Philosophy of Experimental Biology explores some central philosophical issues concerning scientific research in experimental biology, including genetics, biochemistry, molecular biology, ...developmental biology, neurobiology, and microbiology. It seeks to make sense of the explanatory strategies, concepts, ways of reasoning, approaches to discovery and problem solving, tools, models and experimental systems deployed by scientific life science researchers and also integrates developments in historical scholarship, in particular the New Experimentalism. It concludes that historical explanations of scientific change that are based on local laboratory practice need to be supplemented with an account of the epistemic norms and standards that are operative in science. This book should be of interest to philosophers and historians of science as well as to scientists.
Taking a causal perspective, this Element examines to what extent and how developmental biology, having turned molecular about four decades ago, has been able to meet the vitalist challenge. This ...title is also available as Open Access on Cambridge Core.
Tricuspid regurgitation is a prevalent disease associated with high morbidity and mortality, with few treatment options. The aim of the TRILUMINATE trial is to evaluate the safety and effectiveness ...of TriClip, a minimally invasive transcatheter tricuspid valve repair system, for reducing tricuspid regurgitation.
The TRILUMINATE trial is a prospective, multicentre, single-arm study in 21 sites in Europe and the USA. Patients with moderate or greater triscuspid regurgitation, New York Heart Association class II or higher, and who were adequately treated per applicable standards were eligible for enrolment. Patients were excluded if they had systolic pulmonary artery pressure of more than 60 mm Hg, a previous tricuspid valve procedure, or a cardiovascular implantable electronic device that would inhibit TriClip placement. Participants were treated using a clip-based edge-to-edge repair technique with the TriClip tricuspid valve repair system. Tricuspid regurgitation was graded using a five-class grading scheme (mild, moderate, severe, massive, and torrential) that expanded on the standard American Society of Echocardiography grading scheme. The primary efficacy endpoint was a reduction in tricuspid regurgitation severity by at least one grade at 30 days post procedure, with a performance goal of 35%, analysed in all patients who had an attempted tricuspid valve repair procedure upon femoral vein puncture. The primary safety endpoint was a composite of major adverse events at 6 months, with a performance goal of 39%. Patients were excluded from the primary safety analysis if they did not reach 6-month follow-up and did not have a major adverse event during previous follow-ups. The trial has completed enrolment and follow-up is ongoing; it is registered with ClinicalTrials.gov, number NCT03227757.
Between Aug 1, 2017, and Nov 29, 2018, 85 patients (mean age 77·8 years SD 7·9; 56 66% women) were enrolled and underwent successful TriClip implantation. Tricuspid regurgitation severity was reduced by at least one grade at 30 days in 71 (86%) of 83 patients who had available echocardiogram data and imaging. The one-sided lower 97·5% confidence limit was 76%, which was greater than the prespecified performance goal of 35% (p<0·0001). One patient withdrew before 6-month follow-up without having had a major adverse event and was excluded from analysis of the primary safety endpoint. At 6 months, five (6%) of 84 patients experienced a major adverse event, which was less than the prespecified performance goal of 39% (p<0·0001). Single leaflet attachment occurred in five (7%) of 72 patients. No periprocedural deaths, conversions to surgery, device embolisations, or strokes occurred. At 6 months, all-cause mortality had occurred in four (5%) of 84 patients.
The TriClip system appears to be safe and effective at reducing tricuspid regurgitation by at least one grade. This reduction could translate to significant clinical improvement at 6 months post procedure.
Abbott.
Tricuspid regurgitation (TR) is a frequent disease with a progressive increase in mortality as disease severity increases. Transcatheter therapies for treatment of TR may offer a safe and effective ...alternative to surgery in this high-risk population.
The purpose of this report was to study the 1-year outcomes with the TriClip transcatheter tricuspid valve repair system, including repair durability, clinical benefit and safety.
The TRILUMINATE trial (n = 85) is an international, prospective, single arm, multicenter study investigating safety and performance of the TriClip Tricuspid Valve Repair System in patients with moderate or greater TR. Echocardiographic assessment was performed by a core laboratory.
