Detection and quantification of left atrial structural remodeling with delayed-enhancement magnetic resonance imaging in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with diffuse left atrial fibrosis and a reduction in endocardial voltage. These changes are indicators of AF severity and appear to be predictors of treatment outcome. In this study, we report the utility of delayed-enhancement magnetic resonance imaging (DE-MRI) in detecting abnormal atrial tissue before radiofrequency ablation and in predicting procedural outcome. METHODS AND RESULTS: Eighty-one patients presenting for pulmonary vein antrum isolation for treatment of AF underwent 3-dimensional DE-MRI of the left atrium before the ablation. Six healthy volunteers also were scanned. DE-MRI images were manually segmented to isolate the left atrium, and custom software was implemented to quantify the spatial extent of delayed enhancement, which was then compared with the regions of low voltage from electroanatomic maps from the pulmonary vein antrum isolation procedure. Patients were assessed for AF recurrence at least 6 months after pulmonary vein antrum isolation, with an average follow-up of 9.6+/-3.7 months (range, 6 to 19 months). On the basis of the extent of preablation enhancement, 43 patients were classified as having minimal enhancement (average enhancement, 8.0+/-4.2%), 30 as having moderate enhancement (21.3+/-5.8%), and 8 as having extensive enhancement (50.1+/-15.4%). The rate of AF recurrence was 6 patients (14.0%) with minimal enhancement, 13 (43.3%) with moderate enhancement, and 6 (75%) with extensive enhancement (P<0.001). CONCLUSIONS: DE-MRI provides a noninvasive means of assessing left atrial myocardial tissue in patients suffering from AF and might provide insight into the progress of the disease. Preablation DE-MRI holds promise for predicting responders to AF ablation and may provide a metric of overall disease progression.

Magnetic resonance imaging-confirmed ablative debulking of the left atrial posterior wall and septum for treatment of persistent atrial fibrillation: rationale and initial experience.

INTRODUCTION: Though pulmonary vein (PV) isolation has been widely adopted for treatment of atrial fibrillation (AF), recurrence rates remain unacceptably high with persistent and longstanding AF. As evidence emerges for non-PV substrate changes in the pathogenesis of AF, more extensive ablation strategies need further study. METHODS: We modified our PV antrum isolation procedure to include abatement of posterior and septal wall potentials. We also employed recently described image-processing techniques using delayed-enhancement (DE) MRI to characterize tissue injury patterns 3 months after ablation, to assess whether each PV was encircled with scar, and to assess the impact of these parameters on procedural success. RESULTS: 118 consecutive patients underwent debulking procedure and completed follow-up, of which 86 underwent DE-MRI. The total left atrial (LA) radiofrequency delivery correlated with percent LA scarring by DE-MRI (r = 0.6, P < 0.001). Based on DE patterns, complete encirclement was seen in only 131 of 335 PVs (39.1%). As expected, Cox regression analysis showed a significant relationship between the number of veins encircled by delayed enhancement and clinical success (hazard ratio of 0.62, P = 0.015). Also, progressive quartile increases in postablation posterior and septal wall scarring reduced recurrences rates with a HR of 0.65, P = 0.022 and 0.66, P = 0.026, respectively. CONCLUSION: Pathologic remodeling in the septal and posterior walls of the LA helps form the pathogenic substrate for AF, and these early results suggest that more aggressive treatment of these regions appears to correlate with improved ablation outcomes. Noninvasive imaging to characterize tissue changes after ablation may prove essential to stratifying recurrence risk.

Modulation of the sinus rate during ventricular fibrillation.

