Posture and Gender Differentially Affect Heart Rate Variability of Symptomatic Mitral Valve Prolapse and Normal Adults.

BACKGROUND: Heart rate variability (HRV) has been shown to be a useful measure of autonomic activity in healthy and mitral valve prolapsed (MVP) subjects. However, the effects of posture and gender on HRV in symptomatic MVP and normal adults had not been elucidated in Taiwan. METHODS: A total of 118 MVP patients (7 males, 39 ± 7 years old; and 111 females, 42 ± 13 years old) and 148 healthy control (54 males, 28 ± 4 years old; and 94 females, 26 ± 6 years old) were investigated. The diagnosis of MVP was confirmed by cross-sectional echocardiography. A locally developed Taiwanese machine was used to record the HRV parameters for MVP and control groups in three stationary positions. Thereafter, the HRV time-domain parameters, and the frequency-domain parameters derived from fast Fourier transform or autoregressive methods were analyzed. RESULTS: The MVP group showed a decrease in time domain parameters and obtunded postural effects on frequency domain parameters moreso than the control group. Though the parasympathetic tone was dominant in female (higher RMSSD, nHF and lower nLF vs. male), the sympathetic outflow was higher in MVP female (lower SDNN, NN50 and higher nLF vs. normal female). While the parasympathetic activity was lower in male, sympathetic outflow was dominant in MVP male (lower nHF and higher nLF vs. normal male). CONCLUSIONS: Both MVP female and male subjects had elevated levels of sympathetic outflow. The obtunded postural effects on frequency domain measures testified to the autonomic dysregulation of MVP subjects.

Sitagliptin Modulates the Electrical and Mechanical Characteristics of Pulmonary Vein and Atrium.

BACKGROUND: The pulmonary veins (PVs) and atria are important foci during that period when atrial fibrillation (AF) is generated and maintained. It is well understood that hypertension and diabetes mellitus (DM) are important risk factors for AF. Dipeptidyl peptidase-IV (DPP-4) inhibitors are new agents in the fight against type 2 DM, though they have been found to have several cardiovascular effects. However, it is not clear whether DPP-4 may modulate the electrical and mechanical characteristics in hypertensive atrium or PVs. METHODS: Conventional microelectrodes were used to record the action potentials (APs) in isolated PVs, right atrium (RA), and left atrium (LA) in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) with or without sitagliptin (10 mg/kg) for 4 weeks. RESULTS: WKY (n = 5), SHR (n = 7), sitagliptin-treated WKY (n = 5) and sitagliptin-treated SHR (n = 7) had similar PV or sinoatrial spontaneous beating rates. However, the sitagliptin-treated WKY had fewer sinoatrial-PV beating rate differences than WKY, SHR or sitagliptin-treated SHR. WKY and SHR had shorter 90% (APD90) of RA AP duration than sitagliptin-treated WKY or sitagliptin-treated SHR. In contrast, WKY had longer LA APD90 than sitagliptin- treated WKY, but SHR and sitagliptin-treated SHR had similar LA APD90. Sitagliptin-treated WKY or sitagliptin- treated SHR had larger (RA-LA) APD90 differences than WKY or SHR, respectively. Moreover, as compared to WKY the post-rest potentiation of contraction was decreased in SHR, sitagliptin-treated WKY, and sitagliptin-treated SHR. CONCLUSIONS: Sitagliptin significantly affects the electromechanical characteristics of PVs and atria, which can be modulated by hypertension. KEY WORDS: Atrial fibrillation; Atrium; Dipeptidyl peptidase inhibitor-4; Hypertension; Pulmonary vein.

Rivaroxaban modulates electrical and mechanical characteristics of left atrium.

