Two case reports of fulminant giant cell myocarditis treated with rabbit anti-thymocyte globulin.

Background: Giant cell myocarditis (GCM) is an inflammatory form of acute heart failure with high rates of cardiac transplantation or death. Standard acute treatment includes multi-drug immunosuppressive regimens. There is a small but growing number of case reports utilizing rabbit anti-thymocyte globulin in severe cases. Case summary: Two cases are presented with similar presentations and clinical courses. Both are middle-aged patients with no significant past medical history, who presented with new acute decompensated heart failure that quickly progressed to cardiogenic shock requiring inotropic and mechanical circulatory support. Both underwent endomyocardial biopsies that diagnosed GCM. Both were treated with a multi-agent immunosuppressive regimen, notably including rabbit anti-thymocyte globulin, with subsequent resolution of shock and recovery of left ventricular ejection fraction. Both remain transplant-free and without ventricular arrhythmias at 7 months and 26 months, respectively. Discussion: In aggregate, these cases are typical of GCM. They add to growing observational data that upfront rabbit anti-thymocyte globulin may reduce morbidity and mortality in GCM, including potentially preventing the need for complex interventions like orthotopic heart transplantation.

Mitral Regurgitation Complicated by Cardiogenic Shock: Reassessing Risk Stratification and Therapeutic Strategies.

Mitral regurgitation complicated by cardiogenic shock creates a unique and devastating risk profile for patients and poses significant difficulties for physicians who lack a comprehensive range of effective management strategies. Supportive measures such as intravenous vasodilators, intra-aortic balloon pumps, and percutaneous ventricular assist devices are often necessary to stabilize patients prior to definitive treatment with surgical mitral valve replacement or trans-catheter edge-to-edge repair. This review evaluates the evidence for the available supportive and definitive management strategies in patients with mitral regurgitation complicated by cardiogenic shock and presents a framework to aid clinicians in navigating the complex clinical decision-making process. Additionally, the authors review emerging transcatheter mitral valve replacement technologies that hold promise for expanding the therapeutic armamentarium and improving patient outcomes.

Functional Mitral Regurgitation: Patient Selection and Optimization.

Functional mitral regurgitation appears commonly among all heart failure phenotypes and can affect symptom burden and degree of maladaptive remodeling. Transcatheter mitral valve edge-to-edge repair therapies recently became an important part of the routine heart failure armamentarium for carefully selected and medically optimized candidates. Patient selection is considering heart failure staging, relevant comorbidities, as well as anatomic criteria. Indications and device platforms are currently expanding.

Location Matters-Can a Smart Golf Club Detect Where the Club Face Hits the Ball?

In golf, the location of the impact, where the clubhead hits the ball, is of imperative nature for a successful ballflight. Direct feedback to the athlete where he/she hits the ball could improve a practice session. Currently, this information can be measured via, e.g., dual laser technology; however, this is a stationary and external method. A mobile measurement method would give athletes the freedom to gain the information of the impact location without the limitation to be stationary. Therefore, the aim of this study was to investigate whether it is possible to detect the impact location via a motion sensor mounted on the shaft of the golf club. To answer the question, an experiment was carried out. Within the experiment data were gathered from one athlete performing 282 golf swings with an 7 iron. The impact location was recorded and labeled during each swing with a Trackman providing the classes for a neural network. Simultaneously, the motion of the golf club was gathered with an IMU from the Noraxon Ultium Motion Series. In the next step, a neural network was designed and trained to estimate the impact location class based on the motion data. Based on the motion data, a classification accuracy of 93.8% could be achieved with a ResNet architecture.

Cardiac allograft vasculopathy diagnosed by vasodilator myocardial contrast echocardiography perfusion imaging.

