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Background: The major risk of implanting a leadless pacemaker at the right ventricular (RV) apex is cardiac perforation., Objective: The purpose of this study was to describe and prospectively evaluate the safety and feasibility of a technique for midseptal implantation of the Micra leadless pacemaker., Methods: We positioned the device at the center of the cardiac silhouette in the right anterior oblique (RAO) view, toward the left in the left anterior oblique (LAO) view, and away from the sternum in the left lateral view., Results: Among the 51 patients (mean age 81.3 ± 9.3 years; 47% men) included in the study, 29 (57%) were >80 years old, 7 (14%) had body mass index <20 kg/m 2 , 48 (94%) had renal dysfunction, and 33 (65%) had valvular heart disease. The implantation sites were mid and apical septum in 46 (90%) and 5 (10%) patients, respectively. Although RAO and LAO views suggested a septal location, 9 (17.6%) devices were found to be directing at the free wall in the left lateral view and required repositioning. One patient (2%) developed cardiac perforation due to contrast injection against the RV anterior wall before verification of sheath location by lateral view. Mean R-wave sensing and pacing threshold at implantation were 9.7 ± 4.0 mV and 0.61 ± 0.31 V/0.24 ms, respectively. After median follow-up of 218.7 days, the pacing threshold remained stable., Conclusion: In this high-risk patient cohort, midseptal implantation of a leadless pacemaker as guided by RAO, LAO, and left lateral views was achieved in 90% of patients, with a low risk of complications., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Atrial-based pacing is associated with lower risk of atrial fibrillation (AF) in sick sinus syndrome compared with ventricular pacing; nevertheless, the impact of site and rate of atrial pacing on progression of AF remains unclear. We evaluated whether long-term atrial pacing at the right atrial (RA) appendage versus the low RA septum with (ON) or without (OFF) a continuous atrial overdrive pacing algorithm can prevent the development of persistent AF., Methods and Results: We randomized 385 patients with paroxysmal AF and sick sinus syndrome in whom a pacemaker was indicated to pacing at RA appendage ON (n=98), RA appendage OFF (n=99), RA septum ON (n=92), or RA septum OFF (n=96). The primary outcome was the occurrence of persistent AF (AF documented at least 7 days apart or need for cardioversion). Demographic data were homogeneous across both pacing site (RA appendage/RA septum) and atrial overdrive pacing (ON/OFF). After a mean follow-up of 3.1 years, persistent AF occurred in 99 patients (25.8%; annual rate of persistent AF, 8.3%). Alternative site pacing at the RA septum versus conventional RA appendage (hazard ratio=1.18; 95% confidence interval, 0.79-1.75; P=0.65) or continuous atrial overdrive pacing ON versus OFF (hazard ratio=1.17; 95% confidence interval, 0.79-1.74; P=0.69) did not prevent the development of persistent AF., Conclusions: In patients with paroxysmal AF and sick sinus syndrome requiring pacemaker implantation, an alternative atrial pacing site at the RA septum or continuous atrial overdrive pacing did not prevent the development of persistent AF., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00419640.

Introduction: Atrial fibrillation (AF) is suggested to be less common among black and Asian individuals, which could reflect bias in symptom reporting and access to care. In the Asymptomatic AF and Stroke Evaluation in Pacemaker Patients and the AF Reduction Atrial Pacing Trial (ASSERT), patients with hypertension but no history of AF had AF recorded via an implanted pacemaker or defibrillator, thus allowing both symptomatic and asymptomatic AF incidence to be determined without ascertainment bias., Methods and Results: The ASSERT enrolled 2,580 patients in 23 countries in North America, Europe, and Asia. AF was defined as device-recorded AF episodes >190/min, lasting either for >6 minutes or >6 hours in duration. All ethnic groups with >50 patients were enrolled. Ethnic groups studied include Europeans (n = 1900), black Africans (n = 73), Chinese (n = 89), and Japanese (n = 105) patients. Compared to Europeans, black Africans had more risk factors for AF such as heart failure (27.8 vs 14.6%) and diabetes (41.7 vs 26.3%). At 2.5 years follow-up, all 3 non-European races had a lower incidence of AF (8.3%, 10.1%, and 9.5% vs 18.0%, respectively, for AF>6 minutes, P < 0.006). When adjusted for baseline difference, Chinese had a lower incidence of AF > 6 minutes (P < 0.007), and Japanese and black Africans had a lower incidence of AF > 6 hours (P < 0.04 and P = 0.057, respectively)., Conclusions: Black Africans, Chinese, and Japanese had lower incidence of AF compared to Europeans. In the case of black Africans, this is despite an increased prevalence of AF risk factors., (© 2013 Wiley Periodicals, Inc.)

Aims: To study the effects of right low atrial septum (AS) and right atrial appendage (RAA) pacing on atrial mechanical function and dyssynchrony in patients with sinus node disease (SND) and paroxysmal atrial fibrillation (AF)., Methods and Results: Detailed echocardiographic examination was performed on 30 patients with SND and paroxysmal AF and a dual-chamber, dual sensing, dual response pacemaker with atrial lead implantation at AS(n= 15) or RAA(n= 15). Peak atrial velocities were recorded by pulsed tissue Doppler spectrum. The timing of atrial contractions (Ta) was measured at the middle of the left atrial (LA) and right atrial (RA) free wall. Intra-[standard deviation (SD) of time of Ta (Ta-SD)] and inter-atrial delay(Ta-RL) was measured as the SD of time interval among LA six segments and time difference between the LA and RA wall, respectively. The baseline clinical statuses were similar between groups. Indexes of LA function, and intra- or inter-atrial dyssynchrony were also similar during intrinsic sinus rhythm in both groups (all P> 0.05). During atrial pacing, LA ejection fraction (52 ± 16 vs. 39 ± 14%, P= 0.029) and LA active emptying fraction (34 ± 7 vs. 23 ± 15%, P= 0.012) were higher in patients with AS than RAA pacing. Atrial velocity was also higher at the RA free wall (14.3 ± 3.1 vs. 10.3 ± 4.4 cm/s, P= 0.009), LA septal (7.5 ± 2.1 vs. 5.2 ± 1.7 cm/s, P= 0.004) and lateral wall (8.6 ± 2.4 vs. 6.3 ± 3.0 cm/s, P= 0.024) during AS compared with RAA pacing. There was no difference in Ts-SD during atrial pacing, nevertheless Ta-RL was significantly prolonged in patients with RAA compared with those with AS pacing (42 ± 36 vs. 27 ± 25 ms, P= 0.011)., Conclusion: In patients with SND and paroxysmal AF, right low AS pacing significantly improved global and regional atrial mechanical function and synchronized inter-atrial electromechanical contraction compared with RAA pacing.