BACKGROUND: During supraventricular and ventricular tachycardia, the arterial baroreflex predominates with minimal contribution from the cardiopulmonary reflex. To our knowledge, the role of the arterial baroreflex gain (BRG) during and immediately following termination of ventricular fibrillation (VF) has not been characterized. OBJECTIVE: We hypothesized that (1) arterial BRG correlated with sinus node cycle length (SNCL) changes during VF, and that (2) the greater the arterial BRG, the greater the blood pressure (BP) recovery following successful defibrillation. METHODS: Arterial BRG was assessed in 18 patients referred for the implantation of a defibrillator incorporating an atrial lead. The average SNCL was measured during the 5 seconds prior to VF induction and the last 5 seconds during VF before defibrillation. Percent SNCL change (%DeltaSNCL) was determined. Arterial BP recovery was calculated as the difference in mean BP following defibrillation compared to during VF. RESULTS: Arterial BRG ranged between -3 and 18 ms/mmHg. During VF, SNCL shortened in 11 patients (group A, mean %DeltaSNCL =-15%), and surprisingly lengthened in seven patients (group B, mean %DeltaSNCL = 5%). There was no correlation between %DeltaSNCL and arterial BRG. In fact, arterial BRG in group A was lower when compared with group B (P = 0.075). Similarly, there was no correlation between arterial BRG and BP recovery. CONCLUSIONS: We found no correlation between arterial BRG and %DeltaSNCL during VF, or BP recovery following defibrillation. Our findings of SNCL lengthening in 7 of 18 patients suggest that in some patients, arterial BRG plays a minor role during VF with a greater contribution from the cardiopulmonary BRG.

Atrial fibrillation ablation in patients with therapeutic international normalized ratios.

AIMS: Pulmonary vein antrum isolation (PVAI) plays a pivotal role in the comprehensive treatment of atrial fibrillation (AF). The need for effective anticoagulation bridging following PVAI is associated with significant vascular complication rates and increased costs. We investigated the safety of PVAI in patients with therapeutic international normalized ratios (INR) the day of the procedure. METHODS: A case-control analysis was performed on patients who underwent PVAI with therapeutic INR (>2). Patients with normal preprocedure INR served as controls. The incidence of major and minor hematomas, fistulas, vascular injury, and cardiac perforation or tamponade were catalogued. PVAI was performed under fluoroscopic, electro-anatomical, and intracardiac echocardiographic guidance, with an open irrigation ablation technique. RESULTS: A total of 194 patients (mean age 64 +/- 12) were included; 87 patients underwent PVAI with therapeutic INR (cases) and 107 with normal INR (controls). Persistent AF was more prevalent than paroxysmal AF in the therapeutic INR group. The mean INR for cases was 2.8 +/- 0.7 compared to 1.4 +/- 0.3 in the control group (P < 0.01). All procedures were completed without acute complications. Two major adverse events were observed, one in each arm. No significant difference in terms of minor (6.5% vs. 5.7%, P = 0.23) or major (0.93% vs. 1.15%, P = 0.49) vascular events or bleeding was detected between the therapeutic INR and the control group. The combined endpoint of major and minor complications did not differ among groups (9.35% vs. 8.05%, P = 0.19). CONCLUSION: Atrial fibrillation ablation in patients with therapeutic INR on the day of a procedure appears to be safe and feasible. Expensive outpatient anti-coagulation bridging may be safely avoided in this type of population.

Relation of daytime bradyarrhythmias with high risk features of sleep apnea.

Bradyarrhythmias (BA) have been reported in patients with sleep apnea (SA), but the incidence of SA in patients with BA remains unclear. A case-control study was conducted to assess the prevalence of high-risk features of SA in patients with documented BA on 24-hour Holter monitoring compared with patients without BA. Controls were age-matched patients selected from those with no evidence of BA on 24-hour Holter monitoring. BA were defined as the presence of pauses of >3 seconds, regardless of the mechanism, and/or heart rate <40 beats/min during presumed waking hours (8 a.m. to 8 p.m.). High-risk features of SA were determined by the Berlin Questionnaire, with positive results defined as having '2 of 3 positive high-risk categories. Body mass index (BMI), hypertension, beta-blocker use, and other underlying characteristics were cataloged. Nineteen patients with documented BA and 47 with no BA were identified. The mean ages and BMIs in the active and control groups were not statistically significant. High-risk features for SA were present in 57.8% of patients in the BA group compared with 21.3% in the control group (p = 0.003). After controlling for age, BMI, hypertension, and beta-blocker use, patients with BA were 6 times more likely to have high-risk features of SA compared with those without BA (logistic regression odds ratio 6.1, 95% confidence interval 1.5 to 24, p = 0.012). In conclusion, irrespective of BMI, age, and other underlying risk factors, the presence of daytime BA was highly associated with high-risk features of SA.

