Patient-specific computer modelling – its role in the planning of transcatheter aortic valve implantation

Transcatheter aortic valve implantation is increasingly used to treat patients with severe aortic stenosis who are at increased risk for surgical aortic valve replacement and is projected to be the preferred treatment modality. As patient selection and operator experience have improved, it is hypothesised that device-host interactions will play a more dominant role in outcome. This, in combination with the increasing number of valve types and sizes, confronts the physician with the dilemma to choose the valve that best fits the individual patient. This necessitates the availability of pre-procedural computer simulation that is based upon the integration of the patient-specific anatomy, the physical and (bio)mechanical properties of the valve and recipient anatomy derived from in-vitro experiments. The objective of this paper is to present such a model and illustrate its potential clinical utility via a few case studies.     

Introducing transcatheter aortic valve implantation with a new generation prosthesis: Institutional learning curve and effects on acute outcomes

Objectives

We present our single-centre experience with the direct flow medical (DFM) trans-catheter aortic valve implantation (TAVI) prosthesis addressing the impact of learning curve upon outcomes.

Background

The DFM has been recently introduced for TAVI. The prosthesis presents original design and implantation features.

Methods

Patients were divided into three groups according to the chronological implantation sequence that reflected technical skills acquisition of the entire team.

Results

Group I included the first 20 patients (early learning phase), group II the second 20 patients (proctoring to other members of the team), and group III the following 93 patients (technique consolidation). Differences in baseline and procedural variables were analysed. Nonparametric correlation and linear regression were used to identify changes according to institutional cumulative experience. There was a significant correlation between catheterisation time and institutional experience (rho = ?0.4; p < 0.0001) confirmed at linear regression (beta = ?0.2; p = 0.001; CI: ?0.3?–??0.08). Moreover, there was lower rate of valve retrieval in group III (15% vs. 20% vs. 10%; p = 0.5). No intra-procedural mortality was reported and improved early safety (at 30 days) was observed (80% vs. 85% vs. 87.1; p = 0.7). At hospital discharge, valve haemodynamic performance was satisfactory with only mild regurgitation in 10% (I), 20% (II), and 9.7% (III) (p = 0.8).

Conclusions

DFM adequate sizing and implantation can be achieved after the early learning phases. A significant reduction in catheterisation time is reported after the first 20 patients. Results remain satisfactory during the proctoring and technical consolidation phase.

     

Allogenic heart valve bank in the Department of Cardiovascular Surgery and Transplantology of Jagiellonian University in Cracow – 23 years experience in the treatment of aortic valve or aortic root diseases.

Allogenic aortic valves are widely used in case of native aortic valve or root disease as well as failed prosthetic valves with great success. At the Department of Cardiovascular Surgery and Transplantology of the Jagiellonian University in Cracow, aortic valve or aortic root replacement with allogenic aortic valve has been performed for 23 years. Allogenic heart valve bank was founded in 1980. In the bank we prepare both aortic allografts for adult cardiac surgical procedures and pulmonary allografts that are mostly used for repair of congenital heart disease.Allogenic aortic valves implantation was usually considered in our clinic for older patients, patients with infective endocarditis of the native or prosthetic valve, young women in reproductive age and patients with Marfan syndrome. Allografts exhibit excellent clinical performance and acceptable durability with no early failure if properly inserted. Between 1980 and 1992, allografts were obtained only from cadavers during routine autopsies. More than 10% of prepared allografts were exported to other cardiac surgery centres in Poland and foreign countries.Aortic valve replacement using allogenic aortic valves can be performed with acceptable mortality and good long-term results. The procedure although surgically more challenging has the advantage of not requiring anticoagulation therapy, hemodynamic performance of the allogenic valve is excellent, it demonstrates freedom from thromboembolism and infective endocarditis. We would like to emphasize the importance and advantages of the fact that allogenic heart valve bank is placed in the department of cardiovascular surgery and it is able to supply the department in heart valve allografts 24 h a day.     

