HF Etiology and cardiac contractility modulation therapy.

OBJECTIVES: Our study aimed to assess the safety and efficacy of cardiac contractility modulation (CCM) therapy in patients with heart failure with reduced ejection fraction (HFrEF) depending on HF etiology. METHODS: We enrolled 166 patients with optimal medical therapy-resistant HFrEF (median age 59 years, 83.7% males, median NYHA class - 2, median left ventricular ejection fraction (LVEF) - 29.0%) who underwent CCM therapy device implantation from 2013 to 2019 in four medical centers in Russia. The HF etiology was determined based on invasive coronary angiography or cardiac MRI data. Transthoracic echocardiography (TTE), 6-minute walking test (6MWT), and NTproBNP-tests were performed at a baseline and 12 months after the implantation. RESULTS: The ischemic etiology of HF was revealed in 100 patients (61.5%) (ICM group); the non-ischemic group (NICM) evolved 66 patients (38.5%). Patients in the ICM group were significantly older (61[57-69] vs. 55 [42.8-61], p < 0.001), more frequently had hypertension (79% vs. 42.4%, p < 0.001) and chronic kidney disease (43% vs. 22.7%, p = 0.012). Patients in the NICM group had significantly more often atrial fibrillation (AF) (58% vs. 74%, p = 0.048), larger end-diastolic volume (EDV) (249 [208-309] vs. 220 [192-271], p = 0.019) and end-systolic volume (ESV) (183 [147-230] vs. 154 [128-199], p = 0.003). There were no significant differences in mortality between ICM and NICM groups (14.4 vs. 10.8%, p = 0.51). In 12 months, there was a significant increase in LVEF in the NICM group (+ 2.0 [2-6] vs. +7.7 [2-12], p < 0.001), while the improvement in the 6MWT (+ 75 [22-108] vs. +80 [10-160], p = 0.851) and NYHA class did not reach the level of significance. The subanalysis between patients with improved NYHA class and those without improvement revealed that patients without improvement more frequently had AF (56% vs. 89%; p < 0.01), chronic obstructive lung disease (18% vs. 35% p = 0.047), higher blood pressure (110 [105-120] vs. 120[110-129]; p = 0.032). CONCLUSION: In this multicenter retrospective study, patients with non-ischemic HFrEF showed a significantly higher improvement in LVEF and LV reverse remodeling following CCM therapy device implantation. There was no significant association between HF etiology and survival in drug-resistant HFrEF patients following CCM therapy.

Progression of obstructive sleep apnoea after renal denervation is not associated with hypertension exaggeration.

PURPOSE: In a cohort, observational prospective trial, we assessed the long-term dynamics of sleep-disordered breathing in patients with resistant hypertension after renal denervation and their association with blood pressure change at remote follow-up. MATERIALS AND METHODS: Twenty-eight patients with stable hypertension who were recruited for endovascular radiofrequency renal denervation in 2012-2019 and had valid both baseline and follow-up sleep study, were included in the analysis. All patients underwent physical examination, anthropometry, office and ambulatory blood pressure measurements, blood and urine tests, kidney visualization, and full polysomnography before and within 12-36 months after renal denervation. RESULTS: The average follow-up comprised 30.1 ± 8.4 months. At long-term follow-up, no significant changes in creatinine level, estimated glomerular filtration rate, body mass index were registered. There was a significant increase in sleep apnea severity indices: the mean change in apnea-hypopnea index comprised 9.0(-21.1;25.2) episodes/h, in oxygen desaturation index 6.5(-16.8;35.9) episodes/h, in the average SpO2 -1.7(-5.6;1.9)%. Over 12-month follow-up, there were no significant differences in blood pressure response in patients with and without sleep apnea. The baseline apnea-hypopnea and oxygen desaturation indices and the mean SpO2 were associated with the circadian blood pressure profile at follow-up, but did not correlate with the blood pressure response. CONCLUSIONS: Although the severity of sleep apnea worsens at > 12 months follow-up after renal denervation, this is not associated with hypertension exaggeration.

Reprocessing of electrophysiology material in EHRA countries: an EHRA Young EP survey.

