Combined transcatheter treatment of severe mitral regurgitation and secundum atrial septal defect in an inoperable patient: a case report

Background: Chronic mitral regurgitation (MR) is one of the most common valvular heart diseases and is associated with poor outcomes. Although other structural diseases are regularly seen in such patients, concomitant atrial septal defects (ASDs) remain a rarity in the elderly. Case summary: We report a case of an 82-year-old woman with progressive right-sided heart failure (HF) due to MR and an ASD of secundum type, despite optimal medical therapy. Combined transcatheter mitral valve repair (MVR) by utilizing a separate transseptal puncture and ASD closure was performed resulting in amelioration of symptoms. Discussion: Procedural planning for simultaneous transcatheter therapies of coupled structural heart disease entities remains complex. Our case illustrates feasibility of percutaneous edge-to-edge MVR and consecutive closure of a large secundum ASD. Different options of accessing the left atrium should be discussed on an individual basis, while additional ASD closure may be beneficial in terms of right ventricular function and symptoms of right HF

Transcatheter Caval Valve Implantation for Tricuspid Regurgitation After Single Leaflet Device Attachment

An 86-year-old patient experienced progressive heart failure symptoms. Echocardiographic evaluation revealed severe tricuspid regurgitation, which was treated by transcatheter edge-to-edge repair. During the procedure, single leaflet device attachment occurred. On the basis of a prohibitive surgical risk, caval valve implantation was performed, with no notable complications. (Level of Difficulty: Advanced.

Increased Left Ventricular Stiffness Impairs Exercise Capacity in Patients with Heart Failure Symptoms Despite Normal Left Ventricular Ejection Fraction

Aims. Several mechanisms can be involved in the development of exercise intolerance in patients with heart failure despite normal left ventricular ejection fraction (HFNEF) and may include impairment of left ventricular (LV) stiffness. We therefore investigated the influence of LV stiffness, determined by pressure-volume loop analysis obtained by conductance catheterization, on exercise capacity in HFNEF. Methods and Results. 27 HFNEF patients who showed LV diastolic dysfunction in pressure-volume (PV) loop analysis performed symptom-limited cardiopulmonary exercise testing (CPET) and were compared with 12 patients who did not show diastolic dysfunction in PV loop analysis. HFNEF patients revealed a lower peak performance (P = .046), breathing reserve (P = .006), and ventilation equivalent for carbon dioxide production at rest (P = .002). LV stiffness correlated with peak oxygen uptake (r = −0.636, P < .001), peak oxygen uptake at ventilatory threshold (r = −0.500, P = .009), and ventilation equivalent for carbon dioxide production at ventilatory threshold (r = 0.529, P = .005). Conclusions. CPET parameters such as peak oxygen uptake, peak oxygen uptake at ventilatory threshold, and ventilation equivalent for carbon dioxide production at ventilatory threshold correlate with LV stiffness. Increased LV stiffness impairs exercise capacity in HFNEF

Targeting LOXL2 for cardiac interstitial fibrosis and heart failure treatment

Interstitial fibrosis plays a key role in the development and progression of heart failure. Here, we show that an enzyme that crosslinks collagen—Lysyl oxidase-like 2 (Loxl2)—is essential for interstitial fibrosis and mechanical dysfunction of pathologically stressed hearts. In mice, cardiac stress activates fibroblasts to express and secrete Loxl2 into the interstitium, triggering fibrosis, systolic and diastolic dysfunction of stressed hearts. Antibody-mediated inhibition or genetic disruption of Loxl2 greatly reduces stress-induced cardiac fibrosis and chamber dilatation, improving systolic and diastolic functions. Loxl2 stimulates cardiac fibroblasts through PI3K/AKT to produce TGF-β2, promoting fibroblast-to-myofibroblast transformation; Loxl2 also acts downstream of TGF-β2 to stimulate myofibroblast migration. In diseased human hearts, LOXL2 is upregulated in cardiac interstitium; its levels correlate with collagen crosslinking and cardiac dysfunction. LOXL2 is also elevated in the serum of heart failure (HF) patients, correlating with other HF biomarkers, suggesting a conserved LOXL2-mediated mechanism of human HF

