Direct current cardioversion in pregnancy: a multicentre study.

OBJECTIVE: Direct current cardioversion (DCCV) in pregnancy is rarely required and typically only documented in single case reports or case series. A recent UK confidential enquiry reported on several maternal deaths where appropriate DCCV appeared to have been withheld. DESIGN: Retrospective cohort study. SETTING: Seventeen UK and Ireland specialist maternity centres. SAMPLE: Twenty-seven pregnant women requiring DCCV in pregnancy. MAIN OUTCOME MEASURES: Maternal and fetal outcomes following DCCV. RESULTS: Twenty-seven women had a total of 29 DCCVs in pregnancy. Of these, 19 (70%) initial presentations were to Emergency Departments and eight (30%) to maternity settings. There were no maternal deaths. Seventeen of the women (63%) had a prior history of heart disease. Median gestation at DCCV was 28 weeks, median gestation at delivery was 35 weeks, with a live birth in all cases. The abnormal heart rhythms documented at the first cardioversion were atrial fibrillation in 12/27 (44%) cases, atrial flutter in 8/27 (30%), supraventricular tachycardia in 5/27 (19%) and atrial tachycardia in 2/27 (7%). Fetal monitoring was undertaken following DCCV on 14/29 (48%) occasions (10 of 19 (53%) at ≥26 weeks) and on 2/29 (7%) occasions, urgent delivery was required post DCCV. CONCLUSIONS: Direct current cardioversion in pregnancy is rarely required but should be undertaken when clinically indicated according to standard algorithms to optimise maternal wellbeing. Once the woman is stable post DCCV, gestation-relevant fetal monitoring should be undertaken. Maternity units should develop multidisciplinary processes to ensure pregnant women receive the same standard of care as their non-pregnant counterparts.

Psychosocial adjustment and quality of life in children undergoing screening in a specialist paediatric hypertrophic cardiomyopathy clinic.

OBJECTIVE: This study aimed to assess the psychological well-being and quality of life in children with hypertrophic cardiomyopathy and the potential psychosocial impact of screening. METHODS: A total of 152 children (aged 3-18 years) attending a specialist paediatric hypertrophic cardiomyopathy clinic, and their parents completed the Generic Core Scales and Cardiac Module of the Paediatric Quality of Life Inventory (PedsQL) questionnaire as well as the Strengths and Difficulties Questionnaire; 21 patients (14%) had hypertrophic cardiomyopathy (group A); 23 children (15%) harboured hypertrophic cardiomyopathy-causing sarcomeric mutations with normal echocardiograms (group G); and 108 children (71%) had a family history of hypertrophic cardiomyopathy with normal investigations and attended for clinical cardiological screening (group S). RESULTS: In group A, mean PedsQLTM total scores reported by children and parents were lower than those reported by unaffected children (p<0.001). There was no significant difference between unaffected and gene-positive patients. Mean Cardiac module PedsQLTM total scores by children and parents were lower in children with hypertrophic cardiomyopathy compared with unaffected patients [mean child-reported total score 86.4 in group S versus 72.3 in group A (p<0.001) and 80.2 in group G (p=0.25); mean parent-reported total score 91.6 in group S versus 71.4 in group A (p<0.001) and 87 in group G (p=0.4)]. There was no significant difference between group S and group G on any of the scales, or between the three groups of patients in the mean Strengths and Difficulties Questionnaire scores. CONCLUSIONS: Children with hypertrophic cardiomyopathy have a significantly reduced quality of life. Importantly, Quality-of-Life scores among unaffected children attending for screening were not different compared with scores from a normative UK population.

Development and Analysis of a Scale for Meauring Teachers' Sense of Efficacy in Urban Schools (SEUS).