Data on reprocessing of electrophysiology (EP) materials are sparse. Reprocessing of catheters and other materials in daily routine varies through countries and may depend on specific material characteristics, supplier, or federal law. The aim of this study was to collect data on reprocessing usage through EHRA countries. An online survey consisting of 27 questions was distributed to EHRA Young EP members and members of national EP working groups. Two hundred and two participants from 34 EHRA countries completed the survey. One hundred and seven respondents (53.0%) reported having used and using reprocessed EP material, 30 (14.9%) respondents have used reprocessed EP material in the past but not at the time of the survey, 65 (32.2%) had never used reprocessed EP material. The most reprocessed EP materials include cables (70%), diagnostic EP catheters with deflectable (64%) or fixed curve (63%), non-irrigated ablation catheters (51%), and other conventional diagnostic catheters (41%). The most durable material was diagnostic EP catheters with a fixed curve (61%), the most sensitive material was ablation catheters with contact force sensors (21%). Important benefits were seen in reducing costs for the providing hospital (65%) and the healthcare provider (42%) and making EP procedures available for a greater number of patients (42%). Main concerns were on quality aspects (58%), contamination (52%), and loss of precision (47%). Reprocessing of EP materials is heterogeneously managed among EHRA countries. The present survey shows that European electrophysiologists consider the use of reprocessed EP material as generally safe and cost-effective.

Catheter ablation or medical therapy to delay progression of atrial fibrillation: the randomized controlled atrial fibrillation progression trial (ATTEST).

AIMS: Delay of progression from paroxysmal to persistent atrial fibrillation (AF) is an important measure of long-term success of AF treatment. However, published data on the impact of catheter ablation on AF progression are limited. This study evaluates whether radiofrequency (RF) catheter ablation delays the progression of AF compared with antiarrhythmic drug (AAD) treatment using current AF management guidelines. METHODS: This prospective, randomized, controlled, two-arm, open-label trial was conducted at 29 hospitals and medical centres across 13 countries. Patients were randomized 1 : 1 to RF ablation or AAD treatment. The primary endpoint was the rate of persistent AF/atrial tachycardia (AT) at 3 years. RESULTS: After early study termination following slow enrolment, 255 (79%) of the planned 322 patients were enrolled (RF ablation, n = 128, AAD, n = 127); 36% of patients in the RF ablation group and 41% in the AAD group completed 3 years of follow-up. For the primary endpoint, the Kaplan-Meier estimate of the rate of persistent AF/AT at 3 years was significantly lower with RF ablation [2.4% (95% confidence interval (CI), 0.6-9.4%)] than with AAD therapy [17.5% (95% CI, 10.7-27.9%); one-sided P = 0.0009]. Patients ≥65 years were ∼4 times more likely to progress to persistent AF/AT than patients <65 years, suggesting RF ablation can delay disease progression [hazard ratio: 3.87 (95% CI, 0.88-17.00); P = 0.0727]. Primary adverse events were reported for eight patients in the RF ablation group. CONCLUSIONS: Radiofrequency ablation is superior to guideline-directed AAD therapy in delaying the progression from paroxysmal to persistent AF.

Transcatheter radiofrequency pulmonary artery denervation in swine: the evaluation of lesion degree, hemodynamics and pulmonary hypertension inducibility.