Cardiac allograft vasculopathy (CAV) remains a common long-term complication of cardiac transplantation. While invasive coronary angiography is considered the gold standard, it is also invasive and lacks sensitivity to detect early, distal CAV. Although vasodilator stress myocardial contrast echocardiography perfusion imaging (MCE) is used in the detection of microvascular disease in non-transplant patients, there is little data guiding its use in transplant recipients. Herein is a case series of four heart transplant recipients that had vasodilator stress MCE performed in addition to invasive coronary angiography for CAV surveillance. MCE at rest and after regadenason was performed using a continuous infusion of lipid-shelled microbubbles. We describe a case of normal microvascular function, diffuse microvascular dysfunction, patchy sub-endocardial perfusion defects and a focal sub-endocardial perfusion defect. Cardiac allograft vasculopathy can be heralded by several different perfusion patterns on MCE in patients after orthotopic heart transplant. The varying prognoses and potential interventions for these different patterns require further investigation.

Dislocation arrangements in 4H-SiC and their influence on the local crystal lattice properties.

Two wafers of one 4H-silicon carbide (4H-SiC) bulk crystal, one cut from a longitudinal position close to the crystal's seed and the other close to the cap, were characterized with synchrotron white-beam X-ray topography (SWXRT) in back-reflection and transmission geometry to investigate the dislocation formation and propagation during growth. For the first time, full wafer mappings were recorded in 00012 back-reflection geometry with a CCD camera system, providing an overview of the dislocation arrangement in terms of dislocation type, density and homogeneous distribution. Furthermore, by having similar resolution to conventional SWXRT photographic film, the method enables identification of individual dislocations, even single threading screw dislocations, which appear as white spots with a diameter in the range of 10 to 30 µm. Both investigated wafers showed a similar dislocation arrangement, suggesting a constant propagation of dislocations during crystal growth. A systematic investigation of crystal lattice strain and tilt at selected wafer areas with different dislocation arrangements was achieved with high-resolution X-ray diffractometry reciprocal-space map (RSM) measurements in the symmetric 0004 reflection. It was shown that the diffracted intensity distribution of the RSM for different dislocation arrangements depends on the locally predominant dislocation type and density. Moreover, the orientation of specific dislocation types along the RSM scanning direction has a strong influence on the local crystal lattice properties.

Acoustic Voice and Speech Biomarkers of Treatment Status during Hospitalization for Acute Decompensated Heart Failure.

This study investigates acoustic voice and speech features as biomarkers for acute decompensated heart failure (ADHF), a serious escalation of heart failure symptoms including breathlessness and fatigue. ADHF-related systemic fluid accumulation in the lungs and laryngeal tissues is hypothesized to affect phonation and respiration for speech. A set of daily spoken recordings from 52 patients undergoing inpatient ADHF treatment was analyzed to identify voice and speech biomarkers for ADHF and to examine the trajectory of biomarkers during treatment. Results indicated that speakers produce more stable phonation, a more creaky voice, faster speech rates, and longer phrases after ADHF treatment compared to their pre-treatment voices. This project builds on work to develop a method of monitoring ADHF using speech biomarkers and presents a more detailed understanding of relevant voice and speech features.

Novel Photonic Applications of Silicon Carbide.

Silicon carbide (SiC) is emerging rapidly in novel photonic applications thanks to its unique photonic properties facilitated by the advances of nanotechnologies such as nanofabrication and nanofilm transfer. This review paper will start with the introduction of exceptional optical properties of silicon carbide. Then, a key structure, i.e., silicon carbide on insulator stack (SiCOI), is discussed which lays solid fundament for tight light confinement and strong light-SiC interaction in high quality factor and low volume optical cavities. As examples, microring resonator, microdisk and photonic crystal cavities are summarized in terms of quality (Q) factor, volume and polytypes. A main challenge for SiC photonic application is complementary metal-oxide-semiconductor (CMOS) compatibility and low-loss material growth. The state-of-the-art SiC with different polytypes and growth methods are reviewed and a roadmap for the loss reduction is predicted for photonic applications. Combining the fact that SiC possesses many different color centers with the SiCOI platform, SiC is also deemed to be a very competitive platform for future quantum photonic integrated circuit applications. Its perspectives and potential impacts are included at the end of this review paper.

Impact of Mechanical Stress and Nitrogen Doping on the Defect Distribution in the Initial Stage of the 4H-SiC PVT Growth Process.

