Assessment of the Geometric Interaction Between the Lotus Transcatheter Aortic Valve Prosthesis and the Native Ventricular Aortic Interface by 320-Multidetector Computed Tomography

AbstractObjectivesThis study sought to assess the geometric interaction between the Lotus Valve System transcatheter aortic prosthesis (Boston Scientific, Natick, Massachusetts) and the native aortoventricular interface using multidetector computed tomography (MDCT).BackgroundThe interaction between transcatheter aortic valve prostheses and native anatomy is variable, although potentially predictable. The Lotus transcatheter device uses a novel mechanical means of expansion, the effect of which on native anatomic geometry has not previously been described.MethodsForty patients treated with the Lotus prosthesis were enrolled. The patients underwent 320-MDCT imaging before and after implantation. Prosthesis dimensions and relevant interaction parameters, including circularity and expansion, were assessed. The degree of paraprosthetic regurgitation (PAR) and prosthesis gradient were measured by transthoracic echocardiography at the same time points.ResultsThe mean baseline annular eccentricity index (EI) was 0.21 ± 0.06 and left ventricular outflow tract EI was 0.31 ± 0.09. The deployed prostheses had high rates of circularity with a mean EI across all device segments of 0.06 ± 0.04. In noncircular device deployment, an EI >0.1 was identified in 25% of prostheses and was associated with greater native annular eccentricity at baseline compared with circular devices (0.24 ± 0.04 vs. 0.19 ± 0.06; p = 0.01). The median percent of expansion was 97.5 ± 3.8% in the inflow portion of the prosthesis. Twenty-five percent of prostheses were <90% expanded in at least 1 segment with a numerical, but not statistically significant, association between oversizing and underexpansion. No correlation was found between device underexpansion and the mean transprosthesis gradient or between noncircularity and PAR.ConclusionsThe Lotus prosthesis results in nearly full device expansion and circularization of the native basal plane. Awareness of the anatomic interaction between this unique device and the native architecture may help in the formulation of appropriate device-specific sizing algorithms

Hematopoietic Cell Transplantation as Curative Therapy for Idiopathic Myelofibrosis, Advanced Polycythemia Vera, and Essential Thrombocythemia

AbstractA total of 104 patients, aged 18 to 70 years, with a diagnosis of chronic idiopathic myelofibrosis (CIMF), polycythemia vera (PV), or essential thrombocythemia (ET) with marrow fibrosis were transplanted from allogeneic (56 related and 45 unrelated) or syngeneic (n = 3) donors. Busulfan (BU) or total body irradiation (TBI)-based myeloablative conditioning regimens were used in 95 patients, and a nonmyeloablative regimen of fludarabine plus TBI was used in 9 patients. The source of stem cells was bone marrow in 43 patients and peripheral blood in 61 patients. A total of 63 patients were alive at a follow-up of 1.3–15.2 years (median, 5.3 years), for an estimated 7-year actuarial survival rate of 61%. Eleven patients had recurrent/persistent disease, of whom 8 died. Nonrelapse mortality was 34% at 5 years. Patients conditioned with targeted BU (plasma levels 800–900 ng/mL) plus cyclophosphamide (tBUCY) had a higher probability of survival (68%) than other patients. Dupriez score, platelet count, patient age, and comorbidity score were statistically significantly associated with mortality in univariate models. In a multivariable regression model, use of tBUCY (P = .03), high platelet count at transplantation (P = .01 for PV/ET; P = .39 for other diagnoses), younger patient age (P = .04), and decreased comorbidity score (P = .03) remained statistically significant for improved survival. Our findings show that hematopoietic cell transplantation offers potentially curative treatment for patients with ICMF, PV, or ET

Evolution of Melanopsin Photoreceptors: Discovery and Characterization of a New Melanopsin in Nonmammalian Vertebrates

