Zebrafish as a Model System for Brugada Syndrome.

Brugada syndrome (BrS) is an inheritable cardiac arrhythmogenic disease, associated with an increased risk of sudden cardiac death. It is most common in males around the age of 40 and the prevalence is higher in Asia than in Europe and the United States. The pathophysiology underlying BrS is not completely understood, but several hypotheses have been proposed. So far, the best effective treatment is the implantation of an implantable cardioverter-defibrillator (ICD), but device-related complications are not uncommon. Therefore, there is an urgent need to improve diagnosis and risk stratification and to find new treatment options. To this end, research should further elucidate the genetic basis and pathophysiological mechanisms of BrS. Several experimental models are being used to gain insight into these aspects. The zebrafish (Danio rerio) is a widely used animal model for the study of cardiac arrhythmias, as its cardiac electrophysiology shows interesting similarities to humans. However, zebrafish have only been used in a limited number of studies on BrS, and the potential role of zebrafish in studying the mechanisms of BrS has not been reviewed. Therefore, the present review aims to evaluate zebrafish as an animal model for BrS. We conclude that zebrafish can be considered as a valuable experimental model for BrS research, not only for gene editing technologies, but also for screening potential BrS drugs.

Hypertrophic cardiomyopathy and left ventricular non-compaction: Distinct diseases or variant phenotypes of a single condition?

Hypertrophic cardiomyopathy (HCM) is a genetically determined myocardial disease characterized by an increased thickness of the left ventricle (LV) wall that cannot be solely attributed to abnormal loading conditions. HCM may present with an intraventricular or LV outflow tract obstruction, diastolic dysfunction, myocardial fibrosis and/or ventricular arrhythmias. Differentiating HCM from other diseases associated with LV hypertrophy, such as hypertension, aortic stenosis, or LV non-compaction (LVNC), can at times be challenging. LVNC is defined by excessive LV trabeculation and deep recesses between trabeculae, often accompanied by increased LV myocardial mass. Previous studies indicate that the LVNC phenotype may be observed in up to 5% of the general population; however, in most cases, it is a benign finding with no impact on clinical outcomes. Nevertheless, LVNC can occasionally lead to LV systolic dysfunction, manifesting as a phenotype of dilated or non-dilated left ventricular cardiomyopathy, with an increased risk of thrombus formation and arterial embolism. In extreme cases, where LVNC is associated with a very thickened LV wall, it can even mimic HCM. There is growing evidence of an overlap between HCM and LVNC, including similar genetic mutations and clinical presentations. This raises the question of whether HCM and LVNC represent different phenotypes of the same disease or are, in fact, two distinct entities.

Papillary Craniopharyngioma: an integrative and comprehensive review.

Papillary craniopharyngioma (PCP) is a rare type of tumor, comprising ∼20% of all craniopharyngioma (CP) cases. It is now recognized as a separate pathological entity from the adamantinomatous type. PCPs are benign tumors, classified as WHO grade 1, characterized by non-keratinizing squamous epithelium. They typically grow as solid and round papillomatous masses or as unilocular cysts with a cauliflower-like excrescence. PCPs primarily occur in adults (95%), with increased frequency in males (60%) and predominantly affect the hypothalamus. Over 80% of these tumors are located in the third ventricle, expanding either above an anatomically intact infundibulum (strictly third ventricle tumors) or within the infundibulo-tuberal region of the third ventricle floor. Clinical manifestations commonly include visual deficits and a wide range of psychiatric disturbances (45% of patients), such as memory deficits and odd behavior. MRI can identify up to 50% of PCPs by the presence of a basal duct-like recess. Surgical management is challenging, requiring complex approaches to the third ventricle and posing significant risk of hypothalamic injury. The endoscopic endonasal approach allows radical tumor resection and yields more favorable patient outcomes. Of intriguing pathogenesis, over 90% of PCPs harbor the somatic BRAFV600E mutation, which activates the mitogen-activated protein kinase (MAPK/ERK) signaling pathway. A phase 2 clinical trial has demonstrated that PCPs respond well to BRAF/MEK inhibitors. This comprehensive review synthesizes information from a cohort of 560 well-described PCPs and 99 large CP series including PCP cases published from 1856-2023 and represents the most extensive collection of knowledge on PCPs to date.