Background: Automatic pacing capture verification algorithms that are based on detection of local evoked response signals are susceptible to interference from myopotential noise. This is especially true in the atrium where the lower signal amplitude and signal-to-noise ratio make pacing capture verification more challenging. The aim of this study is to evaluate the impact of myopotential noise induced by various maneuvers on the atrial evoked response (AER) signal., Methods: Data were collected from 18 patients (7 M/11 F, 77.6 ± 8.8 years), implanted with a dual chamber rate response (DDDR) pacemaker and acute and chronic right atrial leads and right ventricular leads, at three regular follow-up visits scheduled at 1, 3, and 6 months after pacemaker implantation or replacement procedures. During each study visit, manual atrial pacing threshold tests during unipolar pacing in the DDD mode were conducted with two evoked response sensing configurations (RA(Ring) → Ind and RA(Ring) → V(Tip) ) while patients performed six different maneuvers. Noise estimates were calculated for each maneuver., Results: The greatest noise estimates in both sensing configurations were measured during the hand-pressing exercise (0.649 ± 0.342 mV in the RA(Ring) → Ind vector, 0.309 ± 0.223 mV in the RA(Ring) → V(Tip) vector). No significant differences in overall noise estimates were observed between the follow-up visits. Of the beats that exhibited noise estimates greater than a sensing floor of 0.3 mV, up to 22% of cardiac beats had a signal-to-noise ratio less than 2 in the RA(Ring) → Ind configuration., Conclusions: Results indicate that myopotential noise generated by performing maneuvers has a demonstrable impact on AER sensing. Therefore, noise mitigation processes are necessary in atrial automatic pacing capture verification algorithms based on evoked response signals to identify and appropriately manage noise., (©2010, The Authors. Journal compilation ©2010 Wiley Periodicals, Inc.)

Background: Right ventricular apical (RVA) pacing can induce left ventricular (LV) dyssynchrony and dysfunction. In this article, we describe the prevalence, clinical characteristics, and outcome in a subset of patients with unrecognized LV apical akinetic aneurysmatic area associated with permanent RVA pacing as potential causes of heart failure (HF) and/or ventricular tachyarrhythmias (VT)., Methods and Results: We retrospectively studied 220 patients with permanent RVA pacing and no pre-existing structural heart disease in our follow-up clinic for high-degree atrioventricular block. Patients who presented with new-onset HF, chest pain, or VT following RVA pacing were evaluated by echocardiogram and cardiac catheterization. RVA pacing-induced LV apical akinetic aneurysmatic area was diagnosed in the absence of significant coronary artery disease by left ventriculogram. After a mean 8.8 ± 6.3 years, eight patients (3.6%) had LV apical akinetic aneurysmatic area. Of those with LV apical akinetic aneurysmatic area, four patients presented with or died of VT. There was no evidence of LV apical akinetic aneurysmatic area on echocardiogram or left ventriculogram in the remaining 212 patients. The four patients with LV apical akinetic aneurysmatic area and HF underwent cardiac resynchronization therapy: in all cases LV ejection fraction improved (from 33 ± 6 to 47 ± 10%, P = 0.03), and LV apical akinetic aneurysmatic area resolved in two., Conclusion: Permanent RVA pacing for high-degree atrioventricular block is associated with LV apical akinetic aneurysmatic area. This condition was associated with a high incidence of VT and cardiovascular complication, but was possibly reversible with cardiac resynchronization therapy.

Background: The deleterious effects of right ventricular apical (RVA) pacing may offset the potential benefit of ventricular rate (VR) regularization and rate adaptation during an exercise in patient's atrial fibrillation (AF)., Methods: We studied 30 patients with permanent AF and symptomatic bradycardia who receive pacemaker implantation with RVA (n = 15) or right ventricular septal (RVS, n = 15) pacing. All the patients underwent an acute cardiopulmonary exercise testing using VVI-mode (VVI-OFF) and VVI-mode with VR regularization (VRR) algorithm on (VVI-ON)., Results: There were no significant differences in the baseline characteristics between the two groups, except pacing QRS duration was significantly shorter during RVS pacing than RVA pacing (138.9 +/- 5 vs 158.4 +/- 6.1 ms, P = 0.035). Overall, VVI-ON mode increased the peak exercise VR, exercise time, metabolic equivalents (METs), and peak oxygen consumption (VO(2)max), and decreased the VR variability compared with VVI-OFF mode during exercise (P < 0.05), suggesting that VRR pacing improved exercise capacity during exercise. However, further analysis on the impact of VRR pacing with different pacing sites revealed that only patients with RVS pacing but not patients with RVA pacing had significant increased exercise time, METs, and VO(2)max during VVI-ON compared with VVI-OFF, despite similar changes in peaked exercise VR and VR variability., Conclusion: In patients with permanent AF, VRR pacing at RVS, but not at RVA, improved exercise capacity during exercise.

The Septal Pacing for Atrial Fibrillation Suppression Evaluation (SAFE) study is a single-blinded, parallel randomized designed multicenter study in pacemaker indicated patients with paroxysmal atrial fibrillation (AF). The objective is to evaluate whether the site of atrial pacing--conventional right atrial appendage versus low atrial septal--with or without atrial overdrive pacing will influence the development of persistent AF. The study will provide a definitive answer to whether a different atrial pacing site or the use of AF suppression pacing or both can give incremental antiarrhythmic benefit when one is implanting a device for a patient with a history of paroxysmal AF.

Background: Right ventricular (RV) apical pacing results in abnormal left ventricular (LV) electrical and mechanical activation and is associated with an increased risk of developing heart failure. Chronic RV septal pacing has been shown to be superior to RV apical pacing in newly implanted patients. However, whether RV septal pacing can reverse deleterious effects of RV apical pacing remain unclear., Methods: We evaluated the effects of RV septal pacing on LV performance and functional capacity before and at 18 months after device replacement in 12 patients with previously permanent RV apical pacing and in 12 control patients that continued RV apical pacing. All patients underwent radionuclide ventriculography and 6-minute hallwalk (6-MHW) test before replacement (baseline) and at 18 months afterward to determine changes in LV performance and functional capacity, respectively., Results: After RV septal upgraded, there was a significant decrease in paced QRS duration (171.2 +/- 3.9 ms to 160.4 +/- 3.5 ms, P = 0.0016), increase in LV ejection fraction (55.2 +/- 2.6% vs 60.4 +/- 2.9%, P = 0.0002), the peak ventricular filling rate (2.60 +/- 0.13 s(-1) vs 3.01 +/- 0.14 s(-1), P = 0.046), and 6-MHW (308.2 +/- 31.6 m vs 355.5 +/- 34.2 m, P = 0.015) at 18 months compared with baseline. No changes in these parameters were observed in the control group (P > 0.05)., Conclusion: RV septal pacing upgraded improves LV systolic and diastolic function and functional capacity in patients with previously permanent RV apical pacing. These findings suggest that RV septal pacing can reverse the deleterious effects of RV apical pacing in patients who required permanent ventricular pacing.