Research in teacher self-efficacy has a long history that can be traced back to Bandura (1986) and has been shown to be linked to teacher performance. This article presents evidence for teacher self-efficacy in urban schools, a construct that is separate from but related to the more general construct of teacher self-efficacy. An instrument was developed and validated by a team of university faculty, urban teachers, and school administrators. The Teachers' Sense of Efficacy in Urban Schools (SEUS) is a 15-item instrument designed to address factors that are important for success in teaching in an urban environment, including working effectively with English language learners, students with disabilities, economically disadvantaged students, cultural diversity, literacy, technology, differentiation, and assessment data. The present study analyzes SEUS on multiple levels, using the Rasch partial credit model.

Integration of population genetics with oceanographic models reveals strong connectivity among coral reefs across Seychelles.

Many countries with tropical reef systems face hard choices preserving coral reefs in the face of climate change on limited budgets. One approach to maximising regional reef resilience is targeting management efforts and resources at reefs that export large numbers of larvae to other reefs. However, this requires reef connectivity to be quantified. To map coral connectivity in the Seychelles reef system we carried out a population genomic study of the Porites lutea species complex using 241 sequenced colonies from multiple islands. To identify oceanographic drivers of this connectivity and quantify variability, we further used a 2 km resolution regional ocean simulation coupled with a larval dispersal model to predict the flow of coral larvae between reef sites. Patterns of admixture and gene flow are broadly supported by model predictions, but the realised connectivity is greater than that predicted from model simulations. Both methods detected a biogeographic dispersal barrier between the Inner and Outer Islands of Seychelles. However, this barrier is permeable and substantial larval transport is possible across Seychelles, particularly for one of two putative species found in our genomic study. The broad agreement between predicted connectivity and observed genetic patterns supports the use of such larval dispersal simulations in reef system management in Seychelles and the wider region.

Higher dose dobutamine stress MR imaging in repaired Tetralogy of Fallot: observer variance of volumetric assessment compared with normal volunteers.

PURPOSE: To investigate changes in image quality and observer variance between rest and higher-dose dobutamine stress MR imaging (DS-MR) in tetralogy of Fallot (TOF) patients and in a group of normal healthy volunteers using both axial and short axis orientation for cardiac volumetric assessment. MATERIALS AND METHODS: Eighteen adult patients (age 34 ± 13) with TOF and severe pulmonary regurgitation and 10 healthy volunteers underwent ventricular MR volumetry at baseline and during dobutamine infusion of 10 µg/kg/min and 20 µg/kg/min. Inter-observer and intra-observer agreement was calculated by coefficient of variance (COV). RESULTS: Inter-observer comparison showed good agreement for left ventricle (LV) and right ventricle (RV) end-diastolic volumes at rest and both stress levels in TOF patients (axial geometry) and in normal volunteers (short axis). During dobutamine stress, the COV in TOF patients increased for LV end-systolic volume (LV-ESV) with each level, suggesting less agreement between observers. In contrast, RV-ESV was much more comparable with a COV < 10 at each condition. All volumetric measurements in normal volunteers showed good inter-observer agreement. Excellent intra-observer agreement could be seen for all volumetric parameters with COV levels below 7. CONCLUSION: Volumetric assessment during DS-MR shows excellent inter-observer agreement, except for LV-ESV in the TOF patients at higher doses of dobutamine. The axial geometry appears to be reproducible for assessment of RV parameters, and could be considered superior to short axis imaging in patients with repaired TOF.

COVID-19 in congenital heart disease (COaCHeD) study.

