Circular Network of Coregulated Sphingolipids Dictates Chronic Hypoxia Damage in Patients With Tetralogy of Fallot

Background: Tetralogy of Fallot (TOF) is the most common cyanotic heart disease. However, the association of cardiac metabolic reprogramming changes and underlying molecular mechanisms in TOF-related chronic myocardial hypoxia damage are still unclear.Methods: In this study, we combined microarray transcriptomics analysis with liquid chromatography tandem-mass spectrometry (LC–MS/MS) spectrum metabolomics analysis to establish the metabolic reprogramming that occurs in response to chronic hypoxia damage. Two Gene Expression Omnibus (GEO) datasets, GSE132176 and GSE141955, were downloaded to analyze the metabolic pathway in TOF. Then, a metabolomics analysis of the clinical samples (right atrial tissue and plasma) was performed. Additionally, an association analysis between differential metabolites and clinical phenotypes was performed. Next, four key genes related to sphingomyelin metabolism were screened and their expression was validated by real-time quantitative PCR (QT-PCR).Results: The gene set enrichment analysis (GSEA) showed that sphingolipid metabolism was downregulated in TOF and the metabolomics analysis showed that multiple sphingolipids were dysregulated. Additionally, genes related to sphingomyelin metabolism were identified. We found that four core genes, UDP-Glucose Ceramide Glucosyltransferase (UGCG), Sphingosine-1-Phosphate Phosphatase 2 (SGPP2), Fatty Acid 2-Hydroxylase (FA2H), and Sphingosine-1-Phosphate Phosphatase 1 (SGPP1), were downregulated in TOF.Conclusion: Sphingolipid metabolism was downregulated in TOF; however, the detailed mechanism needs further investigation.

Right atrial myxoma as the first manifestation of granulomatosis with polyangiitis, and a possible association with vascular endothelial growth factor (VEGF) and interleukin 6 (IL-6): a case report and review of the literature

Background Granulomatosis with polyangiitis and myxomas are rare conditions previously described to co-exist. Cardiac masses are often presumed to be myxomas rather than lesions of granulomatosis with polyangiitis. Case presentation We present a review of the symptoms for the two diagnoses along with the first verified case. Conclusions Two possible risk factors for developing myxomas (VEGF and IL-6) are explored and discussed.

Intermittent Occlusion of the Superior Vena Cava to Improve Hemodynamics in Patients With Acutely Decompensated Heart Failure: The VENUS-HF Early Feasibility Study

Background: Reducing congestion remains a primary target of therapy for acutely decompensated heart failure. The VENUS-HF EFS (VENUS-Heart Failure Early Feasibility Study) is the first clinical trial testing intermittent occlusion of the superior vena cava with the preCARDIA system, a catheter mounted balloon and pump console, to improve decongestion in acutely decompensated heart failure. Methods: In a multicenter, prospective, single-arm exploratory safety and feasibility trial, 30 patients with acutely decompensated heart failure were assigned to preCARDIA therapy for 12 or 24 hours. The primary safety outcome was a composite of major adverse cardiovascular and cerebrovascular events through 30 days. Secondary end points included technical success defined as successful preCARDIA placement, treatment, and removal and reduction in right atrial and pulmonary capillary wedge pressure. Other efficacy measures included urine output and patient-reported symptoms. Results: Thirty patients were enrolled and assigned to receive the preCARDIA system. Freedom from device- or procedure-related major adverse events was observed in 100% (n=30/30) of patients. The system was successfully placed, activated and removed after 12 (n=6) or 24 hours (n=23) in 97% (n=29/30) of patients. Compared with baseline values, right atrial pressure decreased by 34% (17±4 versus 11±5 mm Hg, P <0.001) and pulmonary capillary wedge pressure decreased by 27% (31±8 versus 22±9 mm Hg, P <0.001). Compared with pretreatment values, urine output and net fluid balance increased by 130% and 156%, respectively, with up to 24 hours of treatment ( P <0.01). Conclusions: We report the first-in-human experience of intermittent superior vena cava occlusion using the preCARDIA system to reduce congestion in acutely decompensated heart failure. PreCARDIA treatment for up to 24 hours was well tolerated without device- or procedure-related serious or major adverse events and associated with reduced filling pressures and increased urine output. These results support future studies characterizing the clinical utility of the preCARDIA system. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03836079.