Background: Left ventricular stimulation for cardiac resynchronization therapy is largely limited by access and anatomy of coronary veins., Objective: This study sought to apply ultrasound-mediated leadless pacing technology in heart failure patients and to evaluate the effects of respiration and body posture on the acoustic window., Methods: Patients with advanced heart failure and ejection fraction

Background: Recent studies have demonstrated that cardiac resynchronization therapy (CRT) reduces sleep apnea in heart failure (HF); however, the mechanism of benefit remains unclear., Methods: Overnight polysomnography (PSG) was performed in consecutive HF patients who were scheduled for CRT implant. Patients with sleep apnea defined by an apnea-hypopnea index (AHI) of >10/hour were recruited and underwent echocardiogram examination at baseline and 3 months after CRT., Results: Among 37 HF patients screened, 20 patients (54%) had sleep apnea and 15 of them consented for the study. After 3 months of CRT, there was a significant improvement in New York Heart Association functional class (3.1+/-0.1 vs 2.1+/-0.1, P<0.01), quality-of-life (QoL) score (62.9+/-3.3 vs 56.1+/-4.5, P=0.02), left ventricular ejection fraction (LVEF, 28.8+/-2.5% vs 38.1+/-2.3%, P<0.01), and reduction in pulmonary artery systolic pressure (PASP, 41.0+/-2.7 vs 28.6+/-2.2 mmHg; P<0.01) compared with baseline. Repeated PSG after CRT demonstrated a reduction in the duration of arterial oxygen desaturation

Emerging data from experimental and clinical studies have shown that right ventricular (RV) apical pacing led to abnormalities of ventricular activation and contraction, and impairment of myocardial perfusion with adverse left ventricular (LV) remodeling, which was associated with increased risk of cardiac morbidity and mortality. As a result, there is a growing interest in searching for methods to minimize unnecessary RV pacing and preserving normal ventricular activation with alternative ventricular pacing sites. The risk of developing heart failure (HF) after RV apical pacing depends on the interactions between patient-specific factors (baseline atrial rhythm, intrinsic atrioventricular and ventricular conduction, LV ejection fraction, and the presence of HF and myocardial infarction) and pacing-related factors (mode of pacing, site of ventricular pacing, paced QRS duration, and percentage and duration of pacing). In patients with intact atrioventricular conduction, atrial-based pacing should be used to avoid unnecessary ventricular pacing. In patients requiring ventricular pacing, the potential benefits of alternate ventricular pacing sites, such as RV or LV septa, or even biventricular pacing in different patient populations remain unclear and warrant further long-term prospective clinical trial evaluations especially in those patients who are at a higher risk of developing HF after RV apical pacing.

Background: Current strategies of engineering bioartificial pacemakers from otherwise silent yet excitable adult atrial and ventricular cardiomyocytes primarily rely on either maximizing the hyperpolarization-activated I(f) or on minimizing its presumptive opponent, the inwardly rectifying potassium current I(K1)., Objective: The purpose of this study was to determine quantitatively the relative current densities of I(f) and I(K1) necessary to induce automaticity in adult atrial cardiomyocytes., Methods: Automaticity of adult guinea pig atrial cardiomyocytes was induced by adenovirus (Ad)-mediated overexpression of the gating-engineered HCN1 construct HCN1-DeltaDeltaDelta with the S3-S4 linker residues EVY235-7 deleted to favor channel opening., Results: Whereas control atrial cardiomyocytes remained electrically quiescent and had no I(f), 18% of Ad-CMV-GFP-IRES-HCN1-DeltaDeltaDelta (Ad-CGI-HCN1-DeltaDeltaDelta)-transduced cells demonstrated automaticity (240 +/- 14 bpm) with gradual phase 4 depolarization (143 +/- 28 mV/s), a depolarized maximal diastolic potential (-45.3 +/- 2.2 mV), and substantial I(f) at -140 mV (I(f,-140 mV) = -9.32 +/- 1.84 pA/pF). In the remaining quiescent Ad-CGI-HCN1-DeltaDeltaDelta-transduced atrial cardiomyocytes, two distinct immediate phenotypes were observed: (1) 13% had a hyperpolarized resting membrane potential (-56.7 +/- 1.3 mV) with I(f,-140 mV) of -4.85 +/- 0.97 pA/pF; and (2) the remaining 69% displayed a depolarized resting membrane potential (-27.6 +/- 1.3 mV) with I(f,-140 mV) of -23.0 +/- 3.71 pA/pF. Upon electrical stimulation, both quiescent groups elicited a single action potential with incomplete phase 4 depolarization that was never seen in controls. Further electrophysiologic analysis indicates that an intricate balance of I(K1) and I(f) is necessary for induction of atrial automaticity., Conclusion: Optimized pacing induction and modulation can be better achieved by engineering the I(f)/I(K1) ratio rather than the individual currents.

Introduction: Emerging data have suggested that right ventricular (RV) apical pacing results in progressive left ventricular (LV) dysfunction and contributes to the development of heart failure (HF). This study aimed to investigate the prevalence and clinical predictors for the development of new-onset HF after long-term RV apical pacing in patients with acquired atrioventricular (AV) block who require permanent pacing., Methods: We studied the clinical outcomes after long-term RV apical pacing for acquired AV block in 304 patients without a prior history of HF. All patients had >90% ventricular pacing as determined by device diagnostic data., Results: After a median follow-up of 7.8 years, 79 patients (26.0%) developed new-onset HF after RV apical pacing. Univariate Cox-regression analysis revealed that older age at the time of pacemaker implantation (P < 0.001), the presence of coronary artery disease (CAD) (P < 0.001) or atrial fibrillation (P = 0.03), VVI pacemaker (P < 0.001), wider paced QRS duration (P < 0.001), and new-onset myocardial infarction (P < 0.001) were predictors for HF. Multivariate analysis revealed that older age at implantation (Hazard ratio [HR] 1.06, 95% confidential interval [CI] 1.04-1.09, P < 0.001), CAD (HR 1.98, 95% CI 1.12-3.50, P < 0.05), and a wider paced QRS duration (HR 1.27 for each 10 ms increment, 95% CI 1.11-1.45, P = 0.001) were independent predictors of HF. Furthermore, cardiovascular mortality was significantly increased in those with HF (36.7% vs. 2.7%, P < 0.001)., Conclusions: After a median follow-up of 7.8 years, permanent RV apical pacing was associated with HF in 26% of patients. Elderly age at the time of implant, a wider paced QRS duration and the presence of CAD independently predicted new-onset HF. More importantly, HF after RV apical pacing was associated with a higher cardiovascular mortality.