Right ventricular function in mitral stenosis: plays a fundamental role.

The importance of the right ventricle (RV) was neglected or forgotten for decades. The RV has an essential function in cardiovascular physiology and pathology. The RV dysfunction is one of the causes of morbidity and mortality in valvular heart disease (VHD), especially in mitral stenosis (MS). Right ventricular systolic and diastolic function are important for the determination of clinical symptoms, exercise functional capacity, pre-procedure survival, and post-procedure outcome in patients with MS. Right ventricular dysfunction in MS with a sign of systemic venous congestion is easy to recognize, but MS without clinical evidence of RV dysfunction has not been studied. Detecting RV dysfunction earlier in MS is important in clinical practice.

Comparison of pulmonary artery growth between ductus stent and systemic-to-pulmonary shunt as single-ventricle palliation.

OBJECTIVE: We aimed to compare the pulmonary artery (PA) growth between infants with univentricular hearts who underwent a ductus stenting (DS) and those who received a systemic to pulmonary shunt (SPS) as an initial palliation. METHODS: All infants with ductal-dependent pulmonary blood flow who underwent initial palliation with either a DS or SPS between 2009 and 2022 in our institution were reviewed. PA development was compared between the groups using the PA index and the symmetry index. RESULTS: A total of 130 patients were evaluated including 49 patients after DS and 81 after SPS. The most frequent primary diagnosis was tricuspid atresia in 27, followed by pulmonary atresia with intact ventricular septum in 19. At stage II palliation, PA index (p=0.926), right PA index (p=0.692), left PA index (p=0.297) and the symmetry index (p=0.650) were similar between the groups. At stage III Fontan completion, PA index (p=0.115), right PA index (p=0.868), and the symmetry index (p=0.144) were similar between the groups. However, left PA index (60 vs. 74mm2/m2, p=0.015) was lower, and the incidence of veno-venous collaterals (24.2 vs. 7.8%, p=0.036) was higher in DS group compared to SPS group. Freedom from PA interventions between stage II and III palliation was lower in DS group compared to SPS group (p=0.009). CONCLUSIONS: In patients after DS in infants with univentricular heart, freedom from PA interventions after stage II was lower and the left PA index was smaller, compared to those after SPS. Long-term outcomes after the Fontan procedure should be addressed in patients after DS.

Prognostic Value of Echocardiographic Coupling Metrics in Systemic Sclerosis-Associated Pulmonary Vascular Disease.

BACKGROUND: Ineffective right ventricular (RV) adaptation to increasing pulmonary arterial (PA) afterload in pulmonary vascular disease (PVD) significantly contributes to morbidity and mortality. PVD in systemic sclerosis (SSc) arises through various mechanisms, yet detecting abnormal contractile response remains challenging. Here, we examine whether echocardiographic RV-PA coupling metrics correlate with invasive pressure-volume (PV) loops, enhancing the prediction of adverse clinical outcomes in SSc-PVD patients. METHODS: Prospectively enrolled patients with SSc-PVD with paired echocardiogram and PV loops were included. Linear regression and receiver-operating curve (ROC) analysis were used to assess the relationship between tricuspid annular plane systolic excursion (TAPSE)/PA systolic pressure (PASP), fractional area change (FAC)/PASP, tissue Doppler velocity (TDI S')/PASP, RV free wall strain (RVFWS)/PASP and coupling thresholds defined by end-systolic to end-arterial elastance (Ees/Ea), obtained by the multi-beat method. The contribution of right atrial strain (RAS) to RV-PA coupling parameters was also investigated. Kaplan-Meier analysis was used to identify the relationship between coupling ratios and composite outcomes including clinical worsening, lung transplant, and death. RESULTS: 42 patients with SSc were studied with mean age 59 ± 12 years, 91% female and varying degrees of PVD: mPAP 29.5 ± 12.8 mmHg, PVR 4.7 ± 4.2 WU, PCWP 10.3 ± 4.1 mmHg. Echocardiographic coupling metrics including TAPSE/PASP, FAC/PASP, TDI S'/PASP, RVFWSglobal and RVFWSbasal/PASP, and RASreservoir/PASP were linearly associated with Ees/Ea. At cut-points obtained through ROC analysis, all ratios were predictive of RV-PA uncoupling, defined by Ees/Ea, and composite outcomes. Additionally, RASreservoir/RVFWS correlated with Ees/Ea even after adjustment for PASP, suggesting that diminished RAS further impacts RV performance and coupling. CONCLUSION: Echocardiographic RV-PA coupling ratios strongly correlate with invasive Ees/Ea and predict adverse clinical outcomes in SSc patients across the spectrum of PVD. Further, we demonstrate how RAS impacts RV performance. These findings may refine risk stratification and prognostication in this at-risk cohort.

