Severe Ventricular Dilatation Research Articles

A case of pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension - a happily completed odyssey

Chronic thromboembolic pulmonary hypertension is a rare condition that is usually a consequence of prior acute pulmonary embolism. It is caused by persistent obstruction of pulmonary arteries by organized thrombi resulting in redistribution of blood flow and secondary pulmonary microvascular remodelling. Thus, pulmonary vascular resistance and pulmonary artery pressure are increased leading to right ventricle pressure overload, development of right heart failure and death. In eligible patients pulmonary endarterectomy is the standard of care and it can result in complete normalization of haemodynamics and right ventricular morphology and function. We present the case of a patient with chronic thromboembolic pulmonary hypertension with severe right ventricular dilation and dysfunction and refractory heart failure. After successful pulmonary endarterectomy we observed almost complete normalization of hemodynamics and restoration of right ventricular dimensions and function, as well as significant clinical improvement.

Exercise Capacity and Reoperation Late After Transatrial Fallot Repair

The exercise capacity long after repair of tetralogy of Fallot, when performed exclusively with a transatrial repair, is unclear. It is also unknown whether echocardiography and cardiopulmonary exercise testing can predict the risk of reoperation in this patient group. We retrospectively reviewed the clinical records of 59 patients who underwent cardiopulmonary exercise testing after transatrial Fallot repair at a single centre. Patients underwent cardiopulmonary exercise testing at a mean age of 16.6±4.4 years, and at 15.3±4.1 years after Fallot repair. At testing, the volume of oxygen consumption at maximal exercise (VO2 max) was 71%±13% and the oxygen pulse was 80%±17% of predicted values. Seventeen (17) patients (29%) had a VO2 max superior to 80% of the predicted value. Thirty-two (32) patients (56%) had severe pulmonary regurgitation, three (5%) had moderate pulmonary regurgitation, and 12 (21%) had mild pulmonary regurgitation. After a mean of 7.8±3.9 years following cardiopulmonary exercise testing (23±5.3 years after the repair), 21 (40%) patients underwent reoperation. Right ventricular dilation and systolic function on echocardiography were both significantly associated with subsequent reoperation rates. Patients who had severe right ventricular dilation were eight times more likely to undergo subsequent reoperation (hazard ratio 8.67; 1.82-41.3; p=0.007). No cardiopulmonary exercise testing variable independently predicted reoperation. The exercise capacity at adolescence following transatrial repair of tetralogy of Fallot is maintained at around 70% of predicted values. Only the patients with normal right ventricular size and normal right ventricular function seemed to be protected from reoperation over the subsequent decade. We found no exercise variables which predicted reoperation.

Surgically repaired tetralogy of Fallot in the 7th decade: a late presentation of severe pulmonic regurgitation.

Surgically repaired tetralogy of Fallot (TOF) is a congenital heart disease with a cumulative survival rate of 72% in the 4th decade of life in longitudinal single-cohort studies. Debate surrounds conservative versus surgical management in adults with TOF once pulmonary regurgitation occurs. A 73-year-old male with surgically corrected TOF presented with heart failure symptoms. He underwent ToF repair with a classic right Blalock-Taussig shunt at 2years of age with transannular patching at 18years of age. Echocardiography revealed elevated right ventricular systolic pressures, severe right ventricular dilatation, and pulmonary regurgitation. Our patient's new-onset right-sided heart failure was managed medically with diuresis. He received a new pulmonic valve via percutaneous approach on a later planned hospitalization with resolution of symptoms and improved tricuspid regurgitation. It is a class I recommendation for pulmonic valve intervention once greater than moderate PR occurs; however, medical optimization should take place first. Following adequate RV load optimization, our patient underwent successful transcatheter pulmonic valve implantation with resolution of symptoms and cessation of diuretic.

