Uncommon cause of obstruction in the left ventricular outflow tract by a metastasis of adenocarcinoma

Cardiac metastases are rare diagnoses among cardiac disorders. This case demonstrates a unique presence of an obstruction in the left ventricular outflow tract caused by the metastasis of a renal carcinoma. Adequate diagnostic and therapeutic procedures were lifesaving in this potentially fatal diagnosis

Fluvastatin in the first-line therapy of acute coronary syndrome: results of the multicenter, randomized, double-blind, placebo-controlled trial (the FACS-trial)

<p>Abstract</p> <p>Background</p> <p>Statins have been proved to be effective in reduction of mortality and morbidity when started in the early secondary prevention in stabilized patients after acute coronary syndrome (ACS). The safety and efficacy of statin administration directly in the first-line therapy in unstable ACS patients is not clear. The aim of our study was, therefore, to assess the effect of statin treatment initiated immediately at hospital admission of patients with ACS.</p> <p>Methods</p> <p>The trial was stopped prematurely after enrollment of one hundred and fifty-six patients with ACS that were randomized at admission to fluvastatin 80 mg (N = 78) or placebo (N = 78). Study medication was administered immediately after randomization and then once daily for 30 days; all patients were then encouraged to continue in open-label statin therapy and at the end of one-year follow-up 75% in the fluvastatin group and 78% in the placebo group were on statin therapy.</p> <p>Results</p> <p>We did not demonstrate any difference between groups in the level of C-reactive protein, interleukin 6, and pregnancy-associated plasma protein A on Day 2 and Day 30 (primary endpoint). Fluvastatin-therapy, however, significantly reduced one-year occurrence of major adverse cardiovascular events (11.5% vs. 24.4%, odds ratio (OR) 0.40, 95% CI 0.17-0.95, P = 0.038). This difference was caused mainly by reduction of recurrent symptomatic ischemia (7.7% vs. 20.5%, OR 0.32, 95% CI 0.12-0.88, P = 0.037).</p> <p>Conclusions</p> <p>This study failed to prove the effect of fluvastatin given as first-line therapy of ACS on serum markers of inflammation and plaque instability. Fluvastatin therapy was, however, safe and it may reduce cardiovascular event rate that supports immediate use of a statin in patients admitted for ACS.</p> <p>Trial registration</p> <p>NCT00171275</p

Clinical Study Comparison of Long-Term Effect of Dual-Chamber Pacing and Alcohol Septal Ablation in Patients with Hypertrophic Obstructive Cardiomyopathy

Introduction. Nonpharmacological treatment of patients with hypertrophic obstructive cardiomyopathy (HOCM) comprises surgical myectomy (SME), alcohol septal ablation (ASA), and dual-chamber (DDD) pacing. The aim of the study was to compare the long-term effect of DDD pacing and ASA in symptomatic HOCM patients. Patients and Methods. We evaluated retrospective data from three cardiocenters; there were 24 patients treated with DDD pacing included and 52 treated with ASA followed for 101 ± 49 and 87 ± 23 months, respectively. Results. In the group treated with DDD pacing, the left ventricle outflow tract gradient (LVOTG) decreased from 82 ± 44 mmHg to 21 ± 21 mmHg, and NYHA class improved from 2.7 ± 0.5 to 2.1 ± 0.6 (both &lt; 0.001). In the ASA-treated group, a decline in LVOTG from 73 ± 38 mmHg to 24 ± 26 mmHg and reduction in NYHA class from 2.8 ± 0.5 to 1.7 ± 0.8 were observed (both &lt; 0.001). The LVOTG change was similar in both groups ( = 0.264), and symptoms were more affected by ASA ( = 0.001). Conclusion. ASA and DDD pacing were similarly effective in reducing LVOTG. The symptoms improvement was more expressed in patients treated with ASA

Roadmap for Optical Tweezers 2023

Optical tweezers are tools made of light that enable contactless pushing, trapping, and manipulation of objects ranging from atoms to space light sails. Since the pioneering work by Arthur Ashkin in the 1970s, optical tweezers have evolved into sophisticated instruments and have been employed in a broad range of applications in life sciences, physics, and engineering. These include accurate force and torque measurement at the femtonewton level, microrheology of complex fluids, single micro- and nanoparticle spectroscopy, single-cell analysis, and statistical-physics experiments. This roadmap provides insights into current investigations involving optical forces and optical tweezers from their theoretical foundations to designs and setups. It also offers perspectives for applications to a wide range of research fields, from biophysics to space exploration

