Search

Abstract Hysteresis, a ubiquitous regulatory phenomenon, is a salient feature of the adaptation of ventricular repolarization duration to heart rate (HR) change. We therefore compared the QT interval adaptation to rapid HR increase in patients with the long QT syndrome type 1 (LQT1) versus healthy controls because LQT1 is caused by loss‐of‐function mutations affecting the repolarizing potassium channel current IKs, presumably an important player in QT hysteresis. The study was performed in an outpatient hospital setting. HR was increased in LQT1 patients and controls by administering an intravenous bolus of atropine (0.04 mg/kg body weight) for 30 s. RR and QT intervals were recorded by continuous Frank vectorcardiography. Atropine induced transient expected side effects but no adverse arrhythmias. There was no difference in HR response (RR intervals) to atropine between the groups. Although atropine‐induced ΔQT was 48% greater in 18 LQT1 patients than in 28 controls (p

Abstract Background and aims Allergic rhinitis (AR) is an inflammatory disorder triggered by an allergic immune response to inhaled allergens. Birch pollen is the major allergenic tree pollen in parts of Europe. ITULAZAX® is a sublingual immunotherapy tablet for the treatment of adults with moderate‐to‐severe AR and/or conjunctivitis induced by pollen from the birch homologous group. The aim was to compare the costs of treating AR with ITULAZAX® versus subcutaneous ALUTARD SQ® Betula verrucosa (ALUTARD SQ®) from a Danish societal perspective. Methods A cost‐minimization model was developed to capture costs of allergy immunotherapy (AIT), interactions with healthcare professionals (HCPs) in three different care settings (general practice, allergy specialist, and hospital), and indirect costs arising from absenteeism and presenteeism. The cost‐minimization analysis was conducted over a 3‐year time horizon with costs reported in 2021 Danish Kroner (DKK) and Euros (EUR) based on the European Central Bank 365‐day average exchange rate. One‐way sensitivity analyses were performed. Results The base case analysis showed that the total cost of treatment over 3 years was estimated to be DKK 49,117 (EUR 6598) per patient with ALUTARD SQ®, compared with DKK 30,996 (EUR 4164) with ITULAZAX®, reflecting a cost saving of DKK 18,121 (EUR 2434) per patient with ITULAZAX® over 3 years. Over the 3‐year time horizon, costs of AIT were predicted to increase by DKK 17,928 (EUR 2408) with ITULAZAX®, while costs of interactions with HCPs were predicted to decrease by DKK 22,528 (EUR 3027) versus ALUTARD SQ®, more than offsetting the increased cost of ITULAZAX®. Conclusions Given the equivalent effectiveness of the two AIT products, and the cost savings with ITULAZAX® versus ALUTARD SQ® from a Danish societal perspective, ITULAZAX® should be considered as a cost‐saving alternative to ALUTARD SQ® for the treatment of birch pollen‐induced moderate‐to‐severe AR in adults.

Background There are conflicting reports with regard to the allele‐specific gene suppression effects of single nucleotide polymorphisms (SNPs) in the 3'untranslated region (3'UTR) of the KCNQ1 gene in long QT syndrome type 1 (LQT1) populations. Here we assess the allele‐specific effects of 3 previously published 3'UTR‐KCNQ1's SNPs in a LQT1 founder population segregating a dominant‐negative mutation. Methods and Results Bidirectional sequencing of the KCNQ1's 3'UTR was performed in the p.Y111C founder population (n=232, 147 genotype positive), with a minor allele frequency of 0.1 for SNP1 (rs2519184) and 0.6 for linked SNP2 (rs8234) and SNP3 (rs107980). Allelic phase was assessed in trios aided by haplotype data, revealing a high prevalence of derived SNP2/3 in cis with p.Y111C (89%). Allele‐specific association analyses, corrected using a relatedness matrix, were performed between 3'UTR‐KCNQ1 SNP genotypes and clinical phenotypes. SNP1 in trans was associated with a significantly higher proportion of symptomatic phenotype compared with no derived SNP1 allele in trans (58% versus 32%, corrected P=0.027). SNP2/3 in cis was associated with a significantly lower proportion of symptomatic phenotype compared with no derived SNP2/3 allele in cis (32% versus 69%, corrected P=0.010). Conclusions Allele‐specific modifying effects on symptomatic phenotype of 3'UTR‐KCNQ1 SNPs rs2519184, rs8234, and rs107980 were seen in a LQT1 founder population segregating a dominant‐negative mutation. The high prevalence of suppressive 3'UTR‐KCNQ1 SNPs segregating with the founder mutation could contribute to the previously documented low incidence of cardiac events in heterozygous carriers of the p.Y111C KCNQ1 mutation.