Transcatheter aortic valve implantation and surgical aortic valve replacement among hospitalized patients with and without type 2 diabetes mellitus in Spain (2014–2015)

Background

Type 2 diabetes mellitus (T2DM) is strongly related to the in-hospital and short-term prognosis in patients with cardiovascular diseases needing surgical or invasive interventions. How T2DM might influence the treatment of aortic stenosis (AS) has not been completely elucidated for surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI). The aims of this study were: (1) to describe the use of aortic valve replacement procedures (TAVI and SAVR) among hospitalized patients with and without T2DM; and (2) to identify factors associated with in hospital mortality (IHM) among patients undergoing these procedures.

Methods

We analyzed data from the Spanish National Hospital Discharge Database between January 1, 2014 and December 31, 2015 for patients aged ≥ 40 years. We selected patients whose medical procedures included TAVI (ICD-9-CM codes 35.05, 35.06) and SAVR (ICD-9-CM codes 35.21, 35.22). We stratified each cohort by diabetes status: T2DM (ICD-9-CM codes 250.x0, 250.x2) and no diabetes. We retrieved data about specific comorbidities, risk factors, procedures, and specific in-hospital postoperative complications. Hospital outcome variables included IHM, and length of hospital stay (LOHS).

Results

We identified a total of 2141 and 16,013 patients who underwent TAVI (n = 715; 33.39% with T2DM) and SAVR (n = 4057; 25.33% with T2DM). In patients who underwent TAVI we found no differences in IHM (3.64% in T2DM vs. 5.12% in non-T2DM, p = 0.603). In the cohort of SAVR, mean LOHS was significantly lower in patients with T2DM than in non-diabetic patients (13.77 vs. 17.27 days). IHM was lower in patients with T2DM (4.36% vs. 6.31%, p < 0.01). After multivariable adjustment for both procedures, patients with T2DM had significantly lower IHM than patients without diabetes (adjusted OR 0.60; IC 95% 0.37–0.99 for TAVI and adjusted OR 0.80; IC 95% 0.66-0-96 for SAVR).

Conclusions

T2DM diabetic patients with AS undergoing a valvular replacement procedure through SAVR or TAVI did not have a worse prognosis compared to non-diabetic patients during hospitalization, showing lower IHM after multivariable adjustment. However, given the limitations of administrative data more prospective studies and clinical trials aimed at evaluating the influence of these procedures in diabetic patients with AS are needed.

     

Genetic and clinical mosaicism in a patient with neurofibromatosis type 1

Patients with typical features of neurofibromatosis type 1 (NF1) limited to a specific body segment are usually referred to as having segmental NF1, which is generally assumed to be the result of somatic mosaicism for a NF1 mutation. Mosaicism has also been demonstrated at the molecular level in some sporadic cases with phenotypically classic NF1. In the present report, we describe a patient with NF1 disease manifestations throughout the whole body, but leaving a few sharply delineated segments of the skin unaffected, suggestive of revertant mosaicism. A large intragenic deletion was found by mutation analysis using long-range RT-PCR. The intra-exonic breakpoints were characterized in exon 13 and exon 28, resulting in a deletion of 99,571 bp at the genomic level. The presence of two genetically distinct cell populations, confirming mosaicism for this NF1 mutation, was shown by analysis of several tissues. Revertant mosaicism was excluded by demonstrating heterozygosity for markers residing in the deletion region. The findings in this patient demonstrate two things: (1) although the entire body is affected, mosaicism can still be suspected at clinical examination and proven by DNA analysis and skin biopsies; (2) long-range RT-PCR is a feasible method for demonstrating large intragenic deletions in NF1.     

Numerical evaluation of transcatheter aortic valve performance during heart beating and its post-deployment fluid–structure interaction analysis

Biomechanics and Modeling in Mechanobiology - Transcatheter aortic valve replacement (TAVR) is a minimally invasive procedure that provides an effective alternative to open-heart surgical valve...     

