Atrial fibrillation (AF) is commonly associated with congestive heart failure (CHF), and CHF has been shown to be associated with atrial structural remodeling resulting in fibrosis. Atrial ...interstitial fibrosis has been seen in patients with CHF and in animal models of pacing-induced heart failure. With atrial fibrosis, conduction abnormalities result in increased AF vulnerability. The mechanism of AF associated with CHF is under debate, as both focal and reentrant mechanisms have been observed in animal models of CHF. However, recent studies using frequency-domain analysis have shown that the AF within this model is characterized by discrete, stable, high-frequency areas. The precise signaling processes involved in the development of atrial fibrosis are unknown. Angiotensin appears to play a role, as inhibition of angiotensin-converting enzyme (or angiotensin-receptor blocker) blunts atrial fibrosis in animal models of heart failure and decreases the incidence of AF in patients with heart failure. Transforming growth factor-beta (TGF-beta) also appears to play an important role. Mouse models that overexpress TGF-beta1 have profound atrial fibrosis and AF (with normal ventricles). Heart failure in canine models also produces increases in atrial TGF-beta1 expression, and inhibition of this expression prevents atrial fibrosis and the development of a substrate for AF. Atrial fibrosis appears to play a role in the development of a vulnerable substrate for AF, especially in the setting of CHF.
This paper presents an AI-powered solution for detecting and monitoring Autonomic Dysreflexia (AD) in individuals with spinal cord injuries. Current AD detection methods are limited, lacking ...non-invasive monitoring systems. We propose a model that combines skin nerve activity (SKNA) signals with a deep neural network (DNN) architecture to overcome this limitation. The DNN is trained on a meticulously curated dataset obtained through controlled colorectal distension, inducing AD events in rats with spinal cord surgery above the T6 level. The proposed system achieves an impressive average classification accuracy of 93.9% ± 2.5%, ensuring accurate AD identification with high precision (95.2% ± 2.1%). It demonstrates a balanced performance with an average F1 score of 94.4% ± 1.8%, indicating a harmonious balance between precision and recall. Additionally, the system exhibits a low average false-negative rate of 4.8% ± 1.6%, minimizing the misclassification of non-AD cases. The robustness and generalizability of the system are validated on unseen data, maintaining high accuracy, F1 score, and a low false-negative rate. This AI-powered solution represents a significant advancement in non-invasive, real-time AD monitoring, with the potential to improve patient outcomes and enhance AD management in individuals with spinal cord injuries. This research contributes a promising solution to the critical healthcare challenge of AD detection and monitoring.
The electrochemical instability of ether-based electrolyte solutions hinders their practical applications in high-voltage Li metal batteries. To circumvent this issue, here, we propose a dilution ...strategy to lose the Li
/solvent interaction and use the dilute non-aqueous electrolyte solution in high-voltage lithium metal batteries. We demonstrate that in a non-polar dipropyl ether (DPE)-based electrolyte solution with lithium bis(fluorosulfonyl) imide salt, the decomposition order of solvated species can be adjusted to promote the Li
/salt-derived anion clusters decomposition over free ether solvent molecules. This selective mechanism favors the formation of a robust cathode electrolyte interphase (CEI) and a solvent-deficient electric double-layer structure at the positive electrode interface. When the DPE-based electrolyte is tested in combination with a Li metal negative electrode (50 μm thick) and a LiNi
Co
Mn
O
-based positive electrode (3.3 mAh/cm
) in pouch cell configuration at 25 °C, a specific discharge capacity retention of about 74% after 150 cycles (0.33 and 1 mA/cm
charge and discharge, respectively) is obtained.
Skin sympathetic nerve activity (SKNA) is useful for estimating sympathetic tone in humans.
The purpose of this study was to test the hypotheses that (1) increased SKNA is associated with the onset ...and termination of paroxysmal atrial tachycardia (AT) and atrial fibrillation (AF) and (2) sinoatrial node response to SKNA is reduced in patients with more frequent AT or AF episodes.
SKNA and electrocardiogram were recorded in 11 patients (4 men and 7 women; average age 66 ± 10 years), including 3 patients with AT (11 ± 18 episodes per patient) and 8 patients with AF (24 ± 26 episodes per patient).
The average SKNA (aSKNA) 10 seconds before AT onset was 1.07 ± 0.10 μV and 10 seconds after termination was 1.27 ± 0.10 μV; both were significantly (P = .032 and P < .0001) higher than that during sinus rhythm (0.97 ± 0.09 μV). The aSKNA 10 seconds before AF onset was 1.34 ± 0.07 μV and 10 seconds after termination was 1.31 ± 0.07 μV; both were significantly (P < .0001) higher than that during sinus rhythm (1.04 ± 0.07 μV). The aSKNA before onset (P < .0001) and after termination (P = .0011) was higher in AF than in AT. The sinus rate correlated (P < .0001) with aSKNA in each patient (average r = 0.74; 95% confidence interval 0.65-0.84). The r value in each patient negatively correlated with the number of AT and AF episodes (r = -0.6493; 95% confidence interval -0.8990 to -0.08073; P = .0306).