Aims: Paroxysmal atrial fibrillation (PAF) is frequently encountered in pacemaker patients, most commonly in sick sinus syndrome. The combination of site-specific pacing in conjunction with an overdrive algorithm combined with antiarrhythmic drugs on the incidence of PAF in patients with a conventional indication for pacing is unknown., Methods and Results: Patients with pacemaker indication and PAF received a DDDR-pacemaker, which included an automatic atrial overdrive (AO) algorithm. The atrial lead was implanted in either the right atrial appendage (RAA) (n = 83) or the right low-atrial septum (LAS) (n = 94). The algorithm was switched on or off in a 3 month, single blind crossover design and antiarrhythmic drugs were kept stable. A control group of 96 patients (LAS, n = 14; RAA, n = 84) without PAF served as controls to assess any proarrhythmic effect of overdrive pacing. Atrial fibrillation (AF) burden defined as cumulative time in mode switch was not reduced during automatic AO from either the RAA or from the LAS. The reduction was not effective both for AF of short (<24 h) and long (> or =24 h) duration. There was no atrial proarrhythmia induced by the overdrive algorithm in the control group., Conclusions: We could not demonstrate a reduction of AF burden defined as cumulative time in AF by the AO algorithm, in patients who are paced for standard indications and PAF, neither from the RAA nor from the LAS.

Objectives: The purpose of this study was to evaluate the feasibility and safety of a novel technology that uses energy transfer from an ultrasound transmitter to achieve cardiac stimulation without the use of a pacing lead in humans., Background: To overcome the limitations of pacemaker leads, a new technology enabling stimulation without the use of a lead is desirable., Methods: A steerable bipolar electrophysiology catheter incorporating a receiver electrode into the tip and circuitry to convert ultrasound energy to electrical energy was inserted transvenously into the heart. An ultrasound transmitting transducer was placed on the chest wall with ultrasound gel. Ultrasound energy was amplitude-adjusted and transmitted at 313 to 385 kHz. The output waveform of the receiver electrode was monitored while the transmitter was moved on the chest wall to target the receiver. The ultrasound transmission amplitude was limited to a mechanical index of 1.9, the maximum allowed for ultrasound imaging systems. Ultrasound-mediated pacing with minimum voltage but consistent capture was obtained for 12 s., Results: Twenty-four patients (48 +/- 12 years) were tested during or after completion of clinical electrophysiology procedures. A total of 80 pacing sites were tested (mean 3.3 sites/patient): 12 right atrial, 35 right ventricular, and 33 left ventricular (31 endocardial) sites. The transmit-to-receive distance was 11.3 +/- 3.2 cm (range 5.3 to 22.5 cm). Ultrasound-mediated pacing was achieved at all 80 test sites, with consistent capture at 77 sites. The mechanical index during pacing was 0.5 +/- 0.3 (range 0.1 to 1.5). The mean ultrasound-mediated capture threshold was 1.01 +/- 0.64 V. There was no adverse event related to ultrasound pacing. No patient experienced discomfort during pacing., Conclusions: The feasibility and safety of pacing usng ultrasound energy has been shown acutely.

Background: Cardiac resynchronization therapy (CRT) applied by pacing the left and right ventricles (BiV) has been shown to provide synchronous left ventricular (LV) contraction in heart failure patients. CRT may also be accomplished through synchronization of a properly timed LV pacing impulse with intrinsically conducted activation wave fronts. Elimination of right ventricular (RV) pacing may provide a more physiological RV contraction pattern and reduce device current drain. We evaluated the effects of LV and BiV pacing over a range of atrioventricular intervals on the performance of both ventricles., Methods: Acute LV and RV hemodynamic data from 17 patients with heart failure (EF = 30 +/- 1%) and a wide QRS (138 +/- 25 msec) or mechanical dyssynchrony were acquired during intrinsic rhythm, BiV, and LV pacing., Results: The highest LV dP/dt(max) was achieved during LV pre- (LV paced prior to an RV sense) and BiV pacing, followed by that obtained during LV post-pacing (LV paced after an RV sense) and the lowest LV dP/dt(max) was recorded during intrinsic rhythm. Compared with BiV pacing, LV pre-pacing significantly improved RV dP/dt(max) (378 +/- 136 mmHg/second vs 397 +/- 136 mmHg/second, P < 0.05) and preserved RV cycle efficiency (61.6 +/- 14.6% vs 68.6 +/- 11.4%, P < 0.05) and stroke volume (6.6 +/- 4.4 mL vs 9.0 +/- 6.3 mL, P < 0.05). Based on LV dP/dt(max), the optimal atrioventricular interval could be estimated by subtracting 30 msec from the intrinsic atrial to sensed RV interval., Conclusions: Synchronized LV pacing produces acute LV and systemic hemodynamic benefits similar to BiV pacing. LV pacing at an appropriate atrioventricular interval prior to the RV sensed impulse provides superior RV hemodynamics compared with BiV pacing.

Background: Elderly pacemaker patients with chronotropic incompetence (CI) may experience orthostatic hypotension (OH) upon standing. The objective of this study was to determine whether a transient increase in heart rate (HR) by overdrive pacing upon standing prevents OH in elderly pacemaker patients., Methods: We studied the effect of transient overdrive pacing upon standing in mitigating the drop in blood pressure (BP) in 62 pacemaker patients (77 +/- 6 years, 32 F) implanted with DDD pacemaker for sick sinus syndrome (n = 40) or atrioventricular block (n = 22). All patients underwent two standing procedures in random order: a control, with backup (60 bpm) pacing and another with overdrive DDD pacing (at 35 bpm above their baseline rate) for 2 minutes upon standing. Systolic (SBP) and diastolic blood pressure (DBP) and HR were measured while supine (baseline) and 1, 2, and 3 minutes after standing. OH was defined as a drop in SBP > or = 20 mmHg or DBP > or = 10 mmHg during standing. Chronotropic incompetence (CI) was defined as an absence of HR increase of > or = 10 bpm during standing., Results: A total of 17 (27%) patients developed OH upon standing during backup pacing. Baseline clinical characteristics (age, sex, prevalence of diabetes, use of vasoactive medications, and sick sinus syndrome) were similar between patients with or without OH. In patients with or without OH, transient overdrive pacing upon standing increased HR and DBP as compared with baseline (P < 0.05). However, in patients with OH, transient overdrive pacing did not prevent decrease in SBP upon standing and avoided the development of OH in only 10/17 patients (59%). Among those patients with OH, 10/17 (59%) patients had CI. In OH patients with CI, transient overdrive pacing upon standing maintained SBP and DBP as compared to baseline and prevented OH in the majority of patients (80%). By contrast, transient overdrive pacing in OH patients without CI had no significant effect on the decrease in SBP upon standing and prevented OH in only 20% of patients., Conclusions: OH is common (27%) in the elderly pacemaker population. In a subgroup of these patients, CI may be responsible for the occurrence of OH, and OH can be prevented by transient overdrive pacing upon standing.