BACKGROUND: Rivaroxaban reduces stroke in patients with atrial fibrillation (AF). Left atrium (LA) plays a critical role in the pathophysiology of AF. However, the electromechanical effects of rivaroxaban on LA are not clear. RESULTS: Conventional microelectrodes and a whole-cell patch-clamp were used to record the action potentials (APs) and ionic currents in rabbit LA preparations and isolated single LA cardiomyocytes before and after the administration of rivaroxaban. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently reduced LA (n=7) AP durations at 90% repolarization (APD90) from 76±2 to 79±3, 67±4 (P<0.05, vs. control), 59±5, (P<0.01, vs. control), and 56±4 ms (P<0.005, vs. control), respectively. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently increased the LA (n=7) diastolic tension by 351±69 (P<0.05, vs. control), 563±136 (P<0.05, vs. control), 582±119 (P<0.05, vs. control), and 603±108 mg (P<0.005, vs. control), respectively, but did not change LA contractility. In the presence of L-NAME (100 µM) and indomethacin (10 µM), additional rivaroxaban (300 nM) treatment did not significantly further increase the LA (n=7) diastolic tension, but shortened the APD90 from 73±2 to 60±6 ms (P<0.05, vs. control). Rivaroxaban (100 nM) increased the L-type calcium current and ultra-rapid delayed rectifier potassium current, but did not change the transient outward potassium current in isolated LA cardiomyocytes. CONCLUSIONS: Rivaroxaban modulates LA electrical and mechanical characteristics with direct ionic current effects.

Consistency of the automatic algorithm in detecting complex fractionated electrograms using an electroanatomical navigation system.

BACKGROUND: The different settings of the automatic algorithm in the Carto system (Carto XP, Biosense Webster, Diamond Bar, CA, USA) used for detecting complex fractionated electrograms (CFEs) during atrial fibrillation (AF) may influence the identification of the fragmented electrograms. OBJECTIVES: We aimed to evaluate the impact of the different parameters on the detection of CFEs and the efficacy of the substrate modification after pulmonary vein isolation (PVI). METHODS: A total of 1,159 electrograms were analyzed from 11 consecutive patients (age = 56 ± 12 years). The effect of the different algorithm factors, such as the high-voltage thresholds (0.12, 0.25, 0.5, 20 mV), detection algorithms (average complex interval [ACI] vs interval confidence level), and recording duration (2.5 seconds vs 5 seconds), on the disparities of the CFEs was investigated. RESULTS: The proportion of the different grades of CFEs depended on the detection algorithm and recording duration. The high-voltage threshold would not affect the consistency of the CFEs irrespective of the different settings of the detection algorithm or recording duration. High-grade CFEs were most consistent with an ACI algorithm and recording duration of 5 seconds (Cronbach's alpha = 0.952). Ablation consisting of a PVI and high-grade CFE sites converted AF directly to sinus rhythm in eight of 11 patients or into atrial tachycardia in one of 11. CONCLUSIONS: The distribution and consistency of the CFE detection depended on the detection algorithm and recording duration, but not on the high-voltage threshold. Under the ACI algorithm and a recording duration of 5 seconds, high-grade CFE sites remained highest consistency.

The distance between the vein and lesions predicts the requirement of carina ablation in circumferential pulmonary vein isolation.

AIMS: Additional ablation in the pulmonary vein (PV) carina region is sometimes required to achieve electrical isolation following circumferential pulmonary vein isolation (PVI). This study investigated the procedural predictors for the requirement of additional carina ablation to achieve complete electrical isolation with PVI. METHODS AND RESULTS: Eighty patients with drug-refractory paroxysmal AF underwent circumferential PVI. After the first round of PVI, we placed circular catheters inside the veins to identify the residual PV potentials, and also performed electroanatomic mapping to observe the earliest activation sites during sinus rhythm. The requirement of an additional gap and carina ablation, and the optimal distance that predicted an incomplete PV block were assessed. In the first 40 patients, 43% of the ipsilateral PVs were electrically isolated after the initial PVI. Subsequent ablation of the gaps and ablation of the carina were required in the remaining 57% PVs. The only predictor of the requirement of carina ablation was the mean distance between the lesion-related scar and the ostia (P = 0.03). The longer the distance from the isolating lesions to the PV ostia (>8 mm) predicted an incomplete PV isolation after the first round of circumferential isolation. In the next 40 patients, a fixed distance of 8 mm to the PV ostia decreased the requirement of a carina ablation and resulted in a shorter procedure time (P < 0.05). CONCLUSIONS: This study indicated the importance of complete linear lesions and additional carina ablation when the wide area circumferential PV isolation was applied.