Increased SKNA was observed both at the onset and termination of AT and AF. Patients with more frequent AT and AF episodes had a weak correlation between sinus rate and aSKNA, suggesting sinoatrial node remodeling by tachycardia.
Atrial fibrosis is an important substrate in atrial fibrillation (AF), particularly in the setting of structural heart disease. In a canine model, congestive heart failure (CHF) produces significant ...atrial fibrosis and the substrate for sustained AF. This atrial remodeling is a potential therapeutic target. The objective of the present study is to evaluate the effects of the antifibrotic drug pirfenidone (PFD) on arrhythmogenic atrial remodeling in a canine CHF model.
We studied 15 canines, divided equally into 3 groups: control, CHF canines not treated with PFD, and CHF canines treated with PFD. CHF was induced by ventricular tachypacing (220 bpm for 3 weeks), and oral PFD was administered for the 3-week pacing period. We performed electrophysiology and AF vulnerability studies, atrial fibrosis measurements, and atrial cytokine expression studies. Only canines in the untreated CHF group developed sustained AF (>30 minutes, 4 of 5 canines; P<0.05). Treatment of CHF canines with PFD resulted in an attenuation of arrhythmogenic left atrial remodeling, with a significant reduction in left atrial conduction heterogeneity index (median 25% to 75% interquartile range 4.96 3.53 to 5.64 versus 2.52 2.11 to 2.82, P<0.01; pacing cycle length 300 ms), left atrial fibrosis (16.0% 13.0% to 17.5% versus 8.7% 5.7% to 10.6%, P<0.01), and AF duration (1800 1020 to 1800 seconds versus 6 5 to 22 seconds, P<0.01). Immunoblotting studies demonstrated the drug's effects on multiple cytokines, including a reduction in transforming growth factor-beta1 expression.
Treatment of CHF canines with PFD results in significantly reduced arrhythmogenic atrial remodeling and AF vulnerability. Pharmacological therapy targeted at the fibrotic substrate itself may play an important role in the management of AF.
Clinically, chronic atrial dilatation is associated with an increased incidence of atrial fibrillation (AF), but the underlying mechanism is not clear. We have investigated atrial electrophysiology ...and tissue structure in a canine model of chronic atrial dilatation due to mitral regurgitation (MR).
Thirteen control and 19 MR dogs (1 month after partial mitral valve avulsion) were studied. Dogs in the MR group were monitored using echocardiography and Holter recording. In open-chest follow-up experiments, electrode arrays were placed on the atria to investigate conduction patterns, effective refractory periods, and inducibility of AF. Alterations in tissue structure and ultrastructure were assessed in atrial tissue samples. At follow-up, left atrial length in MR dogs was 4.09+/-0.45 cm, compared with 3.25+/-0.28 at baseline (P<0.01), corresponding to a volume of 205+/-61% of baseline. At follow-up, no differences in atrial conduction pattern and conduction velocities were noted between control and MR dogs. Effective refractory periods were increased homogeneously throughout the left and right atrium. Sustained AF (>1 hour) was inducible in 10 of 19 MR dogs and none of 13 control dogs (P<0.01). In the dilated MR left atrium, areas of increased interstitial fibrosis and chronic inflammation were accompanied by increased glycogen ultrastructurally.
Chronic atrial dilatation in the absence of overt heart failure leads to an increased vulnerability to AF that is not based on a decrease in wavelength.
OBJECTIVE:Our objective was to investigate the extent of changes in maternal cardiovascular function, lipids and renal function during normal pregnancy from preconception to postpartum period.
...METHODS:In this prospective study of 54 normal pregnancies, detailed hemodynamics were performed preconception, at 6, 23 and 33 weeks during pregnancy and 16 weeks postpartum.
RESULTS:Although the greatest reduction of blood pressures (BPs) and augmentation index occurred in early pregnancy (Δbrachial systolic4 ± 7 mmHg, Δcentral systolic7 ± 7 mmHg; P < 0.001), the peripheral vascular resistance reached a nadir (Δ222 ± 215 dynes.s.cm; P < 0.001) by the second trimester. The greatest increase in cardiac output occurred by the second trimester (Δ0.6 ± 1 l/min, P < 0.001), whereas the heart rate increased maximally by the third trimester (Δ13 ± 11 bpm; P = 0.001). The unadjusted aortic pulse wave velocity decreased in the second trimester (P < 0.001), however, when adjusted for mean arterial pressure this was not significant (P = 0.06). BPs were lower (Δ brachial systolic5 ± 8 mmHg; P < 0.001) and augmentation index higher (Δ2.5 ± 7%; P = 0.01) postpartum than preconception. The cholesterol:high-density lipoprotein ratio, serum low density lipoprotein and serum creatinine all fell (P < 0.001) in the first trimester.
