Corrected Sinus Node Recovery Time Research Articles

Abstract 13992: The Impact of Dexmedetomidine on the Cardiac Electrophysiological Properties in Patients With Paroxysmal Atrial Fibrillation

Background: Dexmedetomidine (DEX), a selective α2-adrenergic receptor agonist, has increasingly been used as a sedative during ablation of atrial fibrillation. DEX is known to have some suppressive effects on the cardiac conduction system, however, that has not yet been extensively assessed in human adults. We aimed to perform a detailed analysis of the impact of DEX on the cardiac electrophysiological properties in patients with paroxysmal atrial fibrillation (AF). Methods and Results: We measured the cardiac electrophysiological properties in adult patients (65±11 years) undergoing ablation of paroxysmal AF who were assigned to receive DEX (10 minutes of a loading at a dose of 6μg/kg/min followed by a maintenance dose of 0.6μg/kg/min; N=120) or those who were assigned not to receive any sedative (N=120). The patients with DEX were more likely than those without to have a longer sinus cycle length (943±190 vs. 802±142ms; p<0.001), greater corrected sinus node recovery time (547±334 vs. 441±239ms; p<0.001), and more prolonged atrial effective refractory period (234±35 vs. 220±33ms; p<0.001). The AH interval (103±24 vs. 91±20ms; p<0.001), atrioventricular (AV) nodal effective refractory period (324±70 vs. 268±58ms; p<0.001), and Wenckebach cycle length (446±76 vs. 377±55ms; p<0.001) were greater in patients with DEX, while the HV interval was similar between the groups (42±11 vs. 41±8ms; p=0.63). AF was less often induced in the patients with DEX than in those without (8.3% vs. 20.8%; p=0.01), when a single extra stimulus was given within the atrial vulnerable period. Conclusions: DEX may have inhibitory effects on both the sinus node and AV node, and may even reduce the AF inducibility in adult AF patients.

Hyperhomocysteinemia Alters Sinoatrial and Atrioventricular Nodal Function: Role of Magnesium in Attenuating These Effects.

Patients with hyperhomocysteinemia (HHcy), or elevated plasma homocysteine (Hcy), are at higher risk of developing arrhythmias and sudden cardiac death; however, the mechanisms are unknown. In this study, the effects of HHcy on sinus node function, atrioventricular conduction, and ventricular vulnerability were investigated by electrophysiological (EP) analysis, and the role of magnesium (Mg(2+)), an endogenous N-methyl-D-aspartate (NMDA) receptor antagonist, in attenuating EP changes due to HHcy was explored. Wild-type mice (WT) and mice receiving Hcy in the drinking water for 12 weeks (DW) were subjected to electrocardiographic and EP studies. DW compared to WT had significantly shorter RR, PR, QT, and HV intervals, corrected sinus node recovery times (CSNRT), Wenckebach periodicity (WP), atrioventricular nodal effective refractory periods (AVNERP), and right ventricular effective refractory periods (RVERP). To examine the role of Mg(2+) in mitigating conduction changes in HHcy, WT, DW, and heterozygous cystathionine-β-synthase knockout mice (CBS (+/-) ) were subjected to repeat EP studies before and after administration of low-dose magnesium sulfate (20 mg/kg). Mg(2+) had no effect on EP variables in WT, but significantly slowed CSNRT, WP, and AVNERP in DW, as well as WP and AVNERP in CBS (+/-) . These findings suggest that ionic channels modulated by Mg(2+) may contribute to HHcy-induced conduction abnormalities.

Electrocardiographic and electrophysiologic effects of dexmedetomidine on children.