In mammals, the melanopsin gene (Opn4) encodes a sensory photopigment that underpins newly discovered inner retinal photoreceptors. Since its first discovery in Xenopus laevis and subsequent description in humans and mice, melanopsin genes have been described in all vertebrate classes. Until now, all of these sequences have been considered representatives of a single orthologous gene (albeit with duplications in the teleost fish). Here, we describe the discovery and functional characterisation of a new melanopsin gene in fish, bird, and amphibian genomes, demonstrating that, in fact, the vertebrates have evolved two quite separate melanopsins. On the basis of sequence similarity, chromosomal localisation, and phylogeny, we identify our new melanopsins as the true orthologs of the melanopsin gene previously described in mammals and term this grouping Opn4m. By contrast, the previously published melanopsin genes in nonmammalian vertebrates represent a separate branch of the melanopsin family which we term Opn4x. RT-PCR analysis in chicken, zebrafish, and Xenopus identifies expression of both Opn4m and Opn4x genes in tissues known to be photosensitive (eye, brain, and skin). In the day-14 chicken eye, Opn4m mRNA is found in a subset of cells in the outer nuclear, inner nuclear, and ganglion cell layers, the vast majority of which also express Opn4x. Importantly, we show that a representative of the new melanopsins (chicken Opn4m) encodes a photosensory pigment capable of activating G protein signalling cascades in a light- and retinaldehyde-dependent manner under heterologous expression in Neuro-2a cells. A comprehensive in silico analysis of vertebrate genomes indicates that while most vertebrate species have both Opn4m and Opn4x genes, the latter is absent from eutherian and, possibly, marsupial mammals, lost in the course of their evolution as a result of chromosomal reorganisation. Thus, our findings show for the first time that nonmammalian vertebrates retain two quite separate melanopsin genes, while mammals have just one. These data raise important questions regarding the functional differences between Opn4x and Opn4m pigments, the associated adaptive advantages for most vertebrate species in retaining both melanopsins, and the implications for mammalian biology of lacking Opn4x

Clinical Outcomes With a Repositionable Self-Expanding Transcatheter Aortic Valve Prosthesis: The International FORWARD Study

Background Clinical outcomes in large patient populations from real-world clinical practice with a next-generation self-expanding transcatheter aortic valve are lacking. Objectives This study sought to document the clinical and device performance outcomes of transcatheter aortic valve replacement (TAVR) with a next-generation, self-expanding transcatheter heart valve (THV) system in patients with severe symptomatic aortic stenosis (AS) in routine clinical practice. Methods The FORWARD (CoreValve Evolut R FORWARD) study is a prospective, single-arm, multinational, multicenter, observational study. An independent clinical events committee adjudicated safety endpoints based on Valve Academic Research Consortium-2 definitions. An independent echocardiographic core laboratory evaluated all echocardiograms. From January 2016 to December 2016, TAVR with the next-generation self-expanding THV was attempted in 1,038 patients with symptomatic, severe AS at 53 centers on 4 continents. Results Mean age was 81.8 ± 6.2 years, 64.9% were women, the mean Society of Thoracic Surgeons Predicted Risk of Mortality was 5.5 ± 4.5%, and 33.9% of patients were deemed frail. The repositioning feature of the THV was applied in 25.8% of patients. A single valve was implanted in the proper anatomic location in 98.9% of patients. The mean aortic valve gradient was 8.5 ± 5.6 mm Hg, and moderate or severe aortic regurgitation was 1.9% at discharge. All-cause mortality was 1.9%, and disabling stroke occurred in 1.8% at 30 days. The expected-to-observed early surgical mortality ratio was 0.35. A pacemaker was implanted in 17.5% of patients. Conclusions TAVR using the next-generation THV is clinically safe and effective for treating older patients with severe AS at increased operative risk. (CoreValve Evolut R FORWARD Study [FORWARD]; NCT02592369

A systems approach to assessment of left ventricular outflow tract anatomy and function: the aortoventricular interface in the era of transcatheter aortic valve replacement

