Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation.

BACKGROUND: In patients who have chronic heart failure with reduced left ventricular ejection fraction, severe secondary mitral-valve regurgitation is associated with a poor prognosis. Whether percutaneous mitral-valve repair improves clinical outcomes in this patient population is unknown. METHODS: We randomly assigned patients who had severe secondary mitral regurgitation (defined as an effective regurgitant orifice area of >20 mm2 or a regurgitant volume of >30 ml per beat), a left ventricular ejection fraction between 15 and 40%, and symptomatic heart failure, in a 1:1 ratio, to undergo percutaneous mitral-valve repair in addition to receiving medical therapy (intervention group; 152 patients) or to receive medical therapy alone (control group; 152 patients). The primary efficacy outcome was a composite of death from any cause or unplanned hospitalization for heart failure at 12 months. RESULTS: At 12 months, the rate of the primary outcome was 54.6% (83 of 152 patients) in the intervention group and 51.3% (78 of 152 patients) in the control group (odds ratio, 1.16; 95% confidence interval [CI], 0.73 to 1.84; P=0.53). The rate of death from any cause was 24.3% (37 of 152 patients) in the intervention group and 22.4% (34 of 152 patients) in the control group (hazard ratio, 1.11; 95% CI, 0.69 to 1.77). The rate of unplanned hospitalization for heart failure was 48.7% (74 of 152 patients) in the intervention group and 47.4% (72 of 152 patients) in the control group (hazard ratio, 1.13; 95% CI, 0.81 to 1.56). CONCLUSIONS: Among patients with severe secondary mitral regurgitation, the rate of death or unplanned hospitalization for heart failure at 1 year did not differ significantly between patients who underwent percutaneous mitral-valve repair in addition to receiving medical therapy and those who received medical therapy alone. (Funded by the French Ministry of Health and Research National Program and Abbott Vascular; MITRA-FR ClinicalTrials.gov number, NCT01920698 .).

Phenotype/Genotype Relationship in Left Ventricular Noncompaction: Ion Channel Gene Mutations Are Associated With Preserved Left Ventricular Systolic Function and Biventricular Noncompaction: Phenotype/Genotype of Noncompaction.

BACKGROUND: Few data exist concerning genotype-phenotype relationships in left ventricular noncompaction (LVNC). METHODS AND RESULTS: From a multicenter French Registry, we report the genetic and clinical spectrum of 95 patients with LVNC, and their genotype-phenotype relationship. Among the 95 LVNC, 45 had at least 1 mutation, including 14 cases of mutation in ion channel genes. In a complementary analysis including 16 additional patients with ion channel gene mutations, for a total of 30 patients with ion channel gene mutation, we found that those patients had higher median LV ejection fraction (60% vs 40%; P < .001) and more biventricular noncompaction (53.1% vs 18.5%; P < .001) than the 81 other patients with LVNC. Among them, both the 19 patients with an HCN4 mutation and the 11 patients with an RYR2 mutation presented with a higher LV ejection fraction and more frequent biventricular noncompaction than the 81 patients with LVNC but with no mutation in the ion channel gene, but only patients with HCN4 mutation presented with a lower heart rate. CONCLUSIONS: Ion channel gene mutations should be searched systematically in patients with LVNC associated with either bradycardia or biventricular noncompaction, particularly when LV systolic function is preserved. Identifying causative mutations is of utmost importance for genetic counselling of at-risk relatives of patients affected by LVNC.

Mathematics in the archives: deconstructive historiography and the shaping of modern geometry (1837-1852).

This essay explores the research practice of French geometer Michel Chasles (1793-1880), from his 1837 Aperçu historique up to the preparation of his courses on 'higher geometry' between 1846 and 1852. It argues that this scientific pursuit was jointly carried out on a historiographical and a mathematical terrain. Epistemic techniques such as the archival search for and comparison of manuscripts, the deconstructive historiography of past geometrical methods, and the epistemologically motivated periodization of the history of mathematics are shown to have played a crucial role in the shaping of Chasles's own theories. In particular, we present Chasles's approach to the 'material history' of algebraic symbolism and argue that it motivated and informed his subsequent invention of a novel notational technology for the writing of geometrical proofs and propositions. In return, this technology allowed Chasles to carry out a programme for the modernization of geometry in keeping with epistemic requirements he had also delineated via a form of historical writing.

