The sympathetic nervous system is the main stimulator of cardiac function. While acute activation of the β-adrenoceptors exerts positive inotropic and lusitropic effects by increasing cAMP and Ca2+, chronically enhanced sympathetic tone with changed β-adrenergic signaling leads to alterations of gene expression and remodeling. The CREB-regulated transcription coactivator 1 (CRTC1) is activated by cAMP and Ca2+. In the present study, the regulation of CRTC1 in cardiomyocytes and its effect on cardiac function and growth was investigated. In cardiomyocytes, isoprenaline induced dephosphorylation, and thus activation of CRTC1, which was prevented by propranolol. Crtc1-deficient mice exhibited left ventricular dysfunction, hypertrophy and enlarged cardiomyocytes. However, isoprenaline-induced contractility of isolated trabeculae or phosphorylation of cardiac troponin I, cardiac myosin-binding protein C, phospholamban, and ryanodine receptor were not altered, suggesting that cardiac dysfunction was due to the global lack of Crtc1. The mRNA and protein levels of the Gαq GTPase activating protein regulator of G-protein signaling 2 (RGS2) were lower in hearts of Crtc1-deficient mice. Chromatin immunoprecipitation and reporter gene assays showed stimulation of the Rgs2 promoter by CRTC1. In Crtc1-deficient cardiomyocytes, phosphorylation of the Gαq-downstream kinase ERK was enhanced. CRTC1 content was higher in cardiac tissue from patients with aortic stenosis or hypertrophic cardiomyopathy and from two murine models mimicking these diseases. These data suggest that increased CRTC1 in maladaptive hypertrophy presents a compensatory mechanism to delay disease progression in part by enhancing Rgs2 gene transcription. Furthermore, the present study demonstrates an important role of CRTC1 in the regulation of cardiac function and growth.

Transcatheter aortic valves have evolved over the last 15 years. Second- and third- generation devices have considerably improved, and a range of newer devices have also been introduced with the aim of decreasing the incidence of paravalvular leak, reducing the need for permanent pacemaker implantation and minimising procedure- and device-related complications. Areas covered: In this review, we highlight the special features of the latest generation of self-expanding Evolut PRO (Medtronic, Minneapolis, Minnesota) transcatheter aortic valve system. A detailed literature search on the Medtronic Evolut R and Evolut PRO transcatheter aortic valves was undertaken using Ovid, PubMed and Web of Science. Expert Commentary: In a single, small study, the Evolut PRO has shown significant improvement over the Evolut R in terms of reduced paravalvular leak and pacemaker implantation. Larger scaled studies are needed to ascertain the performance of the Evolut PRO.

Surgical management of patients with aortic valve stenosis is declining and Transcatheter aortic valve implantation (TAVI) is becoming the treatment of choice in many patients. The ESC guideline integrated results of randomized controlled trials in patients with intermediate surgical risk for the first time. TAVI showed good and comparable results to the standard surgical approach.Mitral regurgitation (MR) is a complex disease with good surgical results in primary MR and mixed results in secondary MR. Secondary MR is mainly based on left ventricular disease with subsequent dilatation. Interventional treatment with edge-to-edge-repair (Mitraclip) is an alternative therapeutic approach in patients with high surgical risk.The recommendation on treatment of concomitant coronary artery disease in patients with valvular heart disease was updated based on recent scientific results. Proximal coronary artery stenosis ≥ 70 % should be treated by percutaneous coronary intervention before TAVI or alternatively simultaneous surgical bypass grafting during valve surgery should be performed.Due to increasing interventional and surgical therapeutic options for the treatment of all four heart valves, the Heart Team is of upmost importance. The cardiologist and the cardiac surgeon should analyse all diagnostic and therapeutic results and see the patient. Colleagues of other specialities should join the team if necessary. There are several recommended requirements for heart valve centres defined in the guideline. The primary goal is excellent and individualized patient care.

Transcatheter aortic valve implantation (TAVI) has emerged as the gold standard technique for all patients with symptomatic severe aortic stenosis at elevated surgical risk. Much progress has been made to reduce procedural complications and improve patient outcomes. The impressive results of contemporary TAVI can be attributed to a variety of factors, including improving operator experience, pre-operative patient screening, and developments in transcatheter heart valve and delivery system technology. Despite these advances, serious procedural complications continue to occur and there remain some anatomical subsets and patient groups to whom TAVI technology has not been expanded. Herein we discuss these unmet needs in TAVI.

Transcatheter aortic valve implantation (TAVI) is a minimally invasive procedure to treat severe symptomatic aortic stenosis. While the TAVI procedure can be performed safely and provide excellent 5-year results, little is known about long-term durability. TAVI valves are composed of bioprosthetic leaflets are prone to deterioration, which are categorized as structural valve deterioration (SVD) and non-SVD. SVD refers to an intrinsic pathology of the leaflets or stent structure with mechanisms that include leaflet calcification, leaflet tear, stent fracture, or stent creep. Non-SVD processes include valve thrombosis, infective endocarditis and patient prosthesis mismatch. TAVI valves degenerate by similar mechanisms as bioprosthetic surgical aortic valves. Unique mechanisms that contribute to TAVI degeneration include valve crimpling, balloon expansion, stent under-expansion and valve thrombosis. The absence of a universally accepted definition of SVD poses a challenge in estimating valve durability. Traditional surgical bioprosthetic aortic valves have demonstrated excellent durability with clinically relevant SVD of 6.6% at 10-year follow up. Long-term durability of TAVI valves, however, remain poorly defined. From meta-analysis TAVI trials, SVD was estimated at 7% at 5 years. With iterative improvements in TAVI valve construction and deployment techniques, long-term durability may improve. Until long-term outcomes are better understood, TAVI should be used with caution in younger patients.

Transcatheter aortic valve implantation (TAVI) is now the accepted standard of care for patients with symptomatic severe aortic stenosis at elevated risk for conventional surgical valve replacement. Currently, societal guidelines propose the use of dual antiplatelet therapy for the prevention of thromboembolic events after TAVI in patients without an indication for oral anticoagulation. This strategy is empiric and largely based on expert consensus extrapolated from the arena of percutaneous coronary intervention. In this review, we explore the rational for using antiplatelet and/or anticoagulant strategies after TAVI, review current guidelines and the evidence underpinning them, and detail the on-going randomized trials that will shape future recommendations on this important issue.