Septic cardiomyopathy phenotype in the critically ill may depend on antimicrobial resistance

BackgroundSepsis is a life-threatening organ dysfunction, and septic cardiomyopathy (SCM) may complicate the course of the disease. Infection with multidrug-resistant (MDR) pathogens has been linked with worse outcomes. This study aims to evaluate SCM in patients with infections caused by different antimicrobial-resistant phenotypes. MethodThis retrospective study included patients with sepsis/septic shock, hospitalized, and intubated in the intensive care unit of the University Hospital of Larissa between January 2022 and September 2023 with echocardiographic data during the first two days after infection onset. The patients were divided into two groups: non-MDR-SCM group and MDR-SCM group. The cardiac function was compared between the two groups. ResultA total of 62 patients were included in the study. Forty-four patients comprised the MDR-SCM and 18 the non-MDR-SCM group. Twenty-six patients (41.9%) presented with left ventricular (LV) systolic dysfunction, and ≤35% right ventricular fractional area change (RVFAC) was present in 56.4%. LV systolic function was more severely impaired in the non-MDR-SCM group (left ventricular ejection fraction, 35.8% ±4.9% vs. 45.6%±2.4%, P=0.049; LV outflow tract velocity time integral, [10.1±1.4] cm vs. [15.3±0.74] cm, P=0.001; LV-Strain, –9.02%±0.9% vs. –14.02%±0.7%, P=0.001). The MDR-SCM group presented with more severe right ventricular (RV) dilatation (right ventricular end-diastolic area/left ventricular end-diastolic area, 0.81±0.03 vs. 0.7±0.05, P=0.042) and worse RV systolic function (RVFAC, 32.3%±1.9% vs. 39.6%±2.7%, P=0.035; tricuspid annular plane systolic excursion, [15.9±0.9] mm vs. [18.1±0.9] mm, P=0.165; systolic tissue Doppler velocity measured at the lateral tricuspid annulus, [9.9±0.5] cm/s vs. [13.1±0.8] cm/s, P=0.002; RV-strain, –11.1%±0.7% vs. –15.1%±0.9%, P=0.002). ConclusionSCM related to MDR infection presents with RV systolic dysfunction predominance, while non-MDR-SCM is mainly depicted with LV systolic dysfunction impairment.

Abstract 12588: A Hyperactive Heart: A Case of Adderall-Induced Cardiomyopathy

Introduction: Stimulants are commonly used in the treatment of attention deficit hyperactivity disorder (ADHD). Cardiomyopathy is a rare but serious potential side effect of long-term stimulant use, even when done so for therapeutic purposes. Case: We present a 56-year-old female with ADHD and long-term high dose Adderall use who presented for progressively worsening dyspnea over the course of 1 year. Labs were notable for peak hs-troponin 246ng/L and pro-BNP 6598pg/mL. On admission, echocardiogram was notable for reduced left ventricular (LV) ejection fraction (EF) of 20-25% with normal LV wall thickness and mild-moderate valvular disease. ECG showed sinus rhythm 97 bpm, bi-atrial enlargement, normal voltage and no evidence of conduction delay. A left heart catheterization demonstrated no evidence of coronary artery disease. Cardiac MRI at 1.5T was notable for LVEF 18%, severe LV dilation (EDV 189mL/m2), severe right ventricular (RV) dilation (EDV 131mL/m2) with RVEF 26%, native T1 1099 msec, ECV 41%, normal T2*, and a very thin circumferential subendocardial late gadolinium enhancement involving the apical and mid segments (6% of LV mass). TSH, Vitamin B1, and selenium levels were normal, and there was no evidence of tachyarrhythmia throughout her admission. She denied significant alcohol use, illicit substance use, or family history of cardiomyopathy. The absence of paraprotein gap and other stigmata lowered suspicion for amyloidosis. Due to the results of her workup, her Adderall was discontinued as this was thought to be the likely cause of her newly discovered cardiomyopathy. She was discharged home on GDMT with close follow up with advanced heart failure. Discussion: The association between long-term stimulant use and cardiomyopathy is known, but not well described. Common cardiac effects of stimulants include tachycardia, hypertension and increased risk of arrhythmias, all of which are associated with increased workload on the heart and therefore contribute to the development of cardiomyopathy. Although generally rare, long-term use of prescription stimulant medications can contribute to the development of cardiomyopathy and should therefore be used sparingly and for the shortest period possible when necessary for the treatment of ADHD.