Targeted panel sequencing in adult patients with left ventricular non-compaction reveals a large genetic heterogeneity.

Left ventricular non-compaction (LVNC) is a cardiomyopathy that may be of genetic origin; however, few data are available about the yield of mutation, the spectrum of genes and allelic variations. The aim of this study was to better characterize the genetic spectrum of isolated LVNC in a prospective cohort of 95 unrelated adult patients through the molecular investigation of 107 genes involved in cardiomyopathies and arrhythmias. Fifty-two pathogenic or probably pathogenic variants were identified in 40 patients (42%) including 31 patients (32.5%) with single variant and 9 patients with complex genotypes (9.5%). Mutated patients tended to have younger age at diagnosis than patients with no identified mutation. The most prevalent genes were TTN, then HCN4, MYH7, and RYR2. The distribution includes 13 genes previously reported in LVNC and 10 additional candidate genes. Our results show that LVNC is basically a genetic disease and support genetic counseling and cardiac screening in relatives. There is a large genetic heterogeneity, with predominant TTN null mutations and frequent complex genotypes. The gene spectrum is close to the one observed in dilated cardiomyopathy but with specific genes such as HCN4. We also identified new candidate genes that could be involved in this sub-phenotype of cardiomyopathy.

Stand-alone kyphoplasty in recent thoracolumbar split fractures: A series of 36 patients reviewed at 19months.

INTRODUCTION: Spinal fractures with a split component present specific bone union problems (pseudarthrosis). The purpose of this study was to assess the rate of pseudarthrosis after stand-alone percutaneous kyphoplasties and analyze clinical and radiographic parameters that are predictive of its efficacy in thoracolumbar spine fractures with a split-type of injury. HYPOTHESIS: Stand-alone kyphoplasty results in satisfactory bone union of the treated vertebral body despite the diastasis of fracture fragments. MATERIALS AND METHODS: A retrospective single-center study of 36 patients with posttraumatic monosegmental thoracolumbar vertebral fractures, that were classified as either Magerl A2 or A3.2, without any neurologic deficits. Patients were treated with percutaneous kyphoplasty and PMMA bone cement. The assessment included both clinical (visual analog pain scale [VAS] and Oswestry disability index) and radiographic (pseudarthrosis, fracture gap, disk incarceration, vertebral height and length, and vertebral and regional kyphosis) criteria. RESULTS: A total of 36 patients (mean age 58years) were included, with a mean follow-up of 19.1months. Five of these patients (14%) had a pseudarthrosis. The fracture gap was significantly greater in these patients than in those who had bone union preoperatively (+3.94 mm, p<0.001) and at the last follow-up consultation (+9.3 mm, p<0.001). There was an association between the incarceration of adjacent disks located above (p=0.008) and below (p=0.003) the fracture site and the pseudarthrosis. The mean VAS decreased significantly on the first postoperative day (p<0.001) and remained lower than the initial assessment until the last follow-up (p<0.001). DISCUSSION: Stabilization by stand-alone kyphoplasty produces good clinical and radiographic results for split fractures, provided that the extent of the fragment diastasis has been carefully assessed preoperatively to prevent the risk of pseudarthrosis. LEVEL OF EVIDENCE: IV; retrospective.

The Ancients and the Moderns: Chasles on Euclid's lost Porisms and the pursuit of geometry.

Of Euclid's lost manuscripts, few have elicited as much scholarly attention as the Porisms, of which a couple of brief summaries by late-Antiquity commentators are extant. Despite the lack of textual sources, attempts at restoring the content of this absent volume became numerous in early-modern Europe, following the diffusion of ancient mathematical manuscripts preserved in the Arabic world. Later, one similar attempt was that of French geometer Michel Chasles (1793-1880). This paper investigates the historiographical tenets and practices involved in Chasles' restoration of the porisms, as well as the philosophical and mathematical claims tentatively buttressed therewith. Echoes of the Quarrel of the Ancients and the Moderns, and of a long-standing debate on the authority and usefulness of the past, are shown to have decisively shaped Chasles' enterprise-and, with it, his integration of mathematical and historical research.

