device diagnostics and therapies. VA risk was stratified by receiver operating characteristic (Youden index cutoff point) for baseline LVM and baseline/postimplant change in LVM. Multivariate Cox regression model was also used for VA risk stratification. RESULTS: One hundred eighteen patients (71 female patients [60.2%]; mean age 60.5 ± 11.3 years; left ventricular ejection fraction 19.2% ± 7.0%; QRS duration 165.6 ± 20 ms; LVM 313.9 ± 108.8 g) were enrolled and followed up for a median of 90 months (interquartile range 44-158 months). Thirty-five patients (29.6%) received appropriate shocks or antitachycardia pacing at a median of 73.5 months (interquartile range 25-130 months) postimplantation. Males had a higher VA incidence (male patients 18 of 47 [38.3%] vs female patients 17 of 71 [23.9%]; P = .02). Baseline LVM > 308.9 g separated patients with higher VA risk (P = .001). Less than a 20% decrease in LVM increased VA risk (P < .001). Baseline LVM was the only baseline characteristic predicting VA events in the Cox regression model (hazard ratio 1.01; 95% confidence interval 1.001-1.009; log-rank, P = .003). Sex differences in VA risk were eliminated by the baseline LVM parameters. CONCLUSION: VA risk after CRT implantation in nonischemic cardiomyopathy was associated with baseline LV > 308.9 g and a decrease in LVM ≤ 20%, without sex differences.

Association of Acute Incidental Cerebral Microinfarcts With Subsequent Ischemic Stroke in Patients With Cancer: A Population-Based Study.

BACKGROUND AND OBJECTIVES: Incidental diffuse-weighted imaging (DWI)-positive subcortical and cortical lesions, or acute incidental cerebral microinfarcts (CMIs), are a common type of brain ischemia, which can be detected on magnetic resonance DWI for approximately 2 weeks after occurrence. Acute incidental CMI was found to be more common in patients with cancer. Whether acute incidental CMI predicts future ischemic stroke is still unknown. We aimed to examine the association between acute incidental CMI in patients with cancer and subsequent ischemic stroke or transient ischemic attack (TIA). METHODS: This is a retrospective cohort study. We used Clalit Health Services records, representing over half of the Israeli population, to identify adults with lung, breast, pancreatic, or colon cancer who underwent brain MRI between January 2014 and April 2020. We included patients who underwent scan between 1 year before cancer diagnosis and 1 year after diagnosis. Primary outcome was ischemic stroke or TIA using International Classification of Diseases, Ninth Revision codes. Secondary outcomes were intracranial hemorrhage (ICH) and mortality. Records were followed from first MRI until primary outcome, death, or end of follow-up (January 2023). Cox proportional hazards models were used to calculate hazard ratio (HR) for patients with and without acute incidental CMI, as a time-dependent covariate. RESULTS: The study cohort included 1,618 patients with cancer, among whom, 59 (3.6%) had acute incidental CMI on at least 1 brain MRI. The median (interquartile range) time from acute incidental CMI to stroke or TIA was 26 days (14-84). On multivariable analysis, patients with acute incidental CMI had a higher stroke or TIA risk (HR 2.97, 95% CI 1.08-8.18, p = 0.035) compared with their non-CMI counterparts. Acute incidental CMIs were also associated with mortality after multivariable analysis (HR 2.76, 95% CI 2.06-3.71, p < 0.001); no association with ICH was found. DISCUSSION: Acute incidental CMI on brain MRI in patients with active cancer is associated with an increased risk of near-future ischemic stroke or TIA and mortality. This finding might suggest that randomly detected acute incidental CMI in patients with cancer may guide primary cerebrovascular risk prevention and etiologic workup.

Phosphodiesterase-5 Inhibitors and Dementia Risk: A Real-World Study.