The optimal automatic algorithm for the mapping of complex fractionated atrial electrograms in patients with atrial fibrillation.

CFAEs and the Voltage. Introduction: Catheter ablation of atrial fibrillation (AF) can be guided by the identification of complex fractionated atrial electrograms (CFAEs). We aimed to study the prediction of the CFAEs defined by an automatic algorithm in different atrial substrates (high voltage areas vs low voltage areas). Methods and Results: This study included 13 patients (age = 56 +/- 12 years, paroxysmal AF = 8 and persistent AF = 5), who underwent mapping and catheter ablation of AF with a NavX system. High-density voltage mapping of the left atrium (LA) was performed during sinus rhythm (SR) (248 +/- 75 sites per patient) followed by that during AF (88 +/- 24 sites per patient). The CFAE maps were based on the automatic-detection algorithm. "Operator-determined CFAEs" were defined according to Nademannee's criteria. A low-voltage zone (LVZ) was defined as a bipolar voltage of less than 0.5 mV during SR. Among a total of 1150 mapping sites, 459 (40%) were categorized as "operator-determined CFAE sites," whereas 691 (60%) were categorized as "operator-determined non-CFAE sites." The sensitivity and negative predictive value increased as the fractionated interval (FI) value of the automatic algorithm increased, but the specificity and positive predictive value decreased. The automatic CFAE algorithm exhibited the highest combined sensitivity and specificity with an FI of <60 ms for the sites inside the LVZ and FI < 70 ms for the sites outside the LVZ, when compared with a single threshold for both the high- and low-voltage groups combined (i.e., no regard for voltage) (ROC: 0.89 vs 0.86). Conclusions: The clinical relevance of the CFAE map would be improved if the calculated index values were accordingly scaled by the electrogram peak-to-peak amplitude.

The disparities in the electrogram voltage measurement during atrial fibrillation and sinus rhythm.

INTRODUCTION: The peak electrogram voltage is a typical metric applied at each site for voltage mapping. However, the peak amplitude depends on the direction and complexity of the wavefront propagation. The root-mean-square (RMS) measure of the amplitude is a temporal integral that represents the steady-state value. The objective of this study was to investigate the disparities between the electrogram voltage during SR and AF by using 2 recording modalities: the conventional peak voltage and an RMS measurement. METHODS AND RESULTS: This study enrolled 20 patients (age = 59 +/- 13) with paroxysmal AF undergoing catheter ablation guided by Ensite array. The unipolar electrogram voltage during SR and AF (7 seconds in duration) was obtained from the same sites, and labeled by the 3-dimensional (3D) geometry. Overall 1,200 electrograms were analyzed from equally distributed mapping sites in the left atrium. A point-by-point comparison of the unipolar peak negative voltage (PNV) showed less agreement (Bland and Altman test: 10.4% outside 2 standard deviations, and intraclass correlation coefficient [ICC]= 0.64). The RMS voltage demonstrated agreement between SR and AF for all sites (BA test: 5.9% of the sites, and the ICC = 0.81). The probability of predicting a low-voltage during AF using the voltage during SR was significantly lower when using the PNV measurement compared to that when using the RMS voltage (15% vs 61%, P < 0.05). CONCLUSION: The peak electrogram unipolar voltage during AF did not represent the voltage during SR. The RMS amplitude may be an alternative metric for voltage mapping to characterize the myocardial substrate.

The impact of diastolic dysfunction on the atrial substrate properties and outcome of catheter ablation in patients with paroxysmal atrial fibrillation.

