Best anticoagulation strategy with and without appendage occlusion for stroke-prophylaxis in postablation atrial fibrillation patients with cardiac amyloidosis.

INTRODUCTION: Both atrial fibrillation (AF) and amyloidosis increase stroke risk. We evaluated the best anticoagulation strategy in AF patients with coexistent amyloidosis. METHODS: Consecutive AF patients with concomitant amyloidosis were divided into two groups based on the postablation stroke-prophylaxis approach; group 1: left atrial appendage occlusion (LAAO) in eligible patients and group 2: oral anticoagulation (OAC). Group 1 patients were further divided into Gr. 1A: LAAO + half-does NOAC (HD-NOAC) for 6 months followed by aspirin 81 mg/day and Gr. 1B: LAAO + HD-NOAC. In group 1 patients, with complete occlusion at the 45-day transesophageal echocardiogram, patients were switched to aspirin, 81 mg/day at 6 months. In case of leak, or dense "smoke" in the left atrium (LA) or enlarged LA, they were placed on long-term half-dose (HD) NOAC. Group 2 patients remained on full-dose NOAC during the whole study period. RESULTS: A total of 92 patients were included in the analysis; group 1: 56 and group 2: 36. After the 45-day TEE, 31 patients from group 1 remained on baby-aspirin and 25 on HD NOAC. At 1-year follow-up, four stroke, one TIA and six device-thrombus were reported in group 1A, compared to none in patients in group 1B (5/31 vs. 0/25, p = .03). No bleeding events were reported in group 1, whereas group 2 had five bleeding events (one subdural hematoma, one retinal hemorrhage, and four GI bleedings). Additionally, one stroke was reported in group 2 that happened during brief discontinuation of OAC. CONCLUSION: In patients with coexistent AF and amyloidosis, half-dose NOAC following LAAO was observed to be the safest stroke-prophylaxis strategy.

Multicenter experience with andexanet alfa for refractory pericardial bleeding during catheter ablation of atrial fibrillation.

INTRODUCTION: Pericardial bleeding is a rare but life-threatening complication of atrial fibrillation (AF) ablation. Patients taking uninterrupted oral anticoagulation (AC) may be at increased risk for refractory bleeding despite pericardiocentesis and administration of protamine. In such cases, andexanet alfa can be given to reverse rivaroxaban or apixaban. In this study, we aim to describe the rate of acute hemostasis and thromboembolic complications with andexanet for refractory pericardial bleeding during AF ablation. METHODS AND RESULTS: In this multicenter, case series, participating centers identified patients who received a dose of apixaban or rivaroxaban within 24 h of AF ablation, developed refractory pericardial bleeding during the procedure despite pericardiocentesis and administration of protamine and received andexanet. Eleven patients met inclusion criteria, with mean age of 73.5 ± 5.3 years and median CHA2 DS2 -VASc score 4 [3-5]. All patients received protamine and pericardiocentesis, and 9 (82%) received blood products. All patients received a bolus of andexanet followed, in all but one, by a 2-h infusion. Acute hemostasis was achieved in eight patients (73%) while three required emergent surgery. One patient (9%) experienced acute ST-elevation myocardial infarction after receiving andexanet. Therapeutic AC was restarted after a mean of 2.2 ± 1.9 days and oral AC was restarted after a mean of 2.9 ± 1.6 days, with no recurrent bleeding. CONCLUSION: In patients on uninterrupted apixaban or rivaroxaban, who develop refractory pericardial bleeding during AF ablation, andexanet can achieve hemostasis thereby avoiding the need for emergent surgery. However, there is a risk of thromboembolism following administration.

Synthetic female gonadal hormones alter neurodevelopmental programming and behavior in F1 offspring.

