Steven J. Spence

Electrical Remodeling of the Atria in Congestive Heart Failure Electrophysiological and Electroanatomic Mapping in Humans

Background—Atrial fibrillation (AF) frequently complicates congestive heart failure (CHF). However, the electrophysiological substrate for AF in humans with CHF remains unknown. We evaluated the electrophysiological and electroanatomic characteristics of the atria in patients with CHF. Methods and Results—Twenty-one patients (aged 53.7±13.6 years) with symptomatic CHF (left ventricular ejection fraction 25.5±6.0%) and 21 age-matched controls were studied. The following were evaluated: effective refractory periods (ERPs) from the high and low lateral right atrium (LRA), high septal right atrium, and distal coronary sinus (CS); conduction time along the CS and LRA; corrected sinus node recovery times; P-wave duration; and conduction at the crista terminalis. In a subset, electroanatomic mapping was performed to determine atrial activation, regional conduction velocity, double potentials, fractionated electrograms, regional voltage, and areas of electrical silence. Patients with CHF demonstrated an increase in atrial ERP with no change in the heterogeneity of refractoriness, an increase of atrial conduction time along the LRA and the CS, prolongation of the P-wave duration and corrected sinus node recovery times, and greater number and duration of double potentials along the crista terminalis. Electroanatomic mapping demonstrated regional conduction slowing with a greater number of electrograms with fractionation or double potentials, associated with areas of low voltage and electrical silence (scar). Patients with CHF demonstrated an increased propensity for AF with single extrastimuli, and induced AF was more often sustained. Conclusions—Atrial remodeling due to CHF is characterized by structural changes, abnormalities of conduction, sinus node dysfunction, and increased refractoriness. These abnormalities may be responsible in part for the increased propensity for AF in CHF.

Electrophysiological and Electroanatomic Characterization of the Atria in Sinus Node Disease Evidence of Diffuse Atrial Remodeling

Background—The normal sinus pacemaker complex is an extensive structure within the right atrium. We hypothesized that patients with sinus node disease (SND) would have evidence of diffuse atrial abnormalities. Methods and Results—Sixteen patients with symptomatic SND and 16 age-matched controls were studied. The following were evaluated: effective refractory periods (ERPs) from the high and low lateral right atrium (RA), high septal RA, and distal coronary sinus (CS); conduction time along the CS and lateral RA; P-wave duration; and conduction at the crista terminalis. Electroanatomic mapping was performed to define the sinus node complex and determine regional conduction velocity, double potentials, fractionated electrograms, regional voltage, and areas of electrical silence. Patients with SND demonstrated significant increase in atrial ERP at all right atrial sites, increased atrial conduction time along the lateral RA and CS, prolongation of the P-wave duration, and greater number and duration of double potentials along the crista terminalis. Electroanatomic mapping demonstrated the sinus node complex in SND to be more often unicentric, localized to the low crista terminalis at the site of the largest residual voltage amplitude. There was significant regional conduction slowing with double potentials and fractionation associated with areas of low voltage and electrical silence (or scar). Conclusions—SND is associated with diffuse atrial remodeling characterized by structural change, conduction abnormalities, and increased right atrial refractoriness. There was a change in the nature of sinus pacemaker activity with loss of the normal multicentric pattern of activation, caudal shift of the pacemaker complex, and abnormal and circuitous conduction around lines of conduction block.

Remodeling of Sinus Node Function in Patients With Congestive Heart Failure Reduction in Sinus Node Reserve

Background—Experimental and clinical studies have demonstrated diffuse atrial remodeling in congestive heart failure (CHF). We hypothesized that patients with CHF would demonstrate derangement of sinus node function. Methods and Results—Eighteen patients with symptomatic CHF (left ventricular ejection fraction, 26±5%) and 18 age-matched control subjects were studied. Under autonomic blockade, the following were evaluated: intrinsic sinus cycle length, corrected sinus node recovery time (CSNRT), sinoatrial conduction time, number and duration of fractionated electograms or double potentials along the crista terminalis, and location of the earliest sinus activity. Electroanatomic mapping was performed to evaluate the location and nature of the sinus node complex, to characterize sinoatrial propagation, and to evaluate conduction abnormalities and voltage amplitude along the crista terminalis. Patients with CHF demonstrated the following findings compared with age-matched control subjects: prolongation of the intrinsic sinus cycle length (P=0.005), prolongation of CSNRT (P<0.0001), caudal localization of sinus activity both during sinus rhythm (P=0.03) and after pacing (P=0.002), prolongation of sinoatrial conduction time (P=0.02), greater number (P<0.0001) and duration (P<0.0001) of fractionated electrograms or double potentials along the crista terminalis, loss of voltage amplitude along the crista terminalis (P=0.02), and abnormal and circuitous propagation of the sinus impulse. Conclusions—This study demonstrates that patients with CHF have significant sinus node remodeling characterized by anatomic and structural changes along the crista terminalis with a reduction in functional sinus node reserve. This finding may have implications for the development of clinical bradycardia in CHF and for the use of negatively chronotropic agents and pacing in this condition.