Abstract P3126: Atrial Fibrillation Is Associated With Decreased Claudin-5 In Cardiomyocyte

Background: Although it is critically important to understand the underlying molecular and electrophysiological changes that predispose to the induction and maintenance of atrial fibrillation (Af), the underlying mechanism of Af is still poorly defined. Af is characterized as the electrophysiological and membrane integrity abnormality of the atrial cells, and claudin-5, a tight junction protein, may be involved in the pathophysiology of Af, however, the role of claudin-5 in Af is unknown. Methods and Results: Cardiac tissues from the left atrial appendage were obtained from AF patients with rheumatic valvular heart disease undergoing modified radiofrequency ablation maze procedure with approval from local human research ethic review and normal left atrial appendages were obtained from non-AF donors. Western blot, immunofluorescence and transmission electron microscope showed the expression of claudin-5 significantly decreased in cardiomyocytes from left atrium of AF patients compared to non-AF donors. Then proteomics analysis was performed to screen the specific protein expression and signal pathway changed in AF heart tissue vs. non-AF heart tissue, and showed that 83 proteins were downregulated and 102 proteins were upregulated in the left atrial appendage of AF patients. Among them, DAG, CACNA2D2, MYL2 were downregulated and MCU was upregulated. KEGG pathway analysis showed these changes would lead to hypertrophic and dilated cardiomyopathy. Finally, claudin-5 shRNA AAV was injected in mouse left ventricle to knockdown claudin-5 in cardiomyocytes to observe whether change of claudin-5 affects the protein expression in KEGG pathway analysis. We found claudin-5 deficiency caused severe ventricular dilation, ST elevation and arrythmia, and the protein level of DAG, CACNA2D2 and MYL2 were downregulated and MCU was upregulated. Co-immunoprecipitation also confirmed the specific protein-protein interaction between these targeted proteins and claudin-5. Conclusion: We demonstrated that the decrease of claudin-5 in the left atrium of AF patients with rheumatic valvular heart disease. The mechanism of AF might be associated with claudin-5 downregulation-induced decrease of DAG, CACNA2D2, MYL2 and increase of MCU in cardiomyocytes.

The concept of cone creation to treat isolated tricuspid valve dysplasia and the case of a double-orifice tricuspid valve.

Isolated tricuspid valve dysplasia is a rare disease characterized by a wide spectrum of possible anomalies. We describe the use of the Cone concept to treat a patient with a double-orifice tricuspid valve with massive regurgitation and severe deficit of coaptation. Three adult patients with congenital non-Ebstein tricuspid valve anomaly characterized by severe coaptation deficiency underwent tricuspid valve repair applying the Cone technique. In particular, we describe the case of a symptomatic 21-year-old woman with a double-orifice tricuspid valve, with massive regurgitation and severe right ventricular dilatation. The tricuspid valve was transformed from a double-orifice valve into a single-orifice valve. The most superior orifice was opened, and the tissue surrounding the orifice was used to extend the leaflet of the inferior orifice. A Cone was created, and a ring annuloplasty was used to stabilize the result. The patient was discharged home after 7days with trivial residual tricuspid regurgitation and no significant antegrade gradient. The final coaptation height was 2.8cm. The cardiothoracic ratio decreased from 0.77 to 0.59 after 2 months, and symptoms promptly improved. Over the past 2 years, we have applied the Cone creation concept to patients with a severely dysplastic tricuspid valve with excellent early results. One patient had a double-orifice tricuspid valve, and a Cone repair concept was adopted anyway. One orifice was sacrificed, and surrounding tissue was used to augment the leaflets of the other orifice. A Cone was created to improve central coaptation with a good initial result.

Outcomes and prognostic factors of infantile acquired hydrocephalus: a single-center experience

AimTo assess the etiologies and adverse outcomes of infantile acquired hydrocephalus and predict prognosis.MethodsA total of 129 infants diagnosed with acquired hydrocephalus were recruited from 2008 to 2021. Adverse outcomes included death and significant neurodevelopmental impairment which was defined as Bayley Scales of Infant and Toddler Development III score < 70, cerebral palsy, visual or hearing impairment, and epilepsy. Chi-squared was used to evaluate the prognostic factors of adverse outcomes. A receiver operating characteristic curve was calculated to determine the cutoff value.ResultsOf 113 patients with outcome data, 55 patients (48.7%) had adverse outcomes. Late surgical intervention time (13 days) and severe ventricular dilation were associated with adverse outcomes. The combination of surgical intervention time and cranial ultrasonography (cUS) indices was a better predictive marker compared with any of them (surgical intervention time, P = 0.05; cUS indices, P = 0.002). Post-hemorrhage (54/113, 48%), post-meningitis (28/113, 25%), and hydrocephalus arising from both hemorrhage and meningitis (17/113, 15%) accounted for a large proportion of the etiologies in our study. Hydrocephalus occurs secondary to post-hemorrhage and had a favorable outcome compared with other etiologies in both preterm and term groups. A significant difference in adverse outcomes between the inherited error of metabolism as a cause and other etiologies (P = 0.02).ConclusionLate surgical treatment times and severe ventricular dilation can predict adverse outcomes in infants with acquired hydrocephalus. It is crucial to identify the causes of acquired hydrocephalus to predict the adverse outcomes. Research into measures of improving adverse outcomes following infantile acquired hydrocephalus is urgently necessary.