The increased prevalence of neurodevelopmental disorders during the last half-century led us to investigate the potential for intergenerational detrimental neurodevelopmental effects of synthetic female gonadal hormones, typically used in contraceptive pills. We examined 3 separate cohorts of mice over the span of 2 years, a total of 150 female F0 mice and over 300 male and female rodents from their F1 progeny. We demonstrate that F1 male offsprings of female mice previously exposed to the synthetic estrogen 17α-ethinylestradiol (EE2) in combination with the synthetic progestin Norethindrone, exhibit neurodevelopmental and behavioral differences compared to control mice. Because the EE2 + Norethindrone administration resulted in gene expression changes in the exposed F0 mice ovaries persisting after the end of treatment, it is likely that the synthetic hormone treatment caused changes in the germline cells and that led to altered neurodevelopment in the offsprings. An altered gene expression pattern was discovered in the frontal cortex of male mice from the first offspring (F1.1) at infancy and an ADHD-like hyperactive locomotor behavior was exhibited in young male mice from the second offspring (F1.2) of female mice treated with contraceptive pill doses of EE2 + Norethindrone prior to pregnancy. The intergenerational neurodevelopmental effects of EE2 + Norethindrone treatment were sex specific, predominantly affecting males. Our observations in mice support the hypothesis that the use of synthetic contraceptive hormones is a potential environmental factor impacting the prevalence of human neurodevelopmental disorders. Additionally, our results indicate that contraceptive hormone drug safety assessments may need to be extended to F1 offspring.

Assessing the Validity of Echocardiographic Criteria for Left Ventricular Diastolic Dysfunction in Patients with Pulmonary Hypertension.

BACKGROUND: In patients with pulmonary hypertension (PHT), the assessment of left ventricular (LV) diastolic function by echocardiography may not be reliable. PHT can affect Doppler parameters of LV diastolic function such as mitral inflow velocities and mitral annular velocities. The current guidelines for the assessment of LV diastolic function do not recommend specific adjustments for patients with PHT. METHODS: We analyzed 36 patients from the PHT clinic that had an echocardiogram and right heart catheterization performed within 6 months of each other. Early mitral inflow velocity (E), lateral mitral annular velocity (lateral e'), septal mitral annular velocity (septal e'), tricuspid free wall annular velocity (RV e') were measured and compared to the invasively measured intracardiac pressures including pulmonary capillary wedge pressure (PCWP), mean pulmonary artery pressure, and right ventricular end-diastolic pressure. RESULTS: Among patients with PHT, the specificity of the septal e' for LV diastolic dysfunction was 0.19, and the positive predictive value was 0.13 (lower than the lateral e' or E/average e'). By receiver-operating characteristic curve analysis, the area under the curve (AUC) of lateral and septal e' was just 0.64 (p = 0.9) and 0.53 (p = 0.6), respectively, while the AUC of average E/e' was 0.94 (p < 0.001). The septal e' was paradoxically lower at 6.5 ± 1.9 cm/s for normal PCWP compared to 6.9 ± 1.7 cm/s for elevated PCWP (p = 0.04). 81 versus 40% (p = 0.017) of patients with normal versus elevated PCWP had an abnormal septal e' <7 cm/s. By linear regression, there was no correlation between the Doppler parameters of LV diastolic function and the PCWP. CONCLUSION: Our study suggests E/average e' may be the only reliable tissue Doppler parameter of LV diastolic dysfunction in patients with PHT, and that septal e' is paradoxically decreased in patients with PHT and normal left-sided filling pressures.

Correlation of right atrial enlargement on ECG to right atrial volume by echocardiography in patients with pulmonary hypertension.