BACKGROUND: Mechanisms of positive effects of pulmonary artery (PA) denervation (PADN) remain poorly understood. The study aimed to evaluate pulmonary hemodynamic changes after PADN and their association with the extent of PA wall damage in an acute thromboxane A2 (TXA2)-induced pulmonary hypertension (PH) model in swine. METHODS: In this experimental sham-controlled study, 17 normotensive male white Landrace pigs (the mean weight 36.2 ± 4.5 kg) were included and randomly assigned to group I (n = 9)-PH modeling before and after PADN, group II (n = 4)-PADN only, or group III (n = 4)-PH modeling before and after a sham procedure. Radiofrequency (RF) PADN was performed in the PA trunk and at the proximal parts of the right and left PAs. PA wall lesions were characterized at the autopsy study using histological and the immunohistochemical examination. RESULTS: In groups I and II, no statistically significant changes in the mean pulmonary arterial pressure nor systemic blood pressure were found after PADN (-0.8 ± 3.4 vs 4.3 ± 8.6 mmHg, P = 0.47; and 6.0 ± 15.9 vs -8.3 ± 7.5 mmHg, P = 0.1; correspondingly). There was a trend towards a lower diastolic pulmonary arterial pressure after PADN in group I when compared with group III during repeat PH induction (34.4 ± 2.9 vs 38.0 ± 0.8; P = 0.06). Despite the presence of severe PA wall damage at the RF application sites, S100 expression was preserved in the majority of PA specimens. The presence of high-grade PA lesions was associated with HR acceleration after PADN (ρ = 0.68, p = 0.03). No significant correlation was found between the grade of PA lesion severity and PA pressure after PADN with or without PH induction. CONCLUSIONS: Extended PADN does not affect PH induction using TXA2. Significant PA adventitia damage is associated with HR acceleration after PADN. Possible delayed effects of PADN on perivascular nerves and pulmonary hemodynamics require further research in chronic experiments.

An Ovine Model for Percutaneous Pulmonary Artery Laser Denervation: Perivascular Innervation and Ablation Lesion Characteristics.

BACKGROUND: Pulmonary artery denervation (PADN) is an evolving interventional procedure capable to reduce pulmonary artery (PA) pressure. We aimed to compare PA nerve distribution in different specimens and assess the feasibility of an ovine model for a denervation procedure and evaluate the acute changes induced by laser energy. METHODS: The experiment was divided into two phases: (1) the analysis of PA nerve distribution in sheep, pigs, and humans using histological and immunochemical methods; (2) fiberoptic PADN in sheep and postmortem laser lesion characteristics. RESULTS: PA nerve density and distribution in sheep differ from humans, although pigs and sheep share similar characteristics, nerve fibers are observed in the media layer, adventitia, and perivascular tissue in sheep. Necrosis of the intima and focal hemorrhages within the media, adventitia, and perivascular adipose tissue were evidenced post laser PADN. Among the identified lesions, 40% reached adventitia and could be classified as effective for PADN. The use of 20 W ablation energy was safer and 30 W-ablation led to collateral organ damage. CONCLUSIONS: An ovine model is suitable for PADN procedures; however, nerve distribution in the PA bifurcation and main branches differ from human PA innervation. Laser ablation can be safely used for PADN procedures.

A Prospective Registry of Atrial Fibrillation Ablation with the Ablation Index Technology: Rationale and Study Design.

This is a prospective multicenter registry of atrial fibrillation (AF) ablation with the Ablation Index (AI) technology, which has been introduced as a marker predicting ablation lesion depth. The index incorporates the main parameters of radiofrequency point-by-point ablation: power, contact force, and time of ablation. The AI is calculated for every operator depending on personal skills, and there are no strict indications on the range of the parameter considering its safety and efficacy during pulmonary vein isolation. The registry aims to evaluate AI values used in different centers by different operators and to evaluate the optimal limits associated with better acute and long-term AF ablation results.

Characterization of a novel SCN5A genetic variant A1294G associated with mixed clinical phenotype.

Mutations in gene SCN5A, which encodes cardiac voltage-gated sodium channel Nav1.5, are associated with multiple clinical phenotypes. Here we describe a novel A1294G genetic variant detected in a male patient with combined clinical phenotype including atrioventricular II block, Brugada-like ECG, septal fibrosis, right ventricular dilatation and decreased left ventricular contractility. Residue A1294 is located in the IIIS3-S4 extracellular loop, in proximity to several residues whose mutations are associated with sodium channelopathies. The wild-type channel Nav1.5 and mutant Nav1.5-A1294G were expressed in the CHO-K1 and HEK293T cells and whole-cell sodium currents were recorded using the patch-clamp method. The A1294G channels demonstrated a negative shift of steady-state inactivation, accelerated fast and slow inactivation and decelerated recovery from intermediate inactivation. Our study reveals biophysical mechanism of the Nav1.5-A1294G dysfunction, which may underlie the combined phenotypic manifestation observed in the patient.

Biatrial tachycardia following linear anterior wall ablation for the perimitral reentry: incidence and electrophysiological evaluations.

