Leadless vs. transvenous single-chamber ventricular pacing in the Micra CED study: 2-year follow-up.

AIMS: Clinical trials have demonstrated the safety and efficacy of the Micra leadless VVI pacemaker; however, longer-term outcomes in a large, real-world population with a contemporaneous comparison to transvenous VVI pacemakers have not been examined. We compared reinterventions, chronic complications, and all-cause mortality at 2 years between leadless VVI and transvenous VVI implanted patients. METHODS AND RESULTS: The Micra Coverage with Evidence Development study is a continuously enrolling, observational, cohort study of leadless VVI pacemakers in the US Medicare fee-for-service population. Patients implanted with a leadless VVI pacemaker between March 9, 2017, and December 31, 2018, were identified using Medicare claims data linked to manufacturer device registration data (n = 6219). All transvenous VVI patients from facilities with leadless VVI implants during the study period were obtained directly from Medicare claims (n = 10 212). Cox models were used to compare 2-year outcomes between groups. Compared to transvenous VVI, patients with leadless VVI had more end-stage renal disease (12.0% vs. 2.3%) and a higher Charlson comorbidity index (5.1 vs. 4.6). Leadless VVI patients had significantly fewer reinterventions [adjusted hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.45-0.85, P = 0.003] and chronic complications (adjusted HR 0.69, 95% CI 0.60-0.81, P < 0.0001) compared with transvenous VVI patients. Adjusted all-cause mortality at 2 years was not different between the two groups (adjusted HR 0.97, 95% CI 0.91-1.04, P = 0.37). CONCLUSION: In a real-world study of US Medicare patients, the Micra leadless VVI pacemaker was associated with a 38% lower adjusted rate of reinterventions and a 31% lower adjusted rate of chronic complications compared with transvenous VVI pacing. There was no difference in adjusted all-cause mortality at 2 years.

Patient selection, pacing indications, and subsequent outcomes with de novo leadless single-chamber VVI pacing.

AIMS: Patient selection is a key component of securing optimal patient outcomes with leadless pacing. We sought to describe and compare patient characteristics and outcomes of Micra patients with and without a primary pacing indication associated with atrial fibrillation (AF) in the Micra IDE trial. METHODS AND RESULTS: The primary outcome (risk of cardiac failure, pacemaker syndrome, or syncope related to the Micra system or procedure) was compared between successfully implanted patients from the Micra IDE trial with a primary pacing indication associated with AF or history of AF (AF group) and those without (non-AF group). Among 720 patients successfully implanted with Micra, 228 (31.7%) were in the non-AF group. Reasons for selecting VVI pacing in non-AF patients included an expectation for infrequent pacing (66.2%) and advanced age (27.2%). More patients in the non-AF group had a condition that precluded the use of a transvenous pacemaker (9.6% vs. 4.7%, P = 0.013). Atrial fibrillation patients programmed to VVI received significantly more ventricular pacing compared to non-AF patients (median 67.8% vs. 12.6%; P < 0.001). The overall occurrence of the composite outcome at 24 months was 1.8% with no difference between the AF and non-AF groups (hazard ratio 1.36, 95% confidence interval 0.45-4.2; P = 0.59). CONCLUSION: Nearly one-third of patients selected to receive Micra VVI therapy were for indications not associated with AF. Non-AF VVI patients required less frequent pacing compared to patients with AF. Risks associated with VVI therapy were low and did not differ in those with and without AF.

Stroke of Known Cause and Underlying Atrial Fibrillation (STROKE-AF) randomized trial: Design and rationale.

