Pseudoaneurysm of the left ventricle following apical approach TAVI

Symptomatic severe aortic stenosis carries a two year survival of only 50%. However many patients are unsuitable for conventional aortic valve replacement as they are considered too high risk due to significant co-morbidities. Transcatheter Aortic Valve Implantation (TAVI) offers a viable alternative for this high risk patient group, either by the femoral or apical route. This article reports a case of a pseudoaneurysm of the left ventricle following an apical approach TAVI in an elderly lady with severe aortic stenosis. To our knowledge pseduoaneuryms of the left ventricle have been reported infrequently in the literature and has yet to be established as a recognised complication of TAVI

Interleukin 11 therapy causes acute left ventricular dysfunction

Aims: Interleukin 11 (IL11) was initially thought important for platelet production, which led to recombinant IL11 being developed as a drug to treat thrombocytopenia. IL11 was later found to be redundant for haematopoiesis and its use in patients is associated with unexplained and severe cardiac side effects. Here we aim to identify, for the first time, direct cardiomyocyte toxicities associated with IL11, which was previously believed cardioprotective.// Methods and Results: We injected recombinant mouse lL11 (rmIL11) into mice and studied its molecular effects in the heart using immunoblotting, qRT-PCR, bulk RNA-seq, single nuclei RNA-seq (snRNA-seq) and ATAC-seq. The physiological impact of IL11 was assessed by echocardiography in vivo and using cardiomyocyte contractility assays in vitro. To determine the activity of IL11 specifically in cardiomyocytes we made two cardiomyocyte-specific Il11ra1 knockout (CMKO) mouse models using either AAV9-mediated and Tnnt2-restricted (vCMKO) or Myh6 (m6CMKO) Cre expression and an Il11ra1 floxed mouse strain. In pharmacologic studies, we studied the effects of JAK/STAT inhibition on rmIL11-induced cardiac toxicities. Injection of rmIL11 caused acute and dose-dependent impairment of left ventricular ejection fraction (saline: 62.4% ± 1.9; rmIL11: 32.6% ± 2.9, p<0.001, n=5). Following rmIL11 injection, myocardial STAT3 and JNK phosphorylation were increased and bulk RNA-seq revealed upregulation of pro-inflammatory pathways (TNFα, NFκB and JAK/STAT) and perturbed calcium handling. snRNA-seq showed rmIL11-induced expression of stress factors (Ankrd1, Ankrd23, Xirp2), activator protein-1 (AP-1) transcription factor genes and Nppb in the cardiomyocyte compartment. Following rmIL11 injection, ATAC-seq identified the Ankrd1 and Nppb genes and loci enriched for stress-responsive, AP-1 transcription factor binding sites. Cardiomyocyte-specific effects were examined in vCMKO and m6CMKO mice, which were both protected from rmIL11-induced left ventricular impairment and molecular pathobiologies. In mechanistic studies, inhibition of JAK/STAT signalling with either ruxolitinib or tofacitinib prevented rmIL11-induced cardiac dysfunction.// Conclusions: Injection of IL11 directly activates IL11RA/JAK/STAT3 in cardiomyocytes to cause acute heart failure. Our data overturn the earlier assumption that IL11 is cardioprotective and explain the serious cardiac side effects associated with IL11 therapy

Changes in muscle contractile characteristics and jump height following 24 days of unilateral lower limb suspension

