Piezo1 and BKCa channels in human atrial fibroblasts: Interplay and remodelling in atrial fibrillation.

AIMS: Atrial Fibrillation (AF) is an arrhythmia of increasing prevalence in the aging populations of developed countries. One of the important indicators of AF is sustained atrial dilatation, highlighting the importance of mechanical overload in the pathophysiology of AF. The mechanisms by which atrial cells, including fibroblasts, sense and react to changing mechanical forces, are not fully elucidated. Here, we characterise stretch-activated ion channels (SAC) in human atrial fibroblasts and changes in SAC- presence and activity associated with AF. METHODS AND RESULTS: Using primary cultures of human atrial fibroblasts, isolated from patients in sinus rhythm or sustained AF, we combine electrophysiological, molecular and pharmacological tools to identify SAC. Two electrophysiological SAC- signatures were detected, indicative of cation-nonselective and potassium-selective channels. Using siRNA-mediated knockdown, we identified the cation-nonselective SAC as Piezo1. Biophysical properties of the potassium-selective channel, its sensitivity to calcium, paxilline or iberiotoxin (blockers), and NS11021 (activator), indicated presence of calcium-dependent 'big potassium channels' (BKCa). In cells from AF patients, Piezo1 activity and mRNA expression levels were higher than in cells from sinus rhythm patients, while BKCa activity (but not expression) was downregulated. Both Piezo1-knockdown and removal of extracellular calcium from the patch pipette resulted in a significant reduction of BKCa current during stretch. No co-immunoprecipitation of Piezo1 and BKCa was detected. CONCLUSIONS: Human atrial fibroblasts contain at least two types of ion channels that are activated during stretch: Piezo1 and BKCa. While Piezo1 is directly stretch-activated, the increase in BKCa activity during mechanical stimulation appears to be mainly secondary to calcium influx via SAC such as Piezo1. During sustained AF, Piezo1 is increased, while BKCa activity is reduced, highlighting differential regulation of both channels. Our data support the presence and interplay of Piezo1 and BKCa in human atrial fibroblasts in the absence of physical links between the two channel proteins.

Symbiotic cardiac pacemaker.

Self-powered implantable medical electronic devices that harvest biomechanical energy from cardiac motion, respiratory movement and blood flow are part of a paradigm shift that is on the horizon. Here, we demonstrate a fully implanted symbiotic pacemaker based on an implantable triboelectric nanogenerator, which achieves energy harvesting and storage as well as cardiac pacing on a large-animal scale. The symbiotic pacemaker successfully corrects sinus arrhythmia and prevents deterioration. The open circuit voltage of an implantable triboelectric nanogenerator reaches up to 65.2 V. The energy harvested from each cardiac motion cycle is 0.495 µJ, which is higher than the required endocardial pacing threshold energy (0.377 µJ). Implantable triboelectric nanogenerators for implantable medical devices offer advantages of excellent output performance, high power density, and good durability, and are expected to find application in fields of treatment and diagnosis as in vivo symbiotic bioelectronics.

Surgical Ablation of Atrial Fibrillation Using Energy Sources

ABSTRACT Surgical ablation, concomitant with other operations, is an option for treatment in patients with chronic atrial fibrillation. The aim of this study is to present a literature review on surgical ablation of atrial fibrillation in patients undergoing cardiac surgery, considering energy sources and return to sinus rhythm. A comprehensive survey was performed in the literature on surgical ablation of atrial fibrillation considering energy sources, sample size, study type, outcome (early and late), and return to sinus rhythm. Analyzing studies with immediate results (n=5), the percentage of return to sinus rhythm ranged from 73% to 96%, while those with long-term results (n=20) (from 12 months on) ranged from 62% to 97.7%. In both of them, there was subsequent clinical improvement of patients who underwent ablation, regardless of the energy source used. Surgical ablation of atrial fibrillation is essential for the treatment of this arrhythmia. With current technology, it may be minimally invasive, making it mandatory to perform a procedure in an attempt to revert to sinus rhythm in patients requiring heart surgery.

Surgical Ablation of Atrial Fibrillation Using Energy Sources.