BACKGROUND: Approximately 20% of ischemic strokes are associated with clinically apparent atrial fibrillation (AF). Regardless of stroke etiology, detection of AF in patients with ischemic strokes often changes antithrombotic treatment from anti-platelet to oral anticoagulation therapy. The role and the optimum duration of cardiac monitoring to detect AF in patients with strokes presumed due to large vessel atherosclerosis or small vessel disease is unknown. This manuscript describes the design and rationale of the STROKE-AF trial. STUDY DESIGN: STROKE-AF is a randomized, controlled, open-label, post-market clinical trial. Detection of AF will be evaluated using continuous arrhythmia monitoring with an insertable cardiac monitor (ICM) compared with standard of care follow-up in patients with stroke (within the prior 10 days) that is presumed due to large vessel cervical or intracranial atherosclerosis, or to small vessel disease. Approximately 500 patients will be enrolled at approximately 40 centers in the United States. Patients will be randomized 1:1 to arrhythmia monitoring with an ICM (continuous monitoring arm) or standard of care follow-up (control arm). Subjects will be followed for ≥12 months and up to 3 years. OUTCOMES: The primary objective is to compare the incidence rate of detected AF through 12 months of follow-up between the two arms. CONCLUSION: This trial will provide information on the value of ICMs to detect subclinical AF in patients with stroke presumed due to large vessel atherosclerosis or small vessel disease, which will have implications for guiding treatment with oral anticoagulation for secondary stroke prevention.

Impact of operator experience and training strategy on procedural outcomes with leadless pacing: Insights from the Micra Transcatheter Pacing Study.

BACKGROUND: Leadless pacemaker systems have been designed to avoid the need for a pocket and transvenous lead. However, delivery of this therapy requires a new catheter-based procedure. This study evaluates the role of operator experience and different training strategies on procedural outcomes. METHODS: A total of 726 patients underwent implant attempt with the Micra transcatheter pacing system (TPS; Medtronic, Minneapolis, MN, USA) by 94 operators trained in a teaching laboratory using a simulator, cadaver, and large animal models (lab training) or locally at the hospital with simulator/demo model and proctorship (hospital training). Procedure success, procedure duration, fluoroscopy time, and safety outcomes were compared between training methods and experience (implant case number). RESULTS: The Micra TPS procedure was successful in 99.2% of attempts and did not differ between the 55 operators trained in the lab setting and the 39 operators trained locally at the hospital (P = 0.189). Implant case number was also not a determinant of procedural success (P = 0.456). Each operator performed between one and 55 procedures. Procedure time and fluoroscopy duration decreased by 2.0% (P = 0.002) and 3.2% (P < 0.001) compared to the previous case. Major complication rate and pericardial effusion rate were not associated with case number (P = 0.755 and P = 0.620, respectively). There were no differences in the safety outcomes by training method. CONCLUSIONS: Among a large group of operators, implantation success was high regardless of experience. While procedure duration and fluoroscopy times decreased with implant number, complications were low and not associated with case number. Procedure and safety outcomes were similar between distinct training methodologies.

How to Implant a Leadless Pacemaker With a Tine-Based Fixation.

Two major studies have shown that leadless pacemakers are safe and effective for patients requiring right ventricular rate responsive pacing therapy. This positive result recently led to FDA approval of one of the available leadless pacing devices. While this new technology is promising, it requires a different skill set for safe implantation. In this article, we review in detail the different steps required for implantation of tine-based leadless pacemakers while providing tips and tricks to minimize complications.

Initial independent outcomes from focal impulse and rotor modulation ablation for atrial fibrillation: multicenter FIRM registry.

INTRODUCTION: The success of pulmonary vein isolation (PVI) for atrial fibrillation (AF) may be improved if stable AF sources identified by Focal Impulse and Rotor Mapping (FIRM) are also eliminated. The long-term results of this approach are unclear outside the centers where FIRM was developed; thus, we assessed outcomes of FIRM-guided AF ablation in the first cases at 10 experienced centers. METHODS: We prospectively enrolled n = 78 consecutive patients (61 ± 10 years) undergoing FIRM guided ablation for persistent (n = 48), longstanding persistent (n = 7), or paroxysmal (n = 23) AF. AF recordings from both atria with a 64-pole basket catheter were analyzed using a novel mapping system (Rhythm View(TM) ; Topera Inc., CA, USA). Identified rotors/focal sources were ablated, followed by PVI. RESULTS: Each institution recruited a median of 6 patients, each of whom showed 2.3 ± 0.9 AF rotors/focal sources in diverse locations. 25.3% of all sources were right atrial (RA), and 50.0% of patients had ≥1 RA source. Ablation of all sources required a total of 16.6 ± 11.7 minutes, followed by PVI. On >1 year follow-up with a 3-month blanking period, 1 patient lost to follow-up (median time to 1st recurrence: 245 days, IQR 145-354), single-procedure freedom from AF was 87.5% (patients without prior ablation; 35/40) and 80.5% (all patients; 62/77) and similar for persistent and paroxysmal AF (P = 0.89). CONCLUSIONS: Elimination of patient-specific AF rotors/focal sources produced freedom-from-AF of ≈80% at 1 year at centers new to FIRM. FIRM-guided ablation has a rapid learning curve, yielding similar results to original FIRM reports in each center's first cases.

