Background The role of children in household transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains uncertain. Here, we describe the epidemiological and clinical characteristics of children with COVID-19 in Catalonia (Spain) and investigate the dynamics of household transmission. Methods Prospective, observational, multicenter study performed during summer and school periods (1 July-31 October, 2020), in which epidemiological and clinical features, and viral transmission dynamics were analyzed in COVID-19 patients <16 years. A pediatric index case was established when a child was the first individual infected within a household. Secondary cases were defined when another household member tested positive for SARS-CoV-2 before the child. The secondary attack rate (SAR) was calculated, and logistic regression was used to assess associations between transmission risk factors and SARS-CoV-2 infections. Results The study included 1040 COVID-19 patients <16 years. Almost half (47.2%) were asymptomatic, 10.8% had comorbidities, and 2.6% required hospitalization. No deaths were reported. Viral transmission was common among household members (62.3%). More than 70% (756/1040) of pediatric cases were secondary to an adult, whereas 7.7% (80/1040) were index cases. The SAR was significantly lower in households with COVID-19 pediatric index cases during the school period relative to summer (p=0.02), and when compared to adults (p=0.006). No individual or environmental risk factors associated with the SAR were identified. Conclusions Children are unlikely to cause household COVID-19 clusters or be major drivers of the pandemic even if attending school. Interventions aimed at children are expected to have a small impact on reducing SARS-CoV-2 transmission.
Background Left Ventricular (LV) stiffening contributes to Heart Failure with preserved Ejection Fraction (HFpEF), a syndrome with no effective treatment options. Increasing titin’s compliance in the heart has become possible recently through inhibition of the splicing factor RBM20. Here we investigated the effects of increasing titin’s compliance in mice with diastolic dysfunction. Methods Mice in which the RNA recognition motif (RRM) of one of the RBM20 alleles was floxed and which expressed the MerCreMer transgene under control of the αMHC promoter (referred to as cRbm20ΔRRM mice) were used. Mice underwent transverse aortic constriction (TAC) surgery and deoxycorticosterone acetate (DOCA) pellet implantation (TAC/DOCA). RRM deletion in adult mice was triggered by injecting raloxifene (cRbm20ΔRRM-raloxifene) with DMSO injected mice (cRbm20ΔRRM-DMSO) as the control. Diastolic function was investigated using echocardiography and pressure volume analysis; passive stiffness was studied in LV muscle strips and isolated cardiac myocytes before and after elimination of titin-based stiffness. Treadmill exercise performance was also studied. Titin isoform expression was evaluated with Agarose gels. Results cRbm20ΔRRM-raloxifene mice expressed large titins in the hearts, named super compliant titin (N2BAsc), which, within 3 weeks after raloxifene injection, made up ~45% of total titin. TAC/DOCA cRbm20ΔRRM-DMSO mice developed LV hypertrophy and a marked increase in LV chamber stiffness as shown by both pressure-volume analysis and echocardiography. LV chamber stiffness was normalized in TAC/DOCA cRbm20ΔRRM-raloxifene mice that expressed N2BAsc. Passive stiffness measurements on muscle strips isolated from the LV free wall revealed that extracellular matrix (ECM) stiffness was equally increased in both groups of TAC/DOCA mice (cRbm20ΔRRM-DMSO and cRbm20ΔRRM-raloxifene). However, titin-based muscle stiffness was reduced in the mice that expressed N2BAsc (TAC/DOCA cRbm20ΔRRM-raloxifene). Exercise testing demonstrated significant improvement in exercise tolerance in TAC/DOCA mice that expressed N2BAsc. Conclusions Inhibition of the RBM20-based titin splicing system upregulates compliant titins, which improves diastolic function and exercise tolerance in the TAC/DOCA model. Titin holds promise as a therapeutic target for HFpEF.
