2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure.

Cardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing-induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre-procedure evaluation and preparation, implant procedure management, follow-up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure.

Cardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing-induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre-procedure evaluation and preparation, implant procedure management, follow-up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

Worldwide survey on implantation of and outcomes for conduction system pacing with His bundle and left bundle branch area pacing leads.

BACKGROUND: Adoption and outcomes for conduction system pacing (CSP), which includes His bundle pacing (HBP) or left bundle branch area pacing (LBBAP), in real-world settings are incompletely understood. We sought to describe real-world adoption of CSP lead implantation and subsequent outcomes. METHODS: We performed an online cross-sectional survey on the implantation and outcomes associated with CSP, between November 15, 2020, and February 15, 2021. We described survey responses and reported HBP and LBBAP outcomes for bradycardia pacing and cardiac resynchronization CRT indications, separately. RESULTS: The analysis cohort included 140 institutions, located on 5 continents, who contributed data to the worldwide survey on CSP. Of these, 127 institutions (90.7%) reported experience implanting CSP leads. CSP and overall device implantation volumes were reported by 84 institutions. In 2019, the median proportion of device implants with CSP, HBP, and/or LBBAP leads attempted were 4.4% (interquartile range [IQR], 1.9-12.5%; range, 0.4-100%), 3.3% (IQR, 1.3-7.1%; range, 0.2-87.0%), and 2.5% (IQR, 0.5-24.0%; range, 0.1-55.6%), respectively. For bradycardia pacing indications, HBP leads, as compared to LBBAP leads, had higher reported implant threshold (median [IQR]: 1.5 V [1.3-2.0 V] vs 0.8 V [0.6-1.0 V], p = 0.0008) and lower ventricular sensing (median [IQR]: 4.0 mV [3.0-5.0 mV] vs. 10.0 mV [7.0-12.0 mV], p < 0.0001). CONCLUSION: In conclusion, CSP lead implantation has been broadly adopted but has yet to become the default approach at most surveyed institutions. As the indications and data for CSP continue to evolve, strategies to educate and promote CSP lead implantation at institutions without CSP lead implantation experience would be necessary.

[Medical misinformation on social media: should it be corrected or not?] / Foute informatie op sociale media.

A lot of medical misinformation circulates on the Internet - especially social media. During the corona crisis, this became an acute and prominent problem. Countering medical misinformation can be done with debunking (refuting misinformation with fact checks) and prebunking (warning people about misinformation and teaching them to recognize it). Research shows that debunking helps correct misconceptions created by misinformation, although the effect is limited. Although this is sometimes suggested, it is not true that corrections or factchecks actually cause misconceptions to be reinforced. Prebunking is also effective, although it can also cause people to distrust reliable information as well.

Diamond nanopillar arrays for quantum microscopy of neuronal signals.

Significance: Wide-field measurement of cellular membrane dynamics with high spatiotemporal resolution can facilitate analysis of the computing properties of neuronal circuits. Quantum microscopy using a nitrogen-vacancy (NV) center is a promising technique to achieve this goal. Aim: We propose a proof-of-principle approach to NV-based neuron functional imaging. Approach: This goal is achieved by engineering NV quantum sensors in diamond nanopillar arrays and switching their sensing mode to detect the changes in the electric fields instead of the magnetic fields, which has the potential to greatly improve signal detection. Apart from containing the NV quantum sensors, nanopillars also function as waveguides, delivering the excitation/emission light to improve sensitivity. The nanopillars also improve the amplitude of the neuron electric field sensed by the NV by removing screening charges. When the nanopillar array is used as a cell niche, it acts as a cell scaffolds which makes the pillars function as biomechanical cues that facilitate the growth and formation of neuronal circuits. Based on these growth patterns, numerical modeling of the nanoelectromagnetics between the nanopillar and the neuron was also performed. Results: The growth study showed that nanopillars with a 2 - µ m pitch and a 200-nm diameter show ideal growth patterns for nanopillar sensing. The modeling showed an electric field amplitude as high as ≈ 1.02 × 10 10 mV / m at an NV 100 nm from the membrane, a value almost 10 times the minimum field that the NV can detect. Conclusion: This proof-of-concept study demonstrated unprecedented NV sensing potential for the functional imaging of mammalian neuron signals.

Extra-corporeal membrane oxygenation for the post-cardiotomy patient.

Extra-corporeal membrane oxygenation remains the last resort in keeping patients alive in those with profound cardiogenic shock following percutaneous interventions or open surgery on the heart. No guidelines exist on the management of patients on such a device despite a high mortality. We attempt to highlight some universal principles that would be relevant to the current practice of those exposed to this challenging field.