INTRODUCTION: A left atrial (LA) anterior ablation line (AnL), connecting the mitral annulus and right pulmonary veins or a roof line, has been suggested as an alternative to mitral isthmus (MI) ablation for perimitral flutter (PMF). Theoretically, the AnL can exclude the LA septal wall from the reentrant circle, and lead to involvement of the right atrium (RA) in a tachycardia (AT) mechanism. METHODS AND RESULTS: Among 807 patients undergoing atrial fibrillation ablation, PMF was diagnosed in 28 subjects, and AnL was performed in 13, and MI ablation in 15 cases. In 4 (31%) patients, AnL resulted in abrupt AT cycle length prolongation, which was associated with the development of a clockwise biatrial tachycardia (bi-AT). The bi-AT propagated along the lateral and posterior mitral annulus, entered the RA via the coronary sinus, and after activating the RA septum reentered the LA over the Bachmann's bundle. The bi-AT was terminated by ablation in Bachmann's bundle insertion areas in the RA or LA. No bi-AT was documented in the MI group. One patient in the AnL group died of stroke in 10 days following the procedure. Anatomic evaluation showed that at the level of the AnL the RA anteroseptal area was separated from the LA by the aortic root, and was free from ablation damage. CONCLUSION: A bi-AT can develop when an AnL is created for PMF termination. Biatrial entrainment mapping facilitates diagnosis. Termination of the bi-AT is feasible when ablated from either RA or LA.

Effect of Probiotic Bacteria on the Gut Microbiome of Mice with Lipopolysaccharide-Induced Inflammation.

The role of lipopolysaccharide (LPS) in the development of diseases is clear, but the specific mechanisms remain poorly understood. This study aimed to investigate the microbiome aberrations in the guts of mice against the background of LPS, as well as the anti-inflammatory effect of probiotic supplementation with Lactobacillus plantarum from the gut, a mix of commercial probiotic lactic acid bacteria, and Weissella confusa isolated from milk using next-generation sequencing. LPS injections were found to induce inflammatory changes in the intestinal mucosa. These morphological changes were accompanied by a shift in the microbiota. We found no significant changes in the microbiome with probiotic supplementation compared to the LPS group. However, when Lactobacillus plantarum and a mix of commercial probiotic lactic acid bacteria were used, the intestinal mucosa was restored. Weissella confusa did not contribute to the morphological changes of the intestinal wall or the microbiome. Changes in the microbiome were observed with probiotic supplementation of Lactobacillus plantarum and a mix of commercial probiotic lactic acid bacteria compared to the control group. In addition, when Lactobacillus plantarum was used, we observed a decrease in the enrichment of the homocysteine and cysteine interconversion pathways with an increase in the L-histidine degradation pathway.

Catheter ablation of paroxysmal atrial fibrillation in patients with previous amiodarone-induced hyperthyroidism: a case-control study.

INTRODUCTION: Many patients with atrial fibrillation (AF) receive amiodarone. Amiodarone-induced hyperthyroidism (AIH) may develop as a complication. We hypothesized that pulmonary vein (PV) isolation in patients with paroxysmal AF and history of AIH may yield a lower success rate. METHODS AND RESULTS: Among 704 patients who underwent AF ablation in our center between 2007 and 2010, we identified 20 patients (mean age 58.3 ± 5.0 years; 11 males) with paroxysmal AF and overt AIH in the past. The control group consisted of 40 patients with amiodarone-refractory AF and no thyroid dysfunction. All patients underwent circumferential PV isolation. During redo procedures all tachycardias were targeted for ablation. During a 12-month follow-up, in the AIH group 6 (30%) patients were arrhythmia free after a single procedure, in comparison to 25 (62.5%) controls (P = 0.01). Atrial tachycardia (AT) was registered in 7 (35%) AIH patients and in 1 (2.5%) control patient (P = 0.001). AF recurred in 10 (50%) AIH versus 15 (37.5%) control patients (P = 0.2). Redo ablation was performed in 7 (35%) AIH patients and in 3 (7.5%) non-AIH patients (P = 0.01). During a redo procedure a PV-unrelated tachycardia was diagnosed in 5 (25%) AIH patients (vs 0 in the controls, P = 0.003). After the last performed ablation, 12 (60%) AIH patients and 28 (70%) controls had no recurrence, P = 0.56. AIH was an independent predictor of ATs. CONCLUSION: PV isolation alone has a lower efficacy for preventing recurrence in paroxysmal AF in AIH patients. After repeat ablations, overall freedom from tachyarrhythmias is similar to patients with no history of thyroid dysfunction.

