Bioinformation Analysis of Differential Expression Proteins in Different Processes of COVID-19.

COVID-19 is a highly infectious respiratory disease whose progression has been associated with multiple factors. From SARS-CoV-2 infection to death, biomarkers capable of predicting different disease processes are needed to help us further understand the molecular progression of COVID-19 disease. The aim is to find differentially expressed proteins that are associated with the progression of COVID-19 disease or can be potential biomarkers, and to provide a reference for further understanding of the molecular mechanisms of COVID-19 occurrence, progression, and treatment. Data-independent Acquisition (DIA) proteomics to obtain sample protein expression data, using R language screening differentially expressed proteins. Gene Ontology and Kyoto Encyclopedia for Genes and Genomes analysis was performed on differential proteins and protein-protein interaction (PPI) network was constructed to screen key proteins. A total of 47 differentially expressed proteins were obtained from COVID-19 incubation patients and healthy population (L/H), mainly enriched in platelet-related functions, and complement and coagulation cascade reaction pathways, such as platelet degranulation and platelet aggregation. A total of 42 differential proteins were obtained in clinical and latent phase patients (C/L), also mainly enriched in platelet-related functions and in complement and coagulation cascade reactions, platelet activation pathways. A total of 10 differential proteins were screened in recovery and clinical phase patients (R/C), mostly immune-related proteins. The differentially expressed proteins in different stages of COVID-19 are mostly closely associated with coagulation, and key differential proteins, such as FGA, FGB, FGG, ACTB, PFN1, VCL, SERPZNCL, APOC3, LTF, and DEFA1, have the potential to be used as early diagnostic markers.

Trends in the 30-year span of noninfectious cardiovascular implantable electronic device complications in Olmsted County.

Background: Cardiac implantable electronic devices (CIEDs), such as permanent pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy devices, alleviate morbidity and mortality in various diseases. There is a paucity of real-world data on CIED complications and trends. Objectives: We sought to describe trends in noninfectious CIED complications over the past 3 decades in Olmsted County. Methods: The Rochester Epidemiology Project is a medical records linkage system comprising records of over 500,000 residents of Olmsted County from 1966 to present. CIED implantations between 1988 and 2018 were determined. Trends in noninfectious complications within 30 days of implantation were analyzed. Results: A total of 157 (6.2%) of 2536 patients who received CIED experienced device complications. A total of 2.7% of the implants had major complications requiring intervention. Lead dislodgement was the most common (2.8%), followed by hematoma (1.7%). Complications went up from 1988 to 2005, and then showed a downtrend until 2018, driven by a decline in hematomas in the last decade (P < .01). Those with complications were more likely to have prosthetic valves. Obesity appeared to have a protective effect in a multivariate regression model. The mean Charlson comorbidity index has trended up over the 30 years. Conclusion: Our study describes a real-world trend of CIED complications over 3 decades. Lead dislodgements and hematomas were the most common complications. Complications have declined over the last decade due to safer practices and a better understanding of anticoagulant management.

Carotid Baroreceptor Stimulation Improves Pulmonary Arterial Remodeling and Right Ventricular Dysfunction in Pulmonary Arterial Hypertension.

Autonomic nervous system imbalance is intricately associated with the severity and prognosis of pulmonary arterial hypertension (PAH). Carotid baroreceptor stimulation (CBS) is a nonpharmaceutical intervention for autonomic neuromodulation. The effects of CBS on monocrotaline-induced PAH were investigated in this study, and its underlying mechanisms were elucidated. The results indicated that CBS improved pulmonary hemodynamic status and alleviated right ventricular dysfunction, improving pulmonary arterial remodeling and right ventricular remodeling, thus enhancing the survival rate of monocrotaline-induced PAH rats. The beneficial effects of CBS treatment on PAH might be mediated through the inhibition of sympathetic overactivation and inflammatory immune signaling pathways.

Risk Factors and Clinical Characterization of Cardiovascularand Cerebrovascular Events in Elderly Hemodialysis Patients.