We measured changes in maximal voluntary and electrically evoked torque and rate of torque development because of limb unloading. We investigated whether these changes during single joint isometric muscle contractions were related to changes in jump performance involving dynamic muscle contractions and several joints. Six healthy male subjects (21 ± 1 years) underwent 3 weeks of unilateral lower limb suspension (ULLS) of the right limb. Plantar flexor and knee extensor maximal voluntary contraction (MVC) torque and maximal rate of torque development (MRTD), voluntary activation, and maximal triplet torque (thigh; 3 pulses at 300 Hz) were measured next to squat jump height before and after ULLS. MVC of plantar flexors and knee extensors (MVCke) and triplet torque decreased by 12% (P = 0.012), 21% (P = 0.001) and 11% (P = 0.016), respectively. Voluntary activation did not change (P = 0.192). Absolute MRTD during voluntary contractions decreased for plantar flexors (by 17%, P = 0.027) but not for knee extensors (P = 0.154). Absolute triplet MRTD decreased by 17% (P = 0.048). The reduction in MRTD disappeared following normalization to MVC. Jump height with the previously unloaded leg decreased significantly by 28%. No significant relationships were found between any muscle variable and jump height (r < 0.48), but decreases in torque were (triplet, r = 0.83, P = 0.04) or tended to be (MVCke r = 0.71, P = 0.11) related to decreases in jump height. Thus, reductions in isometric muscle torque following 3 weeks of limb unloading were significantly related to decreases in the more complex jump task, although torque in itself (without intervention) was not related to jump performance

Remote ischemic conditioning: from experimental observation to clinical application: report from the 8th Biennial Hatter Cardiovascular Institute Workshop

In 1993, Przyklenk and colleagues made the intriguing experimental observation that 'brief ischemia in one vascular bed also protects remote, virgin myocardium from subsequent sustained coronary artery occlusion' and that this effect'... may be mediated by factor(s) activated, produced, or transported throughout the heart during brief ischemia/reperfusion'. This seminal study laid the foundation for the discovery of 'remote ischemic conditioning' (RIC), a phenomenon in which the heart is protected from the detrimental effects of acute ischemia/reperfusion injury (IRI), by applying cycles of brief ischemia and reperfusion to an organ or tissue remote from the heart. The concept of RIC quickly evolved to extend beyond the heart, encompassing inter-organ protection against acute IRI. The crucial discovery that the protective RIC stimulus could be applied non-invasively, by simply inflating and deflating a blood pressure cuff placed on the upper arm to induce cycles of brief ischemia and reperfusion, has facilitated the translation of RIC into the clinical setting. Despite intensive investigation over the last 20 years, the underlying mechanisms continue to elude researchers. In the 8th Biennial Hatter Cardiovascular Institute Workshop, recent developments in the field of RIC were discussed with a focus on new insights into the underlying mechanisms, the diversity of non-cardiac protection, new clinical applications, and large outcome studies. The scientific advances made in this field of research highlight the journey that RIC has made from being an intriguing experimental observation to a clinical application with patient benefit

A computerized craniofacial reconstruction method for an unidentified skull based on statistical shape models

Craniofacial reconstruction (CFR) has been widely used to produce the facial appearance of an unidentified skull in the realm of forensic science. Many studies have indicated that the computerized CFR approach is fast, flexible, consistent and objective in comparison to the traditional manual CFR approach. This paper presents a computerized CFR system called CFRTools, which features a CFR method based on a statistical shape model (SSM) of living human head models. Given an unidentified skull, a geometrically-similar template skull is chosen as a template, and a non-registration method is used to improve the accuracy of the construction of dense corresponding vertices through the alignment of the template and the unidentified skull. Generalized Procrustes analysis (GPA) and principal component analysis (PCA) are carried out to construct the skull and face SSMs. The sex of the unidentified skull is then predicted based on skull SSM and centroid size, rather than geometric measurements based on anatomical landmarks. Furthermore, a craniofacial morphological relationship which is learnt from the principal component (PC) scores of the skull and face dataset is used to produce a possible reconstructed face. Finally, multiple possible reconstructed faces for the same skull can further be recreated based on adjusting the PC coefficients. The experimental results show that the average rate of sex classification is 97.14% and the reconstructed face of the unidentified skull can be produced. In addition, experts’ understanding and experience can be harnessed in production of face variations for the same skull, which can further be used as a reference for portraiture creation

Ground reaction force differences in the countermovement jump in girls with different levels of performance