Objectives: We investigated the accuracy and feasibility of a 2D echo-independent ultrasonic continuous wave Doppler cardiac output monitoring device (USCOM) operated by trained nurse for the atrio-ventricular interval (AVI) optimization in cardiac resynchronization therapy (CRT)., Background: CRT is of proven benefit in patients with advanced chronic heart failure and ventricular conduction delay. Appropriate AVI selection is critical to optimize hemodynamic in CRT. Currently, most non-invasive methods for AVI optimization are often complicated and labor-intensive., Methods: USCOM method, Ritter method, and aortic outflow cardiac output method were used to determine the optima AVI in 20 patients with CRT. The accuracy and time for measurement of each method were determined., Results: The optimal AVI determined by USCOM method had good correlation with Ritter's method and aortic outflow estimated cardiac output method (r2= 0.78, P < 0.01 and r2= 0.73, P < 0.01, respectively). The optimal AVI determined USCOM method showed good agreement (within 10 msec range) with Ritter's method (85% patients) and aortic outflow estimated cardiac output method (80%). The mean time for determining AVI using USCOM method was shorter than that with aortic outflow method (7.1 +/- 0.7 min vs 12.7 +/- 1.1 min, P < 0.01), whereas the mean time was shortest for Ritter method (4.7 +/- 1.6 min vs 7.1 +/- 0.7 min, P < 0.01)., Conclusion: USCOM device operated by trained nurse can provide a simple, accurate, and fast non-invasive method for the AVI optimization in CRT population.

An international questionnaire survey was carried out in Asia Pacific, Europe, Latin America and North America to assess the impact of reimbursement on the indications, types of device prescription and waiting time for pacemakers, implantable cardioverter defibrillators (ICD) and radiofrequency ablation therapy for cardiac arrhythmias. The indications for cardiac pacing can be restricted to more symptomatic patients when funding is limited, and new therapy such as cardiac resynchronization therapy (CRT) is restricted in many regions. ICD usage may be limited to secondary prevention candidates because of reimbursement, but referral doctor's ambivalence and knowledge are also important issues independent of the types of health care system. Radiofrequency ablation is generally well accepted, but reimbursement is heterogeneous, with non-fluoroscopic mapping being reimbursed only in a limited way worldwide. Thus with the exception of a well-developed health care system, reimbursement has a major impact on the delivery of arrhythmia management devices and procedures worldwide.

Objectives: The purpose of this research was to investigate the effect of using rate-adaptive pacing and atrioventricular interval (AVI) adaptation on exercise performance during cardiac resynchronization therapy (CRT)., Background: The potential incremental benefits of using rate-adaptive pacing and AVI adaptation with CRT during exercise have not been studied., Methods: We studied 20 patients with heart failure, chronotropic incompetence (<85% age-predicted heart rate [AP-HR] and <80% HR reserve), and implanted with CRT. All patients underwent a cardiopulmonary exercise treadmill test using DDD mode with fixed AVI (DDD-OFF), DDD mode with adaptive AVI on (DDD-ON), and DDDR mode with adaptive AVI on (DDDR-ON) to measure metabolic equivalents (METs) and peak oxygen consumption (VO2max)., Results: During DDD-OFF mode, not all patients reached 85% AP-HR during exercise, and 55% of patients had <70% AP-HR. Compared to patients with >70% AP-HR, patients with <70% AP-HR had significantly lower baseline HR (66 +/- 3 beats/min vs. 80 +/- 5 beats/min, p = 0.015) and percentage HR reserve (27 +/- 5% vs. 48 +/- 6%, p = 0.006). In patients with <70% AP-HR, DDDR-ON mode increased peak exercise HR, exercise time, METs, and VO2max compared with DDD-OFF and DDD-ON modes (p < 0.05), without a significant difference between DDD-OFF and DDD-ON modes. In contrast, there were no significant differences in peak exercise HR, exercise time, METs, and VO2max among the three pacing modes in patients with >70% AP-HR. The percentage HR changes during exercise positively correlated with exercise time (r = 0.67, p < 0.001), METs (r = 0.56, p < 0.001), and VO2max (r = 0.55, p < 0.001)., Conclusions: In heart failure patients with severe chronotropic incompetence as defined by failure to achieve >70% AP-HR, appropriate use of rate-adaptive pacing with CRT provides incremental benefit on exercise capacity during exercise.

Unlabelled: Cardiac resynchronization therapy., Background: A significant proportion of patients with dilated cardiomyopathy and left bundle branch block (LBBB) do not respond to cardiac resynchronization therapy (CRT). The purpose of this study was to investigate whether the electromechanical properties of the myocardium would predict acute hemodynamic improvement during left ventricular (LV) pacing., Methods and Results: We studied 10 patients with idiopathic dilated cardiomyopathy and LBBB (ejection fraction (EF): 27%+/-7%; QRS duration: 166+/-16 msec) using three-dimensional electromechanical endocardial mapping technique to assess endocardial activation time (Endo-AT), unipolar voltage, and local linear shortening during sinus rhythm. LV stimulation was performed in VDD mode at five different sites and three atrioventricular delays within the coronary sinus. LV+dP/dtmax changes from baseline were measured during LV stimulation at each site (%DeltadP/dtmax). There was no significant relationship between maximum %DeltadP/dtmax during LV stimulation at the best coronary sinus site and LV EF, baseline LV+dP/dtmax, total LV Endo-AT, baseline QRS duration nor changes in QRS duration during LV pacing. However, the maximum %DeltadP/dtmax was significantly positively correlated with percentage area of late Endo-AT (r=0.97, P<0.001) and preserved LV myocardium (r=0.81, P=0.005), respectively. Patients with >20% of LV area with late Endo-AT and >30% of preserved LV myocardium had five times better acute hemodynamic response with LV stimulation. Multivariate analysis showed that only percentage area of late Endo-AT was independently correlated with %DeltadP/dtmax (P<0.05)., Conclusion: The presence of a larger amount of LV area with late Endo-AT and preserved LV myocardium measured by electromechanical mapping could identify patients who have better acute improvement in systolic performance during LV stimulation.

This advisory summarizes the current database on pacing modalities and algorithms used to prevent and terminate atrial fibrillation (AF). On the basis of the evidence indicating that ventricular pacing is associated with a higher incidence of AF in patients with sinus node dysfunction, a patient who has a history of AF and needs a pacemaker for bradycardia should receive a physiological pacemaker (dual chamber or atrial) rather than a single-chamber ventricular pacemaker. For patients who need a dual-chamber pacemaker, efforts should be made to program the device to minimize the amount of ventricular pacing when atrioventricular conduction is intact. Many pacemakers and implantable defibrillators have features designed to prevent AF and to terminate AF with rapid atrial pacing. The evidence to support their use is limited, although these algorithms appear to be safe and usually add little additional cost. For patients who have a bradycardia indication for pacing and also have AF, no consistent data from large randomized trials support the use of alternative single-site atrial pacing, multisite right atrial pacing, biatrial pacing, overdrive pacing, or antitachycardia atrial pacing. Even fewer data support the use of atrial pacing in the management of AF in patients without symptomatic bradycardia. At present, permanent pacing to prevent AF is not indicated; however, additional studies are ongoing, which will help to clarify the role of permanent pacing for AF.