INTRODUCTION: The purpose of this study was to assess the risk factors and clinical characteristics of cardiovascular and cerebrovascular events in elderly hemodialysis patients. METHODS: Elderly patients undergoing hemodialysis (HD) at Deqing County People's Hospital in Zhejiang, China, from May 2020 to May 2023 were enrolled in this study. They were divided into two groups depending on the occurrence of cardiovascular or cerebrovascular events: the case group and the control group. RESULTS: A total of 106 patients were enrolled in this study. Among them, 49 patients experienced cardiovascular or cerebrovascular events, resulting in an incidence rate of 46.23%. According to whether cardiovascular or cerebrovascular events occurred, 57 patients were assigned to the control group, and 49 patients were assigned to the case group. Comparing the basic information and clinical indicators of the two groups, significant differences were observed in patients with hypertensive nephropathy and diabetic nephropathy (P < .05). There were also significant differences in dialysis duration, smoking history, systolic and diastolic blood pressures, uric acid, blood glucose, total cholesterol (TC), lowdensity lipoprotein cholesterol (TG), C-reactive protein (CRP), and PTH (parathyroid hormone) levels and platelet-to-lymphocyte ratio (PLR), between the two groups (P < .05). Multivariate logistic regression analysis revealed that longer dialysis duration, higher systolic and diastolic blood pressures, elevated uric acid, TC, TG, LDL-C, PTH, and blood glucose levels, smoking history, elevated PLR, and CRP were independent risk factors for cardiovascular and cerebrovascular events. The ROC curve showed that these risk factors predicted cardiovascular and cerebrovascular events in patients. CONCLUSION: Patients with underlying diseases such as hypertensive or diabetic nephropathy are more likely to experience cardiovascular and cerebrovascular events. Longer dialysis duration, higher systolic and diastolic blood pressures, elevated uric acid, TC, TG, LDL-C, PTH and blood glucose levels, and boosted inflammatory reaction are risk factors for these events among elderly HD patients. The purpose of this study is to provide practical guidelines for clinical treatment. Comprehensive measures such as active intervention of risk factors, rational drug use and regular examination should be taken to improve the overall health level to the greatest extent for elderly patients with high-risk HD. DOI: 10.52547/ijkd.7877.

Trends in the 30-year span of Noninfectious Cardiovascular Implantable Electronic Device Complications in Olmsted County.

Background: Cardiovascular implantable electronic devices (CIEDs) such as permanent pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy devices alleviate morbidity and mortality in various diseases. There is a paucity of real-world data on CIED complications and trends. Objectives: Describe trends in noninfectious CIED complications over the past three decades in Olmsted County. Methods: The Rochester Epidemiology Project is a medical records linkage system comprising records of over 500,000 residents of Olmsted County from 1966-current. CIED implants between 1988-2018 were determined. Trends in noninfectious complications within 30 days of implant were analyzed. Results: 175 out of 2536 (6.9%) patients who received CIED experienced device complications. 3.8% of the implants had major complications requiring intervention. Lead dislodgement was the most common (2.9%), followed by hematoma (2.1%). Complications went up from 1988 to 2005, then showed a downtrend until 2018, driven by a decline in hematomas in the last decade (p<0.01). Those with complications were more likely to have prosthetic valves. Obesity appeared to have a protective effect in a multivariate regression model. The mean Charlson comorbidity score has trended up over the 30 years. Conclusions: Our study describes a real-world trend of CIED complications over three decades. Lead dislodgements and hematomas were the most common complications. Complications have declined over the last decade due to safer practices and a better understanding of anticoagulant management.

Carotid baroreceptor stimulation prevents oxidative stress by inhibiting MAO-A and prevents cardiac remodeling in obese rats.

OBJECTIVE: Sympathetic nervous system overactivation and abnormal lipid metabolism are featured in obesity and may lead to cardiac remodeling. The effects of carotid baroreceptor stimulation (CBS) on cardiac remodeling in obese rats and the underlying mechanisms were explored. METHODS: An obesity model was induced by 16-week high-fat diet feeding. A CBS device was implanted at the 8th week. Body weight and blood pressure measurements, electrocardiography, echocardiography, and glucose and insulin tolerance tests were conducted before sampling. Plasma analysis and histological and biological analyses of left ventricle were also performed. Neonatal rat cardiomyocytes cocultured with 3T3-L1 in transwell chambers were used to investigate the mechanisms. RESULTS: CBS alleviated several manifestations of obesity, including increased body weight, high blood pressure, hyperlipidemia, and enhanced sympathetic activity. In obese hearts, norepinephrine levels decreased, and the monoamine oxidase A (MAO-A) and reactive oxygen species level increased; these changes, as well as cardiac fibrosis, lipid metabolic disorders, and heart dysfunction, were inhibited by CBS. Neonatal rat cardiomyocytes incubated with norepinephrine showed MAO-A upregulation, increased reactive oxygen species levels, lipid metabolic disorders, and inflammatory response, which were inhibited by clorgyline, a selective MAO-A inhibitor. CONCLUSIONS: CBS effectively suppresses sympathetic nervous system activity and oxidative stress mediated by MAO-A and prevents cardiac remodeling in obese rats.