BACKGROUND: The presence of diastolic dysfunction increases the risk of atrial fibrillation (AF), and might be associated with the left atrial (LA) substrate. The aim of the present study was to investigate the relationships between the diastolic dysfunction, atrial substrate and outcome of the catheter ablation. METHODS AND RESULTS: Eighty-three patients with paroxysmal AF were enrolled. Diastolic dysfunction was defined as a left ventricular ejection fraction (LVEF) of ≥ 50%, and one of the following criteria: (1) a mitral inflow early filling velocity to atrial filling velocity ratio (E/A) of ≤ 0.75; or (2) an E/A ratio of >0.75 and a ratio of the mitral inflow early filling velocity to the velocity of the early medial mitral annular ascent of >10. Patients with diastolic dysfunction were older than those with normal cardiac function. There were no differences in the other baseline characteristics, LA diameter, or LVEF. A decreased LA voltage, and higher recurrence rate were noted in patients with diastolic dysfunction. In the univariate analysis, the patients with recurrence had a lower LA voltage and greater diastolic dysfunction. The multivariate analysis also indicated diastolic dysfunction and LA voltage as independent predictors of recurrence. CONCLUSIONS: The patients with diastolic dysfunction developed a different atrial substrate and had a worse outcome of catheter ablation for atrial fibrillation.

The impact of left atrial size on long-term outcome of catheter ablation of chronic atrial fibrillation.

BACKGROUND: The left atrial (LA) size is an important predictor of atrial fibrillation (AF) procedural termination and the long-term outcome. We sought to evaluate the long-term outcome in regard to the LA size and procedural termination. METHODS: Eighty-seven consecutive chronic AF patients (72 males, 53 +/- 10 years) underwent 3D mapping (NavX) and ablation. A stepwise approach including circumferential pulmonary vein (PV) isolation, linear ablation, and continuous complex-fractionated electrogram (CFE) ablation (targeting fractionation intervals of < 50 ms). Electrical cardioversion was applied to those without any procedural termination. The freedom from AF was defined as the maintenance of sinus rhythm without the use of any class I or III antiarrhythmic drugs after the blanking period. RESULTS: Among the 87 patients, all received a circumferential PV isolation, 93% a linear ablation, and 59% a continuous CFE ablation. Those with AF procedural termination (n = 30) had a better long-term outcome when compared with those without termination during a follow-up of 21 +/- 12 months. Moreover, a Kaplan-Meier analysis showed that in those with an LA diameter of less than 45 mm (n = 49), the freedom from AF rate was higher when procedural termination was achieved (P = 0.004). On the contrary, the outcome was comparable in those with an LA diameter of >or= 45 mm (n = 38), whether AF procedural termination occurred or not (P = 0.658). CONCLUSIONS: AF procedural termination was related to the long-term success during chronic AF ablation, especially in those with an LA diameter of less than 45 mm. The favorable effect of termination decreased when the LA diameter was >or= 45 mm.

Characteristics of the cavotricuspid isthmus in predicting recurrent conduction in the long-term follow-up.

BACKGROUND: The characteristics of cavotricuspid isthmus (CTI) in patients with atrial fibrillation (AF) and flutter that may predict recurrence of flutter is not known. We aimed to investigate the CTI characteristics in patients who underwent a second ablation procedure for recurrent AF after previous combined pulmonary vein (PV) and CTI ablation. METHODS: Among 196 consecutive patients with drug-refractory symptomatic AF who underwent PV isolation and CTI ablation with bidirectional isthmus block, 49 patients (age 50 +/- 12 years, 43 males) had recurrent AF and received a second procedure 291 +/- 241 days after the first procedure. Right atrial angiography for the evaluation of the CTI morphology, and the biatrial contact bipolar electrograms were obtained before both procedures. RESULTS: In the second procedure, 11 (group 1) of the 49 patients demonstrated recovered CTI conduction. Compared with the patients without CTI conduction (group 2, n = 38), group 1 patients had a higher frequency of a pouch-type anatomy (82% vs 13%, P < 0.001), longer CTI (34.0 +/- 8.6 vs 25.5 +/- 7.5 mm, P = 0.01), longer ablation time, and larger number of radiofrequency applications; furthermore, the preablation bipolar voltage decreased along both the CTI and ablation line in group 2, whereas it remained similar in group 1 in the second procedure. CONCLUSIONS: A high (22%) percentage of CTIs exhibited recurrent conduction in the long-term follow-up. The CTIs with recurrent conduction had a higher incidence of a pouch and longer length compared with those without recurrent conduction.