Endoscopic Ventriculocisternostomy with Stent Placement for Trapped Temporal Horn.

BACKGROUND: Trapped temporal horn (TTH) is a subtype of focal obstructive hydrocephalus. Although a ventriculoperitoneal shunt (VPS) is a traditional treatment approach, it poses risks of shunt failure and infection. The emergence of neuroendoscopy has led to an increased interest in ventriculocisternostomy as an alternative. This study aimed to evaluate the efficacy and safety of endoscopic ventriculocisternostomy with stent placement (EVSP) for TTH. METHODS: We collected data of TTH cases treated with EVSP at our institutions between September 2013 and September 2021 and evaluated baseline characteristics and outcomes. A ventricular stoma was created at the medial wall of the abnormally enlarged temporal horn using a neuroendoscope, and a ventricular stent tube with multiple side holes was placed through the stoma to maintain patency. RESULTS: The study included 10 patients (4 women and 6 men) with a mean age of 56.7±19.7 years. The average follow-up period was 35.0 months (range, 1-96 months). The underlying pathologies were postoperative scarring (5 cases), intraventricular tumor (3 cases), and extraventricular tumor (2 cases). There were no procedural complications; however, one patient experienced recurrence and underwent additional cisternostomy. All patients exhibited partial or complete resolution of the preoperative symptoms and demonstrated shrinkage of the trapped ventricle, with a mean reduction rate of 84.5%±14.9%. CONCLUSIONS: EVSP is a safe and feasible option for the treatment of TTH and is a viable alternative to VPS.

Hepatic T1 Mapping as a Novel Cardio-Hepatic Axis Imaging Biomarker Early after STEMI.

BACKGROUND: The hepatic response after ST-elevation myocardial infarction (STEMI) may be associated with mortality and morbidity. We aimed to assess the cardio-hepatic axis post-STEMI using cardiovascular magnetic resonance (CMR). METHODS: This prospective, observational, single-centre study included consecutive STEMI patients who underwent CMR after primary angioplasty from January 2015 to January 2019. Standard infarct characteristics were analysed, and hepatic T1 and hepatic extracellular volume (ECV) were assessed using pre- and post-contrast T1-mapping sequences. The primary endpoint was the relationship between native hepatic T1-values and ischemic right ventricular (RV) involvement, determined by RV ejection fraction (EF) dysfunction and/or the presence of RV acute myocardial infarction (AMI). The diagnostic performance of hepatic T1 values for detecting RV involvement was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: Of 177 consecutive STEMI patients undergoing CMR, 142 were included. Patients with RV ischemic involvement, compared to those without, had significantly higher native hepatic T1 (p < 0.001) and hepatic ECV (p = 0.016). Hepatic T1 values demonstrated a good diagnostic performance in detecting RV involvement (AUC 0.826, p < 0.001) and correlated positively with NT-proBNP values (r = 0.754, p < 0.001). Patients with high hepatic T1 values (>605 ms) had significantly higher NT-proBNP levels (<0.001), larger RV end-diastolic volume (p < 0.001), lower RV-EF (p < 0.001), and a higher prevalence of RV AMI (p = 0.022) compared to those with hepatic T1 ≤ 605 ms, while left ventricular EF and infarct size were similar. Multivariable logistic regression analysis identified RV-EF (p = 0.010) and NT-proBNP values (p < 0.001) as independent predictors of increased hepatic T1 values. Patients with increased hepatic T1 values had a higher rate of re-hospitalization for heart failure at 17-month follow-up (12.1% vs 2.0%, p = 0.046). CONCLUSIONS: Hepatic T1 mapping has emerged as a possible novel imaging biomarker of the cardio-hepatic axis in STEMI, being associated with RV involvement and increased NT-proBNP values.