Trends in Cardiovascular Implantable Electronic Device Insertion Between 1988 and 2018 in Olmsted County.

OBJECTIVES: This study sought to describe trends in cardiovascular implantable electronic device (CIED) insertion over the past 3 decades in Olmsted County. BACKGROUND: Trends in CIED insertion in the United States have not been extensively studied. METHODS: The Rochester Epidemiology Project is a medical records linkage system comprising the records of all residents of Olmsted County from 1966 to the present. CIED insertion between 1988 and 2018 was determined using International Classification of Diseases-Ninth Revision, International Classification of Diseases-10th Revision, and Current Procedural Terminology codes. Age- and sex-adjusted incidence rates, adjusted to the 2010 US White population, were calculated. Trends in incidence over time, across age groups, and between sex are estimated using Poisson regression models. RESULTS: The age- and sex-adjusted incidence of device implants for the study period were as follows: overall CIED: 82.4 (95% CI: 79.2-85.6); permanent pacemaker (PPM): 62.9 (95% CI: 60.0-65.7); implantable cardioverter-defibrillator (ICD): 14.0 (95% CI: 12.6-15.3); and cardiac resynchronization therapy (CRT): 5.6 (95% CI: 4.7-6.4) per 100,000 per year. The overall incidence of CIED insertion increased between 1988 to 1993 and 2000 to 2005 and then decreased between 2000 to 2005 and 2012 to 218 (P < 0.0001). PPM and ICD insertion incidence followed these trends, whereas the incidence of CRT insertion increased between 2000 to 2005 and 2012 to 2018. CIED insertion incidence increased with age (P < 0.0001). CIED insertion incidence was greater in men (116.3 vs 57.3 per 100,000 per year in men vs women; P < 0.0001). The overall survival of CRT recipients improved (P = 0.0044). CONCLUSIONS: The incidence values for PPM and ICD implants are decreasing, while the incidence of CRT implants is increasing. CIEDs are increasingly inserted in the elderly, men, and patients with higher comorbidities.

Using ensemble of ensemble machine learning methods to predict outcomes of cardiac resynchronization.

INTRODUCTION: The efficacy of cardiac resynchronization therapy (CRT) has been widely studied in the medical literature; however, about 30% of candidates fail to respond to this treatment strategy. Smart computational approaches based on clinical data can help expose hidden patterns useful for identifying CRT responders. METHODS: We retrospectively analyzed the electronic health records of 1664 patients who underwent CRT procedures from January 1, 2002 to December 31, 2017. An ensemble of ensemble (EoE) machine learning (ML) system composed of a supervised and an unsupervised ML layers was developed to generate a prediction model for CRT response. RESULTS: We compared the performance of EoE against traditional ML methods and the state-of-the-art convolutional neural network (CNN) model trained on raw electrocardiographic (ECG) waveforms. We observed that the models exhibited improvement in performance as more features were incrementally used for training. Using the most comprehensive set of predictors, the performance of the EoE model in terms of the area under the receiver operating characteristic curve and F1-score were 0.76 and 0.73, respectively. Direct application of the CNN model on the raw ECG waveforms did not generate promising results. CONCLUSION: The proposed CRT risk calculator effectively discriminates which heart failure (HF) patient is likely to respond to CRT significantly better than using clinical guidelines and traditional ML methods, thus suggesting that the tool can enhanced care management of HF patients by helping to identify high-risk patients.

Effects of carotid baroreceptor stimulation on aortic remodeling in obese rats.

