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.

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.

Novel long-chain neurotoxins from Bungarus candidus distinguish the two binding sites in muscle-type nicotinic acetylcholine receptors.

αδ-Bungarotoxins, a novel group of long-chain α-neurotoxins, manifest different affinity to two agonist/competitive antagonist binding sites of muscle-type nicotinic acetylcholine receptors (nAChRs), being more active at the interface of α-δ subunits. Three isoforms (αδ-BgTx-1-3) were identified in Malayan Krait (Bungarus candidus) from Thailand by genomic DNA analysis; two of them (αδ-BgTx-1 and 2) were isolated from its venom. The toxins comprise 73 amino acid residues and 5 disulfide bridges, being homologous to α-bungarotoxin (α-BgTx), a classical blocker of muscle-type and neuronal α7, α8, and α9α10 nAChRs. The toxicity of αδ-BgTx-1 (LD50 = 0.17-0.28 µg/g mouse, i.p. injection) is essentially as high as that of α-BgTx. In the chick biventer cervicis nerve-muscle preparation, αδ-BgTx-1 completely abolished acetylcholine response, but in contrast with the block by α-BgTx, acetylcholine response was fully reversible by washing. αδ-BgTxs, similar to α-BgTx, bind with high affinity to α7 and muscle-type nAChRs. However, the major difference of αδ-BgTxs from α-BgTx and other naturally occurring α-neurotoxins is that αδ-BgTxs discriminate the two binding sites in the Torpedo californica and mouse muscle nAChRs showing up to two orders of magnitude higher affinity for the α-δ site as compared with α-ε or α-γ binding site interfaces. Molecular modeling and analysis of the literature provided possible explanations for these differences in binding mode; one of the probable reasons being the lower content of positively charged residues in αδ-BgTxs. Thus, αδ-BgTxs are new tools for studies on nAChRs.

Oligoarginine Peptides, a New Family of Nicotinic Acetylcholine Receptor Inhibitors.

Many peptide ligands of nicotinic acetylcholine receptors (nAChRs) contain a large number of positively charged amino acid residues, a striking example being conotoxins RgIA and GeXIVA from marine mollusk venom, with an arginine content of >30%. To determine whether peptides built exclusively from arginine residues will interact with different nAChR subtypes or with their structural homologs such as the acetylcholine-binding protein and ligand-binding domain of the nAChR α9 subunit, we synthesized a series of R3, R6, R8, and R16 oligoarginines and investigated their activity by competition with radioiodinated α-bungarotoxin, two-electrode voltage-clamp electrophysiology, and calcium imaging. R6 and longer peptides inhibited muscle-type nAChRs, α7 nAChRs, and α3ß2 nAChRs in the micromolar range. The most efficient inhibition of ion currents was detected for muscle nAChR by R16 (IC50 = 157 nM) and for the α9α10 subtype by R8 and R16 (IC50 = 44 and 120 nM, respectively). Since the R8 affinity for other tested nAChRs was 100-fold lower, R8 appears to be a selective antagonist of α9α10 nAChR. For R8, the electrophysiological and competition experiments indicated the existence of two distinct binding sites on α9α10 nAChR. Since modified oligoarginines and other cationic molecules are widely used as cell-penetrating peptides, we studied several cationic polymers and demonstrated their nAChR inhibitory activity. SIGNIFICANT STATEMENT: By using radioligand analysis, electrophysiology, and calcium imaging, we found that oligoarginine peptides are a new group of inhibitors for muscle nicotinic acetylcholine receptors (nAChRs) and some neuronal nAChRs, the most active being those with 16 and 8 Arg residues. Such compounds and other cationic polymers are cell-penetrating tools for drug delivery, and we also demonstrated the inhibition of nAChRs for several of the latter. Possible positive and negative consequences of such an action should be taken into account.

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.

Ventricular tachycardia prediction in patients with implantable cardioverter-defibrillators for primary prevention of sudden cardiac death.

Clinical data analysis of 83 patients with implantable cardioverter-defibrillators (ICDs) for sudden cardiac death (SCD) primary prevention has been done. We revealed 5 parameters associated with the detection of life-threatening ventricular arrhythmias. These parameters formed the basis for constructing a logistic regression model. The model makes it possible to obtain the probability of occurrence of a specific event depending on the severity of the predictive parameters and the degree of its influence (risk of true ventricular arrhythmias detection). Estimating the potential risk of the life-threatening arrhythmias, individual programming options are required in implantable cardioverter-defibrillators (ICDs) to reduce the amount of unnecessary electrotherapy, as well as more accurate monitoring of the patient's drug therapy.

