Background The gut microbiota represents a potential treatment target in heart failure (HF) through microbial metabolites such as trimethylamine N-oxide (TMAO) and systemic inflammation. Treatment with the probiotic yeast Saccharomyces boulardii have been suggested to improve left ventricular ejection fraction (LVEF). Methods In a multicentre, prospective randomized open label, blinded end-point trial, we randomized patients with LVEF <40% and New York Heart Association functional class II or III, despite optimal medical therapy, to treatment (1:1:1) with the probiotic yeast Saccharomyces boulardii , the antibiotic rifaximin, or standard of care (SoC) only. The primary endpoint, the baseline-adjusted LVEF at three months, was assessed in an intention-to-treat analysis. Findings We enrolled a total of 151 patients. After three months’ treatment, the LVEF did not differ significantly between the SoC arm and the rifaximin arm (mean difference was -1•2 percentage points; 95% CI -3•2 - 0•7; p=0•22) or between the SoC arm and the Saccharomyces boulardii arm (mean difference -0•2 percentage points; 95% CI -2•2 - 1•9; p=0•87). We observed no significant between-group differences in changes in microbiota diversity, TMAO, or C-reactive protein. Interpretation Three months’ treatment with Saccharomyces boulardii or rifaximin on top of SoC had no significant effect on LVEF, microbiota diversity, or the measured biomarkers in our population with HF. Funding The trial was funded by the Norwegian Association for Public Health, the Blix foundation, Stein Erik Hagen's Foundation for Clinical Heart Research, Ada og Hagbart Waages humanitære og veldedige stiftelse, Alfasigma, and Biocodex.

Graphical abstract

INTRODUCTION congenital pulmonary valve stenosis (PVS) accounts for approximately 7% of all congenital heart defects. In less severe and untreated asymptomatic forms, it might have variable outcomes with progressive stenosis or development and worsening of pulmonary regurgitation . Atrial septal defect (ASD) might be associated in up to 20% of the cases rendering an even more unpredictable outcome and efect on right ventricular (RV) volumes and function. Cardiac magnetic ressonance is considered the gold standard method to measure RV function and volumes. Three dimensional echocardiography (3D echo) emerges as a valuable, redproducible and portable alternative not only for RV volume and function analysis but also for structural evaluation. PURPOSE To describe the added value of 3D echo for the diagnostic work-up, decision making and post surgical outcome in a patient with longstanding untreated PVS associated with ASD. CASE PRESENTATION a 56 year old asymptomatic , non syndromic man , was referred by the cardiac surgeon for a comprehensive echocardiographic evaluation (CEE) due to a previous diagnosis of PVS .The patient was aware of this diagnosis since the age of 17 and no intervention was undertaken at that time. More recently a conventional echocardiogram described a moderate PVS with RV enlargement (RVE) and no futher details regarding RV function or surgical feasibility. CEE showed RVE due to volume overload (VO) with indexed end diastolic volume (EDV) of 144ml/m2 (upper limit 76ml/m2), end sistolic volume (ESV) of 57ml/m2 (upper limit 37ml/m2) and an RV ejection fraction (RVEF) of 60% (lower limit 45%) on 3D echo. RV free wall strain (RVFWS) was -25,3% , TAPSE 32mm and fractional area change 46%, all paramenters within the normal range except for RV volumes. Anatomical analysis showed PVS with three leaflets, partial comissural fusion and retraction of the edges yelding a closure gap of at least 8mm and consequent severe regurgitation. Peak transvalvular gradient was 38mmHg and pulmonary artery was dilated measuring 6.4cm. An ostium secundum atrial septal defect (ASD) with left to right shunt measuring 15x9mm by 3D echo contributed for futher RVVO. With these information , surgical intervention was undertaken and consisted of PV replacement, excision and reconstruction of the pulmonary trunk dilation and correction of the ASD. The patient recovered well and returned three months after, for a new evaluation. At that time RV volumes reduced dramatically with EDV and ESV respectively of 44ml/m2 and 19ml/m2 RVEF of 55,7% and RWFWS of -25,6%. CONCLUSION untreated congenital PVS associated with ASD may have a variable outcome . Follow-up is mandatory. In the present case a CEE including more recent technologies like 3D echo and strain imaging helped in defining anatomical findings and RV function analysis thus stating the appropriatness for surgical intervention. Abstract P1467 Figure. 3Decho pre and post surgical analysis

INTRODUCTION Mitral annular calcification (MAC) is a chronic degenerative process involving calcification of the fibrous base of the mitral valve accounting for 12% to 26% of all mitral stenosis (MS) and eventually for significant mitral regurgitation. Calcification often extends to other parts of the mitral valve apparatus but, unlike rheumatic stenosis, does not produce commissural fusion. Surgical treatment carries a high mortality rate due to technical difficulties involving the heavily calcified annulus, advanced age and comorbidities of affected patients. In recent years, transcatheter mitral valve replacement using ballon expandable transcatheter aortic valves in severe MAC (valve-in-MAC) has been used with acceptable success rates. PURPOSE To describe the added value of 3D echo in the diagnostic work-up, decision making and monitoring during the interventional procedure of valve-in-MAC. CASE PRESENTATION Two years ago a 90-year-old female in sinus rhythm with hypertension and known coronary artery disease (CAD) was admitted with symptoms of pulmonary congestion (PC). At that time, a transthoracic 3D echocardiogram showed important MAC with a mitral valve area (MVA) estimated through 3D planimetry of 1.1 cm2, pulmonary artery pressure (PAP) of 53 mmHg, preserved biventricular function and left atrial enlargement. One year later, she was readmitted with unstable CAD and treated with percutaneous transluminal angioplasty. At that time a 3D transesophageal echocardiogram (3DTOE) showed worsening of the MVA now estimated in 0.6 cm2, a mean gradient of 19 mmHg and PAP of 88 mmHg. Albeit optimized medical therapy, her functional status worsened and less than a month later she was again readmitted in NYHA functional class III. Therefore decision making for valve-in-MAC was undertaken. Valve sizing was performed with computed tomography (CT) using the D-shape method with similar findings when compared with 3D TOE measurements. Both methods showed a favourable anatomy of the left ventricular outflow tract. Valve-in-MAC procedure was performed through transvenous transseptal access and an Edwards Sapien3-nr 29 balloon-expandable valve was deployed uneventfully, except for a residual interatrial septal defect measuring 2.2x0.8cm closed two weeks after, as she persisted with PC and pulmonary hypertension. During the procedure, 3DTOE showed a partial thrombosis involving one of the prosthesis leaflets with preserved transvalvular gradients despite anticoagulation. After that, PC resolved and PAP dropped dramatically. The patient was discharged under lifelong anticoagulation and remains asymptomatic until now. CONCLUSION Diagnosing and treating patients with severe MS due to MAC remains a challenge as traditional parameters and interventional procedures don’t apply for this population. Valve-in-MAC is a feasible alternative and 3DTOE may have a pivotal role in the diagnostic work-up and interventional monitoring of these cases. Abstract P247 Figure. 3D echo timeline valve in MAC

No abstract