Assessment of Biventricular Systolic and Diastolic Function Using Conventional and Strain Echocardiography in Children with Sickle Cell Disease Surviving 1-year After Hematopoietic Stem Cell Transplant.

Hematopoietic stem cell transplant (HSCT) is a potentially curative therapy for children with sickle cell disease (SCD). The effects of HSCT on ventricular function are not well characterized in children with SCD. Echocardiograms from children with SCD who underwent HSCT between 2007 and 2017 were retrospectively analyzed before and 1-year after HSCT. Left ventricular (LV) volumes, mass, and ejection fraction were calculated by the 5/6 area*length method. LV end-diastolic and systolic dimensions, septal, and posterior wall thickness, and fractional shortening were measured by M-mode. Mitral and tricuspid inflow Dopplers (E and A waves) as well as mitral, tricuspid, and septal tissue Dopplers (E', A') were assessed. E/A, E'/A' and E/E' ratios were calculated. Biventricular strain imaging was performed using speckle-tracking echocardiography. Peak global systolic longitudinal and circumferential LV strain, and global longitudinal right ventricular strain, as well as early and late diastolic strain rate, were measured on LV apical 4-chamber, LV short-axis mid-papillary, and RV apical views, respectively. Forty-seven children (9.7 ± 5.5 years, 60% male) met inclusion criteria. Pre-HSCT, subjects had mild LV dilation with normal LV systolic function by conventional measure of ejection fraction and fractional shortening. There was a significant reduction in LV volume, mass, and ejection fraction after HSCT, but measurements remained within normal range. LV longitudinal and circumferential strain were normal pre-HSCT and showed no significant change post-HSCT. RV strain decreased after HSCT, but the absolute change was small, and mean values were normal both pre- and post-HSCT. Conventional measures of diastolic function were all normal pre-HSCT. Post-HSCT there was a reduction in select parameters, but all parameters remained within normal range. Early and late diastolic strain rate parameters showed no significant change from pre- to post-HSCT. At one-year after HSCT in children with SCD conventional measures of systolic and diastolic function are within normal limits. Except for a small decrease in RV systolic strain with values remaining within normal limits, systolic strain and diastolic strain rate values did not significantly change 1-year after HSCT.

Obstructive hydrocephalus due to choroid plexus carcinoma of third ventricle in pediatric: A rare case report.

Choroid plexus carcinoma (CPC) is an uncommon tumor that accounts for less than 1% of all pediatric brain tumors. CPC usually originates in the lateral ventricle, followed by the fourth ventricle; the incidence in the third ventricle is only 5% of all CPC cases (children and adults). We report an extremely rare tumor arising from the choroid plexus of the third ventricle in a 6-year-old child with progressive headache, macrocephaly, left hemiparesis, and sunset eyes. The imaging found a well-defined, lobulated mass with strong enhancement in the posterior part of the third ventricle, resulting in obstructive hydrocephalus. The patient underwent an endoscopic biopsy and histopathological examination, which resulted in choroid plexus carcinoma.

The effects of standardized intravenous treprostinil in pulmonary arterial hypertension patients after total cavo-pulmonary connection procedure.