Orthosteric and/or Allosteric Binding of α-Conotoxins to Nicotinic Acetylcholine Receptors and Their Models.

α-Conotoxins from Conus snails are capable of distinguishing muscle and neuronal nicotinic acetylcholine receptors (nAChRs). α-Conotoxin RgIA and αO-conotoxin GeXIVA, blocking neuronal α9α10 nAChR, are potential analgesics. Typically, α-conotoxins bind to the orthosteric sites for agonists/competitive antagonists, but αO-conotoxin GeXIVA was proposed to attach allosterically, judging by electrophysiological experiments on α9α10 nAChR. We decided to verify this conclusion by radioligand analysis in competition with α-bungarotoxin (αBgt) on the ligand-binding domain of the nAChR α9 subunit (α9 LBD), where, from the X-ray analysis, αBgt binds at the orthosteric site. A competition with αBgt was registered for GeXIVA and RgIA, IC50 values being in the micromolar range. However, high nonspecific binding of conotoxins (detected with their radioiodinated derivatives) to His6-resin attaching α9 LBD did not allow us to accurately measure IC50s. However, IC50s were measured for binding to Aplysia californica AChBP: the RgIA globular isomer, known to be active against α9α10 nAChR, was more efficient than the ribbon one, whereas all three GeXIVA isomers had similar potencies at low µM. Thus, radioligand analysis indicated that both conotoxins can attach to the orthosteric sites in these nAChR models, which should be taken into account in the design of analgesics on the basis of these conotoxins.

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.

Validation of the mapping accuracy of a novel non-invasive epicardial and endocardial electrophysiology system.

AIMS: Use of a non-invasive electrocardiographic mapping system may aid in rapid diagnosis of atrial or ventricular arrhythmias or the detection of ventricular dyssynchrony. The aim of the present study was to validate the mapping accuracy of a novel non-invasive epi- and endocardial electrophysiology system (NEEES). METHODS AND RESULTS: Patients underwent pre-procedural computed tomography or magnetic resonance imaging of the heart and torso. Radiographic data were merged with the data obtained from the NEEES during pacing from implanted pacemaker leads or pacing from endocardial sites using an electroanatomical mapping system (CARTO 3, Biosense Webster). The earliest activation as denoted on the NEEES three-dimensional heart model was compared with the true anatomic location of the tip of the pacemaker lead or the annotated pacing site on the CARTO 3 map. Twenty-nine patients [mean age: 62 ± 11 years, 6/29 (11%) female, 21/29 (72%) with ischaemic cardiomyopathy] were enrolled into the pacemaker verification group. The mean distance from the non-invasively predicted pacing site to the anatomic reference site was 10.8 ± 5.4 mm for the right atrium, 7.7 ± 5.8 mm for the right ventricle, and 7.9 ± 5.7 mm for the left ventricle activated via the coronary sinus lead. Five patients [mean age 65 ± 4 years, 2 (33%) females] underwent CARTO 3 verification study. The mean distance between non-invasively reconstructed pacing site and the reference pacing site was 7.4 ± 2.7 mm for the right atrium, 6.9 ± 2.3 mm for the left atrium, 6.5 ± 2.1 mm for the right ventricle, and 6.4 ± 2.2 for the left ventricle, respectively. CONCLUSION: The novel NEEES was able to correctly identify the site of pacing from various endo- and epicardial sites with high accuracy.

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.

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.

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.

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).

Performance of the ablation index during pulmonary vein isolation: periprocedural data from a multicenter registry.

PURPOSE: Our study aimed to assess the achievement of target ablation index (AI) values and their impact on first-pass pulmonary vein isolation (FPI) as well as to identify FPI predictors. METHODS: Atrial fibrillation (AF) ablation was performed according to the local practice, and target AIs were evaluated. The actual AI was calculated as the median value of all ablation points for the anterior and posterior left atrial (LA) walls. RESULTS: A total of 450 patients from nine centers were enrolled. Patients with first-time ablation (n = 408) were divided into the FPI and non-FPI groups. In the FPI group, a higher median target AI was reported for both the anterior and posterior LA walls than those in the non-FPI group. A higher actual AI was observed for the anterior LA wall in the FPI group. The actual AI was equal to or higher than the target AI for the posterior, anterior, and both LA walls in 54%, 47%, and 35% (n = 158) cases, respectively. Parameters such as hypertension, stroke, ablation power, actual AI value on the anterior wall, target AI values on both LA walls, AI achievement on the posterior wall, carina ablation, and operator experience were all associated with FPI in a univariate logistic regression model; only carina ablation was an independent predictor of FPI. CONCLUSIONS: According to our multicenter study, FPI and a target AI were not achieved in a significant proportion of AF ablation procedures. Higher actual and target AI values were associated with FPI, but only carina ablation can independently predict FPI.