Regular atrial tachycardias developing after cryoballoon pulmonary vein isolation: incidence, characteristics, and predictors.

AIMS: Cryoballoon ablation (CBA) is a well-used technique when performing pulmonary vein (PV) isolation in patients with paroxysmal atrial fibrillation (AF). Our aim is to describe incidence, characteristics, and clinical predictors for developing atrial tachycardias (ATs) after cryoballoon PV isolation in patients with paroxysmal AF. METHODS AND RESULTS: The study population consisted of 181 consecutive patients undergoing a first CBA. All patients received an event-recorder before cryoablation and transmitted daily electrocardiogram (ECG) during 1 month before ablation and 3 months after. Further follow-up consisted of 24 h Holter monitoring and ECG registration every 3 months and also in patients presenting with symptoms. A mean follow-up period was 497.9 ± 283.9 days, and 175 patients completed follow-up. In 14 (8%) patients regular ATs were registered. In multivariate logistic regression model, the following parameters were independently associated with ATs after ablation: an additional right PV, treatment with beta-blockers, and presence of AT on event-recording strips before ablation. Seven (4%) patients with registered AT underwent a redo procedure. In two (1.1%) patients ATs were originated in reconnected PVs. In other patients no left AT was induced. No macro re-entrant left AT was documented in any patient. During follow-up, after a redo ablation, no AT was registered. CONCLUSION: The incidence of left AT after CBA is low, and no left atrial macro re-entrant tachycardia was found. The following independent predictors of AT development have been identified: an additional right PV, regular AT registered before ablation, and the use of beta-blockers.

Characteristics of the Fecal Microbiome of Piglets with Diarrhea Identified Using Shotgun Metagenomics Sequencing.

Diarrhea in piglets is one of the most common diseases leading to high mortality and, as a result, to economic losses. Shotgun metagenomic sequencing was performed on the DNBSEQ-G50, MGI system to study the role of the fecal microbiome in the development of diarrhea in newborn piglets. Analysis of the study data showed that the composition of the fecal microbiome at the level of bacteria and fungi did not differ in piglets with diarrhea from the healthy group. Bacteria belonging to the phyla Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Fusobacteria were the most abundant. However, a higher level of bacterial alpha diversity was observed in the group of piglets with diarrhea, which may be due to dysbacteriosis and inflammation. The study of the virome showed the difference between the two types of phages: Bacteroides B40-8 prevailed in diseased piglets, while Escherichia virus BP4 was found in greater numbers in healthy piglets. The results of our study suggest that the association between the fecal microbiome and susceptibility to diarrhea in suckling piglets may have been previously overestimated.

Laser renal denervation: A comprehensive evaluation of microstructural renal artery lesions.

Renal artery denervation (RDN) has been proposed for resistant arterial hypertension. Beyond conventional radiofrequency (RF) ablation, there are emerging RDN technologies, including laser catheter ablation. We aimed at evaluamting the local effects of laser ablation on the renal artery and perivascular nerve injury in comparison with radiofrequency ablation. Thirteen pigs (mean weight 36.7 ± 4.7 kg, age 3 months) were divided into three groups: (1) laser ablation in normotensive pigs (LA; n = 3), (2) bipolar RF ablation in normotensive pigs (RF; n = 7), and (3) a sham group (SHAM; n = 3). Transcatheter laser and RF ablations were performed under general anesthesia. After euthanasia, pathology and immunohistochemical studies were performed. Artery wall and perivascular nerve lesions were found in the LA and RF groups. A lower rate of intimal microdissections was evaluated after laser ablation when compared with RF ablation (0 vs. 1.5 [1;2.75] per artery; p < .05). There was a numerical prevalence of nerves with tyrosine hydroxylase expression loss after laser RDN when compared with RF ablation (16.7 [4; 18] vs. 9.1 [0;18] per specimen). Laser ablation is noninferior to RF ablation regarding perivascular nerve injury and is associated with less intimal layer damage.

