Search

Aims Cryoballoon pulmonary vein isolation (PVI) is a safe and effective treatment for atrial fibrillation (AF). Current limitations include incomplete vein occlusion due to balloon rigidity and inconsistent electrogram recording, which impairs identification of isolation. We aimed to evaluate the acute safety and performance of a novel cryoballoon system. Methods and results The system includes a steerable sheath, mapping catheter, and a balloon that maintains uniform inflation pressure and size following initiation of ablation. Protocol-directed cryoablation was delivered for 180 s for isolation documented in ≤60 s, otherwise freeze duration was 240 s. Primary endpoints were acute safety and vein isolation. Pulmonary vein isolation was confirmed at ≥30 min post-isolation. Data were compared across vein locations. Thirty patients with paroxysmal AF were enrolled at two centres and underwent PVI. Pulmonary vein isolation was achieved with cryoablation only in 100% of veins (120/120). Nadir temperature was −53.1 ± 5.3°C. The number of applications to achieve PVI was 1.4 ± 0.4 per vein. Of the 120 veins, 89 were isolated with a single cryothermal application (10/30 patients required only 4 total cryoablations). There were no procedural- or device-related serious adverse events at 30 days post-procedure. A subset (24/30) of patients was followed for 1-year and 71% (17/24) remained free of atrial arrhythmias. Six patients with arrhythmia recurrence were remapped and three had durable PVI for all four veins. Conclusion In this first human experience, the novel cryoballoon platform was safe, efficacious, and demonstrated a high proportion of successful single ablation isolation.

Background Recently, a novel cryoballoon ablation catheter has demonstrated acute safety and efficacy in de novo pulmonary vein isolation (PVI) procedures in patients with paroxysmal atrial fibrillation (PAF). However, there are limited studies demonstrating the long-term efficacy. The aim of this study was to evaluate the long-term safety and efficacy of this novel cryoballoon in treating PAF. Methods This was a non-randomized, prospective, multicentre study enrolling 58 consecutive patients. Cryoablation was delivered for 180 s if time to isolation was ≤ 60 s. Otherwise a 240-s cryoablation was performed. One centre performed pre- and post-ablation high-density mapping (n = 9) to characterize lesion formation. After a 3-month blanking period, recurrence was defined as having any documented, symptomatic episode(s) of AF or atrial tachycardia. All patients were followed for 1 year. Results Acute PVI was achieved in 230 of 231 pulmonary veins (99.6%) with 5.3 ± 1.6 cryoablations per patient (1.3 ± 0.7 cryoablations per vein). Forty-three (77%) patients remained arrhythmia-free at 1-year follow-up. Four patients (6.9%) experienced phrenic nerve injury (3 resolved during the index procedure; 1 resolved at 6 months). One serious adverse device event was reported: femoral arterial embolism event occurring 2 weeks post-index procedure. For patients who underwent high-density mapping, cryoablation was antral with 50% of the posterior wall ablated. Conclusions Initial multicentre clinical experience with a novel cryoballoon has demonstrated safety and efficacy of PVI in patients with PAF. Ablation with this cryoballoon provides a wide, antral lesion set with significant debulking of the posterior wall of the left atrium.

Research Letter regarding the 1-year follow-up of the original FreezeCompliant cohort

The article "Comparison of the 1-year clinical outcome of a novel cryoballoon to an established cryoballoon technology", written by Sing-Chien Yap, Ante Anic, Toni Breskovic, Annika Haas, Rohit E. Bhagwandien, Zrinka Jurisic, Tamas Szili-Torok and Armin Luik, was originally published online on the publisher’s internet portal on 07 June 2022 with Open Access under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. With the author’s/authors' decision to cancel Open Access the copyright of the article changed on 06 July 2022 to © The Author(s), under exclusive licence to Springer Science + Business Media, LLC, part of Springer Nature 2022 with all rights reserved. The original article has been corrected.

Purpose: Catheter ablation is a cornerstone of the therapy for paroxysmal atrial fibrillation. The importance of effective lesion size formation during pulmonary vein isolation is gauged through conduction recovery and recurrence of arrhythmia. Therefore, the lesion size index (LSI) is designed to utilize traditional intraprocedural parameters and predict procedural success. The impact of the optimal LSI index and the respective segments of the pulmonary veins has not been commonly evaluated. We aimed to assess whether higher and targeted LSI on the different segments of pulmonary veins could actually lead to better clinical outcomes of paroxysmal atrial fibrillation ablation. Methods: Retrospective analyses of drug-refractory paroxysmal atrial fibrillation patients who underwent first catheter ablation were conducted. Targeted LSI of 6.5 at the anterior wall and 5.2 at the posterior wall, roof, and floor of the pulmonary vein was applied. The primary endpoint was defined as arrhythmias recurrence assessed by routine electrocardiograms and 24-h ambulatory electrocardiographic monitoring at 3, 6, and 12 months post-ablation. Results: Among the included 39 patients, the single-procedure 12- month freedom from arrhythmias was reached in 92.3% of patients. Interestingly, there was no tendency towards an increased number of adverse effects using a higher LSI index. Conclusions: Atrial fibrillation ablation guided by targeted LSI value showed efficiency on the freedom from arrhythmias during 1-year follow-up period without harmful effects.