Heart rate variability measures during sinus rhythm predict cycle length entropy during atrial fibrillation.

INTRODUCTION: Several noninvasive measures of cardiac risk such as heart rate variability (HRV) cannot be used in patients with atrial fibrillation (AF). One promising exception is the measure of ventricular cycle length entropy (VCLE) where initial data suggest that a reduction in VCLE portends an increased risk of cardiac death in patients with chronic AF. In this study, we hypothesized that measures of short-term HRV during sinus rhythm would correlate with measures of cycle length entropy during paroxysms of AF. METHODS: We tested 25 Holter recordings of paroxysmal AF from the Physionet AF Prediction Database. We calculated HRV parameters including standard deviation of all NN intervals (SDNN), the root mean square root of the differences between adjacent NN intervals (RMSSD), standard deviation of 5-minute averages of NN intervals (SDANN), percentage of adjacent NN interval differences >50 ms (pNN50), and interbeat correlation coefficient (ICC) from 30 minutes of normal sinus rhythm, and entropy measures (the Shannon Informational Entropy [ShEn] and Average of Approximate Entropy [ApEn]) from 5 minutes of AF that occurred during the same 24-hour monitor. Pairwise correlations were used to assess associations, as regression residuals were normally distributed. RESULTS: The mean entropy measures during AF were: ShEn: 4.78 +/- 0.82, ApEn: 0.198 +/- 0.21. When assessed during the 30 minutes immediately preceding AF onset, ICC showed a significant negative correlation with both ShEn (r =-0.65, P < 0.001) and ApEn (r =-0.60, P < 0.01). RMSSD also correlated with both ShEn (r = 0.41, P = 0.04) and ApEn (r = 0.39, P = 0.05), but other HRV measures showed no correlation with VCLE during AF. CONCLUSION: Reductions in RMSSD or increases in ICC, two short-term HRV measures that are known to reflect parasympathetic function in sinus rhythm, are correlated with reductions in the entropy of ventricular response intervals during AF. Our findings suggest that entropy during AF may be modulated, in part, by vagal innervation.

Scatter in repolarization timing predicts clinical events in post-myocardial infarction patients.

BACKGROUND: Increased spatial and temporal dispersion of repolarization contributes to ventricular arrhythmogenesis. Beat-to-beat fluctuations in T-wave timing are thought to represent such dispersion and may predict clinical events. OBJECTIVE: The purpose of this study was to assess whether a novel noninvasive measure of beat-to-beat instability in T-wave timing would provide additive prognostic information in post-myocardial infarction patients. METHODS: We studied 678 patients from 12 hospitals with 32-lead 5-minute electrocardiogram recordings 6-8 weeks after myocardial infarction. Custom software identified R wave-to-T wave intervals (RTIs) and diastolic intervals (DIs). Repolarization scatter (RTI:DI(StdErr)) was then calculated as the standard error about the RTI:DI regression line. In addition, left ventricular ejection fraction (LVEF), short-term heart rate variability (HRV) parameters, and QT variability index were measured. Patients were followed for the composite endpoint of death or life-threatening ventricular arrhythmia. RESULTS: After a mean follow-up of 63 months, 134 patients met the composite endpoint. An RTI:DI(StdErr) >5.50 ms was associated with a 210% increase in arrhythmias or deaths (P <.001). After adjusting for LVEF, RTI:DI(StdErr) remained an independent predictor (P <.001). RTI:DI(StdErr) was also independent of short-term HRV parameters and the QT variability index. CONCLUSIONS: Increased repolarization scatter, a measure of high-frequency, cycle-length-dependent repolarization instability, predicts poor outcomes in patients after myocardial infarction.

