Comparison of the Hemodynamic Performance of Percutaneous and Surgical Bioprostheses for the Treatment of Severe Aortic Stenosis

ObjectivesThis study was undertaken to compare the hemodynamic performance of a percutaneous bioprosthesis to that of surgically implanted (stented and stentless) bioprostheses for the treatment of severe aortic stenosis.MethodsFifty patients who underwent percutaneous aortic valve implantation (PAVI) with the Cribier-Edwards or Edwards SAPIEN bioprosthetic valve (Edwards Lifesciences, Inc., Irvine, California) were matched 1:1 for sex, aortic annulus diameter, left ventricular ejection fraction, body surface area, and body mass index, with 2 groups of 50 patients who underwent surgical aortic valve replacement (SAVR) with a stented valve (Edwards Perimount Magna [SAVR-ST group]), or a stentless valve (Medtronic Freestyle, Medtronic, Minneapolis, Minnesota [SAVR-SL group]). Doppler echocardiographic data were prospectively obtained before the intervention, at discharge, and at 6- to 12-month follow-up.ResultsMean transprosthetic gradient at discharge was lower (p < 0.001) in the PAVI group (10 ± 4 mm Hg) compared with the SAVR-ST (13 ± 5 mm Hg) and SAVR-SL (14 ± 6 mm Hg) groups. Aortic regurgitation (AR) occurred more frequently in the PAVI group (mild: 42%, moderate: 8%) compared with the SAVR-ST (mild: 10%, moderate: 0%) and SAVR-SL (mild: 12%, moderate: 0%) groups (p < 0.0001). At follow-up, the mean gradient in the PAVI group remained lower (p < 0.001) than that of the SAVR-ST group, but was similar to that of the SAVR-SL group. The incidence of severe prosthesis-patient mismatch was significantly lower (p = 0.007) in the PAVI group (6%) compared with the SAVR-ST (28%) and SAVR-SL (20%) groups. However, the incidence of AR remained higher (p < 0.0001) in the PAVI group compared with the 2 other groups.ConclusionsPAVI provided superior hemodynamic performance compared with the surgical bioprostheses in terms of transprosthetic gradient and prevention of severe prosthesis-patient mismatch, but was associated with a higher incidence of AR

Myocardial injury following transcatheter aortic valve implantation : insights from delayed-enhancement cardiovascular magnetic resonance

Aims: The aim of this study was to evaluate the presence, localisation and extent of myocardial injury as determined by late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) imaging in patients undergoing transcatheter aortic valve implantation (TAVI). Methods and results: A total of 37 patients, who underwent successful TAVI with a balloon-expandable valve (transapical [TA], n=11; non-TA, n=26), were included. Cardiac biomarker (CK-MB and cTnT) lev- els were determined at baseline and following TAVI. CMR was performed within a week before and within 30 days following TAVI. Some increase in cardiac biomarkers was detected in 97% of the patients as deter- mined by a rise in cTnT, and in 49% of the patients as determined by a rise in CK-MB. Following TAVI, no new myocardial necrosis defects were observed with the non-TA approach. Nonetheless, all patients who underwent TAVI through the TA approach had new focal myocardial necrosis in the apex, with a median myo-cardial extent and necrotic mass of 5% [2.0-7.0] and 3.5 g [2.3-4.5], respectively. Conclusions: Although some increase in cardiac biomarkers of myocardial injury was systematically detected following TAVI, new myocardial necrosis as evaluated by CMR was observed only in patients undergoing the procedure through the TA approach, involving ~5% of the myocardium in the apex

The origins and spread of domestic horses from the Western Eurasian steppes

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: All collapsed and paired-end sequence data for samples sequenced in this study are available in compressed fastq format through the European Nucleotide Archive under accession number PRJEB44430, together with rescaled and trimmed bam sequence alignments against both the nuclear and mitochondrial horse reference genomes. Previously published ancient data used in this study are available under accession numbers PRJEB7537, PRJEB10098, PRJEB10854, PRJEB22390 and PRJEB31613, and detailed in Supplementary Table 1. The genomes of ten modern horses, publicly available, were also accessed as indicated in their corresponding original publications57,61,85-87.NOTE: see the published version available via the DOI in this record for the full list of authorsDomestication of horses fundamentally transformed long-range mobility and warfare. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling at Botai, Central Asia around 3500 BC. Other longstanding candidate regions for horse domestication, such as Iberia and Anatolia, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 BC, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 BC driving the spread of Indo-European languages. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium BC Sintashta culture