BACKGROUND: COVID-19 has caused significant worldwide morbidity and mortality. Congenital heart disease (CHD) is likely to increase vulnerability and understanding the predictors of adverse outcomes is key to optimising care. OBJECTIVE: Ascertain the impact of COVID-19 on people with CHD and define risk factors for adverse outcomes. METHODS: Multicentre UK study undertaken 1 March 2020-30 June 2021 during the COVID-19 pandemic. Data were collected on CHD diagnoses, clinical presentation and outcomes. Multivariable logistic regression with multiple imputation was performed to explore predictors of death and hospitalisation. RESULTS: There were 405 reported cases (127 paediatric/278 adult). In children (age <16 years), there were 5 (3.9%) deaths. Adjusted ORs (AORs) for hospitalisation in children were significantly lower with each ascending year of age (OR 0.85, 95% CI 0.75 to 0.96 (p<0.01)). In adults, there were 24 (8.6%) deaths (19 with comorbidities) and 74 (26.6%) hospital admissions. AORs for death in adults were significantly increased with each year of age (OR 1.05, 95% CI 1.01 to 1.10 (p<0.01)) and with pulmonary arterial hypertension (PAH; OR 5.99, 95% CI 1.34 to 26.91 (p=0.02)). AORs for hospitalisation in adults were significantly higher with each additional year of age (OR 1.03, 95% CI 1.00 to 1.05 (p=0.04)), additional comorbidities (OR 3.23, 95% CI 1.31 to 7.97 (p=0.01)) and genetic disease (OR 2.87, 95% CI 1.04 to 7.94 (p=0.04)). CONCLUSIONS: Children were at low risk of death and hospitalisation secondary to COVID-19 even with severe CHD, but hospital admission rates were higher in younger children, independent of comorbidity. In adults, higher likelihood of death was associated with increasing age and PAH, and of hospitalisation with age, comorbidities and genetic disease. An individualised approach, based on age and comorbidities, should be taken to COVID-19 management in patients with CHD.

Cardiovascular MR dobutamine stress in adult tetralogy of Fallot: disparity between CMR volumetry and flow for cardiovascular function.

PURPOSE: To evaluate the MR agreement of cardiac function parameters between volumetric (cine SSFP) and phase contrast flow (PC-flow) assessment in patients with repaired tetralogy of Fallot (r-TOF) and chronic pulmonary regurgitation (PR) at rest and under dobutamine stress (DS-MR). MATERIALS AND METHODS: We studied 18 patients with r-TOF and severe chronic PR (34 ± 12.7 years, PR fraction([flow]) 44 ± 15%) by cardiac MR at rest, 10 and 20 µg/kg/min of dobutamine. We compared analogous functional parameters by volumetry and PC-flow: (i) Systemic output [left ventricle stroke volume (LV(SV)) versus aortic forward flow (AO(FF))], (ii) Pulmonary output [right ventricle stroke volume (RV(SV)) versus pulmonary forward flow (PA(FF))], (iii) PR volume [(RV(SV)-LV(SV)) versus pulmonary backward flow (PA(BF))], (iv) PR fraction [(RV(SV)-LV(SV)/RV(SV)) versus (PA(BF)/PA(FF))]. RESULTS: We found excellent Bland-Altman agreement (mean difference ± limits of agreement, mL/beat/m(2)) at rest for both the systemic (-0.8 ± 5.7) and pulmonary strokes volumes (-0.1 ± 7.6), which slightly deteriorates during DS-MR. The PR volume showed acceptable agreement at rest (-3.6 ± 15.1), but also further deteriorated during stress (5.4 ± 24). In contrast, the PR fraction showed poor agreement equally at rest (-5.6 ± 22.8) and DS-MR (3.2 ± 19.2). CONCLUSION: In r-TOF with chronic PR, analogous functional parameters should not be used interchangeably between volumetric and PC-flow assessment during DS-MR evaluation.

Complete mitochondrial genomes of three reef forming Acropora corals (Acroporidae, Scleractinia) from Chagos Archipelago, Indian Ocean.

We present the first mitochondrial genomes from Chagos Archipelago, Indian Ocean, of three putative species of reef forming Acropora (Acropora aff. tenuis, Acropora aff.cytherea and Acropora aff. orbicularis). The circular genome consists respectively of 18,334 bp, 18,353 bp and 18,584 bp. All mitochondrial genomes recovered comprise 13 protein-coding genes, two transfer RNA genes and two ribosomal RNA genes, with an overall GC content ranging from 37.9% to 38.0%. These new genomic data contribute to our increased understanding of genus Acropora and its species boundaries, ultimately aiding species monitoring and conservation efforts.

Naming errors and dysfunctional tissue metrics predict language recovery after acute left hemisphere stroke.