Introduction: Recently a novel cryoballoon system (POLARx, Boston Scientific) became available for the treatment of atrial fibrillation. This cryoballoon is comparable with Arctic Front Advance Pro (AFA-Pro, Medtronic), however, it maintains a constant balloon pressure. We compared the procedural efficacy and biophysical characteristics of both systems. Methods: One hundred and ten consecutive patients who underwent first-time cryoballoon ablation (POLARx: n = 57; AFA-Pro: n = 53) were included in this prospective cohort study. Results: Acute isolation was achieved in 99.8% of all pulmonary veins (POLARx: 99.5% vs. AFA-Pro: 100%, p = 1.00). Total procedure time (81 vs. 67 min, p

Purpose of review Pulsed field ablation is a nonthermal ablative modality that uses short living, strong electrical field created around catheter to create microscopic pores in cell membranes (electroporation). When adequately dosed/configured it shows a preference for myocardial tissue necrosis. Thus, it holds a promise to become a 'perfect' energy source for cardiac ablation to treat arrhythmias. Herein, we present update on platforms in clinical development. Recent findings First in human series using pulsed field ablation for atrial fibrillation ablation have been completed and data published for several platforms. Acute safety outcomes are similar across the platforms with exceptionally low rate of those complications that are typically reported for thermal ablation methods (esophageal injury, pulmonary vein stenosis, phrenic nerve palsy). Promising acute data on pulmonary vein isolation had been corroborated with satisfactory 1-year clinical follow-up for a single platform, whereas reports are pending for the rest. Research efforts are being expanded to a development of focal catheters, and therefore, pulsed field ablation application for ventricular arrhythmias. Summary As the reports confirming its safety and efficacy build up, there seems to be no way that the promise of pulsed field ablation could end in a blind alley.

Objectives This study sought to determine whether durable pulmonary vein isolation (PVI) using pulsed field ablation (PFA) translates to freedom from atrial fibrillation recurrence without an increase in adverse events. Background PFA is a nonthermal ablative modality that, in preclinical studies, is able to preferentially ablate myocardial tissue with minimal effect on surrounding tissues. Herein, we present 1-year clinical outcomes of PFA. Methods In 3 multicenter studies (IMPULSE [A Safety and Feasibility Study of the IOWA Approach Endocardial Ablation System to Treat Atrial Fibrillation], PEFCAT [A Safety and Feasibility Study of the FARAPULSE Endocardial Ablation System to Treat Paroxysmal Atrial Fibrillation], and PEFCAT II [Expanded Safety and Feasibility Study of the FARAPULSE Endocardial Multi Ablation System to Treat Paroxysmal Atrial Fibrillation]), paroxysmal atrial fibrillation patients underwent PVI using a basket or flower PFA catheter. Invasive remapping was performed at ∼2 to 3 months, and reconnected PVs were reisolated with PFA or radiofrequency ablation. After a 90-day blanking period, arrhythmia recurrence was assessed over 1-year follow-up. Results In 121 patients, acute PVI was achieved in 100% of PVs with PFA alone. PV remapping, performed in 110 patients at 93.0 ± 30.1 days, demonstrated durable PVI in 84.8% of PVs (64.5% of patients), and 96.0% of PVs (84.1% of patients) treated with the optimized biphasic energy PFA waveform. Primary adverse events occurred in 2.5% of patients (2 pericardial effusions or tamponade, 1 hematoma); in addition, there was 1 transient ischemic attack. The 1-year Kaplan-Meier estimates for freedom from any atrial arrhythmia for the entire cohort and for the optimized biphasic energy PFA waveform cohort were 78.5 ± 3.8% and 84.5 ± 5.4%, respectively. Conclusions PVI with a “single-shot” PFA catheter results in excellent PVI durability and acceptable safety with a low 1-year rate of atrial arrhythmia recurrence. These data mitigate concern that the nonthermal ablative mechanism of PFA might mask undiscovered compromises to clinical success. (IMPULSE: A Safety and Feasibility Study of the IOWA Approach Endocardial Ablation System to Treat Atrial Fibrillation, NCT03700385 ; A Safety and Feasibility Study of the FARAPULSE Endocardial Ablation System to Treat Paroxysmal Atrial Fibrillation, NCT03714178 ; PEFCAT II Expanded Safety and Feasibility Study of the FARAPULSE Endocardial Multi Ablation System to Treat Paroxysmal Atrial Fibrillation [PEFCAT II], NCT04170608 )

Background Recently, a novel cryoballoon (CB; POLARx) has been developed with increased steerability which maintains size and pressure throughout the ablation. Initial clinical data has demonstrated acute procedural safety and efficacy in de novo pulmonary vein isolation (PVI) procedures in patients with paroxysmal atrial fibrillation (AF). However, there are limited studies demonstrating the long-term efficacy of the CB. Purpose To evaluate the long-term safety and efficacy of the novel CB in treating paroxysmal AF. Methods This was a non-randomized, prospective, multi-center study. Fifty-eight consecutive patients with paroxysmal AF were enrolled at 4 centers for de novo PVI procedures. Cryoablation was delivered for 180s if time to isolation was ≤60s. Otherwise a 240s cryoablation was performed. PVI was confirmed with entrance and exit block testing. Patients were followed for 1 year with 24-hour Holter monitoring at 3, 6, and 12 months. After a 3-month blanking period, recurrence was defined as having any documented, symptomatic episode(s) of AF or atrial tachycardia. Results Acute isolation with the CB was achieved in 230 of 231 pulmonary veins (99.6%) with 5.2±1.5 cryoapplications per patient (1.3±0.6 cryoapplications per vein). There were 4 patients (6.9%) with phrenic nerve injury (3 resolved during the index procedure; 1 resolved at 6 months follow-up). One serious adverse device event was reported: femoral arterial embolism event occurring 2 weeks post index procedure (1.7%). Of the 56 patients that had complete 12-month follow-up, 43 (76.8%) were free from recurrent atrial arrhythmias. Conclusion Initial multicenter clinical experience with the novel CB has demonstrated long-term safety and efficacy of PVI in patients with paroxysmal AF. Further studies are underway to confirm these findings. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Boston Scientific