Surgical ablation, concomitant with other operations, is an option for treatment in patients with chronic atrial fibrillation. The aim of this study is to present a literature review on surgical ablation of atrial fibrillation in patients undergoing cardiac surgery, considering energy sources and return to sinus rhythm. A comprehensive survey was performed in the literature on surgical ablation of atrial fibrillation considering energy sources, sample size, study type, outcome (early and late), and return to sinus rhythm. Analyzing studies with immediate results (n=5), the percentage of return to sinus rhythm ranged from 73% to 96%, while those with long-term results (n=20) (from 12 months on) ranged from 62% to 97.7%. In both of them, there was subsequent clinical improvement of patients who underwent ablation, regardless of the energy source used. Surgical ablation of atrial fibrillation is essential for the treatment of this arrhythmia. With current technology, it may be minimally invasive, making it mandatory to perform a procedure in an attempt to revert to sinus rhythm in patients requiring heart surgery.

[Radiofrequency catheter ablation for ventricular premature beats of left coronary cusp under the guidance of 3-dimensional mapping system].

OBJECTIVE: To explore the efficacy and safety of radiofrequency catheter ablation (RCA) for ventricular premature beats originating from left coronary sinus under the guidance of 3-dimensional mapping system (CARTO). METHODS: A total of 15 patients with premature ventricular contractions (PVCs) originating from left coronary sinus underwent CARTO-guided RCA. Anatomical structures were constructed and three-dimension (3D) electrical activation sequence was plotted for left ventricle and aortic sinus. The distance of earliest activation point of PVCs and origin of left coronary artery were surveyed after left coronary arteriography. RESULTS: The electrocardiogram (ECG) results showed that R-wave was upward in leads II, III and avF, QRS waves in lead I was mainly of rS, rs and rsr types, QS type in lead avL, RS, Rs and rS type in lead V(1), RS type in lead V(3) and absence of S wave in lead V(5)/V(6). Intraoperative mapping detected the earliest activation point on the posterior-inferior origin of left coronary artery (LMCA) ostium (n = 7), on the anterio-inferior of LMCA ostium (n = 3) and on the inferior of LMCA ostium (n = 5). The earliest activation point (local activation time) was shorter 86 - 120 ms than surface electrocardiogram QRS wave, discharge melting on the earliest activation point and nearby succeeded. PVCs disappeared, PVCs failed to be induced under similar preoperative conditions (aleudrin intravenous) and no complication occurred intraoperatively and postoperatively. CONCLUSION: The CARTO-guided RCA is a safe and effective in the treatment of PVCs originating from left coronary sinus.

Novel transitional zone index allows more accurate differentiation between idiopathic right ventricular outflow tract and aortic sinus cusp ventricular arrhythmias.

BACKGROUND: Although several ECG algorithms have been proposed for differentiating the origins of outflow tract ventricular arrhythmia (OT-VA), their accuracy still is limited in cases with cardiac rotation. OBJECTIVE: The purpose of this study was to assess whether a novel "cardiac rotation-corrected" transitional zone (TZ) index would be a useful marker for differentiating right ventricular outflow tract (RVOT) origin from aortic sinus cusp (ASC) origin. METHODS: Surface ECGs of OT-VAs with left bundle branch block morphology and inferior axis in 112 patients who were successfully ablated in the RVOT (n = 87) or the ASC (n = 25) were analyzed. The TZ index was defined according to the site of R-wave transition of sinus beats and OT-VAs. RESULTS: The TZ index was significantly lower in the ASC origin than in the RVOT origin (-1.2 ± 0.9 vs 0.3 ± 0.7, P <.0001). A cutoff value of the TZ index <0 predicted the ASC origin with 88% sensitivity and 82% specificity. The previously reported R-wave duration index ≥ 50% had a high specificity of 85% but a low sensitivity of 44%, and R/S-wave amplitude index ≥ 30% had 68% sensitivity and 79% specificity. The area under the curve by receiver operating characteristic curve analysis was 0.90 for the TZ index, which was significantly higher than the R-wave duration index and R/S-wave amplitude index of 0.74 and 0.76, respectively. CONCLUSION: This novel TZ index can be a more useful marker for differentiating RVOT origin from ASC origin.

Heat shock protein70: a new marker for subsequent atrial fibrillation development?

