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Tropic fever can have several causes. It is important to investigate thoroughly and consider less obvious explanations. This paper presents the case of a biologist in close contact with chimpanzees, who developed fever in the tropics. Despite treatment for some tropical diagnosis, the fever persisted. On arrival in Belgium, further diagnostics revealed an unexpected diagnosis: Citrobacter koseri endocarditis of the native aortic valve. He was treated with ceftriaxone and amikacin and underwent aortic valve replacement. C koseri is a commensal in humans and animals. It is likely that the patient was infected with this bacterium through his close contact with chimpanzees. Only a few cases of C koseri endocarditis have been published worldwide, with most patients being immunocompromised. Patients with tropical fever may have unsuspected underlying causes, like endocarditis., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Left ventricular (LV) hypertrophy is a common clinical finding. Differential diagnosis includes Fabry disease, a rare and progressive, but treatable storage disease caused by deficiency of α-galactosidase A. However, diagnosis of Fabry is often hampered by its clinical heterogeneity, LV hypertrophy phenocopies and unawareness of the clinician., Methods: This review summarises clinical data, family history, electrocardiogram (ECG) and imaging (echocardiogram and cardiovascular magnetic resonance (CMR)) characteristics to differentiate aetiologies of LV hypertrophy including clues for the diagnosis of Fabry., Results: LV hypertrophy is a consequence of pressure overload mostly, but differential diagnosis includes hypertrophic cardiomyopathy and infiltrative diseases. Clinical data, ECG, type and degree of LV hypertrophy, functional and tissue characteristics differ among aetiologies. LV hypertrophy in Fabry is progressive and mostly concentric but may copy any hypertrophic cardiomyopathy. Dependent on residual alfa-galactosidase A enzyme activity, degree of LV hypertrophy in Fabry may vary. Initially, low myocardial CMR T1-map values are calculated. At a later stage, midwall late gadolinium enhancement of the inferolateral LV wall may occur. Global longitudinal strain may be depressed in the inferolateral wall. Voltage criteria for LV hypertrophy and short PQ interval are common. Right ventricular (RV) hypertrophy is frequent. In addition, multisystemic symptoms including neuropathic pain, hypohidrosis, proteinuria, renal insufficiency and familial young stroke are pointing to Fabry., Conclusions: LV hypertrophy should raise suspicion of Fabry disease, especially if LV hypertrophy is unexplained and/or associated with RV hypertrophy. In Fabry, LV hypertrophy may be heterogeneous and mimic any hypertrophic cardiomyopathy. ECG, multisystemic symptoms and imaging may provide clues for Fabry.

Tricuspid regurgitation (TR) is a prevalent valvular disease with a significant mortality rate. The evaluation of TR severity and associated right heart remodeling and dysfunction is crucial to determine the optimal therapeutic strategy and to improve prognosis. While echocardiography remains the first-line imaging technique to evaluate TR, it has many limitations, both operator- and patient-related. Cardiovascular magnetic resonance imaging (CMR) has emerged as an innovative and comprehensive non-invasive cardiac imaging technique with additional value beyond routine echocardiographic assessment. Besides its established role as the gold standard for the evaluation of cardiac volumes, CMR can add important insights with regard to valvular anatomy and function. Accurate quantification of TR severity, including calculation of regurgitant volume and fraction, can be performed using either the well-known indirect volumetric method or novel 4D flow imaging. In addition, CMR can be used to assess the impact on the right heart, including right heart remodeling, function and tissue characterization. Several CMR-derived parameters have been associated with outcome, highlighting the importance of multi-modality imaging in patients with TR. The aim of this review is to provide an overview of the current role of CMR in the assessment and management of patients with TR and its future applications.

