Blood pressure-related electrocardiographic findings in healthy young individuals

Purpose: Elevated blood pressure induces electrocardiographic changes and is associated with an increase in cardiovascular disease later in life compared to normal blood pressure levels. The purpose of this study was to evaluate the association between normal to high normal blood pressure values (90–139/50–89 mmHg) and electrocardiographic parameters related to cardiac changes in hypertension in healthy young adults. Methods: Data from 1449 volunteers aged 18–30 years collected at our centre were analyzed. Only subjects considered healthy by a physician after review of collected data with systolic blood pressure values between 90 and 139 mmHg and diastolic blood pressure values between 50 and 89 mmHg were included. Subjects were divided into groups with 10 mmHg systolic blood pressure increment between groups for analysis of electrocardiographic differences. Backward multivariate regression analysis with systolic and diastolic blood pressure as a continuous variable was performed. Results: The mean age was 22.7 ± 3.0 years, 73.7% were male. P-wave area, ventricular activation time, QRS-duration, Sokolow–Lyon voltages, Cornell Product, J-point–T-peak duration corrected for heart rate and maximum T-wave duration were significantly different between systolic blood pressure groups. In the multivariate model with gender, body mass index and cholesterol, ventricular rate (standardized coefficient (SC): +0.182, p <.001), ventricular activation time in lead V6 (SC= +0.065, p =.048), Sokolow–Lyon voltage (SC= +0.135, p <.001), and Cornell product (SC= +0.137, p <.001) were independently associated with systolic blood pressure, while ventricular rate (SC= +0.179, p <.001), P-wave area in lead V1 (SC= +0.079, p =.020), and Cornell product (SC= +0.091, p =.006) were independently associated with diastolic blood pressure. Conclusion: Blood pressure-related electrocardiographic changes were observed incrementally in a healthy young population with blood pressure in the normal range. These changes were an increased ventricular rate, increased atrial surface area, ventricular activation time and increased ventricular hypertrophy indices on a standard 12 lead electrocardiogram

The association between body temperature and electrocardiographic parameters in normothermic healthy volunteers

Background: Previous studies reported that hypo- and hyperthermia are associated with several atrial and ventricular electrocardiographical parameters, including corrected QT (QTc) interval. Enhanced characterization of variations in QTc interval and normothermic body temperature aids in better understanding the underlying mechanism behind drug induced QTc interval effects. The analysis’ objective was to investigate associations between body temperature and electrocardiographical parameters in normothermic healthy volunteers. Methods: Data from 3023 volunteers collected at our center were retrospectively analyzed. Subjects were considered healthy after review of collected data by a physician, including a normal tympanic body temperature (35.5-37.5°C) and in sinus rhythm. A linear multivariate model with body temperature as a continuous was performed. Another multivariate analysis was performed with only the QT subintervals as independent variables and body temperature as dependent variable. Results: Mean age was 33.8 ± 17.5 years and mean body temperature was 36.6 ± 0.4°C. Body temperature was independently associated with age (standardized coefficient [SC] = −0.255, P <.001), female gender (SC = +0.209, P <.001), heart rate (SC = +0.231, P <.001), P-wave axis (SC = −0.051, P <.001), J-point elevation in lead V4 (SC = −0.121, P <.001), and QTcF duration (SC = −0.061, P =.002). In contrast, other atrial and atrioventricular (AV) nodal parameters were not independently associated with body temperature. QT subinterval analysis revealed that only QRS duration (SC = −0.121, P <.001) was independently associated with body temperature. Conclusion: Body temperature in normothermic healthy volunteers was associated with heart rate, P-wave axis, J-point amplitude in lead V4, and ventricular conductivity, the latter primarily through prolongation of the QRS duration

Differences between gap-related persistent conduction and carina-related persistent conduction during radiofrequency pulmonary vein isolation