Dexmedetomidine (DEX) is a highly selective alpha-2-adrenergic agonist approved for short-term sedation and monitored anesthesia care in adults. Its effects on the electrocardiography and cardiac conduction tissue are not well described in the literature. Therefore, we aimed to characterize the electrocardiographic and electrophysiologic effects of DEX in children. Twenty children (11 boys and nine girls) between the ages of eight and 17 undergoing electrophysiology study and ablation of the supraventricular tachycardia had hemodynamic and cardiac electrophysiologic variables measured before and during the administration of DEX (1 microgram/kg IV over 10 minutes followed by a 10-minute continuous infusion of 0.5 microgram/kg/h). A significant decrease in heart rate was seen after the administration of DEX, but the systolic-diastolic-mean arterial pressure, respiratory rate, and end-tidal carbon dioxide did not change. Corrected sinus node recovery times and baseline sinus cycle lengths, which are markers of sinus nodal function, were both lengthened with the administration of DEX. Atrioventricular (AV) nodal function, as evidenced by the Wenckebach cycle length, the ventriculoatrial block cycle length, and AV nodal effective refractory periods, was lengthened significantly. We also found that DEX increased the atrial refractory period and diminished atrial excitability. DEX significantly depressed sinus and AV nodal function in pediatric patients without significant electrocardiogram interval changes, other than a trend toward lower heart rates. Although no spontaneous AV nodal block and no clinically significant bradycardia were seen, we recommend that DEX be used with caution in patients at risk for bradycardia and/or AV nodal dysfunction due to its associated comorbidities.

Altered parasympathetic nervous system regulation of the sinoatrial node in Akita diabetic mice

Cardiovascular autonomic neuropathy (CAN) is a serious complication of diabetes mellitus that impairs autonomic regulation of heart rate (HR). This has been attributed to damage to the nerves that modulate spontaneous pacemaker activity in the sinoatrial node (SAN). Our objective was to test the hypothesis that impaired parasympathetic regulation of HR in diabetes is due to reduced responsiveness of the SAN to parasympathetic agonists. We used the Akita mouse model of type 1 diabetes to study the effects of the parasympathetic agonist carbachol (CCh) on SAN function using intracardiac programmed stimulation, high resolution optical mapping and patch-clamping of SAN myocytes. CCh decreased HR by 30% and increased corrected SAN recovery time (cSNRT) by 123% in wildtype mice. In contrast, CCh only decreased HR by 12%, and only increased cSNRT by 37% in Akita mice. These alterations were due to smaller effects of CCh on SAN electrical conduction and spontaneous action potential firing in isolated SAN myocytes. Voltage clamp experiments demonstrate that the acetylcholine-activated K+ current (IKACh) is reduced in Akita SAN myocytes due to enhanced desensitization and faster deactivation kinetics. These IKACh alterations were normalized by treating Akita SAN myocytes with PI(3,4,5)P3 or an inhibitor of regulator of G-protein signaling 4 (RGS4). There was no difference in the effects of CCh on the hyperpolarization-activated current (If) between wildtype and Akita mice. Our study demonstrates that Akita diabetic mice demonstrate impaired parasympathetic regulation of HR and SAN function due to reduced responses of the SAN to parasympathetic agonists. Our experiments demonstrate a key role for insulin-dependent phosphoinositide 3-kinase (PI3K) signaling in the parasympathetic dysfunction seen in the SAN in diabetes.

Impaired sinoatrial node function and increased susceptibility to atrial fibrillation in mice lacking natriuretic peptide receptor C.

Natriuretic peptides (NPs) are critical regulators of the cardiovascular system that are currently viewed as possible therapeutic targets for the treatment of heart disease. Recent work demonstrates potent NP effects on cardiac electrophysiology, including in the sinoatrial node (SAN) and atria. NPs elicit their effects via three NP receptors (NPR-A, NPR-B and NPR-C). Among these receptors, NPR-C is poorly understood. Accordingly, the goal of this study was to determine the effects of NPR-C ablation on cardiac structure and arrhythmogenesis. Cardiac structure and function were assessed in wild-type (NPR-C(+/+)) and NPR-C knockout (NPR-C(-/-)) mice using echocardiography, intracardiac programmed stimulation, patch clamping, high-resolution optical mapping, quantitative polymerase chain reaction and histology. These studies demonstrate that NPR-C(-/-) mice display SAN dysfunction, as indicated by a prolongation (30%) of corrected SAN recovery time, as well as an increased susceptibility to atrial fibrillation (6% in NPR-C(+/+) vs. 47% in NPR-C(-/-)). There were no differences in SAN or atrial action potential morphology in NPR-C(-/-) mice; however, increased atrial arrhythmogenesis in NPR-C(-/-) mice was associated with reductions in SAN (20%) and atrial (15%) conduction velocity, as well as increases in expression and deposition of collagen in the atrial myocardium. No differences were seen in ventricular arrhythmogenesis or fibrosis in NPR-C(-/-) mice. This study demonstrates that loss of NPR-C results in SAN dysfunction and increased susceptibility to atrial arrhythmias in association with structural remodelling and fibrosis in the atrial myocardium. These findings indicate a critical protective role for NPR-C in the heart.