Contemporaneous Comparison of Outcomes Among Patients Implanted With a Leadless vs Transvenous Single-Chamber Ventricular Pacemaker.

Importance: The safety and efficacy of leadless VVI pacemakers have been demonstrated in multiple clinical trials, but the comparative performance of the device in a large, real-world population has not been examined. Objective: To compare patient characteristics and complications among patients implanted with leadless VVI and transvenous VVI pacemakers. Design, Setting, Participants: The Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers (Micra CED) is a continuously enrolling observational cohort study evaluating complications, utilization, and outcomes of leadless VVI pacemakers in the US Medicare fee-for-service population. Patients implanted between March 9, 2017, and December 1, 2018, were identified and included. All Medicare patients implanted with leadless VVI and transvenous VVI pacemakers during the study period were enrolled. Patients with less than 12 months of continuous enrollment in Medicare prior to leadless VVI or transvenous VVI implant and with evidence of a prior cardiovascular implantable electronic device were excluded, leaving 5746 patients with leadless VVI pacemakers and 9662 patients with transvenous VVI pacemakers. Data were analyzed from May 2018 to April 2021. Exposures: Medicare patients implanted with leadless VVI pacemakers or transvenous VVI pacemakers. Main Outcomes and Measures: The main outcomes were acute (30-day) complications and 6-month complications. Results: Of 15 408 patients, 6701 (43.5%) were female, and the mean (SD) age was 81.0 (8.7) years. Compared with patients with transvenous VVI pacemakers, patients with leadless VVI pacemakers were more likely to have end-stage kidney disease (690 [12.0%] vs 226 [2.3%]; P < .001) and a higher mean (SD) Charlson Comorbidity Index score (5.1 [3.4] vs 4.6 [3.0]; P < .001). The unadjusted acute complication rate was higher in patients with leadless VVI pacemakers relative to transvenous VVI pacemakers (484 of 5746 [8.4%] vs 707 of 9662 [7.3%]; P = .02). However, there was no significant difference in overall acute complication rates following adjustment for patient characteristics (7.7% vs 7.4%; risk difference, 0.3; 95% CI, -0.6 to 1.3; P = .49). Pericardial effusion and/or perforation within 30 days was significantly higher among patients with leadless VVI pacemakers compared with patients with transvenous VVI pacemakers in both unadjusted and adjusted models (unadjusted, 47 of 5746 [0.8%] vs 38 of 9662 [0.4%]; P < .001; adjusted, 0.8% vs 0.4%; risk difference, 0.4; 95% CI, 0.1 to 0.7; P = .004). Patients implanted with leadless VVI pacemakers had a lower rate of 6-month complications compared with patients implanted with transvenous VVI pacemakers (unadjusted hazard ratio, 0.84; 95% CI, 0.68-1.03; P = .10; adjusted hazard ratio, 0.77; 95% CI, 0.62-0.96; P = .02). Conclusions and Relevance: In this study, despite significant differences in patient characteristics, patients in whom a leadless pacemaker was implanted were observed to have higher rates of pericardial effusion and/or perforation but lower rates of other device-related complications and requirements for device revision at 6 months. Understanding the benefits and risks associated with leadless VVI pacemakers compared with transvenous VVI pacemakers can help clinicians and patients make informed treatment decisions.