Surgical correction of severe mitral regurgitation (MR) can reverse left ventricular (LV) remodeling in patients with mitral valve prolapse (MVP). However, whether this process is similar to the case in Barlow's Disease (BD) and Fibro-elastic Deficiency (FED) is currently unknown. The aim of this study is to evaluate post-operative LV reverse remodeling and function in patients with BD versus FED. In this study, 100 MVP patients (BD = 37 and FED = 63) with severe MR who underwent mitral valve surgery at three Belgian centers were retrospectively included. Transthoracic echocardiography was used to assess MR severity, LV volumes and function before surgery and 6 months thereafter. Baseline MR severity, LV ejection fraction (LVEF), indexed LV end-diastolic (LVEDVi) and end-systolic volumes (LVESVi) were not different between the groups. After a median follow-up of 278 days, there was a similar decrease in LVEDVi, but a trend towards a smaller decrease in LVESVi in BD compared to FED (-3.0 ± 11.2 mL/m 2 vs. -5.3 ± 9.0 mL/m 2 ; p = 0.154). This resulted in a significantly larger decrease in LVEF in BD (-8.3 ± 9.6%) versus FED (-3.9 ± 6.9%) after adjusting for baseline LVEF ( p < 0.001) and type of surgical intervention ( p = 0.01). These findings suggest that LV (reverse) remodeling in BD could be affected by other mechanisms beyond volume overload, potentially involving concomitant cardiomyopathy.

Background: Evidence-based recommendations for antithrombotic treatment in patients who have an indication for oral anticoagulation (OAC) after transcatheter edge-to-edge mitral valve repair (TEER) are lacking., Aims: To compare bleeding and thrombotic risk for different antithrombotic regimens post-TEER with MitraClip in an unselected population with the need for OACs., Methods: Bleeding and thrombotic complications (stroke and myocardial infarction) up to 3 months after TEER with mitraclip were evaluated in 322 consecutive pts with an indication for OACs. These endpoints were defined by the Mitral Valve Academic Research Consortium criteria and were compared between two antithrombotic regimens: single antithrombotic therapy with OAC (single ATT) and double/triple ATT with a combination of OAC and aspirin and/or clopidogrel (combined ATT)., Results: Collectively, 108 (34%) patients received single ATT, 203 (63%) received double ATT and 11 (3%) received triple ATT. Bleeding events occurred in 67 patients (20.9%), with access site related events being the most frequent cause (37%). Bleeding complications were observed more frequently in the combined ATT group than in the single ATT group: 24% versus 14% [p = 0.03, adjusted RR: 0.55 (0.3-0.98)]. Within the combined group, the bleeding risk was 23% in the double ATT and 45% in the triple ATT group. Thrombotic complications occurred in only three patients (0.9%), and all belonged to the combined ATT group., Conclusions: In patients with an indication for OACs, withholding of antiplatelet therapy post-TEER with Mitraclip was associated with a 45% reduction in bleeding and without a signal of increased thrombotic risk., (© 2023 Wiley Periodicals LLC.)

Three-dimensional echocardiography (3DE) is the most accurate cardiac ultrasound technique to assess cardiac structure. 3DE has shown close correlation with cardiac magnetic resonance imaging (CMR) in various populations. There is limited data on the accuracy of 3DE in athletes and its value in detecting alterations during follow-up. Indexed left and right ventricular end-diastolic volume (LVEDVi, RVEDVi), end-systolic volume, ejection fraction (LVEF, RVEF) and left ventricular mass (LVMi) were assessed by 3DE and CMR in two-hundred and one competitive endurance athletes (79% male) from the Pro@Heart trial. Sixty-four athletes were assessed at 2 year follow-up. Linear regression and Bland-Altman analyses compared 3DE and CMR at baseline and follow-up. Interquartile analysis evaluated the agreement as cardiac volumes and mass increase. 3DE showed strong correlation with CMR (LVEDVi r = 0.91, LVEF r = 0.85, LVMi r = 0.84, RVEDVi r = 0.84, RVEF r = 0.86 p < 0.001). At follow up, the percentage change by 3DE and CMR were similar (∆LVEDVi r = 0.96 bias - 0.3%, ∆LVEF r = 0.94, bias 0.7%, ∆LVMi r = 0.94 bias 0.8%, ∆RVESVi r = 0.93, bias 1.2%, ∆RVEF r = 0.87 bias 0.4%). 