Atrial cardiomyocytes orchestrate the development of profibrotic inflammatory profile associated with atrial fibrillation vulnerability

Atrial fibrillation (AF) is the most common type of arrhythmia encountered clinically. AF risk factors include hypertension, respiratory diseases, obesity, or heart failure. Right heart disease (RHD) has also been described among AF risk factors associated with an atrial inflammatory profile leading to AF. Studies focusing on the cardiomyocytes (CM) orchestration of the tri-factorial relation between RHD, inflammation, and AF are rare. This project aims to characterize the proarrhythmogenic remodeling affecting atrial cardiomyocyte in a rat model of RHD induced by permanent pulmonary trunk constriction. Characterize RHD induced electrophysiological and morphological CM remodeling leading to atrial inflammation and fibrosis, responsible for increased AF susceptibility. Pulmonary artery banding (PAB) was performed on Wistar rats weighing 225–275 g to induce right-sided cardiac hypertrophy and dilation. Sham animals did not receive the PAB surgery. Cardiac echography and electrophysiological studies were performed in vivo on all animals before sacrifice, 21 days post-surgery. Optical mapping was performed ex-vivo on Langendorff-perfused hearts. Freshly isolated right ventricular (RV), as well as right and left atrial (RA and LA) CM, underwent contractility recording in vitro. Histological analyses were performed to assess myocardial fibrosis and Connexin-43 levels. Genes and protein levels were obtained by qPCR and Western-blot analyses respectively. PAB animals developed severe ventricular and atrial myocardial hypertrophy and dilation compared to Sham, as assessed by echocardiography. PAB animals were significantly more susceptible to AF compared to Sham. Freshly isolated CM revealed that overall CM size was increased in PAB animals, and contractile activity of CM was increased compared to the Sham rats. Analyses of targeted protein and gene expression levels by immunohistochemistry and qPCR analyses showed enhanced expression of fibrosis and inflammation-related compounds in whole-RA and RA CM from PAB, compared to Sham. RHD induces electro-physiological remodeling influencing the RA CM contractile machinery which in turn, leads to the development of pro-arrhythmogenic substrate including atrial inflammation, fibrosis, and enhanced AF inducibility.

Longitudinal evolution of central nervous system anomalies in fetuses with open spina bifida fetoscopic repair and correlation with neurologic outcome