OBJECTIVE: Total cavo-pulmonary connection (TCPC) is a palliative treatment for single ventricular malformations. For high-risk patients (preoperative mean pulmonary arterial pressure, mPAP > 15 mmHg), between the inhaled and oral targeted medications, the application of intravenous treprostinil as a bridge therapy to achieve "seamless" management is core postoperative treatment. This study intends to explore the effect of different administration regimens on early postoperative recovery. METHODS: This was a retrospective cohort study. High-risk pediatric patients (age ≤ 14 years) who underwent TCPC procedure in Fu Wai Hospital from 2015 to 2022 were included. Since the regimen of treprostinil was standardized in our center in 2021, the patients in 2020 and before were included in group 1, patients in 2021 and 2022 were included in group 2. The hemodynamic parameters were compared before and after the maintenance dose of treprostinil. The differences of demographic characteristics, surgical data and postoperative recovery were compared between the two groups. RESULTS: A total of 51 pediatric patients were included. Group 1 included 35 patients who received treprostinil at 1-3 postoperative days and an average dose of 12 ± 4 ng/(kg·min). Group 2 included 16 patients who received treprostinil within postoperative 1 day and an average dose of 22 ± 7 ng/(kg·min). There were no significant differences between the two groups in terms of age, weight, preoperative percutaneous oxygen saturation and mPAP,  heterotaxy syndrome, TCPC procedure type, other concurrent procedure, cardiopulmonary bypass time and aortic cross-clamp proportion (p > 0.05). After 24 h of treprostinil treatment, the mPAP in group 1 reduced from 17 ± 3 mmHg to 15 ± 2 mmHg (p < 0.001), and in group 2 from 17 ± 2 mmHg to 14 ± 2 mmHg (p < 0.001), with no difference between groups. In the postoperative recovery, patients in Group 2 exhibited a reduced duration of mechanical ventilation, 19 (11, 25) hours vs 69 (23, 189) hours, p = 0.001; a shorter stay in the ICU, 8 (6, 12) days vs 16 (9,26) days, p = 0.006; and a shorter postoperative length of stay, 27 (17,55) days vs 39 (29,58) days, p = 0.032. Patients in Group 2 also exhibited a lower incidence of thromboembolic events, 0 (0/26) vs 26% (9/35), p = 0.043; and the need for renal replacement therapy, 0 (0/26) vs 31% (11/35), p = 0.011. CONCLUSION: Treprostinil reduces pulmonary artery pressure after TCPC procedure. The standardized application of treprostinil may improve the postoperative recovery which should be proven by randomized controlled trials or matched cohort studies in the future.

Fontan Conversion in an Adult With Hypoplastic Left Heart Syndrome: A 38-Year-Old Norwood Success.

A 38-year-old man with a functional single ventricle secondary to hypoplastic left heart syndrome presented with exertional fatigue. His last palliation was an intra-atrial conduit Fontan procedure. Comprehensive evaluation showed elevated liver enzyme values and a small, calcified conduit. Successful conversion to a nonfenestrated extracardiac conduit Fontan was performed with normalization of his liver enzyme values.

Prenatally Diagnosed Case of Successful Survival of an Unguarded Mitral Valve Orifice.

An unguarded mitral valve orifice is a rare condition characterized by a thinned, hypocontractile left ventricle on fetal echocardiogram. This is the first report of an unguarded mitral valve orifice with a double-outlet right ventricle and intact ventricular septum diagnosed prenatally from these typical ultrasound features.

Two-dimensional echocardiographic right heart ratios for assessment of right heart size in dogs: Reference intervals and reproducibility.

BACKGROUND: Reference intervals for simple body weight-independent measurements of right heart size and function are limited. OBJECTIVES: Generate reference intervals for measurements of right heart size indexed to the long-axis aortic valve diameter (AoD) or corresponding left heart structure (right heart ratios) and describe the reproducibility of these indices. ANIMALS: Ninety healthy adult dogs of variable body weight. METHODS: Prospective study. All dogs underwent an echocardiogram performed by the same operator. Numerous linear 2-dimensional measurements of right heart size and function from different imaging planes were performed. Eight dogs underwent repeated echocardiograms by the same operator on 3 different days, and 3 different operators performed repeated echocardiograms on the same day. Reference intervals were generated using the Clinical Laboratory Standards Institute method. Reproducibility was quantitated using coefficients of variation (CVs) and reproducibility coefficients. RESULTS: Reference intervals for right heart ratios were generated and allow simple assessments of right heart size and function that do not require a scaling exponent or body weight table. Right heart ratios did not show clinically relevant associations with body weight. All CVs were <22.6%. In general, CVs for right heart measurements indexed to AoD were lower compared with right heart measurements indexed to the corresponding left heart structure. CONCLUSIONS AND CLINICAL IMPORTANCE: Reference intervals for simple body weight-independent right heart ratios are available to help detect abnormalities of right heart size and function. Reproducibility coefficients might be useful to help identify meaningful changes in right heart size during serial evaluations.

The Relationship Between Right Ventricular Longitudinal Strain and Adverse Outcome in Hypertensive Patients: 10-year Follow-up.