The aim of this study was to investigate the effect of the Ventricular Response Pacing (VRP) algorithm, which regularizes ventricular rate during atrial fibrillation (AF), on symptoms, quality of life, and functional capacity. VRP regularizes the ventricular rate during AF without increasing the mean ventricular rate, thereby reducing the severity of AF-related symptoms in patients with persistent AF. However, VRP did not improve general quality of life (Medical Outcomes Study 36-item Short-Form General Health Survey), the performance of routine activities (Duke Activity Status Index), or functional capacity (hall walk) in patients with AF.

Patients with advanced heart failure have a high mortality and morbidity despite medical therapy. Depending on the underlying heart disease and severity of heart failure, 3.7 to 52.8% of patients have a QRS complex > or =120 ms who may have interventricular and intraventricular dyssynchrony correctible by cardiac resynchronization therapy (CRT). The latter is usually achieved with biventricular pacing, with the left ventricular lead placed in a tributary of the coronary sinus (CS), with a reported success rate between 88-92%. The technical advances for implantation include preformed guide sheaths to cannulate the CS, over the wire leads with passive fixation mechanism, and surgical placement methods. Device-specific CRT features include optimizing heart failure through insurance of a high percentage of pacing, heart failure monitoring, atrioventricular and interventricular timing, and avoiding double ventricular sensing. Furthermore, arrhythmic co-morbidities of heart failure such as atrial fibrillation and ventricular tachyarrhythmias can also be managed. Recent prospective trials suggest that there is a 30% reduction in heart failure hospitalization with CRT, and preliminary results suggest a survival benefit with CRT and implantable cardioverter defibrillator over optimal medical therapy.

Background: The effect of left ventricular (LV) systolic function on the long-term left ventricular pacing and sensing threshold is unclear., Methods and Results: We studied the effect of LV ejection fraction (LVEF) on the LV pacing and sensing threshold in 56 patients (mean age: 70.2 +/- 10.5 years) underwent permanent LV pacing using a self-retaining coronary sinus lead (Model 1055 K, St Jude Medical, USA). In 49 patients, the LV lead was implanted for conventional pacemaker indication (sick sinus syndrome = 14, heart block = 26 or slow atrial fibrillation = 9). The remaining 7 patients were implanted for congestive heart failure. The LV pacing and sensing threshold, and lead impedance were compared between patients with LVEF <40% (Group 1, n = 28) and LVEF >40% (Group 2, n = 28) during implant and at 3-month follow up. The LV pacing lead was successfully implanted in all patients without any lead dislodgement on follow-up. At implant, Group 1 patients had a significant lower R wave amplitude, but similar LV pacing threshold and lead impedance as compared to Group 2. However, at 3-month follow-up, Group 1 patients had a significantly higher LV pacing threshold compared to Group 2 patients. There were no significant differences in the sensing threshold and lead impedance between the two groups. Furthermore, there was also a significant interval increase in LV pacing threshold in Group 1 patients (0.94 +/- 0.12 V) after 3 months, but not in Group 2 patients (0.16 +/- 0.08 V, p < 0.01)., Conclusions: The results of this study suggest that the LV systolic function has a significant impact on the long-term LV pacing threshold. The long-term left ventricular pacing threshold in patients with left ventricular systolic dysfunction increased after implant and was higher than patients with normal left ventricular systolic function.

We studied the Medtronic Thera and Kappa 400 dual chamber pacemakers to determine the causes and mechanism of shortening of the sensed AV delay during normal sinus rhythm. When the sensed AV delay shortens to less than its programmed value, it lengthens gradually and returns to its programmed duration after a number of pacing cycles. This behavior is linked to the relatively slow automatic mode switching algorithm (AMS) and was observed when a transient increase in the sensed atrial rate failed to reach the point where AMS was activated and also upon exit from the AMS mode.

Left ventricular (LV) pacing is increasingly used in the management of congestive heart failure. Optimization of the atrioventricular (AV) interval is essential to maximize the hemodynamic benefits of this therapy. Although Doppler echocardiography (echo) is the most widely used method, it is time-consuming, expensive, and operator-dependent. We examined the value of an impedance cardiography (IC)-based method of cardiac output (CO) measurement to optimize the AV interval in 5 men and 1 woman (mean age = 72 +/- 11 years) during permanent LV pacing with a 4.8 Fr unipolar coronary sinus pacing lead. Simultaneous measurements of CO by IC and echo were performed at AV intervals of 50, 80, 110, 150, 180, and 225 ms during DDD pacing at 85 beats/min. The optimal AV interval varied between 110 and 180 ms. In 5 of 6 patients (83%), the optimal AV interval by echo and IC was identical. While CO measurements were higher with IC than with echo (6.1 +/- 0.4 L/min vs 4.7 +/- 0.3 L/min, P < 0.05), CO measurements by IC and echo were closely correlated r = 0.67, P < 0.001). In conclusion, our initial experience suggests that IC is a reliable method of AV interval optimization during LV pacing. IC and echo measurements of CO during LV pacing were closely correlated.

Objectives: We sought to evaluate the long-term effects of alternative right ventricular pacing sites on myocardial function and perfusion., Background: Previous studies have demonstrated that asynchronous ventricular activation due to right ventricular apical (RVA) pacing alters regional myocardial perfusion and functions., Methods: We randomized 24 patients with complete atrioventricular block to undergo permanent ventricular stimulation either at the RVA (n = 12) or right ventricular outflow (RVOT) (n = 12). All patients underwent dipyridamole thallium myocardial scintigraphy and radionuclide ventriculography at 6 and 18 months after pacemaker implantation., Results: After pacing, the mean QRS duration was significantly longer during RVA pacing than during RVOT pacing (151 +/- 6 vs. 134 +/- 4 ms, p = 0.03). At six months, the incidence of myocardial perfusion defects (50% vs. 25%) and regional wall motion abnormalities (42% vs. 25%) and the left ventricular ejection fraction (LVEF) (55 +/- 3% vs. 55 +/- 1%) were similar during RVA pacing and RVOT pacing (p > 0.05). However, at 18 months, the incidence of myocardial perfusion defects (83% vs. 33%) and regional wall motion abnormalities (75% vs. 33%) were higher and LVEF (47 +/- 3 vs. 56 +/- 1%) was lower during RVA pacing than during RVOT pacing (all p < 0.05). Patients with RVA pacing had a significant increase in the incidence of myocardial perfusion defects (p < 0.05) and a decrease in LVEF (p < 0.01) between 6 and 18 months, but patients with RVOT pacing did not (p > 0.05)., Conclusions: This study demonstrates that preserved synchronous ventricular activation with RVOT pacing prevents the long-term deleterious effects of RVA pacing on myocardial perfusion and function in patients implanted with a permanent pacemaker.