Current Account Imbalances and Structural Adjustment in the Euro Area: How to Rebalance Competitiveness

Low international competitiveness of a set of euro area countries, which have become evident by large current account deficits and rising risk premiums on government bonds, is one of the most challenging economic policy issues for Europe. We analyse the role of private restructuring and public structural reforms for the urgently needed readjustment of intra-euro area imbalances. A panel regression reveals a significant impact of private restructuring and public structural reforms on intra-euro area competitiveness. This implies that private restructuring and public reforms are rather than public transfers the best way to preserve long-term economic stability in Europe

The Alpine Fault Hangingwall Viewed From Within: Structural Analysis of Ultrasonic Image Logs in the DFDP-2B Borehole, New Zealand

International audienceUltrasonic image logs acquired in the DFDP‐2B borehole yield the first continuous, subsurface description of the transition from schist to mylonite in the hangingwall of the Alpine Fault, New Zealand, to a depth of 818 m below surface. Three feature sets are delineated. One set, comprising foliation and foliation‐parallel veins and fractures, has a constant orientation. The average dip direction of 145° is subparallel to the dip direction of the Alpine Fault, and the average dip magnitude of 60° is similar to nearby outcrop observations of foliation in the Alpine mylonites that occur immediately above the Alpine Fault. We suggest that this foliation orientation is similar to the Alpine Fault plane at ∼1 km depth in the Whataroa valley. The other two auxiliary feature sets are interpreted as joints based on their morphology and orientation. Subvertical joints with NW‐SE (137°) strike occurring dominantly above ∼500 m are interpreted as being formed during the exhumation and unloading of the Alpine Fault's hangingwall. Gently dipping joints, predominantly observed below ∼500 m, are interpreted as inherited hydrofractures exhumed from their depth of formation. These three fracture sets, combined with subsidiary brecciated fault zones, define the fluid pathways and anisotropic permeability directions. In addition, high topographic relief, which perturbs the stress tensor, likely enhances the slip potential and thus permeability of subvertical fractures below the ridges, and of gently dipping fractures below the valleys. Thus, DFDP‐2B borehole observations support the inference of a large zone of enhanced permeability in the hangingwall of the Alpine Fault

Aficamten and cardiopulmonary exercise test performance: a substudy of the SEQUOIA-HCM randomized clinical trial

Importance: Impaired exercise capacity is a cardinal manifestation of obstructive hypertrophic cardiomyopathy (HCM). The Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic Obstructive HCM (SEQUOIA-HCM) is a pivotal study characterizing the treatment effect of aficamten, a next-in-class cardiac myosin inhibitor, on a comprehensive set of exercise performance and clinical measures. Objective: To evaluate the effect of aficamten on exercise performance using cardiopulmonary exercise testing with a novel integrated measure of maximal and submaximal exercise performance and evaluate other exercise measures and clinical correlates. Design, Setting, and Participants: This was a prespecified analysis from SEQUOIA-HCM, a double-blind, placebo-controlled, randomized clinical trial. Patients were recruited from 101 sites in 14 countries (North America, Europe, Israel, and China). Individuals with symptomatic obstructive HCM with objective exertional intolerance (peak oxygen uptake [pVO₂] ≤90% predicted) were included in the analysis. Data were analyzed from January to March 2024. Interventions: Randomized 1:1 to aficamten (5-20 mg daily) or matching placebo for 24 weeks. Main Outcomes and Measures: The primary outcome was change from baseline to week 24 in integrated exercise performance, defined as the 2-component z score of pVO₂ and ventilatory efficiency throughout exercise (minute ventilation [VE]/carbon dioxide output [VCO₂] slope). Response rates for achieving clinically meaningful thresholds for change in pVO2 and correlations with clinical measures of treatment effect (health status, echocardiographic/cardiac biomarkers) were also assessed. Results: Among 282 randomized patients (mean [SD] age, 59.1 [12.9] years; 115 female [40.8%], 167 male [59.2%]), 263 (93.3%) had core laboratory–validated exercise testing at baseline and week 24. Integrated composite exercise performance improved in the aficamten group (mean [SD] z score, 0.17 [0.51]) from baseline to week 24, whereas the placebo group deteriorated (mean [SD] z score, −0.19 [0.45]), yielding a placebo-corrected improvement of 0.35 (95% CI, 0.25-0.46; P &lt;.001). Further, aficamten treatment demonstrated significant improvements in total workload, circulatory power, exercise duration, heart rate reserve, peak heart rate, ventilatory efficiency, ventilatory power, and anaerobic threshold (all P &lt;.001). In the aficamten group, large improvements (≥3.0 mL/kg per minute) in pVO₂ were more common than large reductions (32% and 2%, respectively) compared with placebo (16% and 11%, respectively). Improvements in both components of the primary outcome, pVO₂ and VE/VCO₂ slope throughout exercise, were significantly correlated with improvements in symptom burden and hemodynamics (all P &lt;.05). Conclusions and Relevance: This prespecified analysis of the SEQUOIA-HCM randomized clinical trial found that aficamten treatment improved a broad range of exercise performance measures. These findings offer valuable insight into the therapeutic effects of aficamten. Trial Registration: ClinicalTrials.gov Identifier: NCT0518681