INTRODUCTION Patients with D- transposition of the great arteries (TGA) treated with Senning or Mustard surgeries have several atrial scars that predispose them to develop atrial tachycardias (AT). Identification of scar zones and possible arrhythmic isthmus in voltage mapping will help to guide the ablation. AIM To describe the feasibility of using a specific mapping catheter to identify possible arrhythmic isthmus in this set of patients. METHODS Prospective observational study in patients with history of SVT and atrial switch surgery, that underwent electrophysiologic study (EP) and electroanatomic (EA) mapping with a new 8Fr deflectable, multipoint wavefront-activation-orientation independent Grid catheter, in a third level hospital since April 2018 until May 2019, with medium-term follow-up. RESULTS A total of 8 EPs were performed in 7 patients (3 (57%) Female, median age 35 ± 6,3 y.o.). Figure 1A shows the localization and percentage of scar identified in both atria. A total of 6 AT were induced. In this, an arrhythmogenic isthmus was identified and, in all patients, at least one non-arrhytmogenic isthmus was documented. Figure 1B shows anatomical and electrophysiological characteristics of the isthmus. Arrhythmogenic isthmus had slower conduction velocity than non-arrhytmogenic ( mean 0,44m/s (IQI 0,17-0,62) vs 1,05 m/s (IQI 0,86-1,39) p = 0.008) and fractionated potentials were detected more frequently (100% vs 50% p = 0.089) CONCLUSION EA mapping with a new a multipoint, high-definition, Grid Cather is feasible and allows the identification and electrophysiological characterization of arrhythmogenic and non-arrhytmogenic isthmus in patients with TGA treated with atrial switch surgery. Abstract Figure 1
indicating a slower myosin cross-bridge turnover rate of the mutant. Likewise, stopped flow kinetics of the ATP induced dissociation of the acto-myosin complex showed a significantly reduced slope of the kobs-[MgATP] relationship for IVS6-1 reconstituted myosin (4.350.02Â105 M-1 s-1, n=5), depicting slower second-order MgATP binding rates compared with WT (5.350.02Â105 M-1 s-1, n=5). Steady-state fluorescence binding experiments of mutant vs. WT reconstituted myosin to pyrene labeled F-actin under rigor conditions demonstrated significantly reduced binding affinity of IVS6-1 (Kd=16.752.8 nM, n=3) compared with WT (Kd=4.651.3 nM, n=3). In skinned porcine cardiac muscles, a significant decrease in maximal force was observed for IVS6-1 reconstituted fibers compared with WT (27.151.0 kN/m2 vs. 34.952.4 kN/m2, n=6). The Ca 2þ sensitivity and cooperativity were significantly different in IVS6-1 (pCa50=5.6650.01, nH=2.950.15) vs. WT (pCa50=5.4850.01, nH=2.250.14). In conclusion, we demonstrate that IVS6-1 may lead to cardiac dysfunction by disrupting the acto-myosin interaction (steady-state and kinetics) and compromising the ability of the mutant myosin to develop contractile force.
Introduction The arrhythmic risk stratification of patients with repaired Tetralogy of Fallot (TOF) is still controversial. The performance of an electrophysiologic (EP) study before pulmonary valve replacement (PVR), regardless of patient's risk factors, is an extended practice in some centers that is not recommended in current guidelines. The aim of our study was to explore the differences in ventricular tachycardia (VT) inducibility in patients with TOF during programmed ventricular stimulation (PVS) depending on the clinical indication. Methods All patients with repaired TOF who underwent an EP study with PVS between January 2001 and October 2020 were included. EP studies performed in the context of ventricular or supraventricular tachycardia ablations that had been previously diagnosed were excluded. We defined two clinical scenarios for performing the EP study: pre-PVR (performed previous to pulmonary valve replacement) or diagnostic EP study (performed due to high risk symptoms which included palpitations, syncope or presyncope). Baseline clinical information, electrocardiogram, echocardiogram and cardiac MRI parameters were retrospective recorded. Results A total of 139 EP studies with PVS were included; 87 in the pre-PVR group and 52 in the diagnostic EP study group. There was a greater incidence of palpitations, syncope and presyncope in the “Diagnostic EP study” group. Moreover, there were statistical significant differences in right ventricle dimensions and function between groups. The repair surgical approach was similar in both groups. It was detected a statistical significant difference in VT induction between the pre-PVR group and the diagnostic indicated group (16,1% vs 34,6%, p=0,012). Conclusions Differences in VT induction are observed during PVS performing in TOF patients depending on the clinical indication. Symptomatology is an important parameter that must be taken into account in order to decide whether to perform an EP study in this population. FUNDunding Acknowledgement Type of funding sources: None.