While the hemodynamic and clinical significance of automatic mode switching (AMS) in patients with pacemakers has been demonstrated, the clinical behavior of AMS algorithms differ widely according to the manufacturers and pacemaker models. In general, a "rate-cutoff" detection method of atrial tachyarrhythmias provides a rapid AMS onset and resynchronization to sinus rhythm at the termination of atrial tachyarrhythmias, but may cause intermittent oscillations between the atrial tracking and AMS mode. This can be minimized with a "counter" of total number of high rate events before the AMS occurs. The use of a "running average" algorithm results in more stable rate control during AMS by reducing the incidence of oscillations, but at the expense of delayed AMS onset and resynchronization to sinus rhythm. Algorithms may be combined to fine tune the AMS response and to avoid rapid fluctuation in pacing rate. Appropriate programming of atrial sensitivity, and the avoidance of ventriculoatrial cross-talk are essential for optimal AMS performance.

Automatic mode switching (AMS) is now a programmable function in most contemporary dual chamber pacemakers. Atrial tachyarrhythmias are detected when the sensed atrial rate exceeds a "rate-cutoff," "running average," "sensor-based physiological" rate, or using "complex" detection algorithms. AMS algorithms differ in their atrial tachyarrhythmia detection method, sensitivity, and specificity and, thus, respond differently to atrial tachyarrhythmia in terms of speed to the AMS onset, rate stability of the response, and speed to resynchronize to sinus rhythm. AMS is hemodynamically beneficial, and most patients with atrial tachyarrhythmias are symptomatically better with an AMS algorithm in their pacemakers. New diagnostic capabilities of pacemaker especially stored electrograms not only allow programming of the AMS function, but enable quantification of atrial fibrillation burden that facilitate clinical management of patients with implantable devices who have concomitant atrial tachyarrhythmia.

Atrial pacing has been shown to delay the onset of atrial fibrillation (AF) when compared with ventricular pacing in patients with sick sinus syndrome. The role for pacing in the control of AF in patients without bradycardia is uncertain. We performed a randomized, crossover, single-blinded study in 22 patients (14 women, aged 63 +/- 10 years) with paroxysmal AF refractory to treatment with oral sotalol (202 +/- 68 mg/day) and no bradycardic indication for pacing. All patients received a dual-chamber pacemaker with 2 atrial pacing leads positioned at the high right atrium and coronary sinus ostium, respectively. Patients were randomized in a crossover fashion to be paced for 12 weeks, either with high right atrial (RA) pacing at 30 beats/min ("Off") or dual-site RA pacing with an overdrive algorithm that maintained atrial pacing at a rate slightly above the sinus rate ("On"). Treatment on resulted in a significantly higher percentage of atrial pacing and a reduction in atrial ectopic frequency than the treatment off period. The time to the first clinical AF recurrence was prolonged (15 +/- 17 to 50 +/- 35 days, p = 0.006), and total AF burden was reduced (45 +/- 34% vs 22 +/- 29%, p = 0.04) in the on-treatment phase. However, there was no difference in AF checklist symptom scores or overall quality-of-life measures. Dual-site RA pacing with continued sinus overdrive prolonged the time to AF recurrence and decreased AF burden in patients with paroxysmal AF. The absence of a major impact on symptom control suggests that pacing should be used as an adjunctive therapy with other treatment modalities for AF.

Introduction: Recent studies have demonstrated that premature depolarizations that trigger atrial fibrillation often arise in pulmonary veins. The purpose of this study was to evaluate whether P wave polarity is helpful in distinguishing which of the 4 pulmonary veins is the site of origin of a premature depolarization., Methods and Results: In 28 patients without structural heart disease who underwent focal ablation of paroxysmal atrial fibrillation, P wave polarity on a 12-lead electrocardiogram (ECG) was analyzed during sinus rhythm, and during pacing at a cycle length of 500--600 ms in the high right atrium and within each of the 4 pulmonary veins. P waves were categorized as positive, negative, biphasic or isoelectric. A negative or biphasic P wave in lead I (sensitivity 85 %, specificity 71 %) or a positive P wave in V1 (sensitivity 85 %, specificity 89 %) were helpful in predicting a pulmonary venous site of origin as opposed to a right atrial site of origin. A positive P wave in lead II and III distinguished superior from inferior pulmonary veins (sensitivity 90 %, specificity 84 %). The sensitivity and specificity of negative or biphasic P waves in lead aVL in distinguishing a left from right pulmonary vein site of origin were 94 % and 42 %, respectively., Conclusions: Analysis of P waves polarity may be helpful in localizing the pulmonary vein that is the site of origin of a premature depolarization. Among the 12 ECG leads, I, II, III, aVL, and V1 are the most helpful in regionalizing premature depolarizations arising in the pulmonary veins.

Introduction: The purpose of this study was to evaluate the effects of an acute increase in atrial pressure on refractoriness (mechanoelectrical feedback) and the vulnerability to atrial fibrillation (AF) and to investigate the effects of autonomic blockade and verapamil on mechanoelectrical feedback in humans., Methods and Results: Right atrial pressure and effective refractory period (ERP) at the right atrial appendage (RAA) and high right atrial septum were measured during sinus rhythm, and during atrial and simultaneous AV pacing at a cycle length of 300 msec, either in the absence (n = 25) or presence (n = 22) of pharmacologic autonomic blockade. In another 15 patients, the protocol was performed before and after infusion of verapamil 0.15 mg/kg. In the absence of autonomic blockade, AV pacing resulted in a higher mean right atrial pressure (11.7 +/- 3.3 vs 4.3 +/- 3.0 mmHg, P < 0.001) and a shorter atrial RAA ERP (144 +/- 23 msec vs 161 +/- 21 msec; P < 0.001) compared with atrial pacing; AF was induced more often during AV pacing (87%) than during atrial pacing (20%) and was related directly to the right atrial pressure (r = 0.39, P = 0.004) and indirectly to the RAA ERP (r = -0.42, P < 0.001). The susceptibility to sustained AF was greatly enhanced by autonomic blockade. Verapamil markedly attenuated the shortening of ERP and the propensity for AF that occurred during simultaneous AV pacing., Conclusion: An acute increase in atrial pressure during tachycardia is associated with shortening of atrial refractoriness and a propensity for AF, i.e., atrial mechanoelectrical feedback, which may be enhanced by autonomic blockade and attenuated by calcium channel blockade.