Introduction: Low nadir temperature (N T ) and long thaw times with cryoballoon ablation are associated with successful PVI. Recently, a cryo-system was designed to improve catheter stability during ablation via a balloon (CB, POLARx™, Boston Scientific) that maintains uniform pressure and size. The purpose of this study was to evaluate whether the CB biophysical parameters, including time to -40 o C (TT40), N T , time to thaw (iTT0), and time to 15 o C (iTT15), are associated with acute PVI success in paroxysmal AF patients. Methods: Ablation was delivered for 180s if isolation was achieved in ≤ 60s or 240s if isolation occurred after 60s. PVI was confirmed via entrance and exit block. Biophysical parameters were evaluated for 3 groups: block with 180s ablation, block with 240s ablation, and for unsuccessful initial treatments (gap veins). The diagnostic accuracy for predicting PVI was assessed using area under (AUC) the receiver operator characteristic (ROC) curve for ablations > 120s. Results: Forty-six consecutive de novo PVI procedures at 4 centers were analyzed (n=234 ablations). All PVs were isolated using the CB alone, with the vast majority within 60s. During freeze, TT40 and N T were significantly shorter and colder for isolated veins compared to gap veins (Table). During thaw, iTT0 and iTT15 were significantly longer for isolated veins compared to gap veins (Table). ROC analysis found iTT15 had the highest diagnostic accuracy for isolation (AUC: 0.85) followed by N T (AUC: 0.81), iTT0 (AUC: 0.77), and TT40 (AUC: 0.72). Optimal cutoff values for iTT15 and N T were 33.5s and -48 o C, which had positive predictive values for acute block of 96.6% and 93.5%. Conclusions: When using the novel CB, ablations reaching < -48 o C and having thaw times to 15 o C > 33.5s were predictive of acute block in PVI, providing guidance toward improved workflow and potential reduction in procedural time.

This study sought to determine whether durable pulmonary vein isolation (PVI) using pulsed field ablation (PFA) translates to freedom from atrial fibrillation recurrence without an increase in adverse events.PFA is a nonthermal ablative modality that, in preclinical studies, is able to preferentially ablate myocardial tissue with minimal effect on surrounding tissues. Herein, we present 1-year clinical outcomes of PFA.In 3 multicenter studies (IMPULSE [A Safety and Feasibility Study of the IOWA Approach Endocardial Ablation System to Treat Atrial Fibrillation], PEFCAT [A Safety and Feasibility Study of the FARAPULSE Endocardial Ablation System to Treat Paroxysmal Atrial Fibrillation], and PEFCAT II [Expanded Safety and Feasibility Study of the FARAPULSE Endocardial Multi Ablation System to Treat Paroxysmal Atrial Fibrillation]), paroxysmal atrial fibrillation patients underwent PVI using a basket or flower PFA catheter. Invasive remapping was performed at ∼2 to 3 months, and reconnected PVs were reisolated with PFA or radiofrequency ablation. After a 90-day blanking period, arrhythmia recurrence was assessed over 1-year follow-up.In 121 patients, acute PVI was achieved in 100% of PVs with PFA alone. PV remapping, performed in 110 patients at 93.0 ± 30.1 days, demonstrated durable PVI in 84.8% of PVs (64.5% of patients), and 96.0% of PVs (84.1% of patients) treated with the optimized biphasic energy PFA waveform. Primary adverse events occurred in 2.5% of patients (2 pericardial effusions or tamponade, 1 hematoma); in addition, there was 1 transient ischemic attack. The 1-year Kaplan-Meier estimates for freedom from any atrial arrhythmia for the entire cohort and for the optimized biphasic energy PFA waveform cohort were 78.5 ± 3.8% and 84.5 ± 5.4%, respectively.PVI with a "single-shot" PFA catheter results in excellent PVI durability and acceptable safety with a low 1-year rate of atrial arrhythmia recurrence. These data mitigate concern that the nonthermal ablative mechanism of PFA might mask undiscovered compromises to clinical success. (IMPULSE: A Safety and Feasibility Study of the IOWA Approach Endocardial Ablation System to Treat Atrial Fibrillation, NCT03700385; A Safety and Feasibility Study of the FARAPULSE Endocardial Ablation System to Treat Paroxysmal Atrial Fibrillation, NCT03714178; PEFCAT II Expanded Safety and Feasibility Study of the FARAPULSE Endocardial Multi Ablation System to Treat Paroxysmal Atrial Fibrillation [PEFCAT II], NCT04170608).

Background: Unlike for paroxysmal atrial fibrillation (AF), pulmonary vein isolation (PVI) alone is considered insufficient for many patients with persistent AF. Adjunctive ablation of the left atrial posterior wall (LAPW) may improve outcomes, but is limited by both the difficulty of achieving lesion durability and concerns of damage to the esophagus-situated behind the LAPW. Objectives: This study sought to assess the safety and lesion durability of pulsed field ablation (PFA) for both PVI and LAPW ablation in persistent AF. Methods: PersAFOne is a single-arm study evaluating biphasic, bipolar PFA using a multispline catheter for PVI and LAPW ablation under intracardiac echocardiographic guidance. A focal PFA catheter was used for cavotricuspid isthmus ablation. No esophageal protection strategy was used. Invasive remapping was mandated at 2 to 3 months to assess lesion durability. Results: In 25 patients, acute PVI (96 of 96 pulmonary veins [PVs] ; mean ablation time: 22 min ; interquartile range [IQR]: 15 to 29 min) and LAPW ablation (24 of 24 patients ; median ablation time: 10 min ; IQR: 6 to 13 min) were 100% acutely successful with the multispline PFA catheter alone. Using the focal PFA catheter, acute cavotricuspid isthmus block was achieved in 13 of 13 patients (median: 9 min ; IQR: 6 to 12 min). The median total procedure time was 125 min (IQR: 108 to 166 min) (including a median of 28 min [IQR: 25 to 33 min] for voltage mapping), with a median of 16 min (IQR: 12 to 23 min) fluoroscopy. Post- procedure esophagogastroduodenoscopy and repeat cardiac computed tomography revealed no mucosal lesions or PV narrowing, respectively. Invasive remapping demonstrated durable isolation (defined by entrance block) in 82 of 85 PVs (96%) and 21 of 21 LAPWs (100%) treated with the pentaspline catheter. In 3 patients, there was localized scar regression of the LAPW ablation, albeit without conduction breakthrough. Conclusions: The unique safety profile of PFA potentiated efficient, safe, and durable PVI and LAPW ablation. This extends the potential role of PFA beyond paroxysmal to persistent forms of AF. (Pulsed Fields for Persistent Atrial Fibrillation [PersAFOne] ; NCT04170621).