Annual variation in biomass and the community structure of crustacean zooplankton over 5 years in Lake Toya, Japan

The biomass and population dynamics of crustacean zooplankton were determined in oligotrophic Lake Toya in Japan over 5 years from May 1992 to May 1997. In 1992 and 1993, zooplankton biomass was up to 4.3 g dry weight m^?2, whereas it decreased to <1 g dry weight m^?2 after 1994. This extreme change in biomass was associated with the succession of dominant species from larger ones, such as Daphnia longispina and Cyclops strenuus (s. lat.), to smaller ones, such as Eubosmina tanakai and Bosmina longirostris. Consequently, this biomass change seemed to cause an increase in the chlorophyll a concentration in the euphotic zone and a decline in lake transparency. Because the birth rates of the dominant species were somewhat higher after 1994, the decline in the populations of larger crustaceans seemed to depend more on their rate of death rather than rate of birth, and this higher death rate is not considered to be attributed to food shortage. Although these results strongly suggest a top-down cascading effect of fish predation upon crustaceans, annual catches of two commercially important planktivorous fish species have also decreased in the lake, coincidentally with decreases in zooplankton biomass. This may be attributable to fishing regulations that prohibit catching smaller fish, implying that such smaller fish affect zooplankton and phytoplankton, as well as lake transparency.     

Dynamics of vegetation and soil carbon and nitrogen accumulation over 26 years under controlled grazing in a desert shrubland

For decades, arid desert ecosystems in northwest China, covering one-fourth the country’s land surface, have experienced a rapid decline in plant species diversity, productivity and soil carbon stock owing to degradation by overgrazing. In this study, plant community composition, diversity and productivity, as well as soil carbon (C) and nitrogen (N) stocks, were monitored over 26 years from 1981 to 2006 in a severely degraded Haloxylon ammodendron-dominated shrubland where livestock densities were reduced from 4–5 to 1–2 dry sheep equivalent ha^-1. The objective was to assess long-term grazing effects on vegetation and soil C and N accumulation dynamics. Results showed that the reduction of grazing pressure significantly increased vegetation cover, plant diversity and productivity, resulting primarily from an increase in livestock-preferred species. Controlled grazing also led to marked increases in soil C and N stocks in the top 30 cm of soil. This increase was strongly associated with increased plant species richness, vegetation cover and biomass production. Averaged over 26 years, soil C and N accumulated at rates of 89.9 g?C and 8.4 g?N m^-2?year^-1, respectively, but rates of C and N accumulation varied greatly at different time periods. The greatest species regeneration occurred in the first 8 years, but the largest C and N accumulation took place during years 9–18, with a time-lag in response to changes in vegetation. Our results provide insights into the long-term recovery patterns of different ecosystem components from the influence of prolonged overgrazing disturbance that cannot be inferred from a short-term study. The findings are important for assessing the resilience of these livestock-disturbed desert ecosystems and developing a more effective strategy for the management of this important biome from a long-term perspective.     

Estimates of annual survival,growth, and recruitment of a white-tailed ptarmigan population in Colorado over 43 years

Long-term datasets for high-elevation species are rare, and considerable uncertainty exists in understanding how high-elevation populations have responded to recent climate warming. We present estimates of demographic vital rates from a 43-year population study of white-tailed ptarmigan (Lagopus leucura), a species endemic to alpine habitats in western North America. We used capture-recapture models to estimate annual rates of apparent survival, population growth, and recruitment for breeding-age ptarmigan, and we fit winter weather covariates to models in an attempt to explain annual variation. There were no trends in survival over the study period but there was strong support for age and sex effects. The average rate of annual growth suggests a relatively stable breeding-age population ( \( \bar{\lambda } \)  = 1.036), but there was considerable variation between years for both population growth and recruitment rates. Winter weather covariates only explained a small amount of variation in female survival and were not an important predictor of male survival. Cumulative winter precipitation was found to have a quadratic effect on female survival, with survival being highest during years of average precipitation. Cumulative winter precipitation was positively correlated with population growth and recruitment rates, although this covariate only explained a small amount of annual variation in these rates and there was considerable uncertainty among the models tested. Our results provide evidence for an alpine-endemic population that has not experienced extirpation or drastic declines. However, more information is needed to understand risks and vulnerabilities of warming effects on juveniles as our analysis was confined to determination of vital rates for breeding-age birds.     

Has laparoscopic cholecystectomy changed patterns of practice and patient outcome in Ontario?