Background: During pulmonary vein isolation (PVI), nonisolation after initial encircling of the pulmonary veins (PVs) may be due to gaps in the initial ablation line, or alternatively, earliest PV activation may occur on the intervenous carina and ablation within the wide-area circumferential ablation (WACA) circle is needed to eliminate residual conduction. This study investigated prognostic implications and predictors of gap-related persistent conduction (gap-RPC) and carina-related persistent conduction (carina-RPC) during PVI. Methods and Results: Two hundred fourteen atrial fibrillation (AF) patients (57% paroxysmal, 61% male, mean age 62 ± 9 years) undergoing first contact force-guided radiofrequency PVI were studied. Preprocedural cardiac computed tomography imaging was used to assess left atrial and PV anatomy. PVI was assessed directly after initial WACA circle creation, after a minimum waiting period of 30 minutes, and after adenosine infusion. Persistent conduction was targeted for additional ablation and classified as gap-RPC or carina-RPC, depending on the earliest activation site. The 1-year AF recurrence rate was higher in patients with gap-RPC (47%) compared to patients without gap-RPC (28%; P =.003). No significant difference in 1-year recurrence rate was found between patients with carina-RPC (37%) and patients without carina-RPC (31%; P =.379). Multivariate analyses identified paroxysmal AF and WACA circumference as independent predictors of gap-RPC, whereas carina width and WACA circumference correlated with carina-RPC. Conclusions: Gap-RPC is associated with increased AF recurrence risk after PVI, whereas carina-RPC does not predict AF recurrence. Moreover, gap-RPC and carina-RPC have different correlates and may thus have different underlying mechanisms

First Clinical Study with AP30663 - a KCa2 Channel Inhibitor in Development for Conversion of Atrial Fibrillation

Pharmacological cardioversion of atrial fibrillation (AF) is frequently inefficacious. AP30663, a small conductance Ca2+ activated K+ (KCa2) channel blocker, prolonged the atrial effective refractory period in preclinical studies and subsequently converted AF into normal sinus rhythm. This first-in-human study evaluated the safety and tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) effects were explored. Forty-seven healthy male volunteers (23.7 ± 3.0 years) received AP30663 intravenously in ascending doses. Due to infusion site reactions, changes to the formulation and administration were implemented in the latter 24 volunteers. Extractions from a 24-hour continuous electrocardiogram were used to evaluate the PD effect of AP30663. Data were analyzed with a repeated measure analysis of covariance, noncompartmental analysis, and concentration-effect analysis. In total, 33 of 34 adverse events considered related to AP30663 exposure were related to the infusion site, mild in severity, and temporary in nature, although full recovery took up to 110 days. After formulation and administration changes, the local infusion site reaction remained, but the median duration was shorter despite higher dose levels. AP30663 displayed a less than dose proportional increase in peak plasma concentration (Cmax) and a terminal half-life of around 5 hours. In healthy volunteers, no effect of AP30663 was observed on electrocardiographic parameters, other than a concentration-dependent effect on the corrected QT Fridericia’s formula interval (+18.8 ± 4.3 ms for the highest dose level compared with time matched placebo). In conclusion, administration of AP30663, a novel KCa2 channel inhibitor, was safe and well-tolerated systemically in humans, supporting further development in patients with AF undergoing cardioversion

Impact of local left atrial wall thickness on the incidence of acute pulmonary vein reconnection after Ablation Index-guided atrial fibrillation ablation

Background: Although Ablation Index (AI)-guided ablation facilitates creation of lesions of consistent depth, pulmonary vein (PV) reconnection is still commonly observed after AI-guided pulmonary vein isolation (PVI). The present study aimed to investigate the impact of local left atrial wall thickness on the incidence of acute PV reconnection after AI-guided atrial fibrillation (AF) ablation. Methods and results: Seventy patients (63% paroxysmal AF, 67% male, mean age 63 ± 8 years) who underwent preprocedural CT imaging and AI-guided AF ablation were studied. Occurrence of acute PV reconnection after initial PVI was assessed after a 30-minute waiting period. Ablation procedures were retrospectively analyzed and each ablation circle was subdivided into 8 segments. Minimum AI, force-time integral, contact force, ablation duration, power, impedance drop and maximum interlesion distance were determined for each segment. PV antrum wall thickness was assessed for each segment on reconstructed CT images based on patient-specific thresholds in Hounsfield Units. Acute reconnection occurred in 27/1120 segments (2%, 15 anterior/roof, 12 posterior/inferior) in 19/140 ablation circles (14%). Reconnected segments were characterized by a greater local atrial wall thickness, both in anterior/roof (1.87 ± 0.42 vs. 1.54 ± 0.42 mm; p < 0.01) and posterior/inferior (1.43 ± 0.20 vs. 1.16 ± 0.22 mm; p < 0.01) segments. Minimum AI, force-time integral, contact force, ablation duration, power, impedance drop and maximum interlesion distance were not associated with acute reconnection. Conclusions: Local atrial wall thickness is associated with acute pulmonary vein reconnection after AI-guided PVI. Individualized AI targets based on local wall thickness may be of use to create transmural ablation lesions and prevent PV reconnection after PVI

