Abstract
The structural characterization of microgels at interfaces is fundamental to understand both their 2D phase behavior and their role as stabilizers that enable emulsions to be broken on ...demand. However, this characterization is usually limited by available experimental techniques, which do not allow a direct investigation at interfaces. To overcome this difficulty, here we employ neutron reflectometry, which allows us to probe the structure and responsiveness of the microgels in-situ at the air-water interface. We investigate two types of microgels with different cross-link density, thus having different softness and deformability, both below and above their volume phase transition temperature, by combining experiments with computer simulations of in silico synthesized microgels. We find that temperature only affects the portion of microgels in water, while the strongest effect of the microgels softness is observed in their ability to protrude into the air. In particular, standard microgels have an apparent contact angle of few degrees, while ultra-low cross-linked microgels form a flat polymeric layer with zero contact angle. Altogether, this study provides an in-depth microscopic description of how different microgel architectures affect their arrangements at interfaces, and will be the foundation for a better understanding of their phase behavior and assembly.
Impurities in crystals generally cause point defects and can even suppress crystallization. This general rule, however, does not apply to colloidal crystals formed by soft microgel particles Iyer ...ASJ, Lyon LA (2009) Angew Chem Int Ed 48:4562–4566, as, in this case, the larger particles are able to shrink and join the crystal formed by a majority of smaller particles. Using small-angle X-ray scattering, we find the limit in large-particle concentration for this spontaneous deswelling to persist. We rationalize our data in the context of those counterions that are bound to the microgel particles as a result of the electrostatic attraction exerted by the fixed charges residing on the particle periphery. These bound counterions do not contribute to the suspension osmotic pressure in dilute conditions, as they can be seen as internal degrees of freedom associated with each microgel particle. In contrast, at sufficiently high particle concentrations, the counterion cloud of each particle overlaps with that of its neighbors, allowing these ions to freely explore the space outside the particles. We confirm this scenario by directly measuring the osmotic pressure of the suspension. Because these counterions are then no longer bound, they create an osmotic pressure difference between the inside and outside of the microgels, which, if larger than the microgel bulk modulus, can cause deswelling, explaining why large, soft microgel particles feel the squeeze when suspended with a majority of smaller particles. We perform small-angle neutron scattering measurements to further confirm this remarkable behavior.
Differences in terms of safety and efficacy of percutaneous edge-to-edge mitral repair between patients with functional and degenerative mitral regurgitation (MR) are not well established. We ...performed a systematic review and meta-analysis to clarify these differences.
PubMed, EMBASE, Google scholar database and international meeting abstracts were searched for all studies about MitraClip. Studies with <25 patients or where 1-year results were not delineated between MR aetiology were excluded. This study is registered with PROSPERO.
A total of nine studies investigating the mid-term outcome of percutaneous edge-to-edge repair in patients with functional versus degenerative MR were included in the meta-analysis (n=2615). At 1 year, there were not significant differences among groups in terms of patients with MR grade≤2 (719/1304 vs 295/504; 58% vs 54%; risk ratio (RR) 1.12; 95% CI: 0.86 to 1.47; p=0.40), while there was a significantly lower rate of mitral valve re-intervention in patients with functional MR compared with those with degenerative MR (77/1770 vs 80/818; 4% vs 10%; RR 0.60; 95% CI: 0.38 to 0.97; p=0.04). One-year mortality rate was 16% (408/2498) and similar among groups (RR 1.26; 95% CI: 0.90 to 1.77; p=0.18). Functional MR group showed significantly higher percentage of patients in New York Heart Association class III/IV (234/1480 vs 49/583; 16% vs 8%; p<0.01) and re-hospitalisation for heart failure (137/605 vs 31/220; 23% vs 14%; p=0.03). No differences were found in terms of single leaflet device attachment (25/969 vs 20/464; 3% vs 4%; p=0.81) and device embolisation (no events reported in both groups) at 1 year.
This meta-analysis suggests that percutaneous edge-to-edge repair is likely to be an efficacious and safe option in patients with both functional and degenerative MR. Large, randomised studies are ongoing and awaited to fully assess the clinical impact of the procedure in these two different MR aetiologies.