Rate-control algorithms for non-embedded wavelet-based image coding

During the last decade, there has been an increasing interest in the design of very fast wavelet image encoders focused on specific applications like interactive real-time image and video systems, running on power-constrained devices such as digital cameras, mobile phones where coding delay and/or available computing resources (working memory and power processing) are critical for proper operation. In order to reduce complexity, most of these fast wavelet image encoders are non-(SNR)-embedded and as a consequence, precise rate control is not supported. In this work, we propose some simple rate control algorithms for these kind of encoders and we analyze their impact to determine if, despite their inclusion, the global encoder is still competitive with respect to popular embedded encoders like SPIHT and JPEG2000. In this study we focus on the non-embedded LTW encoder, showing that the increase in complexity due to the rate control algorithm inclusion, maintains LTW competitive with respect to SPIHT and JPEG2000 in terms of R/D performance, coding delay and memory consumption. © Springer Science+Business Media, LLC 2011This work was funded by Spanish Ministry of education and Science under grant DPI2007-66796-C03-03.Lopez Granado, OM.; Onofre Martinez-Rach, M.; Pinol Peral, P.; Oliver Gil, JS.; Perez Malumbres, MJ. (2012). Rate-control algorithms for non-embedded wavelet-based image coding. Journal of Signal Processing Systems. 68(2):203-216. https://doi.org/10.1007/s11265-011-0598-6S203216682Antonini, M., Barlaud, M., Mathieu, P., & Daubechies, I. (1992). Image coding using wavelet transform. IEEE Transaction on Image Processing, 1(2), 205–220.Cho, Y., & Pearlman, W.A. (2007). Hierarchical dynamic range coding of wavelet subbands for fast and efficient image compression. IEEE Transactions on Image Processing, 16, 2005–2015.Chrysafis, C., Said, A., Drukarev, A., Islam, A., & Pearlman, W. (2000). SBHP—A low complexity wavelet coder. In IEEE international conference on acoustics, speech and signal processing.CIPR: http://www.cipr.rpi.edu/resource/stills/kodak.html . Center for Image Processing Research.Davis, P. J. (1975) Interpolation and approximation. Dover Publications.Grottke, S., Richter, T., & Seiler, R. (2006). Apriori rate allocation in wavelet-based image compression. In Second international conference on automated production of cross media content for multi-channel distribution, 2006. AXMEDIS ’06 (pp. 329–336). doi: 10.1109/AXMEDIS.2006.12 .Guo, J., Mitra, S., Nutter, B., & Karp, T. (2006). Backward coding of wavelet trees with fine-grained bitrate control. Journal of Computers, 1(4), 1–7. doi: 10.4304/jcp.1.4.1-7 .ISO/IEC 10918-1/ITU-T Recommendation T.81 (1992). Digital compression and coding of continuous-tone still image.ISO/IEC 15444-1 (2000). JPEG2000 image coding system.Kakadu, S. (2006). http://www.kakadusoftware.com .Kasner, J., Marcellin, M., & Hunt, B. (1999). Universal trellis coded quantization. IEEE Transactions on Image Processing, 8(12), 1677–1687. doi: 10.1109/83.806615 .Lancaster, P. (1986). Curve and surface fitting: An introduction. Academic Press.Oliver, J., & Malumbres, M. (2001). A new fast lower-tree wavelet image encoder. In Proceedings of international conference on image processing, 2001 (Vol. 3, pp. 780–783). doi: 10.1109/ICIP.2001.958236 .Oliver, J., & Malumbres, M. P. (2006). Low-complexity multiresolution image compression using wavelet lower trees. IEEE Transactions on Circuits and Systems for Video Technology, 16(11), 1437–1444.Pearlman, W. A. (2001). Trends of tree-based, set partitioning compression techniques in still and moving image systems. In Picture coding symposium.Said, A., & Pearlman, A. (1996). A new, fast and efficient image codec based on set partitioning in hierarchical trees. IEEE Transactions on Circuits, Systems and Video Technology, 6(3), 243–250.Table Curve 3D 3.0 (1998). http://www.systat.com. Systat Software Inc.Wu, X. (2001). The transform and data compression handbook, chap. Compression of wavelet transform coefficients, (pp. 347–378). CRC Press.Zhidkov, N., & Kobelkov, G. (1987). Numerical methods. Moscow: Nauka

Targeting LOXL2 for cardiac interstitial fibrosis and heart failure treatment

Interstitial fibrosis plays a key role in the development and progression of heart failure. Here, we show that an enzyme that crosslinks collagen-Lysyl oxidase-like 2 (Loxl2)-is essential for interstitial fibrosis and mechanical dysfunction of pathologically stressed hearts. In mice, cardiac stress activates fibroblasts to express and secrete Loxl2 into the interstitium, triggering fibrosis, systolic and diastolic dysfunction of stressed hearts. Antibody-mediated inhibition or genetic disruption of Loxl2 greatly reduces stress-induced cardiac fibrosis and chamber dilatation, improving systolic and diastolic functions. Loxl2 stimulates cardiac fibroblasts through PI3K/AKT to produce TGF-β2, promoting fibroblast-to-myofibroblast transformation; Loxl2 also acts downstream of TGF-β2 to stimulate myofibroblast migration. In diseased human hearts, LOXL2 is upregulated in cardiac interstitium; its levels correlate with collagen crosslinking and cardiac dysfunction. LOXL2 is also elevated in the serum of heart failure (HF) patients, correlating with other HF biomarkers, suggesting a conserved LOXL2-mediated mechanism of human HF