Previous attempts to validate ECG criteria for right atrial (RA) enlargement (RAE) have been limited by sample sizes and lack of accepted standards for measuring RA size. New guidelines have recommended that RA volume (RAV) be used to determine RA size. Since these guidelines were released, no studies have been published that correlate RAE by ECG to RAV using the new standards. We aimed to validate previously proposed ECG criteria for RAE, commonly called P pulmonale, and to establish whether a correlation exists between P wave amplitudes and RAV as determined by echocardiogram in patients from the pulmonary hypertension (PHT) clinic. We identified patients from the PHT clinic that had an echocardiogram and ECG done at most 30days apart. We defined increased P wave amplitude as ≥2mm in lead II and ≥1mm in lead V1. The RA was determined to be enlarged if the RAV index (RAVI) was ≥39mL/m2 for men and ≥33mL/m2 for women. Patients were stratified into four groups: those with P II≥2mm, those with P V1≥1mm, those that met both criteria, and those that met neither. Right atrial volumes were then compared. Sixty-three patients were included in the study (7 men, 56 women). Three men and 36 women had an ECG that met criteria for P pulmonale. Five men and 28 women had an enlarged RA on echocardiogram. Sixty-nine percent of ECGs that met criteria for RAE were associated with increased RAV by echocardiogram. The specificity of each of the ECG criteria for P pulmonale at detecting RAE was 100% for men. The criterion with the highest specificity among women was P II≥2mm AND P V1≥1mm (94%). The least specific criterion for women was P II≥2mm (70%). The sensitivity of each criterion was much lower. The most sensitive criteria for men and women were P V1≥1mm (66.6%) and P II≥2mm (48%), respectively. The correlation of P wave amplitude in leads II and V1 and RAVI was not statistically significant for any of the ECG criteria for P pulmonale. In patients from the PHT clinic, the specificity of P pulmonale for detecting RAE is high, but the sensitivity is relatively low. These results suggest that in PHT, P pulmonale can be used to confirm that the RA is enlarged, but it is not a reliable test for diagnosing RAE.

Multiscale in-situ characterization of static recrystallization using dark-field X-ray microscopy and high-resolution X-ray diffraction.

Dark-field X-ray microscopy (DFXM) is a high-resolution, X-ray-based diffraction microstructure imaging technique that uses an objective lens aligned with the diffracted beam to magnify a single Bragg reflection. DFXM can be used to spatially resolve local variations in elastic strain and orientation inside embedded crystals with high spatial (~ 60 nm) and angular (~ 0.001°) resolution. However, as with many high-resolution imaging techniques, there is a trade-off between resolution and field of view, and it is often desirable to enrich DFXM observations by combining it with a larger field-of-view technique. Here, we combine DFXM with high-resolution X-ray diffraction (HR-XRD) applied to an in-situ investigation of static recrystallization in an 80% hot-compressed Mg-3.2Zn-0.1Ca wt.% (ZX30) alloy. Using HR-XRD, we track the relative grain volume of > 8000 sub-surface grains during annealing in situ. Then, at several points during the annealing process, we "zoom in" to individual grains using DFXM. This combination of HR-XRD and DFXM enables multiscale characterization, used here to study why particular grains grow to consume a large volume fraction of the annealed microstructure. This technique pairing is particularly useful for small and/or highly deformed grains that are often difficult to resolve using more standard diffraction microstructure imaging techniques.

Acute Kidney Injury Resulting From Hemoglobinuria After Pulsed-Field Ablation in Atrial Fibrillation: Is it Preventable?

BACKGROUND: High-voltage pulses can cause hemolysis. OBJECTIVES: The authors evaluated the occurrence of hemoglobinuria after pulsed-field ablation (PFA) and its impact on renal function in patients with atrial fibrillation (AF). METHODS: A consecutive series of patients with AF undergoing PFA were included in this analysis. The initial patients who did not receive postablation hydration immediately after the procedure were classified as group 1 (n = 28), and the rest of the study patients who received planned fluid infusion (0.9% sodium chloride ≥2 L) after the procedure were categorized as group 2 (n = 75). RESULTS: Of the 28 patients in group 1, 21 (75%) experienced hemoglobinuria during the 24 hours after catheter ablation. The mean postablation serum creatinine (S-Cr) was significantly higher than the baseline value in those 21 patients (1.46 ± 0.28 mg/dL vs 0.86 ± 0.24 mg/dL, P < 0.001). Of those 21 patients, 4 (19%) had S-Cr. >2.5 mg/dL (mean: 2.95 ± 0.21 mg/dL). The mean number of PF applications was significantly higher in those 4 patients than in the other 17 patients experiencing hemoglobinuria (94.63 ± 3.20 vs 46.75 ± 9.10, P < 0.001). In group 2 patients, no significant changes in S-Cr were noted. The group 2 patients received significantly higher amounts of fluid infusion after catheter ablation than did those in group 1 (2,082.50 ± 258.08 mL vs 494.01 ± 71.65 mL, P < 0.001). In multivariable analysis, both hydration (R2 = 0.63, P < 0.01) and number of PFA applications (R2 = 0.33, P < 0.01) were independent predictors of postprocedure acute kidney injury. CONCLUSIONS: On the basis of our findings, both the number of PFA applications and postablation hydration were independent predictors of renal insult that could be prevented using planned fluid infusion immediately after the procedure.