INTRODUCTION: Biological and scarce epidemiological evidence suggested that phosphodiesterase-5 inhibitors (PDE5i) might reduce dementia risk. We aimed to examine the association between PDE5i and dementia using real-world data. METHODS: Two retrospective cohorts within the database of Clalit, the largest healthcare provider in Israel (2005-2023), were studied. The first cohort included new daily users, older than 50 years of age, of low-dose tadalafil, prescribed for benign prostatic hypertrophy (BPH), propensity-score matched to new-users of alpha-1 blockers, and analyzed using 2-year lag time. The second cohort included patients with erectile dysfunction, with/without any PDE5i treatment, using time-dependent analysis. Individuals in the cohorts were followed through May 2023 for the occurrence of dementia. RESULTS: The first cohort included 5,204 tadalafil initiators propensity-score matched to 18,565 alpha-1 blockers initiators. There was no association between tadalafil use and dementia risk, HR = 0.99 (95% CI: 0.88-1.12), p = 0.927. Similar results were obtained in a competing risk analysis, and in a sensitivity analysis in which we restricted the cohort to patients older than 60 years at cohort entry. The second cohort of 133,336 patients with erectile dysfunction included new users and nonusers of any PDE5i. In a mean follow-up of 7.9 years, 8,631 patients were newly diagnosed with dementia. In a time-dependent multivariable analysis, PDE5i use was not associated with reduced dementia risk, HR = 0.95 (95% CI: 0.86-1.04). Results were not changed in sensitivity analyses (patients older than 60 years or stratification by PDE5i type). CONCLUSION: This study suggests that the use of PDE5 inhibitors is not associated with decreased risk of dementia.

Acute post-procedural inducibility is a poor predictor of clinical outcomes in high-risk patients (PAINESD > 17) undergoing scar-related ventricular tachycardia ablation.

AIMS: Ventricular tachycardia (VT) non-inducibility in response to programmed ventricular stimulation (PVS) is a widely used procedural endpoint for VT ablation despite inconclusive evidence with respect to clinical outcomes in high-risk patients. The aim is to determine the utility of acute post-ablation VT inducibility as a predictor of VT recurrence, mortality, or mortality equivalent in high-risk patients. METHODS AND RESULTS: We conducted a retrospective analysis of high-risk patients (defined as PAINESD > 17) who underwent scar-related VT ablation at our institution between July 2010 and July 2022. Patients' response to PVS (post-procedure) was categorized into three groups: Group A, no clinical VT or VT with cycle length > 240 ms inducible; Group B, only non-clinical VT with cycle length > 240 ms induced; and Group C, all other outcomes (including cases where no PVS was performed). The combined primary endpoint included death, durable left ventricular assist device placement, and cardiac transplant (Cox analysis). Ventricular tachycardia recurrence was considered a secondary endpoint (competing risk analysis). Of the 1677 VT ablation cases, 123 cases met the inclusion criteria for analysis. During a 19-month median follow-up time (interquartile range 4-43 months), 82 (66.7%) patients experienced the composite primary endpoint. There was no difference between Groups A and C with respect to the primary [hazard ratio (HR) = 1.21 (0.94-1.57), P = 0.145] or secondary [HR = 1.18 (0.91-1.54), P = 0.210] outcomes. These findings persisted after multivariate adjustments. The size of Group B (n = 13) did not permit meaningful statistical analysis. CONCLUSION: The results of post-ablation PVS do not significantly correlate with long-term outcomes in high-risk (PAINESD > 17) VT ablation patients.

Evaluation of Ablation Parameters to Predict Irreversible Lesion Size During Pulsed Field Ablation.

BACKGROUND: During pulsed field ablation (PFA), relationships between ablation parameters (contact force [CF], number of burst pulses, impedance decrease, and electrode temperature) and lesion size in beating hearts have not been well validated. METHODS: A 7.5F-catheter with a 3.5-mm ablation electrode and CF sensor (ThermoCool SmartTouch SF-Dual-Energy, Biosense Webster, Inc, Irwindale, CA) was connected to a PFA system (TRUPULSE2, Biosense Webster, Inc). In 11 closed-chest swine, biphasic PFA current was delivered between the ablation electrode and the skin patch at 219 sites in left ventricle and right ventricle using 12, 18, and 24 burst pulses with 4 different levels of CF: (1) low (n=57; CF, 4-15g; median, 10g); (2) moderate (n=60; CF, 16-30g; median, 22.5g); (3) high (n=68; CF, 32-65g; median, 40g); and (4) no electrode contact (n=34), 2 mm away from the endocardium. Swine were euthanized 2 hours after ablation, and lesion size was measured using triphenyl tetrazolium chloride staining. RESULTS: All PFA lesions with electrode-myocardium contact were well demarcated with triphenyl tetrazolium chloride staining, demonstrating (1) pale central zone (contraction band necrosis with minimal coagulation necrosis), (2) dark brown zone (contraction band necrosis with hemorrhage), and (3) hyperstained red zone by triphenyl tetrazolium chloride (unaffected normal myocardium with preserved mitochondrial activity, consistent with reversible zone). Lesion depth increased significantly with increasing CF and the number of PFA burst pulses. An exponential/logarithmic formula combined with CF and the number of PFA burst pulses correlated lesion depth with high accuracy: R=0.809, P<0.0001, ±1.0-mm accuracy in 128 of 163 (79%) lesions, and ±1.5-mm accuracy in 153 of 163 (94%) lesions. Impedance decrease and electrode temperature were poor predictors of lesion size. There were no detectable lesions resulting from ablation without electrode contact. CONCLUSIONS: Acute PFA ventricular lesions demonstrate irreversible and reversible lesion boundaries. Electrode-tissue contact is required for effective lesion formation. Lesion depth increases significantly with increasing CF and PFA burst pulses. A new exponential/logarithmic formula combined with CF and the number of PFA burst pulses correlates lesion depth with high accuracy.