Implementation of an in situ simulation-based training adapted from Morbidity and Mortality conference cases: effect on the occurrence of adverse events-study protocol of a cluster randomised controlled trial.

BACKGROUND: Morbidity and Mortality conference provides the necessary improvement measures for patient safety. However, they are an underused resource mainly because the conclusions to be drawn from the discussion and their implications for practice are not always well integrated by inpatient care teams. We therefore propose in this study two interventions to optimise their effectiveness: a passive feedback with wide dissemination by e-mail and/or on paper of the results of the Morbidity and Mortality conference to inpatient care teams and an active feedback with in situ inter-professional simulation-training programme in which scenarios will be based on cases studied in Morbidity and Mortality conference. In the present study, we hypothesise that the greatest reduction the occurrence of adverse event will be in the active feedback arm. METHODS: A cluster randomised controlled study will be performed at four study sites. The unit of randomisation is wards within the study sites. Fifteen wards will be randomly assigned to passive feedback, active feedback, or a standard MMC (control arm). Passive feedback and active feedback arms will be compared to standard arm in terms of occurrence of adverse events. The trigger tool methodology used to identify adverse events is a retrospective review of inpatient records using "triggers": an adverse event is defined as a patient's stay with at least one positive trigger. DISCUSSION: The in situ simulation training based on cases processed in Morbidity and Mortality conference is built according to the main topics identified for the successful implementation of healthcare simulation in patient safety programmes: technical skills, nontechnical skills, assessment, effectiveness, and system probing. The in situ simulation-training programme conducted as part of the study has the potential to improve patient safety during hospitalisation. We therefore expect the greatest reduction in the occurrence of adverse events in patients hospitalised in the active feedback arm. This expected result would have a direct impact on patient safety and would place in situ simulation at the highest level of the Kirkpatrick model. TRIAL REGISTRATION: Clinicaltrials.gov NCT02771613. Registered on May 12, 2016. All items from the WHO Trial Registration Data Set can be found within the protocol.

Prognosis of Adults With Isolated Left Ventricular Non-Compaction: Results of a Prospective Multicentric Study.

Background: Whether left ventricular non-compaction (LVNC) bears a different prognosis than dilated cardiomyopathy (DCM) is still a matter of debate. Methods: From a multicenter French prospective registry, we compared the outcomes of 98 patients with LVNC and 65 with DCM. The primary endpoint combined cardiovascular death, heart transplantation, and hospitalization for cardiovascular events. The two groups presented similar outcomes but different left ventricular ejection fractions (LVEF) (43.3% in LVNC vs. 35.95% in DCM, p = 0.001). For this reason, a subgroup analysis was performed comparing only patients with LVEF ≤ 45%, including 56 with LVNC and 49 with DCM. Results: Among patients with LVEF≤ 45%, at 5-year follow-up, the primary endpoint occurred in 33 (58.9%) among 56 patients with LVNC and 18 (36.7%) among 49 patients with DCM (p = 0.02). Hospitalization for heart failure (18 [32.14%] vs. 5 [10.20%], p = 0.035) and heart transplantation were more frequent in the LVNC than in the DCM group. The incidences of rhythmic complications (24 [42.85%] vs. 12 [24.48%], p = 0.17), embolic events, and cardiovascular death were similar between LVNC and DCM cases. Among the 42 patients with LVNC and LVEF > 45%, the primary endpoints occurred in only 4 (9.52%) patients, including 2 hospitalizations for heart failure and 3 rhythmic complications, but no embolic events. Conclusion: In this prospective cohort, patients with LVNC who have left ventricular dysfunction present a poorer prognosis than DCM patients. Heart failure events were especially more frequent, but embolic events were not. Patients with LVNC and preserved ejection fraction present very few events in 5 years.

Valvular heart disease associated with benfluorex therapy: high prevalence in patients with unexplained restrictive valvular heart disease.