The geometric model and fat reduction.

BACKGROUND AND OBJECTIVE: Assessing the efficacy of noninvasive fat removal relies on measurements that are subject to error and subjective comparisons. Even the integrity of photographic comparisons, an accepted assessment tool, is difficult to control. With the emergence of noninvasive fat reduction technologies, there is a greater need for standardized assessments of efficacy. MATERIALS AND METHODS: A geometric model is described that correlates circumference and fat layer changes following noninvasive body contouring procedures. To validate the geometric model, abdominal measurements were taken with and without an artificial fat pad in place with: 1) a tape measure, 2) ultrasound, and 3) micrometer. The model was then used to analyze the published results of fat layer reduction and circumference changes following noninvasive body contouring procedures. RESULTS: While there was a high correlation (R2=0.8943) between our ultrasound method and the model with 6 subjects, the correlation between the tape measure method and the model was low (R2=0.0142). CONCLUSION: Our results underscore the need for a highly accurate and standardized method for fat measurement. The efficacy in previous studies that had been assessed by tape measure in combination with ultrasound or computed tomography imaging does not conform to the model prediction, which leads us to conclude that the measurements used in those studies were not reliable. Studies reporting efficacy should use such a geometric model to ensure consistency between various measurement methods and to minimize errors due to weight change and measurement technique.

Determinants of Response to Cardiac Resynchronization Therapy.

Cardiac resynchronization therapy (CRT) is a well-established treatment modality for ambulatory patients with heart failure (HF) who have prolonged QRS, left bundle branch block, reduced left ventricular (LV) ejection fraction, and New York Heart Association class II-IV. CRT has been shown to induce reverse LV remodeling and improve HF symptoms and clinical outcomes. About one-third of CRT recipients are considered non-responders. Patient selection, LV lead location, LV lead selection, multipoint pacing, and optimization of the atrioventricular and ventriculo-ventricular intervals were all shown to be associated with a better CRT response rate. Herein, we review the determinants of CRT response.

Focal Atrial Tachycardia Arising From the Posterior Wall of the Left Atrium.

Potential foci for atrial tachycardia have been previously described in various locations including crista terminalis, tricuspid annulus, coronary sinus ostium, pulmonary vein ostia. In this report, we present a case of a focal atrial tachycardia arising from the posterior wall of the left atrium which has not been described before. (Level of Difficulty: Advanced.).

Novel Use of a Rotating Mechanical Dilator Sheath for S-ICD Lead Extraction.

A 53-year-old man with a subcutaneous implantable cardioverter-defibrillator (S-ICD) presented with inappropriate shocks. He underwent device extraction, and the lead was freed using a rotating mechanical dilator sheath. As patients with S-ICDs get older, extractions will become more complicated and more common. We have described a novel method of S-ICD lead extraction. (Level of Difficulty: Advanced.).

A quantitative study of stress fields ahead of a slip band blocked by a grain boundary in unalloyed magnesium.

Stress localization ahead of a slip band blocked by a grain boundary is measured for three different grain boundaries in unalloyed Mg using high-resolution electron backscatter diffraction (HR-EBSD). The results are compared with a theoretical dislocation pile-up model, from which slip system resistance and micro-Hall-Petch coefficients for different grain boundary types are deduced. The results indicate that grain boundary character plays a crucial role in determining micro-Hall-Petch coefficients, which can be used to strengthen classical crystal plasticity constitutive models to make predictions linked to the effect of grain boundary strengthening.