The aortoventricular interface describes the functional syncytium between the left ventricle and proximal aorta, necessary for normal central haemodynamic operation. Normal function would be considered as providing for optimal passage of oxygenated blood delivered from the left ventricle through the aortic valve to the systemic circulation. Non-­‐optimal function of the aortic valve through congenital malformation or degenerative processes is associated with a clear constellation of clinical signs and symptoms and with a well established natural history. These can all be understood on the basis of loss of normal function. Narrowing of the aortic orifice results in decreased systemic blood pressure, syncope, decreased exercise ability, left ventricular remodelling compensating for increased wall stress, secondary mitral and atrial dysfunction and increased pulmonary pressures. Aortic incompetence with its well known features of left ventricular dilatation, exertional fatigue, dyspnoea and palpitations is also explained by the deranged haemodynamic effects due to loss of hydraulic separation (temporal and spatial) between the low and high pressure components across the aortoventricular interface. The common connection between these clinical entities is the disruption of appropriate flow across the left ventricular outflow tract – aortic valve – proximal aorta anatomical continuum. In health the structure of this interface functions to provide optimally matched volume blood flow with appropriate direction and timing for optimal energy utilisation and supply. Disturbance in the normal anatomy and its associated clinical symptoms or signs are well described but the failure in underlying function not usually acknowledged. This thesis aims, in the first instance, to review and, thereafter, to investigate, the potential influence of anatomy and function on both sides of the aortoventricular interface in populations without aortic valve disease, with aortic valve stenosis and post-­‐ treatment. Assessment based on modern anatomical imaging technology provides a concrete structural representation of left ventricular – aortic mechanisms. This thesis will present work aimed at integrating structural assessment by computed tomography with assessment of clinical function in patients affected by stenosis of the aortic valve and following percutaneous aortic valve intervention

Embryonic globins of the marsupial the Tammar Wallaby (Macropus Eugenii): bird like and mammal like.

Examines the characterization and sequencing of the embryonic globins of the Tammar Wallaby. Determination of the provisional phylogenetic tree of beta-like globins; Description of the Tammar Wallaby; Properties of the embryonic type blood of the Tammar.Holland, Robert A.B.; Gooley, Andrew A.; Hope, Rory M

COVID-19 Pandemic Impact on Percutaneous Coronary Intervention for Acute Coronary Syndromes: An Australian Tertiary Centre Experience

BACKGROUND: Countries who suffered large COVID-19 outbreaks reported a decrease in acute coronary syndrome (ACS) presentations and percutaneous coronary intervention (PCI). The impact of the pandemic in countries like Australia, with relatively small outbreaks yet significant social restrictions, is relatively unknown. There is also limited and conflicting data regarding the impact on clinical outcomes, symptom-to-door time (STDT) and door-to-balloon time (DTBT). METHODS: Consecutive ACS patients treated with PCI were prospectively recruited from a tertiary hospital network in Melbourne, Australia. The pre-pandemic period (11 March 2019-10 March 2020) was compared to the pandemic period (11 March 2020-10 May 2020) using an interrupted time series analysis with a primary endpoint of number PCI-treated ACS per day. Secondary endpoints included STDT, DTBT, total mortality and major adverse cardiac events (MACE). RESULTS: A total 984 ACS patients (14.8% during the pandemic period) received PCI. Mean number of PCI-treated ACS per day did not differ between the two periods (2.3 vs 2.4, p=0.61) with no difference in STDT [+51.3 mins, 95% confidence interval (CI) -52.4 to 154.9, p=0.33], 30-day mortality (5% vs 5.3%, p=0.86) or MACE (5.2% vs 6.1%, p=0.68). DTBT was significantly longer during the pandemic versus the pre-pandemic period (+18.1 mins, 95% CI 1.6-34.5, p=0.03) and improved with time (slope estimate: -0.76, 95% CI -1.62 to 0.10). CONCLUSIONS: Despite significant social restrictions imposed in Melbourne, numbers of ACS treated with PCI and 30-day outcomes were similar to pre-pandemic times. DTBT was significantly longer during the COVID-19 pandemic period, likely reflecting infection control measures, which reassuringly improved with time