Objective:Bronchiolitis is a major cause of respiratory illness in infants. Few studies have demonstrated arrhythmias during bronchiolitis, including bradycardia and atrioventricular block, some requiring pacemaker implantation. However, the association between bronchiolitis and cardiac arrhythmias remains unclear. In this work we sought to investigate the incidence and characteristics of arrhythmias during bronchiolitis in infants younger than 1 year of age. Study design:A single-center, prospective cohort study was conducted on infants hospitalized with a clinical diagnosis of bronchiolitis. Demographic and clinical data were collected via questionnaire. All infants underwent overnight Holter monitoring during hospitalization. Results:Among 100 enrolled infants (79% positive for respiratory syncytial virus), 18 (18%) demonstrated arrhythmias: sinus arrest (2-13 seconds) in 8 infants, bradycardia <60 bpm in 7 infants, and frequent atrial premature complexes (3%-18% of beats) in 3 infants. Follow-up Holter recordings in 7 patients (38%) showed resolution of arrhythmias within 1-4 months. No significant demographic or clinical predictors were identified. None of the infants exhibited symptoms (eg, cyanosis, unresponsiveness) associated with arrhythmia severity. Conclusions:Our study shows that bronchiolitis is associated with significant arrhythmias in infants, particularly sinus arrest, bradycardia, and atrial premature complexes. In our cohort, none of the infants with significant arrhythmia required arrhythmia intervention. Clinicians should be aware of this association and consider delaying decisions regarding pacemaker implantation until after the resolution of bronchiolitis even in cases of infants with severe bradycardia. Future investigations should explore the pathophysiology and prognostic implications of this phenomenon.

Background A significant percentage of patients with congenital heart disease surviving into adulthood will develop arrhythmias. These arrhythmias are associated with an increased risk of adverse events and death. We aimed to assess arrhythmia prevalence, risk factors, and associated health care usage in a large national cohort of patients with adult congenital heart disease. Methods and Results Adults with a documented diagnosis of congenital heart disease, insured by Clalit and Maccabi health services between January 2007 and December 2011, were included. We assessed the associations between arrhythmia and subsequent hospitalization rates and death with mixed negative binomial and Cox proportional hazard models, respectively. Among 11 653 patients with adult congenital heart disease (median age, 47 years [interquartile range, 31–62]), 8.7% had a tachyarrhythmia at baseline, 1.5% had a conduction disturbance, and 0.5% had both. Among those without a baseline arrhythmia, 9.2% developed tachyarrhythmias, 0.9% developed a conduction disturbance, and 0.3% developed both during the study period. Compared with no arrhythmia (reference group), arrhythmia in the previous 6 months was associated with a higher multivariable adjusted hospitalization rate, 1.33‐fold higher than the rate of the reference group (95% CI, 1.00–1.76) for ventricular arrhythmia, 1.27‐fold higher (95% CI, 1.17–1.38) for atrial arrhythmias, and 1.33‐fold higher (95% CI, 1.04–1.71) for atrioventricular block. Atrial tachyarrhythmias were associated with an adjusted mortality hazard ratio (HR) of 1.65 (95% CI, 1.44–2.94), and ventricular tachyarrhythmias with a >2‐fold increase in mortality risk (HR, 2.06 [95% CI, 1.44–2.94]). Conclusions Arrhythmias are significant comorbidities in the adult congenital heart disease population and have a significant impact on health care usage and survival.

The authors declare no conflict of interest. The data are available from the corresponding author on reasonable request.