AIMS: Restrictive valvular disease (RVD) has recently been reported in patients after benfluorex exposure. However, little is known about its prevalence and echocardiographic features. The aim of our study was to assess the frequency of benfluorex exposure in patients with RVD and to describe their echocardiographic characteristics. METHODS AND RESULTS: In a single centre study, patients with a final diagnosis of unexplained RVD were studied. Patients were interrogated for their previous use of benfluorex or other appetite-suppressant drugs (ASDs). Forty seven consecutive patients, aged 59 ± 9.6 years, with RVD were found [42 (91%) women]. Among them, 35 (74%) had previous treatment with ASD, including benfluorex in 34 patients. Among the latter, 14 (40%) have been exposed to benfluorex alone, 20 (60%) in combination with another ASD. Echocardiographic features included isolated mitral or aortic restricted valve motion in 19 patients (40%), and combined mitral and aortic involvement in 28 (60%).Twenty-seven (96%) of the latter had been exposed to benfluorex. As compared with the 'no ASD' group (n= 12), patients in the benfluorex group (n= 34) were more frequently female, had more frequent arterial hypertension and hypertriglyceridemia, and presented more frequently with combined mitral and aortic disease (79 vs. 8%, P < 0.001). Valve stenosis and tricuspid involvement were rare in the benfluorex group. CONCLUSION: The frequency of benfluorex exposure is high in patients with unexplained RVD. Combined aortic and mitral restrictive valve regurgitation is highly suggestive of valvular disease associated with benfluorex or other ASD therapy and may alert clinician about the possibility of this diagnosis.

Left atrial dysfunction as marker of poor outcome in patients with hypertrophic cardiomyopathy.

BACKGROUND: The incremental prognostic value of left atrial (LA) dysfunction, emerging in various clinical contexts, remains poorly explored in hypertrophic cardiomyopathy (HCM). OBJECTIVE: To assess LA strain correlation with outcome in HCM. METHODS: A cohort of all 307 consecutive patients presenting with HCM between 2007 and 2017 (54±17 years; 34% women), with comprehensive echocardiography at diagnosis and LA peak longitudinal strain (PALS) and LA peak contraction strain (PACS) measurement, was enrolled and occurrence of HCM related cardiac events analysed. RESULTS: Clinically, atrial fibrillation (AF) was present in 13%, New York Heart Association functional class II-III in 54%, and B-type natriuretic peptide (BNP) concentration was 199±278pg/mL. By echocardiography, left ventricular (LV) ejection fraction (EF) was 67±10%, LV thickness 21±5mm and European Society of Cardiology HCM risk score 3±3%, with 109 patients (36%) presenting obstructive HCM (LV outflow gradient 21±32mmHg). LA diameter was 41±8mm [with 109 (36%) presenting LA diameter ≥40mm], LA volume index 50±26mL/m2, PALS 24±13%, PACS 11±7% and LA peak systolic strain rate (LASRs) 1.7±0.6 s-1. In addition to AF, age, BNP, LVEF and LV thickness were all independent determinants of lower PALS, with odd ratios almost unchanged after adjustment (all P ≤0.0004). At a mean follow-up of 21 (range 18-23) months, patients with adverse cardiac events (n=65) presented with more impaired LA function (all P ≤0.0005), with a significant association between impaired PALS and worse outcome, hazard ratio 0.94 [95% confidence interval (CI) 0.92-0.97, P<0.0001]. After comprehensive adjustment, PALS remained strongly associated with worse outcome, adjusted hazard ratio 0.86 (95% CI 0.79-0.94; P=0.0008). CONCLUSIONS: The present study, by gathering a unique HCM cohort, suggests a strong link between LA dysfunction and poor outcome, to be further investigated.

Direct measurement of the flow field around swimming microorganisms.

Swimming microorganisms create flows that influence their mutual interactions and modify the rheology of their suspensions. While extensively studied theoretically, these flows have not been measured in detail around any freely-swimming microorganism. We report such measurements for the microphytes Volvox carteri and Chlamydomonas reinhardtii. The minute (∼0.3%) density excess of V. carteri over water leads to a strongly dominant Stokeslet contribution, with the widely-assumed stresslet flow only a correction to the subleading source dipole term. This implies that suspensions of V. carteri have features similar to suspensions of sedimenting particles. The flow in the region around C. reinhardtii where significant hydrodynamic interaction is likely to occur differs qualitatively from a puller stresslet, and can be described by a simple three-Stokeslet model.