At 1 year, TR was reduced to moderate or less in 71% of subjects compared with 8% at baseline (p < 0.0001). Patients experienced significant clinical improvements in New York Heart Association (NYHA) functional class I/II (31% to 83%, p < 0.0001), 6-minute walk test (272.3 ± 15.6 to 303.2 ± 15.6 meters, p = 0.0023) and Kansas City Cardiomyopathy Questionnaire (KCCQ) score (improvement of 20 ± 2.61 points, p < 0.0001). Significant reverse right ventricular remodeling was observed in terms of size and function. The overall major adverse event rate and all-cause mortality were both 7.1% at 1 year.
Transcatheter tricuspid valve repair using the TriClip device was found to be safe and effective in patients with moderate or greater TR. The repair itself was durable at reducing TR at 1 year and was associated with a sustained and marked clinical benefit with low mortality after 1 year in a fragile population that was at high surgical risk. (TRILUMINATE Study With Abbott Transcatheter Clip Repair System in Patients With Moderate or Greater TR; NCT03227757)
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This study aimed to assess the anatomical leaflet variation and investigate its impact on the procedural outcome in patients undergoing transcatheter edge-to-edge tricuspid repair.
Tricuspid ...regurgitation (TR) is associated with a poor prognosis.
The study participants were consecutive patients who underwent transcatheter edge-to-edge tricuspid repair with the MitraClip, TriClip, or PASCAL systems from June 2015 to July 2020 at the Bonn Heart Center. The tricuspid leaflet morphologies were imaged using 2-dimensional and 3-dimensional transesophageal echocardiography. The severity of TR was assessed according to the 5-grade scheme. The primary endpoint was residual TR ≥3+ within 30 days.
Of the 145 study participants, 103 (71.1%) participants were categorized as the 3-leaflet configuration, while 42 (28.9%) were categorized as the 4-leaflet configuration. Successful device implantation was achieved in 136 (93.8%) patients, with no statistical difference between the 3-leaflet and 4-leaflet configuration groups. However, compared with patients with a 3-leaflet configuration, patients with 4-leaflet configuration more frequently had residual TR ≥3+ (18.4% vs 38.1%; P = 0.018). In the multivariable model, the 4-leaflet configuration was associated with an increased risk of residual TR ≥3+ (odds ratio: 2.65; 95% CI 1.15-6.10; P = 0.022), independent of baseline TR grade, coaptation gap width, and TR jet location. After 1-year follow-up, compared with patients with residual TR <3+, patients with residual TR ≥3+ had a significantly higher incidence of the composite of all-cause mortality or heart failure hospitalization (27.7% vs 56.1%; P = 0.016).
A 4-leaflet configuration of the tricuspid valve is observed in approximately one-third of patients undergoing transcatheter edge-to-edge tricuspid repair, which is associated with an increased risk of residual TR after the procedure.
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This study sought to investigate the clinical impact of leaflet-to-annulus mismatch on residual mitral regurgitation (MR) after percutaneous edge-to-edge mitral repair.
Annular dilation is a common ...feature of secondary MR, which requires concomitant annuloplasty in surgical mitral valve repair.
Consecutive MR patients undergoing MitraClip (Abbott Vascular, Santa Clara, California) implantation in the Heart Center Bonn were enrolled. Residual MR was defined as a post-procedural MR ≥2+ and patients were stratified into 2 groups according to the residual MR. The study calculated the leaflet-to-annulus index (LAI) using pre-procedural 2- and 3-dimensional transesophageal echocardiography. All-cause death within a 1-year follow-up was examined.