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.

Repeat ablation and hospitalization following cryoballoon ablation of atrial fibrillation at a single tertiary medical center.

Cryoablation for atrial fibrillation (AF) has rapidly become a mainstream treatment for AF. In this report, 163 patients who had undergone a cryoablation procedure at one clinical center were contacted by telephone 33.1 ± 3.3 months after the procedure. All patients had received cryoablation of the pulmonary vein ostia, although concomitant procedures were performed at the same time in over 50% of the patients, including radiofrequency and/or cryoablation of other areas of the left atrium. Freedom from a repeat ablation procedure was 87%, while freedom from recurrent hospitalization for AF was 89%, as compared to previous reports of 65%. Of the 13 patients who had a repeat ablation procedure, only one was found to have a reconnection of pulmonary veins, while 4 were found to have atrial flutter. Cryoablation for AF produces a durable result in most patients out to 3 years with better outcomes than previously reported.

In-office insertion of a miniaturized insertable cardiac monitor: Results from the Reveal LINQ In-Office 2 randomized study.

BACKGROUND: Recent miniaturization of an insertable cardiac monitor (ICM) may make it possible to move device insertion from a hospital to office setting. However, the safety of this strategy is unknown. OBJECTIVES: The primary objective was to compare the safety of inserting the Reveal LINQ ICM in an office vs a hospital environment. Ancillary objectives included summarizing device- and procedure-related adverse events and responses to a physician questionnaire. METHODS: Five hundred twenty-one patients indicated for an ICM were randomized (1:1 ratio) to undergo ICM insertion in a hospital or office environment at 26 centers in the United States in the Reveal LINQ In-Office 2 study (ClinicalTrials.gov identifier NCT02395536). Patients were followed for 90 days. RESULTS: ICM insertion was successful in all 482 attempted patients (office: 251; hospital: 231). The untoward event rate (composite of unsuccessful insertion and ICM- or insertion-related complications) was 0.8% (2 of 244) in the office and 0.9% (2 of 227) in the hospital (95% confidence interval, -3.0% to 2.9%; 5% noninferiority: P < .001). In addition, adverse events occurred during 2.5% (6 of 244) of office and 4.4% (10 of 227) of hospital insertions (95% confidence interval [office minus inhospital rates], -5.8% to 1.9%; 5% noninferiority: P < .001). Physicians indicated that for procedures performed in an office vs a hospital, there were fewer delays >15 minutes (16% vs 35%; P < .001) and patient response was more often "very positive." Physicians considered the office location "very convenient" more frequently than the hospital location (85% vs 27%; P < .001). CONCLUSION: The safety profile for the insertion of the Reveal LINQ ICM is excellent irrespective of insertion environment. These results may expand site of service options for LINQ insertion.

A leadless pacemaker in the real-world setting: The Micra Transcatheter Pacing System Post-Approval Registry.

BACKGROUND: First-in-man studies of leadless pacemakers have demonstrated high rates of implant success, and safety and efficacy objectives were achieved. Outside of the investigational setting, there are concerns, particularly over cardiac effusion and perforation, device dislodgement, infection, telemetry, and battery issues. OBJECTIVE: The acute performance of the Micra transcatheter pacemaker from a worldwide Post-Approval Registry is reported. METHODS: The registry is an ongoing prospective single-arm observational study designed to assess the safety and effectiveness of Micra in the post-approval setting. The safety end point was system- or procedure-related major complications at 30 days post implant. We compared the major complication rate with that of the 726 patients from the investigational study. Electrical performance was also characterized. RESULTS: The device was successfully implanted in 792 of 795 registry patients (99.6%) by 149 implanters at 96 centers in 20 countries. Through 30 days post implant, a total of 13 major complications occurred in 12 patients, for a major complication rate of 1.51% (95% confidence interval, 0.78%-2.62%). Major complications included cardiac effusion/perforation (1, 0.13%), device dislodgement (1, 0.13%), and sepsis (1, 0.13%). After adjusting for baseline differences, the rate of major complications in the registry trended lower than the investigational trial (odds ratio, 0.58, 95% confidence interval, 0.27-1.25; P = .16). Early pacing capture thresholds were low and stable. CONCLUSION: Performance of the Micra transcatheter pacemaker in a real-world setting demonstrates a high rate (99.6%) of implant success and low rate (1.51%) of major complications through 30 days post implant. In particular, the rates of pericardial effusion, device dislodgement, and infection were low, reinforcing the positive results seen in the investigational study.