Echocardiographic probability of pulmonary hypertension: a validation study

BackgroundAccording to current guidelines, the diagnosis of pulmonary hypertension (PH) relies on echocardiographic probability followed by right heart catheterization. How echocardiography predicts PH recently re-defined by a mean pulmonary artery pressure (mPAP) >20 mmHg instead of ≥25 mmHg and pulmonary vascular disease defined by a pulmonary vascular resistance (PVR) >3 or >2 Wood units has not been established.MethodsA total of 278 patients referred for PH underwent a comprehensive echocardiography followed by a right heart catheterization. Fifteen patients (5.4%) were excluded because of insufficient quality echocardiography.ResultsWith PH defined by a mPAP >20 mmHg, 23 patients had no PH, 146 had pre-capillary and 94 post-capillary PH. At univariate analysis, maximum velocity of tricuspid regurgitation (TRV) ≥2.9 and ≤3.4 m s−1, left ventricle (LV) eccentricity index >1.1, right ventricle (RV) outflow tract (OT) notching or acceleration time <105 ms, RV-LV basal diameter >1 and PA diameter predicted PH, whereas inferior vena cava diameter and right atrial area did not. At multivariable analysis, only TRV ≥2.9 m s−1 independently predicted PH. Additional independent prediction of PVR >3 Wood units was offered by LV eccentricity index >1.1 and RVOT acceleration time <105 ms and/or notching, but with no improvement of optimal combination of specificity and sensibility or positive prediction.ConclusionsEchocardiography as recommended in current guidelines can be used to assess the probability of re-defined PH in a referral center. However, the added value of indirect signs is modest and sufficient quality echocardiographic signals may not be recovered in some patients.

Cross-talk between cAMP and Ca2+ signalling in cardiac pacemaker cells involves IP3-evoked Ca2+ release and stimulation of adenylyl cyclase 1

Atrial arrhythmias, such as atrial fibrillation (AF), are a major mortality risk and a leading cause of stroke. The IP3 signalling pathway has been proposed as an atrial specific target for AF therapy, and atrial IP3 signalling has been linked to the activation of calcium sensitive adenylyl cyclases AC1 and AC8. Here we investigated the involvement of AC1 in the response of intact mouse atrial tissue and isolated guinea pig atrial and sinoatrial node (SAN) cells to the α-adrenoceptor agonist phenylephrine (PE) using the selective AC1 inhibitor ST034307. The maximum rate change of spontaneously beating mouse right atrial tissue exposed to PE was reduced from 14.46 % to 8.17% (P = 0.005) in the presence of 1 μM ST034307, whereas the increase in tension generated in paced left atrial tissue in the presence of PE was not inhibited by ST034307 (Control = 14.20 %, ST034307 = 16.32 %; P > 0.05). Experiments were performed using isolated guinea pig atrial and SAN cells loaded with Fluo-5F-AM to record changes in calcium transient amplitude (CaT) generated by 10μM PE in the presence and absence of 1μM ST034307. ST034307 significantly reduced the beating rate of SAN cells (0.34-fold decrease; P = 0.004), but did not result in an inhibition of CaT amplitude increase in response to PE in atrial cells. The results presented here demonstrate the involvement of AC1 in the downstream response of atrial pacemaker activity to α-adrenoreceptor stimulation and IP3R calcium release.

Recurrent cardiac hydatid cyst located near the root of the superior vena cava and the interatrial septum: a case report