OBJECTIVE: To examine the effect of the introduction of laparoscopic cholecystectomy (LC) on patterns of practice (number of cholecystectomy procedures, case-mix and length of hospital stay) and patient outcomes in Ontario. DESIGN: Cross-sectional population-based time trends using hospital discharge data. SETTING: All acute care hospitals in Ontario where cholecystectomy was provided. PATIENTS: All 119,821 Ontario residents who underwent cholecystectomy between 1989-90 and 1993-94. After exclusions (initial bile duct exploration, cancer, incidental cholecystectomy, or missing codes for age, sex or residence) 108,442 patients remained. OUTCOME MEASURES: Number of cholecystectomy procedures, proportion of patients with acute or chronic gallstone disease, length of hospital stay, and rates of death, readmission, and bile duct injury and other in-hospital complications after cholecystectomy by year. RESULTS: The number of cholecystectomy procedures increased by 30.4% between 1989-90 and 1993-94. The number of patients with chronic gallstone disease increased by 33.6%, and the number who underwent elective surgery increased by 48.3%. The proportion of procedures performed as LC increased from 1.0% in 1990-91 to 85.6% in 1993-94. Patients who received LC tended to be younger female patients with chronic gallstone disease with no coexisting conditions undergoing elective operations. The mean length of stay, adjusted for case-mix differences, was significantly lower in 1993-94 than in 1989-90 (2.6 days v. 7.5 days) (p < 0.05); the values for LC and open cholecystectomy in 1993-94 were 1.8 days and 7.3 days respectively. The decrease in the crude death rate over the study period (0.3% to 0.2%) was not significant (relative odds 1.10, 95% confidence interval [CI] 0.72 to 1.69). In 1993-94 the adjusted risk of readmission to hospital within 30 days was 1.38 (95% CI 1.19 to 1.58) as compared with 1989-90. Over the 5 years the rate of bile duct injuries tripled (0.3% in 1989-90 v. 0.9% in 1993-94). The adjusted risk of having at least one complication after cholecystectomy in 1993-94 was 1.90 (95% CI 1.75 to 2.07) as compared with 1989-90. CONCLUSIONS: LC has had a substantial effect on the number of cholecystectomy procedures performed, the type of patient having the gallbladder removed and the length of hospital stay. Death rates are unchanged, but the odds of readmission and in-hospital complications are both increased. Future research should be directed toward determining the reasons for the overall increase in rates, developing methods to reduce bile duct injuries and identifying other relevant outcomes, such as patient satisfaction with the procedure.     

Radical changes in the Wadden Sea fauna and flora over the last 2,000 years

Humans have interacted with the Wadden Sea since its origin 7,500 years ago. However, exploitation, habitat alteration and pollution have strongly increased since the Middle Ages, affecting abundance and distribution of many marine mammals, birds, fish, invertebrates and plants. Large whales and some large birds disappeared more than 500 years ago. Most small whales, seals, birds, large fish and oysters were severely reduced by the late 19th and early 20th centuries, leading to the collapse of several traditional fisheries. In the 20th century, conservation efforts have enabled some breeding birds and seals to recover. But other species declined further due to continuing exploitation, habitat destruction, pollution and eutrophication. Moreover, complex three-dimensional habitats such as oyster banks, Sabellaria reefs and subtidal eelgrass beds have been lost completely. In contrast, several opportunistic species such as gulls, polychaetes, green algae and exotic invaders increased during the 20th century. Taken together, multiple human impacts have caused dramatic losses of large predators and habitat-building species in the Wadden Sea over the last 500 years. Although still of high natural value and global importance, the Wadden Sea is a fundamentally changed ecosystem. On the other hand, reduced hunting pressure, increased habitat protection and reduced river pollution have enabled the recent recovery of several species and an increase in environmental quality. These successes, together with a historical vision of what was once possible, should guide current and future conservation, restoration and management efforts towards a more sustainable interaction between man and the sea.     

Decline in seminal quality in Indian men over the last 37 years

Background

Since the first report of a decline in semen quality in 1974, there have been several reports of similar declines across populations. Despite some scattered reports of declining semen quality in the Indian sub-continent, comprehensive studies analyzing semen quality over the last few decades have not been undertaken. We undertook the present study to investigate the temporal trend in semen parameters in Indian populations over a period of 37 years (1979–2016).