Recurrent Post-Ablation Paroxysmal Atrial Fibrillation Shares Substrates With Persistent Atrial Fibrillation : An 11-Center Study.

INTRODUCTION: The role of atrial fibrillation (AF) substrates is unclear in patients with paroxysmal AF (PAF) that recurs after pulmonary vein isolation (PVI). We hypothesized that patients with recurrent post-ablation (redo) PAF despite PVI have electrical substrates marked by rotors and focal sources, and structural substrates that resemble persistent AF more than patients with (de novo) PAF at first ablation. METHODS: In 175 patients at 11 centers, we compared AF substrates in both atria using 64 pole-basket catheters and phase mapping, and indices of anatomical remodeling between patients with de novo or redo PAF and first ablation for persistent AF. RESULTS: Sources were seen in all patients. More patients with de novo PAF (78.0%) had sources near PVs than patients with redo PAF (47.4%, p=0.005) or persistent AF (46.9%, p=0.001). The total number of sources per patient (p=0.444), and number of non-PV sources (p=0.701) were similar between groups, indicating that redo PAF patients had residual non-PV sources after elimination of PV sources by prior PVI. Structurally, left atrial size did not separate de novo from redo PAF (49.5±9.5 vs. 49.0±7.1mm, p=0.956) but was larger in patients with persistent AF (55.2±8.4mm, p=0.001). CONCLUSIONS: Patients with paroxysmal AF despite prior PVI show electrical substrates that resemble persistent AF more closely than patients with paroxysmal AF at first ablation. Notably, these subgroups of paroxysmal AF are indistinguishable by structural indices. These data motivate studies of trigger versus substrate mechanisms for patients with recurrent paroxysmal AF after PVI.

Long-term outcomes in leadless Micra transcatheter pacemakers with elevated thresholds at implantation: Results from the Micra Transcatheter Pacing System Global Clinical Trial.

BACKGROUND: Device repositioning during Micra leadless pacemaker implantation may be required to achieve optimal pacing thresholds. OBJECTIVE: The purpose of this study was to describe the natural history of acute elevated Micra vs traditional transvenous lead thresholds. METHODS: Micra study VVI patients with threshold data (at 0.24 ms) at implant (n = 711) were compared with Capture study patients with de novo transvenous leads at 0.4 ms (n = 538). In both cohorts, high thresholds were defined as >1.0 V and very high as >1.5 V. Change in pacing threshold (0-6 months) with high (1.0 to ≤1.5 V) or very high (>1.5 V) thresholds were compared using the Wilcoxon signed-rank test. RESULTS: Of the 711 Micra patients, 83 (11.7%) had an implant threshold of >1.0 V at 0.24 ms. Of the 538 Capture patients, 50 (9.3%) had an implant threshold of >1.0 V at 0.40 ms. There were no significant differences in patient characteristics between those with and without an implant threshold of >1.0 V, with the exception of left ventricular ejection fraction in the Capture cohort (high vs low thresholds, 53% vs 58%; P = .011). Patients with an implant threshold of >1.0 V decreased significantly (P < .001) in both cohorts. Micra patients with high and very high thresholds decreased significantly (P < .01) by 1 month, with 87% and 85% having 6-month thresholds lower than the implant value. However, when the capture threshold at implant was >2 V, only 18.2% had a threshold of ≤1 V at 6 months and 45.5% had a capture threshold of >2 V. CONCLUSIONS: Pacing thresholds in most Micra patients with elevated thresholds decrease after implant. Micra device repositioning may not be necessary if the pacing threshold is ≤2 V.