Antiplatelet and Anti-Coagulation Therapy for Left-Sided Catheter Ablations: What Is beyond Atrial Fibrillation?

Aim: International guidelines on the use of anti-thrombotic therapies in left-sided ablations other than atrial fibrillation (AF) are lacking. The data regarding antiplatelet or anticoagulation strategies after catheter ablation (CA) procedures mainly derive from AF, whereas for the other arrhythmic substrates, the anti-thrombotic approach remains unclear. This survey aims to explore the current practices regarding antithrombotic management before, during, and after left-sided endocardial ablation, not including atrial fibrillation (AF), in patients without other indications for anti-thrombotic therapy. Material and Methods: Electrophysiologists were asked to answer a questionnaire containing questions on antiplatelet (APT) and anticoagulation therapy for the following left-sided procedures: accessory pathway (AP), atrial (AT), and ventricular tachycardia (VT) with and without structural heart disease (SHD). Results: We obtained 41 answers from 41 centers in 15 countries. For AP, before ablation, only four respondents (9.7%) used antiplatelets and two (4.9%) used anticoagulants. At discharge, APT therapy was prescribed by 22 respondents (53.7%), and oral anticoagulant therapy (OAC) only by one (2.4%). In patients with atrial tachycardia (AT), before ablation, APT prophylaxis was prescribed by only four respondents (9.7%) and OAC by eleven (26.8%). At discharge, APT was recommended by 12 respondents (29.3%) and OAC by 24 (58.5%). For VT without SHD, before CA, only six respondents (14.6%) suggested APT and three (7.3%) suggested OAC prophylaxis. At discharge, APT was recommended by fifteen respondents (36.6%) and OAC by five (12.2%). Regarding VT in SHD, before the procedure, eight respondents (19.5%) prescribed APT and five (12.2%) prescribed OAC prophylaxis. At discharge, the administration of anti-thrombotic therapy depended on the LV ejection fraction for eleven respondents (26.8%), on the procedure time for ten (24.4%), and on the radiofrequency time for four (9.8%), with a cut-off value from 1 to 30 min. Conclusions: Our survey indicates that the management of anti-thrombotic therapy surrounding left-sided endocardial ablation of patients without other indications for anti-thrombotic therapy is highly variable. Further studies are necessary to evaluate the safest approach to these procedures.

Dynamics of Changes in the Gut Microbiota of Healthy Mice Fed with Lactic Acid Bacteria and Bifidobacteria.

Probiotics are living microorganisms that provide numerous health benefits for their host. Probiotics have various effects on the body; for example, they change gut microbiota, improve the integrity of the epithelial barrier and have anti-inflammatory effects. The use of probiotic supplements that are based on lactic acid bacteria and bifidobacteria is one of the approaches that are used to balance gut microflora. In our study, we evaluated the effects of supplements, which were based on members of the Lactobacillaceae family and bifidobacteria, on the gut microbiome of healthy mice using the 16S rRNA sequencing method. The data that were obtained demonstrated that when mice received the probiotic supplements, statistically significant changes occurred in the composition of the microbiome at the phylum level, which were characterized by an increase in the number of Actinobacteriota, Bacteroidota, Verrucomicrobia and Proteobacteria, all of which have potentially positive effects on health. At the generic level, a decrease in the abundance of members of the Nocardioides, Helicobacter and Mucispirillum genus, which are involved in inflammatory processes, was observed for the group of mice that was fed with lactic acid bacteria. For the group of mice that was fed with bifidobacteria, a decrease was seen in the number of members of the Tyzzerella and Akkermansia genus. The results of our study contribute to the understanding of changes in the gut microbiota of healthy mice under the influence of probiotics. It was shown that probiotics that are based on members of the Lactobacillaceae family have a more positive effect on the gut microbiome than probiotics that are based on bifidobacteria.

Transcutaneous Spinal Cord Stimulation Attenuates Blood Pressure Drops in Orthostasis.