Atrial fibrillation (AF) is a common arrhythmia, after cardiac surgery, and it is associated with a twofold increase in cardiovascular mortality and morbidity. Reperfusion injury and inflammation associated with cardiac surgery are thought to be involved in its pathogenesis. Heat shock proteins (HSPs) are a family of chaperone proteins which assist in preservation of cellular integrity by maintaining proteins in their correctly folded state. The aim of this study was to investigate pre-postoperative heat shock protein70 (HSP70) and high-sensitivity C-reactive protein in serum from patients in preoperative sinus rhythm. We prospectively screened 45 consecutive patients admitted to the hospital for elective coronary artery bypass surgery (CABG). Electrocardiogram characteristics and cardiovascular risk profile were documented. Pre- and postoperative blood samples were collected. HSP70 value was 8.9 +/- 4.8 ng/mL in Group A (study group) preoperatively and decreased to 7.7 +/- 7.0 ng/mL postoperatively. In contrast, preoperative value of HSP70 was 4.2 +/- 2.2 ng/mL and decreased to 2.7 +/- 2.6 ng/mL postoperatively in Group B (control group). Statistical analysis showed significant difference regarding preoperative HSP70 levels in Group A compared to Group B. To our knowledge, with this study, the association of pre- and postoperative circulating HSP70 with postoperative AF was demonstrated for the first time.

Ablation of permanent AF: adjunctive strategies to pulmonary veins isolation: targeting AF NEST in sinus rhythm and CFAE in AF.

Atrial fibrillation (AF) is highly prevalent and accounts for significant morbidity, mortality, and health care costs. Catheter ablation has become a therapeutic option in the management of this challenging arrhythmia. To optimize procedure safety and long-term efficacy, innovative technologies and ablation strategies have been targeting either the triggers initiating AF or the substrate responsible for its maintenance. Pulmonary vein (PV) isolation, initially limited to the PVs, has been modified to encompass the left atrial myocardium surrounding the PV ostia, namely the LA-PV antra. Our current intracardiac echo-guided approach to PV antra isolation, including the adjunct of superior vena cava isolation, has likely accounted for higher success rates by electrically isolating further AF trigger sites, modifying the substrate for AF maintenance and possibly by modulating a dysfunctional autonomic cardiac nervous system. However, the long-term outcome following ablation of permanent AF can be further improved by incorporating adjunctive ablation strategies to PV isolation, such as targeting ablation at sites exhibiting complex atrial fractionated electrograms (CFAEs)during AF or at sites exhibiting the so-called AF nests during real-time spectral mapping in sinus rhythm.

Restoring sinus rhythm in patients with previous pacemaker implantation submitted to cardiac surgery and concomitant surgical ablation of atrial fibrillation.

OBJECTIVE: Some patients submitted to cardiac surgery have concomitant atrial fibrillation and a previously implanted pacemaker. Because it is unknown if there is any potential for these patients to reassume a regular rate sinus rhythm after ablation of atrial fibrillation, we reviewed the results of all patients with pacemaker enrolled in the Registry of Atrial Fibrillation. MATERIALS: Thirty-six patients were included in this study. Twenty-six had valve disease, seven had coronary disease and three had congenital heart disease. They were submitted concomitantly to ablation of atrial fibrillation using biatrial approaches (seven patients), left sided (27), or right sided (three patients). Thirty-three hospital survivors had a mean follow-up of 18 months, and a maximum of 25 months. RESULTS: At 1 year (n=21), patients' rhythm was sinus non-pacing dependent (52%), sinus pacing-dependent (14%), and atrial fibrillation (14%). At 2 years (n=14), patients' rhythm was sinus non-pacing dependent (57%) and atrial fibrillation (43%). The only factor that may have had impact on the recovery of sinus rhythm at 1 year was the small size of the left atrium (p=0.05). CONCLUSIONS: We conclude that in a significant number of patients, having a pacemaker before surgery does not preclude sinus rhythm recovery after a cardiac operation and ablation for concomitant atrial fibrillation.

Glomectomy in carotid sinus syncope and associated arrythmias: symptomatic bradycardia, atrial flutter and atrial fibrillation.