Various Manifestations of 5-Fluorouracil Cardiotoxicity: A Multicenter Case Series and Review of Literature.

5-Fluorouracil is a key element to the treatment of colon cancer. But it is also one of the most cardiotoxic chemotherapies, and the management of those that experience cardiotoxicity can be challenging. We present three cases of 5-FU cardiac toxicity that manifested as myocardial infarction, cardiogenic shock, and ventricular fibrillation. Additionally, we discuss the current literature regarding 5-fluorouracil cardiotoxicity mechanisms as well as management.

Determination of pyridoxal-5'-phosphate (PLP)-bonding sites in proteins: a peptide mass fingerprinting approach based on diagnostic tandem mass spectral features of PLP-modified peptides.

Peptides modified by pyridoxal-5'-phosphate (PLP), linked to a lysine residue via reductive amination, exhibit distinct spectral characteristics in the collision-induced dissociation (CID) tandem mass (MS/MS) spectra that are described here. The MS/MS spectra typically display two dominant peaks whose m/z values correspond to neutral losses of [H3PO4] (-98 Da) and the PLP moiety as [C8H10NO5P] (-231 Da) from the precursor peptide ion, respectively. Few other peaks are observed. Recognition of this distinct fragmentation behavior is imperative since determining sequences and sites of modifications relies on the formation of amide backbone cleavage products for subsequent interpretation via proteome database searching. Additionally, PLP-modified peptides exhibit suppressed precursor ionization efficiency which diminishes their detection in complex mixtures. Presented here is a protocol which describes an enrichment strategy for PLP-modified peptides combined with neutral loss screening and peptide mass fingerprinting to map the PLP-bonding site in a known PLP-dependent protein. This approach represents an efficient alternative to site-directed mutagenesis which has been the traditional method used for PLP-bonding site localization in proteins.

Interpretation of laser desorption mass spectra of unexpected inorganic species found in a cosmetic sample of forensic interest: fingernail polish.

When analytes containing color are irradiated with a pulsed UV laser in the ion source of a mass spectrometer, molecules such as dyes or pigments absorb energy, resulting in their desorption and ionization. This method, laser desorption mass spectrometry (LDMS), has been used successfully to analyze colorants of forensic interest in a wide variety of materials. Here, we present and interpret the most complex of such spectra obtained to date from a sample of fingernail polish. Interpretation of the spectrum provides a unique opportunity to characterize the laser desorption mass spectra of some unexpected inorganic materials found in cosmetics, such as "broken glass", cyanide compounds, and heavy metals. Also, the possibility of a useful forensic database of LDMS spectra of fingernail polishes is considered.

Cryolipolysis for noninvasive fat cell destruction: initial results from a pig model.

BACKGROUND: Liposuction is one of the most frequently performed cosmetic procedures in the United States, but its cost and downtime has led to the development of noninvasive approaches for adipose tissue reduction. OBJECTIVE: To determine whether noninvasive controlled and selective destruction of fat cells (Cryolipolysis) can selectively damage subcutaneous fat without causing damage to the overlying skin or rise in lipid levels. METHODS: Three Yucatan pigs underwent Cryolipolysis at 22 sites: 20 at cooling intensity factor (CIF) index 24.5 (-43.8 mW/cm(2)), one at CIF 24.9 (-44.7 mW/cm(2)), and one at CIF 25.4 (-45.6 mW/cm(2)). Treated areas were evaluated using photography, ultrasound, and gross and microscopic pathology. Lipids were at various times points. One additional pig underwent Cryolipolysis at various days before euthanasia. RESULTS: The treatments resulted in a significant reduction in the superficial fat layer without damage to the overlying skin. An inflammatory response triggered by cold-induced apoptosis of adipocytes preceded the reduction in the fat layer. Evaluation of lipids over a 3-month period following treatment demonstrated that cholesterol and triglyceride values remained normal. CONCLUSIONS: Cryolipolysis is worthy of further study because it has been shown to significantly decrease subcutaneous fat and change body contour without causing damage to the overlying skin and surrounding structures or deleterious changes in blood lipids.