The effect of deep hypothermia on the human pulmonary circulation.

OBJECTIVE: Acute rises in pulmonary artery pressures following complex cardiac surgery are associated with high morbidity and mortality. We hypothesised that periods of deep hypothermia predispose to elevated pulmonary pressures upon rewarming. We investigated the effect of this hypothermic preconditioning on isolated human pulmonary arteries and isolated perfused lungs. METHODS: Isometric tension was measured in human pulmonary artery rings (n=24). We assessed the constriction and dilation of these arteries at 37 °C and 17 °C. Isolated perfused human lung models consisted of lobes ventilated via a bronchial cannula and perfused with Krebs via a pulmonary artery cannula. Bronchial and pulmonary artery pressures were recorded. We investigated the effect of temperature using a heat exchanger. RESULTS: Rewarming from 17 °C to 37 °C caused a 1.3 fold increase in resting tension (p<0.05). Arteries constricted 8.6 times greater to 30 nM KCl, constricted 17 times greater to 1 nM Endothelin-1 and dilated 30.3 times greater to 100 µM SNP at 37 °C than at 17 °C (p<0.005). No difference was observed in the responses of arteries originally maintained at 37 °C compared to those arteries maintained at 17 °C and rewarmed to 37 °C. Hypothermia blunted the increase in pulmonary artery pressures to stimulants such as potassium chloride as well as to H-R but did not precondition arteries to higher pulmonary artery pressures upon re-warming. CONCLUSIONS: Deep hypothermia reduces the responsiveness of human pulmonary arteries but does not, however, precondition an exaggerated response to vasoactive agents upon re-warming.

Complex aortic surgery in a regional center in the United Kingdom. Should the United Kingdom now adopt a United States-style supercenter model?

BACKGROUND: The United States has established aortic supercenters, which have demonstrated clear improvements in the short-term and long-term outcomes after surgery on the thoracic aorta. This model of care does not exist in the United Kingdom. We have looked at our recent experience of emergency and elective thoracic aortic surgery and describe and compare our operative outcomes and 10-year survival with other regional centers and supercenters worldwide. METHODS: This was a retrospective analysis of data collected prospectively from our cardiac database on patients who underwent surgery on the thoracic aorta (n=318) between November 1999 and November 2012. The outcome measures were adjusted operative mortality, postoperative complications, and long-term survival. RESULTS: Type A dissection was carried out on 23.90% of the patients and 76.10% had surgery on the aortic root and thoracic aorta for nondissection. The mean age of the patients was 62.21±14.1 years. The mean logistic EuroSCORE was 26 in the dissection group and 19 in the nondissection group. Hospital mortality was significantly greater (P<.05) in the dissection group compared with the nondissection group (23.7% vs 12.8%). Survival after dissection and nondissection surgery was 66.3%±5.6% versus 77.4%±2.8%, respectively, at 3 years, 63.9%±5.9% versus 71.8%±3.2% at 5 years, and 53.7%±7.4% versus 47.1%±6.0% at 10 years. CONCLUSIONS: Our outcomes are comparable with other regional centers worldwide; however, they are not as good as those reported from the aortic supercenters. There should be continued impetus regarding the establishment of thoracic aortic surgery guidelines and specialist aortic centers in the United Kingdom.

Hyperoxic vasoconstriction of human pulmonary arteries: a novel insight into acute ventricular septal defects.

Objectives. Acute rises in pulmonary artery pressures following postinfarction ventricular septal defects present a challenge. We hypothesised that the abnormally high oxygen content exposure to the pulmonary arteries may be a factor. We investigated the contractile responses of human pulmonary arteries to changes in oxygen tension. Methods. Isometric tension was measured in large and medium sized pulmonary artery rings obtained from lung resections for patients with bronchial carcinoma (n = 30). Fresh rings were mounted in organ baths bubbled under basal conditions with hyperoxic or normoxic gas mixes and the gas tensions varied during the experiment. We studied whether voltage-gated calcium channels and nitric oxide signalling had any role in responses to oxygen changes. Results. Hypoxia caused a net mean relaxation of 18.1% ± 15.5 (P < 0.005) from hyperoxia. Subsequent hyperoxia caused a contraction of 19.2% ± 13.5 (P < 0.005). Arteries maintained in normoxia responded to hyperoxia with a mean constriction of 14.8% ± 3.9 (P < 0.005). Nifedipine inhibited the vasoconstrictive response (P < 0.05) whilst L-NAME had no effect on any hypoxic vasodilatory response. Conclusions. We demonstrate that hyperoxia leads to vasoconstriction in human pulmonary arteries. The mechanism appears to be dependent on voltage-gated calcium channels. Hyperoxic vasoconstriction may contribute to acute rises in pulmonary artery pressures.