BACKGROUND AND AIM: Our previous study found carotid baroreceptor stimulation (CBS) reduces body weight and white adipose tissue (WAT) weight, restores abnormal secretion of adipocytokines and inflammation factors, decreases systolic blood pressure (SBP) by inhibiting activation of sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in obese rats. In this study, we explore effects of CBS on aortic remodeling in obese rats. METHODS AND RESULTS: Rats were fed high-fat diet (HFD) for 16 weeks to induce obesity and underwent either CBS device implantation and stimulation or sham operation at 8 weeks. BP and body weight were measured weekly. RAS activity of WAT, histological, biochemical and functional profiles of aortas were detected after 16 weeks. CBS effectively decreased BP in obese rats, downregulated mRNA expression of angiotensinogen (AGT) and renin in WAT, concentrations of AGT, renin, angiotensin II (Ang II), protein levels of Ang II receptor 1 (AT1R) and Ang II receptor 2 (AT2R) in WAT were declined. CBS inhibited reactive oxygen species (ROS) generation, inflammatory response and endoplasmic reticulum (ER) stress in aortas of obese rats, restrained vascular wall thickening and vascular smooth muscle cells (VSMCs) phenotypic switching, increased nitric oxide (NO) synthesis, promoted endothelium-dependent vasodilatation by decreasing protein expression of AT1R and leptin receptor (LepR), increasing protein expression of adiponectin receptor 1 (AdipoR1) in aortic VSMCs. CONCLUSION: CBS reduced BP and reversed aortic remodeling in obese rats, the underlying mechanism might be related to the suppressed SNS activity, restored adipocytokine secretion and restrained RAS activity of WAT.

Simultaneous noninvasive recording of electrocardiogram and skin sympathetic nerve activity (neuECG).

neuECG, the simultaneous noninvasive recording of ECG and skin sympathetic nerve activity (SKNA), directly records sympathetic nerve activity over a long period of time. It can be used to measure sympathetic tone in healthy subjects and in subjects with non-cardiovascular diseases. The electrical activity that can be measured on the surface of the skin originates from the heart, the muscle or nerve structures. Because the frequency content of nerve activity falls in a higher frequency range than that of the ECG and myopotential, it is possible to use high-pass or band-pass filtering to specifically isolate the SKNA. neuECG is voltage calibrated and does not require invasive procedures to impale electrodes in nerves and thus has advantages over microneurography. Here, we present a protocol that takes <10 min to set up. The neuECG can be continuously recorded over a 24-h period or longer. We also describe methods to efficiently analyze neuECG from humans using commercially available hardware and software to facilitate adoption of this technology in clinical research.

Night-Time Premature Ventricular Complex Positively Correlates With Cardiac Sympathetic Activity in Patients Undergoing Radiofrequency Catheter Ablation.

BACKGROUND: Patients with premature ventricular complexes (PVCs) usually experience accompanying alterations of the autonomic nerve system. The timing of PVC occurrence is associated with different circadian rhythms, which may be related to the autonomic nerve imbalance. The relationship between night-time PVC and cardiac autonomic nervous activity is still obscure. Our study aimed to investigate the relationship between the number of night-time PVCs and cardiac autonomic nervous activity. METHOD: We enrolled 72 patients with frequent PVCs and 27 without PVCs. The patients with PVCs were divided into two groups based on the number of night-time PVCs (i.e., PVCs occurring between 10 pm and 6 am/24-hr total PVCs; group 1: n=34, <30%; group 2: n=38, >30%). At baseline, 12-lead electrocardiogram and 24-hour Holter recording were performed. When the number of PVCs declined significantly after radiofrequency catheter ablation, Holter monitoring was performed again. Heart rate (HR) variability, mean 24-hour HR, mean daytime HR, and mean night-time HR were analysed. RESULTS: With a greater number of night-time PVCs, group 2 had a lower standard deviation of all NN intervals (SDNN; 116.5±38.3 vs 135.3±37.8 ms; p=0.035) and increased mean 24-hour HR (77.3±9.2 vs 73.4±7.5 beats per min; p=0.05) than group 1. The SDNN was negatively correlated with the number of night-time PVCs and mean night-time HR (r= -3.04 and r= -0.504, respectively; p=0.009 and p=<0.001, respectively), and night-time PVC proportion was positively correlated with the ratio of low-frequency power (LF)/high-frequency power (HF; r=0.319 [p=0.013]). Multivariate linear regression analysis showed that the number of night-time PVCs was an independent predictor of decreased SDNN (ß= -0.446, p=0.030) and increased LF/HF ratio (ß=0.027, p=0.038). After PVCs disappeared, SDNN increased significantly and the frequency domain of the square root of the mean of the sum of the squares of differences between adjacent NN intervals, NN50 count divided by the total number of all NN intervals, the time domain of natural logarithm of HF, natural logarithm of LF, and mean 24-hour HR were significantly decreased in the two PVC groups. CONCLUSIONS: An increased number of night-time PVCs was accompanied by enhanced cardiac sympathetic activity. After PVCs diminished, both cardiac parasympathetic and sympathetic nervous activity declined.