Of 420 consecutive patients, 117 (27.9%) patients had residual MR (≥2+). Patients with residual MR had a significantly lower pre-procedural LAI than did those with MR <2+ (median 1.14 interquartile range (IQR): 1.07 to 1.20 vs. 1.18 IQR: 1.12 to 1.29; p < 0.001). A multivariable analysis revealed that the LAI value was significantly associated with residual MR (odds ratio: 0.95; p < 0.001). After 1-year follow-up, patients with residual MR had a significantly worse prognosis than did patients with MR <2+ (estimated mortality rate 17.4% vs. 7.3%; log-rank p = 0.002), and the presence of residual MR was independently correlated with 1-year mortality (hazard ratio: 2.74; p = 0.004).
The LAI value is associated with residual MR after MitraClip implantation, which is independently correlated with 1-year mortality. This index might be a useful tool to identify patients with the need for concomitant annuloplasty before edge-to-edge repair.
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Interstitial lung disease (ILD) comprises a wide variety of pulmonary parenchymal disorders within which progressive fibrosing ILD (PF-ILD) constitutes a phenotypic subset. By use of speckle ...tracking-based strain analysis we aimed to evaluate the degree of left ventricular (LV) dysfunction in progressive vs. non-progressive fibrosing ILD (non-PF-ILD).
A total of 99 ILD patients (mean age 63.7 ± 13.5 years, 37.4% female), composed of 50 PF-ILD and 49 non-PF-ILD patients, and 33 controls were prospectively enrolled and underwent conventional and speckle tracking echocardiography. Additional laboratory and pulmonary function testing, as well as six-minute walk test were performed.
As compared to the non-PF-ILD cohort, PF-ILD patients exhibited a significantly impaired forced vital capacity (2.4 ± 1.0l vs. 3.1 ± 0.9l, p = 0.002), diffusion capacity for carbon monoxide (DLCO, 25.6 ± 16.3% predicted vs. 43.6 ± 16.67% predicted, p <0.001) and exercise capacity response as measured by the six-minute walk test distance (268.1 ± 178.2m vs. 432.6 ± 94.2m, p <0.001). Contrary to conventional echocardiographic LV parameters, both regional and global longitudinal LV strain measurements were significantly altered in ILD patients as compared to controls. No differences in LV strain were found between both patient groups. Significant correlations were observed between global longitudinal strain, on the one hand, and systemic inflammation markers, total lung capacity (TLC) and DLCO, on the other hand (high-sensitivity C-reactive protein: Pearson´s r = -0.30, p< 0.001; interleukin-6: Pearson´s r = -0.26, p = 0.007; TLC % predicted: Pearson´s r = 0.22, p = 0.02; DLCO % predicted: Pearson´s r = 0.21, p = 0.02).
ILD is accompanied by LV dysfunction. LV functionality inversely correlates with the severity of the restrictive ventilatory defect and inflammation marker levels. These observations support the assumption of persistent low-grade systemic inflammation that may link systemic cardiovascular function to ILD status.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recurrent mitral regurgitation (MR) following MitraClip has not been thoroughly investigated. We aimed to examine the predictive factors, morphology, and long-term outcome of recurrent MR after ...MitraClip.
We assessed data from the Heart Failure Network Rhineland registry from August 2010 to October 2018. Competing risk analyses were performed using the Fine and Gray model to assess the risk of recurrent MR.
Among 685 MitraClip patients with a reduction in MR to ≤2+, 61 patients developed recurrent MR within the first 12 months. Flail leaflet (hazard ratio, 3.68;
=0.002) and residual MR (MR grade 2+ versus ≤1+: hazard ratio, 2.56;
=0.03) were the predictors of recurrent MR in primary MR patients, while left atrial volume (per 10 mL increase: hazard ratio, 1.11;
<0.001) and residual MR (hazard ratio, 2.45;
=0.01) were independently associated with recurrent MR in secondary MR patients. In primary MR patients, loss of leaflet insertion or leaflet tear were the predominant morphologies with recurrent MR. In secondary MR patients, more than half of the patients with recurrent MR did not show any disorder of the clip or leaflets. Patients with recurrent MR were more likely to experience unplanned heart failure hospitalization or heart failure symptom with New York Heart Association scale III/IV (54.1% versus 37.8%;
=0.018) and undergo a repeat mitral valve intervention (9.8% versus 2.2%;
=0.005) during the follow-up. In the landmark survival analysis, patients with recurrent MR tended to have lower long-term survival (58.7% versus 83.9%;
=0.08) than patients without recurrent MR.
