Transcatheter Repair and Replacement Technologies for Mitral Regurgitation:a European Perspective

PURPOSE OF REVIEW: We aimed to picture the contemporary landscape of available catheter-based repair and replacement solutions for mitral regurgitation (MR) in Europe. RECENT FINDINGS: Edge-to-edge repair remains the dominant technique for transcatheter mitral valve repair especially in the context of secondary mitral regurgitation. Two recent randomized trials reported seemingly contradicting clinical results with transcatheter edge-to-edge repair for patients with heart failure and severe secondary MR. A proportionality framework related to secondary MR was proposed to help explain inconsistencies but requires further research. (In)Direct annuloplasty primarily aims to correct secondary MR; however, the scientific basis seems less robust. One dedicated transcatheter heart valve has the CE mark for mitral valve replacement but requires transapical access. Balloon-expandable transcatheter aortic valve platforms are emerging for transvenous transseptal mitral replacement in the context of mitral annular calcification, a failing surgical mitral bioprosthesis, or annuloplasty. Advanced computed tomography imaging techniques improved pre-procedural planning and introduced the option for modeling and simulation. SUMMARY: Development of a toolbox of catheter-based technologies, complementary imaging modalities, and refined patient selection offer novel perspectives to high-risk patients with primary or secondary MR. Clinical trials are required to help formulate evidence-based guidelines for the management of mitral valve disease

Photochemistry and structural aspects of the photosystem 2 reaction centre

In this Thesis, a number of spectroscopic measurements are presented on Photosystem II (PsII) preparations from spinach, which provide some new information on the PSII reaction centre structure and function.The experimental part of this thesis is preceded by a general introduction (Chapter 1) and a brief overview of methods and techniques used (Chapter 2).In Chapter 3, a low temperature Electron Paramagnetic Resonance (EPR) study on PSII-enriched membranes is presented. The redox dependencies of the light-inducible signals from the spin-polarised reaction centre triplet state and signals from the semiquinone-iron (Q A-Fe 2+) acceptor complex were studied. It was found that the reaction centre triplet signal was only seen after the Q A-Fe 2+signal had disappeared on double reduction of Q A .In Chapter 4, a time-resolved fluorescence study at ambient temperature is presented on samples in which Q A was oxidised, singly reduced or doubly reduced. Two types of preparations were used: PSII-enriched membranes (with large antenna size) and PSII core complexes (partly stripped of antenna). The results indicated that the effective rate of charge separation was larger when Q A was oxidised or doubly reduced than when it was singly reduced. In addition, it was found that the lifetime of the primary radical pair state increases when going from the singly reduced state of Q A to the doubly reduced state. The differences between the two types of preparation and the reversibility of the double reduction of Q A were also investigated.In Chapter 5, a more detailed EPR study of the reversibility of the double reduction of Q A in PSII-enriched membranes is presented. Only a small degree of reversibility was found. In addition, the non-heme iron was found to be irreversibly modified (possibly lost) upon double reduction of Q A , which may explain the lack of reversibility.In Chapter 6, the orientation dependence of the reaction centre triplet EPR signal was determined in oriented samples. Both PSII-enriched membranes and D 1 D 2 reaction centre preparations were used. The reaction centre triplet state was found to be localised on a reaction centre chlorophyll of which the tetrapyrrolic plane is oriented at 30° to the membrane plane.In Chapter 7, time-resolved EPR experiments on oriented samples (PSII-enriched membranes) are described. Thus, the risetime of the reaction centre triplet state was estimated to be of the order of 300 - 400 ns.In Chapter 8, low temperature flash-induced absorbance difference measurements are presented on PSII enriched membranes under several redox conditions, including those having Q A singly or doubly reduced. These experiments provided an unexpected explanation for the absence of a detectable EPR triplet signal when Q A is singly reduced (see above): the lifetime is too short to give a measurable signal under continuous illumination. Furthermore, the lifetime of the primary radical pair state was found to increase when going from the singly reduced state of Q A to the doubly reduced state. Finally, low temperature absorbance difference spectra are presented and analysed. These were found to be significantly different from difference spectra in the literature obtained using D 1 D 2 preparations. It was concluded that presently available D 1 D 2 preparations are considerably modified on the donor side compared to PSII-enriched membrane preparations

The effect of transcatheter aortic valve implantation on pulmonary artery pressures in a patient suffering from chronic heart failure:A case report

BACKGROUND: Pulmonary hypertension (PH) is most commonly caused by left-sided heart disease and may negatively affect the long-term prognosis and quality of life of patients with chronic heart failure (CHF). CardioMEMS (Micro-Electro-Mechanical-System) allows physicians to monitor pulmonary artery (PA) pressures remotely and optimize heart failure treatment based on haemodynamic parameters, which provides further insight into the effect of valvular interventions. CASE SUMMARY: We present a case of a 61-year-old male patient with an ischaemic cardiomyopathy, poor LV function, moderate to severe mitral regurgitation, and severe aortic valve regurgitation in refractory heart failure. Right heart catheterization and CardioMEMS monitoring revealed severe pulmonary hypertension with mean PA pressures of 55 mmHg and a mean pulmonary capillary wedge pressure of 21 mmHg despite up titration of heart failure medication and sildenafil. Pulmonary and systemic causes of pulmonary hypertension were excluded. After heart team consensus, the patient underwent transcatheter aortic valve implantation (TAVI) which resulted in normalization of PA pressures and a significant improvement of functional performance. DISCUSSION: To the best of our knowledge, this is the first case report describing the direct effects of TAVI on continuous PA pressures in a patient with poor LV function and severe aortic regurgitation. Elective TAVI appeared to be safe and very effective in reverting severe pulmonary hypertension. Most strikingly, drug interventions could not affect the elevated pulmonary pressures, but TAVI corrected the aortic valve insufficiency with normalization of left-sided pulmonary hypertension