Sodium Hydroxide Pinpoint Pressing Permeation Method for the Animal Modeling of Sick Sinus Syndrome.

Sodium hydroxide pinpoint pressing permeation (SHPPP) was investigated in order to build a rat model of sick sinus syndrome (SSS), which is easy to operate and control the degree of damage, with fewer complications and applicable for large and small animals.Thirty healthy Wistar rats (15 males and 15 females, weighing 250-350 g) were randomly divided into 3 groups, namely a formaldehyde thoracotomy wet compressing group (FTWC), formaldehyde pinpoint pressing permeation group (FPPP) group, and SHPPP group. The number of surviving rats, heart rate (HR), sinoatrial node recovery time (SNRT), corrected SNRT (CSNRT), and sinoatrial conduction time (SACT) were recorded 3 days, one week, and two weeks after modeling.The achievement ratio of modeling was 10% in the FTWC group, 40% in the FPPP group, and 70% in the SHPPP group, and the differences were statistically significant (χ(2) = 7.250, P = 0.007). Meanwhile, the HR was reduced by about 37% in these 3 groups 3 days after modeling, while the reduction was maintained only in SHPPP (P > 0.05) and the HR was re-elevated in the FTWC and FPPP groups 2 weeks after modeling (P < 0.05). Additionally, the SNRT, cS-NRT, and SACT were significantly prolonged compared with pre-modeling in all 3 groups (P < 0.01).SHPPP was the best method with which to build an SSS model with stable and lasting low HR and high success rate of modeling, which might be helpful for further studies on the SSS mechanisms and drugs.

Function and dysfunction of human sinoatrial node.

Sinoatrial node (SAN) automaticity is jointly regulated by a voltage (cyclic activation and deactivation of membrane ion channels) and Ca2+ clocks (rhythmic spontaneous sarcoplasmic reticulum Ca2+ release). Using optical mapping in Langendorff-perfused canine right atrium, we previously demonstrated that the β-adrenergic stimulation pushes the leading pacemaker to the superior SAN, which has the fastest activation rate and the most robust late diastolic intracellular calcium (Cai) elevation. Dysfunction of the superior SAN is commonly observed in animal models of heart failure and atrial fibrillation (AF), which are known to be associated with abnormal SAN automaticity. Using the 3D electroanatomic mapping techniques, we demonstrated that superior SAN served as the earliest atrial activation site (EAS) during sympathetic stimulation in healthy humans. In contrast, unresponsiveness of superior SAN to sympathetic stimulation was a characteristic finding in patients with AF and SAN dysfunction, and the 3D electroanatomic mapping technique had better diagnostic sensitivity than corrected SAN recovery time testing. However, both tests have significant limitations in detecting patients with symptomatic sick sinus syndrome. Recently, we reported that the location of the EAS can be predicted by the amplitudes of P-wave in the inferior leads. The inferior P-wave amplitudes can also be used to assess the superior SAN responsiveness to sympathetic stimulation. Inverted or isoelectric P-waves at baseline that fail to normalize during isoproterenol infusion suggest SAN dysfunction. P-wave morphology analyses may be helpful in determining the SAN function in patients at risk of symptomatic sick sinus syndrome.

