THREE DIMENSIONAL PACKAGING OF BARE IC INTO PRINTED CIRCUIT BOARDS FOR SIP

ABSTRACT The demand to miniaturize products especially for mobile applications and autonomous systems is continuing to drive the evolution of electronic products and manufacturing methods. To further the miniaturization of future products the integration of functions on miniaturized subsystems, i.e. System-inPackage (SiP) is a promising approach. Here, use of recent manufacturing methods allows to merge the SiP concept with a volumetric integration of IC´s. Up to now, most of the systems make use of single-or double-sided populated system carriers. A new challenge is to incorporate not only passive components, but as well active circuitry (IC´s) and the necessary thermal management. Ultra thin chips (i.e. silicon dies thinned down to <50µm total thickness) lend themselves to reach these goals. Chips with that thickness can be embedded in the dielectric layers of modern laminate PCB´s. Micro via technology allows to contact the embedded chip to the outer faces of the system circuitry. The aspects of embedding and making the electrical contact as well as the thermal management are highlighted. Results on FEM simulations and technical achievements are presented

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 <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 <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 <50%. There were no treatment interruptions or heart failure worsening for LVEF <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

2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery

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