3DE underestimated volumes (LVEDVi bias - 18.5 mL/m 2 , RVEDVi bias - 25.5 mL/m 2 ) and the degree of underestimation increased with larger dimensions (Q1vsQ4 LVEDVi relative bias - 14.5 versus - 17.4%, p = 0.016; Q1vsQ4 RVEDVi relative bias - 17 versus - 21.9%, p = 0.005). Measurements of cardiac volumes, mass and function by 3DE correlate well with CMR and 3DE accurately detects changes over time. 3DE underestimates volumes and the relative bias increases with larger cardiac size., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Aims: Purpose of this study is to compare the clinical course and outcome of patients with recurrent versus first-episode infective endocarditis (IE)., Methods: Patients with recurrent and first-episode IE enrolled in the EUROpean ENDOcarditis (EURO-ENDO) registry including 156 centres were identified and compared using propensity score matching. Recurrent IE was classified as relapse when IE occurred ≤6 months after a previous episode or reinfection when IE occurred >6 months after the prior episode., Results: 3106 patients were enrolled: 2839 (91.4%) patients with first-episode IE (mean age 59.4 (±18.1); 68.3% male) and 267 (8.6%) patients with recurrent IE (mean age 58.1 (±17.7); 74.9% male). Among patients with recurrent IE, 13.2% were intravenous drug users (IVDUs), 66.4% had a repaired or replaced valve with the tricuspid valve being more frequently involved compared with patients with first-episode IE (20.3% vs 14.1%; p=0.012). In patients with a first episode of IE, the aortic valve was more frequently involved (45.6% vs 39.5%; p=0.061). Recurrent relapse and reinfection were 20.6% and 79.4%, respectively. Staphylococcus aureus was the microorganism most frequently observed in both groups (p=0.207). There were no differences in in-hospital and post-hospitalisation mortality between recurrent and first-episode IE. In patients with recurrent IE, in-hospital mortality was higher in IVDU patients. Independent predictors of poorer in-hospital and 1-year outcome, including the occurrence of cardiogenic and septic shock, valvular disease severity and failure to undertake surgery when indicated, were similar for recurrent and first-episode IE., Conclusions: In-hospital and 1-year mortality was similar in patients with recurrent and first-episode IE who shared similar predictors of poor outcome., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

We report a case of a fatal retrograde Type A aortic dissection following thoracic endovascular aortic repair (TEVAR). The patient was diagnosed with vascular Ehlers-Danlos syndrome (vEDS) only postoperatively, which is a relative contraindication for TEVAR. The patient had no major or minor criteria for vEDS. This case report emphasizes pitfalls of TEVAR in patients with a connective tissue disorder., Competing Interests: The authors declare no conflict of interest related to this article., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Mitral valve prolapse (MVP) is a common valvular disorder that can be associated with mitral regurgitation (MR), heart failure, ventricular arrhythmias and sudden cardiac death. Given the prognostic impact of these conditions, it is important to evaluate not only mitral valve morphology and regurgitation, but also the presence of left ventricular (LV) function and remodeling. To date, several possible hypotheses have been proposed regarding the underlying mechanisms of LV remodeling in the context of non-syndromic MVP, but the exact pathophysiological explanation remains elusive. Overall, volume overload related to severe MR is considered the main cause of LV dilatation in MVP. However, significant LV remodeling has been observed in patients with MVP and no/mild MR, particularly in patients with bileaflet MVP or Barlow's disease, generating several new hypotheses. Recently, the concept of "prolapse volume" was introduced, adding a significant volume load to the LV on top of the transvalvular MR volume. Another possible hypothesis is the existence of a concomitant cardiomyopathy, supported by the link between MVP and myocardial fibrosis. The origin of this cardiomyopathy could be either genetic, a second hit (e.g., on top of genetic predisposition) and/or frequent ventricular ectopic beats. This review provides an overview of the different mechanisms and remaining questions regarding LV remodeling in non-syndromic MVP. Since technical specifications of imaging modalities impact the evaluation of MR severity and LV remodeling, and therefore might influence clinical decision making in these patients, this review will also discuss assessment of MVP using different imaging modalities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pype, Bertrand, Paelinck, Heidbuchel, Van Craenenbroeck and Van De Heyning.)