Language recovery following acute left hemisphere (LH) stroke is notoriously difficult to predict. Global language measures (e.g., overall aphasia severity) and gross lesion metrics (e.g., size) provide incomplete recovery predictions. In this study, we test the hypothesis that the types of naming errors patients produce, combined with dysfunctional brain tissue metrics, can provide additional insight into recovery following acute LH stroke. One hundred forty-eight individuals who were hospitalized with a new LH stroke completed clinical neuroimaging and assessments of naming and global language skills. A subset of participants again completed language testing at subacute, early (5-7 months post-stroke), and late (≥11 months post-stroke) chronic phases. At each time point, we coded naming errors into four types (semantic, phonological, mixed and unrelated) and determined error type totals and proportions. Dysfunctional tissue measures included the percentage of damage to language network regions and hypoperfusion in vascular territories. A higher proportion of semantic errors was associated with better acute naming, but higher proportions of other error types was related to poorer accuracy. Naming and global language skills significantly improved over time , but naming error profiles did not change. Fewer acute unrelated errors and less damage to left angular gyrus resulted in optimal naming and language recovery by the final testing time point, yet patients with more acute errors and damage to left middle temporal gyrus demonstrated the greatest increases in language over time. These results illustrate that naming error profiles, particularly unrelated errors, add power to predictions of language recovery after stroke.

Maternal and neonatal outcomes in women with history of coronary artery disease.

BACKGROUND: Pregnancy outcomes in women with pre-existing coronary artery disease (CAD) are poorly described. There is a paucity of data therefore on which to base clinical management to counsel women, with regard to both maternal and neonatal outcomes. METHOD: We conducted a retrospective multicentre study of women with established CAD delivering at 16 UK specialised cardiac obstetric clinics. We included pregnancies of 24 weeks' gestation or more, delivered between January 1998 and October 2018. Data were collected on maternal cardiovascular, obstetric and neonatal events. RESULTS: 79 women who had 92 pregnancies (94 babies including two sets of twins) were identified. 35.9% had body mass index >30% and 24.3% were current smokers. 18/79 (22.8%) had prior diabetes, 27/79 (34.2%) had dyslipidaemia and 21/79 (26.2%) had hypertension. The underlying CAD was due to atherosclerosis in 52/79 (65.8%), spontaneous coronary artery dissection (SCAD) in 11/79 (13.9%), coronary artery spasm in 7/79 (8.9%) and thrombus in 9/79 (11.4%).There were six adverse cardiac events (6.6% event rate), one non-ST elevation myocardial infarction at 23 weeks' gestation, two SCAD recurrences (one at 26 weeks' gestation and one at 9 weeks' postpartum), one symptomatic deterioration in left ventricular function and two women with worsening angina. 14% of women developed pre-eclampsia, 25% delivered preterm and 25% of infants were born small for gestational age. CONCLUSION: Women with established CAD have relatively low rates of adverse cardiac events in pregnancy. Rates of adverse obstetric and neonatal events are greater, highlighting the importance of multidisciplinary care.

Birth weight in pregnancies complicated by maternal heart disease.

OBJECTIVE: To assess median and percentile birthweight distribution in women with various groups of heart disease relative to a contemporaneous comparison group. METHODS: Data on birth weight and gestational age were collected from 1321 pregnancies ≥24 weeks' gestation in 1053 women with heart disease from seven UK maternity units. Women were assigned to one of 16 groups according to their cardiac lesion. In units where it was possible, data on two births, one delivering before and one after index cases, were collected, giving 2307 comparators. Birthweight percentiles (corrected for gestational age, sex and parity) were calculated using Aberdeen norms. We assessed the association of birth weight with cardiac lesion, maternal hypoxaemia (saturations <90%), systemic ventricular function and beta-blockers. RESULTS: 1321 pregnancies in women with heart disease and 2307 comparators were studied. Almost all groups with heart disease had lower median and percentile birth weights than comparators, significantly in 10 groups, the biggest effect seen in women with Fontan circulation, pulmonary hypertension, prosthetic heart valves, systemic right ventricle, Marfan syndrome, repaired tetralogy of Fallot and cardiomyopathy (in that order). In 307 pregnancies, women took beta-blockers; median birth weight adjusted for maternal age, parity and the effect of the cardiac lesion was 3116.7 g (IQR 790.4) when beta-blockers were used and 3354.3 g (IQR 634.1) when they were not (p<0.001). 17 women had saturations <90%, and median birth weight was significantly lower, 3105.4 g (IQR 1288.9) versus 3387.7 g (IQR 729.8) (p=0.006). CONCLUSION: Our findings identify specific groups of women with heart disease at risk of having a small baby.

