The Evolution of Percutaneous Mitral Valve Repair Therapy Lessons Learned and Implications for Patient Selection

AbstractMitral regurgitation (MR) is the most common valve disease in the United States. However, a significant number of patients are denied surgery due to increased age, poor ventricular function, or associated comorbidities, putting them at high risk for adverse events. Moreover, the benefit of surgery for MR is unclear in patients with functional (secondary) MR. Recently, percutaneous repair of the mitral valve with a particular device (MitraClip, Abbott, Menlo Park, California) has emerged as a novel therapeutic option for patients with secondary MR or those deemed to be high risk for surgery. We review data from its initial concept through clinical trials and current data available from several registries. We focused on lessons learned regarding adequate patient selection, along with current and future perspectives on the use of device therapy for the treatment of MR

Atrial secondary tricuspid regurgitation: pathophysiology, definition, diagnosis, and treatment.

Atrial secondary tricuspid regurgitation (A-STR) is a distinct phenotype of secondary tricuspid regurgitation with predominant dilation of the right atrium and normal right and left ventricular function. Atrial secondary tricuspid regurgitation occurs most commonly in elderly women with atrial fibrillation and in heart failure with preserved ejection fraction in sinus rhythm. In A-STR, the main mechanism of leaflet malcoaptation is related to the presence of a significant dilation of the tricuspid annulus secondary to right atrial enlargement. In addition, there is an insufficient adaptive growth of tricuspid valve leaflets that become unable to cover the enlarged annular area. As opposed to the ventricular phenotype, in A-STR, the tricuspid valve leaflet tethering is typically trivial. The A-STR phenotype accounts for 10%-15% of clinically relevant tricuspid regurgitation and has better outcomes compared with the more prevalent ventricular phenotype. Recent data suggest that patients with A-STR may benefit from more aggressive rhythm control and timely valve interventions. However, little is mentioned in current guidelines on how to identify, evaluate, and manage these patients due to the lack of consistent evidence and variable definitions of this entity in recent investigations. This interdisciplinary expert opinion document focusing on A-STR is intended to help physicians understand this complex and rapidly evolving topic by reviewing its distinct pathophysiology, diagnosis, and multi-modality imaging characteristics. It first defines A-STR by proposing specific quantitative criteria for defining the atrial phenotype and for discriminating it from the ventricular phenotype, in order to facilitate standardization and consistency in research

State-of-the-Art Review: Anatomical and Imaging Considerations During Transcatheter Tricuspid Valve Repair Using an Annuloplasty Approach

Transcatheter techniques for the treatment of tricuspid regurgitation (TR) are being more frequently used and several new devices are in development. Since 90% of patients with TR have secondary TR, catheter based systems which reduce the dilated tricuspid annulus area are of particular interest. In order to perform an annuloplasty procedure effectively and safely, knowledge about the anatomy of the tricuspid valve apparatus and especially of the annulus in relation to the important neighboring structures such as the aortic root, the RCA, the electrical pathways and the CS is fundamental. In addition, comprehensive understanding of the device itself, the delivery system, its maneuverability and the individual procedural steps is required. Furthermore, the use of multi-modality imaging is important. For each step of the procedure the appropriate imaging modality as well as the optimal; imaging planes are crucial to provide the necessary information to best guide the individual procedural step

Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): A randomised controlled trial

Activation of renal sympathetic nerves is key to pathogenesis of essential hypertension. We aimed to assess effectiveness and safety of catheter-based renal denervation for reduction of blood pressure in patients with treatment-resistant hypertension. In this multicentre, prospective, randomised trial, patients who had a baseline systolic blood pressure of 160 mm Hg or more (≥150 mm Hg for patients with type 2 diabetes), despite taking three or more antihypertensive drugs, were randomly allocated in a one-to-one ratio to undergo renal denervation with previous treatment or to maintain previous treatment alone (control group) at 24 participating centres. Randomisation was done with sealed envelopes. Data analysers were not masked to treatment assignment. The primary effectiveness endpoint was change in seated office-based measurement of systolic blood pressure at 6 months. Primary analysis included all patients remaining in follow-up at 6 months. This trial is registered with ClinicalTrials.gov, number NCT00888433. 106 (56) of 190 patients screened for eligibility were randomly allocated to renal denervation (n=52) or control (n=54) groups between June 9, 2009, and Jan 15, 2010. 49 (94) of 52 patients who underwent renal denervation and 51 (94) of 54 controls were assessed for the primary endpoint at 6 months. Office-based blood pressure measurements in the renal denervation group reduced by 32/12 mm Hg (SD 23/11, baseline of 178/96 mm Hg, p<0·0001), whereas they did not differ from baseline in the control group (change of 1/0 mm Hg [21/10], baseline of 178/97 mm Hg, p=0·77 systolic and p=0·83 diastolic). Between-group differences in blood pressure at 6 months were 33/11 mm Hg (p<0·0001). At 6 months, 41 (84) of 49 patients who underwent renal denervation had a reduction in systolic blood pressure of 10 mm Hg or more, compared with 18 (35) of 51 controls (p<0·0001). We noted no serious procedure-related or device-related complications and occurrence of adverse events did not differ between groups; one patient who had renal denervation had possible progression of an underlying atherosclerotic lesion, but required no treatment. Catheter-based renal denervation can safely be used to substantially reduce blood pressure in treatment-resistant hypertensive patients. Ardian. © 2010 Elsevier Ltd