Características do estudo eletrofisiológico na Doença de Chagas

ABSTRACTObjective:Chagas disease has become a global problem due to changing migration patterns. An electrophysiological study is generally indicated for assessing sinus node function, conduction through the atrioventricular node and His-Purkinje system, in addition to evaluating the mechanisms of arrhythmia. The aim of this study was to describe the characteristics of electrophysiological study findings in patients with Chagas disease.Methods:A retrospective descriptive study of 115 consecutive patients with Chagas disease undergoing an electrophysiological study over the last three years in a tertiary hospital in Brazil. Baseline characteristics, electrocardiogram, echocardiogram, and 24-hour Holter monitoring findings were recorded and correlated with the electrophysiological study findings.Results:The corrected sinus node recovery time and sinoatrial conduction time were abnormal in 6.9% and 26.1% of patients, respectively. Thirty-seven (32.2%) had abnormal atrioventricular conduction. Intraventricular conduction was abnormal in 39 (33.9%). Approximately 48% had induced sustained ventricular arrhythmias, most of which were monomorphic (83.6%). Right bundle branch block was the most common morphology (52.7%). Fifty-one percent were associated with symptoms/hemodynamic instability, 60% required electrical cardioversion, and 27.3% needed overdrive suppression. The most common site of origin was the left ventricular inferoseptal wall (18.2%), followed by the left ventricular posterobasal wall (11%). Patients with an ejection fraction<40% had a 1.94-fold increased risk of ventricular arrhythmias compared to those with an ejection fraction>60% (OR: 1.94; 95%CI: 1.12-3.38; p=0.01). The presence of complex ventricular arrhythmias on Holter did not predict inducible ventricular arrhythmias.Conclusions:Chagas patients with a low ejection fraction have an increased risk of inducible ventricular arrhythmias. Sinus node dysfunction, and atrioventricular node and His-Purkinje conduction abnormalities occur in about one-third of patients. Complex ventricular arrhythmias on Holter were not associated with an increased risk of inducible ventricular arrhythmias.

Effects of deep sedation on cardiac electrophysiology in patients undergoing radiofrequency ablation of supraventricular tachycardia: impact of propofol and ketamine

Propofol is commonly used as an anaesthetic during catheter ablation. Bradycardia and termination of supraventricular tachycardia (SVT) under propofol are reported. Ketamine is used for cardiac catheterization procedures and increases heart rate and blood pressure. Our study aimed to determine the effects of propopfol and ketamine on atrial electrophysiology. Thirty-one patients undergoing electrophysiological study prior to SVT ablation were enrolled. Patients received a combination of propofol/midazolam (n = 10), ketamine/midazolam (n = 9), or midazolam alone (n = 12). Electrophysiological study was performed before and after administration of the anaesthetic agents. Blood pressure, corrected sinus node recovery time, Wenckebach cycle length, and atrial conduction time were measured. We found a significant increase in heart rate, systolic, and diastolic blood pressure and a significant shortening of atrial conduction time after administration of ketamine compared with propofol and the control. Results for ketamine, propofol and the control, respectively: mean (SD) change in heart rate was 12.4 (8.3), -1.4 (8), and 1 (7.5) b.p.m. (P = 0.002); mean (SD) change in systolic blood pressure was 19.2 (8.1), -22 (9), and 0.1 (5.7) mmHg (P < 0.001); mean (SD) change in diastolic blood pressure was 6.6 (9.7), -7.8 (2.9), and 2.3 (4.5) mmHg (P = 0.001); and mean (SD) change in atrial conduction time was -13.7 (16.4), 4.5 (11.1), and -0.3 (3.8) ms (P = 0.008). No significant affection of sinus node or antrioventricular node function was seen. Our results show stimulatory effects of ketamine on heart rate, atrial conduction, and blood pressure. Ketamine, therefore, may be beneficial in patients with pre-existing hypotension and bradycardia.