Trends of Cardiovascular Implantable Electronic Device Infection in 3 Decades: A Population-Based Study.

OBJECTIVES: This study assessed trends in the incidence of cardiovascular implantable electronic device (CIED) infection in the last 3 decades using a population-based records linkage study. BACKGROUND: Infection remains an important issue associated with increased implantation rate and dwell time of CIEDs. METHODS: We identified a cohort of all adults with CIEDs who resided in Olmsted County, Minnesota, from 1988 to 2015, using the medical linkage system of the Rochester Epidemiology Project. Standardized criteria were used to identify all CIED infection cases. The cumulative rate of CIED infection was estimated using the Kaplan-Meier method, and the trends of CIED infection incidence were calculated with person-years of follow-up after device implantation. RESULTS: The cumulative probabilities of overall CIED infection were 6.2% (95% confidence interval [CI]: 4.0% to 8.4%) at 15 years and 11.7% (95% CI: 6.8% to 17.3%) at 25 years of follow-up. The incidence of CIED infection every 7 years from 1988 to 2015 was 1.3, 5.7, 4.1, and 4.7 per 1,000-person years, respectively. The 15-year cumulative probabilities of CIED infection after the initial, second, and third procedures were 2.6% (95% CI: 1.4% to 3.8%), 2.7% (95% CI: 1.2% to 4.2%), and 24.1% (95% CI: 3.8% to 44.4%), respectively. Generator changes (hazard ratio [HR]: 3.91; 95% CI: 1.47 to 10.37; p = 0.006) and upgrades (HR: 3.08; 95% CI: 1.24 to 7.62; p = 0.02) were significantly associated with infection. CONCLUSIONS: The incidence of CIED infection had a trend of increasing in the past 2 decades. Contemporary implantable cardioverter-defibrillator and cardiac resynchronization therapies and repeated manipulation of device pockets introduced a greater risk of CIED infection.

Carotid baroreceptor stimulation suppresses ventricular fibrillation in canines with chronic heart failure.

Carotid baroreceptor stimulation (CBS) has been shown to improve cardiac dysfunction and pathological structure remodelling. This study aimed to investigate the effects of CBS on the ventricular electrophysiological properties in canines with chronic heart failure (CHF). Thirty-eight beagles were randomized into control (CON), CHF, low-level CBS (LL-CBS), and moderate-level CBS (ML-CBS) groups. The CHF model was established with 6 weeks of rapid right ventricular pacing (RVP), and concomitant LL-CBS and ML-CBS were applied in the LL-CBS and ML-CBS groups, respectively. After 6 weeks of RVP, ventricular electrophysiological parameters and left stellate ganglion (LSG) neural activity and function were measured. Autonomic neural remodelling in the LSG and left ventricle (LV) and ionic remodelling in the LV were detected. Compared with the CHF group, both LL-CBS and ML-CBS decreased spatial dispersion of action potential duration (APD), suppressed APD alternans, reduced ventricular fibrillation (VF) inducibility, and inhibited enhanced LSG neural discharge and function. Only ML-CBS significantly inhibited ventricular repolarization prolongation and increased the VF threshold. Moreover, ML-CBS inhibited the increase in growth-associated protein-43 and tyrosine hydroxylase-positive nerve fibre densities in LV, increased acetylcholinesterase protein expression in LSG, and decreased nerve growth factor protein expression in LSG and LV. Chronic RVP resulted in a remarkable reduction in protein expression encoding both potassium and L-type calcium currents; these changes were partly amended by ML-CBS and LL-CBS. In conclusion, CBS suppresses VF in CHF canines, potentially by modulating autonomic nerve and ion channels. In addition, the effects of ML-CBS on ventricular electrophysiological properties, autonomic remodelling, and ionic remodelling were superior to those of LL-CBS.