Objective: This study was undertaken to determine the plasma concentration and pharmacokinetic variability of fenfluramine (FFA) and its main active metabolite norfenfluramine (norFFA) in relation to the prevalence of adverse effects in patients with refractory epilepsy treated with FFA. In addition, the interaction with concomitant antiseizure medications including stiripentol (STP) is studied., Methods: Patients were recruited at our center from two open-label sources, an investigator-initiated observational study and an international multicenter extension study. Venous blood samples were collected between June 2015 and December 2020. Plasma FFA and norFFA concentrations were determined by liquid chromatography tandem spectrometric analysis. Clinical data were collected retrospectively. Intrapatient coefficient of variation was calculated for all patients with at least three samples. Interpatient variability was calculated based on the concentration to weight-adjusted dose ratio (C/D) of all patients., Results: We collected 321 samples from 61 patients (49 with Dravet syndrome, seven with Lennox-Gastaut syndrome, and five with a developmental and epileptic encephalopathy). With a mean daily dose of .33 mg/kg/day (SD = ±.16), the median FFA plasma concentration was 41.4 µg/L (range = 5.1-712.5) and median norFFA concentration 28.1 µg/L (range = 2.6-149.6). The FFA plasma concentration was linearly related to the daily dose (p < .001) and norFFA levels (p < .001). The C/D of FFA increased with age (p < .001). Median FFA C/D was 428% higher (p < .001), norFFA C/D 83% lower (p < .001), and norFFA/FFA 23% lower (p < .001) in patients treated with STP comedication. Higher FFA concentration was associated with fatigue (p = .001) and somnolence (p < .001), but not anorexia (p = .0619) or reduction in seizure frequency (p = .772). Gender and other ASMs were not associated with significant variations in (nor)FFA C/D ratio., Significance: Most FFA levels are in the lower range (<50 µg/L), although a high interpatient and intrapatient variability is present. In combination with STP, the dose of FFA should be reduced., (© 2022 International League Against Epilepsy.)

The present study aims to assess the clinical and hemodynamic impact of percutaneous edge-to-edge mitral valve repair with MitraClip in patients with atrial functional mitral regurgitation (A-FMR) compared with ventricular functional mitral regurgitation (V-FMR). Mitral regurgitation (MR) grade, functional status (New York Heart Association class), and major adverse cardiac events (MACE; all-cause mortality or hospitalization for heart failure) were evaluated in 52 patients with A-FMR and in 307 patients with V-FMR. In 56 patients, hemodynamic assessment during exercise echocardiography was performed before and 6 months after intervention. MR reduction after MitraClip implantation was noninferior in A-FMR compared with V-FMR (MR grade ≤2 at 6 months in 94% vs 82%, respectively, p <0.001 for noninferiority) and was associated with improvement of functional status (New York Heart Association class ≤2 at 6 months in 90% vs 80%, respectively, p = 0.2). Hemodynamic assessment revealed that cardiac output at 6 months was higher in A-FMR at rest (5.1 ± 1.5 L/min vs 3.8 ± 1.5 L/min, p = 0.002) and during peak exercise (7.9 ± 2.4 L/min vs 6.1 ± 2.1 L/min, p = 0.02). In addition, the reduction in systolic pulmonary artery pressure at rest was more pronounced in A-FMR: Δ SPAP -13.1 ± 15.1 mm Hg versus -2.2 ± 13.3 mm Hg (p = 0.03). MACE rate at follow-up was significantly lower in A-FMR versus V-FMR, with an adjusted odds ratio of 0.46 (95% confidence interval 0.24 to 0.88), which was caused by a reduction in hospitalization for heart