INTRODUCTION: Previous studies showed the importance of right ventricular (RV) remodeling in patients with arterial hypertension and RV longitudinal strain was recognized as very sensitive parameter for detection of subtle cardiac impairment. However, its clinical importance in arterial hypertension has not been established so far. AIM: The present study aimed to evaluate the association between RV longitudinal strain (global and free-wall) on adverse outcomes measured by MACE in the large group of hypertensive patients who were followed for mean period of 10 years. METHODS: This retrospective study finally included 544 hypertensive patients who underwent full echocardiographic examination including 2D speckle tracking imaging. between January 2010 and December 2014. MACE was considered as the primary outcome and it was defined by all-cause mortality, cardiovascular mortality, myocardial infarction, coronary artery by-pass, coronary stent implantation, stroke, development of heart failure, and occurrence of atrial fibrillation during follow-up. RESULTS: Patients who experienced MACE were older than those who did not. There was no difference in demographic and clinical parameters between MACE and non-MACE patients. There was no difference in RV diameter, but MACE patients had higher RV wall thickness. RV systolic function parameters were similar between the two groups. RV global and free-wall longitudinal strain were significantly lower in MACE patients (-22.3 ± 3.6 vs. -24.7 ± 3.9%, p < 0.001 and - 25.8 ± 4.2 vs. -28.1 ± 4.5%, p < 0.001; respectively). Reduced RV GLS [OR 1.10; 95%: 1.02-1.20] and reduced RV free-wall longitudinal strain [OR 1,21; 95%CI: 1.05-1.39] were independently of clinical and echocardiographic parameters related with adverse outcome measured by MACE. CONCLUSION: RV GLS and RV free-wall longitudinal strain were independently related with adverse outcomes during 10-year follow-up in initially uncomplicated hypertensive patients.

Cerebellopontine angle craniopharyngioma in familial adenomatous polyposis.

Background: Craniopharyngiomas are benign tumors arising in the sellar and suprasellar regions. Although ectopic tumors do occur, it is usually due to local spread or recurrent tumors. Purely ectopic cerebellopontine angle (CPA) or 4th ventricle tumors are extremely rare and have been found to be significantly associated with familial adenomatous polyposis (FAP), a genetic disorder. Case Description: Only four cases of ectopic CPA craniopharyngioma associated with FAP have been reported to date. Here, we present the 5th case of ectopic CPA craniopharyngioma on a background of FAP. The previously described cases have been elaborated as well. Conclusion: CPA tumor with a background of FAP should raise a differential diagnosis of craniopharyngioma, and similarly, a CPA primary ectopic craniopharyngioma may raise suspicion of underlying APC gene mutation.

Sex-specific Genetic Determinants of Right Ventricular Structure and Function.

RATIONALE: While sex differences in right heart phenotypes have been observed, the molecular drivers remain unknown. OBJECTIVES: To provide biological insights into sex differences in the structure and function of the right ventricle (RV) using common genetic variation. METHODS: RV phenotypes were obtained from cardiac magnetic resonance imaging in 18,156 women and 16,171 men from the UK Biobank. Observational analyses and sex-stratified genome-wide association studies were performed. Candidate female-specific loci were evaluated against invasively measured cardiac performance in 479 female patients with idiopathic or heritable pulmonary arterial hypertension (PAH), recruited to the UK NIHR BioResource Rare Diseases study. MEASUREMENTS AND MAIN RESULTS: Sex was associated with differences in RV volumes and ejection fraction in models adjusting for left heart counterparts, blood pressure, lung function and sex hormone levels. Six genome-wide significant loci (13%) revealed heterogeneity of allelic effects between women and men, and significant sex-by-genotype interaction. These included two sex-specific candidate loci present in women only: a locus for RV ejection fraction in BMPR1A and a locus for RV end-systolic volume near DMRT2. Epigenetic data in RV tissue indicate that variation at the BMPR1A locus likely alters transcriptional regulation. In female patients with PAH, a variant located in the promoter of BMPR1A was significantly associated with cardiac index (effect size 0.16 l/min/m2), despite similar RV afterload. CONCLUSIONS: BMPR1A has emerged as a biologically plausible candidate gene for female-specific genetic determination of RV function, showing associations with cardiac performance under chronically increased afterload in female patients with PAH.