Mycosands: Fungal diversity and abundance in beach sand and recreational waters — Relevance to human health

The goal of most studies published on sand contaminants is to gather and discuss knowledge to avoid faecal contamination of water by run-offs and tide-retractions. Other life forms in the sand, however, are seldom studied but always pointed out as relevant. The Mycosands initiative was created to generate data on fungi in beach sands and waters, of both coastal and freshwater inland bathing sites. A team of medical mycologists and water quality specialists explored the sand culturable mycobiota of 91 bathing sites, and water of 67 of these, spanning from the Atlantic to the Eastern Mediterranean coasts, including the Italian lakes and the Adriatic, Baltic, and Black Seas. Sydney (Australia) was also included in the study. Thirteen countries took part in the initiative. The present study considered several fungal parameters (all fungi, several species of the genus Aspergillus and Candida and the genera themselves, plus other yeasts, allergenic fungi, dematiaceous fungi and dermatophytes). The study considered four variables that the team expected would influence the results of the analytical parameters, such as coast or inland location, urban and non-urban sites, period of the year, geographical proximity and type of sediment. The genera most frequently found were Aspergillus spp., Candida spp., Fusarium spp. and Cryptococcus spp. both in sand and in water. A site-blind median was found to be 89 Colony-Forming Units (CFU) of fungi per gram of sand in coastal and inland freshwaters, with variability between 0 and 6400 CFU/g. For freshwater sites, that number was 201.7 CFU/g (0, 6400 CFU/g (p = 0.01)) and for coastal sites was 76.7 CFU/g (0, 3497.5 CFU/g). For coastal waters and all waters, the median was 0 CFU/ml (0, 1592 CFU/ml) and for freshwaters 6.7 (0, 310.0) CFU/ml (p 0.001). The results advocate that beaches should be monitored for fungi for safer use and better management. © 2021 Elsevier B.V.A. Abdillah, M. C. Esposto, J. Kabtani, K. Sarioglou, P. E. Verweij and F. Vieira for their collaboration in this study; the European Confederation of Medical Mycology for a seeding grant; the International Society for Human and Animal Mycology for some financial support; financial support from CESAM ( UID/AMB/50017-POCI-01-0145-FEDER-007638 ) and CITAB ( UID/AGR/04033/2019 ), via FCT/MCTES, from national funds (PIDDAC), cofounded by FEDER, (PT2020 Partnership Agreement and Compete 2020) and an NHMRC APP1121936 to W. Meyer; National and Kapodistrian University of Athens, Greece, Special Accounts for Research Grants (SARG K.A. 70/3/6915).UID/AGR/04033/2019; Centro de Estudos Ambientais e Marinhos, Universidade de Aveiro, CESAM: UID/AMB/50017-POCI-01-0145-FEDER-007638; National Health and Medical Research Council, NHMRC: APP1121936; Fundação para a Ciência e a Tecnologia, FCT; National and Kapodistrian University of Athens: 70/3/6915; Ministério da Ciência, Tecnologia e Ensino Superior, MCTE

-Active AKT signaling triggers CLL towards Richter's transformation via over-activation of Notch1

Richter's transformation (RT) is an aggressive lymphoma which occurs upon progression from chronic lymphocytic leukemia (CLL). Transformation has been associated with genetic aberrations in the CLL-phase involving TP53, CDKN2A, MYC, and NOTCH1, however a significant proportion of RT cases lack CLL-phase associated events. Here, we report that high levels of AKT phosphorylation occurs both in high-risk CLL patients harboring TP53 and NOTCH1 mutations as well as in RT patients. Genetic over-activation of Akt in the murine E-TCL1 CLL mouse model resulted in CLL to RT with significantly reduced survival and an aggressive lymphoma phenotype. In the absence of recurrent mutations, we identified a profile of genomic aberrations intermediate between CLL and DLBCL. Multi-omics assessment by phosphoproteomic/proteomic and single-cell transcriptomic profiles of this Akt-induced murine RT revealed a S100-protein-defined subcluster of highly aggressive lymphoma cells, which developed from CLL cells, through activation of Notch via Notch ligand expressed by T cells. Constitutively active Notch1 similarly induced RT of murine CLL. We identify Akt activation as an initiator of CLL transformation towards aggressive lymphoma by inducing Notch signaling between RT cells and microenvironmental T cells