Introduction The electrophysiologic (EP) evaluation with programmed electrical stimulation (PVS) is generally recommended in patients with repaired Tetralogy of Fallot and additional risk factors for sudden cardiac death. Nevertheless, different PVS protocols have been described. The aim of our study was to evaluate the differences in ventricular tachycardia (VT) inducibility of patients with TOF after the implementation of a standard PVS protocol in the EP laboratory of a Congenital Heart Disease reference center. Methods All patients with repaired TOF who underwent an EP study with PVS between January 2001 and October 2020 were included. The new standardized PVS protocol was performed in 2 ventricular sites (apex and outflow tract) with 3 drive trains (cycle lengths 400, 500 and 600ms) and up to 3 extrastimuli. In absence of VT induction, the protocol was repeated under isoprenaline infusion. This new protocol was implemented since January 2012. Non protocolized PVS studies before 2012 were defined as “Non-standardized”. Baseline clinical information about symptoms and previous arrhythmias was recorded as well as electrocardiogram, echocardiogram and cardiac MRI parameters. Finally, the follow-up events (ICD implantation, sudden cardiac death, global mortality, arrythmias and ICD therapies) were also retrospective recorded. Results A total of 154 EP studies with PVS were performed in 128 patients with repaired TOF. 31 of them were performed before the 1st January 2012 (non-standardized PVS) and 112 were performed with the new standardized protocol. The median follow-up was 6,5 years. Both groups had similar baseline characteristics except LVEF and RVEF, that were lower in the “Non-standardized PVS” group. There were no differences between the ventricular tachycardia inducibility of both protocols (22,3% vs 33,3%; p=0,162). The risk factors for VT inducibility were the QRS length (184,46ms vs 169,34 ms; p=0,038), the RVEF (36,25% vs 43,79; p=0,0007), the presence of ventricular ectopia (VE) (38,5% vs 20,0%; p=0,024) and previous VT (35,9% vs 13,9%; p=0,003). VT induction during EP study was related with ICD implantation (71,8% vs 21,7%, p≤0,001), VT (30,8% vs 20%, p<0,001) and all kind of arrythmias (VT, non-sustained VT, VE and auricular flutter) (41% vs 21,7%, p=0,005) during follow-up. A total of 6 deaths (1 in the group with induced VT and 5 in the group with non-induced VT) were recorded. Conclusions The implementation of a standardized and more complete PVS protocol in patients with repaired TOF has not shown differences in the experience of our center. The risk factors for VT inducibility were the QRS length, the RVEF, the presence of ventricular ectopia and previous VT, which have also been reported as risk factors for sudden cardiac death in previous studies. The presence of VT induction entailed more ICD implantation and more arrythmias at follow-up. FUNDunding Acknowledgement Type of funding sources: None.