High-density mapping and ablation of concealed low-voltage activity within pulmonary vein antra results in improved freedom from atrial fibrillation compared to pulmonary vein isolation alone.

BACKGROUND: Despite advancements, the goal of durable pulmonary vein isolation (PVI) in all patients undergoing ablation for atrial fibrillation (AF) remains elusive. New high-density mapping (HDM) allows detection of concealed low-voltage signals (CLVSs) that persist after PVI and may represent vulnerabilities in the lesion set. OBJECTIVE: The purpose of this study was to determine the incidence of CLVSs after PVI and the effect of CLVS ablation on outcomes. METHODS: We conducted a case control study comparing 150 patients undergoing HDM-guided PVI and subsequent CLVS mapping and ablation (39 redo, 111 de novo) against 452 historical controls undergoing traditional PVI alone. PVI was similarly performed and confirmed in both groups. RESULTS: Baseline characteristics were similar, except left atrial size was larger in the HDM-guided group. Acute PVI was achieved in nearly all patients in both groups. In the HDM group, 31 of 150 patients exhibited CLVS after luminal PVI, and all were subsequently eliminated. During mean follow-up of 320 days, after controlling for baseline characteristics, the HDM-guided group exhibited a hazard ratio of 0.19 in freedom from AF (P <.001). De novo patients exhibited a hazard ratio of 0.44 relative to redo patients in the HDM-guided group. Both subgroups exhibited significantly lower event rates compared to controls in log-rank analysis (P <.001). CONCLUSION: CLVSs are commonly identified with HDM after PVI, likely representing vulnerabilities in antral lesion sets. Ablation of these targets seems to significantly improve freedom from AF compared to PVI alone.

Randomized comparison between open irrigation technology and intracardiac-echo-guided energy delivery for pulmonary vein antrum isolation: procedural parameters, outcomes, and the effect on esophageal injury.

INTRODUCTION: We performed a prospective study to compare efficacy and safety of both open irrigation tip (OIT) technology with intracardiac echo (ICE)-guided energy delivery in patients presenting for PVAI. METHODS AND RESULTS: Fifty-three patients presenting for PVAI were randomized to ablation using an OIT catheter (Group 1, 26 patients; temperature and power were set at 50 degrees and 50 W, respectively, with a saline pump flow rate of 30 mL/min) or radiofrequency (RF) energy delivery under ICE guidance (Group 2, 27 patients; energy was titrated based on microbubbles formation). The mean procedure time and fluoroscopy exposure were lower in Group 1 (164 +/- 42 min and 7,560 +/- 2,298 microGray m2 vs 204 +/- 47 min and 12,240 +/- 4,356 microGray m2; P = 0.005 and 0.008, respectively). Moreover, the durations of RF lesions applied per PV antrum was lower in Group 1 compared with Group 2 (5.1 +/- 2.2 min vs 9.2 +/- 3.2 min, P = 0.03, respectively). Within 24 hours after PVAI in 35.7% (all erythema) of Group 1 and 57.1% (21.4% erythema and 35.7% necrosis) of Group 2, patients' esophageal wall changes were documented. After 14 +/- 2 months of follow up, recurrences were documented in 19.2% of Group 1 and 22.2% of Group 2 patients. CONCLUSION: Although both OIT and ICE-guided energy delivery possess a similar effect in treating AF, OIT seems to be superior in terms of achieving isolation and shortening fluoroscopy exposure. Moreover, a lower incidence of esophageal wall injury was observed utilizing OIT for PVAI.

Heart rate turbulence parameters correlate with post-premature ventricular contraction changes in muscle sympathetic activity.