Exceptional biodiversity of the cryptofaunal decapods in the Chagos Archipelago, central Indian Ocean.

The Chagos Archipelago is geographically remote and isolated from most direct anthropogenic pressures. Here, we quantify the abundance and diversity of decapod crustaceans inhabiting dead coral colonies, representing a standardised microhabitat, across the Archipelago. Using morphological and molecular techniques we recorded 1868 decapods from 164 nominal species within 54 dead coral colonies, but total species estimates (Chao1 estimator) calculate at least 217 species. Galatheids were the most dominant taxa, though alpheids and hippolytids were also very abundant. 32% of species were rare, and 46% of species were found at only one atoll. This prevalence of rarer species has been reported in other cryptofauna studies, suggesting these assemblages maybe comprised of low-abundance species. This study provides the first estimate of diversity for reef cryptofauna in Chagos, which will serve as a useful baseline for global comparisons of coral reef biodiversity.

Trait and phylogenetic diversity provide insights into community assembly of reef-associated shrimps (Palaemonidae) at different spatial scales across the Chagos Archipelago.

Coral reefs are the most biodiverse marine ecosystem and one of the most threatened by global climate change impacts. The vast majority of diversity on reefs is comprised of small invertebrates that live within the reef structure, termed the cryptofauna. This component of biodiversity is hugely understudied, and many species remain undescribed. This study represents a rare analysis of assembly processes structuring a distinct group of cryptofauna, the Palaemonidae, in the Chagos Archipelago, a reef ecosystem under minimal direct human impacts in the central Indian Ocean. The Palaemonidae are a diverse group of Caridae (infraorder of shrimps) that inhabit many different niches on coral reefs and are of particular interest because of their varied habitat associations. Phylogenetic and trait diversity and phylogenetic signal were used to infer likely drivers of community structure. The mechanisms driving palaemonid community assembly and maintenance in the Chagos Archipelago showed distinct spatial patterns. At local scales, among coral colonies and among reefs fringing individual atolls, significant trait, and phylogenetic clustering patterns suggest environmental filtering may be a dominant ecological process driving Palaemonidae community structure, although local competition through equalizing mechanisms may also play a role in shaping the local community structure. Importantly, we also tested the robustness of phylogenetic diversity to changes in evolutionary information as multi-gene phylogenies are resource intensive and for large families, such as the Palaemonidae, are often incomplete. These tests demonstrated a very modest impact on phylogenetic community structure, with only one of the four genes (PEPCK gene) in the phylogeny affecting phylogenetic diversity patterns, which provides useful information for future studies on large families with incomplete phylogenies. These findings contribute to our limited knowledge of this component of biodiversity in a marine locality as close to undisturbed by humans as can be found. It also provides a rare evaluation of phylogenetic diversity methods.

Retrospective UK multicentre study of the pregnancy outcomes of women with a Fontan repair.