Open spina bifida is associated with central nervous system anomalies such as abnormal corpus callosum and heterotopias. However, the impact of prenatal surgery over these structures remains unclear. This study aimed to describe longitudinal changes of central nervous system anomalies before and after prenatal open spina bifida repair and to evaluate their relationship with postnatal neurologic outcomes. Retrospective cohort study of fetuses with open spina bifida who underwent percutaneous fetoscopic repair from January 2009 to August 2020. All women had presurgical and postsurgical fetal magnetic resonance imaging, at an average of 1 week before and 4 weeks after surgery, respectively. We evaluated defect characteristics in the presurgical magnetic resonance images; and fetal head biometry, clivus supraocciput angle, and the presence of structural central nervous system anomalies, such as abnormalities in corpus callosum, heterotopias, ventriculomegaly, and hindbrain herniation, in both presurgical and postsurgical magnetic resonance images. Neurologic assessment was performed using the Pediatric Evaluation of Disability Inventory scale in children who were 12 months or older, covering 3 different sections, namely self-care, mobility, and social and cognitive function. A total of 46 fetuses were evaluated. Presurgery and postsurgery magnetic resonance imaging were performed at a median gestational age of 25.3 and 30.6 weeks, with a median interval of 0.8 weeks before surgery, and 4.0 weeks after surgery. There was a 70% reduction in hindbrain herniation (100% vs 32.6%; P<.001), and a normalization of the clivus supraocciput angle after surgery (55.3 [48.8-61.0] vs 79.9 [75.2-85.4]; P<.001). No significant increase in abnormal corpus callosum (50.0% vs 58.7%; P=.157) or heterotopia (10.8% vs 13.0%; P=.706) was observed. Ventricular dilation was higher after surgery (15.6 [12.7-18.1] vs 18.8 [13.7-22.9] mm; P<.001), with a higher proportion of severe ventricular dilation after surgery (≥15mm) (52.2% vs 67.4%; P=.020). Thirty-four children underwent neurologic assessment, with 50% presenting a global optimal Pediatric Evaluation of Disability Inventory result and 100% presenting a normal social and cognitive function. Children with optimal global Pediatric Evaluation of Disability Inventory presented a lower rate of presurgical anomalies in corpus callosum and severe ventriculomegaly. When analyzed as independent variables to global Pediatric Evaluation of Disability Inventory scale, the presence of abnormal corpus callosum and severe ventriculomegaly showed an odds ratio of 27.7 (P=.025; 95% confidence interval, 1.53-500.71) for a suboptimal result. Prenatal open spina bifida repair did not change the proportion of abnormal corpus callosum nor heterotopias after surgery. The combination of presurgical abnormal corpus callosum and severe ventricular dilation (≥15 mm) is associated with an increased risk of suboptimal neurodevelopment.

317 IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR IN ARRHYTMIC MITRAL VALVE PROLAPSE: YOU'LL BE CONSIDER IT FOR PRIMARY PREVENTION OF SUDDEN CARDIAC DEATH?

Abstract A 50-year-old female with a history of bileaflet mitral valve prolapse (MVP) was admitted to our Department for persistent palpitation. Physical examination revealed a mid-systolic click, followed by a mid-to-late apical systolic murmur. The electrocardiogram showed sinus rhythm with negative T-waves in inferior leads and repetitive polymorphic premature ventricular contractions (PVCs) with a right bundle branch block pattern and superior axis morphology suggestive of a possible origin from the posterior papillary muscle. The echocardiography confirmed normal ventricular ejection fraction, bileaflet MVP with moderate regurgitation, systolic curling and mitral annulus disjunction. Exercise stress testing demonstrated an increase of polymorphic PVCs during maximum effort. The cardiac magnetic resonance showed an underlying late gadolinium enhancement at the level of the papillary muscles and in the inferobasal region. After a multidisciplinary evaluation, a transvenous implatable cardioverter defibrillator (ICD) was implanted for primary prevention without clear indications deriving from current guidelines. After eleven years, the patients experienced two appropriate shocks due to polymorfic ventricular tachycardia while she was sleeping. Furthermore, the patient underwent successful mechanical transvenous lead extraction and ICD re-implantation for lead failure. During this hospitalization a subsequent echocardiography detected severe ventricular dilatation with moderate systolic disfunction. Conclusion Our report demonstrated that MVP represents potentially cause of life-threatening ventricular arrhythmias and tachycardia induced cardiomyopathy. Beta-blockers are often inadequate in order to reduce PVCs burden. We need more arrhytmic predictors to assestment of sudden cardiac death risk and evaluate ICD for primary prevention. Obtain left ventricular function recovery is difficult and it requires a multidisciplinary approach. It will be important in the future to better define the role will play cathether ablation and mitral valve repair or replacement to prevent malignant arrhytmias.

Epidemiology of post-hemorrhagic ventricular dilatation in very preterm infants.

To describe the incidence, trends, management's variability and short-term outcomes of preterm infants with severe post-hemorrhagic ventricular dilatation (sPHVD). We reviewed infants &lt;33 weeks' gestation who had PHVD and were admitted to the Canadian Neonatal Network between 2010 and 2018. We compared perinatal characteristics and short-term outcomes between those with sPHVD and those with mild/moderate PHVD and those with and without ventriculo-peritoneal (VP) shunt. Of 29,417 infants, 2439 (8%) had PHVD; rate increased from 7.3% in 2010 to 9.6% in 2018 (P = 0.005). Among infants with PHVD, sPHVD (19%) and VP shunt (29%) rates varied significantly across Canadian centers and between geographic regions (P &lt; 0.01 and P = 0.0002). On multivariable analysis, sPHVD was associated with greater mortality, seizures and meningitis compared to mild/moderate PHVD. Significant variability in sPHVD and VP shunt rates exists between centers and regions in Canada. sPHVD was associated with increased mortality and morbidities.