We sought to characterize the patterns of active pressure development of the inspiratory and expiratory rib cage muscles (P(rcm, i) and P(rcm, e)), the diaphragm (P(di, i)), and the expiratory abdominal muscles (P(abm, e)) during maximal "dry" breath holding in trained apnea divers (n = 8). METHODS: Respiratory contractions were assessed via esophageal and gastric manometry. It was expected that inspiratory/expiratory pressures would progressively increase in both magnitude and frequency during the struggle phase, and that inspiratory rib cage muscle pressures would rise at a rate exceeding that of the diaphragm by the break point. RESULTS: P(rcm, i), P(di, i), P(rcm, e), and P(abm, e) significantly increased from the beginning until the end of the struggle phase (P < 0.05). Moreover, P(di, i)/P(rcm, i) and P(abm, e)/P(rcm, e) ratios had declined by the break point (P < 0.05), indicating that rib cage muscles increased their contribution to net inspiratory/expiratory pressure development by the end of the breath hold, relative to that contributed by the diaphragm and abdominal muscles. The pressure-time indices of the diaphragm and inspiratory rib cage muscles continuously increased over the struggle phase (P < 0.05). CONCLUSIONS: The "extradiaphragmatic" shift in inspiratory muscle recruitment, commensurate with increasing P(rcm, e) and P(abm, e), may reflect an extreme loading response to breathing against a heavy elastance (i.e., closed glottis). In addition, the relative intensity of diaphragmatic and inspiratory rib cage muscle contractions approaches potentially "fatiguing" levels by the break point of maximal breath holding.

Castleman’s disease (in the literature also known as angiofollicular hyperplasia) is a rare benign lymphoproliferative disease. Clinically, it can manifest as unicentric or multicentric disease. Unicentric disease is most often diagnosed by accident or by symptomatology resulting from compression upon the adjoining anatomical structures. Considering its lymphatic origin, tumor mass can theoretically occur in any body region. We present a case of paracardiac localization of unicentric Castleman’s disease in a previously healthy 24-year-old woman. In such clinical cases, the specific localization of the tumor and its radiological properties can pose a differential diagnostic dilemma. Correct diagnosis is only possible after complete surgical excision and histopathologic analysis, which is the optimal therapeutic approach in this disease.

The purpose of the study was to provide insight in diaphragmatic involuntary breathing movements (IBM) during struggle phase of apnea at total lung capacity (TLC) and functional residual capacity (FRC) using magnetic resonance imaging along with measurements of hemodynamics and arterial oxygenation. The study was performed in eight elite breath-hold divers. There was a similar increase in diaphragmatic cranio-caudal excursions towards the end of TLC and FRC apnea. The greatest diaphragmatic excursion in both apneas and during tidal breathing was in the middle and posterior part of the diaphragm. Diaphragm thickness in elite BHD was within the reference range of normal values suggesting no diaphragmatic hypertrophy in this population. We found that the range of diaphragmatic excursions increases toward the end of apneas. Additionally, our data suggest that the diaphragm participates in IBM occurrence and that various segments of the diaphragm behave nonhomogenously both in tidal breathing and IBMs.

Premature ventricular contractions (PVC) elicit larger bursts of multiunit muscle sympathetic nerve activity (MSNA), reflecting the ability to increase postganglionic axonal recruitment. We tested the hypothesis that chronic heart failure (CHF) limits the ability to recruit postganglionic sympathetic neurons as a response to PVC due to the excessive sympathetic activation in these patients. Sympathetic neurograms of sufficient signal-to-noise ratio were obtained from six CHF patients and from six similarly aged control individuals. Action potentials (APs) were extracted from the multiunit sympathetic neurograms during sinus rhythm bursts and during the post-PVC bursts. These APs were classified on the basis of the frequency per second, the content per burst, and the peak-to-peak amplitude, which formed the basis of binning the APs into active clusters. Compared with controls, CHF had higher APs per burst and higher number of active clusters per sinus rhythm burst ( P < 0.05). Compared with sinus rhythm bursts, both groups increased AP frequency and the number of active clusters in the post-PVC burst ( P < 0 .05). However, compared with controls, the increase in burst integral, AP frequency, and APs per burst during the post-PVC burst was less in CHF patients. Nonetheless, the PVC-induced increase in active clusters per burst was similar between the groups. Thus, these CHF patients retained the ability to recruit larger APs but had a diminished ability to increase overall AP content.

Evidence suggests that the autonomic nervous system may actively regulate the cerebral vasculature. In this study, central hemodynamics and brain oxy-hemoglobin, deoxy-hemoglobin and total hemoglobin changes (bO₂Hb, bdHb and bTHb) were monitored during infusion of epinephrine (0.06 μg/kg/min over 6 min, and 0.12 μg/kg/min for 3 min) in 12 men. Epinephrine decreased mean arterial pressure (MAP) and total peripheral resistance (TPR), while heart rate (HR), stroke volume (SV) and cardiac output (CO) increased, but did not affect bO₂Hb, bdHb or bTHb. However, upon the cessation of epinephrine infusion an increase in both Oxy- and Total Hb occurred which peaked at 3 min post infusion (+6.0±4.6 and +4.9±4.8 μmol/L respectively, P

We tested the hypothesis that breath-hold divers (BHD) attain higher level of sympathetic activation than controls due to the duration of breath-hold rather than a different recruitment strategy. In 6 control subjects and 8 BHD we measured muscle sympathetic neural activity (MSNA) prior to and during functional residual capacity (FRC) and total lung capacity (TLC) breath-holding. On a subset of subjects we applied a new technique for the detection of action potentials (APs) in multiunit MSNA. Compared with controls, BHD group had lower burst AP content (13±7 vs. 6±3AP/burst ; P=0.05) and number of active clusters (5±1 vs. 3±1clusters/burst ; P=0.05) at baseline. However, the overall sympathetic AP/unit-time was comparable between the groups (131±105 vs. 173±152AP/min ; P=0.62) due to increased burst frequency in BHD group (20±4bursts/min) vs. controls (13±3bursts/min) (P=0.039). The achieved level in total MSNA during FRC breath-holds was higher in divers (2298±780 vs. 1484±575a.u./min ; P=0.039). Total MSNA at the end of TLC breath-hold was comparable between the groups (157±50 (controls) vs. 214±41s (BHD) ; P=0.61). FRC and TLC breath-holds increased AP frequency, burst AP content and active clusters/bursts in both groups but the response magnitude was determined by the type of the breath-hold. The divers used fewer number of APs/burst and active clusters/burst. In both groups breath-holds resulted in similar increases in MSNA which were reached both by an increase in firing frequency and by recruitment of previously silent, larger (faster conducting) sympathetic neurons, and possibly by repeated firing within the same burst.