Pulmonary and Systemic Hemodynamics following Multielectrode Radiofrequency Catheter Renal Denervation in Acutely Induced Pulmonary Arterial Hypertension in Swine.

OBJECTIVE: We aimed to assess the effects of renal denervation (RDN) on systemic and pulmonary hemodynamics in a swine model of thromboxane A2- (TXA2-) induced pulmonary arterial hypertension (PAH). METHODS: The study protocol comprised two PAH inductions with a target mean pulmonary artery pressure (PAP) of 40 mmHg at baseline and following either the RDN or sham procedure. Ten Landrace pigs underwent the first PAH induction; then, nine animals were randomly allocated in 1 : 1 ratio to RDN or sham procedure; the second PAH induction was performed in eight animals (one animal died of pulmonary embolism during the first PAH induction, and one animal died after RDN). In the RDN group, ablation was performed in all available renal arteries, and balloon inflation within artery branches was performed in controls. An autopsy study of the renal arteries was performed. RESULTS: At baseline, the target mean PAP was achieved in all animals with 25.0 [20.1; 25.2] mcg of TXA2. The second PAH induction required the same mean TXA2 dose and infusion time. There was no statistically significant difference in the mean PAP at second PAH induction between the groups (39.0 ± 5.3 vs. 39.75 ± 0.5 mmHg, P > 0.05). In the RDN group, the second PAH induction resulted in a numerical but insignificant trend toward a decrease in the mean systemic blood pressure and systemic vascular resistance, when compared with the baseline induction (74 ± 18.7 vs. 90.25 ± 28.1 mmHg and 1995.3 ± 494.3 vs. 2433.7 ± 1176.7 dyn∗sec∗cm -5, P > 0.05, respectively). No difference in hemodynamic parameters was noted in the sham group between the first and second PAH induction. Autopsy demonstrated artery damage in both groups, but RDN resulted in more severe lesions. CONCLUSIONS: According to our results, RDN does not result in significant acute pulmonary or systemic hemodynamic changes in the TXA2-induced PAH model. The potential chronic effects of RDN on PAH require further research.

Different Expressions of Pericardial Fluid MicroRNAs in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy and Ischemic Heart Disease Undergoing Ventricular Tachycardia Ablation.

Introduction: Pericardial fluid is enriched with biologically active molecules of cardiovascular origin including microRNAs. Investigation of the disease-specific extracellular microRNAs could shed light on the molecular processes underlying disease development. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease characterized by life-threatening arrhythmias and progressive heart failure development. The current data about the association between microRNAs and ARVC development are limited. Methods and Results: We performed small RNA sequence analysis of microRNAs of pericardial fluid samples obtained during transcutaneous epicardial access for ventricular tachycardia (VT) ablation of six patients with definite ARVC and three post-infarction VT patients. Disease-associated microRNAs of pericardial fluid were identified. Five microRNAs (hsa-miR-1-3p, hsa-miR-21-5p, hsa-miR-122-5p, hsa-miR-206, and hsa-miR-3679-5p) were found to be differentially expressed between patients with ARVC and patients with post-infarction VT. Enrichment analysis of differentially expressed microRNAs revealed their close linkage to cardiac diseases. Conclusion: Our data extend the knowledge of pericardial fluid microRNA composition and highlight five pericardial fluid microRNAs potentially linked to ARVC pathogenesis. Further studies are required to confirm the use of pericardial fluid RNA sequencing in differential diagnosis of ARVC.

Stimulation Mapping of the Pulmonary Artery for Denervation Procedures: an Experimental Study.

Transcatheter pulmonary artery denervation (PADN) has been developed for the correction of pulmonary hypertension. We investigated pulmonary artery stimulation mapping and its role in PADN procedures. Artery stimulation was performed in 17 Landrace pigs. Low-frequency stimulation defined areas of ventricular and atrial capture. High-frequency stimulation evoked the following responses: sinus rhythm slowing and/or atrial rhythm acceleration in 59% of animals, phrenic nerve capture in 100%, and laryngeal recurrent nerve capture in 23%. The sites with evoked heart rate responses were marked by discrete radiofrequency ablations (RFA). An autopsy showed nerves in the adventitia and perivascular fat under the RFA sites, and the lack of muscarinic-1, tyrosine hydroxylase, and dopamine-5 receptors' expression. During PADN, areas adjacent to the course of phrenic and recurrent laryngeal nerves should be avoided. RFA at points with heart rate responses leads to the non-reproducibility of evoked reactions and the disappearance of neural markers' expression. Graphical abstract.