BACKGROUND: The population of women of childbearing age palliated with a Fontan repair is increasing. The aim of this study was to describe the progress of pregnancy and its outcome in a cohort of patients with a Fontan circulation in the UK. METHODS: A retrospective study of women with a Fontan circulation delivering between January 2005 and November 2016 in 10 specialist adult congenital heart disease centres in the UK. RESULTS: 50 women had 124 pregnancies, resulting in 68 (54.8%) miscarriages, 2 terminations of pregnancy, 1 intrauterine death (at 30 weeks), 53 (42.7%) live births and 4 neonatal deaths. Cardiac complications in pregnancies with a live birth included heart failure (n=7, 13.5%), arrhythmia (n=6, 11.3%) and pulmonary embolism (n=1, 1.9%). Very low baseline maternal oxygen saturations at first obstetric review were associated with miscarriage. All eight women with saturations of less than 85% miscarried, compared with 60 of 116 (51.7%) who had baseline saturations of ≥85% (p=0.008). Obstetric and neonatal complications were common: preterm delivery (n=39, 72.2%), small for gestational age (<10th percentile, n=30, 55.6%; <5th centile, n=19, 35.2%) and postpartum haemorrhage (n=23, 42.6%). There were no maternal deaths in the study period. CONCLUSION: Women with a Fontan circulation have a high rate of miscarriage and, even if pregnancy progresses to a viable gestational age, a high rate of obstetric and neonatal complications.

Identifying zooplankton community changes between shallow and upper-mesophotic reefs on the Mesoamerican Barrier Reef, Caribbean.

Mesophotic coral ecosystems (MCEs, reefs 30-150 m) are understudied, yet the limited research conducted has been biased towards large sessile taxa, such as scleractinian corals and sponges, or mobile taxa such as fishes. Here we investigate zooplankton communities on shallow reefs and MCEs around Utila on the southern Mesoamerican Barrier Reef using planktonic light traps. Zooplankton samples were sorted into broad taxonomic groups. Our results indicate similar taxonomic zooplankton richness and overall biomass between shallow reefs and MCEs. However, the abundance of larger bodied (>2 mm) zooplanktonic groups, including decapod crab zoea, mysid shrimps and peracarid crustaceans, was higher on MCEs than shallow reefs. Our findings highlight the importance of considering zooplankton when identifying broader reef community shifts across the shallow reef to MCE depth gradient.

Injuries and illnesses among American Red Cross responders-United States, 2008-2012.

OBJECTIVE: Occupational injury and illness rates for volunteer responders have not been well documented. We analyzed data specific to volunteers from the American Red Cross (ARC). METHODS: Data collected by the ARC between 2008 and 2012 were analyzed to identify disaster factors associated with responder injuries and illnesses. We focused on disaster-relief operation (DRO) level (indicating operational costs, ranging from 3 [lower] to 5+ [higher]); disaster type; region; and year. We calculated injury and illness rates and estimated rate ratios (RR) with 95% CI, using negative binomial regression. Also, we analyzed a total of 113 disasters. RESULTS: Hurricanes had the highest rates of injuries (14/1000 responders) and illnesses (18/1000 responders). In the adjusted model for injuries, RRs were higher for DRO levels 4 (3.6 [CI, 2.0-6.7]) and 5+ (4.9 [CI, 2.2-11.0]) than for level 3. In the adjusted model for illnesses, RRs also were higher for DRO levels 4 (4.4 [CI, 2.6-7.3]) and 5+ (8.6 [CI, 4.1-17.7]) than for level 3. CONCLUSIONS: Higher DRO levels were a significant predictor of greater rates of occupational injuries and illnesses. Careful selection of responders, including volunteers, has been warranted for deployments to such disasters. (Disaster Med Public Health Preparedness. 2014;0:1-7).

Pathophysiology and Management of Arrhythmias Associated with Atrial Septal Defect and Patent Foramen Ovale.

Atrial septal defects (ASDs) are among the most common of congenital heart defects and are frequently associated with atrial arrhythmias. Atrial and ventricular geometrical remodelling secondary to the intracardiac shunt promotes evolution of the electrical substrate, predisposing the patient to atrial fibrillation and other arrhythmias. Closure of an ASD reduces the immediate and long-term prevalence of atrial arrhythmias, but the evidence suggests that patients remain at an increased long-term risk in comparison with the normal population. The closure technique itself and its timing impacts future arrhythmia risk profile while subsequent transseptal access following surgical or device closure is complicated. Newer techniques combined with increased experience will help to alleviate some of the difficulties associated with optimal management of arrhythmias in these patients.

