Prospective Evaluation of Transseptal TMVR for Failed Surgical Bioprostheses: MITRAL Trial Valve-in-Valve Arm 1-Year Outcomes

OBJECTIVES: The aim of this study was to assess 1-year clinical outcomes among high-risk patients with failed surgical mitral bioprostheses who underwent transseptal mitral valve-in-valve (MViV) with the SAPIEN 3 aortic transcatheter heart valve (THV) in the MITRAL (Mitral Implantation of Transcatheter Valves) trial. BACKGROUND: The MITRAL trial is the first prospective study evaluating transseptal MViV with the SAPIEN 3 aortic THV in high-risk patients with failed surgical mitral bioprostheses. METHODS: High-risk patients with symptomatic moderate to severe or severe mitral regurgitation (MR) or severe mitral stenosis due to failed surgical mitral bioprostheses were prospectively enrolled. The primary safety endpoint was technical success. The primary THV performance endpoint was absence of MR grade ≥2+ or mean mitral valve gradient ≥10 mm Hg (30 days and 1 year). Secondary endpoints included procedural success and all-cause mortality (30 days and 1 year). RESULTS: Thirty patients were enrolled between July 2016 and October 2017 (median age 77.5 years [interquartile range (IQR): 70.3 to 82.8 years], 63.3% women, median Society of Thoracic Surgeons score 9.4% [IQR: 5.8% to 12.0%], 80% in New York Heart Association functional class III or IV). The technical success rate was 100%. The primary performance endpoint in survivors was achieved in 96.6% (28 of 29) at 30 days and 82.8% (24 of 29) at 1 year. Thirty-day all-cause mortality was 3.3% and was unchanged at 1 year. The only death was due to airway obstruction after swallowing several pills simultaneously 29 days post-MViV. At 1-year follow-up, 89.3% of patients were in New York Heart Association functional class I or II, the median mean mitral valve gradient was 6.6 mm Hg (interquartile range: 5.5 to 8.9 mm Hg), and all patients had MR grade ≤1+. CONCLUSIONS: Transseptal MViV in high-risk patients was associated with 100% technical success, low procedural complication rates, and very low mortality at 1 year. The vast majority of patients experienced significant symptom alleviation, and THV performance remained stable at 1 year

Perioperative echocardiography-guided hemodynamic therapy in high-risk patients:a practical expert approach of hemodynamically focused echocardiography

The number of high-risk patients undergoing surgery is growing. To maintain adequate hemodynamic functioning as well as oxygen delivery to the vital organs (DO2) amongst this patient population, a rapid assessment of cardiac functioning is essential for the anesthesiologist. Pinpointing any underlying cardiovascular pathophysiology can be decisive to guide interventions in the intraoperative setting. Various techniques are available to monitor the hemodynamic status of the patient, however due to intrinsic limitations, many of these methods may not be able to directly identify the underlying cause of cardiovascular impairment. Hemodynamic focused echocardiography, as a rapid diagnostic method, offers an excellent opportunity to examine signs of filling impairment, cardiac preload, myocardial contractility and the function of the heart valves. We thus propose a 6-step-echocardiographic approach to assess high-risk patients in order to improve and maintain perioperative DO2. The summary of all echocardiographic based findings allows a differentiated assessment of the patient's cardiovascular function and can thus help guide a (patho)physiological-orientated and individualized hemodynamic therapy