Purpose: The aim of this study was to ascertain the biomechanical differences between better and poorer performers of the vertical jump in a homogeneous group of children. Method: Twenty-four girls were divided into low-scoring (LOW; M age = 6.3 ± 0.8 years) and high-scoring (HIGH; M age = 6.6 ± 0.8 years) groups based on their performance on the vertical jump. The force-, velocity-, displacement-, and rate of force development (RFD)-time curves of vertical jumps were analyzed to determine the differences between groups. Results: The analysis of the data showed differences in the pattern of the ensemble mean curves of the HIGH and LOW groups, although the majority of the differences occurred during the eccentric contraction phase of the jump. The differences in the HIGH group with respect to the LOW group were: lower force at the beginning of the movement, higher speed and RFD during the eccentric phase, high force at the beginning of the concentric phase, higher velocity during the concentric phase, and a higher position at takeoff. Conclusion: The results showed that the HIGH group achieved a higher jump height than did the LOW group by increasing the effectiveness of the countermovement and achieving a more advantageous position at takeoff.Centro de Investigación en Rendimiento Físico y Deportiv

Assessment of Skeletal Muscle Contractile Properties by Radial Displacement: The Case for Tensiomyography

Skeletal muscle operates as a near-constant volume system; as such muscle shortening during contraction is transversely linked to radial deformation. Therefore, to assess contractile properties of skeletal muscle, radial displacement can be evoked and measured. Mechanomyography measures muscle radial displacement and during the last 20 years, tensiomyography has become the most commonly used and widely reported technique among the various methodologies of mechanomyography. Tensiomyography has been demonstrated to reliably measure peak radial displacement during evoked muscle twitch, as well as muscle twitch speed. A number of parameters can be extracted from the tensiomyography displacement/time curve and the most commonly used and reliable appear to be peak radial displacement and contraction time. The latter has been described as a valid non-invasive means of characterising skeletal muscle, based on fibre-type composition. Over recent years, applications of tensiomyography measurement within sport and exercise have appeared, with applications relating to injury, recovery and performance. Within the present review, we evaluate the perceived strengths and weaknesses of tensiomyography with regard to its efficacy within applied sports medicine settings. We also highlight future tensiomyography areas that require further investigation. Therefore, the purpose of this review is to critically examine the existing evidence surrounding tensiomyography as a tool within the field of sports medicine

Cardiomyocyte BRAF and type 1 RAF inhibitors promote cardiomyocyte and cardiac hypertrophy in mice in vivo

The extracellular signal-regulated kinase 1/2 (ERK1/2) cascade promotes cardiomyocyte hypertrophy and is cardioprotective, with the three RAF kinases forming a node for signal integration. Our aims were to determine if BRAF is relevant for human heart failure, whether BRAF promotes cardiomyocyte hypertrophy, and if Type 1 RAF inhibitors developed for cancer (that paradoxically activate ERK1/2 at low concentrations: the “RAF paradox”) may have the same effect. BRAF was upregulated in heart samples from patients with heart failure compared with normal controls. We assessed the effects of activated BRAF in the heart using mice with tamoxifen-activated Cre for cardiomyocyte-specific knock-in of the activating V600E mutation into the endogenous gene. We used echocardiography to measure cardiac dimensions/function. Cardiomyocyte BRAFV600E induced cardiac hypertrophy within 10 d, resulting in increased ejection fraction and fractional shortening over 6 weeks. This was associated with increased cardiomyocyte size without significant fibrosis, consistent with compensated hypertrophy. The experimental Type 1 RAF inhibitor, SB590885, and/or encorafenib (a RAF inhibitor used clinically) increased ERK1/2 phosphorylation in cardiomyocytes, and promoted hypertrophy, consistent with a “RAF paradox” effect. Both promoted cardiac hypertrophy in mouse hearts in vivo, with increased cardiomyocyte size and no overt fibrosis. In conclusion, BRAF potentially plays an important role in human failing hearts, activation of BRAF is sufficient to induce hypertrophy, and Type 1 RAF inhibitors promote hypertrophy via the “RAF paradox”. Cardiac hypertrophy resulting from these interventions was not associated with pathological features, suggesting that Type 1 RAF inhibitors may be useful to boost cardiomyocyte function