Abstract Background The association of a Classical left bundle branch block (LBBB) contraction pattern and better outcome after cardiac resynchronization therapy (CRT) has only been studied using vendor-specific software for echocardiographic speckle-tracked longitudinal strain analysis. The purpose of this study was to assess whether a Classical LBBB contraction pattern on longitudinal strain analysis using vendor-independent software is associated with clinical outcome in CRT recipients with LBBB. Methods This was a retrospective cohort study including CRT recipients with LBBB, heart failure, and left ventricular (LV) ejection fraction ≤35%. Speckle-tracked echocardiographic longitudinal strain analysis was performed retrospectively on echocardiograms using vendor-independent software. The presence of a Classical LBBB contraction pattern was determined by consensus of two readers. The primary end point was a composite of time to death, heart transplantation or LV assist device implantation. Secondary outcome was ≥15% reduction in LV end-systolic volume. Intra- and inter-reader agreement of the longitudinal strain contraction pattern was assessed by calculating Cohen’s κ. Results Of 283 included patients, 113 (40%) were women, mean age was 66 ± 11 years, and 136 (48%) had ischemic heart disease. A Classical LBBB contraction pattern was present in 196 (69%). The unadjusted hazard ratio for reaching the primary end point was 1.93 (95% confidence interval, 1.36–2.76, p

Aims: To assess the relation between atrial fibrillation (AF) characteristics and health-related quality of life (QoL), and which AF characteristic had the greatest impact. Method: The AF characteristics burden (percentage of time in AF), duration and number of AF episodes/month were obtained from implantable cardiac monitors during the 2-month run-in period in 150 patients included in the randomized CAPTAF trial comparing early ablation and antiarrhythmic drug therapy. The QoL was measured by the General Health and Vitality dimensions of the 36-Item Short-Form Health Survey. AF characteristics were analysed continuously and in quartiles (Q1-Q4). Results: Greater AF burden (p = 0.003) and longer AF episodes (p = 0.013) were associated with impaired QoL (Vitality score only) in simple linear regression analyses. Greater AF burden was, however, the only AF characteristic associated with lower QoL, when adjusted for sex, type of AF, hypertension, heart rate above 110 beats per minute during AF, and beta-blocker use in multiple linear regression analyses. For every 10% increase in AF burden there was a 1.34-point decrease of Vitality score (95% confidence interval (CI) −2.67 to −0.02, p = 0.047). The Vitality score was 12 points lower (95% CI −22.73 to −1.27, p = 0.03) in patients with an AF burden > 33% (Q4) versus those with

Abstract Background Sequence variants in the NOS1AP gene have repeatedly been reported to influence QTc, albeit with moderate effect sizes. In the long QT syndrome (LQTS), this may contribute to the substantial QTc variance seen among carriers of identical pathogenic sequence variants. Here we assess three non-coding NOS1AP sequence variants, chosen for their previously reported strong association with QTc in normal and LQTS populations, for association with QTc in two Swedish LQT1 founder populations. Methods This study included 312 individuals (58% females) from two LQT1 founder populations, whereof 227 genotype positive segregating either Y111C (n = 148) or R518* (n = 79) pathogenic sequence variants in the KCNQ1 gene, and 85 genotype negatives. All were genotyped for NOS1AP sequence variants rs12143842, rs16847548 and rs4657139, and tested for association with QTc length (effect size presented as mean difference between derived and wildtype, in ms), using a pedigree-based measured genotype association analysis. Mean QTc was obtained by repeated manual measurement (preferably in lead II) by one observer using coded 50 mm/s standard 12-lead ECGs. Results A substantial variance in mean QTc was seen in genotype positives 476 ± 36 ms (Y111C 483 ± 34 ms; R518* 462 ± 34 ms) and genotype negatives 433 ± 24 ms. Female sex was significantly associated with QTc prolongation in all genotype groups (p