BACKGROUND Altered coagulation is a striking feature of COVID-19. Adult patients with congenital heart disease (ACHD) are prone to thromboembolic (TE) and bleeding complications. OBJECTIVES The purpose of this study was to investigate the prevalence and risk factors for COVID-19 TE/bleeding complications in ACHD patients. METHODS COVID-19-positive ACHD patients were included between May 2020 and November 2021. TE events included ischemic cerebrovascular accident, systemic and pulmonary embolism, deep venous thrombosis, myocardial infarction, and intracardiac thrombosis. Major bleeding included cases with hemoglobin drop >2 g/dl, involvement of critical sites, or fatal bleeding. Severe infection was defined as need for intensive care unit, endotracheal intubation, renal replacement therapy, extracorporeal membrane oxygenation, or death. Patients with TE/bleeding were compared to those without events. Factors associated with TE/bleeding were determined using logistic regression. RESULTS Of 1,988 patients (age 32 [IQR: 25-42] years, 47% male, 59 ACHD centers), 30 (1.5%) had significant TE/bleeding: 12 TE events, 12 major bleeds, and 6 with both TE and bleeding. Patients with TE/bleeding had higher in-hospital mortality compared to the remainder cohort (33% vs 1.7%; P < 0.0001) and were in more advanced physiological stage (P = 0.032) and NYHA functional class (P = 0.01), had lower baseline oxygen saturation (P = 0.0001), and more frequently had a history of atrial arrhythmia (P < 0.0001), previous hospitalization for heart failure (P < 0.0007), and were more likely hospitalized for COVID-19 (P < 0.0001). By multivariable logistic regression, prior anticoagulation (OR: 4.92; 95% CI: 2-11.76; P = 0.0003), cardiac injury (OR: 5.34; 95% CI: 1.98-14.76; P = 0.0009), and severe COVID-19 (OR: 17.39; 95% CI: 6.67-45.32; P < 0.0001) were independently associated with increased risk of TE/bleeding complications. CONCLUSIONS ACHD patients with TE/bleeding during COVID-19 infection have a higher in-hospital mortality from the illness. Risk of coagulation disorders is related to severe COVID-19, cardiac injury during infection, and use of anticoagulants. (c) 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Abstract Objective We compared pregnancy and delivery outcomes between women with cardiac disease versus matched healthy controls. The primary outcome was the frequency of unplanned cesarean delivery. Methods In this single-center retrospective case-control study, women with cardiac disease were identified and matched (1:2 ratio, according to maternal age, parity, number of prior cesareans, gestational age, delivery onset and fetal presentation) to healthy controls who delivered within the same year. Outcomes were frequency of unplanned cesarean delivery, complications during pregnancy and postpartum course, intensive care unit (ICU) admissions, and length of hospitalization. Results One hundred and twelve women with cardiac disease (exposed group, 225 deliveries) were identified and matched with 450 healthy women (controls, 2003-2014). The cohort comprised of 103 women (204 deliveries) with acquired heart disease (valve disease [n = 69], arrhythmia [n = 31], 3 with cardiomyopathy and peri/myocarditis, and 9 women (21 deliveries) with congenital heart disease. The frequency of unplanned cesarean was 14 (7.9%) for the exposed group as compared with 12 (3.4%) in controls with an odds ratio of 2.33 (95% CI = 1.0.2–5.32, p = .045). This difference was accentuated in a sub-group of women with severe cardiac disease (15% vs. 4.2% in matched control group, p = .028). Seventy-one (31.6%) exposed women exhibited obstetric and cardiovascular complications during pregnancy as compared with 65 (14.4%) controls, p < .001. Twenty-five (13.9%) exposed women experienced postpartum complications versus 26 (7.5%) in the control group (p = .019). Maternal ICU admission occurred in 13 (7.3%) of the exposed group as compared with only 2 (0.6%) in controls (p < .001). Conclusions Women with a background cardiac condition, particularly those with severe disease, are at a higher risk for an unplanned cesarean delivery and other peripartum complications as compared with matched healthy controls.

Objective. Women with congenital heart disease (CHD) are at risk for cardiac deterioration. Previous studies focused on women after one or two pregnancies. We investigated the effect of parity on maternal cardiac status by comparing women with CHD and ≥3 live births to women with <3 live births. Design. Matched case-controlled study. Setting. Tertiary medical center, clinic for adults with CHD. Population. Twenty-nine women with ≥3 live births, matched (CHD, age) with women with <3 live births. Methods. Women with CHD were identified from the Adult CHD clinic (2010-2018), and data retrieved from medical records. Outcomes were compared for women with ≥3 live births versus <3 live births using the McNemar test. Main outcome measures. New York Heart Association (NYHA) functional classification, and cardiac impairment score assigned according to echocardiography by a cardiologist blinded to parity. Results. For 29 matched pairs with mean age 42.4 (SD 14.2) and 186 live births, the mean difference in number of live births between matched pairs was 3.8 (SD 2.5). In 17 (58.6%) pairs, women with ≥3 live births and those with <3 live births had concordant NYHA class. Echocardiography score was concordant for 19 (65.5%) pairs. Women with ≥3 live births had lower NYHA class in 8 (27.5%) pairs and lower echocardiography scores in 6 (20.6%) pairs. Differences were not significant (p=0.129, p=0.801). Conclusions. Cardiac status was similar for women with CHD and ≥3 live births compared to women with <3 live births. Keywords. Pregnancy, Birth, Congenital Heart Disease (CHD), NYHA, Parity.