Patent foramen ovale: Unanswered questions

The foramen ovale is a remnant of the fetal circulation that remains patent in 20-25% of the adult population. Although long overlooked as a potential pathway that could produce pathologic conditions, the presence of a patent foramen ovale (PFO) has been associated with a higher than expected frequency in a variety of clinical syndromes including cryptogenic stroke, migraines, sleep apnea, platypnea-orthodeoxia, deep sea diving associated decompression illness, and high altitude pulmonary edema. A unifying hypothesis is that a chemical or particulate matter from the venous circulation crosses the PFO conduit between the right and left atria to produce a variety of clinical syndromes. Although observational studies suggest a therapeutic benefit of PFO closure compared to medical therapy alone in patients with cryptogenic stroke, 3 randomized controlled trials (RCTs) did not confirm the superiority of PFO closure for the secondary prevention of stroke. However, meta-analyses of these RCTs demonstrate a significant benefit of PFO closure over medical therapy alone. Similarly, observational studies provide support for PFO closure for symptomatic relief of migraines. But one controversial randomized study failed to replicate the results of the observational studies while another two demonstrated a partial benefit. The goal of this review is to discuss the clinical conditions associated with PFO and provide internists and primary care physicians with current data on PFO trials, and clinical insight to help guide their patients who are found to have a PFO on echocardiographic testing

PM Dimensional Characterization in an Urban Mediterranean Area: Case Studies on the Separation between Fine and Coarse Atmospheric Aerosol

Fine particulate matter (PM) is object of particular attention due to its health effects. It is currently regulated by adopting PM2.5 as an indicator to control anthropogenic combustion emissions. Therefore, it is crucial to collect aerosol samples representative of such sources, without including PM from natural sources. Thus, a clean separation between coarse and fine mode aerosol should be set. With this purpose, aerosol size mass distribution was taken in the aerodynamic diameter range from 0.5 to 10 µm. In comparison with a base scenario, characterized by local pollution sources, three case studies were considered, involving desert dust advection, sea salt advection and forest fire aerosol from a remote area. In the base scenario, PM2.5 represented a suitable fine-mode indicator, whereas it was considerably affected by coarse PM in case of desert dust and sea salt aerosol advection. Such interference was considerably reduced by setting the fine/coarse separation at 1.0 µm. Such separation underrepresented fine PM from forest fire long-range transport, nonetheless in the case studies considered, PM1 represented the best indicator of fine aerosol since less affected by coarse natural sources. The data presented clearly support the results from other studies associating the health effects of PM2.5 to PM1, rather than to PM1–2.5. Overall, there is a need to reconsider PM2.5 as an indicator of fine atmospheric aerosol

MINERALOGICAL METHODS FOR THE CHARACTERIZATION OF 2.5 PARTICULATE MATTER IN THE URBAN AREA OF ROME, ITALY.

The characterization of the airborne particulate represents a real issue. Many studies have examined the effects of the particulate matter on human health suggesting that the small particles represent a severe problem. In the present work chemical and mineralogical investigations on the particulate matter of the city of Rome were carried out. The particulate samples (PM2.5) were collected in Rome since April 2010. Polycarbonate filters were used to trap and recover airborne particles according to a standard procedure, and then utilized for different analytical techniques. Preliminary investigations on PM2.5 filters (SEM-EDS, X-ray and DTA) provided information about the inorganic compound. High iron content was highlighted as oxides, hydro-oxides, and sulphates. In particular, the presence of melanterite FeSO4.7(H2O)[1] was evidenced. Ca-sulphates and clays were also found. Moreover, innovative methodologies, such as Atomic Force Microscopy (AFM), resulted useful for morphological and dimensional investigations of the micro and nano-particles[2]. Hygroscopic properties of mixed urban aerosol can be monitored by FT-IR. Furthermore a complete functional group characterization of PM2.5 phases in the 4000-400 cm-1 spectral range, with a procedure based on diffuse reflectance (DRIFT), is in progress. The association in the atmospheric dust particles of amorphous phases and heavy metals is known to increase the release of these dangerous chemical elements. To obtain the bulk chemical composition of the particulate material the Regional Protection Agency usually utilize ion mass spectrometry (ICP-MS) on a little amount of particulate matter (2 mg; D.M. 60/2002). In this work ICP-MS analyses were performed on a high content of material (35 mg). The high amount was here used to investigate the presence of heavy metals and their release in biological environment. Data on PM2.5 samples was fully comparable with those typically observed by Regional Protection Agencies (ARPA). Test of release were executed in physiological solution (PH 7.4, 37 °C, 30 days). Release evidence were obtained for Fe, V, Pb, As and Cr. These results confirm that the release of heavy metals in the biological environments already occurs from the first hours. In vitro experiments are in progress to assess the relation between the fine and ultrafine particles and the health effects