Efficacy of additional ablation of complex fractionated atrial electrograms for catheter ablation of nonparoxysmal atrial fibrillation.

BACKGROUND: The efficacy of ablation of complex fractionated atrial electrograms (CFEs) in the single ablation procedure for nonparoxysmal atrial fibrillation (AF) patients is not well demonstrated. The aim of this study was to compare the ablation strategies of pulmonary vein isolation (PVI) plus linear ablation with and without additional ablation ofCFEs in these patients. METHODS: Consecutive 60 patients (49 +/- 11 years old, 50 male, 10 female) with nonparoxysmal AF underwent catheter ablation guided by a NavX mapping system. A stepwise approach included a circumferential PVI and left atrial (LA) linear ablation followed by either the additional ablation of continuous CFEs in the LA/coronary sinus (the first 30 patients) or not (the second 30 patients), detected by an automatic algorithm. RESULTS: There was no difference in the baseline characteristics between the two groups. Complete PVI eliminated some continuous CFEs and altered the distribution of CFEs. Following PVI and linear ablation,the remaining continuous CFEs were identified in 7.9 +/-10% mapping sites of the LA and CS, and were ablated successfully with a procedural AF termination rate of 53%. With a follow-up of 19 +/-11 months, a Kaplan-Meier analysis showed that the patients with additional ablation of the CFEs had a higher rate of sinus rhythm maintenance. Multivariate analysis showed the single procedure success could be predicted by the procedural AF termination and the additional ablation of continuous CFEs in the LA/CS. CONCLUSIONS: Ablation of continuous CFEs after PVI and LA linear ablation had a better long-term efficacy based on the results of single-ablation procedure.

Characteristics of complex fractionated electrograms in nonpulmonary vein ectopy initiating atrial fibrillation/atrial tachycardia.

BACKGROUND: Nonpulmonary vein (PV) ectopy initiating atrial fibrillation (AF)/atrial tachycardia (AT) is not uncommon in patients with AF. The relationship of complex fractionated atrial electrograms (CFAEs) and non-PV ectopy initiating AF/AT has not been assessed. We aimed to characterize the CFAEs in the non-PV ectopy initiating AF/AT. METHODS: Twenty-three patients (age 53 +/- 11 y/o, 19 males) who underwent a stepwise AF ablation with coexisting PV and non-PV ectopy initiating AF or AT were included. CFAE mapping was applied before and after the PV isolation in both atria by using a real-time NavX electroanatomic mapping system. A CFAE was defined as a fractionation interval (FI) of less than 120 ms over 8-second duration. A continuous CFAE (mostly, an FI < 50 ms) was defined as electrogram fractionation or repetitive rapid activity lasting for more than 8 seconds. RESULTS: All patients (100%) with non-PV ectopy initiating AF or AT demonstrated corresponding continuous CFAEs at the firing foci. There was no significant difference in the FI among the PV ostial or non-PV atrial ectopy or other atrial CFAEs (54.1 +/- 5.6, 58.3 +/- 11.3, 52.8 +/- 5.8 ms, P = 0.12). Ablation targeting those continuous CFAEs terminated the AF and AT and eliminated the non-PV ectopy in all patients (100%). During a follow-up of 7 months, 22% of the patients had an AF recurrence with PV reconnections. There was no recurrence of any ablated non-PV ectopy during the follow-up. CONCLUSION: The sites of the origin of the non-PV ectopies were at the same location as those of the atrial continuous CFAEs. Those non-PV foci were able to initiate and sustain AF/AT. By limited ablation targeting all atrial continuous CFAEs, the AF could be effectively eliminated.

Histone deacetylase inhibition attenuates atrial arrhythmogenesis in sterile pericarditis.