Clinical efficacy of noninvasive cryolipolysis and its effects on peripheral nerves.

BACKGROUND: Cryolipolysis provides a method for noninvasive fat reduction that significantly reduces subcutaneous fat in a pig model without apparent damage to skin and surrounding structures. This study aimed to determine whether fat reduction in humans caused by cold exposure is associated with alteration in local sensory function or nerve fibers. METHODS: In this study, 10 subjects were treated with a prototype cooling device. Fat reduction was assessed in 9 of the 10 subjects via ultrasound before treatment and at the follow-up visit. Sensory function was assessed by neurologic evaluation (n = 9), and biopsies (n = 1) were collected for nerve staining. RESULTS: Treatment resulted in a normalized fat layer reduction of 20.4% at 2 months and 25.5% at 6 months after treatment. Transient reduction in sensation occurred in six of nine subjects assessed by neurologic evaluation. However, all sensation returned by a mean of 3.6 weeks after treatment. Biopsies showed no long-term change in nerve fiber structure. There were no lasting sensory alterations or observations of skin damage in any of the subjects evaluated. CONCLUSION: Noninvasive cryolipolysis results in substantial fat reduction within 2 months of treatment without damage to skin. The procedure is associated with modest reversible short-term changes in the function of peripheral sensory nerves.

Cloud System Evolution in the Trades-CSET: Following the Evolution of Boundary Layer Cloud Systems with the NSF/NCAR GV.

The Cloud System Evolution in the Trades (CSET) study was designed to describe and explain the evolution of the boundary layer aerosol, cloud, and thermodynamic structures along trajectories within the north-Pacific trade-winds. The study centered on 7 round-trips of the NSF NCAR Gulfstream V (GV) between Sacramento, CA and Kona, Hawaii between 1 July and 15 August 2015. The CSET observing strategy was to sample aerosol, cloud, and boundary layer properties upwind from the transition zone over the North Pacific and to resample these areas two days later. GFS forecast trajectories were used to plan the outbound flight to Hawaii with updated forecast trajectories setting the return flight plan two days later. Two key elements of the CSET observing system were the newly developed HIAPER Cloud Radar (HCR) and the High Spectral Resolution Lidar (HSRL). Together they provided unprecedented characterizations of aerosol, cloud and precipitation structures that were combined with in situ measurements of aerosol, cloud, precipitation, and turbulence properties. The cloud systems sampled included solid stratocumulus infused with smoke from Canadian wildfires, mesoscale cloud-precipitation complexes, and patches of shallow cumuli in very clean environments. Ultra-clean layers observed frequently near the top of the boundary layer were often associated with shallow, optically thin, layered veil clouds. The extensive aerosol, cloud, drizzle and boundary layer sampling made over open areas of the Northeast Pacific along 2-day trajectories during CSET is unprecedented and will enable modeling studies of boundary layer cloud system evolution and the role of different processes in that evolution.

Identification of colorants in pigmented pen inks by laser desorption mass spectrometry.

Pigments are rapidly replacing dyes as colorants in pen and printer inks, due to their superior colors and stability. Unfortunately, tools commonly used in questioned document examination for analyzing pen inks, such as TLC, cannot be used for the analysis of insoluble pigments on paper. Laser desorption mass spectrometry is demonstrated here as a tool for analyzing pigment-based pen inks. A pulsed nitrogen laser can be focused onto a pen stroke from a pigmented ink pen on paper, and positive and negative ions representative of the pigment can be generated for subsequent mass spectrometric analysis. Targeted pens for this work were a set of Uni-ball 207 pigmented ink pens containing blue, light blue, orange, green, violet, red, pink, and black inks. Copper phthalocyanine was identified as the pigment used to make both blue inks. A mixture of halogenated copper phthalocyanines were identified in the green ink. Unexpectedly, the pink ink was found to contain a red pigment, Pigment Red 12, treated with a mixture of water-soluble dyes. Each sample yielded ions representative of the pigments present.