Frequency of and Prognostic Significance of Atrial Fibrillation in Patients Undergoing Transcatheter Aortic Valve Implantation.

The prognostic implications of preexisting atrial fibrillation (AF) and new-onset AF (NOAF) in transcatheter aortic valve implantation (TAVI) remain uncertain. This study assesses the epidemiology of AF in patients treated with TAVI and evaluates their outcomes according to the presence of preexisting AF or NOAF. A retrospective analysis of 708 patients undergoing TAVI from 2 heart hospitals was performed. Patients were divided into 3 study groups: sinus rhythm (n = 423), preexisting AF (n = 219), and NOAF (n = 66). Primary outcomes of interest were all-cause death and stroke both at 30-day and at 1-year follow-up. Preexisting AF was present in 30.9% of our study population, whereas NOAF was observed in 9.3% of patients after TAVI. AF and NOAF patients showed a higher rate of 1-year all-cause mortality compared with patients in sinus rhythm (14.6% vs 6.5% for preexisting AF and 16.3% vs 6.5% for NOAF, p = 0.007). No differences in 30-day mortality were observed between groups. In patients with AF (either preexisting and new-onset), those discharged with single antiplatelet therapy displayed higher mortality rates at 1 year (42.9% vs 11.7%, p = 0.006). Preexisting AF remained an independent predictor of mortality at 1-year follow-up (hazard ratio [HR] 2.34, 95% CI 1.22 to 4.48, p = 0.010). Independent predictors of NOAF were transapical and transaortic approach as well as balloon postdilatation (HR 3.48, 95% CI 1.66 to 7.29, p = 0.001; HR 5.08, 95% CI 2.08 to 12.39, p <0.001; HR 2.76, 95% CI 1.25 to 6.08, p = 0.012, respectively). In conclusion, preexisting AF is common in patients undergoing TAVI and is associated with a twofold increased risk of 1-year mortality. This negative effect is most pronounced in patients discharged with single antiplatelet therapy compared with other antithrombotic regimens.

Serotonin reuptake inhibitor (Paxil) does not prevent the vasovagal reaction associated with carotid sinus massage and/or lower body negative pressure in healthy volunteers.

BACKGROUND: The purpose of this study was to assess the effect of the serotonin reuptake inhibitor paroxetine hydrochloride (Paxil, SmithKline Beecham) on cardiovascular reflexes. We hypothesized that Paxil prevents neurally mediated syncope (NMS) by attenuating the sympathoinhibition and vagotonia associated with a vasovagal reaction. METHODS AND RESULTS: In a double-blind randomized study, 25 healthy subjects with a positive response to either carotid sinus massage (CSM) or lower body negative pressure (LBNP) received Paxil (20 mg/d) or placebo for 6 weeks. Arterial baroreflex sensitivity (BRS), muscle sympathetic nerve activity (SNA), baroreflex control of SNA, blood pressure, and heart rate responses to CSM and LBNP were measured at baseline and at 6 weeks. Nineteen subjects completed the study (Paxil, n=9; placebo, n=10). In the Paxil group, BRS decreased significantly compared with baseline (15.8+/-4.0 ms/mm Hg versus 11.0+/-2.6 ms/mm Hg, P=0.05); however, all 9 subjects continued to have a positive response to LBNP with presyncope. Paxil did not attenuate the sympathoinhibition or vagotonia associated with a positive LBNP response and had no significant effect on baroreflex control of SNA. In the control group, no significant change in BRS was noted compared with baseline. Seven out of 9 subjects who had a positive LBNP response at baseline had a repeat positive LBNP response, and the subject with a positive CSM at baseline had a negative response at 6 weeks. CONCLUSIONS: Paxil decreases arterial BRS but does not prevent the presyncope associated with LBNP. The effect of Paxil on the autonomic reflexes in patients with neurally mediated syncope remains unclear.

Effect of atrial fibrillation and an irregular ventricular response on sympathetic nerve activity in human subjects.