Funding Acknowledgements Type of funding sources: None. Background. Myocardial work (MW) is a new imaging technique to assess left ventricular (LV) systolic function. It incorporates both deformation parameters (global longitudinal strain -GLS-) and loading conditions and gives information on global constructive work (GCW), global wasted work (GWW), global LV myocardial work index (GWI) and global LV myocardial work efficiency (GWE). Purpose. The aim of this study was to describe the prognostic role of MW in predicting major adverse cardiovascular events (MACE) in patients with reduced LV ejection fraction (LVEF), and to compare it with GLS and LVEF. Methods. We retrospectively included consecutive patients from 2012 to 2019 with dilated LV and LVEF < 50% of any aetiology. Clinical variables were collected and LVEF, GLS and MW were evaluated from baseline echocardiogram. MACE was defined as heart failure (HF) and/or ventricular arrhythmia (VA) and/or cardiac arrest and/or all cause death. Results. 99 patients were included, 26 were women (26.3%), mean age at diagnosis was 57 years (SD 23). Mean LVEF was 32.5% (SD 10.3). Baseline patients characteristics are described in Table 1. During a median follow-up of 25 months (IQR 12), 24 MACE were recorded (24.4%). Patients with MACE had worse MW parameters: significantly lower MWI (805 ± 360 % vs 638 ± 277 %, p = 0.04) and lower GCW (1116 ± 535 mmHg vs 874 ± 458 mmHg, p = 0.05), and a tendency to lower GWE (83 ± 11 % vs 77 ± 16 %, p = 0.084). Of note, both LVEF (33 ± 10% vs 29 ± 9%, p = 0.123) and GLS (-9.99 ± 3.7% vs -8.8 ± 3.0, p = 0.170) showed a trend but were not significantly associated with outcomes. This might suggest that MW variables are stronger prognostic predictors than traditional imaging parameters. Conclusions. In patients with reduced LVEF, MW parameters including global MWI and GCW were associated with major adverse cardiovascular events. Of note, both EF and GLS seem to have less prognostic implications in this cohort when compared with MW. Our results are preliminary and larger studies are needed in order to fully understand the clinical utility of MW beyond traditional parameters. Baseline patient characteristics GLOBAL EVENTS NO EVENTS p Hypertension, % 41 67 29 0.014 Ischaemic etiology, % 14 20 12 0.448 Creatinine, mean (SD) - mg/dL 0.96 (0.04) 1.11 (0.09) 0.90 (0.04) 0.021 Bblockers, % 98 100 97 0.514 Nitrates, % 4 13 0 0.025 Diuretics, % 65 93 53 0.006 SD standard deviation Abstract Figure. Results
Background Myocardial work (MW) is a new imaging technique to assess left ventricular (LV) systolic function. It incorporates both deformation parameters (global longitudinal strain -GLS-) and loading conditions and gives information on global constructive work (GCW), global wasted work (GWW), global LV myocardial work index (GWI) and global LV myocardial work efficiency (GWE). Purpose The aim of this study was to describe the prognostic role of MW in predicting major adverse cardiovascular events (MACE) in patients with reduced LV ejection fraction (LVEF), and to compare it with GLS and LVEF. Methods We retrospectively included consecutive patients from 2012 to 2019 with dilated LV and LVEF <50% of any aetiology. Clinical variables were collected and LVEF, GLS and MW were evaluated from baseline echocardiogram. MACE was defined as heart failure (HF) and/or ventricular arrhythmia (VA) and/or cardiac arrest and/or all cause death. Results 99 patients were included, 26 were women (26.3%), mean age at diagnosis was 57 years (SD 23). Mean LVEF was 32.5% (SD 10.3). Baseline patients characteristics are described in Table 1. During a median follow-up of 25 months (IQR 12), 24 MACE were recorded (24.4%). Patients with MACE had worse MW parameters: significantly lower MWI (805±360% vs 638±277%, p=0.04) and lower GCW (1116±535 mmHg vs 874±458 mmHg, p=0.05), and a tendency to lower GWE (83±11% vs 77±16%, p=0.084). Of note, both LVEF (33±10% vs 29±9%, p=0.123) and GLS (−9.99±3.7% vs −8.8±3.0, p=0.170) showed a trend but were not significantly associated with outcomes. This might suggest that MW variables are stronger prognostic predictors than traditional imaging parameters. Conclusions In patients with reduced LVEF, MW parameters including global MWI and GCW were associated with major adverse cardiovascular events. Of note, both EF and GLS seem to have less prognostic implications in this cohort when compared with MW. Our results are preliminary and larger studies are needed in order to fully understand the clinical utility of MW beyond traditional parameters. Results Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Universitary Hospital Vall d'Hebron
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