Sinus node disease in subjects with type 1 ECG pattern of Brugada syndrome

BackgroundThe spectrum of phenotypes related to mutations of the SCN5A gene include Brugada syndrome (BS), long QT syndrome, progressive cardiac conduction defect, and sinus node disease (SND). The present study investigated the incidence of SND in subjects with type 1 electrocardiogram (ECG) pattern of BS. Methods and resultsThe study population consisted of 68 individuals (55 males, mean age 44.8±12.8 years) with spontaneous (n=27) or drug-induced (n=41) type 1 ECG pattern of BS. Twenty-eight subjects were symptomatic with a history of syncope (41.2%). SND was observed in 6 symptomatic subjects (8.8%), and was mainly attributed to sino-atrial block with sinus pauses. Two patients were initially diagnosed with SND, and received a pacemaker. Patients with SND displayed an increased P-wave duration in leads II and V2, PR interval in leads II and V2, QRS duration in leads II and V2, and increased QTc interval in lead V2 (p<0.05). AH and HV intervals as well as corrected sinus node recovery time (cSNRT) were significantly prolonged in subjects with SND (p<0.05). During a mean follow-up period of 5.0±3.6 years, five subjects with a history of syncope suffered appropriate implantable cardioverter defibrillator (ICD) discharges due to ventricular arrhythmias (7.4%). None of those diagnosed with SND suffered syncope or ICD therapies. ConclusionSND is not an uncommon finding in subjects with type 1 ECG pattern of BS. The occurrence of SND in relatively young patients may deserve meticulous investigation including sodium channel blocking test.

Chronic Amiodarone Therapy Impairs the Function of the Superior Sinoatrial Node in Patients With Atrial Fibrillation

The mechanisms underlying amiodarone-induced sinoatrial node (SAN) dysfunction remain unclear, so we used 3-dimensional endocardial mapping of the right atrium (RA) to investigate. In a matched-cohort design, 18 patients taking amiodarone before atrial fibrillation (AF) ablation (amiodarone group) were matched for age, sex and type of AF with 18 patients who had undergone AF ablation without taking amiodarone (no-amiodarone group). The amiodarone group had a slower heart rate than the no-amiodarone group at baseline and during isoproterenol infusion. Only the amiodarone group had sick sinus syndrome (n=4, 22%, P=0.03) and abnormal (>550ms) corrected SAN recovery time (n=5, 29%; P=0.02). The median distance from the junction of the superior vena cava (SVC) and RA to the most cranial earliest activation site (EAS) was longer in the amiodarone group than in the no-amiodarone group at baseline (20.5 vs. 10.6mm, P=0.04) and during isoproterenol infusion (12.8 vs. 6.3mm, P=0.03). The distance from the SVC-RA junction to the EAS negatively correlated with the P-wave amplitudes of leads II (r=-0.47), III (r=-0.60) and aVF (r=-0.56) (P<0.001 for all). In a quarter of the AF patients, amiodarone causes superior SAN dysfunction, which results in a downward shift of the EAS and reduced P-wave amplitude in leads II, III and aVF at baseline and during isoproterenol infusion.

Influence of racemic higenamine on the sinus node

The aim of this study was to explore the mechanism of racemic higenamine in the treatment of sick sinus syndrome (SSS). A total of 40 New Zealand rabbits were randomly divided into normal sinus node and damaged sinus node (SND) groups, and each group was randomly divided into treatment and control groups (n=10). The SND model was established by formaldehyde wet dressing of the sinus node area. The treatment groups were administered an intravenous infusion of 0.04 mg/kg racemic higenamine via the marginal ear vein within 5 min. The electrophysiological indicators of sinoatrial function, including the sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), total sinoatrial conduction time (TSACT) and sinus cycle length (SCL), were determined before and 20 min after medication and the changes in these indicators were evaluated. The two control groups were administered 10 ml physiological saline. Following the administration of racemic higenamine, the SNRT, CSNRT, TSACT and SCL in the normal sinus node and SND groups were significantly shortened compared with those in the control groups (P<0.01). The electrophysiological influence of racemic higenamine on sinoatrial function in the SND group was significantly greater than that in the normal sinus node group (P<0.01), and its effect in the treatment of arrhythmia caused by a damaged sinus node was statistically significant (P<0.05). The main electrophysiological mechanism of racemic higenamine in the treatment of SSS was the enhancement of sinus node self-discipline and improvement of sinoatrial and atrioventricular conduction function.