Left-ventricular non-compaction-comparison between different techniques of quantification of trabeculations: Should the diagnostic thresholds be modified?

BACKGROUND: Diagnosis of left ventricular non-compaction (LVNC) is challenging, and different imaging techniques propose different criteria. AIM: To compare the value of two-dimensional transthoracic echocardiography (2D-TTE) and cardiac magnetic resonance (CMR) criteria in diagnosing LVNC, and to test a new trabecular quantification method obtained by 2D-TTE, exploring its relationship with CMR non-compacted mass quantification. METHODS: From a multicentre French study, we selected 48 patients with LVNC and 20 with dilated cardiomyopathy (DCM) who underwent 2D-TTE and CMR. Current 2D-TTE (Jenni et al.) and CMR criteria (Petersen et al., Jacquier et al.), were tested. A new 2D-TTE method of trabecular quantification (percentage of trabecular area) was also proposed, and compared with current criteria. RESULTS: The best cut-off values for the diagnosis of LVNC were a non-compacted/compacted ratio≥2.3 (Petersen et al.), a trabeculated left ventricular mass≥20% (Jacquier et al.) and a non-compacted/compacted ratio≥1.8 (Jenni et al.). Lowering the threshold for the criterion of Jenni et al. from>2 to ≥1.8 improved its sensitivity from 69% to 98%. The 2D-TTE percentage of trabecular area was 25.9±8% in the LVNC group vs. 9.9±4.4% in the DCM group (P<0.05), and was well correlated with CMR non-compacted mass (r=0.65; P<0.05). A 15.8% threshold value for 2D-TTE percentage of trabecular area predicted LVNC diagnosis with a specificity of 95% and a sensitivity of 92%; its sensitivity was better than that for the criteria of Jenni et al. (P<0.01) and Petersen et al. (P=0.03). CONCLUSIONS: Revision of the current threshold for the criterion of Jenni et al. from>2 to ≥1.8 is necessary to improve LVNC diagnosis in patients with left ventricular dysfunction. A new 2D-TTE trabecular quantification method improves TTE diagnosis of LVNC.

Cortisol concentration of regrown hair and hair from a previously unshorn area in dairy cows.

This study determined cortisol concentrations in hair that had grown for one month and in hair from a previously unshorn area and examined the effects of calendar month, pregnancy and illness on hair cortisol concentrations in dairy cows. The study was conducted over a one-year period using 27 cows. Electric clippers were used to collect two hair samples per cow each month. The first sample (A sample) consisted of hair that had grown for one month in a pre-clipped area and the second sample (B sample) comprised all hair from a previously unshorn area. Liquid chromatography tandem mass-spectrometry was used for cortisol measurement. The overall mean concentrations for A and B samples did not differ. Cortisol concentrations of A samples were significantly higher in the winter (0.86±0.37pg/mg) than in the fall (0.67±0.33pg/mg). The hair cortisol concentration in A samples increased during pregnancy and the maximum concentration of 1.40±1.08pg/mg hair in the month of calving was significantly higher than the concentration measured in the first month (0.66±0.32pg/mg). The findings show that the effect of short-term stressors such as parturition on hair cortisol concentrations are more easily detected in hair that has grown for one month than in hair from a previously unshorn area.

Determination of phase transition temperatures of lipids by light scattering.

Various techniques have been proposed to specify the phase transition temperatures of surfactant molecules. The work reported herein deals with a new general method of T(c) determination based on the optical properties' modifications of aqueous surfactant solutions when the phase transitions occur in the phospholipid membrane. The shape alteration of supramolecular systems induced by the phase transition was correlated with the refraction and absorption coefficients of their aqueous dispersion. The mean count rate (average number of photons detected per second) measured with a Zetasizer Nano-S model ZEN1600 Dynamic Light Scattering Instrument, is representative of an emerging macroscopic phenomenon, but not directly size dependent and has been adapted to our expectations. Changes in the measured scattering intensity reflect changes in the optical properties of the material during temperature variations. Thus, this method allowed to specify the phase transition temperature of many natural or synthetic surfactants independently of their polar head or hydrophobic part.