Effect of Chronic Right Atrial Stretch on Atrial Electrical Remodeling in Patients With an Atrial Septal Defect

Background—Adults with an atrial septal defect (ASD) frequently develop late atrial arrhythmias. We sought to characterize the pattern and persistence of atrial electrical remodeling caused by chronic right atrial (RA) stretch in this group. Methods and Results—Thirteen ASD patients without atrial arrhythmia (42±10 years old; RA volume, 65±16 mL) and 17 normal control subjects (44±11 years old; RA volume, 38±8 mL) had electrophysiological study to measure (1) atrial effective refractory period (AERP) from the low lateral/high lateral/high septal RA and distal coronary sinus (CS), (2) dispersion of AERP, (3) lateral-RA and CS conduction time during constant pacing, (4) conduction delay across the crista terminalis measuring the number of crista catheter bipoles (0–10) recording discrete double potentials during pacing, (5) corrected sinus node recovery time, and (6) P-wave duration. After ASD closure (8.3±5.6 months), follow-up echo studies (n=12) and electrophysiological study (n=4) were performed. The low-lateral AERP, P-wave duration, sinus node recovery time, and extent of conduction delay across the crista terminalis were significantly greater in ASD patients. No differences were found for other measured electrophysiological study parameters. At follow-up, there was incomplete resolution of RA volume (47±12 mL;P <0.01 versus before surgery), a trend toward shortening of the AERP at the lateral RA and an increase at the distal CS and high septal RA, but persisting extensive, widely split crista double potentials. Conclusions—Chronic RA stretch because of ASD causes electrical remodeling with modest increases in RA ERP, conduction delay at the crista terminalis, and sinus node dysfunction. Conduction delay at the crista terminalis persists beyond ASD closure and may contribute to the long-term atrial arrhythmia substrate in this condition.

Epicardial wave mapping in human long-lasting persistent atrial fibrillation: transient rotational circuits, complex wavefronts, and disorganized activity

OBJECTIVES To characterize the nature of atrial fibrillation (AF) activation in human persistent AF (PerAF) using modern tools including activation, directionality analyses, complex-fractionated electrogram, and spectral information. BACKGROUND The mechanism of PerAF in humans is uncertain. METHODS AND RESULTS High-density epicardial mapping (128 electrodes/6.75 cm(2)) of the posterior LA wall (PLAW), LA and RA appendage (LAA, RAA), and RSPV-LA junction was performed in 18 patients with PerAF undergoing open heart surgery. Continuous 10 s recordings were analysed offline. Activation patterns were characterized into four subtypes (i) wavefronts (broad or multiple), (ii) rotational circuits (≥2 rotations of 360°), (iii) focal sources with centrifugal activation of the entire mapping area, or (iv) disorganized activity [isolated chaotic activation(s) that propagate ≤3 bipoles or activation(s) that occur as isolated beats dissociated from the activation of adjacent bipole sites]. Activation at a total of 36 regions were analysed (14 PLAW, 3 RSPV-LA, 12 LAA, and 7 RAA) creating a database of 2904 activation patterns. In the majority of maps, activation patterns were highly heterogeneous with multiple unstable activation patterns transitioning from one to another during each recording. A mean of 3.8 ± 1.6 activation subtypes was seen per map. The most common patterns seen were multiple wavefronts (56.2 ± 32%) and disorganized activity (24.2 ± 30.3%). Only 2 of 36 maps (5.5%) showed a single stable activation pattern throughout the 10-s period. These were stable planar wavefronts. Three transient rotational circuits were observed. Two of the transient circuits were located in the posterior left atrium, while the third was located on the anterior surface of the LAA. Focal activations accounted for 11.3 ± 14.2% of activations and were all short-lived (≤2 beats), with no site demonstrating sustained focal activity. CONCLUSION Human long-lasting PerAF is characterized by heterogeneous and unstable patterns of activation including wavefronts, transient rotational circuits, and disorganized activity.

Electroanatomic Remodeling of the Left Atrium in Paroxysmal and Persistent Atrial Fibrillation Patients Without Structural Heart Disease

Atrial Remodeling in Atrial Fibrillation. Introduction: The nature of the atrial substrate thought to contribute toward maintaining atrial fibrillation (AF) outside the pulmonary veins remains poorly defined. Therefore, our objective was to determine whether patients with paroxysmal and persistent AF have an abnormal electroanatomic substrate within the left atrium (LA).

Long-term effects of catheter ablation for lone atrial fibrillation: progressive atrial electroanatomic substrate remodeling despite successful ablation.