Dosing and safety profile of aficamten in symptomatic obstructive hypertrophic cardiomyopathy: results from from SEQUOIA‐HCM

Background: Aficamten, a novel cardiac myosin inhibitor, reversibly reduces cardiac hypercontractility in obstructive hypertrophic cardiomyopathy. We present a prespecified analysis of the pharmacokinetics, pharmacodynamics, and safety of aficamten in SEQUOIA‐HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM). Methods and Results: A total of 282 patients with obstructive hypertrophic cardiomyopathy were randomized 1:1 to daily aficamten (5–20 mg) or placebo between February 1, 2022, and May 15, 2023. Aficamten dosing targeted the lowest effective dose for achieving site‐interpreted Valsalva left ventricular outflow tract gradient &lt;30 mm Hg with left ventricular ejection fraction (LVEF) ≥50%. End points were evaluated during titration (day 1 to week 8), maintenance (weeks 8–24), and washout (weeks 24–28), and included major adverse cardiac events, new‐onset atrial fibrillation, implantable cardioverter‐defibrillator discharges, LVEF &lt;50%, and treatment‐emergent adverse events. At week 8, 3.6%, 12.9%, 35%, and 48.6% of patients achieved 5‐, 10‐, 15‐, and 20‐mg doses, respectively. Baseline characteristics were similar across groups. Aficamten concentration increased by dose and remained stable during maintenance. During the treatment period, LVEF decreased by −0.9% (95% CI, −1.3 to −0.6) per 100 ng/mL aficamten exposure. Seven (4.9%) patients taking aficamten underwent per‐protocol dose reduction for site‐interpreted LVEF &lt;50%. There were no treatment interruptions or heart failure worsening for LVEF &lt;50%. No major adverse cardiovascular events were associated with aficamten, and treatment‐emergent adverse events were similar between treatment groups, including atrial fibrillation. Conclusions: A site‐based dosing algorithm targeting the lowest effective aficamten dose reduced left ventricular outflow tract gradient with a favorable safety profile throughout SEQUOIA‐HCM

fNIRS reproducibility varies with data quality, analysis pipelines, and researcher experience

As data analysis pipelines grow more complex in brain imaging research, understanding how methodological choices affect results is essential for ensuring reproducibility and transparency. This is especially relevant for functional Near-Infrared Spectroscopy (fNIRS), a rapidly growing technique for assessing brain function in naturalistic settings and across the lifespan, yet one that still lacks standardized analysis approaches. In the fNIRS Reproducibility Study Hub (FRESH) initiative, we asked 38 research teams worldwide to independently analyze the same two fNIRS datasets. Despite using different pipelines, nearly 80% of teams agreed on group-level results, particularly when hypotheses were strongly supported by literature. Teams with higher self-reported analysis confidence, which correlated with years of fNIRS experience, showed greater agreement. At the individual level, agreement was lower but improved with better data quality. The main sources of variability were related to how poor-quality data were handled, how responses were modeled, and how statistical analyses were conducted. These findings suggest that while flexible analytical tools are valuable, clearer methodological and reporting standards could greatly enhance reproducibility. By identifying key drivers of variability, this study highlights current challenges and offers direction for improving transparency and reliability in fNIRS research