Electrophysiologic effects and outcomes of sympatholysis in patients with recurrent ventricular arrhythmia and structural heart disease.

INTRODUCTION: Autonomic modulation has been used as a therapy to control recurrent ventricular arrhythmia (VA). This study was to explore stellate ganglion block (SGB) effect on cardiac electrophysiologic properties and evaluate the long-term outcome of cardiac sympathetic denervation (CSD) for patients with recurrent VA and structural heart disease (SHD). MATERIALS AND METHODS: Patients who had recurrent VA due to SHD were enrolled prospectively. Electrophysiologic study and ventricular tachycardia (VT) induction were performed before and after left and right SGB. VA burden and long-term outcomes were assessed for a separate patient group who underwent left or bilateral CSD for drug-refractory VA due to SHD. RESULTS: Electrophysiologic study of nine patients showed that baseline mean (SD) corrected sinus node recovery time (cSNRT) increased from 320.4 (73.3) ms to 402.9 (114.2) ms after left and 482.4 (95.7) ms after bilateral SGB (P = .03). SGB did not significantly change P-R, QRS, and Q-T intervals and ventricular effective refractory period, nor did the inducibility of VA. Nineteen patients underwent left (n = 14) or bilateral (n = 5) CSD. CSD reduced VA burden and appropriate ICD therapies from a median (interquartile range) of 2.5 (0.4-11.6) episodes weekly to 0.1 (0.0-2.4) episodes weekly at 6-month follow-up (P = .002). Three-year freedom from orthotopic heart transplant (OHT) and death was 52.6%. New York Heart Association functional class III/IV and VT rate less than 160 beats per minute were predictors of recurrent VA, OHT, and death. CONCLUSION: SGB increased cSNRT without changing heart rate. CSD was more beneficial for patients with mild-to-moderate heart failure and faster VA.

Characterization of skin sympathetic nerve activity in patients with cardiomyopathy and ventricular arrhythmia.

BACKGROUND: Heightened sympathetic nerve activity is associated with occurrence of ventricular arrhythmia (VA). OBJECTIVE: To investigate the association of skin sympathetic nerve activity (SKNA) and VA occurrence. METHODS: We prospectively enrolled 65 patients with severe cardiomyopathy. Of these, 39 had recent sustained VA episodes (VA-1 group), 11 had intractable VA undergoing sedation with general anesthesia (VA-2 group), and 15 had no known history of VA (VA-Ctrl group). All patients had simultaneous SKNA and electrocardiogram recording. SKNA was assessed using an average value (aSKNA), a variable value (vSKNA), and the number of bursts of SKNA (bSKNA). RESULTS: The VA-1 group had higher aSKNA and vSKNA compared with the VA-Ctrl group (aSKNA: 1.41 ± 0.53 µV vs 0.98 ± 0.41 µV, P = .003; vSKNA: 0.52 ± 0.22 µV vs 0.30 ± 0.16 µV, P < .001) and the VA-2 group (aSKNA: 0.83 ± 0.22 µV, P < .001; vSKNA: 0.23 ± 0.11 µV; P < .001). Although the VA-2 group had more VA episodes than the VA-1 group (median, 5 vs 2; P = .01), their SKNA was the lowest among the 3 groups. Multivariate Cox regression analysis showed that a higher aSKNA at baseline was an independent predictor of lower VA recurrence rate during a 417 ± 279-day follow-up (hazard ratio, 0.325; 95% confidence interval [CI], 0.119-0.883; P = .03). A >15% reduction in aSKNA after therapy was associated with a lower subsequent VA event rate (hazard ratio, 0.222; 95% CI, 0.057-0.864; P = .03). CONCLUSION: Patients with VA had increased SKNA as compared with control. Both SKNA and sustained VA could be suppressed by general anesthesia. The aSKNA at baseline was an independent predictor of VA recurrence.

Carotid baroreceptor stimulation in obese rats affects white and brown adipose tissues differently in metabolic protection.