Orthostatic hypotension is a complex medical problem with various underlying pathogenic mechanisms and limited modalities for its correction. Since transcutaneous spinal cord stimulation (t-SCS) leads to immediate blood pressure (BP) elevation in a supine position, we suggested that t-SCS may attenuate blood pressure drops in orthostasis. We aimed to evaluate the hemodynamic effects of t-SCS during tilt testing in a feasibility study in three patients with documented orthostatic hypotension. Four sessions on two different days of tilt testing on and off t-SCS were performed on each patient. While tilting with t-SCS off showed typical significant BP drops in every patient, active t-SCS resulted in systemic vascular resistance (SVR) elevation in all patients and significantly higher values of systolic and diastolic BP in two patients. T-SCS requires further investigation on a larger patient population. However, our preliminary results demonstrate its ability for SVR and BP elevation in subjects with severe orthostatic hypotension.

Device-based neuromodulation for cardiovascular diseases and patient' s age.

The autonomic nervous system plays an important role in the pathogenesis of cardiovascular diseases. With aging, autonomic activity changes, and this impacts the physiological reactions to internal and external signals. Both sympathetic and parasympathetic responses seem to decline, reflecting functional and structural changes in nervous regulation. Although some investigators suggested that both the sympathetic and parasympathetic activities were suppressed, others found that only the parasympathetic activity was suppressed while the sympathetic activity increased. In addition, cardiac innervation progressively diminishes with aging. Therefore, one may suggest that neuromodulation interventions may have different effects, and older age groups can express an attenuated response. This article aims to discuss the effect of device-based neuromodulation in different cardiovascular diseases, depending on the patient's age. Thus, we cover renal denervation, pulmonary artery denervation, baroreceptor activation therapy, vagus nerve stimulation, spinal cord stimulation, ganglionated plexi ablation for the management of arterial and pulmonary hypertension, heart failure, angina and arrhythmias. The results of many clinical studies appeared to be unconvincing. In view of the low rate of positive findings in clinical studies incorporating neuromodulation approaches, we suggest the underestimation of advanced age as a potential contributing factor to poorer response. Analysis of outcomes between different age groups in clinical trials may shed more light on the true effects of neuromodulation when neutral/ambiguous results are obtained.

Bromhexine Hydrochloride Prophylaxis of COVID-19 for Medical Personnel: A Randomized Open-Label Study.

BACKGROUND: Bromhexine hydrochloride has been suggested as a TMPRSS2 protease blocker that precludes the penetration of SARS-CoV-2 into cells. We aimed to assess the preventive potential of regular bromhexine hydrochloride intake for COVID-19 risk reduction in medical staff actively involved in the evaluation and treatment of patients with confirmed or suspected SARS-CoV-2 infection. METHODS: In a single-centre randomized open-label study, medical staff managing patients with suspected and confirmed COVID-19 were enrolled and followed up for 8 weeks. The study began at the initiation of COVID-19 management in the clinic. The study was prematurely terminated after the enrollment of 50 participants without a history of SARS-CoV-2 infection: 25 were assigned to bromhexine hydrochloride treatment (8 mg 3 times per day), and 25 were controls. The composite primary endpoint was a positive nasopharyngeal swab polymerase chain reaction (PCR) test for SARS-CoV-2 or signs of clinical infection within 28 days and at week 8. Secondary endpoints included time from the first contact with a person with COVID-19 to the appearance of respiratory infection symptoms; the number of days before a first positive SARS-CoV-2 test; the number of asymptomatic participants with a positive nasopharyngeal swab test; the number of symptomatic COVID-19 cases; and adverse events. RESULTS: The rate of the combined primary endpoint did not differ significantly between the active treatment group (2/25 [8%]) and control group (7/25 [28%]); P=0.07. A fewer number of participants developed symptomatic COVID-19 in the treatment group compared to controls (0/25 vs. 5/25; P=0.02). CONCLUSION: Although the study was underpowered, it showed that Bromhexine hydrochloride prophylaxis was associated with a reduced rate of symptomatic COVID-19. The prophylactic treatment was not associated with a lower combined primary endpoint rate, a positive swab PCR test, or COVID-19 (ClinicalTrials.gov number, NCT04405999).