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In this work, the reactivity of tetrel-functionalized phosphorus clusters toward organoazides is probed. Clusters (Me3Si)3P7 (1) and (Me3Ge)3P7 (2) were reacted with benzyl azide, phenyl azide, and 4-bromophenyl azide, and it was found that the [RN] (R = benzyl, phenyl, and 4-bromophenyl) unit from the azide inserted into the phosphorus-tetrel bonds on the cluster, accompanied by N2 elimination. Through control of the azide stoichiometry, the mono-, bis-, and tris-inserted products could be observed, consistent with these insertions proceeding in a stepwise manner. The bonding between the amine moieties and clusters was further investigated by computational chemistry, and the findings were consistent with the phosphorus cluster having undergone a formal oxidation. These insertion reactions are a convenient means of accessing Zintl clusters functionalized with exo-nitrogen-bonded moieties, which, to the best of our knowledge, were previously unknown.

Abstract Aim The diagnosis of hypertrophic cardiomyopathy (HCM) with moderate hypertrophy is challenging. Hypertensive heart disease (HHD) is the most common differential diagnosis that mimics the LVH of HCM. The aim of this study was to compare the QRS duration in HCM and HHD to create a novel diagnostic tool to identify primary HCM. Methods and results We conducted an international retrospective multicentre study enrolling patients with true HCM and HHD. A total of 547 individuals with HCM and 139 with HHD were included. The median QRS duration was significantly shorter in HCM than in HHD (88 ms [80–94] vs. 98 ms [88–108]; P

BackgroundLittle is known about left ventricular (LV) sequences of contraction and electrical activation in hypertrophic cardiomyopathy (HCM). A better understanding of the underlying relation between mechanical and electrical activation may allow the identification of predictive response criteria to right ventricular DDD pacing in obstructive patients.ObjectiveTo describe LV mechanical and electrical activation sequences in HCM patients compared to controls.Materials and methodsWe prospectively studied, in 40 HCM patients (20 obstructive and 20 non-obstructive) and 20 healthy controls: (1) mechanical activation using echocardiography at rest and cardiac magnetic resonance imaging, (2) electrical activation using 3-dimensional electrocardiographic mapping (ECM).ResultsIn echocardiography, healthy controls had a physiological apex-to-base delay (ABD) during contraction (23.8 ± 16.2 ms). Among the 40 HCM patients, 18 HCM patients presented a loss of this ABD (

Background: Hypertrophic cardiomyopathies (HCM) can be complicated by left ventricular outflow-tract obstruction (LVOTO) responsible for disabling exercise symptoms, a phenomenon influenced by hemodynamic factors including venous return. Methods: We aimed to evaluate venous dysfunction in obstructive HCM patients compared to healthy controls, and to investigate the relationship between venous dysfunction parameters and LVOTO in HCM. This is a clinical, monocentric, prospective, pilot study, in a tertiary care center. We investigated venous function using venous air plethysmography, and endothelial function. Results: Among the 30 symptomatic obstructive HCM patients, 30% (n = 9) presented abnormal venous residual volume fraction (RVFv) which translates in elevated ambulatory venous pressure vs. 0% in the 10 healthy controls (p

Aim: The diagnosis of hypertrophic cardiomyopathy (HCM) with moderate hypertrophy is challenging. Hypertensive heart disease (HHD) is the most common differential diagnosis that mimics the LVH of HCM. The aim of this study was to compare the QRS duration in HCM and HHD to create a novel diagnostic tool to identify primary HCM. Methods and results: We conducted an international retrospective multicentre study enrolling patients with true HCM and HHD. A total of 547 individuals with HCM and 139 with HHD were included. The median QRS duration was significantly shorter in HCM than in HHD (88 ms [80–94] vs. 98 ms [88–108]; P < 0.01). Multivariable logistic regression identified for the novel diagnostic HCM (D‐HCM) score: absence of antihypertensive drugs (+2); family history of unexplained sudden death (+2); QRS duration [<95 ms] = +1; maximum wall thickness (mm) [≥17] = +1. A cumulative QRS‐HCM score ≥2 supports the diagnostic certainty of true HCM with a sensitivity of 79%, specificity of 99%, negative predictive value (NPV) of 55%, and positive predictive value (PPV) of 99%. Conclusion: The QRS duration in patient with HCM is significantly shorter compared with patients with HHD‐related LVH. QRS duration can be used as a diagnosis marker to distinguish between HCM and HHD. The D‐HCM score is a novel, simple, and accurate diagnosis tool for HCM patients with mild to moderate phenotypes. [ABSTRACT FROM AUTHOR]