Dobutamine stress MRI in repaired tetralogy of Fallot with chronic pulmonary regurgitation: a comparison with healthy volunteers.

BACKGROUND: To compare the ventricular response to dobutamine stress between adult patients with chronic pulmonary regurgitation (PR) after repair of tetralogy of Fallot (r-TOF) and healthy volunteers using a staged dobutamine stress MR (DS-MR) protocol. METHODS: Eighteen r-TOF patients (median age 31.9 years, range 16.2-60.1) with severe PR and 10 healthy controls (median age 40.6 years, range 23.9-51.8) completed staged DS-MR (baseline, 10 and 20 µg/kg/min) with ventricular volumetry and pulmonary flow quantification. Comparative analysis involved 3-way ANOVA, t-test, regression analysis, and coefficient of variance. RESULTS: All controls had significant increase of ejection fraction (EF) at each stress level for both ventricles (normal contractile reserve, all p<0.05). In r-TOF patients (RV-EDV 126 ± 27 ml/m(2), RV-EF 55 ± 7%, LV-EF 58 ± 6%, PR-fraction 43 ± 15%), low-dose DS-MR at 10 µg/kg/min demonstrated normal biventricular contractile reserve as seen in volunteers. On increase from 10 to 20 µg/kg/min a subgroup showed worsening ejection fraction (n=8, p<0.05), mainly due to lack of reduction or even increase of RV-ESV, while the remainder responded with further reduction of RV-ESV and RV-EDV (n=10, p<0.05) and a non-significant trend to increased EF. This different response could not be predicted at baseline. CONCLUSIONS: In r-TOF patients with chronic PR, DS-MR at 10 µg/kg/min showed normal biventricular systolic response compared with controls. Increase to 20 µg/kg/min provoked abnormal RV-ESV response in some r-TOF patients, suggesting presence of ventricular systolic dysfunction not evident at rest.

Paced electrogram fractionation analysis of arrhythmogenic tendency in DeltaKPQ Scn5a mice.

INTRODUCTION: Gain-of-function mutations within Scn5a, including the DeltaKPQ 1505-1507 deletion in the inactivation domain compromising myocardial repolarization, are implicated in human long QT 3 syndrome (LQT3), associated with ventricular arrhythmogenesis and sudden death. METHODS AND RESULTS: Patch clamp studies on isolated ventricular Scn5a+/Delta myocytes from DeltaKPQ mice produced by homologous recombination in embryonic stem (ES) cells confirmed such altered electrophysiological properties of the mutant channel. Programmed electrical stimulation (PES) with decremental pacing from the basal right ventricular epicardial surface and paced electrogram fractionation analysis (PEFA) of electrograms recorded from the basal left ventricular epicardial surface of Langendorff-perfused whole heart preparations demonstrated ventricular tachycardia (VT) in 8 of 9 Scn5a+/Delta mutant (but no Scn5a+/+ (wild-type (WT)) controls; n = 17), with increased electrogram durations (EGD) and more dispersed conduction curves. Isoproterenol (100 nM) was without effect on tachycardic Scn5a+/Delta hearts (n = 9) yet propranolol (1 microM) prevented VT in all isoproterenol-infused WT control (n = 4) but no Scn5a+/Delta hearts (n = 4). Furthermore propranolol itself increased EGD and dispersion in Scn5a+/Delta hearts. In contrast, mexiletine (10 microM) suppressed VTs in 4 of 5 Scn5a+/Delta hearts without altering EGD or dispersion. CONCLUSION: Beta-adrenoreceptor blockade does not confer an antiarrhythmic effect and may even enhance arrhythmogenesis by increasing reentrant substrate in Scn5a+/Delta hearts while mexiletine protects against VT without modifying conduction characteristics. Together these findings permit a scheme where VT in LQT3 is initiated by triggered mechanisms but propagated by reentry.