Methods

Publications providing semen analysis details for fertile and infertile men from the Indian sub-continent were collected by a thorough literature search. Semen quality data for 6466 normal fertile or presumptive normal men (from 119 studies/data sets) and 7020 infertile men (from 63 studies/data sets) published between 1979 and 2016 were retrieved. We undertook systematic review and quantitative analysis of mean sperm count, motility, normal morphology and other available parameters. Data were analyzed to estimate semen parameters reference values for Indian men and to assess temporal trends in infertile, fertile and all subjects.

Results

Seminal quality shows a decreasing temporal trend and the decrease is higher in infertile than fertile males. In pooled analysis for all individuals, significant (p?<?0.05 or?<?0.001) declines in sperm concentration and normal morphology are observed; however, isolated analysis for each group shows declines without statistical significance. The mean (± SD) semen volume, sperm concentration, total motility, rapid linear progressive motility, normal sperm morphology and sperm viability for Indian fertile men are 2.88?±?0.77 ml, 81.08?±?29.21 million/ml, 66.37?±?10.95%, 52.64?±?15.78%, 56.68?±?20.23% and 72.63?±?8.31%, respectively, whereas in infertile these are 3.07?±?1.27 ml, 37.94?±?26.41 million/ml, 40.22?±?13.76%, 26.79?±?15.47%, 36.41?±?21.66% and 55.25?±?11.99%, respectively. The mean seminal parameter values were significantly lower (p?<?0.001) in infertile as compared to fertile men, except semen volume.

Conclusions

Semen parameters in Indian men have declined with time and the deterioration is quantitatively higher in the infertile group. The study also provides reference values for semen parameters in Indian men.

     

Historical changes in the aquatic environment and input of polycyclic aromatic hydrocarbons over 1000 years in Lake Kitaura,Japan

We examined the vertical distributions of total organic carbon (TOC), total nitrogen (TN), total sulfur (TS), and 21 polycyclic aromatic hydrocarbons (PAHs) in a 100-cm-long sediment core collected from Lake Kitaura, a small and shallow eutrophic freshwater lake in central Japan, to elucidate changes in its aquatic environment and the input of PAHs with respect to human activity over the last 1000 years. Using a cross-plot of TOC and TS, the aquatic environment of this lake was well classified into four stages: a marine–brackish water period (≤1321 AD), a brackish–freshwater period (1394–1646 AD), a freshwater period (1726–1958 AD), and a eutrophication period (≥1971 AD). During the current eutrophication period, both TOC and TN have increased dramatically and TOC/TN (which is a useful indicator for distinguishing between aquatic and terrestrial plant sources) has decreased because algal production has markedly increased recently due to eutrophication. The vertical distributions of PAHs (which have derived primarily from combustion over the last 1000 years) showed increases in layers corresponding to periods of volcanic activity in the 18th century, as well as dramatic increases from 1971 to the present. Thus, both the aquatic environment and the input of PAHs in Lake Kitaura have been strongly affected by recent human activity. On the other hand, among all of the PAHs, only perylene—which is known to be of biological origin—was consistently formed via first-order kinetics over the period covered by the core. Its formation was barely influenced by fluctuations in the input of the precursor of perylene or how reductive the environment in the bottom water was.     

Nutrient fluxes and water quality in the drainage network of the Scheldt basin over the last 50 years