Cardiac surgery is complicated with atrial fibrillation (AF). Histone deacetylase (HDAC) inhibition reduces AF occurrence. In pericarditis, HDAC inhibition may modulate AF trigger and substrate. We recorded electrocardiograms in control and pericardiotomic (op) rabbits without and with an intraperitoneal injection of MPT0E014 (HDAC inhibitor). Conventional microelectrodes recorded action potentials (APs) in pulmonary veins (PVs), the right and left atrium (LA). Masson's trichrome was used to identify collagen fibers in PVs and the LA. Electrocardiograms showed frequent atrial premature contractions in op rabbits, but not in the other 3 groups. The beating rates in PVs and opPVs were decreased by MPT0E014 treatment. Spontaneous burst firings occurred in opPVs (36.4%), but not in control PVs. H2O2 induced greater burst firings in opPVs (72.7%) than in control PVs (11.1%), MPT0E014-treated PVs (16.7%), and MPT0E014-treated opPVs (12.5%). The AP duration at a repolarization extent of 90% (APD90) was shorter in the opLA than that in the control LA. In the presence of isoproterenol (1 µM), rapid atrial pacing (RAP, 20 Hz) induced a higher incidence of burst firings in the opLA (90%) than in the other groups. In contrast, acetylcholine (5 mM) and RAP induced a lower incidence of burst firing in the MPT0E014-treated LA (33.3%) than in the other groups. Fibrosis prevailed in opPVs and the opLA compared to the respective control PVs and LA, which was attenuated in those that received MPT0E014. In conclusion, a pericardiotomy increased fibrosis and arrhythmogenesis in PVs and the LA, which were prevented by HDAC inhibition.

Factor Xa inhibitors differently modulate electrical activities in pulmonary veins and the sinoatrial node.

Factor Xa inhibitors reduce stroke in patients with atrial fibrillation. Pulmonary veins (PVs) and the sinoatrial node (SAN) are crucial for genesis of atrial fibrillation. However, the electrophysiological effects of factor Xa inhibitors (edoxaban and rivaroxaban) on PVs and the SAN remain unclear. Conventional microelectrodes were used to record the action potential in isolated rabbit PVs and SAN preparations before and after administration of edoxaban (0.1, 0.3, and 1 µM) or rivaroxaban (0.01, 0.03, 0.1, and 0.3 µM). A whole-cell patch-clamp was used to record the late sodium current (INa-late) in isolated single rabbit PV cardiomyocytes. Edoxaban significantly reduced PV spontaneous beating rates at 0.3 and 1 µM (N = 6 rabbits, P < 0.05), and reduced SAN beating rates at 1 µM (N = 6, P < 0.05). Similarly, rivaroxaban reduced PV spontaneous beating rates at 0.1 and 0.3 µM (N = 7, P < 0.05), and reduced SAN beating rates at 0.3 µM (N = 6, P < 0.05). However, neither edoxaban (1 µM) nor rivaroxaban (0.3 µM) reduced PV spontaneous beating rates in the presence of 1 µM BMS200261 (an inhibitor of protease-activated receptors type 1, PAR1 inhibitor) or 10 µM ranolazine (an inhibitor of late sodium current, INa-late inhibitor). Edoxaban (0.3 and 1 µM) and rivaroxaban (0.1 and 0.3 µM) respectively decreased the INa-late by 47%, 47%, 36%, and 49% (n = 9 PV cardiomyocytes from 5 rabbits, P < 0.05). In conclusion, Factor Xa inhibitors reduce PV spontaneous activities and may modulate occurrence of atrial fibrillation by inhibiting PAR1 and reducing the INa-late in PVs.

Clinical outcomes of infrarenal abdominal aortic aneurysms that underwent endovascular repair in a district general hospital.