Comparative Efficacy and Safety of Pulsed Field Ablation Versus Radiofrequency Ablation of Idiopathic LV Arrhythmias.

BACKGROUND: Comparative efficacy and safety data on radiofrequency ablation (RFA) versus pulsed field ablation (PFA) for common idiopathic left ventricular arrhythmia (LV-VAs) locations are lacking. OBJECTIVES: This study sough to compare RFA with PFA of common idiopathic LV-VAs locations. METHODS: Ten swine were randomized to PFA or RFA of LV interventricular septum, papillary muscle, LV summit via distal coronary sinus, and LV epicardium via subxiphoid approach. Ablations were delivered using an investigational dual-energy (RFA/PFA) contact force (CF) and local impedance-sensing catheter. After 1-week survival, animals were euthanized for lesion assessment. RESULTS: A total of 55 PFA (4 applications/site of 2.0 KV, target CF ≥10 g) and 36 RFA (CF ≥10 g, 25-50 W targeting ≥50 Ω local impedance drop, 60-second duration) were performed. LV interventricular septum: average PFA depth 7.8 mm vs RFA 7.9 mm (P = 0.78) and no adverse events. Papillary muscle: average PFA depth 8.1 mm vs RFA 4.5 mm (P < 0.01). Left ventricular summit: average PFA depth 5.6 mm vs RFA 2.7 mm (P < 0.01). Steam-pop and/or ventricular fibrillation in 4 of 12 RFA vs 0 of 12 PFA (P < 0.01), no ST-segment changes observed. Epicardium: average PFA depth 6.4 mm vs RFA 3.3 mm (P < 0.01). Transient ST-segment elevations/depressions occurred in 4 of 5 swine in the PFA arm vs 0 of 5 in the RFA arm (P < 0.01). Angiography acutely and at 7 days showed normal coronaries in all cases. CONCLUSIONS: In this swine study, compared with RFA, PFA of common idiopathic LV-VAs locations produced deeper lesions with fewer steam pops. However, PFA was associated with higher rates of transient ST-segment elevations and depressions with direct epicardium ablation.

Lipid-lowering therapy with inclisiran in the real-world setting: Initial data from a national health care service.

BACKGROUND: Inclisiran, a small-interfering RNA enabling long-term inhibition of PCSK9 synthesis, demonstrates good safety and efficacy profile in clinical trials. Real-world data on the potential to attain lipid-goals and reduce treatment gaps is lacking. OBJECTIVES: To investigate the implementation of inclisiran in real-world clinical setting. METHODS: Data from a nationwide healthcare organization on patients initiating inclisiran between 3/2022-11/2023. Patients' characteristics, lipid-lowering therapies, post-treatment reduction in low-density lipoprotein cholesterol (LDL-C), and attainment of treatment goals, were evaluated. RESULTS: Inclisiran was initiated by 503 patients (57 % women; mean age 66±11 years). Cardiovascular disease was present in 54 %, and peak LDL-C levels >190 mg/dL documented in 64 %. Prior exposure to PCSK9 monoclonal antibodies was evident in 28 %. Lipid profile >2 months after filling first prescription, was available in 397 patients (347 with ≥2 injections). In patients treated by inclisiran only (n = 254), median LDL-C reduction from peak levels was 57 % (IQR, 48 %-67 %), and from pre-injection levels 40 % (19 %-54 %). In those with concomitant lipid-lowering therapies (n = 143), median LDL-C reduction from peak levels was 66 % (IQR, 55 %-73 %), and from pre-injection levels 46 % (23 %-59 %). LDL-C < 70 mg/dL was attained by 39 % and LDL-C < 55 mg/dL by 21.9 %. Of those treated with concomitant statin therapy, 38 % attained LDL-C < 55 mg/dL. Overall, 6.5 % discontinued inclisiran therapy after initial injection. CONCLUSIONS: In real-world practice, inclisiran showed good efficacy in reducing LDL-C with high interindividual variability. However, attainment rates of lipid-goals were suboptimal due to limited use of combination lipid-lowering therapy and high-rates of severe hypercholesterolemia in our patient population cohort.