The sympathetic nervous system (SNS) regulates the functions of white adipose tissue (WAT) and brown adipose tissue (BAT) tightly. Carotid baroreceptor stimulation (CBS) efficiently inhibits SNS activation. We hypothesized that CBS would protect against obesity. We administered CBS to obese rats and measured sympathetic and AMP-activated protein kinase (AMPK)/ PPAR pathway responses as well as changes in perirenal WAT (PWAT), epididymal WAT (EWAT), and interscapular BAT (IBAT). CBS alleviated obesity-related metabolic changes, improving insulin resistance; reducing adipocyte hypertrophy, body weight, and adipose tissue weights; and decreasing norepinephrine but increasing acetylcholine in plasma, PWAT, EWAT, and IBAT. CBS also downregulated fatty acid translocase (CD36), fatty acid transport protein (FATP), phosphorylated and total hormone sensitive lipase, phosphorylated and total protein kinase A, and PPARγ in obese rats. Simultaneously, CBS upregulated phosphorylated adipose triglyceride lipase, phosphorylated and total AMPK, and PPARα in PWAT, EWAT, and IBAT. However, BAT and WAT responses differed; although many responses were more sensitive in IBAT, responses of CD36, FATP, and PPARγ were more sensitive in PWAT and EWAT. Overall, CBS decreased chronically activated SNS and ameliorated obesity-related metabolic disorders by regulating the AMPK/PPARα/γ pathway.

Comparative outcomes of subcutaneous and transvenous cardioverter-defibrillators.

BACKGROUND: The comparative outcomes of subcutaneous implantable cardioverter-defibrillator (S-ICD) and transvenous ICD (T-ICD) have not been well studied. The aim of this study was to evaluate the safety and efficacy of currently available S-ICD and T-ICD. METHODS: The study included 86 patients who received an S-ICD and 1:1 matched to those who received single-chamber T-ICD by gender, age, diagnosis, left ventricular ejection fraction (LVEF), and implant year. The clinical outcomes and implant complications were compared between the two groups. RESULTS: The mean age of the 172 patients was 45 years, and 129 (75%) were male. The most common cardiac condition was hypertrophic cardiomyopathy (HCM, 37.8%). The mean LVEF was 50%. At a mean follow-up of 23 months, the appropriate and inappropriate ICD therapy rate were 1.2% vs. 4.7% (χ = 1.854, P = 0.368) and 9.3% vs. 3.5% (χ = 2.428, P = 0.211) in S-ICD and T-ICD groups respectively. There were no significant differences in device-related major and minor complications between the two groups (7.0% vs. 3.5%, χ = 1.055, P = 0.496). The S-ICD group had higher T-wave oversensing than T-ICD group (9.3% vs. 0%, χ = 8.390, P = 0.007). Sixty-five patients had HCM (32 in S-ICD and 33 in T-ICD). The incidence of major complications was not significantly different between the two groups. CONCLUSIONS: The efficacy of an S-ICD is comparable to that of T-ICD, especially in a dominantly HCM patient population. The S-ICD is associated with fewer major complications demanding reoperation.

Carotid baroreceptor stimulation improves cardiac performance and reverses ventricular remodelling in canines with pacing-induced heart failure.

AIMS: Carotid baroreceptor stimulation (CBS) has potential protective effects on chronic heart failure (CHF). The aim of our study was to investigate the effects of CBS on more detailed aspects of ventricular remodelling and the underlying mechanisms in a CHF canine model. MAIN METHODS: Twenty-four beagles were randomised into Con (n = 8), CHF (n = 8), and CHF-CBS (n = 8) groups. The CHF and CHF-CBS groups underwent 6 weeks of rapid ventricular pacing (RVP) at 250 beats per minute to establish a CHF model. Concomitant CBS was delivered together with RVP in the CHF-CBS group. KEY FINDINGS: RVP for 6 weeks caused typical heart failure in the CHF group. CBS significantly reversed the decrease in the high-frequency heart rate variability component and increase in low-frequency/high-frequency ratio induced by RVP. CBS significantly reduced cardiac dilation, improved left ventricle ejection fraction, and inhibited the increase in natriuretic peptide mRNA expression of LV tissue. CBS alleviated collagen volume fraction and reduced protein expression of transforming growth factor ß1, matrix metallopeptidase 2, and matrix metallopeptidase 9, as well as decreased the percentage of TUNEL-positive nuclei and protein expression of Caspase-3 in LV tissue. The intracellular PKA signalling pathway and cardiac inflammation of LV tissue were upregulated in the CHF group, and markedly inhibited by CBS. SIGNIFICANCE: Our study found that CBS improved cardiac performance and reversed ventricular remodelling in CHF canines by rebalancing the autonomic nervous system; the suppression of the intracellular PKA signalling pathway and cardiac inflammation might underly the mechanisms.