Abstract Background Novel coronavirus (COVID-19) has been a world concern since December 2019. The knowledge about vertical transmission and fetal morbidity and mortality from maternal COVID-19 infection is limited. We detected an increase in the number of cases of term and near-term neonates with persistent pulmonary hypertension (PPHN) during the COVID-19 pandemic in 2020. Methods and results We collected data on all newborns with PPHN born between 2018 and 2020. We excluded premature infants (<34+0 weeks) and infants with other significant pathology or genetic syndromes. Compared to 5 cases of PPHN of 22930 live births in 2018, and 6 cases of PPHN of 22270 live births in 2019 (2-year average 0.02%, 95% CI 0.013%-0.043%), there were 16 PPHN cases from 22323 live births in 2020 (0.07%, 95% CI 0.044%-0.12%), a 3 fold increase (p<0.01). We report 5 cases of term and near-term neonates born to mothers who had highly suspected (2) and PCR proven (3) COVID-19 infection during the third trimester of pregnancy, who presented with PPHN during COVID-19 pandemic in 2020. All had otherwise unexplained pulmonary hypertension, right ventricular hypertrophy (RVH) and dilatation. Two patients needed endotracheal intubation, one was supported by nasal continuous positive airway pressure (CPAP) without intubation, two needed O2 support by nasal cannula only ant two newborns (one of them was intubated) needed Nitric oxide (NO) as pulmonary vasodilator therapy. No patient required Extracorporeal membrane oxygenation (ECMO) or died, and no prolonged residual cardiovascular or pulmonary morbidity was recorded during a median follow up of 4.8 months (range 4–6 months). Conclusions The increase in the incidence of PPHN during the COVID-19 pandemic, and the cases presented, suggest an intrauterine effect of maternal COVID-19 infection on the fetal pulmonary circulation. It is possible that the maternal infection affected the fetal pulmonary vascular resistance, or altered the normal decline in the resistance after birth. The right ventricular hypertrophy and dilatation with reduced function may be secondary to this hypothetical increased afterload or a direct effect of the infection. Further studies are warranted to elucidate the pathogenesis and clinical implications of this phenomenon. Funding Acknowledgement Type of funding sources: None.

Background Several studies have examined hospitalizations among patients with adult congenital heart disease (ACHD). Few investigated other services or utilization patterns. Our aim was to study service utilization patterns and predictors among patients with ACHD. Methods and Results We identified 11 653 patients with ACHD aged ≥18 years (median, 47 years), through electronic records of 2 large Israeli healthcare providers (2007–2011). The association between patient, disease, and sociogeographic characteristics and healthcare resource utilization were modeled as recurrent events accounting for the competing death risk. Patients with ACHD had high healthcare utilization rates compared with the general population. The highest standardized service utilization ratios (SSRs) were found among patients with complex congenital heart disease including primary care visits (SSR, 1.53; 95% CI, 1.47–1.58), cardiology outpatient visits (SSR, 5.17; 95% CI, 4.69–5.64), hospitalizations (SSR, 6.68; 95% CI, 5.82–7.54), and days in hospital (SSR, 15.37; 95% CI, 14.61–16.12). Adjusted resource utilization hazard increased with increasing lesion complexity. Hazard ratios (HRs) for complex versus simple disease were: primary care (HR, 1.14; 95% CI, 1.06–1.23); cardiology outpatient visits (HR, 1.40; 95% CI, 1.24–1.59); emergency department visits (HR, 1.19; 95% CI, 1.02–1.39); and hospitalizations (HR, 1.75; 95% CI, 1.49–2.05). Effects attenuated with age for cardiology outpatient visits and hospitalizations and increased for emergency department visits. Female sex, geographic periphery, and ethnic minority were associated with more primary care visits, and female sex (HR versus men, 0.89 [95% CI, 0.84–0.94]) and periphery (HR, 0.72 [95% CI, 0.58–0.90] for very peripheral versus very central) were associated with fewer cardiology visits. Arab minority patients also had high hospitalization rates compared with the majority group of Jewish or other patients. Conclusions Healthcare utilization rates were high among patients with ACHD. Female sex, geographic periphery, and ethnicity were associated with less optimal service utilization patterns. Further research should examine strategies to optimize service utilization in these groups.