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Outcome of diabetic foot infections treated conservatively: a retrospective cohort study with long-term follow-up

BACKGROUND: Diabetic foot lesion is associated with increased morbidity and high resource use. Although early amputation has been advocated in case of osteomyelitis, conservative treatment is a more attractive alternative. OBJECTIVE: To identify criteria predictive of failure of conservative treatment of diabetic foot ulcer at time of admission to the hospital. METHODS: We conducted a 5-year retrospective cohort study with prospective long-term follow-up of all diabetic patients admitted for a foot lesion at a large (1600-bed) teaching institution. Predetermined criteria were used for the diagnosis and classification of diabetic foot lesions (Wagner classification). Study variables included patient demographics and clinical parameters related to infection and diabetes. The average follow-up after hospital discharge was 2 years. Failure of conservative treatment was the main outcome measure. Independent predictor variables were selected by logistic regression analysis. RESULTS: A total of 120 diabetic patients were admitted for foot lesions; complications of contiguous osteomyelitis, deep tissue involvement, and/or gangrenous lesions occurred in 78 (74%) of the 105 patients for whom charts were available. Fourteen patients (13%) underwent immediate amputation. Conservative treatment was successful for 57 (63%) of the 91 remaining patients. Success was achieved in 21 (81%) of 26 patients presenting with skin ulcer, 35 (70%) of 50 patients with deep tissue infection or suspected osteomyelitis, and 1 (7%) of 15 patients with gangrene (P<.001, chi2 for trend). Independent factors predictive of failure were the presence of fever (odds ratio [OR]=1.1 per degrees Celcius; 95% confidence interval [CI], 1.0-1.2) and increased serum creatinine level (OR=1.002 per micromoles per liter; 95% CI, 1.0020-1.0021) on admission, prior hospitalization for diabetic foot lesion (OR=1.4; 95% CI, 1.2-1.6), and gangrenous lesion (OR=1.8; 95% CI, 1.5-2.2). Other patient characteristics, demographics, duration of diabetes mellitus, neutrophil count, or the anatomical site of the lesion failed to predict outcome. CONCLUSIONS: Conservative treatment, including prolonged, culture-guided parenteral and oral antibiotics, is successful without amputation in a large proportion of diabetic patients admitted for a foot skin ulcer or suspected osteomyelitis. Future studies comparing early amputation with novel therapeutic strategies for severe diabetic foot infection should take into account currently identified factors that predicted failure of conservative treatment on admission to the hospital

Validation and characterization of transcatheter aortic valve effective orifice area measured by Doppler echocardiography

Objectives : The objectives were to compare different Doppler echocardiographic methods for the measurement of prosthetic valve effective orifice area (EOA) following transcatheter aortic valve implantation (TAVI) and to determine the factors influencing the EOA of transcatheter balloon expandable valves.Background : Previous studies have used different methods for the measurement of the valve EOA following TAVI. Factors influencing the EOA of transcatheter valves are unknown.Methods : A total of 122 patients underwent TAVI with the use of the Edwards-SAPIEN valve (Edwards Lifesciences, Irvine, California). The EOA was measured by transthoracic echocardiography at hospital discharge, 6 months and 1 year after TAVI with the use of 2 methods as described in previous studies. In Method #1 (EOA1), LVOT diameter (LVOTd) entered in the continuity equation was measured at the base of prosthesis cusps whereas, in Method #2 (EOA2), LVOTd was measured immediately proximal to the prosthesis stent.Results : The average EOA2 (1.57 ± 0.41 cm2) was larger (p 23 mm.Conclusions : When estimating the EOA of Edwards-SAPIEN valves by Doppler-echocardiography, it is recommended to use the LVOT diameter and velocity measured immediately proximal to the stent. The main determinant of the EOA of transcatheter valves is the patient's annulus size and these valves provide excellent hemodynamics even in patients with a small aortic annulus

Data-driven model of virtual patient for doctor social training

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