P1514: MULTI-PARAMETRIC CARDIAC MAGNETIC RESONANCE FOR RISK PREDICTION OF HEART FAILURE DEATH IN THALASSEMIA MAJOR

Background: Iron-induced heart failure (HF) is the main cause of mortality in patients with thalassemia major (TM). Cardiovascular Magnetic Resonance (CMR) plays a key role in the management of these patients, assessing myocardial iron overload (MIO), biventricular function, and myocardial fibrosis. Aims: We evaluated the prognostic value of CMR parameters in predicting death for HF. Methods: We followed prospectively 1681 white TM patients who performed a baseline CMR exam within the Myocardial Iron Overload in Thalassemia (MIOT) network. All prognostic variables associated with the outcome at the univariate Cox model were placed in the multivariate model and were ruled out if they did not significantly improve the adjustment. Results: At baseline the mean age was 31.11±9.01 years and 874 (52.0%) patients were females. During a mean follow-up of 4.76±2.07 years, 47.3% of the patients changed at least once the chelation regimen, that is switched to a different type of chelator or underwent dose/frequency modification. Sixteen (1.0%) patients died for heart failure. No association was detected between age or gender and HF mortality. Patients who died for HF had significantly lower baseline global heart T2* values (19.45±15.11 ms vs 29.52±12.02 ms, P=0.006) and significantly higher baseline MR liver iron concentration (LIC) values (19.17±15.95 mg/g dw vs 8.72±10.63 mg/g dw, P=0.005) than patients still alive or died for a different cause, but the presence of a pathologic MRI LIC (>3 mg/g dw) was not associated with an increased risk of HF mortality. Heart iron, ventricular dysfunction, and ventricular dilatation were significant univariate prognosticators. In the multivariate analysis the independent predictive factors were a global heart T2*<10 ms (compared to a global heart T2*≥20 ms) (hazard ratio-HR=5.38, 95%CI=1.79-16.22, P=0.003) and ventricular dilatation (HR=4.59, 95%CI=1.55-13.59, P=0.006). The Figure shows the Kaplan–Meier survival curves. The log-rank test revealed a significant difference in the curves for each predictor (severe MIO: P<0.0001 and ventricular dilatation: P<0.0001). Image:Summary/Conclusion: We detected few HF deaths thanks to a MR-guided patient-specific adjustment of the chelation therapy. Severe MIO and ventricular dilatation identified TM patients at high risk for heart failure death. So, a widespread program using CMR exploiting its multi-parametric potential can have considerable power for further opening the prognosis of TM patients.

Claudin-5a is essential for the functional formation of both zebrafish blood-brain barrier and blood-cerebrospinal fluid barrier

BackgroundMammalian Claudin-5 is the main endothelial tight junction component maintaining blood-brain barrier (BBB) permeability, while Claudin-1 and -3 seal the paracellular space of choroid plexus (CP) epithelial cells contributing to the blood-cerebrospinal fluid barrier (BCSFB). In zebrafish, two paralogs of claudin-5a and -5b are expressed while their roles in the formation of BBB and BCSFB are unclear.MethodsThe expression patterns of Claudin-5a and -5b in zebrafish brains were systematically analyzed by immunofluorescence (IF) assay. The developmental functions of Claudin-5a and -5b were characterized by generating of claudin-5a and -5b mutants respectively. Meanwhile, the cerebral inflammation and cell apoptosis in claudin-5a-/- were assessed by live imaging of transgenic zebrafish, RT-qPCR, IF, and TUNEL assay. The integrity of BBB and BCSFB was evaluated by in vivo angiographic and dye permeation assay. Finally, RT-qPCR, whole-mount RNA in situ hybridization (WISH), and transmission electron microscopy (TEM) analyses were performed to investigate the development of cerebral vessels and choroid plexus.ResultsWe showed that Claudin-5a and -5b are both expressed in zebrafish cerebrovascular endothelial cells (ECs). In addition, Claudin-5a was strongly expressed in CP epithelial cells. Loss of Claudin-5b showed no effect on zebrafish vasculogenesis or BBB function. In contrast, the knockout of claudin-5a caused a lethal phenotype of severe whole-brain oedema, ventricular dilatation, and cerebral hernia in zebrafish larvae, although the cerebral vasculogenesis and the development of CP were not altered. In claudin-5a-/- , although ultrastructural analysis of CP and cerebral capillary showed intact integrity of epithelial and endothelial tight junctions, permeability assay indicated a disruption of both BBB and BCSFB functions. On the molecular level, it was found that ZO-1 was upregulated in the CP epithelium of claudin-5a-/-, while the notch and shh pathway responsible for CP development was not affected due to loss of Claudin-5a.ConclusionsOur findings verified a non-functional role of zebrafish Claudin-5b in the BBB and identified Claudin-5a as the ortholog of mammalian Claudin-5, contributing to the development and the functional maintenance of both BBB and BCSFB.