BACKGROUND Adults with congenital heart disease (CHD) have been considered potentially high risk for novel coronavirus disease-19 (COVID-19) mortality or other complications. OBJECTIVES This study sought to define the impact of COVID-19 in adults with CHD and to identify risk factors associated with adverse outcomes. METHODS Adults (age 18 years or older) with CHD and with confirmed or clinically suspected COVID-19 were included from CHD centers worldwide. Data collection included anatomic diagnosis and subsequent interventions, comorbidities, medications, echocardiographic findings, presenting symptoms, course of illness, and outcomes. Predictors of death or severe infection were determined. RESULTS From 58 adult CHD centers, the study included 1,044 infected patients (age: 35.1 +/- 13.0 years; range 18 to 86 years; 51% women), 87% of whom had laboratory-confirmed coronavirus infection. The cohort included 118 (11%) patients with single ventricle and/or Fontan physiology, 87 (8%) patients with cyanosis, and 73 (7%) patients with pulmonary hypertension. There were 24 COVID-related deaths (case/fatality: 2.3%; 95% confidence interval: 1.4% to 3.2%). Factors associated with death included male sex, diabetes, cyanosis, pulmonary hypertension, renal insufficiency, and previous hospital admission for heart failure. Worse physiological stage was associated with mortality (p = 0.001), whereas anatomic complexity or defect group were not. CONCLUSIONS COVID-19 mortality in adults with CHD is commensurate with the general population. The most vulnerable patients are those with worse physiological stage, such as cyanosis and pulmonary hypertension, whereas anatomic complexity does not appear to predict infection severity. (C) 2021 by the American College of Cardiology Foundation.

BACKGROUND Fetal complete atrioventricular block (CAVB) is usually autoimmune mediated. The risk of developing CAVB is 2% to 3% in anti-Ro/SS-A seropositive pregnancies and it increases 10 times after previous CAVB in siblings. Despite being a rare complication, CAVB carries a 20% mortality rate and substantial morbidity, as about 65% of newborns will eventually need life-long pacing. Once found, fetal CAVB is almost always irreversible, despite aggressive immunotherapy. This poor outcome prompted some research groups to address this situation. All groups followed anti-Ro/SS-A seropositive pregnancies on a weekly basis during the second trimester of pregnancy and tried to detect first degree atrioventricular block (AVB) using accurate echocardiographic tools, assuming they may characterize the initiation of the immune damage to the A-V conduction system, at which point the process might still be reversible. Some of the groups treated fetuses with first degree AVB with maternal oral fluorinated steroids. We summarized the results of all groups, including our group. We describe a case of a fetus that developed CAVB 6 days after normal sinus rhythm (NSR), who under aggressive dexamethasone therapy gradually reverted to NSR. This fetus had a previous sibling with CAVB. We assumed the immune damage to the conduction system in this small group of fetuses with a previous CAVB sibling may have occurred more quickly than usual. We therefore recommend a twice-weekly follow-up with these fetuses.