Background: Sleep apnea is common in patients with atrial fibrillation, but the effect of the cardioversion of atrial fibrillation to sinus rhythm on central and obstructive apneas is mainly unknown. The primary aim of the study was to analyze the association between cardioversion of atrial fibrillation and sleep apneas, to investigate whether obstructive or central sleep apneas are reduced following cardioversion. A secondary objective was to study the effect on sleep quality. Methods: Twenty-three patients with atrial fibrillation were investigated using overnight polysomnography, including esophagus pressure monitoring and ECG, before and after the cardioversion of persistent atrial fibrillation. Results: Obstructive sleep apnea occurred in 17/23 patients (74%), and central sleep apnea in 6/23 patients (26%). Five patients had both obstructive and central sleep apnea. Sinus rhythm at follow-up was achieved in 16 patients. The obstructive apnea-hypopnea index, central apnea-hypopnea index, and the number of patients with obstructive or central sleep apnea did not differ before and after restoration of sinus rhythm. Sleep time, sleep efficiency, time in different sleep stages, and subjective daytime sleepiness were normal and unaffected by cardioversion. Conclusions: Both obstructive and central sleep apneas are highly prevalent in patients with persistent atrial fibrillation. Obstructive sleep apneas are unaffected by the cardioversion of atrial fibrillation to sinus rhythm. The sleep pattern is normal and unaffected by cardioversion in patients with atrial fibrillation. Clinical Trial Registration: Trial number NCT00429884.

Background Firefighter first responders dispatched in parallel with emergency medical services (EMS) personnel for out‐of‐hospital cardiac arrests (OHCA) can provide early defibrillation to improve survival. We examined whether survival following first responder defibrillation differed according to driving distance from nearest fire station to OHCA site. Methods and Results From the CARES (Cardiac Arrest Registry to Enhance Survival) registry, we identified non‐EMS witnessed OHCAs of presumed cardiac cause from 2010 to 2014 in Durham, Mecklenburg, and Wake counties, North Carolina. We used logistic regression to estimate the association between calculated driving distances (≤1, 1–1.5, 1.5–2, and >2 miles) and survival to hospital discharge following first responder defibrillation compared with defibrillation by EMS personnel. In total, 5020 OHCAs were included in the study. First responders more often applied the first automated external defibrillators at the shortest distances (≤1 mile) versus longest distances (>2 miles) (53.4% versus 46.6%, respectively, P2.0 miles), survival following first responder defibrillation did not differ from EMS defibrillation (odds ratio 0.77 [95% confidence interval 0.48–1.21] and odds ratio 0.97 [95% confidence interval 0.67–1.41], respectively). Conclusions Shorter driving distance from nearest fire station to OHCA location was associated with improved survival following defibrillation by first responders. These results suggest that the location of first responder units should be considered when organizing prehospital systems of OHCA care.

BackgroundThe electrocardiographic interatrial block (IAB) has been associated with atrial fibrillation (AF). We aimed to test whether IAB can improve risk prediction of AF for the individual person. Methods and ResultsDigital ECGs of 152 759 primary care patients aged 50 to 90 years were collected from 2001 to 2011. We identified individuals with P‐wave ≥120 ms and the presence of none, 1, 2, or 3 biphasic P‐waves in inferior leads. Data on comorbidity, medication, and outcomes were obtained from nationwide registries. We observed a dose‐response relationship between the number of biphasic P‐waves in inferior leads and the hazard of AF during follow‐up. Discrimination of the 10‐year outcome of AF, measured by time‐dependent area under the curve, was increased by 1.09% (95% confidence interval 0.43–1.74%) for individuals with cardiovascular disease at baseline (CVD) and 1.01% (95% confidence interval 0.40–1.62%) for individuals without CVD, when IAB was added to a conventional risk model for AF. The highest effect of IAB on the absolute risk of AF was observed in individuals aged 60 to 70 years with CVD. In this subgroup, the 10‐year risk of AF was 50% in those with advanced IAB compared with 10% in those with a normal P‐wave. In general, individuals with advanced IAB and no CVD had a higher risk of AF than patients with CVD and no IAB. ConclusionsIAB improves risk prediction of AF when added to a conventional risk model. Clinicians may consider monitoring patients with IAB more closely for the occurrence of AF, especially for high‐risk subgroups.