BACKGROUND: Heart rate turbulence (HRT) has been shown to be vagally mediated with a strong correlation to baroreflex indices. However, the relationship between HRT and peripheral sympathetic nerve activity (SNA) after a premature ventricular contraction (PVC) remains unclear. OBJECTIVE: We sought to evaluate the relationship between HRT and the changes in peripheral SNA after PVCs. METHODS: We recorded postganglionic muscle SNA during electrocardiogram monitoring in eight patients with spontaneous PVCs. Fifty-two PVCs were observed and analyzed for turbulence onset (TO) and slope (TS). SNA was quantified during (1) the dominant burst after the PVC (dominant burst area) and (2) the 10 seconds after the dominant burst (postburst SNA). RESULTS: The mean TO was 0.1% +/- 4.6%, and the mean TS was 6.1 +/- 6.6. The dominant burst area negatively correlated with TO (r = -0.50, P = .0002). The postburst SNA showed a significant positive correlation with TO (r = 0.44, P = .001) and a negative correlation with TS (r = -0.42, P = .002). These correlations remained significant after controlling for either the PVC coupling interval or the left ventricular ejection fraction. CONCLUSIONS: Our findings highlight the relationship between perturbations in HRT and pathology in the sympathetic limb of the autonomic nervous system. Future studies are needed to evaluate the prognostic role of baroreflex control of sympathetic activity in patients with structural heart disease.

The effects of rate and irregularity on sympathetic nerve activity in human subjects.

BACKGROUND: We have recently shown that atrial fibrillation is associated with an increase in sympathetic nerve activity (SNA) compared with sinus rhythm. It remains unclear, however, whether these findings are true at various rates and whether the magnitude of sympathoexcitation is related to the degree of irregularity. OBJECTIVE: To determine the role of irregularity in mediating the SNA changes at various pacing rates. Univariate analysis showed that as the irregularity increased, SBP increased (r = 0.44, P < .001) but that MAP and DBP did not change significantly. METHODS: Using custom-made software, atrioventricular sequential pacing with predetermined rates (100, 120, and 140 bpm) and irregularities (standard deviation = 0%, 5%, 15%, and 25% of mean cycle length) was performed in 23 patients referred for electrophysiologic evaluation. Pacing at each rate/irregularity was performed for 2 minutes, with 2 minutes of recovery in between. Systolic, diastolic, and mean arterial blood pressure (SBP, DBP, and MAP), central venous pressure (CVP), and SNA were measured at baseline and during pacing. RESULTS: Univariate analysis showed that as the irregularity increased, SBP increased (r = 0.44, P < .001 but that MAP and DBP did not change significantly. A significant correlation was found between the pacing irregularity and SNA, with greater sympathoexcitation noted at greater degrees of irregularity (r = 0.2, P = .04). A five-variable linear model using DBP, MAP, CVP, and degree of pacing irregularity to predict SNA was highly statistically significant (r = 0.46, P < .001). After controlling for hemodynamic changes, for every 1% increase in irregularity, there was a 6.1% increase in SNA. CONCLUSION: We have shown that greater degrees of irregularity cause greater sympathoexcitation and that the effects of irregular pacing on SNA are independent of the hemodynamic changes.

Bipolar lumenless lead performance in children and adults with congenital heart disease.

BACKGROUND: Because of small size and anatomic variation, implantation of intracardiac leads for permanent pacing in pediatric and congenital heart disease (CHD) patients can be challenging. A novel 4.1F bipolar catheter-delivered lead offers potential advantages for this population. OBJECTIVE; The purpose of this study was to retrospectively evaluate this lead performance in this specific population. METHODS: We performed a retrospective descriptive analysis of all pediatric and adult CHD patients at a single center implanted with a 4.1F bipolar catheter-delivered active fixation pacemaker lead (Medtronic model 3830, Medtronic, Inc, Minneapolis, MN, USA). RESULTS: Over 10 months, 42 leads were implanted in 27 patients. Twenty-six atrial and 16 ventricular leads were placed. Patient ages were 1-28 years (mean 15 +/- 7), and weights were 7.8-104 kg (mean 51.5 +/- 26.6). Ventricular septal defect and D-transposition of great arteries were the most prevalent CHD diagnoses. Implant capture thresholds were 1.2 +/- 0.8 V at 0.5 ms in the atrium and 0.8 +/- 0.5 V at 0.5 ms in the ventricle. Implant sensing thresholds were 4.1 +/- 2.7 mV in the atrium and 12.1 +/- 4.9 mV in the ventricle. Phrenic nerve stimulation was avoided in all, and selective site pacing was achieved in most cases. Pacing and sensing thresholds remained stable during 90 +/- 52 days follow-up. No lead related complications, failures, or extractions were observed. CONCLUSIONS: In our single-center experience with pediatric and CHD patients, a novel small, catheter-delivered bipolar lead has proven safe and effective for atrial and ventricular pacing in acute and subacute time periods. Longer performance trends will be required to determine chronic efficacy.