The first human experience of a contact force sensing catheter for epicardial ablation of ventricular tachycardia

Contact force (CF) is one of the major determinants for sufficient lesion formation. CF-guided procedures are associated with enhanced lesion formation and procedural success.We report our initial experience in epicardial ventricular tachycardia (VT) ablation with a force-sensing catheter using a new approach with an angioplasty balloon. Two patients with arrhythmogenic right ventricular cardiomyopathy who underwent prior unsuccessful endocardial ablation were treated with epicardial VTablation. CF data were used to titrate force, power and ablation time

Epidemic processes in complex networks

In recent years the research community has accumulated overwhelming evidence for the emergence of complex and heterogeneous connectivity patterns in a wide range of biological and sociotechnical systems. The complex properties of real-world networks have a profound impact on the behavior of equilibrium and nonequilibrium phenomena occurring in various systems, and the study of epidemic spreading is central to our understanding of the unfolding of dynamical processes in complex networks. The theoretical analysis of epidemic spreading in heterogeneous networks requires the development of novel analytical frameworks, and it has produced results of conceptual and practical relevance. A coherent and comprehensive review of the vast research activity concerning epidemic processes is presented, detailing the successful theoretical approaches as well as making their limits and assumptions clear. Physicists, mathematicians, epidemiologists, computer, and social scientists share a common interest in studying epidemic spreading and rely on similar models for the description of the diffusion of pathogens, knowledge, and innovation. For this reason, while focusing on the main results and the paradigmatic models in infectious disease modeling, the major results concerning generalized social contagion processes are also presented. Finally, the research activity at the forefront in the study of epidemic spreading in coevolving, coupled, and time-varying networks is reported.Comment: 62 pages, 15 figures, final versio

Multi-Layer Cyber-Physical Security and Resilience for Smart Grid

The smart grid is a large-scale complex system that integrates communication technologies with the physical layer operation of the energy systems. Security and resilience mechanisms by design are important to provide guarantee operations for the system. This chapter provides a layered perspective of the smart grid security and discusses game and decision theory as a tool to model the interactions among system components and the interaction between attackers and the system. We discuss game-theoretic applications and challenges in the design of cross-layer robust and resilient controller, secure network routing protocol at the data communication and networking layers, and the challenges of the information security at the management layer of the grid. The chapter will discuss the future directions of using game-theoretic tools in addressing multi-layer security issues in the smart grid.Comment: 16 page

Insights in a restricted temporary pacemaker strategy in a lean transcatheter aortic valve implantation program

OBJECTIVES: To study the safety and feasibility of a restrictive temporary‐RV‐pacemaker use and to evaluate the need for temporary pacemaker insertion for failed left ventricular (LV) pacing ability (no ventricular capture) or occurrence of high‐degree AV‐blocks mandating continuous pacing. BACKGROUND: Ventricular pacing remains an essential part of contemporary transcatheter aortic valve implantation (TAVI). A temporary‐right‐ventricle (RV)‐pacemaker lead is the standard approach for transient pacing during TAVI but requires central venous access. METHODS: An observational registry including 672 patients who underwent TAVI between June 2018 and December 2020. Patients received pacing on the wire when necessary, unless there was a high‐anticipated risk for conduction disturbances post‐TAVI, based on the baseline‐ECG. The follow‐up period was 30 days. RESULTS: A temporary‐RV‐pacemaker lead (RVP‐cohort) was inserted in 45 patients, pacing on the wire (LVP‐cohort) in 488 patients, and no pacing (NoP‐cohort) in 139 patients. A bailout temporary pacemaker was implanted in 14 patients (10.1%) in the NoP‐cohort and in 24 patients (4.9%) in the LVP‐cohort. One patient in the LVP‐cohort needed an RV‐pacemaker for incomplete ventricular capture. Procedure time was significantly longer in the RVP‐cohort (68 min [IQR 52–88.] vs. 55 min [IQR 44–72] in NoP‐cohort and 55 min [IQR 43–71] in the LVP‐cohort [p < 0.005]). Procedural high‐degree AV‐block occurred most often in the RVP‐cohort (45% vs. 14% in the LVP and 16% in the NoP‐cohort [p ≤ 0.001]). Need for new PPI occurred in 47% in the RVP‐cohort, versus 20% in the NoP‐cohort and 11% in the LVP‐cohort (p ≤ 0.001). CONCLUSION: A restricted RV‐pacemaker strategy is safe and shortens procedure time. The majority of TAVI‐procedures do not require a temporary‐RV‐pacemaker

Immediate versus staged revascularisation of non-culprit arteries in patients with acute coronary syndrome: a systematic review and meta-analysis

Although there is robust evidence that revascularisation of non-culprit vessels should be pursued in patients presenting with an acute coronary syndrome (ACS) and multivessel coronary artery disease (MVD), the optimal timing of complete revascularisation remains disputed. In this systematic review and meta-analysis our results suggest that outcomes are comparable for immediate and staged complete revascularisation in patients with ACS and MVD. However, evidence from randomised controlled trials remains scarce and cautious interpretation of these results is recommended. More non-biased evidence is necessary to aid future decision making on the optimal timing of complete revascularisation