Comparative study between original and traditional method in establishing a chronic sinus node damage model in rabbit

Sick Sinus Syndrome is a common and refractory arrhythmia, needing further study in which setting up a credible sinus node damage model is important. To explore the feasibility and superiority of an original formaldehyde pinpoint pressing permeation (FPPP) method for building a chronic sinus node damage (CSND) model, 5 rabbits were chosen from 35 as a sham-operation group, and the remaining were randomly divided into two groups: the formaldehyde wet compressing (FWC) group, in which models were established by applying a cotton bud dipped in 20% formaldehyde onto the sinus node (SN) area, and the FPPP group, in which models were established by injecting formaldehyde into the SN area through a self-made pinpointing and injecting electrode. We found that in both groups, the HR at 2 h, 24 h, 1 wk, and 2 wk after modeling decreased compared with premodeling; sinoatrial conduction time, sinus node recovery time, and corrected sinus node recovery time were prolonged compared with premodeling. The indexes mentioned shortened by 2 wk after modeling compared with 2 h in the FWC group, whereas they were stable after modeling in the FPPP group. The modeling achievement ratio in the FPPP group was higher and the death rate was lower. Under light microscope, paraffin sections of the SN tissue and cells showed severe injury in both groups. The results indicate that the CSND models in rabbits can be successfully established by the FPPP method, with higher achievement ratio, lower death rate, better stabilization effect, and less damaging comparing with the traditional method.

Relevance of Electrical Remodeling in Human Atrial Fibrillation

Background— In animal models of atrial fibrillation (AF), changes in atrial electrophysiological properties are associated with the development of AF. Their relevance to human AF is unclear. Methods and Results— The Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial enrolled 2580 patients receiving a dual-chamber pacemaker, who were older than the age of 65 and had a history of hypertension, but no history of AF. Serial noninvasive electrophysiological testing was performed over 2 years in a subgroup of 485 patients. There were no differences in the clinical characteristics between patients with and those without device-detected atrial tachyarrhythmias during the first year. Patients with atrial tachyarrhythmias had longer paced (153±29 versus 145±28 ms; P =0.046) and sensed (128±46 versus 118±25 ms; P =0.06) P-wave durations and were more likely to have AF induced during electrophysiological testing (23.5% versus 13.6%; P =0.03). They had similar corrected sinus node recovery times at 90 bpm (388±554 versus 376 ± 466 ms; P =0.86), atrial effective refractory periods at 90 bpm (250±32 versus 248±36 ms; P =0.70), and rate-adaptive shortening of the atrial effective refractory periods (14±13 versus 12±14 ms; P =0.11). There were no significant differences in the change in electrophysiological properties over 2 years between patients with and those without atrial tachyarrhythmias. Conclusions— Prolonged P-wave duration, but not differences in atrial effective refractory periods, was associated with the development of atrial tachyarrhythmias in pacemaker patients.

Preprocedural Ventricular Rate Predicts Subsequent Sick Sinus Syndrome after Ablation for Long‐Standing Persistent Atrial Fibrillation

Concealed sick sinus syndrome may become manifest after restoration of sinus rhythm by ablation in patients with long-standing persistent atrial fibrillation (AF). The purpose of this study was to investigate the association between the preprocedural ventricular rate during AF and sinus node function in patients with long-standing persistent AF. Consecutive patients (n = 102) who underwent ablation for long-standing persistent AF were enrolled. We measured the ventricular rate during AF before ablation in the absence of antiarrhythmic drugs. Sinus node function was assessed by electrophysiological study and serial Holter recordings after ablation. Patients in the lowest quartile of ventricular rate during AF had longer corrected sinus node recovery time (1.06 ± 1.39 seconds) than those in the other quartiles (0.54 ± 0.31 seconds; P = 0.006) and lower mean heart rate on 24-hour Holter recording 3 months after ablation (68 ± 9 beats/min vs 75 ± 10 beats/min, P = 0.01). During a mean follow-up of 23 ± 10 months, sick sinus syndrome necessitating permanent pacemaker implantation developed in five (5%) patients, and multivariate analysis revealed that a low ventricular rate during AF rate was an independent risk factor for sick sinus syndrome (odds ratio = 0.90 for a 1 beat/min increase in AF rate, P = 0.04). A low preprocedural ventricular rate during AF indicates the existence of sinus node dysfunction after restoration of sinus rhythm by ablation in patients with long-standing persistent AF.