Right ventricular dysfunction in patients with COVID-19 pneumonitis whose lungs are mechanically ventilated: amulticentre prospective cohort study.

SummaryCardiovascular complications due to COVID‐19, such as right ventricular dysfunction, are common. The combination of acute respiratory distress syndrome, invasive mechanical ventilation, thromboembolic disease and direct myocardial injury creates conditions where right ventricular dysfunction is likely to occur. We undertook a prospective, multicentre cohort study in 10 Scottish intensive care units of patients with COVID‐19 pneumonitis whose lungs were mechanically ventilated. Right ventricular dysfunction was defined as the presence of severe right ventricular dilation and interventricular septal flattening. To explore the role of myocardial injury, high‐sensitivity troponin and N‐terminal pro B‐type natriuretic peptide plasma levels were measured in all patients. We recruited 121 patients and 118 (98%) underwent imaging. It was possible to determine the primary outcome in 112 (91%). Severe right ventricular dilation was present in 31 (28%), with interventricular septal flattening present in nine (8%). Right ventricular dysfunction (the combination of these two parameters) was present in seven (6%, 95%CI 3–13%). Thirty‐day mortality was 86% in those with right ventricular dysfunction as compared with 45% in those without (p = 0.051). Patients with right ventricular dysfunction were more likely to have: pulmonary thromboembolism (p < 0.001); higher plateau airway pressure (p = 0.048); lower dynamic compliance (p = 0.031); higher plasma N‐terminal pro B‐type natriuretic peptide levels (p = 0.006); and raised plasma troponin levels (p = 0.048). Our results demonstrate a prevalence of right ventricular dysfunction of 6%, which was associated with increased mortality (86%). Associations were also observed between right ventricular dysfunction and aetiological domains of: acute respiratory distress syndrome; ventilation; thromboembolic disease; and direct myocardial injury, implying a complex multifactorial pathophysiology.

Ventricular tachycardia in Arrhythmogenic Right Ventricular Cardiomyopathy: How to Manage?

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a condition characterized by fibrofatty replacement of the RV myocardium due to genetic abnormality. Structural changes may be absent or minor in the early stages of the disease and be localized in a specific region of the RV. Clinically it appears as RV electrical instability. To reduce the risk of arrhythmic events or sudden cardiac death, device therapy and pharmacotherapy may be recommended. In this paper, we describe a case of a female with ARVC and a brief discussion based on a literature review. The patient presented with chest discomfort accompanied by palpitation. An electrocardiogram (ECG) showed ventricular tachycardia of RV apex origin, and convert to symmetric inverted T-waves and probable epsilon waves in the right precordial leads, mimicking a pseudo-right bundle branch block (RBBB) pattern following electrical cardioversion. The parasternal short-axis view of echocardiography shows severe right ventricular dilatation. Subsequent workup using CMR was planned but the patient refused. We diagnosed this patient with ventricular tachycardia on a background of suspicious arrhythmogenic right ventricular cardiomyopathy. We were able to provide accurate diagnosis and treatment, avoiding potentially fatal consequences. As a result, it is critical to recognize potential ARVC ECG findings and to know when to pursue further research and implement therapies.