Flail leaflet and residual MR were the predictors of recurrent MR in primary MR patients, while a larger left atrial volume and residual MR were associated with recurrent MR in secondary MR patients, which may be associated with long-term clinical outcomes of patients after MitraClip.
The aim of this study was to assess the value of echocardiographic right ventricular (RV) and systolic pulmonary artery pressure (sPAP) assessment in predicting transcatheter tricuspid edge-to-edge ...valve repair (TTVR) outcome.
RV dysfunction and pulmonary hypertension are associated with poor prognosis and are systematically sought during tricuspid regurgitation evaluation. The value of echocardiographic assessment in predicting TTVR outcome is unknown.
Data were taken from the TriValve (Transcatheter Tricuspid Valve Therapies) registry, which includes patients undergoing TTVR at 14 European and North American centers. The primary outcome was 1-year survival free from hospitalization for heart failure, and secondary outcomes were 1-year survival and absence of hospital admission for heart failure at 1 year.
Overall, 249 patients underwent TTVR between June 2015 and 2018 (mean tricuspid annular plane systolic excursion TAPSE 15.8 ± 15.3 mm, mean sPAP 43.6 ± 16.0 mm Hg). Tricuspid regurgitation grade ≥3+ was found in 96.8% of patients at baseline and 29.4% at final follow-up; 95.6% were in New York Heart Association functional class III or IV initially, compared with 34.3% at follow-up (p < 0.05). Final New York Heart Association functional class did not differ among TAPSE and sPAP quartiles, even when both low TAPSE and high sPAP were present. Rates of 1-year survival and survival free from hospitalization for heart failure were 83.9% and 78.7%, respectively, without significant differences according to baseline echocardiographic RV characteristics (TAPSE, fractional area change, and end-diastolic area) and sPAP (p > 0.05 for all).
TTVR provides clinical improvement, with 1-year survival free from hospital readmission >75% in patients with severe tricuspid regurgitation. Conventional echocardiographic parameters used to assess RV function and sPAP did not predict clinical outcome after TTVR.
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To explore the feasibility of CT-derived myocardial strain measurement in patients with advanced cardiac valve disease and to compare it to strain measurements derived from transthoracic ...echocardiography (TTE). 43 consecutive patients with advanced cardiac valve disease and clinically indicated retrospectively gated cardiac CTs were retrospectively analyzed. The longitudinal, circumferential as well as radial systolic strain were determined in all patients utilizing a commercially available CT strain software. In 36/43 (84%) patients, CT-derived longitudinal strain was compared to speckle-tracking TTE. Pearson's correlation coefficients as well as Bland-Altman analysis were used to compare the CT-derived strain measurements to TTE. The intra- and inter-reader-reliability of the CT-derived strain measurements were assessed by intra-class correlation coefficients (ICCs). Strain measurements were feasible in all patients. CT-derived global longitudinal strain (GLS) correlated moderately with TTE-derived GLS (r = 0.6, p < 0.001). A moderate correlation between CT-derived GLS and CT-derived left ventricular ejection fraction was found (LVEF, r = - 0.66, p = 0.036). Bland-Altman analysis showed a systematic underestimation of myocardial strain by cardiac CT compared to TTE (mean difference: - 5.8%, 95% limit of agreement between - 13.3 and 1.8%). Strain measurements showed an excellent intra- and inter-reader-reliability with an intra-reader ICC of 1.0 and an inter-reader ICC of 0.99 for GLS measurements. CT-derived myocardial strain measurements are feasible in patients with advanced cardiac valve disease. They are highly reproducible and correlate with established parameters of strain measurements. Our results encourage the implementation of CT-derived strain measurement into clinical routine.
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