SCUBA diving is regularly associated with asymptomatic changes in cardiac, pulmonary and vascular function. The aim of this study was to evaluate the changes in vascular/endothelial function following SCUBA diving and to assess the potential difference between two breathing gases: air and nitrox 36 (36% oxygen and 64% nitrogen). Ten divers performed two 3-day diving series (no-decompression dive to 18 m with 47 min bottom time with air and nitrox, respectively), with 2 weeks pause in between. Arterial/endothelial function was assessed using SphygmoCor and flow-mediated dilation measurements, and concentration of nitrite before and after diving was determined in venous blood. Production of nitrogen bubbles post-dive was assessed by ultrasonic determination of venous gas bubble grade. Significantly higher bubbling was found after all air dives as compared to nitrox dives. Pulse wave velocity increased slightly (~6%), significantly after both air and nitrox diving, indicating an increase in arterial stiffness. However, augmentation index became significantly more negative after diving indicating smaller wave reflection. There was a trend for post-dive reduction of FMD after air dives ; however, only nitrox diving significantly reduced FMD. No significant differences in blood nitrite before and after the dives were found. We found that nitrox diving affects systemic/vascular function more profoundly than air diving by reducing FMD response, most likely due to higher oxygen load. Both air and nitrox dives increased arterial stiffness, but decreased wave reflection suggesting a decrease in peripheral resistance due to exercise during diving. These effects of nitrox and air diving were not followed by changes in plasma nitrite.

Limited information exists concerning arterial blood pressure (BP) changes in underwater breath-hold diving. Simulated chamber dives to 50 m of freshwater (mfw) reported very high levels of invasive BP in two divers during static apnea (SA), whereas a recent study using a noninvasive subaquatic sphygmomanometer reported unchanged or mildly increased values at 10 m SA dive. In this study we investigated underwater BP changes during not only SA but, for the first time, dynamic apnea (DA) and shortened (SHT) DA in 16 trained breath-hold divers. Measurements included BP (subaquatic sphygmomanometer), ECG, and pulse oxymetry (arterial oxygen saturation, SpO2, and heart rate). BP was measured during dry conditions, at surface fully immersed (SA), and at 2 mfw (DA and SHT DA), whereas ECG and pulse oxymetry were measured continuously. We have found significantly higher mean arterial pressure (MAP) values in SA (∼40%) vs. SHT DA (∼30%). Postapneic recovery of BP was slightly slower after SHT DA. Significantly higher BP gain (mmHg/duration of apnea in s) was found in SHT DA vs. SA. Furthermore, DA attempts resulted in faster desaturation vs. SA. In conclusion, we have found moderate increases in BP during SA, DA, and SHT DA. These cardiovascular changes during immersed SA and DA are in agreement with those reported for dry SA and DA.

Purpose: During SCUBA diving, breathing at increased pressure leads to a greater tissue gas uptake. During ascent, tissues may become supersaturated, and the gas is released in the form of bubbles that typically occur on the venous side of circulation. These venous gas emboli (VGE) are usually eliminated as they pass through the lungs, although their occasional presence in systemic circulation (arterialization) has been reported and it was assumed to be the main cause of the decompression sickness. The aims of the present study were to assess the appearance of VGE after air dives where no stops in coming to the surface are required and to assess their potential occurrence and frequency in the systemic circulation. Methods: Twelve male divers performed six dives with 3 d of rest between them following standard no-decompression dive procedures: 18/60, 18/70, 24/30, 24/40, 33/15, and 33/20 (the first value indicates depth in meters of sea water and the second value indicates bottom time in minutes). VGE monitoring was performed ultrasonographically every 20 min for 120 min after surfacing. Results: Diving profiles used in this study produced unexpectedly high amounts of gas bubbles, with most dives resulting in grade 4 (55/69 dives) on the bubble scale of 0-5 (no to maximal bubbles). Arterializations of gas bubbles were found in 5 (41.7%) of 12 divers and after 11 (16%) of 69 dives. These VGE crossovers were only observed when a large amount of bubbles was concomitantly present in the right valve of the heart. Conclusions: Our findings indicate high amounts of gas bubbles produced after no-decompression air dives based on standardized diving protocols. High bubble loads were frequently associated with the crossover of VGE to the systemic circulation. Despite these findings, no acute decompression-related pathology was detected

Breath hold divers are faced with two main physiological challenges: pressure induced compression and extended time without breathing, exposing them to extremes of hypoxia/hypercapnia. Current world records are 214 m for depth and 11:35 min for duration. Hypoxic loss of consciousness is frequently observed during competitions. The major physiological components of the diving response that occurs during breath holding are peripheral vasoconstriction, bradycardia, decreased cardiac output, increased cerebral and myocardial blood flow, increased blood pressure, splenic contraction and preserved O(2) delivery to the brain and the heart. Sympathetic nervous activity is exceptionally engaged at the end of voluntary breath holds. We hypothesize that these adaptations to extended cessation of breathing ending with extreme hypoxia can be used as a model of brain survival response during conditions involving profound brain deoxygenation and in some instances reduced brain perfusion.