Nitrogen incorporation changes the lattice spacing of SiC and can therefore lead to stress during physical vapor transport (PVT). The impact of the nitrogen-doping concentration during the initial phase of PVT growth of 4H-SiC was investigated using molten potassium hydroxide (KOH) etching, and the doping concentration and stress was detected by Raman spectroscopy. The change in the coefficient of thermal expansion (CTE) caused by the variation of nitrogen doping was implemented into a numerical model to quantitatively determine the stress induced during and after the crystal growth. Furthermore, the influence of mechanical stress related to the seed-mounting method was studied. To achieve this, four 100 mm diameter 4H-SiC crystals were grown with different nitrogen-doping distributions and seed-mounting strategies. It was found that the altered CTE plays a major role in the types and density of defect present in the grown crystal. While the mounting method led to increased stress in the initial seeding phase, the overall stress induced by inhomogeneous nitrogen doping is orders of magnitude higher.

Optimizing sodium-glucose co-transporter 2 inhibitor use in patients with heart failure with reduced ejection fraction: A collaborative clinical practice statement.

Heart failure with reduced ejection fraction (HFrEF) is a debilitating disease that is associated with substantial morbidity, mortality, and societal costs. The past three decades have brought about significant advancements in the pharmacologic management of HFrEF, and a corresponding reduction in morbidity and mortality. However, the progress to improve clinical outcomes in real-world settings has stalled in recent years, largely due to underutilization of guideline directed medical therapies (GDMT). The discovery of significant cardio-renal protection from sodium-glucose co-transporter 2 inhibitors (SGLT2i) has ushered in a new treatment paradigm for HFrEF management with SGLT2i therapy becoming an essential component of GDMT. Our Preventive Cardiology and Heart Failure services have established an innovative, multi-disciplinary, collaborative protocol to optimize management of cardiovascular risk factors and facilitation SGLT2i use in patients with HFrEF. The goal of this collaboration is to enhance utilization and safety of SGLT2i for HFrEF management by circumventing medication access issues, the major obstacle to therapy initiation. Within this protocol, our heart failure providers identify patients for the addition of SGLT2i to a background of heart failure GDMT. The patient is then referred to preventive cardiology where the team performs a comprehensive cardiovascular risk assessment, optimizes cardiovascular risk factors, and initiates SGLT2i with an emphasis on medication access, cost minimization, and mitigation of potential side effects. The heart failure team assumes responsibility for modification of heart failure-based therapies, and the preventive team manages diabetes, lipid, and metabolic-based therapies. The patient is followed by both cardiology services in a structured fashion, comparing outcome measures at regular intervals and utilizing our patient registry and bio-repository. This clinical practice statement provides a detailed evidentiary review on the cardiovascular and renal benefits of SGLT2i, outlines the rational for creation of a collaborative protocol, details a structured program that may serve as a template for enhanced heart failure management in other health systems, and addresses challenges encountered and recommendations for use.

Optimization of the SiC Powder Source Material for Improved Process Conditions During PVT Growth of SiC Boules.

We have studied the influence of different SiC powder size distributions and the sublimation behavior during physical vapor transport growth of SiC in a 75 mm and 100 mm crystal processing configuration. The evolution of the source material as well as of the crystal growth interface was carried out using in situ 3D X-ray computed tomography (75 mm crystals) and in situ 2D X-ray visualization (100 mm crystals). Beside the SiC powder size distribution, the source materials differed in the maximum packaging density and thermal properties. In this latter case of the highest packaging density, the in situ X-ray studies revealed an improved growth interface stability that enabled a much longer crystal growth process. During process time, the sublimation-recrystallization behavior showed a much smoother morphology change and slower materials consumption, as well as a much more stable shape of the growth interface than in the cases of the less dense SiC source. By adapting the size distribution of the SiC source material we achieved to significantly enhance stable growth conditions.

Subclinical cardiac stiffness is associated with arterial stiffness in healthy young nulligravid women: Potential links to preeclampsia.