Background Transcatheter aortic valve replacement (TAVR)-in-TAVR is a possible treatment for transcatheter heart valve (THV) degeneration. However, the displaced leaflets of the first THV will create ...a risk plane (RP) under which the passage of a coronary catheter will be impossible. The aim of our study was to evaluate the potential risk of impaired coronary access (CA) after TAVR-in-TAVR. Methods and Results We prospectively performed coronary angiography after TAVR with different THVs in 137 consecutive patients, looking where the catheter crossed the valve frame. If coronary cannulation was achieved from below the RP, the distance between valve frame and aortic wall was measured by aortic angiography. CA after TAVR-in-TAVR was defined as feasible if the catheter passed above the RP, as theoretically feasible if passed under the RP with valve-to-aorta distance >2 mm, and as unfeasible if passed under the RP with valve-to-aorta distance ≤2 mm. Seventy-two patients (53%) received a Sapien 3 THV, 26 (19%) received an Evolut Pro/R THV, and 39 (28%) received an Acurate Neo THV. CA after TAVR-in-TAVR was considered feasible in 40.9% (68.1%, 19.2%, and 5.1%, respectively;
<0.001), theoretically feasible in 27.7% (8.3%, 42.3%, and 53.8%, respectively;
<0.001), and unfeasible in 31.4% (23.6%, 38.5%, and 41.1%, respectively;
=0.116). Independent predictors of impaired CA after TAVR-in-TAVR were female sex (odds ratio OR, 3.99; 95% CI, 1.07-14.86;
=0.040), sinotubular junction diameter (OR, 0.62; 95% CI, 0.48-0.80;
<0.001), and implantation of a supra-annular THV (OR, 6.61; 95% CI, 1.98-22.03;
=0.002). Conclusions CA after TAVR-in-TAVR might be unfeasible in >30% of patients currently treated with TAVR. Patients with a small sinotubular junction and those who received a supra-annular THV are at highest risk of potential CA impairment with TAVR-in-TAVR.
Microgels composed of thermoresponsive polymer poly(N-isopropylacrylamide) (PNIPAM) are interfacial active. Their adsorption leads to deformation, causing conformational changes that have profound ...effects on the macroscopic properties of these films. Yet, methods to quantitatively probe the local density are lacking. We introduced scanning force microscopy (SFM) to quantitatively probe the internal structure of microgels physically adsorbed on a solid (SiO2)/water interface. Using a sharp SFM tip, we investigated the two types of microgels: (i) core–shell microgels featuring a hard silica core and a PNIPAM shell and (ii) hollow microgels obtained by dissolution of the silica core. Thus, both systems have the same polymer network as the peripheral structure but a distinctly different internal structure, that is, a rigid core versus a void. By evaluating the force–distance curves, the force profile during insertion of the tip into the polymer network enables to determine a depth-dependent contact resistance, which closely correlates with the density profiles determined in solution by small-angle neutron scattering. We found that the cavity of the swollen hollow microgels is still present when adsorbed to the solid substrate. Remarkably, while currently used techniques such as colloidal probe or reflectometry only provide an average of the z-profile, the methodology introduced herein actually probes the real three-dimensional density profile, which is ultimately important to understand the macroscopic behavior of microgel films. This will bridge the gap between the colloidal probe experiments that deform the microgel globally and the insertion in which the disturbance is located near the tip.
COAPT-trial entry criteria are useful to identify patients with better outcomes after transcatheter edge-to-edge repair (TEER). However, up to one-half of real-world patients with secondary mitral ...regurgitation (SMR) undergoing TEER do not meet these highly selective criteria and no study has formally investigated them. The aim of this study was to evaluate the predictors of good outcome after TEER in COAPT-ineligible patients.
All consecutive patients with SMR and heart failure (HF) treated with MitraClip at 3 European centres were retrospectively screened. The presence of at least 1 COAPT exclusion criterion was used to define a COAPT-ineligible profile, allowing the inclusion in the study population. Freedom from all-cause death or HF hospitalisation was evaluated at 2-year follow-up (primary end point).