BACKGROUND Whether curative ablation can prevent progression of the atrial electroanatomic remodeling associated with atrial fibrillation (AF) is not known. OBJECTIVE The purpose of this study was to determine whether successful radiofrequency ablation (RFA) of AF can prevent progression of the atrial substrate associated with AF. METHODS Detailed right atrial electroanatomic maps from 11 patients without apparent structural heart disease undergoing RFA of AF at baseline and ≥6 months following successful RFA were compared to 11 control patients undergoing electrophysiologic evaluation of supraventricular tachycardia. Bipolar voltage, conduction, effective refractory periods (ERPs), and signal complexity were assessed. RESULTS At baseline compared with the control group, the AF group demonstrated (1) lower voltage (P <.001); (2) slowed conduction (P = .005); (3) more prevalent complex signals (P <.001); (4) prolonged regional refractoriness (P <.05), and (5) left atrial dilation (P = .01). At 10 ± 13 month follow-up, the AF group demonstrated the following compared to baseline: (1) lower voltage (P <.05); (2) either no improvement or further slowing of conduction; (3) further prolongation of regional refractoriness (P <.05); and (4) reversal of left atrial dilation (P <.05). CONCLUSION Patients with lone AF demonstrate evidence of an abnormal atrial substrate at baseline compared to control patients without AF. This substrate does not appear to reverse even after successful catheter ablation. These findings may have implications for long-term outcomes of ablation and for timing of ablative intervention.

Atrial Electrical and Structural Changes Associated with Longstanding Hypertension in Humans: Implications for the Substrate for Atrial Fibrillation

Atrial Remodeling in Human Hypertension Introduction: Hypertension (HT) is the most common modifiable risk factor for atrial fibrillation (AF), yet little is known of the atrial effects of chronic HT in humans. We aimed to characterize the electrophysiologic (EP) and electroanatomic (EA) remodeling of the right atrium (RA) in patients with chronically treated systemic HT and left ventricular hypertrophy (LVH) without a history of AF.

Atrial electrophysiology is altered by acute hypercapnia but not hypoxemia: implications for promotion of atrial fibrillation in pulmonary disease and sleep apnea.

BACKGROUND Chronic pulmonary disease and sleep apnea have been associated with the development of atrial fibrillation (AF). OBJECTIVE The purpose of this study was to characterize the atrial electrical changes that occur with hypercapnia and hypoxemia and to determine their role in AF development. METHODS Seventeen sheep (6 control, 5 hypercapnia, 6 hypoxemia) underwent open chest electrophysiologic evaluation under autonomic blockade. A 64-electrode endocardial basket catheter was positioned in the right atrium, and 2 x 128 electrode epicardial plaques were sutured to the right atrial and left atrial appendages to determine atrial refractoriness (effective refractory period [ERP]) at 9 sites and 5 cycle lengths, conduction time to fixed points on each plaque, and AF vulnerability. RESULTS Hypercapnia was associated with a 152% lengthening of ERP from baseline and increased conduction time. ERPs rapidly returned to baseline, but recovery of conduction was delayed at least 117 +/- 24 minutes following resolution of hypercapnia. AF vulnerability was reduced during hypercapnia (with increased ERP) but increased significantly with subsequent return to eucapnia (when ERP normalized but conduction time remained prolonged). No significant changes in ERP, atrial conduction time, or AF vulnerability occurred in hypoxemic or control groups. CONCLUSION Differential recovery of ERP and conduction that occurs following hypercapnia might account for the increased vulnerability to AF observed in the phase after return to eucapnia. This may explain in part the increased prevalence of AF in pulmonary disease and sleep apnea.

Effect of respiration on catheter-tissue contact force during ablation of atrial arrhythmias

BACKGROUND Catheter-tissue contact is important for effective lesion creation. OBJECTIVE To assess the effect of respiration on contact force (CF) during atrial fibrillation and cavotricuspid isthmus (CTI)-dependent atrial flutter ablation. METHODS Patients undergoing CTI ablation alone (n = 15) and pulmonary vein (PV) isolation alone (n = 12) under general anesthesia were recruited. Lesions were delivered under ventilation (30 seconds) alternating with lesions delivered under apnea (30 seconds) at an adjacent anatomical site at CTI or PV antra. The average force (F(av)), force-time integral (FTI), and force variability were measured in a region-specific manner by using a novel CF-sensing ablation catheter. Operators were blinded to CF data. RESULTS F(av) and FTI were higher with apnea than with ventilation in all CTI and PV segments (P <.05), an effect attributed to drop in CF with each respiratory swing, resulting in greater force variability during ventilation (P <.05). Low FTI lesions (<500 g) were strongly associated with longer ablation time to achieve bidirectional CTI block (r(2) = .81; P <.001), left PVI (r(2) = .65; P = .009), and right PVI (r(2) = .41; P = .05). Sites with transient CTI block were associated with lower F(av) and FTI than were sites with persistent CTI block (P <.05). Sites of acute PV reconnection were associated with lower F(av) and FTI compared with non-reconnected sites (P <.001). CONCLUSIONS Catheter-tissue CF is critically influenced by respiration; greater CF is observed with ablation during apnea. Poor CF is implicated in longer ablation time to achieve CTI block or PV isolation and in acute reconnection.