UNLABELLED: The main causes of neurally mediated syncope (NMS) are carotid sinus syndrome (CSS) and vasovagal syncope. Long before, carotid sinus denervation was performed for different diseases, but for the first time we consider glomectomy (G) as a surgical treatment for NMS and related arrhythmias, alone or associated with cardiac pacing (PM). METHODS: We used Nakayama's technique for bronchial asthma, modified by us: removal of hypersensitive carotid glomus and presinusal lymphadenectomy. Forty five patients (pts) with recurrent NMS (cardioinhibitory 14 pts, mixed 31 pts) were included: 41 males, 4 females, aged 23-84 (mean 60 yrs). The diagnosis was documented clinically by carotid sinus massage, ECG-Holter, electrophysiologic studies, head-up tilt test. Malignant orthostatic syndrome was present in 4 pts, tussive syncope in one, sick sinus syndrome (SSS) in 6 pts, atrial fibrillation and flutter in 6 pts, AV block in 2 pts. Thirty four pts underwent G alone; 6 pts-G and PM; 5 pts-PM alone, 3 pts-G plus carotid endarterectomy. RESULTS: of G were excellent. All pts became free of syncope (max. follow-up 10 yrs). In addition, stable sinus rhythm was obtained in two pts (one with severe atrial fibrillation, another with persistent atrial fibrillation). In pts with SSS, A-V block or atrial fibrillation with bradycardia, PM was inserted (DDDR or VVIR). However, in pts with vasodepressor component of NMS, symptoms persist until G was performed. CONCLUSIONS: We conclude that our data support the efficiency of G in pts with NMS (either cardioinhibitor or vasodepressor), as well as in related arrhythmias. PM is indicated in pts with associated diseases: intrinsic SSS, AV block, atrial fibrillation with bradycardia.

Substrate-modification using electroanatomical mapping in sinus rhythm to treat ventricular tachycardia in patients with ischemic cardiomyopathy.

UNLABELLED: The treatment especially of frequent ischemic VT remains a challenge for medical and catheter ablation procedures. We evaluated the efficacy of a substrate-based procedure to eliminate clinical VTs in this patient collective. METHODS: In 25 consecutive patients (ejection fraction 37+/-12%) with frequent symptomatic medically refractory ischemic VT (with recurrent ICD-shocks), left ventricular anatomic scar mapping (Biosense Webster CARTO) was performed in order to modify the underlying myocardial substrate. Scar tissue was identified as having bipolar voltages <0.5 mV. Prior to the procedure an electrophysiological study (EPS) to determine number and morphology of inducible VTs was performed. Linear ablation procedures (8 mm tip, 70 Watts, 70 degrees C) were based on the findings of scar areas and proximity to anatomic obstacles. Correct location of ablation was documented by similarity of the morphology during pace-mapping. Follow-up included clinical evaluation, ICD holter interrogation plus holter ECG recording. RESULTS: The clinical VT was eliminated by linear catheter ablation in 23/25 patients (92%) (failure due to unstable catheter position during transaortic approach in 1 and epicardial origin of VT in 1). In 16/23 patients (70%) complete success could be produced with no VT inducible after substrate modification (1.7+/-1.0 lines per patient). In 7 patients (30%) only partial success was documented with further VTs inducible after ablation. No procedure-related complications occurred. During follow- up (10+/-4 months) 4 patients (16%) had occurrences of new VTs documented on ICD holter (3 patients with initially partial success and 1 with initial complete success) differing in cycle length and morphology from the clinical VT. Comparing patients with complete to those with partial success, there was a statistically significant difference of 93 vs. 48% freedom of arrhythmia (p=0.03). No difference in regard to baseline characteristics existed in these two patient subgroups. CONCLUSIONS: Ablation of frequent VTs in patients with ischemic cardiomyopathy can be safely performed using electro-anatomic scar mapping with a high procedural success of 90%. Based on the morphological findings, linear ablation can suppress inducibility of all VTs in 70% of patients with high mid-term efficacy. In patients with only partial ablation success, non-clinical VTs often occur early during follow-up (50%).

Catheter ablation of atypical atrial flutter and atrial tachycardia within the coronary sinus after left atrial ablation for atrial fibrillation.