failure. In conclusion, percutaneous edge-to-edge mitral valve repair with MitraClip is at least as effective in A-FMR as in V-FMR in reducing MR. However, the hemodynamic improvement and reduction of MACE were significantly better in A-FMR., Competing Interests: Disclosures M. Claeys has received honoraria fees (<10,000 euro) from Abbott company. The remaining authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Detailed multidimensional assessment of patent foramen ovale (PFO) size with transesophageal echocardiography (TOE) may help to determine PFO pathogenicity in cryptogenic stroke patients. We explored the potential additive value of Live xPlane and three-dimensional (3D) TOE anatomical PFO sizing techniques., Methods: Imaging data of 45 patients who underwent a 3D TOE-assisted percutaneous PFO closure were studied. The two-dimensional (2D) PFO separation distance and right-to-left (RL) contrast shunt magnitude were assessed on preprocedural TOE recordings. Peri-procedural measurements of the triangular anatomical PFO opening (base, height, and area) were performed after positioning of a stiff guidewire (SW) through the PFO, using Live xPlane imaging and 3D Zoom mode., Results: The PFO SW base appeared on average 5 times larger than the preprocedural 2D PFO separation (median difference [IQR] = 13[5] mm; P < .001). For a same PFO separation, the width of the PFO base may vary significantly. The PFO SW base was significantly larger in patients with a large versus a small-to-moderate PFO RL contrast shunt (18 vs 15 mm; P = .007) and in those with a spontaneous versus a provoked shunt (18 vs 14 mm; P = .003)., Conclusion: Live xPlane and 3D Zoom TOE allow peri-procedural measurement of the largest dimension of a PFO, which is the PFO base. Patients with a large or spontaneous RL contrast shunt appear to have a larger PFO base. The anatomical PFO base dimension may be taken into account for optimization of device and patient selection strategies., (© 2020 Wiley Periodicals LLC.)

Aim: To evaluate the acute hemodynamic effects after MitraClip implantation and to identify predictors of afterload mismatch and its prognostic implications., Methods: Acute hemodynamic effects were assessed intraoperatively by right heart catheterization and by transesophageal echocardiography before and after MitraClip implantation in 62 consecutive patients with severe mitral regurgitation (MR) (functional MR, 73.8%; EuroScore 2, 7.1 ± 4.9%; left ventricular ejection fraction [LVEF], 36 ± 15%; New York Heart Association class III/IV, 65%). Afterload mismatch was defined as a >15% decrease in LVEF (acute LV depression) or a >15% increase in LV end-diastolic volume (acute adverse LV remodeling). Patients were followed over a period of 24 months (mean, 18 ± 3 months) with all-cause mortality as the primary endpoint., Results: Successful MitraClip implantation with residual MR ≤2 was achieved in 85% of patients. Acute LV depression was observed in 23% of patients, and acute adverse LV remodeling was observed in 15% of patients. Acute adverse LV remodeling occurred in 40% of patients with EuroScores >12 vs in 10% of patients with EuroScores ≤12 (P=.02). Although acute adverse LV remodeling was well tolerated in the acute phase, it was associated with a higher mortality rate during follow-up (62% vs 26%; log-rank P=.04). In a multivariate model, EuroScore 2, but not afterload mismatch, was the most important prognostic risk factor, with an adjusted hazard ratio of 1.1 (95% confidence interval, 1.0-1.2)., Conclusion: Afterload mismatch, as assessed intraoperatively, is not uncommon after MitraClip implantation in patients with impaired LV function and is a risk marker of poor clinical outcome.