BACKGROUND: Although the hemodynamic changes associated with atrial fibrillation (AF) have been extensively studied, the neural changes remain unclear. We hypothesized that AF is associated with an increase in sympathetic nerve activity (SNA) and that the irregular ventricular response contributes to this state of sympathoexcitation. METHODS AND RESULTS: In 8 patients referred for an electrophysiological study, SNA, blood pressure (BP), central venous pressure (CVP), and heart rate were recorded during 3 minutes of normal sinus rhythm (NSR) and 3 minutes of induced AF. In 5 of 8 patients who converted to NSR, right atrial (RA) pacing was performed for 3 minutes in atrial pacing triggered by ventricular sensing mode triggered by playback of an FM tape previously recorded from the right ventricle during AF (RA-irregular) and atrial pacing inhibited by atrial sensing mode at a rate equal to the mean heart rate obtained during AF (RA-regular). SNA data were expressed as percentage of baseline during NSR. SNA increased in all 8 patients during induced AF compared with NSR (171+/-40% versus 100%, respectively; P<0.01). This was associated with a trend for a decrease in BP and an increase in CVP (P=0.02). Similarly, SNA was significantly higher during RA-irregular pacing compared with RA-regular pacing (124+/-24% versus 91+/-20%, respectively; P=0.03). BP and CVP were not significantly different between the 2 pacing modes. CONCLUSIONS: Induced AF results in a significant increase in SNA, which is in part attributable to the irregular ventricular response. Our findings suggest that restoring NSR or regularity might be beneficial, particularly in patients with heart failure.

Relation of echocardiographic wall motion score index and response to dobutamine stress to defibrillation threshold at the time of implantation of a cardiac defibrillator.

Predictors of defibrillation threshold (DFT) at implantation remain poorly defined. It was hypothesized that a greater wall motion score index (WMSI) at rest on echocardiography and an ischemic or biphasic response on dobutamine stress echocardiography (DSE) would predict a greater DFT. Consecutive patients who underwent implantable cardiac-defibrillator implantation underwent echocardiography and DSE. DFT at implantation was assessed using the step-down method. Thirteen men aged 68 +/- 10 years with left ventricular ejection fractions of 28 +/- 10% participated in the study. DFTs ranged from 5 to 25 J (mean 14 +/- 8). A WMSI at rest of > or = 2.5 had a 71% positive predictive value and an 83% negative predictive value for a DFT > or = 15 J. An ischemic or biphasic response during DSE did not predict a greater DFT at implantation.

Effects of resynchronization therapy on sympathetic activity in patients with depressed ejection fraction and intraventricular conduction delay due to ischemic or idiopathic dilated cardiomyopathy.

This study assesses the effect of biventricular pacing on sympathetic nerve activity (SNA) in patients with depressed ejection fraction and intraventricular conduction delay (IVCD). Biventricular pacing has been shown to result in hemodynamic improvement in patients with depressed ejection fraction and IVCD. The effect of biventricular pacing on SNA, however, remains unclear. A total of 15 men with a mean ejection fraction of 25 +/- 4% were enrolled. Arterial pressure, central venous pressure and SNA were recorded during 3 minutes of right atrial (RA) pacing and RA-biventricular pacing. Pacing was performed at a rate 5 to 10 beats faster than sinus rhythm, with an atrioventricular interval equal to 100 ms during RA-biventricular pacing. RA-biventricular pacing resulted in greater arterial pressures (p <0.05) than RA pacing (146 +/- 15/83 +/- 11 vs 141 +/- 15/80 +/- 10 mm Hg). There were no differences in central venous pressures between the 2 pacing modes (p = 0.76). SNA was significantly less during RA-biventricular pacing (727 +/- 242 U) than during RA pacing (833 +/- 332 U) (p <0.02). Furthermore, there was a positive correlation between baseline QRS duration and the decrease in SNA noted with RA-biventricular pacing (r = 0.58, p = 0.03). Biventricular pacing results in improved hemodynamics and a decrease in SNA compared with intrinsic conduction in patients with left ventricular dysfunction and IVCD. If the current findings are also present with chronic biventricular pacing, then this form of therapy may have a positive impact on mortality.