The ionic atmosphere around A-RNA: Poisson-Boltzmann and molecular dynamics simulations.

The distributions of different cations around A-RNA are computed by Poisson-Boltzmann (PB) equation and replica exchange molecular dynamics (MD). Both the nonlinear PB and size-modified PB theories are considered. The number of ions bound to A-RNA, which can be measured experimentally, is well reproduced in all methods. On the other hand, the radial ion distribution profiles show differences between MD and PB. We showed that PB results are sensitive to ion size and functional form of the solvent dielectric region but not the solvent dielectric boundary definition. Size-modified PB agrees with replica exchange molecular dynamics much better than nonlinear PB when the ion sizes are chosen from atomistic simulations. The distribution of ions 14 Å away from the RNA central axis are reasonably well reproduced by size-modified PB for all ion types with a uniform solvent dielectric model and a sharp dielectric boundary between solvent and RNA. However, this model does not agree with MD for shorter distances from the A-RNA. A distance-dependent solvent dielectric function proposed by another research group improves the agreement for sodium and strontium ions, even for shorter distances from the A-RNA. However, Mg(2+) distributions are still at significant variances for shorter distances.

Understanding the physical basis of the salt dependence of the electrostatic binding free energy of mutated charged ligand-nucleic acid complexes.

The predictions of the derivative of the electrostatic binding free energy of a biomolecular complex, ΔG(el), with respect to the logarithm of the 1:1 salt concentration, d(ΔG(el))/d(ln[NaCl]), SK, by the Poisson-Boltzmann equation, PBE, are very similar to those of the simpler Debye-Hückel equation, DHE, because the terms in the PBE's predictions of SK that depend on the details of the dielectric interface are small compared to the contributions from long-range electrostatic interactions. These facts allow one to obtain predictions of SK using a simplified charge model along with the DHE that are highly correlated with both the PBE and experimental binding data. The DHE-based model developed here, which was derived from the generalized Born model, explains the lack of correlation between SK and ΔG(el) in the presence of a dielectric discontinuity, which conflicts with the popular use of this supposed correlation to parse experimental binding free energies into electrostatic and nonelectrostatic components. Moreover, the DHE model also provides a clear justification for the correlations between SK and various empirical quantities, like the number of ion pairs, the ligand charge on the interface, the Coulomb binding free energy, and the product of the charges on the complex's components, but these correlations are weak, questioning their usefulness.

Using Correlated Monte Carlo Sampling for Efficiently Solving the Linearized Poisson-Boltzmann Equation Over a Broad Range of Salt Concentration.

Dielectric continuum or implicit solvent models provide a significant reduction in computational cost when accounting for the salt-mediated electrostatic interactions of biomolecules immersed in an ionic environment. These models, in which the solvent and ions are replaced by a dielectric continuum, seek to capture the average statistical effects of the ionic solvent, while the solute is treated at the atomic level of detail. For decades, the solution of the three-dimensional Poisson-Boltzmann equation (PBE), which has become a standard implicit-solvent tool for assessing electrostatic effects in biomolecular systems, has been based on various deterministic numerical methods. Some deterministic PBE algorithms have drawbacks, which include a lack of properly assessing their accuracy, geometrical difficulties caused by discretization, and for some problems their cost in both memory and computation time. Our original stochastic method resolves some of these difficulties by solving the PBE using the Monte Carlo method (MCM). This new approach to the PBE is capable of efficiently solving complex, multi-domain and salt-dependent problems in biomolecular continuum electrostatics to high precision. Here we improve upon our novel stochastic approach by simultaneouly computating of electrostatic potential and solvation free energies at different ionic concentrations through correlated Monte Carlo (MC) sampling. By using carefully constructed correlated random walks in our algorithm, we can actually compute the solution to a standard system including the linearized PBE (LPBE) at all salt concentrations of interest, simultaneously. This approach not only accelerates our MCPBE algorithm, but seems to have cost and accuracy advantages over deterministic methods as well. We verify the effectiveness of this technique by applying it to two common electrostatic computations: the electrostatic potential and polar solvation free energy for calcium binding proteins that are compared with similar results obtained using mature deterministic PBE methods.

Comparing the Predictions of the Nonlinear Poisson-Boltzmann Equation and the Ion Size-Modified Poisson-Boltzmann Equation for a Low-Dielectric Charged Spherical Cavity in an Aqueous Salt Solution.