OBJECTIVES: Preeclampsia is an independent risk factor for subsequent cardiovascular disease and diastolic dysfunction and has been linked to arterial stiffness. We hypothesized that arterial stiffness would be associated with echocardiographic markers of diastolic dysfunction in healthy nulligravid women. STUDY DESIGN: 31 healthy nulligravid women underwent assessment of peripheral arterial stiffness via aorto-femoral pulse wave velocity, popliteal distensibility and ß stiffness measures as well as hemodynamic response to volume challenge. 22 underwent cardiac assessment via conventional and stress echocardiography with a focus on diastolic function utilizing tissue/pulse wave Doppler imaging and 3D speckle tracking. Bivariate associations between variables were evaluated using correlation coefficients (Pearson r) and Student's t-tests. RESULTS: No participants had echocardiographic values meeting criteria for overt diastolic dysfunction. Baseline global circumferential strain was significantly correlated with distensibility and ß stiffness (n = 18, r = -0.61, p = 0.007, n = 18, r = 0.56, p = 0.01). Peak deceleration time was correlated with ßstiffness (n = 9; r = 0.80, p = 0.01). Pulse wave velocity was not significantly correlated with cardiac measures (p > 0.05). Family history of a first or second degree relative with myocardial infarction or hypertension was associated with decreased popliteal artery distensibility (p = 0.02 and p = 0.03, respectively). CONCLUSIONS: In healthy nulligravid women there is evidence that markers of decreased left ventricular relaxation are associated with increased peripheral vascular stiffness as is a family history of myocardial infarction or hypertension. These findings raise the possibility that the diastolic dysfunction and arterial stiffness observed in the setting of preeclampsia are driven by underlying properties present prior to pregnancy and contribute to lifetime cardiovascular risk.

Influence of Morphological Changes in a Source Material on the Growth Interface of 4h-Sic Single Crystals.

In this study, the change of mass distribution in a source material is tracked using an in situ computer tomography (CT) setup during the bulk growth of 4H- silicon carbide (SiC) via physical vapor depostion (PVT). The changing properties of the source material due to recrystallization and densification are evaluated. Laser flash measurement showed that the thermal properties of different regions of the source material change significantly before and after the growth run. The Si-depleted area at the bottom of the crucible is thermally insulating, while the residual SiC source showed increased thermal conductivity compared to the initially charged powder. Ex situ CT measurements revealed a needle-like structure with elongated pores causing anisotropic behavior for the heat conductivity. Models to assess the thermal conductivity are applied in order to calculate the changes in the temperature field in the crucible and the changes in growth kinetics are discussed.

Limitations during Vapor Phase Growth of Bulk (100) 3C-SiC Using 3C-SiC-on-SiC Seeding Stacks.

The growth of 3C-SiC shows technological challenges, such as high supersaturation, a silicon-rich gas phase and a high vertical temperature gradient. We have developed a transfer method creating high-quality 3C-SiC-on-SiC (100) seeding stacks, suitable for use in sublimation "sandwich" epitaxy (SE). This work presents simulation data on the change of supersaturation and the temperature gradient between source and seed for the bulk growth. A series of growth runs on increased source to seed distances was characterized by XRD and Raman spectroscopy. Results show a decrease in quality in terms of single-crystallinity with a decrease in supersaturation. Morphology analysis of as-grown material indicates an increasing protrusion dimension with increasing thickness. This effect limits the achievable maximal thickness. Additional polytype inclusions were observed, which began to occur with low supersaturation (S ≤ 0.06) and prolonged growth (increase of carbon gas-species).

Analysis of the Basal Plane Dislocation Density and Thermomechanical Stress during 100 mm PVT Growth of 4H-SiC.

Basal plane dislocations (BPDs) in 4H silicon carbide (SiC) crystals grown using the physical vapor transport (PVT) method are diminishing the performance of SiC-based power electronic devices such as pn-junction diodes or MOSFETs. Therefore, understanding the generation and movement of BPDs is crucial to grow SiC suitable for device manufacturing. In this paper, the impact of the cooldown step in PVT-growth on the defect distribution is investigated utilizing two similar SiC seeds and identical growth parameters except for a cooldown duration of 40 h and 70 h, respectively. The two resulting crystals were cut into wafers, which were characterized by birefringence imaging and KOH etching. The initial defect distribution of the seed wafer was characterized by synchrotron white beam X-ray topography (SWXRT) mapping. It was found that the BPD density increases with a prolonged cooldown time. Furthermore, small angle grain boundaries based on threading edge dislocation (TED) arrays, which are normally only inherited by the seed, were also generated in the case of the crystal cooled down in 70 h. The role of temperature gradients inside the crystal during growth and post-growth concerning the generation of shear stress is discussed and supported by numerical calculations.