Meeting abstracts from the 15th international conference on neonatal and childhood pulmonary vascular disease

Meeting abstracts from the 15th international conference on neonatal and childhood pulmonary vascular disease

Heart failure presentation thirty years after tricuspid valvectomy for infective endocarditis

Heart failure presentation thirty years after tricuspid valvectomy for infective endocarditis

179 ICD or not ICD? A difficult choice for a young patient presenting with palpitations in emergency department

Abstract A fit-and-well 52-year-old worker, with negative familiar story, was admitted to Emergency Department (ED) with haemodynamically unstable but well bore broad complex tachycardia of 180 b.p.m. (Figure 1). Twenty years before the patient had heart-surgery to repair atrial septal venous sinus defect with patch. The defect determined anomalous pulmonary venous return in right atrium with left to right shunt and moderate pulmonary hypertension. The surgery, 20 years before, was complicated by a single event of supraventricular tachycardia pharmacology resolved. Next follow-up was normal although at transthoracic echocardiography severe right ventricular (RV) dilation was reported. In the ED the patient had palpitation but not chest pain or dyspnoea. General clinical examination was normal but he was hypertensive (170/137 mmHg) and with heart rate of 180 b.p.m. Valsalva manoeuver was performed and adenosine (6 mg–12 mg–12 mg) was administered without benefit. Eventually, the patient was cardioverted to sinus rhythm with a single 100 J shock. His baseline ECG (Figure 2) showed sinus rhythm, normal axis, as well as right bundle branch block and T-wave inversion in leads V1–V4 and a waves with a small spike upward in lead V1 which represent characteristic epsilon waves. Successively patient was admitted to Cardiology Department where transthoracic echocardiography showed severe RV dilation and moderate hypokinesia with a tricuspid annular plane excursion of 15 mm, TAV 9.6 cm/s, fractional area change of 29%. The right atrium was moderate dilated (volume 70 ml, indexed volume 35.53 ml/m2). Left chambers were normal. No shunts were observed. An electrophysiology study with isoprenaline infusion was performed but no arrhythmias were induced. Cardiac magnetic resonance imaging (MRI) was normal save for global RV dilatation, increased RV end diastolic volume (156 ml/m2), and global RV systolic dysfunction (reduction of RV ejection fraction 31%). Arrhythmogenic cardiomyopathy was excluded as patient’s background suggested RV dilation was due the overload caused by the history of left–right shunt. Blood tests and personal history negative initially exclude myocarditis and cardiac MRI confirmed the absence of oedema. An accurate ECG analysis excluded Brugada syndrome. Following discussion between electrophysiologists, clinical cardiologists, and the patient who first need to be informed, trans-venous ICD was implanted. 179 Figure 1ECG in ED. Figure 2 Baseline ECG. Figure 3 Cardiac MRI.

Predictive value of brain MRI at term-equivalent age in extremely preterm children on neurodevelopmental outcome at school-age.

This study's objective was to correlate the abnormalities in brain MRIs performed at corrected-term age for minor or moderate neurocognitive disorders in children school-age born extremely premature (EPT) and without serious sequelae such as autism, cerebral palsy, mental impairment. Data were issued from a cross-sectional multicenter study (GP-Qol study, number NCT01675726). Clinical examination and psychometric assessments were performed when the children were between 7 and 10years old during a day-long evaluation. Term-equivalent age brain MRIs on EPT were analyzed with a standardized scoring system. There were 114 children included in the study. The mean age at the time of evaluation, was 8.47years old (± 0.70). 59% of children with at least one cognitive impairment and 53% who had a dysexecutive disorder. Only ten EPT (8.7%) presented moderate to severe white and grey matter abnormalities. These moderate to severe grey matter abnormalities were associated with at least two abnormal executive functions [OR 3.08 (95% CI 1.04-8.79), p = 0.04] and language delay [OR 3.25 (95% CI 1.03-9.80), p = 0.04]. These results remained significant in the multivariate analysis. Moderate to severe ventricular dilatation abnormalities (15%, n = 17) were associated with ideomotor dyspraxia [OR 7.49 (95% CI 1.48-35.95), p = 0.02] and remained significant in multivariate analysis [OR 11.2 (95% CI 1.45-131.4), p = 0.02]. Biparietal corrected diameters were moderate abnormal in 20% of cases (n = 23) and were associated to visuo spatial integration delay [OR 4.13 (95% CI 1.23-13.63), p = 0.02]. Cerebral MRI at term-equivalent age with scoring system analysis can provide information on long-term neuropsychological outcomes at school-age in EPTs children having no severe disability.