The ion size-modified Poisson Boltzmann equation (SMPBE) is applied to the simple model problem of a low-dielectric spherical cavity containing a central charge, in an aqueous salt solution to investigate the finite ion size effect upon the electrostatic free energy and its sensitivity to changes in salt concentration. The SMPBE is shown to predict a very different electrostatic free energy than the nonlinear Poisson-Boltzmann equation (NLPBE) due to the additional entropic cost of placing ions in solution. Although the energy predictions of the SMPBE can be reproduced by fitting an appropriatelysized Stern layer, or ion-exclusion layer to the NLPBE calculations, the size of the Stern layer is difficult to estimate a priori. The SMPBE also produces a saturation layer when the central charge becomes sufficiently large. Ion-competition effects on various integrated quantities such the total number of ions predicted by the SMPBE are qualitatively similar to those given by the NLPBE and those found in available experimental results.

Changing operative characteristics of patients undergoing operations for coronary artery disease: impact on early outcomes.

BACKGROUND: Aggressive nonsurgical revascularization results in high-risk patients presenting for operation at a later stage of coronary artery disease (CAD). This study investigated the effect of temporal changes in operative characteristics on outcomes of surgical revascularization. METHODS: We compared preoperative, intraoperative, and postoperative variables of 5633 patients who underwent surgical revascularization for CAD between April 1998 and January 2007, divided into early (1998 to 2002, n = 2746) and late (2004 to 2007, n = 2887) eras. End points were major adverse outcomes (postoperative myocardial infarction, stroke, new dialysis) and operative mortality. RESULTS: Median age (66 vs 68 years, p < 0.0001), prevalence of left ventricular systolic dysfunction, left main stem disease, prior angioplasty, diabetes mellitus, concomitant valve operation, and aprotinin use increased steadily over time. Severe symptoms, nonelective operations, mean number of grafts, postoperative bleeding, reopening for bleeding, and blood transfusion declined. Major complications were evenly distributed between the eras. Operative mortality for isolated coronary artery bypass grafting did not change (2.0% vs 1.8% p = 0.62) despite increasing operative risk (p < 0.0001); there was a 100% reduction in the absolute risk (110% to 210%) over time. The markers for operative difficulties, such as longer bypass times, were determinants of operative mortality and, in addition to other predictors like age and left ventricular systolic dysfunction, were more prevalent in the late era. CONCLUSIONS: Coronary operations are increasingly performed in higher-risk patients; however, surgical revascularization is nearly twice as safe in current practice compared with a decade ago.

Early and late survival after surgical revascularization for ischemic ventricular fibrillation/tachycardia.

BACKGROUND: Ischemic ventricular fibrillation/tachycardia (VF/VT) treated by myocardial revascularization, often with an implanted cardioverter defibrillator, prevents sudden cardiac death. Early series have suggested that recurrent VF/VT threatens survival even after treatment. As late outcome is unknown, we sought to determine if the early survival benefit is sustained. METHODS: From January 1999 through January 2007, 93 consecutive patients (75 male, 81%) presented with ischemic VF/VT; 21% survived cardiac arrest and underwent coronary artery bypass graft surgery at our institution. We analyzed their early and late survival. RESULTS: Median age was 66 years (range, 44 to 88). Clinical presentation included class III/IV angina (46%), controlled heart failure (43%), prior myocardial infarction (68%), left ventricular ejection fraction less than 0.30 (23%) and 0.30 to 0.50 (35%), left main stem disease (24%), and triple-vessel disease (67%). Surgical revascularization, mostly nonelective (urgent 73%, emergency 7%), was combined with aortic valve replacement in 5 patients and left ventricular pseudoaneurysm repair in 3. Ischemic territories and mean number of diseased coronaries (2.6) corresponded to the grafted territories and average number of grafts (2.5). Operative mortality was 6.5% (n = 6, median EuroSCORE [European System for Cardiac Operative Risk Evaluation] predicted mortality 9). Recurrent VF/VT occurred early postoperatively in 21 patients (24%). All patients had electrophysiologic studies postoperatively and 40% received an implanted cardioverter defibrillator. Of 12 late deaths (16%) at follow-up extending to 8 years, 4 (33%) were due to cardiac causes. Five-year survival was 88%, equivalent to that (83% to 85%) reported for patients with sinus rhythm preoperatively. CONCLUSIONS: Complete myocardial revascularization for ischemic VF/VT yields excellent early and late results; 5-year survival is comparable to that of patients with preoperative sinus rhythm.

Proptosis--an uncommon presentation of orbital metastases secondary to prostate cancer.

We report the case of a man with advanced prostate cancer who presented as an emergency with proptosis of his right eye. Cross-sectional imaging of his head confirmed the cause to be orbital metastases secondary to his prostate cancer. The patient responded well to treatment with dexamethasone and palliative orbital radiotherapy.