Pro-Inflammatory Biomarkers in Stable Versus Acutely Decompensated Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Underlying inflammation has been increasingly recognized in heart failure with a preserved ejection fraction (HFpEF). In this study we tested the hypothesis that pro-inflammatory biomarkers are elevated in patients with acutely decompensated HFpEF (AD-HFpEF) compared with patients with stable HFpEF (S-HFpEF). METHODS AND RESULTS: Using a post hoc analysis the serum biomarkers tumor necrosis factor-alpha, high-sensitivity C-reactive protein interleukin 6 and pentraxin 3 (PTX3) and clinical, demographic, echocardiographic-Doppler and clinical outcomes data were analyzed in HFpEF patients enrolled in NHLBI Heart Failure Research Network clinical trials which enrolled patients with either AD-HFpEF or S-HFpEF. Compared to S-HFpEF, AD-HFpEF patients had higher levels of PTX3 (3.08 ng/mL versus 1.27 ng/mL, P<0.0001), interleukin-6 (4.14 pg/mL versus 1.71 pg/mL, P<0.0001), tumor necrosis factor-alpha (11.54 pg/mL versus 8.62 pg/mL, P=0.0015), and high-sensitivity C-reactive protein (11.90 mg/dL versus 3.42 mg/dL, P<0.0001). Moreover, high-sensitivity C-reactive protein, interleukin-6 and PTX3 levels were significantly higher in AD-HFpEF compared with S-HFpEF patients admitted for decompensated HF within the previous year. PTX3 was positively correlated with left atrial volume index (r=0.41, P=0.0017) and left ventricular mass (r=0.26, P=0.0415), while tumor necrosis factor-alpha was inversely correlated with E/A ratio (r=-0.31, P=0.0395). CONCLUSIONS: Levels of pro-inflammatory biomarkers are strikingly higher in AD-HFpEF compared with S-HFpEF patients. PTX3 and tumor necrosis factor-alpha are correlated with echocardiographic-Doppler evidence of diastolic dysfunction. Taken together these data support the concept that a heightened pro-inflammatory state has a pathophysiologic role in the development of AD-HFpEF.

Mechanical Intervention for Aortic Valve Stenosis in Patients With Heart Failure and Reduced Ejection Fraction.

The risk and benefit of mechanical interventions in valvular heart disease have been primarily described among patients with normal ejection fraction. The advent of nonsurgical mechanical interventions for aortic stenosis (transcatheter aortic valve replacement) may alter the risk-benefit ratio for patients who would otherwise be at increased risk for valve surgery. This review describes the epidemiology and pathophysiology of aortic stenosis with heart failure and reduced ejection fraction and summarizes the current registry and clinical trial data applicable to this frequently encountered high-risk group. It concludes with discussion of ongoing trials, new approaches, emerging indications, and a potential clinical algorithm incorporating optimal mechanical intervention for patients with aortic stenosis and concomitant reduced ejection fraction.

Acoustic speech analysis of patients with decompensated heart failure: A pilot study.

This pilot study used acoustic speech analysis to monitor patients with heart failure (HF), which is characterized by increased intracardiac filling pressures and peripheral edema. HF-related edema in the vocal folds and lungs is hypothesized to affect phonation and speech respiration. Acoustic measures of vocal perturbation and speech breathing characteristics were computed from sustained vowels and speech passages recorded daily from ten patients with HF undergoing inpatient diuretic treatment. After treatment, patients displayed a higher proportion of automatically identified creaky voice, increased fundamental frequency, and decreased cepstral peak prominence variation, suggesting that speech biomarkers can be early indicators of HF.