Sinus node dysfunction in atrial fibrillation patients: the evidence of regional atrial substrate remodelling

It remains unclear as to whether regional atrial substrates of certain areas of the atrium in patients with atrial fibrillation (AF) can be related to sinoatrial node dysfunction. We investigated the relationship between the biatrial substrate characteristics and sinus node function in these patients. The study enrolled 34 patients (aged 57 ± 11 years old; 20 males) who underwent catheter ablation for symptomatic paroxysmal AF. Sinus node dysfunction was defined as having corrected sinus node recovery time longer than 550 ms. Atrial substrate analyses of both atria and atrial conductive properties were investigated in patients with (Group 1) and without sinus node dysfunction (Group 2). The mean global bipolar voltage of both atria and the atrial refractory period were similar between the two groups. Regional analysis showed that the mean bipolar voltage for patients in Group 1 was lower than in Group 2 (1.0 ± 0.3 vs. 2.1 ± 0.7 mV, P < 0.001) only in the sinus node region, while the electrophysiological properties were similar for both groups in other anatomic regions of both atria. The right atrial total activation time was significantly longer (97 ± 9 vs. 89 ± 10 ms, P = 0.023) and the conduction velocity along the crista terminalis was significantly slower (1.0 ± 0.2 vs. 1.2 ± 0.3 m/s, P = 0.019) in Group 1 patients than in Group 2 patients. In patients with AF, regional atrial remodelling near the sinus node area was associated with sinus node dysfunction.

Atrial Electrical and Structural Remodeling Associated with Longstanding Pulmonary Hypertension and Right Ventricular Hypertrophy in Humans

Pulmonary hypertension (PH) is common to a range of cardiopulmonary conditions and is associated with atrial arrhythmias. However, little is known of the isolated atrial effects of PH and right atrial dilatation (RA) in humans. To avoid the confounding effects of PH-associated disease states, we performed detailed electrophysiological (EP) and electroanatomic (EA) mapping of the RA in patients with idiopathic PH. Eight PH patients (mean pulmonary arterial [PA] pressure 39.0 ± 15.8 mmHg) and 16 age-matched controls (mean PA pressure 11.5 ± 4.1 mmHg, P < 0.0001) were studied. Corrected sinus node recovery times (cSNRT), atrial effective refractory periods (ERPs), conduction delay at the crista terminalis (CT), and inducibility of atrial fibrillation (AF) were evaluated. EA mapping (pacing cycle length 600 and 300 milliseconds) was performed to determine RA global and regional voltage, conduction velocities, atrial activation times, fractionated electrograms and double potentials. Patients with PH demonstrated a prolongation in cSNRT without significant change in atrial ERP and an increase in AF inducibility. PH was associated with lower tissue voltage (1.8 ± 0.4 mV in PH vs 2.2 ± 0.4 mV in controls, P = 0.02), increased low voltage areas (13.7 ± 8.2% in PH vs 6.2 ± 3.7% in controls, P < 0.01) and the presence of electrically silent areas. Conduction velocities were slower (global 67.3 ± 5.6 cm/s vs 92.8 ± 4.0 cm/s, P < 0.001) and fractionated electrograms and double potentials were more prevalent (14.7 ± 4.4% vs 6.3 ± 4.1, P < 0.01) in PH compared with controls, respectively. Idiopathic PH is associated with RA remodeling characterized by: generalized conduction slowing with marked regional abnormalities; reduced tissue voltage; and regions of electrical silence. These changes provide important insights into the isolated effects of PH fundamental to a range of clinical conditions associated with AF.

Prediction of sinus node dysfunction in patients with long-standing persistent atrial fibrillation using the atrial fibrillatory cycle length