CONCLUSION:We have shown that normal pregnancy, irrespective of parity, is associated with significant changes commencing very early in pregnancy, continuing throughout pregnancy, and some of these changes persisted postpartum. Therefore, first trimester or postpartum baselines will underestimate the true extent of pregnancy-related changes. Prospective studies of cardiovascular function from preconception to postpartum will provide more reliable estimates of the influence of cardiovascular maladaptation during pregnancy complications and their effect on longer term cardiovascular function.
Three recent renal denervation studies in both drug-naïve and drug-treated hypertensive patients demonstrated a significant reduction of ambulatory blood pressure compared with respective sham ...control groups. Improved trial design, selection of relevant patient cohorts, and optimized interventional procedures have likely contributed to these positive findings. However, substantial variability in the blood pressure response to renal denervation can still be observed and remains a challenging and important problem. The International Sympathetic Nervous System Summit was convened to bring together experts in both experimental and clinical medicine to discuss the current evidence base, novel developments in our understanding of neural interplay, procedural aspects, monitoring of technical success, and others. Identification of relevant trends in the field and initiation of tailored and combined experimental and clinical research efforts will help to address remaining questions and provide much-needed evidence to guide clinical use of renal denervation for hypertension treatment and other potential indications.
The autonomic nervous system plays an important role in the genesis of atrial fibrillation and is one of the candidate targets for atrial fibrillation therapy. This review focuses on the role of the ...autonomic nervous system in atrial fibrillation development and discusses the results of the ganglionated plexi catheter and surgical ablation in preclinical and clinical studies. The heart is innervated by the extrinsic and intrinsic autonomic nervous systems. The intrinsic autonomic nervous system consists of multiple ganglionated plexi and axons, which innervate the neighboring atrial myocardium and control their electrophysiological properties. Abnormal autonomic innervation has been observed in an animal model of atrial fibrillation and in humans. Direct recordings of autonomic nerve activity in canine models showed that atrial tachyarrhythmia episodes were invariably preceded by intrinsic cardiac autonomic nerve activity, thus supporting the importance of intrinsic cardiac autonomic nerve activity as the triggers for atrial tachyarrhythmia. Targeting ganglionated plexi with catheter ablation improves the outcomes of paroxysmal atrial fibrillation ablation in addition to pulmonary vein antrum isolation. Ablation of ganglionated plexi alone without pulmonary vein isolation is also useful in controlling paroxysmal atrial fibrillation in some patients. However, surgical ganglionated plexi ablation in patients with a large left atrium, persistent atrial fibrillation, and/or a history of prior catheter ablation does not result in additional benefits. These different outcomes suggest that ganglionated plexi ablation is effective in managing patients with paroxysmal atrial fibrillation, but its effects in patients with persistent atrial fibrillation and advanced atrial diseases might be limited.
The COVID‐19 disease induces long term heart health complications and may induce autonomic nervous system dysfunction. Heart Rate Variability (HRV) is a measure of sympathetic (SNS) and ...parasympathetic (PNS) control of heart function. Recently, studies have shown that HRV analysis may be used as a predictor of COVID‐19 symptoms and correlates with progression of the disease. We aimed to uncover the interplay between SNS and PNS in hospitalized COVID‐19 patients at the time of admission and compare it with similar measurements in healthy patients (no comorbidities) and patients with cardiovascular disease. We hypothesized that COVID‐19 would induce autonomic dysfunction similar to patients with cardiovascular disease (CVD). ECG telemetry recordings of 30‐60 minutes in duration were acquired from patients that were admitted to Indiana University Health system hospitals for either COVID‐19 complications or for complications associated with cardiovascular disease (CVD) states (arrhythmia, heart failure, coronary artery disease). In addition, 20‐minute ECG Lead I recordings were obtained from healthy volunteers with no associated comorbidities. HRV parameters were calculated during sinus rhythm in the time, frequency, and nonlinear domains from the ECG telemetry recordings. The patient population was composed of 50 COVID‐19 patients (average age 63, range 26‐94), 32 healthy (average age 32.7, range 17‐69) and 49 patients with cardiovascular disease (average age 65.4, range 30‐88) as control groups. The COVID‐19 group had a higher percentage of patients with BMI>30 (obese) than the control groups (55% vs 36%). Also, the COVID‐19 and CVD patients had significantly higher heart rate and time‐domain HRV parameters (including SDRR, RMSSD, SDSD) and SD1 in the non‐linear domain when compared to healthy patients (88.8±53.0 and 87.9±55.2 vs 49.5±31.3, p<0.01). In the frequency domain, the LF/HF ratio was significantly lower in the COVID and CVD groups compared to healthy controls (0.5±0.76 and 0.55±0.50 vs 1.05±0.96, p<0.01). COVID‐19 patients have significant HRV alterations which suggest increased vagal tone than in healthy volunteers but similar to patients with severe cardiovascular disease comorbidities. Even though the COVID patients had an increased heart rate, the results of the HRV analysis indicate increased vagal tone which would support autonomic nervous system dysfunction in these patients.
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