Glossopharyngeal insufflation (lung packing) is a common maneuver among experienced apnea divers by which additional air is pumped into the lungs. It has been shown that packing may compromise cardiovascular homeostasis. We tested the hypothesis that the packing-mediated increase in intrathoracic pressure enhances the baroreflex-mediated increase in muscle sympathetic nerve activity (MSNA) in response to an exaggerated drop in cardiac output (CO). We compared changes in hemodynamics and MSNA (peroneal microneurography) during maximal breath-holds without and with prior moderate packing (0.79 ± 0.40 liters) in 14 trained divers (12 men, 2 women, 26.7 ± 4.5 yr, body mass index 24.8 ± 2.4 kg/m2). Packing did not change apnea time (3.8 ± 1.0 vs. 3.8 ± 1.2 min), hemoglobin oxygen desaturation (−17.6 ± 12.3 vs. −18.7 ± 12.8%), or the reduction in CO (1 min: −3.65 ± 1.83 vs. −3.39 ± 1.96 l/min; end of apnea: −2.44 ± 1.33 vs. −2.16 ± 1.44 l/min). On the other hand, packing dampened the early, i.e., 1-min increase in mean arterial pressure (MAP, 1 min: 9.2 ± 8.3 vs. 2.4 ± 11.0 mmHg, P < 0.01) and in total peripheral resistance (relative TPR, 1 min: 2.1 ± 0.5 vs. 1.9 ± 0.5, P < 0.05) but it augmented the concomitant rise in MSNA (1 min: 28.0 ± 11.7 vs. 39.4 ± 12.7 bursts/min, P < 0.001; 32.8 ± 16.4 vs. 43.9 ± 14.8 bursts/100 heart beats, P < 0.01; 3.3 ± 2.1 vs. 4.8 ± 3.2 au/min, P < 0.05). We conclude that the early sympathoactivation 1 min into apnea after moderate packing is due to mechanisms other than excessive reduction in CO. We speculate that lower MAP despite increased MSNA after packing might be explained by vasodilator substances released by the lungs. This idea should be addressed in future studies.

SCUBA diving is associated with generation of gas emboli due to gas release from the supersaturated tissues during decompression. Gas emboli arise mostly on the venous side of circulation, and they are usually eliminated as they pass through the lung vessels. Arterialization of venous gas emboli (VGE) is seldom reported, and it is potentially related to neurological damage and development of decompression sickness. The goal of the present study was to evaluate the generation of VGE in a group of divers using a mixture of compressed oxygen, helium, and nitrogen (trimix) and to probe for their potential appearance in arterial circulation. Seven experienced male divers performed three dives in consecutive days according to trimix diving and decompression protocols generated by V-planner, a software program based on the Varying Permeability Model. The occurrence of VGE was monitored ultrasonographically for up to 90 min after surfacing, and the images were graded on a scale from 0 to 5. The performed diving activities resulted in a substantial amount of VGE detected in the right cardiac chambers and their frequent passage to the arterial side, in 9 of 21 total dives (42%) and in 5 of 7 divers (71%). Concomitant measurement of mean pulmonary artery pressure revealed a nearly twofold augmentation, from 13.6 ± 2.8, 19.2 ± 9.2, and 14.7 ± 3.3 mmHg assessed before the first, second, and the third dive, respectively, to 26.1 ± 5.4, 27.5 ± 7.3, and 27.4 ± 5.9 mmHg detected after surfacing. No acute decompression-related disorders were identified. The observed high gas bubble loads and repeated microemboli in systemic circulation raise questions about the possibility of long-term adverse effects and warrant further investigation.

Epikardna VT ablacija je vrlo invazivna procedura, no kada se radi u centrima s kardiokirurskom podrskom i velikim volumenom ablacijskih procedura, nudi mogucnost sigurnog izvođenja i daje sansu ostvariti kontrolu nad aritmijama koje ugrožavaju ne samo kvalitetu, vec i život ovih pacijenata.

Is there an ordered pattern in the recruitment of postganglionic sympathetic neurones? Using new multi-unit action potential detection and analysis techniques we sought to determine whether the activation of sympathetic vasomotor neurones during stress is governed by the size principle of recruitment. Multi-unit postganglionic sympathetic activity (fibular nerve) was collected from five male subjects at rest and during periods of elevated sympathetic stress (end-inspiratory apnoeas; 178 ± 37 s(mean ± S.D.)). Compared to baseline (0.24 ± 0.04 V), periods of elevated stress resulted in augmented sympathetic burst size (1.34 ± 0.38 V, P < 0.05). Increased burst size was directly related to both the number of action potentials within a multi-unit burst of postganglionic sympathetic activity (r= 0.88 ± 0.04, P < 0.001 in all subjects), and the amplitude of detected action potentials (r= 0.88 ± 0.06, P < 0.001 in all subjects). The recruitment of larger, otherwise silent, neurons accounted for approximately 74% of the increase in detected action potentials across burst sizes. Further, action potential conduction velocities (inverse of latencies) were increased as a function of action potential size (R2= 0.936, P= 0.001). As axon diameter is positively correlated with action potential size and conduction velocity, these data suggest that the principle of ordered recruitment based on neuronal size applies to postganglionic sympathetic vasomotor neurones. This information may be pertinent to our understanding of reflex-specific recruitment strategies in postganglionic sympathetic nerves, patterns of vasomotor control during stress, and the malleability of sympathetic neuronal properties and recruitment in health and disease.

The aim of this study was to assess the effects of successive deep dives on endothelial function of large conduit arteries and plasma pro-oxidant and antioxidant activity. Seven experienced divers performed six dives in six consecutive days using a compressed mixture of oxygen, helium and nitrogen (trimix) with diving depths ranging from 55 to 80 m. Before and after first, third and sixth dive, venous gas emboli formation and brachial artery function (flow-mediated dilation, FMD) was assessed by ultrasound. In addition, plasma antioxidant capacity (AOC) was measured by ferric reducing antioxidant power, and the level of oxidative stress was assessed by thiobarbituric acid-reactive substances (TBARS) method. Although the FMD was reduced to a similar extent after each dive, the comparison of predive FMD showed a reduction from 8.6% recorded before the first dive to 6.3% before the third (P = 0.03) and 5.7% before the sixth dive (P = 0.003). A gradual shift in baseline was also detected with TBARS assay, with malondialdehyde values increasing from 0.10 ± 0.02 μmol l⁻¹ before the first dive to 0.16 ± 0.03 before the sixth (P = 0.005). Predive plasma AOC values also showed a decreasing trend from 0.67 ± 0.20 mmol l⁻¹ trolox equivalents (first day) to 0.56 ± 0.12 (sixth day), although statistical significance was not reached (P = 0.08). This is the first documentation of acute endothelial dysfunction in the large conduit arteries occurring after successive deep trimix dives. Both endothelial function and plasma pro-oxidant and antioxidant activity did not return to baseline during the course of repetitive dives, indicating possible cumulative and longer lasting detrimental effects.