Imaging modalities in cardiac electrophysiology.

Cardiac imaging, both noninvasive and invasive, has become a crucial part of evaluating patients during the electrophysiology procedure experience. These anatomical data allow electrophysiologists to not only assess who is an appropriate candidate for each procedure, but also to determine the rate of success from these procedures. This article incorporates a review of the various cardiac imaging techniques available today, with a focus on atrial arrhythmias, ventricular arrhythmias and device therapy.

Ablation strategies for atrial fibrillation.

Atrial fibrillation remains the most common arrhythmia in the USA and is associated with an increased risk for stroke, congestive heart failure and overall mortality. There has been a tremendous advance in the field of catheter ablation of atrial fibrillation that has resulted in better outcomes for patients. The approach for ablation of atrial fibrillation can be different depending on patients' presentation of paroxysmal or persistent atrial fibrillation. Pulmonary vein isolation remains the cornerstone of any ablation strategy for atrial fibrillation; however, further ablation, end points of the procedure, clinical end points for successful ablation and appropriate follow-up remain controversial. We aim to discuss these different approaches and the major controversies in catheter ablation of atrial fibrillation.

Real-time imaging in left atrial mapping and ablation.

The catheter-based ablation of atrial fibrillation has been transformed greatly by the introduction of new technologies and techniques. This article describes the major advancements in real-time navigation systems, including both 3D mapping systems and 2D echocardiography. The relative strengths and weakness of these systems and their accuracy on clinical outcome is also discussed. Finally, we explore current and emerging MRI technologies that will allow the assessment of disease progression and enable procedural planning.

The acute effect of atrioventricular pacing on sympathetic nerve activity in patients with normal and depressed left ventricular function.

Although modest elevations in pacing rate improve cardiac output and induce reflex sympathoinhibition, the threshold rate above which hemodynamic perturbations induce reflex sympathoexcitation remains unknown. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressures (MAP) and sympathetic nerve activity (SNA) were measured during normal sinus rhythm (NSR) and atrioventricular (AV) sequential pacing in 25 patients. Pacing was performed at 100, 120, and 140 beats/min with an AV interval of 100 ms. Patients were divided into two groups based on normal or abnormal left ventricular ejection fraction (LVEF): group 1 (n = 11; mean LVEF, 55%) and group 2 (n = 14; mean LVEF, 31%). In group 1, relative to NSR, SBP decreased an average of 2%, 3%, and 8% at 100, 120, and 140 beats/min (P < 0.001), respectively. DBP and MAP increased 9%, 15%, and 15% (P = 0.001) and 3%, 6%, and 5% [P = not significant (NS)], respectively. In group 2, SBP reductions were even greater, with an average decrease of 4%, 8%, and 16% (P < 0.001). Whereas DBP increased 9%, 9%, and 8% at 100, 120, and 140 beats/min (P = NS), MAP increased 3% and 2% at 100 and 120 beats/min but decreased 3% at 140 beats/min (P = 0.001). SNA recordings were obtained in 11 patients (6 in group 1 and 5 in group 2). In group 1, SNA decreased during all rates, with a mean 21% reduction. In group 2, however, SNA decreased at 100 and 120 beats/min (49% and 38%) but increased 24% at 140 beats/min. Patients with depressed LVEF exhibited altered hemodynamic and sympathetic responses to rapid sequential pacing. The implications of these findings in device programming and arrhythmia rate control await future studies.