Aims: The effect of MitraClip implantation on left ventricular (LV) remodelling has been shown to be highly variable. The present study wants to assess patterns of LV remodelling and its relationship with outcome., Methods and Results: Serial echocardiography before, 1 and 6 months after MitraClip implantation was performed in 79 pts with severe mitral regurgitation (MR) (age 74 ± 10 years, New York Heart Association III/IV 80%, LV ejection fraction 38 ± 13%, logistic EuroSCORE 21 ± 15, and functional MR 81%). LV reverse/adverse remodelling was defined as a >15% decrease/>10% increase in LV end-diastolic volume (LVEDV), respectively. Patients were followed over a period of 32 ± 16 months with all-cause mortality as the primary endpoint. A sustained (6 month) reduction of MR ≤ 2 post-MitraClip implantation was observed in 83% of patients. The average decrease in LVEDV 6 months after intervention was 13% ± 16%. Reverse remodelling at 6 months occurred in 40 patients (51%), and adverse remodelling occurred in 6 patients (8%). Patients with adverse remodelling showed a 38% increase of LVEDV at 1 month vs. no early change in LVEDV in patients with reverse remodelling. During follow-up, a total of 25 patients (32%) died. Patients with adverse remodelling died more frequently than patients with reverse remodelling [67% vs. 27%, adjusted odds ratio of 5.6 (95% CI 1.5-21)]., Conclusion: The majority of patients undergoing MitraClip implantation for severe MR showed LV reverse remodelling. However, there was a small group in whom afterload mismatch resulted in sustained adverse remodelling with subsequent high mortality., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Percutaneous closure is the treatment of choice for secundum-type atrial septal defects (ASD). Balloon sizing (BS) has been the method of choice for deciding on device size. Improved 2D- and 3D-transesophageal echocardiographic (TEE) imaging challenged the necessity of BS. Balloon sizing was performed with two additional techniques to measure the stretched dimension of the ASD. The 1st method uses a stiff guide wire which stretches the ASD and 2D TEE. The second technique uses 3D TEE. Two hundred and thirty-six patients with minimum 1-year follow-up were enrolled. The population was classified into three groups: BS (group 1) n = 90, 2D-TEE (group 2) n = 87, and 3D-TEE (group 3) n = 59. All groups showed a distinct correlation between the maximum baseline dimensions and the device size (R = 0.821). The relative expansion rate did not differ between BS and 3D-TEE. Group 2 (2D-TEE) showed a significantly lower expansion rate. Procedural success and complications did not differ statistically between the 3 groups. 2D TEE sizing was the simplest method without loss of accuracy. 3D sizing offers the advantage of accurate and fast shape assessment, but resulted in more undersizing. Accurate sizing of ASDs with a floppy septum remains a challenge.

Objective: Dravet syndrome (DS) is a rare, treatment-resistant epilepsy syndrome for which current treatment regimens are often ineffective. Fenfluramine is currently in development for treatment of DS, based on reports in the 1980s and 1990s of its anti-epileptic activity in pediatric patients with intractable epilepsy. However, fenfluramine was withdrawn from global markets in 1997 following reports of its association with pulmonary hypertension and heart valve disease in adult patients treated for obesity. This review was conducted to assess cardiac safety of fenfluramine when used at lower doses for treatment of DS., Methods: Pubmed was searched for clinical studies of fenfluramine in obese adults who reported incidence of heart valve disease. These data were reviewed against published results from Belgian patients with DS who have been treated with low-dose fenfluramine for up to 28 years., Results: Nine controlled studies of fenfluramine and related compounds (dexfenfluramine and/or phentermine) which assessed incidence and severity of cardiac valve disease in 3,268 treated patients and 2,017 control subjects have been reported. Mild or greater aortic valve regurgitation was found in 9.6% of treated patients compared with 3.9% of control subjects, and moderate or greater mitral valve regurgitation was found in 3.1% of treated patients and 2.5% of control subjects. Nineteen DS patients have been treated for up to 28 years with 10-20 mg/day fenfluramine, with no clinical signs or symptoms of cardiac valve disease or pulmonary hypertension. Slight and clinically unimportant changes in valve structure have been seen on echocardiography in five patients at some time during the observation period., Conclusions: A different benefit-risk relationship appears to be emerging when fenfluramine is used at low doses for extended periods in young patients with DS. Continued cardiac assessments during ongoing Phase 3 clinical trials will provide additional safety information for this potential new and effective treatment.