Comparison of the angiotensin II antagonist UP269-6 with the angiotensin converting enzyme inhibitor enalapril in normotensive volunteers challenged with angiotensin I

We assessed the inhibitory effect of UP269-6, a new orally active angiotensin II (ANG II) receptor antagonist, on the pressor action of exogenous ANG I in healthy male volunteers maintained on an unrestricted sodium intake and compared it with that of enalapril. Seven different single doses of UP269-6 ranging from 5 to 180 mg, 20 mg enalapril, or placebo were administered to 16 subjects in a double-blind fashion. The order of placebo and enalapril was randomized, and UP269-6 was given in an ascending dose order. The peak systolic blood pressure (SBP) response to a test dose of ANG I was determined serially before and after oral drug administration by monitoring finger BP by a photoplethysmographic method. No drug-related side effect was observed. There was a dose-dependent inhibition of the SBP response to the ANG I challenge. Doses as low as 40 to 80 mg had blocking effects quite similar to that of enalapril 20 mg. Ten hours after the 20- and 40-mg doses of UP269-6, the SBP response was still attenuated when drug levels no longer were measurable in plasma. UP269-6 also produced a dose-related increase in active renin and ANG II levels at 24 h after drug intake. In these volunteers on unrestricted salt intake, no statistically significant effect on 24-h urinary aldosterone excretion was observed. Based on these preliminary data, the pharmacokinetic drug half-life (t 1/2) was estimated at 4.7 h and the EC50 was estimated at 41 ng/ml. UP269-6 appears to be a well-tolerated, potent, orally active, antagonist of ANG II receptors in men. Doses of 40-80 mg might block the ANG I pressor response as does enalapril 20 mg

Environmental concentrations of fibers with fluoro-edenitic composition and population exposure in Biancavilla (Sicily, Italy)

Introduction: The town of Biancavilla (Sicily) was included in the National Priorities List of Contaminated Sites due to environmental dispersion of amphibole fibers owing to the extraction of materials from a local quarry. The present report summarizes results from several, hitherto unpublished, environmental surveys carried out in the area, as well as from published analyses of the chemistry and composition of fibers. Methods: Data included here comprises environmental fiber concentrations by scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS) analysis in soil, indoor and outdoor air, personal monitoring, as well as a chemical characterization of the fibers. The full chemical structure and spectroscopic characterization of fibers were obtained through a multi-analytical approach: SEM-EDS, X-ray powder diffraction (XRPD), as well as Mössbauer (MS) and Fourier transform infrared (FT-IR) spectroscopies. Results: Data analyzed provided a spatial and temporal picture of fiber concentrations in Biancavilla, and a qualitative assessment of population exposure. Results suggest that until 2000, the population had been exposed to high levels of amphibole fibers. Mitigation measures adopted since 2001, gradually reduced exposure levels to about 0.1-0.4 ff/l. Previous studies on fibrous amphiboles from Biancavilla reported considerable chemical variability. Differences in composition, especially concerning the presence of Si, Ca, Fe, and Na, were found both within and between samples. Compared to the previously investigated prismatic fluoro-edenite, these fibrous fluorine amphiboles consistently showed higher average values of Si and Fe content, whereas Ca was significantly lower, which we consider a distinctive characteristic of the fluorine fibrous variety. Conclusions: The population of Biancavilla had been highly exposed to a suite of fibrous amphiboles for over 50 years. Dust mitigation measures have gradually reduced exposure, but continuous environmental follow-up is necessary in order to monitor exposure levels and prevent adverse health effects for future generations