BACKGROUND: The purpose of this study was to compare the outcomes of elective endovascular abdominal aortic aneurysm repair (EVAR) and ruptured abdominal aortic aneurysm (rAAA) in patients at a district general hospital. METHODS: A retrospective clinical study was conducted using data on 16 patients with elective abdominal aortic aneurysm (AAA) and nine patients with consecutive rAAA treated with EVAR from January 2010 to December 2014 in a district general hospital in Taiwan. RESULTS: The preoperative characteristics of the two groups are listed. Thirty-six percent (9/25) of the patients were referred from other hospitals that did not offer surgical services. The percentage of patients with rAAA that were transferred from other hospitals was 55.5% (5/9). The stay durations in the intensive care unit for elective EVAR cases were shorter than those for emergent EVAR (1.75±1 d elective vs. 10±13.37 d emergent; P<0.019). The hospitalization days (11.06±4.07 d elective vs. 21.89±18.36 d emergent; P<0.031), operative time (183.63±57.24 min elective vs. 227.11±59.92 min emergent; P<0.009), and blood loss volumes (115.63±80.41 mL elective vs. 422.22±276.26 mL emergent; P<0.005) are shown; statistics for use of Perclose ProGlide(®) (7 cases elective vs. 0 case emergent; P<0.024) are compared. The overall 30-d mortality rate was 11.11% (1/9). CONCLUSIONS: The results confirm that EVAR surgery can be safely performed in a district general hospital with an integrated health care system. Using Perclose ProGlide(®) for selected cases may reduce blood loss and operative time.

Gap junction modifiers regulate electrical activities of the sinoatrial node and pulmonary vein: Therapeutic implications in atrial arrhythmogenesis.

BACKGROUND: Gap junction (GJ) dysfunctions predispose cardiac tissues to various arrhythmias. Sinoatrial node (SAN) and pulmonary veins (PVs) are closely related atrial dysrhythmia. This study evaluated whether GJ modifications modulate SAN and PVs electrical activities. METHODS: Conventional microelectrodes were used to record action potentials in isolated rabbit SAN, PVs, and connected PV-SAN tissue preparations before and after heptanol (GJ inhibitor) and PQ1 (GJ enhancer) administration with and without isoproterenol. A whole-cell patch clamp was used to record the electrical activities before and after heptanol in single SAN and PV cardiomyocytes. RESULTS: Heptanol (1, 3, and 10µM) reduced the spontaneous beating rates of isolated SAN preparations but not PVs. Heptanol (10µM) decelerated the SAN leading rhythm in the PV-SAN preparations and induced PV burst firings without (3 of 6, 50%) and with (6 of 6, 100%) isoproterenol (1µM). Heptanol (10µM) also reduced the spontaneous beating rates in single SAN cardiomyocyte, but not PV cardiomyocyte, with a decreased pacemaker current. PQ1 (50 and 500nM) treatment did not change the spontaneous beating rates in isolated SAN and PV preparations. In the connected PV-SAN preparations, PQ1 (500nM) did not induce any PV firing even having additional isoproterenol treatment (1µM). Moreover, PQ1 (500nM) prevented heptanol-induced electrical changes in SAN and PVs preparations. CONCLUSION: GJ dysfunction modulates SAN and PV electrical activity, which may contribute to atrial arrhythmogenesis. GJ enhancer has a therapeutic potential in SAN dysfunction and atrial arrhythmogenesis.

Selective and non-selective non-steroidal anti-inflammatory drugs differentially regulate pulmonary vein and atrial arrhythmogenesis.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of atrial fibrillation (AF). This study investigated whether selective and non-selective NSAIDs differentially regulate the arrhythmogenesis of pulmonary veins and atria. METHODS: Conventional microelectrodes were used to record action potentials (APs) in isolated rabbit PVs, sinoatrial node (SAN), left atrium (LA), and right atrium (RA) preparations before and after celecoxib or indomethacin administration. A whole-cell patch clamp was used to record the sodium-calcium exchanger (NCX) current, L-type calcium current (ICa-L), and late sodium current (INa-late) before and after celecoxib administration in isolated PV cardiomyocytes. RESULTS: Celecoxib (0.3, 1, and 3 µM) reduced PV spontaneous beating rates, and induced delayed afterdepolarizations and burst firings in four of eight PV preparations (50%, p<0.05). Celecoxib also reduced SAN beating rates and decreased AP durations (APDs) in RA and LA, but did not change the resting membrane potential. Indomethacin (0.3, 1, 3, and 10 µM) changed neither the PV or SAN beating rates nor RA APDs, but it reduced LA APDs. Celecoxib (3 µM) significantly increased the NCX current and decreased the ICa-L, but did not change the INa-late. Ranolazine (10 µM) suppressed celecoxib (3 µM)-induced PV burst firings in 6 (86%, p<0.05) of 7 PVs. KB-R7943 (10 µM) suppressed celecoxib (3 µM)-induced PV burst firings in 5 (71%, p<0.05) of 7 PVs. CONCLUSIONS: Selective and non-selective NSAIDs differentially modulate PV and atrial electrophysiological characteristics. Celecoxib increased PV triggered activity through enhancement of the NCX current, which contributed to its arrhythmogenesis.