A total of 305 patients (47%) had a COAPT-ineligible profile. An overall 58% rate of all-cause death or HF hospitalisation was detected at 2 years. Patients with a single COAPT exclusion criterion experienced fewer adverse events than those with multiple criteria (55% vs 69%). At multivariable Cox regression analysis, New York Heart Association functional class II, younger age (< 75 years), lower serum creatinine (< 2 mg/dL), lower left ventricular end-diastolic volume (< 240 mL), and the absence of hemodynamic instability, atrial fibrillation, and chronic obstructive pulmonary disease were independently associated with good outcome.
In this real-world series of patients with SMR undergoing TEER, a COAPT-ineligible profile was common. The presence of only 1 COAPT exclusion criterion or the absence of hemodynamic instability were associated with the most favourable outcomes.
Les critères d’admission à l’étude COAPT (CardiovascularOutcomesAssessment of the MitraClipPercutaneousTherapy for Heart Failure Patients With Functional Mitral Regurgitation) sont utiles pour identifier les patients susceptibles d’obtenir de meilleurs résultats après une réparation mitrale percutanée bord à bord (RMPBB). Cependant, en contexte réel, jusqu’à la moitié des patients atteints d'insuffisance mitrale secondaire (IMS) qui subissent une RMPBB ne répondent pas à ces critères hautement sélectifs et aucune étude formelle ne les a formellement étudiés. La présente étude visait à évaluer les prédicteurs d’une issue favorable à la suite d’une RMPBB chez les patients non admissibles selon les critères de l’étude COAPT.
Tous les patients consécutifs atteints d'IMS et d’insuffisance cardiaque (IC) traités au moyen d’un dispositif MitraClip dans trois centres européens ont été choisis de façon rétrospective. La présence d’au moins un critère d’exclusion de l’étude COAPT a été utilisée pour définir un profil non admissible selon les critères COAPT, et admettre les patients dans la population de la présente étude. L’absence de décès toutes causes confondues et d’hospitalisation pour IC a été évaluée après un suivi de deux ans (critère d’évaluation principal).
Au total, 305 patients (47 %) présentaient un profil non admissible selon les critères COAPT. Un taux global de 58 % de décès toutes causes confondues ou d’hospitalisation pour IC a été observé après un suivi de deux ans. Chez les patients présentant un seul critère d’exclusion de l’étude COAPT, la fréquence de manifestations indésirables a été plus faible que chez les patients présentant plus d’un critère d’exclusion (55 % vs 69 %). Dans une analyse de régression de Cox multivariée, la classe II de la classification de la NYHA, un âge moins avancé (< 75 ans), un taux sérique de créatinine faible (< 2 mg/dl), un volume télédiastolique faible dans le ventricule gauche (< 240 ml), et l’absence d’instabilité hémodynamique, de fibrillation auriculaire et de maladie pulmonaire obstructive chronique ont été des variables associées de façon indépendante à une issue favorable.
Chez cette série de patients traités en contexte réel qui étaient atteints d'IMS et qui ont été soumis à une RMPBB, un profil non admissible selon les critères de l’étude COAPT était une ca- ractéristique courante. La présence d’un seul critère d’exclusion de l’étude COAPT ou l’absence d’instabilité hémodynamique ont été associées aux issues les plus favorables.
ABSTRACT
Aims
Low serum albumin levels are associated with poor prognosis in numerous chronic disease states but the relationship between albumin and outcomes in patients with heart failure (HF) and ...secondary mitral regurgitation (SMR) has not been described.