Management and research in cancer treatment-related cardiovascular toxicity: Challenges and perspectives.

Cardiovascular toxicity is a potentially serious complication that can result from the use of various cancer therapies and can impact the short- and long-term prognosis of treated patients as well as cancer survivors. In addition to their potential acute cardiovascular adverse events, new treatments can lead to late toxicity even after their completion because patients who survive longer generally have an increased exposure to the cancer therapies combined to standard cardiovascular risk factors. These complications expose the patient to the risk of cardiovascular morbi-mortality, which makes managing cardiovascular toxicity a significant challenge. Cardio-oncology programs offer the opportunity to improve cardiovascular monitoring, safety, and management through a better understanding of the pathogenesis of toxicity and interdisciplinary collaborations. In this review, we address new challenges, perspectives, and research priorities in cancer therapy-related cardiovascular toxicity to identify strategies that could improve the overall prognosis and survival of cancer patients. We also focus our discussion on the contribution of cardio-oncology in each step of the development and use of cancer therapies.

Exotic aqueous behavior of synthetic lipids: formation of vesicular nanotubes.

The work reported herein deals with the synthesis and the aggregation behavior studies of synthetic lipids bearing a non-ionic polar head made up of a tris(hydroxymethyl) aminomethane (tris) moiety linked with an aminoglycerol interface. The hydrophobic chains with variable lengths were grafted onto the hydroxyl functions of the aminoglycerol residue through ester or carbamate bonds. Tiny chemical modifications within this family of non-ionic surfactants brought about major variations in their aggregation behavior. They formed vesicles, tubules, and also small stable end-capped tubules - called vesicular nanotubes -, when the polar head bore two heptadecyl chains linked through a carbamate bond. Various techniques (nanosizer measurements, freeze fracture electron microscopy (FFEM), transmission electron microscopy (TEM), carboxyfluorescein (CF)) encapsulation were used to specify the structure of these assemblies. Notably, the vesicular nanotubes exhibited a small size, a fair polydispersity, great stability in an aqueous solution (up to 1 year) and a good efficiency to entrap and slowly release a probe such as carboxyfluoresceine: all these properties are perfectly suitable for their use as potential drug carriers.

Adrenal venous sampling is crucial before an adrenalectomy whatever the adrenal-nodule size on computed tomography.

OBJECTIVE: To assess the additional value of adrenal venous sampling (AVS) to diagnose primary aldosteronism sub-types in patients who have a unilateral nodule detected by computed tomography (CT scan) and who should undergo an adrenalectomy. METHODS: A retrospective study to assess consecutive patients with primary aldosteronism undergoing an adrenal CT scan and AVS. Criterion for selective cannulation was an equal or higher cortisol level in the adrenal vein compared to the inferior vena cava. An adrenal-vein aldosterone-to-cortisol ratio of at least two times higher than the other side defined lateralization of aldosterone production. RESULTS: Sixty-seven patients (mean age 52 years, 39 men) underwent a CT scan and AVS. In nine patients (13%), cannulation of the right adrenal vein led to a technical failure. Both procedures led to diagnosis of 29 patients with adenoma-producing aldosterone (APA; 50%), 23 bilateral adrenal hyperplasias (40%), and six unilateral adrenal hyperplasias (10%). Of the 45 patients with a nodule detected by CT, subsequent AVS showed bilateral secretion in 16 patients (36%). Compared to the strategy of coupling CT scans with AVS to diagnosis APA, a CT scan alone had an accuracy of 72.4% (P < 0.001). Among patients with a macronodule detected by CT, 13 (37%) had bilateral secretion as assessed by AVS. The patients with a macronodule detected by CT alone had the same risk of a discrepancy as those with a small nodule (P = 0.99). CONCLUSION: AVS is essential to diagnose the unilateral hypersecretion of aldosterone, even in patients in whom a unilateral macronodule is detected by CT, to avoid unnecessary surgery.