Introduction: Cardiac localization of hydatid disease is rare (<3%) even in endemic countries. Affection characterized by a long functional tolerance and a large clinical and paraclinical polymorphism. Serious cardiac hydatitosis because of the risk of rupture requiring urgent surgery. The diagnosis is based on serology and echocardiography. The aim of this work is to show a case of recurrent cardiac hydatid cyst discovered incidentally during a facial paralysis assessment. Methods: We report the observation of a 26-year-old woman operated on in 2012 for pericardial hydatid cyst presenting a cardiac hydatid cyst located near the abutment of the SCV discovered incidentally during an exploration for left facial paralysis: NYHA stage II dyspnea. Chest x-ray: CTI at 0.48. ECG: RSR. Echocardiography: Image of cystic appearance at the level of the abutment of the SVC. SAPP: 38 mmhg, EF: 65%. Thoracic scan: 30/27 mm cardiac hydatid cyst bulging the lateral wall of the right atrium and the trunk of the right pulmonary artery with fissured cardiac hydatid cyst of the apical segment of the right lung of the right lower lobe with multiple bilateral intra parenchymal and sub pleural nodules. The patient was operated on under CPB. Intraoperative exploration: Presence of a hard and whitish mass, about 03 / 03cm developed in the full right atrial wall opposite the entrance to the superior vena cava. Procedure: Resection of the mass removing the roof of the LA, the AIS and the wall of the RA with reconstruction of the roof of the RA by patch in Dacron and reconstruction of the IAS and the wall of the RA by a single patch in Dacron. Results: The postoperative suites were simple. Conclusion: The hydatid cyst is still a real endemic in Algeria, the cardiac location is rare but serious and can constitute a real surgical emergency, hence the importance of prevention. Keywords: Hydatid cyst of the heart; Recurrence; Surgery; Cardiopulmonary Bypass; Prevention

Association of left atrial strain by cardiovascular magnetic resonance with recurrence of atrial fibrillation following catheter ablation

Background Atrial fibrillation (AF) is a progressive condition, which is characterized by inflammation/fibrosis of left atrial (LA) wall, an increase in the LA size/volumes, and decrease in LA function. We sought to investigate the relationship of anatomical and functional parameters obtained by cardiovascular magnetic resonance (CMR), with AF recurrence in paroxysmal AF (pAF) patients after catheter ablation. Methods We studied 80 consecutive pAF patients referred for ablation, between January 2014 and December 2019, who underwent pre- and post-ablation CMR while in sinus rhythm. LA volumes were measured using the area–length method and included maximum, minimum, and pre-atrial-contraction volumes. CMR-derived LA reservoir strain (ℇR), conduit strain (ℇCD), and contractile strain (ℇCT) were measured by computer assisted manual planimetry. We used a multivariate logistical regression to estimate the independent predictors of AF recurrence after ablation. Results Mean age was 58.6 ± 9.4 years, 75% men, mean CHA2DS2-VASc score was 1.7, 36% had prior cardioversion and 51% were taking antiarrhythmic drugs. Patients were followed for a median of 4 years (Q1–Q3 = 2.5–6.2 years). Of the 80 patients, 21 (26.3%) patients had AF recurrence after ablation. There were no significant differences between AF recurrence vs. no recurrence groups in age, gender, CHA2DS2-VASc score, or baseline comorbidities. At baseline, patients with AF recurrence compared to without recurrence had lower LV end systolic volume index (32 ± 7 vs 37 ± 11 mL/m2; p = 0.045) and lower ℇCT (7.1 ± 4.6 vs 9.1 ± 3.7; p = 0.05). Post-ablation, patients with AF recurrence had higher LA minimum volume (68 ± 32 vs 55 ± 23; p = 0.05), right atrial volume index (62 ± 20 vs 52 ± 19 mL/m2; p = 0.04) and lower LA active ejection fraction (24 ± 8 vs 29 ± 11; p = 0.05), LA total ejection fraction (39 ± 14 vs 46 ± 12; p = 0.02), LA expansion index (73.6 ± 37.5 vs 94.7 ± 37.1; p = 0.03) and ℇCT (6.2 ± 2.9 vs 7.3 ± 1.7; p = 0.04). Adjusting for clinical variables in the multivariate logistic regression model, post-ablation minimum LA volume (OR 1.09; CI 1.02–1.16), LA expansion index (OR 0.98; CI 0.96–0.99), and baseline ℇR (OR 0.92; CI 0.85–0.99) were independently associated with AF recurrence. Conclusion Significant changes in LA volumes and strain parameters occur after AF ablation. CMR derived baseline ℇR, post-ablation minimum LAV, and expansion index are independently associated with AF recurrence.