Lead extraction for reduction of chronic pain related to cardiovascular implantable electronic device.

AIMS: Chronic pain at the cardiovascular implantable electronic device (CIED) generator or lead insertion site that is not otherwise manageable carries a IIA indication for extraction. However, limited data exist evaluating causes of pain and outcomes of extraction in eliminating pain. A multi-centre retrospective observational study was conducted to evaluate outcomes of patients undergoing device extraction for treatment of chronic device pain. METHODS AND RESULTS: Twenty-seven out of 2188 lead extraction candidates (1.3%) met the chronic pain IIA indication for extraction [50 ± 16 years; 14 (51%) women]. Onset, severity, triggers, and pain management were measured before and after extraction. Device type, procedure done (with/without reimplantation), and positive tissue cultures were noted. Pain was reported as constant (n = 14; 50%), intermittent (n = 13; 46%), and movement-triggered (n = 14; 50%). Average severity of pain was seven out of 10 (10 being the worst). Post-extraction, 18 (66%) received freedom from pain, including all patients with poorly formed pockets (n = 2) and subclinical infections (n = 2). Of the 18, 11 underwent reimplantation (61%) without recurrent pain. Nine still had pain (44 ± 17 years; seven women) after extraction. Eight of the nine underwent reimplantation, three on the contralateral chest wall and five ipsilaterally. Pain severity decreased (n = 5), increased (n = 1), or was unchanged (n = 3). CONCLUSION: Chronic pain at the CIED generator site can present as chronic or movement-triggered pain, and can be due to subclinical infection or a poorly formed device pocket. Extraction relieved constant and intermittent pain in two-thirds of patients. Extraction appears less successful in eliminating pain in women who undergo subsequent reimplantation.

Real-world experience with leadless cardiac pacing.

BACKGROUND: Leadless cardiac pacing (LCP) has emerged as a new modality for permanent pacing. We sought to describe comparative outcomes between LCP and transvenous pacemakers. METHODS: Patients receiving LCP (Micra [Medtronic, Minneapolis, MN, USA] and Nanostim [St. Jude Medical/Abbott Laboratories, Chicago, IL, USA]) between 2014 and 2017 at the Mayo Clinic Heart Rhythm Enterprise practice (Rochester, MN, USA; Jacksonville, FL, USA; and Scottsdale, AZ, USA) were identified. We identified 1:1 age- and sex-matched controls receiving single-chamber transvenous ventricular pacemakers (TVP). Statistical analyses were performed with JMP 13.0.0 (SAS, Institute Cary, NC, USA). RESULTS: Ninety patients underwent LCP implantation (73 Micra and 17 Nanostim) with a median follow-up duration of 62 (interquartile range 28-169) days. Both groups had 100% successful device implant rates. There were no differences in procedure-related major (0% vs 1%) or minor complications (8% vs 3%) in the LCP versus TVP groups (P > 0.05). Excluding Nanostim patients, there was a lower rate of device-related revision or extraction in the Micra versus TVP groups (0% vs 5%, P = 0.028). Device endocarditis was more common in the TVP group (0% vs 3%, P = 0.04). Estimated longevity was greater for the LCP group (median 12.0 vs 10.0 years, P < 0.0001). An increase in severity of tricuspid valve regurgitation (TR) by ≥2 grades occurred in none of the LCP patients, and in 19% of the TVP patients (P = 0.017). CONCLUSION: There are no significant differences in procedural complications among patients receiving LCP versus TVP. The Micra group had lower rates of device-related revision/extraction compared to the TVP group. Patients with leadless pacemaker were less likely to develop endocarditis or worsening TR.