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Neue echokardiographische Modalitäten zur Evaluation der Pathophysiologie und Diagnostik bei Herzinsuffizienz mit normaler Ejektionsfraktion

This thesis is focused on studies investigating the role of novel echocardiographic modalities for the evaluation of LV diastolic function in heart failure with a normal ejection fraction. New non-invasive techniques have been validated against the invasive gold standard catheterization method in order to provide the diagnostic and prognostic accuracy of HFNEF. Despite of high prevalence and mortality in HFNEF, the exact pathomechanisms are still uncertain and diagnostic procedures unreliable. Conventional echocardiography, a widespread non-invasive method of choice yielded low sensitivity and specificity in direct comparison with pressure-volume relationship analysis. Novel tissue Doppler diastolic velocity parameters provided strong correlation with LV relaxation and stiffness, crucial haemodynamic determinants of diastolic dysfunction. They showed significantly higher diagnostic accuracy in early and mild forms of LV dysfunction. In particular, the LV filling index E/E’ correlated with passive cardiac properties like the LV stiffness coefficient. An additional study demonstrated that tissue Doppler velocities including E/E’ index were associated with myocardial collagen amounts and the level of cardiac fibrosis obtained from endomyocardial biopsies, which have impact on LV stiffness. Besides tissue Doppler imaging, further echocardiographic modality, and deformation imaging also reflected intrinsic myocardial changes which showed a significant correlation of diastolic strain rate with relaxation index and LV stiffness. By this, deformation parameters were not found to be superior to the tissue Doppler imaging in diagnostic HFPEF. However, in the settings of clinical routine where extended echocardiographic analysis is not available, a simple diagnostic tool with an additional determination of NT-proBNP level to the conventional echocardiography improved the diagnostic accuracy up to the level of tissue Doppler imaging and showed a prognostic value by predicting a re- hospitalisation rate involving HFNEF. New techniques extended the understanding of pathophysiology in HFNEF as evidenced by their relation to cardiac fibrosis, and by their clarifying diastolic ventricular interactions in primary pulmonary arterial hypertension. The bottom line of these evaluated studies is that novel echocardiographic methods optimize diagnostic accuracy in HFNEF based on an improved characterization of intrinsic myocardial properties.Im Mittelpunkt dieser kumulativen Habilitationsschrift stehen Arbeiten, die die Rolle der neuen echokardiographischen Modalitäten für die Beurteilung der LV diastolischen Funktion bei Herzinsuffizienz mit normaler Ejektionsfraktion untersuchen. Die neuen nicht-invasiven Techniken wie gewebedoppler, myokardiale Deformationsimaging inklusiv strain rate und speckle tracking analyse, sowie auch neue Biomarker für Herzinsuffizienz wurden gegen invasive Goldstandard Katheterverfahren mit linksventrikulärer Druck-Volumen Analyse validiert, um die diagnostische und prognostische Genauigkeit der Methoden bei HFNEF zu überprüfen. Es wurden nicht nur neue nicht-invasive diagnostische tools evaluiert sondern auch neue pathophysiologische mechanismen wie der Enfluss von kardialen Fibrose und primärer pulmonaler Hypertonie auf die LV diastoliche Funktion und Symptomatik bei HFNEF postuliert und analysiert. Die Quintessenz der vorgelegten Arbeiten ist es, dass neue echokardiographische Methoden eine diagnostische Zuverläßigkeit bei HFNEF Patienten optimieren, basierend auf verbesserter Charakterisierung der intrinsischen myokardialen Eigenschaften

Percutaneous Edge-to-Edge Tricuspid Valve Repair in a Patient with Cor Triatriatum Dexter: A Case Report

Background: Tricuspid regurgitation is gaining importance due to its high morbidity and mortality. Especially in the elderly, novel technologies in percutaneous therapies have become valuable options due to the commonly present high surgical risk. Case presentation: We report a case of a 78-year-old female suffering from massive tricuspid regurgitation with repetitive right-sided heart failure hospitalizations. As the patient was very frail and deemed as high surgical risk, we used the TriClip® system to improve her symptomatic status. During diagnostic work-up, an additional membrane separating the right atrium, consistent with the definition of a cor triatriatum dexter, was found. Although increasing the complexity of the procedure, implantation of 3 clips with reduction of tricuspid regurgitation to a mild-to-moderate degree was achieved without any notable complications. The patient was discharged with ameliorated symptoms on the fourth postoperative day. Conclusions: Our case highlights the feasibility of percutaneous edge-to-edge tricuspid valve repair in an elderly woman with cor triatriatum dexter. Accurate echocardiographic visualization is an absolute requirement to gain access to the tricuspid valve without interacting with prevailing additional membranes