An increasing number of recreational self- contained underwater breathing apparatus (SCUBA) divers use trimix of oxygen, helium, and nitrogen for dives deeper than 60 m of sea water. Although it was seldom linked to the development of pulmonary edema, whether SCUBA diving affects the extravascular lung water (EVLW) accumulation is largely unexplored. Methods: Seven divers performed six dives on consecutive days using compressed gas mixture of oxygen, helium, and nitrogen (trimix), with diving depths ranging from 55 to 80 m. The echocardiographic parameters (bubble grade, lung comets, mean pulmonary arterial pressure (PAP), and left ventricular function) and the blood levels of the N-terminal part of pro- brain natriuretic peptide (NT-proBNP) were assessed before and after each dive. Results: Venous gas bubbling was detected after each dive with mean probability of decompression sickness ranging from 1.77% to 3.12%. After each dive, several ultrasonographically detected lung comets rose significantly, which was paralleled by increased pulmonary artery pressure (PAP) and decreased left ventricular contractility (reduced ejection fraction at higher end-systolic and enddiastolic volumes) as well as the elevated NT-proBNP. The number of ultrasound lung comets and mean PAP did not return to baseline values after each dive. Conclusions: This is the first report that asymptomatic SCUBA dives are associated with accumulation of EVLW with concomitant increase in PAP, diminished left ventricular contractility, and increased release of NT- proBNP, suggesting a significant cardiopulmonary strain. EVLW and PAP did not return to baseline during repetitive dives, indicating possible cumulative effect with increasing the risk for pulmonary edema.

Apnea divers are exposed to repeated massive arterial oxygen desaturation, which could perturb chemoreflexes. An earlier study suggested that peripheral chemoreflex regulation of sympathetic vasomotor tone and ventilation may have recovered 4 or more weeks into the off season. Therefore, we tested the hypothesis that peripheral chemoreflex regulation of ventilation and sympathetic vasomotor tone is present during the training season. We determined ventilation, heart rate, blood pressure, cardiac stroke volume, and muscle sympathetic nerve activity (MSNA) during isocapnic hypoxia in 10 breath hold divers and 11 matched control subjects. The study was carried out at the end of the season of intense apnea trainings. Baseline MSNA frequency was 30+/-4bursts/min in control subjects and 25+/-4bursts/min in breath hold divers (P=0.053). During hypoxia burst frequency and total sympathetic activity increased similarly in both groups. Sympathetic activity normalized during the 30-minute recovery. Hypoxia-induced stimulation of minute ventilation was similar in both groups, although in divers it was maintained by higher tidal volumes and lower breathing frequency compared with control subjects. In both groups, hypoxia increased heart rate and cardiac output whereas total peripheral resistance decreased. Blood pressure remained unchanged. We conclude that peripheral chemoreflex regulation of ventilation and sympathetic vasomotor tone is paradoxically preserved in apnea divers, both, during the off and during the training season. The observation suggests that repeated arterial oxygen desaturation may not be sufficient explaining sympathetic reflex abnormalities similar to those in obstructive sleep apnea patients. Copyright © 2009 Elsevier B.V. All rights reserved.

Recently, an increase in extravascular lung water (EVLW) accumulation with diminished left ventricular contractility within 60 min after SCUBA diving was reported. We have observed previously that diving was associated with reduced diffusing lung capacity for carbon monoxide (DLCO) and arterial oxygen pressure for up to 60-80 min postdive. Here we investigated whether increased EVLW persists 2- 3h after successive deep dives in a group of seven male divers. The echocardiographic indices of pulmonary water accumulation (ultrasound lung comets (ULC)) and left ventricular function, respiratory functional measurements and arterial oxygen saturation (SaO(2)) were assessed 2-3h post diving, while venous gas bubbles (VGB) and the blood levels of NT-proBNP and proANP were analyzed 40 min after surfacing. Spirometry values, flow- volume, DLCO, SaO(2) and ULC were unchanged after each dive, except for significant increase in ULC after the second dive. Left ventricular function was reduced, while NT- proBNP and proANP levels were significantly elevated after majority of dives, suggesting a cardiac strain.

The use of trimix (a mixture of oxygen, helium, and nitrogen) has significantly increased among the diver population. However, data indicating how trimix dives at most common depths affect the cardiovascular function are sparse. The purpose of this study was to investigate the cardiovascular effects of trimix dives and compare them with air dives and to determine whether the repetition of dives in successive days affects their extent.Nine professional divers performed four dives in consecutive days where the dive depth was progressively increased to the maximum of 55 m. Divers used air in the first dive, nitrox 25 in the second, and trimix 20/30 in the third and fourth dives. Echocardiography was performed before and after each dive.After each dive, a significantly decreased left ventricular ejection fraction and fractional shortening and an increased end-systolic volume without a change in end-diastolic volume were found, indicating a depressed systolic function of the left side of the heart. Assessment of the ratio between pulmonary artery acceleration time and right ventricular ejection time (used as an indicator of pulmonary artery pressure (PAP)) revealed an increase in PAP after all the dives. No physiologically relevant cumulative effects of the multiple dives or signs of acclimatization were found.The current study shows that the cardiovascular effects of trimix dives do not differ from those of the dives with compressed air. However, it suggests that even a very safe and conservative trimix diving profile exerts significant cardiovascular effects.