Background and Purpose: Dravet syndrome (DS) is a severe, drug-resistant epilepsy. Fenfluramine has been reported to have a long-term clinically meaningful anticonvulsive effect in patients with DS., Methods: This prospective, open-label study assessed the safety and effectiveness of low-dose fenfluramine in a new cohort of patients with DS. Following a 3-month baseline period, fenfluramine was added to each patient's current antiepileptic drug regimen at a dose of 0.25-1.0 mg/kg/day (max. 20 mg/day). The incidence of major motor seizures (tonic, clonic, tonic-clonic, atonic and myoclonic seizures lasting >30 s) in both the baseline and treatment periods was assessed via a seizure diary. Periodic echocardiographic examinations during the treatment period were used to assess cardiovascular safety., Results: Nine patients (aged 1.2-29.8 years) enrolled in the study and were treated with fenfluramine for a median duration of 1.5 (range, 0.3-5.1) years. Median frequency of major motor seizures was 15.0/month in the baseline period. All patients demonstrated a reduction in seizure frequency during the treatment period with a median reduction of 75% (range, 28-100%). Seven patients (78%) experienced a ≥50% reduction in major motor seizure frequency. The most common adverse events were somnolence (n = 5) and anorexia (n = 4). No evidence of cardiac valvulopathy or pulmonary hypertension was observed., Conclusions: The effectiveness and safety of low-dose fenfluramine as an add-on therapy for DS in this new prospective cohort supports previous findings., (© 2016 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objectives: Studies evaluating the long-term outcome of adults with ventricular septal defect (VSD) are important to inform patients about prognosis. This study investigated the long-term outcome of patients with perimembranous VSD (pmVSD) followed in the Belgian Registry on Adult Congenital Heart Disease., Methods: All pmVSD patients in the registry were analyzed., Results: Two hundred and sixty-six patients were studied. Fifteen patients had Eisenmenger syndrome. One hundred and seventy-three had isolated pmVSD and 78 had pmVSD with concomitant lesions. Of the patients with isolated pmVSD, 52% were male, median age was 29 years (IQR 24-35 years) and median follow-up duration was 18 years (IQR 10-25 years). Fifty-three (31%) patients underwent VSD closure and 10 (19%) had a residual shunt. Most (93%) patients were in NYHA class I. No patients died. Two (4%) patients developed atrial arrhythmia and 2 (4%) required pacemaker implantation. Seven (14%) developed left ventricular outflow tract obstruction (LVOTO). In the unrepaired pmVSD group, 4 developed endocarditis. In the entire group, moderate or severe aortic regurgitation (AR) occurred in 9 (5%) patients., Conclusions: Long-term survival in patients with isolated pmVSD was not uneventful. Moderate or severe AR might develop and endocarditis occurred in patients without VSD repair. Complications after VSD closure included atrial arrhythmia, pacemaker implantation and LVOTO., (© 2016 S. Karger AG, Basel.)

Dravet syndrome (DS) is a rare and therapy-resistant epilepsy syndrome. A retrospective analysis of add-on fenfluramine treatment in 12 patients with DS was published in 2012 and provided evidence of a meaningful long-term response. Herein we present the results of a subsequent 5-year prospective observation of this original cohort. Ten patients with a mean current age of 24 years were followed prospectively from 2010 until 2014. The mean current dose of fenfluramine was 0.27 mg/kg/day, with a mean treatment duration of 16.1 years. Seizure frequency was derived from a seizure diary. Cardiac examinations and assessments of clinical effectiveness and adverse events were performed at least annually. Three patients were seizure-free for the entire 5 years, and an additional four patients experienced seizure-free intervals of at least 2 years. Fenfluramine was generally well-tolerated. Two patients had mild (stable) valve thickening on the last echocardiography that was deemed clinically insignificant. No patient had any clinical or echocardiographic signs of pulmonary hypertension. These findings support the long-term control of convulsive seizures by low-dose fenfluramine while being well tolerated in this cohort of patients with DS. After up to 27 years of treatment, no patient has developed any clinical signs or symptoms of cardiac valvulopathy or pulmonary hypertension., (© 2016 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.)