BackgroundSinus node dysfunction (SND) occasionally coexists with long-standing atrial fibrillation (AF) but is unidentifiable during AF. We aimed to identify the predictors of underlying SND when deciding the indications for long-standing persistent AF ablation. MethodsWe included 105 patients undergoing ablation of long-standing persistent AF to assess the frequency of a permanent pacemaker implantation (PMI) for SND that manifested after sinus conversion and to determine the relationship between the corrected sinus node recovery time (CSNRT) and other clinical parameters obtained before the ablation including the atrial fibrillatory cycle length (AFCL). ResultsWe identified 7 patients (7%) requiring a PMI for SND after AF termination. The patients with a PMI were nearly all females (6/7) and had a significantly longer CSNRT (1197 ± 647 vs 612 ± 349 milliseconds; P = .0046) and more prolonged AFCL (179 ± 19 vs 153 ± 22 milliseconds; P = .0028) than those without. The age (r = 0.26; P = .011), female sex (r = 0.25; P = .012), hypertension (r = 0.22; P = .038), and AFCL (r = 0.4; P < .0001) were significantly correlated with the CSNRT. A stepwise multivariate linear regression analysis including these parameters revealed that the AFCL was the only independent determinant of the CSNRT (β = 0.38; P = .0012). A receiver operating characteristic curve identified an AFCL of more than 162 milliseconds as the optimal cutoff value for predicting SND requiring a PMI (area under the curve, 0.84; sensitivity, 86%; specificity, 74%; P = .0066). ConclusionsA prolonged AFCL was significantly associated with SND. Thus, assessing the AFCL in the patients with long-standing persistent AF may be helpful for the risk stratification of underlying SND.

Sinus nodal response to adenosine relates to the severity of sinus node dysfunction

It is unknown as to whether the result of adenosine testing for the diagnosis of sinus node dysfunction (SND) depends on the clinical presentation. We investigated whether syncope or presyncope are associated with a more pronounced sinus nodal inhibition by adenosine in SND. We studied 46 patients with SND, 33 with syncope or presyncope and 13 without such history. Controls were 30 subjects undergoing electrophysiological studies for supraventricular tachycardia or unexplained syncope. We calculated the corrected sinus node recovery time after intravenous adenosine 0.15 mg/kg (ADSNRT) as well as after atrial pacing (CSNRT). Corrected sinus node recovery time values >525 ms were considered abnormal. Corrected sinus node recovery time after adenosine injection was more prolonged in SND patients with syncope or presyncope as compared with those without such history [median: 4900 inter-quartile range (IQR): 920-8560 ms vs. median: 280 IQR: 5-908 ms; P< 0.005]. In SND patients with syncope or presyncope ADSNRT was more prolonged than CSNRT (median: 4900 IQR: 920-8560 ms vs. median: 680 IQR: 359-1650 ms, P< 0.01). In SND patients without syncope or presyncope no statistical difference was noted between ADSNRT and CSNRT (median: 280 IQR: 5-908 ms vs. median: 396 IQR: 270-600 ms, P = 0.80). The sensitivity of CSNRT for SND diagnosis was 57% and the specificity was 100%. A cut-off of 1029 ms for ADSRNT yields the same sensitivity with a specificity of 96.6%. In patients with SND syncope or presyncope relate to an exaggerated sinus nodal suppression by adenosine. Prolonged ADSNRT can diagnose cases with severe underlying SND where a more aggressive management strategy is probably warranted.

Ageing-dependent remodelling of ion channel and Ca2+clock genes underlying sino-atrial node pacemaking

The function of the sino-atrial node (SAN), the pacemaker of the heart, is known to decline with age, resulting in pacemaker disease in the elderly. The aim of the study was to investigate the effects of ageing on the SAN by characterizing electrophysiological changes and determining whether changes in gene expression are involved. In young and old rats, SAN function was characterized in the anaesthetized animal, isolated heart and isolated right atrium using ECG and action potential recordings; gene expression was characterized using quantitative PCR. The SAN function declined with age as follows: the intrinsic heart rate declined by 18 ± 3%; the corrected SAN recovery time increased by 43 ± 13%; and the SAN action potential duration increased by 11 ± 3% (at 75% repolarization). Gene expression in the SAN changed considerably with age, e.g. there was an age-dependent decrease in the Ca(2+) clock gene, RYR2, and changes in many ion channels (e.g. increases in Na(v)1.5, Na(v)β1 and Ca(v)1.2 and decreases in K(v)1.5 and HCN1). In conclusion, with age, there are changes in the expression of ion channel and Ca(2+) clock genes in the SAN, and the changes may provide a partial explanation for the age-dependent decline in pacemaker function.