and use and urban activity in the catchment of the Scheldt river system have deeply changed during the last 50 years, modifying in turn the water quality of the drainage network and the fluxes of nutrient transferred to the estuary and to the sea. Based on the RIVERSTRAHLER model, developed for establishing the link between the biogeochemical functioning of large river systems and the constraints set by the meteorology, the morphology of the drainage network and the human activity in the watershed, we reassembled the data available to document these constraints in the Scheldt basin since the last half of the XXth century and we used them to reconstruct the variations of nutrient and oxygen concentrations at the outlet of the Scheldt drainage network. We compared the results with the water quality data at the entrance of the estuarine zone available since the 1960s. Both model results and observational data show a very severe deterioration of water quality (with deep oxygen depletion) in the beginning of the 1960s, while a clear trend to improvement is apparent since the late 1980s. The budget of nutrient loadings from the watershed, retention within the drainage network and delivery to the estuarine zone is established on an annual basis for the 50 last years. The yearly fluxes of nutrient delivered by the river to the estuary and the sea show a severe depletion of silica with respect to nitrogen compared with the requirements of diatoms, and a clear shift from the early 1990s from nitrogen to phosphorus potential limitation. Seasonal variations of nutrient delivery are however much more pronounced for nitrogen, with much less inputs during the dry seasons, while phosphorus inputs, mainly from point sources are more constant, so that nitrogen limitation can still occur during summer. Compared with similar budget estimations carried out for the Seine river system, the Scheldt basin, in spite of its much higher population density, does not deliver higher specific fluxes of nutrient (presently about 2000 kgN/km²/yr, 80 kgP/km²/yr and 1000 kgSi/km²/yr), owing to very efficient processes of nutrient retention.     

Floristic composition and diversity changes over 60 years in eastern mulga communities of south central Queensland,Australia

Botanical surveys from prior to 1949 documented the plant species composition of the mulga (Acacia aneura) communities in the eastern Mulga Lands Bioregion of Queensland, Australia. These surveys recorded 282 vascular plant species including 268 natives and 14 exotics. Since 1949, mulga communities have experienced considerable modification through continuous grazing by domestic sheep and cattle even during drought periods and extensive vegetation clearance. To increase our knowledge on floristic composition and diversity change over this time, floristic data were recollected from mulga communities in the same region between 2007 and 2010 using a more systematic procedure. These surveys recorded 292 vascular plant species including 269 natives and 23 exotics. Species richness and composition within five life forms: tree, shrub, vine, forb and graminoid were compared between the recent survey data and the historical survey data. The majority of native plant species were either in the forb (45.4% of total native species) or graminoid (25.7% of total native species) life forms over the 60-year period. There was no significant difference in species richness between the historical and recent surveys within tree or shrub life forms, but there were differences in species richness in vine, forb and graminoid life forms over time. Similarities in native species between the historical and recent surveys were high. Sorensen Similarity Indices (ISS) were: 0.77 at species level, 0.84 at genus level and 0.87 at family level. In contrast, the similarity indices for exotic species was low (0.59) for species and genera (0.61), but high for families (0.86). More exotic species were recorded recently than historically. Among these, buffel grass (Pennisetum ciliare) and colocynth (Citrullus colocynthis) were more commonly encountered than other exotic species in the eastern mulga communities of south central Queensland, Australia.     

Does clinical data quality affect fluid-structure interaction simulations of patient-specific stenotic aortic valve models?

Numerical models are increasingly used in the cardiovascular field to reproduce, study and improve devices and clinical treatments. The recent literature involves a number of patient-specific models replicating the transcatheter aortic valve implantation procedure, a minimally invasive treatment for high-risk patients with aortic diseases. The representation of the actual patient’s condition with truthful anatomy, materials and working conditions is the first step toward the simulation of the clinical procedure.The aim of this work is to quantify how the quality of routine clinical data, from which the patient-specific models are built, affects the outputs of the numerical models representing the pathological condition of stenotic aortic valve.Seven fluid–structure interaction (FSI) simulations were performed, completed with a sensitivity analysis on patient-specific reconstructed geometries and boundary conditions. The structural parts of the models consisted of the aortic root, native tri-leaflets valve and calcifications. Ventricular and aortic pressure curves were applied to the fluid domain.The differences between clinical data and numerical results for the aortic valve area were less than 2% but reached 12% when boundary conditions and geometries were changed. The difference in the aortic stenosis jet velocity between measured and simulated values was less than 11% reaching 27% when the geometry was changed. The CT slice thickness was found to be the most sensitive parameter on the presented FSI numerical model.In conclusion, the results showed that the segmentation and reconstruction phases need to be carefully performed to obtain a truthful patient-specific domain to be used in FSI analyses.