Objectives: The aim of this study was to validate recently proposed risk scores for the prediction of mortality up to 1 year after transcatheter aortic valve implantation (TAVI), using a self-expandable valve (CoreValve)., Methods: In this single-centre study, 225 consecutive patients with severe symptomatic aortic valve stenosis, who underwent TAVI between December 2007 and January 2015, were included. Conventional surgical risk scores (logistic EuroSCORE, EuroSCORE II and STS score) were calculated as well as newly proposed TAVI risk scores (TAVI2-SCORe, STT Score and OBSERVANT score). Medium-term survival of the patients was assessed up to 1 year after TAVI., Results: The median age was 82 (77-86) years and 45.3% were male. Patients were categorized into 'non-high risk' or 'high risk' according to logistic EuroSCORE >20%, EuroSCORE II >8%, STS score >10%, TAVI2-SCORe >2, STT score >12% and OBSERVANT score >6. Thirty-day and 1-year survival rates were significantly different between 'non-high-risk' and 'high-risk' patients according to the STS score (1 year: low: 84.4% vs high: 67.0%, P = 0.010) and according to OBSERVANT score (1 year: low: 85.2% vs high: 68.4%, P = 0.005). In contrast, TAVI2-SCORe and STT score did not discriminate 'non-high-risk' and 'high-risk' patients. This was confirmed by Cox regression analysis [STS score >10%: hazard ratio: 2.484 (1.206-5.115), P = 0.014; OBSERVANT score >6: hazard ratio: 2.532 (1.295-4.952), P = 0.007]., Conclusions: In this single-centre study, OBSERVANT and STS score most accurately predicted early and mid-term survival in patients undergoing TAVI, using a self-expandable valve (CoreValve)., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The aim of this study was to determine if red cell distribution width (RDW) could improve the prediction of prognosis after transcatheter aortic valve implantation (TAVI)., Methods: In this single-centre study, 197 consecutive patients underwent TAVI (median age 82 (77-86), 46.2% men). Normal RDW at baseline was defined as ≤15.5%, elevated RDW at baseline was defined as >15.5%. Ouctomes according to the Valve Academic Research Consortium 2 and survival up to one year were compared between these groups., Results: Compared with the patients with RDW ≤15.5% (n = 168), those with RDW >15.5% (n = 29) had a higher Society of Thoracic Surgeon (STS) score (7.2 vs 5.0%, P = 0.041), higher systolic pulmonary arterial pressure (50 vs 41 mmHg, P = 0.021) and lower haemoglobin (11.5 vs 12.4 mg/dl, P = 0.003). Patients with RDW >15.5% developed significantly more adverse events after TAVI (major vascular complications: 10.3 vs 1.8%, P = 0.042; aortic regurgitation grade II-IV: 50.0 vs 18.0%, P = 0.001) and survival up to 1 year was significantly lower (85.6 vs 65.2%, log-rank: P = 0.007). In addition, RDW >15.5% at baseline was the most significant predictor for mortality (hazard ratio: 2.701 (1.279-5.704), P = 0.009), even when the STS score was added to the model [RDW >15.5%: hazard ratio: 2.276 (1.045-4.954), P = 0.038]., Conclusions: Elevated RDW is a significant predictor for adverse events and increased 1-year mortality after TAVI. Adding RDW to the classical STS score could be a valuable strategy to improve preoperative risk assessment in potential TAVI candidates., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: With the expanding use of transcatheter aortic valve implantation (TAVI), we have encountered increasing numbers of patients without ideal femoral access. Although many alternatives have been described, vascular access and access-related complications remain a point of concern. We report our series of 20 patients undergoing TAVI via brachiocephalic artery access., Methods: Between September 2011 and May 2014, we performed 107 consecutive CoreValve bioprosthesis implantations, of which 20 were by the brachiocephalic approach due to unfavourable iliac or femoral anatomy., Results: No vascular or access-related complications were seen. Procedural feasibility, device success and early safety, as defined by the Valve Academic Research Consortium-2 criteria, were good, at 100, 95 and 95%, respectively. No stroke, transient ischaemic attack, acute kidney injury, major vascular or major bleeding complications were observed. At a mean follow-up of 497 days, the 1-year survival rate is 75.0%. Echocardiography at discharge confirmed moderate paravalvular regurgitation in 1 patient and mild paravalvular leakage in 3 patients, and no paravalvular leak more than moderate was seen. Echocardiography at discharge, 6 months and 1 year after TAVI confirmed persistent low mean transvalvular gradients (9, 9 and 10 mmHg, respectively)., Conclusions: TAVI implantation through the brachiocephalic artery is safe and feasible. The distance between the point of access and the aortic valve annulus is short, improving catheter stability and implant site accuracy. We consider it to be a valuable alternative in patients without femoral access., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)