Background and Purpose: Physiology exercise employing simulated diving is used in our curriculum to integrate knowledge in cardio-respiratory physiology. Aim was to improve model used in physiology exercise by employing continuous recordings of arterial pressure and heart rate. Materials and Methods: Total of 55 medical and dental students volunteered for the exercise. They were instrumented with photoplethysmographic blood pressure and heart rate device, as well as with pulse oxymetry. Continuous measurement of variables was undertaken while students performed apneas or breathed through snorkel in air or in cold water, or temperature change was applied to their forehead. Results: Employment of continuous recordings enabled detailed insight into changes in selected cardiovascular parameters during 30 seconds breathholding. Time course of the changes showed marked biphasic response. When face was submerged in cold water during apnea, arterial pressure initially decreased and heart rate increased. At the end of breath-hold, arterial pressure increased and heart rate decreased, respectively. Corresponding changes were less pronounced when breath-hold was performed without face immersion. Conclusion: Improved protocol in laboratory exercise enabled us to show two distinct phases in changes of cardiovascular variables which are characteristic of diving reflex. We showed students how modern technology can improve their studies in near future and encouraged and motivate them to participate actively in exercise.

AimsTo examine whether dynamic cerebral autoregulation is acutely impaired during maximal voluntary apnoea in trained divers.MethodsMean arterial pressure (MAP), cerebral blood flow-velocity (CBFV) and end-tidal partial pressures of O2 and CO2 (PETO2 and PETCO2) were measured in eleven trained, male apnoea divers (28 ± 2 yr; 182 ± 2 cm, 76 ± 7 kg) during maximal "dry" breath holding. Dynamic cerebral autoregulation was assessed by determining the strength of phase synchronisation between MAP and CBFV during maximal apnoea.ResultsThe strength of phase synchronisation between MAP and CBFV increased from rest until the end of maximal voluntary apnoea (PConclusionsThis study is the first to report that dynamic cerebral autoregulation is acutely impaired in trained divers performing maximal voluntary apnoea. Furthermore, our data suggest that the impaired autoregulatory response is related to the change in PETCO2, but not PETO2, during maximal apnoea in trained divers.

The current study tested the hypothesis that modification in central hemodynamics during short-term continuous positive airway pressure (CPAP) application was accompanied by altered firing patterns of sympathetic nerve activity in CHF patients and healthy subjects.Muscle sympathetic nerve activity (MSNA), hemodynamic and ventilatory parameters were obtained from 8 healthy middle aged subjects and 7 CHF patients. Action potentials (APs) were extracted from MSNA neurograms, quantified as AP frequency and classified into different sized clusters. While on CPAP at 10cm H2O, multi-unit MSNA, AP frequency and mean burst area/min increased in healthy middle aged subjects (p

The effects of involuntary respiratory contractions on the cerebral blood flow response to maximal apnoea is presently unclear. We hypothesised that while respiratory contractions may augment left ventricular stroke volume, cardiac output and ultimately cerebral blood flow during the struggle phase, these contractions would simultaneously cause marked 'respiratory' variability in blood flow to the brain. Respiratory, cardiovascular and cerebrovascular parameters were measured in ten trained, male apnoea divers during maximal 'dry' breath holding. Intrathoracic pressure was estimated via oesophageal pressure. Left ventricular stroke volume, cardiac output and mean arterial pressure were monitored using finger photoplethysmography, and cerebral blood flow velocity was obtained using transcranial ultrasound. The increasingly negative inspiratory intrathoracic pressure swings of the struggle phase significantly influenced the rise in left ventricular stroke volume (R (2) = 0.63, P

Elite breath-hold divers are unique athletes challenged with compression induced by hydrostatic pressure and extreme hypoxia/hypercapnia during maximal field dives. The current world records for men are 214 meters for depth (Herbert Nitsch, No-Limits Apnea discipline), 11:35 minutes for duration (Stephane Mifsud, Static Apnea discipline), and 281 meters for distance (Goran Čolak, Dynamic Apnea with Fins discipline). The major physiological adaptations that allow breath-hold divers to achieve such depths and duration are called the “diving response” that is comprised of peripheral vasoconstriction and increased blood pressure, bradycardia, decreased cardiac output, increased cerebral and myocardial blood flow, splenic contraction, and preserved O2 delivery to the brain and heart. This complex of physiological adaptations is not unique to humans, but can be found in all diving mammals. Despite these profound physiological adaptations, divers may frequently show hypoxic loss of consciousness. The breath-hold starts with an easy-going phase in which respiratory muscles are inactive, whereas during the second so-called “struggle” phase, involuntary breathing movements start. These contractions increase cerebral blood flow by facilitating left stroke volume, cardiac output, and arterial pressure. The analysis of the compensatory mechanisms involved in maximal breath-holds can improve brain survival during conditions involving profound brain hypoperfusion and deoxygenation.

Scuba diving is associated with breathing gas at increased pressure, which often leads to tissue gas supersaturation during ascent and the formation of venous gas emboli (VGE). VGE crossover to systemic arteries (arterialization), mostly through the patent foramen ovale, has been implicated in various diving-related pathologies. Since recent research has shown that arterializations frequently occur in the absence of cardiac septal defects, our aim was to investigate the mechanisms responsible for these events. Divers who tested negative for patent foramen ovale were subjected to laboratory testing where agitated saline contrast bubbles were injected in the cubital vein at rest and exercise. The individual propensity for transpulmonary bubble passage was evaluated echocardiographically. The same subjects performed a standard air dive followed by an echosonographic assessment of VGE generation (graded on a scale of 0–5) and distribution. Twenty-three of thirty-four subjects allowed the transpulmonary passage of saline contrast bubbles in the laboratory at rest or after a mild/moderate exercise, and nine of them arterialized after a field dive. All subjects with postdive arterialization had bubble loads reaching or exceeding grade 4B in the right heart. In individuals without transpulmonary passage of saline contrast bubbles, injected either at rest or after an exercise bout, no postdive arterialization was detected. Therefore, postdive VGE arterialization occurs in subjects that meet two criteria: 1) transpulmonary shunting of contrast bubbles at rest or at mild/moderate exercise and 2) VGE generation after a dive reaches the threshold grade. These findings may represent a novel concept in approach to diving, where diving routines will be tailored individually.