Sex-specific differences in outcome and risk stratification of ventricular arrhythmias in implantable cardioverter defibrillator patients

Aims: Risk stratification models of sudden cardiac death (SCD) are based on the assumption that risk factors of SCD affect risk to a similar extent in both sexes. The aim of the study is to evaluate differences in clinical outcomes between sexes and evaluate whether risk factors associated with appropriate device therapy (ADT) differ between men and women. Methods and results: We performed a cohort study of implantable cardioverter defibrillator (ICD) patients referred for primary or secondary prevention of SCD between 2009 and 2018. Multivariable Cox regression models for prediction of ADT were constructed for men and women separately. Of 2300 included patients, 571 (25%) were women. Median follow-up was 4.6 (inter-quartile range: 4.4–4.9) years. Time to ADT was shorter for men compared with women [hazard ratio (HR) 1.71, P < 0.001], as was time to mortality (HR 1.37, P = 0.003). In women, only secondary prevention ICD therapy (HR 1.82, P < 0.01) was associated with ADT, whereas higher age (HR 1.20, P < 0.001), absence of left bundle branch block (HR 0.72, P = 0.01), and secondary prevention therapy (HR 1.80, P < 0.001) were independently associated with ADT in men. None of the observed parameters showed a distinctive sex-specific pattern in ADT. Conclusions: Male ICD patients were at higher risk of ADT and death compared with female ICD patients, irrespective of an ischaemic or non-ischaemic underlying cardiomyopathy. Our study highlights the importance to stratify outcomes of ICD trials by sex, as study results differ between men and women. However, none of the available clinical parameters showed a clear sex-specific relation to ventricular arrhythmias. As a consequence, sex-specific risk stratification models of SCD using commonly available clinical parameters could not be derived

Sex-specific differences in outcome and risk stratification of ventricular arrhythmias in implantable cardioverter defibrillator patients

Aims: Risk stratification models of sudden cardiac death (SCD) are based on the assumption that risk factors of SCD affect risk to a similar extent in both sexes. The aim of the study is to evaluate differences in clinical outcomes between sexes and evaluate whether risk factors associated with appropriate device therapy (ADT) differ between men and women. Methods and results: We performed a cohort study of implantable cardioverter defibrillator (ICD) patients referred for primary or secondary prevention of SCD between 2009 and 2018. Multivariable Cox regression models for prediction of ADT were constructed for men and women separately. Of 2300 included patients, 571 (25%) were women. Median follow-up was 4.6 (inter-quartile range: 4.4–4.9) years. Time to ADT was shorter for men compared with women [hazard ratio (HR) 1.71, P &lt; 0.001], as was time to mortality (HR 1.37, P = 0.003). In women, only secondary prevention ICD therapy (HR 1.82, P &lt; 0.01) was associated with ADT, whereas higher age (HR 1.20, P &lt; 0.001), absence of left bundle branch block (HR 0.72, P = 0.01), and secondary prevention therapy (HR 1.80, P &lt; 0.001) were independently associated with ADT in men. None of the observed parameters showed a distinctive sex-specific pattern in ADT. Conclusions: Male ICD patients were at higher risk of ADT and death compared with female ICD patients, irrespective of an ischaemic or non-ischaemic underlying cardiomyopathy. Our study highlights the importance to stratify outcomes of ICD trials by sex, as study results differ between men and women. However, none of the available clinical parameters showed a clear sex-specific relation to ventricular arrhythmias. As a consequence, sex-specific risk stratification models of SCD using commonly available clinical parameters could not be derived.</p

Low 30-Day Mortality After Atrial Fibrillation Ablation: Results From the Netherlands Heart Registration

This study presents the 30-day mortality of patients who underwent atrial fibrillation (AF) ablation between 2013 - 2020 and were registered in the Netherlands Heart Registration. In total, 30,197/30,238 (99.9%) patients were analyzed. Fifteen (0.05%) died within 30 days. Nine deaths were considered procedurally related, four were considered non-procedural related, and in two patients the cause of death was unknown