MitraClip (Abbott Laboratories, Abbott Park, IL) is validated in high-risk patients with severe degenerative mitral regurgitation (MR); however, it is not well established for functional MR in hypertrophic cardiomyopathy (HCM). We share a case of a 68-year-old man with HCM hospitalized for multiple incidents of acute pulmonary edema caused by a dynamic MR and successfully treated with the MitraClip device. Novel teaching points emerging from this case are that MRs in HCM can often be explained by mixed mechanisms, and properly identifying the MR mechanism is essential to choose optimal treatment. Furthermore, MitraClip can simultaneously treat MR secondarily to annular dilation and systolic anterior motion. Résumé: Il a été établi démque Le Mitraclip (Abbott Laboratories, Abbott Park, Il) est une intervention percutanée validée pour la prise en charge des patients à haut risque chirurgical qui présente une régurgitation mitrale (RM) sévère dégénérative. Toutefois, cette technique est moins bien établie dans une RM fonctionnelle dans le cadre d'une cardiomyopathie hypertrophique (CMH). Nous faisons part d'un cas d’un homme de 68 ans atteint d’une CMH et hospitalisé en raison de multiples œdèmes aigus du poumon causés une la RM dynamique dont le traitement par MitraClip s’est avéré une réussite. Les nouveaux d'enseignement à enseigner qui émergent de ce cas portent sur le fait que les RM dans le cadre d’une CMH s’expliquent souvent par des mécanismes mixtes et que la détermination exacte du mécanisme de la RM est essentielle pour choisir le traitement qui convient le mieux au patient. De plus, le MitraClip permet de traiter simultanément les deux mécanismes d'une RM due à une dilatation annulaire et au mouvement systolique antérieur.

A single missense variant of the TMPO/LAP2α gene, encoding LAP2 proteins, has been associated with cardiomyopathy in two brothers. To further evaluate its role in cardiac muscle, we included TMPO in our cardiomyopathy diagnostic gene panel. A screening of ~5000 patients revealed three novel rare TMPO heterozygous variants in six males diagnosed with hypertrophic or dilated cardiomypathy. We identified in different cellular models that (1) the frameshift variant LAP2α p.(Gly395Glufs*11) induced haploinsufficiency, impeding cell proliferation and/or producing a truncated protein mislocalized in the cytoplasm; (2) the C-ter missense variant LAP2α p.(Ala240Thr) led to a reduced proximity events between LAP2α and the nucleosome binding protein HMGN5; and (3) the LEM-domain missense variant p.(Leu124Phe) decreased both associations of LAP2α/β with the chromatin-associated protein BAF and inhibition of the E2F1 transcription factor activity which is known to be dependent on Rb, partner of LAP2α. Additionally, the LAP2α expression was lower in the left ventricles of male mice compared to females. In conclusion, our study reveals distinct altered properties of LAP2 induced by these TMPO/LAP2 variants, leading to altered cell proliferation, chromatin structure or gene expression-regulation pathways, and suggests a potential sex-dependent role of LAP2 in myocardial function and disease.

[Display omitted] • We aimed to identify the real-life target population for a selective cMI in HCM. • We studied 1059 adult patients with HCM enrolled in REMY (a French HCM registry) • 325 (30.7%) of these patients were potential candidates for a cMI. • 9% more became eligible for a cMI during follow-up. The efficacy of current pharmacological therapies in hypertrophic cardiomyopathy is limited. A cardiac myosin inhibitor, mavacamten, has recently been approved as a first-in-class treatment for symptomatic hypertrophic obstructive cardiomyopathy. To assess the profile and burden of cardiac myosin inhibitor candidates in the hypertrophic cardiomyopathy prospective Register of hypertrophic cardiomyopathy (REMY) held by the French Society of Cardiology. Data were collected at baseline and during follow-up from patients with hypertrophic cardiomyopathy enrolled in REMY by the three largest participating centres. Among 1059 adults with hypertrophic cardiomyopathy, 461 (43.5%) had obstruction; 325 (30.7%) of these were also symptomatic, forming the "cardiac myosin inhibitor candidates" group. Baseline features of this group were: age 58 ± 15 years; male sex (n = 196; 60.3%); diagnosis-to-inclusion delay 5 (1–12) years; maximum wall thickness 20 ± 6 mm; left ventricular ejection fraction 69 ± 6%; family history of hypertrophic cardiomyopathy or sudden cardiac death (n = 133; 40.9%); presence of a pathogenic sarcomere gene mutation (n = 101; 31.1%); beta-blocker or verapamil treatment (n = 304; 93.8%), combined with disopyramide (n = 28; 8.7%); and eligibility for septal reduction therapy (n = 96; 29%). At the end of a median follow-up of 66 (34–106) months, 319 (98.2%) were treated for obstruction (n = 43 [13.2%] received disopyramide), 46 (14.2%) underwent septal reduction therapy and the all-cause mortality rate was 1.9/100 person-years (95% confidence interval 1.4–2.6) (46 deaths). Moreover, 41 (8.9%) patients from the initial hypertrophic obstructive cardiomyopathy group became eligible for a cardiac myosin inhibitor. In this cohort of patients with hypertrophic cardiomyopathy selected from the REMY registry, one third were eligible for a cardiac myosin inhibitor. [ABSTRACT FROM AUTHOR]

We present and characterize an original experimental model to create a chronic ischemic heart failure in pig. Two ameroid constrictors were placed around the LAD and the circumflex artery. Two months after surgery, pigs presented a poor LV function associated with a severe mitral valve insufficiency. Echocardiography analysis showed substantial anomalies in radial and circumferential deformations, both on the anterior and lateral surface of the heart. These anomalies in function were coupled with anomalies of perfusion observed in echocardiography after injection of contrast medium. No demonstration of myocardial infarction was observed with histological analysis. Our findings suggest that we were able to create and to stabilize a chronic ischemic heart failure model in the pig. This model represents a useful tool for the development of new medical or surgical treatment in this field.

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)