OBJECTIVES: The goal of this study was to describe the prevalence and ablation of coronary sinus (CS) arrhythmias after left atrial ablation for atrial fibrillation (AF). BACKGROUND: The CS has been implicated in a variety of supraventricular arrhythmias. METHODS: Thirty-eight patients underwent mapping and ablation of atypical flutter that developed during (n = 5) or after (n = 33) ablation for AF. Also included were two patients with focal CS arrhythmias that occurred during an AF ablation procedure. A tachycardia was considered to be originating from the CS if the post-pacing interval in the CS matched the tachycardia cycle length and/or if it terminated during ablation in the CS. RESULTS: Among the 33 patients who developed atypical flutter late after AF ablation, 9 (27%) were found to have a CS origin. Overall, 16 of the 40 patients in this study had a CS arrhythmia. The tachycardia was macro-re-entrant in 14 patients (88%) and focal in two patients. Radiofrequency ablation with an 8-mm-tip catheter was successful in 15 patients (94%) without complication. In eight patients (50%), > or = 45 W was required for successful ablation. Thirteen of the 15 patients (87%) with a successful ablation acutely remained arrhythmia-free during 5 +/- 5 months of follow-up. CONCLUSIONS: The musculature of the CS serves as a critical component of the re-entry circuit in approximately 25% of patients with atypical flutter after ablation for AF. The CS may also generate focal atrial arrhythmias that may play a role in triggering and/or maintaining AF. Catheter ablation of these arrhythmias in the CS can be performed safely.

Safety and feasibility of cryothermal ablation within the mid- and distal coronary sinus.

INTRODUCTION: The aim of this study was to assess the safety and feasibility of catheter-based cryothermal ablation lesions in the mid- and distal coronary sinus. METHODS AND RESULTS: Cryothermal ablation lesions were delivered using a 7-French catheter at the mid- (n = 13) and distal (n = 12) coronary sinus in 14 swine under general anesthesia. Lesions were delivered for 2 or 4 minutes in a 1:2 randomized ratio such that seven 2-minute lesions and eighteen 4-minute lesions were delivered to a maximum negative temperature of -70 degrees C. Integrity of the circumflex artery was assessed by angiography before and after each lesion application. In five animals, arterial Doppler flow velocity was continuously monitored and coronary flow reserve assessed. Histologic assessment of the left AV ring was made after a 48-hour survival period and lesions graded for depth and transmurality. Eighteen of 25 lesions were >3 mm deep: five of seven 2-minute lesions and thirteen of eighteen 4-minute lesions. Lesions were transmural in 18 of 25 cases. Two transmural lesions were limited in depth due to their epicardial position. One 2-minute mid-coronary sinus lesion was not found. Adherent thrombus was seen grossly in the coronary sinus at one site and only on microscopic examination in three other lesions. Angiography demonstrated no arterial spasm or thrombosis. Continuous-flow Doppler remained unchanged throughout lesion production. Coronary flow reserve was unchanged (1.7 +/- 0.8 preablation vs 1.7 +/- 1.0 postablation, P = 0.6). The media and intima were preserved in all cases. Necrosis of the adventitia was seen in one arterial segment. CONCLUSION: Catheter-based cryoablation can produce lesions in the musculature of the adjacent atrium and ventricle when accessed from the coronary sinus without significant injury to the coronary sinus or adjacent artery. This method has potential application as the ablation method of choice when such lesions are required.

Right and left inferior extensions of the atrioventricular node may represent the anatomic substrate of the slow pathway in humans.

OBJECTIVES: The purpose of this study was to investigate the electrophysiologic characteristics of the inferior extensions of the human atrioventricular (AV) node and their possible relationship to slow pathway conduction. BACKGROUND: The human heart contains right and left inferior extensions of the AV node that relate to right and left atrial inputs. METHODS: Fourteen patients admitted for catheter ablation of left-sided accessory pathways were studied. Atrial pacing was performed from multiple sites in both atria, and simultaneous His-bundle recordings from right and left sides of the septum were made. RESULTS: Significant differences of A-H and stimulus to His (St-H) intervals with pacing at various sites were found. St-H intervals were similar during constant pacing from the low right atrium or the left inferoparaseptal area (112 +/- 28 ms vs 112 +/- 26 ms, P = .8, for right His recordings and 114 +/- 23 ms vs 111 +/- 25 ms, P = .9, for left His recordings). At maximum decrement, there were significantly shorter St-H intervals during left inferoparaseptal pacing compared to low right atrial pacing (201 +/- 24 ms vs 218 +/- 44 ms, P = .02, for right His recordings, and 200 +/- 24 ms vs 219 +/- 41 ms, P = .009, for left His recordings). Differences on right His recordings between St-H intervals at maximum decrement and at constant pacing from the low right atrium were significantly higher than corresponding differences on left His recordings during pacing from the left inferoparaseptal area (P = .035). CONCLUSIONS: Our findings support the concept that the right and left inferior extensions of the human AV node may represent the anatomic substrate of the slow pathway as defined electrophysiologically.