Medications and Acute Hemolysis in G6PD-Deficient Patients - A Real-World Study.

Many drug labels contain precautions of use in G6PD-deficient patients due to hemolytic concerns, but much of this is based on scarce clinical, epidemiological, or structural data. In this real-world study, we aimed to examine if the administration of presumably risky medications for G6PD-deficient patients was followed by hemolysis. The study is based on data from Clalit Health Services database that provides inclusive health care for more than half of the Israeli population (~ 4.7 million). Within the database, we identified all G6PD-deficient patients by G6PD <6 U/g Hb. Within the G6PD-deficient cohort, we identified all hospitalizations with a discharge diagnosis of hemolysis (January 1, 2010 to December 31, 2022), validated the cases, and identified the culprit event. For the rest of the G6PD-deficient patients with no-hemolysis, we recorded filled prescriptions of medications listed as presumably risky. We identified 31,962 G6PD-deficient patients. Within the cohort, there were 71 cases of major hemolysis requiring hospitalization (0.2% of the cohort), of whom 51 (71.8%) had been caused by ingestion of fava beans, six (8.5%) were associated with an infection, and three (4.2%) suggested to be associated with medications (nitrofurantoin, phenazopyridine, and a "pain killer"). Within the 31,875 patients with no major hemolysis, nitrofurantoin has been prescribed safely to 1,366 G6PD-deficient males and females; hundreds/thousands of G6PD-deficient patients had been prescribed safely ciprofloxacin, glibenclamide, ofloxacin, phenazopyridine, sulfamethoxazole/cotrimoxazole, sulfasalazine, hydroxychloroquine, glimepiride, mesalazine, and sulfacetamide. In this real-world study, we are showing that a list of medications, suspected previously as carrying risks for hemolysis in G6PD-deficient patients, have been prescribed safely to G6PD-deficient patients, providing reassurance to patients, prescribers, and regulators.

COVID-19 Vaccine Effectiveness among Patients with Psoriatic Disease: A Population-Based Study.

Limited information is available on the effectiveness of COVID-19 vaccination in patients with psoriasis and psoriatic arthritis (psoriatic disease (PsD)). The objective of our research was to assess the effectiveness of mRNA COVID-19 vaccination in preventing SARS-CoV-2 positivity and severe infection in a cohort of patients with PsD and the association of immunosuppressants on SARS-CoV-2 infection-related outcomes from December 2020 to December 2021. Vaccine effectiveness was assessed in a matched nested case control study using conditional logistic regression adjusted for demographics, comorbidities and immunosuppressant use. Study outcomes included SARS-CoV-2 positivity and severe COVID-19 (moderate-to-severe COVID-19-related hospitalizations or death). At least one dose of mRNA COVID-19 vaccine was associated with reduced risk of SARS-CoV-2 positivity and severe COVID-19 (OR = 0.41 (95% CI, 0.38-0.43) and OR = 0.15 (95% CI, 0.11-0.20), respectively). A more significant effect was found among patients who received three vaccines doses compared with those who did not receive any (OR (for positive SARS-CoV-2) = 0.13 (95% CI, 0.12-0.15) and OR (for severe disease) = 0.02 (0.01-0.05)). Etanercept and methotrexate were associated with higher risk of SARS-CoV-2 positivity (1.58 (1.19-2.10), p = 0.001 and 1.25 (1.03-1.51), p = 0.03, respectively). In conclusion, our results show that mRNA COVID-19 vaccines are effective in reducing both infection and severe COVID-19-related outcomes.