Methods and results
The randomized COAPT trial evaluated the safety and effectiveness of transcatheter edge‐to‐edge repair (TEER) with the MitraClipTM plus guideline‐directed medical therapy (GDMT) versus GDMT alone in patients with symptomatic HF and moderate‐to‐severe or severe SMR. Baseline serum albumin levels were measured at enrolment. Among 614 patients enrolled in COAPT, 559 (91.0%) had available baseline serum albumin levels (median 4.0 g/dl, interquartile range 3.7–4.2 g/dl). Patients with albumin <4.0 g/dl compared with ≥4.0 g/dl were older and more likely to have ischaemic cardiomyopathy and a hospitalization within the year prior to enrolment. After multivariable adjustment, patients with albumin <4.0 g/dl had higher 4‐year rates of all‐cause death (63.7% vs. 47.6%; adjusted hazard ratio 1.34, 95% confidence interval 1.02–1.74; p = 0.032), but there were no significant differences in HF hospitalizations (HFH) or all‐cause hospitalizations according to baseline serum albumin level. The relative effectiveness of TEER plus GDMT versus GDMT alone was consistent in patients with low and high albumin levels (pinteraction = 0.19 and 0.35 for death and HFH, respectively).
Conclusion
Low baseline serum albumin levels were independently associated with reduced 4‐year survival in patients with HF and severe SMR enrolled in the COAPT trial, but not with HFH. Patients treated with TEER derived similarly robust reductions in both death and HFH regardless of baseline albumin level.
Patients with heart failure with moderate‐severe/severe mitral regurgitation stratified by serum albumin level. CI, confidence interval; GDMT, guideline‐directed medical therapy; HFH, heart failure hospitalization; HR, hazard ratio; TEER, transcatheter edge‐to‐edge repair.
As one of the most prevalent valvular pathologies affecting millions globally, moderate-to-severe tricuspid regurgitation (TR) predisposes to increased mortality. Despite the well-established risk of ...adverse outcomes, an overwhelming majority of TR patients are managed conservatively due to challenges associated with timely diagnosis, clinical course of the disease, competing comorbities that carry prohibitive surgical risk, and poor surgical outcomes. These challenges highlight the importance of transcatheter tricuspid valve replacement (TTVR) which has restructured TR management in promising and innovative ways.Background and ObjectiveAs one of the most prevalent valvular pathologies affecting millions globally, moderate-to-severe tricuspid regurgitation (TR) predisposes to increased mortality. Despite the well-established risk of adverse outcomes, an overwhelming majority of TR patients are managed conservatively due to challenges associated with timely diagnosis, clinical course of the disease, competing comorbities that carry prohibitive surgical risk, and poor surgical outcomes. These challenges highlight the importance of transcatheter tricuspid valve replacement (TTVR) which has restructured TR management in promising and innovative ways.We start with an overview of the pathophysiology of TR considering its implications in management. We then elaborate on the current state of TR management, including its limitations, thereby highlighting the unique role of TTVR. This is followed by a review of perioperative considerations such as careful patient selection, role of multimodality imaging, the various imaging techniques that are available and their contribution towards successful TTVR. We then review the valves that are currently available and under investigation, including the latest data available on device efficacy and safety, and highlight the ongoing clinical trials.MethodsWe start with an overview of the pathophysiology of TR considering its implications in management. We then elaborate on the current state of TR management, including its limitations, thereby highlighting the unique role of TTVR. This is followed by a review of perioperative considerations such as careful patient selection, role of multimodality imaging, the various imaging techniques that are available and their contribution towards successful TTVR. We then review the valves that are currently available and under investigation, including the latest data available on device efficacy and safety, and highlight the ongoing clinical trials.TTVR is evolving at an exponential pace and has made its mark in the treatment of severe symptomatic tricuspid regurgitation. The promising results sustained by currently available devices and ongoing investigation of valves under development continue to pave the path for further innovation in transcatheter interventions. However, it is important to acknowledge and appreciate the novelty of this approach, the lack of long-term data on safety, efficacy, morbidity, and mortality, and use the lessons learned from real-world experiences to provide a definitive and reproducible solution for patients with symptomatic TR.Results and ConclusionsTTVR is evolving at an exponential pace and has made its mark in the treatment of severe symptomatic tricuspid regurgitation. The promising results sustained by currently available devices and ongoing investigation of valves under development continue to pave the path for further innovation in transcatheter interventions. However, it is important to acknowledge and appreciate the novelty of this approach, the lack of long-term data on safety, efficacy, morbidity, and mortality, and use the lessons learned from real-world experiences to provide a definitive and reproducible solution for patients with symptomatic TR.
PDF