Background: The significance of depression/anxiety among ACHD patients in terms of health care utilization is unknown and data on the association with mortality are scarce. Methods: Analyses comprised 8334 ACHD patients, age >= 18 years, insured by a large healthcare organization (2007-2011). Depression/anxiety were determined by diagnoses and treatments recorded in the organization database. Adjusted utilization relative rates (RRs) were estimated with negative binomial models and mortality hazard ratios (HRs) with the Cox proportional hazard model. Results: ACHD patients with depression/anxiety (N=2950, 35%) were more likely to be older (mean +/- SD: 54 +/- 17 vs. 45 +/- 18 years), women (61% vs. 45%), and have comorbidities than counterparts without depression/anxiety. Following multivariable adjustment, patients with depression/anxiety had more primary care and cardiology clinic visits, more emergency department visits and more hospitalizations. RRs (95% confidence interval) were: 1.31 (1.27-1.35); 1.07 (1.01-1.13); 1.60 (1.46-1.77); and 1.18 (1.08-1.29) respectively, for diagnosis before the study period, and 1.36 (1.31-1.42); 1.22 (1.14-1.30); 1.43 (1.24-1.60) and 1.47 (1.33-1.64), respectively, for diagnosis during the study. Stratifying by age, the highest adjusted primary care and cardiology visit RRs were found among 18-24 years old patients and the lowest among patients >= 65 years. Between 2007 and 2017, 905 patients died. Depression/anxiety were associated with increased mortality risk with adjusted HRs: 1.10 (95% CI: 0.94-1.29) for past diagnosis and 1.40 (1.17-1.67) for study period depression/anxiety diagnosis. Conclusions: Depression/anxiety in ACHD patients is associated with increased health-care utilization and a higher risk of death. The efficacy of addressing patients' psychosocial needs in optimizing health-care utilization and improving prognosis needs further evaluation. (c) 2018 Elsevier B.V. All rights reserved.

Valvular heart disease is observed in approximately 2% of the general population1. Although the initial observation is often localized (for example, to the aortic or mitral valve), disease manifestations are regularly observed in the other valves and patients frequently require surgery. Despite the high frequency of heart valve disease, only a handful of genes have so far been identified as the monogenic causes of disease2-7. Here we identify two consanguineous families, each with two affected family members presenting with progressive heart valve disease early in life. Whole-exome sequencing revealed homozygous, truncating nonsense alleles in ADAMTS19 in all four affected individuals. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype. Expression analysis using a lacZ reporter and single-cell RNA sequencing highlight Adamts19 as a novel marker for valvular interstitial cells; inference of gene regulatory networks in valvular interstitial cells positions Adamts19 in a highly discriminatory network driven by the transcription factor lymphoid enhancer-binding factor 1 downstream of the Wnt signaling pathway. Upregulation of endocardial Krüppel-like factor 2 in Adamts19 knockout mice precedes hemodynamic perturbation, showing that a tight balance in the Wnt-Adamts19-Klf2 axis is required for proper valve maturation and maintenance.

Abstracts We report the case of a patient with rhabdomyoma of the left ventricular outflow tract, causing severe obstruction at birth. The tumour regressed completely by 6 years of age, leaving a punch-out lesion. The potential for spontaneous regression of these tumours and the formation of a myocardial lesion following rhabdomyoma regression are discussed.

Background: Pulmonary arterial hypertension (PAH) is a significant consequence of congenital heart disease (CHD). Its presence and severity is associated with increased morbidity and mortality. Objectives: To evaluate the clinical and demographic characteristics of adults with congenital heart diseases (ADCHD) and PAH at a single center. Methods: A prospective registry of all patients with PAH was conducted between 2009 and 2015. Results: Thirty-two patients were identified. The mean age at the last visit was 44 years (range 19-77 years). The prevalence of PAH among all ADCHD patients was 6% (95% confidence interval 4.3%-8.4%). A much higher prevalence (53%) was found in patients with Down syndrome. Most patients with PAH had moderate or severe disease. Fifteen patients (47%) were treated with pulmonary vasodilators and 6 (19%) with combination therapy. The average World Health Organization functional class was 2.6. Morbidity included cerebral vascular accident or transient ischemic attack in 22% (mostly in patients with right-to-left shunt) and arrhythmia in 37% of the patients. During a median follow-up of 3.5 years, 5 patients (15.6%) died. Of 13 women with no mental retardation, 11 were or had been married and all had children (between 1 and 13, mean 3.3). Conclusions: Patients with congenital heart disease and PAH have significant morbidity and mortality. PAH is more prevalent in patients with Down syndrome. While pulmonary pressure during the reproductive years was not always known, 27% of women with PAH at the time of the study were multiparous.