Ablation of androgen receptor gene triggers right ventricular outflow tract ventricular tachycardia.

BACKGROUND: Sex hormones and calcium (Ca(2+)) regulation play roles in the pathophysiology of ventricular tachycardia from right ventricular outflow tract (RVOT). The purpose of this study was to evaluate whether androgen receptor knockout (ARKO) can increase RVOT arrhythmogenesis through modulating RVOT electrophysiology and Ca(2+) homeostasis. METHODS: Conventional microelectrodes were used to study the action potential (AP) in RVOT tissues prepared from wild type (WT) and ARKO mice (aged 6-10 months) before and after caffeine (1mM), isoproterenol (1 µM), adenosine (10 µM) and flecainide (5 µM) administration. The Fluo-3 fluorescence Ca(2+) imaging with confocal microscopy and western blots were used to investigate intracellular Ca(2+) (Ca(2+)i) transients, Ca(2+) sparks, and the expressions of ionic channel proteins in ARKO and WT RVOT myocytes. RESULTS: We found that ARKO RVOTs (n = 13) had longer AP duration, faster burst firing (5.4 ± 0.7 vs. 3.4 ± 0.7 Hz, P < 0.05), and higher incidence of early afterdepolarizations (82% vs. 8%, P < 0.001) than WT RVOTs (n = 11). Adenosine and flecainide can suppress caffeine- or isoproterenol-induced spontaneous rates and burst firing in WT RVOTs, but not in ARKO RVOTs. ARKO RVOT myocytes had a higher frequency (7.7 ± 2.8 vs. 1.3 ± 0.4 spark/mm/s, P < 0.05) and incidence (89% vs. 47%, P < 0.05) of Ca(2+) sparks, and greater expressions of Cav1.2, NCX, phosphorylated RyR (s2814), phosphorylated phospholamban (Thr17), CAMKII and GRK2 than WT RVOT myocytes. However, ARKO and WT RVOT myocytes exhibit similar Ca(2+)i transients and SR Ca(2+) content, and less expression of calsequestrin. CONCLUSIONS: ARKO changes RVOT electrophysiology and Ca(2+) homeostasis with increased ventricular arrhythmogenesis.

Self-management intervention to improve self-care and quality of life in heart failure patients.

Self-management intervention is a good method to improve self-care ability, as such, to promote quality of life. However, the research focused on self-management intervention in heart failure patients in Taiwan is very limited. Therefore, the purposes of this study were to test the effectiveness of self-management intervention in patients with heart failure in Taiwan and examine the relationship between self-care ability and quality of life. A quasi-experimental design was used in this study with convenience sampling. Of the 82 subjects participating in this study, 40 of them chose to join the experimental (self-management intervention plus usual care) and 42 of them chose to join control (usual care) group. Three questionnaires were used to collect the data, which were the demographic questionnaire, the self-care questionnaire (Self-Care of HF Index V 6), and the quality of life questionnaire (Minnesota Living with Heart Failure Questionnaire). To examine the effectiveness of the intervention, self-care ability and quality of life were measured, using a pretest, 1- and 2-month follow-up assessment. Generalized estimation equations (GEE) were used to compare changes over time among groups for outcomes to ensure the effectiveness of the intervention. This study confirmed the effectiveness of the self-management intervention. The clinical provider should increase the awareness of the importance of self-management skills and self-care ability especially for heart failure patients. The designated disease-specific self-management patient book and individualize intervention should be dispensing and implementing.