Automatic mode switching (AMS) allows patients with dual chamber pacemakers who develop paroxysmal AF to have a controlled ventricular rate. The aim of this study was to (1) compare the rate-controlled behavior of three AMS algorithms in response to AF, in terms of speed and stability of response and resynchronization to sinus rhythm, and (2) compare the influence of pacemaker programming on optimal mode switching. We studied 17 patients (12 men, 5 women; mean age 59 +/- 15 years) who developed AF during electrophysiological study. Unfiltered bipolar atrial electrograms during sinus rhythm and AF were recorded onto high fidelity tapes and replayed into the atrial port of three dual chamber pacemakers with different mode switching algorithms (Thera, Marathon, Meta). The Thera pacemaker uses rate smoothing, and mode switches occur when mean sensed atrial rate exceeds the predefined AMS rate (MR). Marathon mode switches after a programmable number of consecutive rapid atrial events (NR). Meta DDDR monitors the atrial rate by a counter for atrial cycles faster than the programmed AMS rate. It increases or decreases the counter if the atrial cycle length is shorter or longer than the programmed AMS interval, respectively. Mode switch occurs when the AF detection criteria are met (CR). A total of 260 rhythms were studied. NR was significantly faster than MR and CR (latency 2.5 +/- 3 s vs 26 +/- 7 s vs 15 +/- 22 s, respectively, P < 0.0001). During sustained AF, MR resulted in the most stable and regular ventricular rhythm compared to NR or CR. In CR, ventricular rate oscillated between AMS and atrial tracking (cycle length variations: 44 +/- 2 s vs 346 +/- 109 s vs 672 +/- 84 s, P < 0.05). At resumption of sinus rhythm, MR resynchronized after 143 +/- 22 s versus 3.4 +/- 0.7 s for NR and 5.9 +/- 1.1 s for CR, resulting in long periods of AV dissociation when a VVI/VVIR mode is used after AMS. Programming of atrial refractory periods did not affect AMS response, although the speed of AMS onset can be adjusted by programming of onset criteria in the Meta DDDR. AMS algorithms differ in their ability to handle recorded clinical atrial arrhythmias. The rapid-responding algorithm exhibits rate instability, whereas slow responding algorithm shows a long delay in response and risk of AV dissociation. Thus different instrumentation of AMS may have clinical implications in patients with dual chamber pacemakers who develop AF.

Recent studies have suggested that dual-site right atrial (RA) pacing via the high RA and coronary sinus ostium (CSos) prevents atrial fibrillation (AF). However, the programming of the atrioventricular (AV) interval associated with optimal left atrial (LA) mechanical function during high RA and dual-site RA pacing has not been defined. LA mechanical function was studied by measuring transmitral pulsed Doppler echocardiographic peak A wave velocity and percent A wave filling, in six women and three men, 67 +/- 8 years of age, who had received dual-site RA pacemakers in a randomized study. Serial echocardiographic measurements were performed during high RA or dual-site RA pacing at 80 beats/min with AV intervals of 50, 100, 150, or 200 ms tested in random order. High RA and dual-site RA pacing at an AV interval of 50 ms were associated with significantly lower peak A wave velocity and percent A wave filling, compared to the other AV intervals (all P < 0.05). Compared with high RA pacing, dual-site RA pacing was associated with significantly higher peak A wave velocity (85 +/- 12 vs 72 +/- 17 cm/s, P = 0.04) and percent A wave filling (24 +/- 3 vs 20 +/- 4%, P = 0.02) at an AV interval of 100 ms, but a lower peak A wave velocity at an AV interval of 200 ms (77 +/- 10 vs 84 +/- 8 cm/s, P = 0.004). In conclusion, variations in the AV interval during atrial pacing have significant effects on LA function. As a consequence of altered atrial activation, the AV interval associated with optimal LA mechanical function during dual-site RA pacing was significantly shorter than that during RA pacing. This observation has important implications with respect to the programming of dual-site RA pacemakers implanted to prevent AF for hemodynamic purpose.

This study evaluated the performance of a new lead for permanent left ventricular (LV) pacing via the coronary sinus (CS) in four men and nine women (mean age = 71 +/- 13 years) with sick sinus syndrome. It consists of a 75-cm-long, 4.8-Fr, unipolar ventricular lead with a distal portion preshaped in an S curve to provide steerability and stability within the CS. Its efficacy and stability for permanent LV pacing were tested at implant, predischarge, and at 1, 3 and 6 months of follow-up. The lead was successfully implanted in 11/13 patients (85%) within a mean fluoroscopy time of 35 +/- 22 minutes. The final positions of the electrodes at the tip of the lead within venous tributaries of the CS were: (1) anterior (n = 2, 18%); (2) posterolateral (n = 5, 45%); and (3) the lateral (n = 4, 36%). Unsuccessful implants were due to unstable lead position (n = 1), or high pacing threshold (n = 1). There was no postprocedural lead dislodgment or significant changes in the R wave amplitude, LV pacing threshold and lead impedance up to 6 months of follow-up. In summary, this initial experience suggests that this new lead offers safe and reliable permanent LV pacing via the CS in the majority of patients and may be used in isolation or in conjunction with right ventricular pacing for biventricular synchronization.

Synchronous biventricular pacing is a new nonpharmacological supplemental treatment of advanced heart failure associated with electromechanical conduction delay. However, the role of pacing on left ventricular remodeling is unknown. Eleven patients with New York Heart Association Class III to IV heart failure, a left ventricular ejection fraction < 35%, and a QRS duration > or = 140 ms received a biventricular dual chamber pacemaker. Serial echocardiography, 6-minute hall walk, and Minnesota Living with Heart Failure quality-of-life (QOL) questionnaire were performed before and after up to 3 months of pacing. At 3 months there was a significant increase in fractional shortening (P < 0.001), ejection fraction (P < 0.001), and cardiac output (P < 0.05). The left ventricular end-diastolic volume (245 +/- 70 vs 185 +/- 37 mL, P < 0.05), end-systolic volume (209 +/- 69 vs 140 +/- 44 mL P < 0.05), and mitral regurgitation were reduced (P < 0.05), and diastolic filling time was lengthened (P < 0.05). There were also improvements in heart failure symptoms, an increase in 6-minute walk distance, and a decrease in QOL scores. Synchronous biventricular pacing for 3 months was associated with hemodynamic improvements, reversal of left ventricular remodeling, and increase in left ventricular systolic function, and a decrease in secondary mitral regurgitation.

Peak endocardial acceleration (PEA) measured by an implantable acceleration sensor inside the tip of a pacing lead reflects ventricular filling and myocardial contractility. The contribution of the plateau phase of PEA as an indicator of optimal ventricular filling, hence of the appropriate atrioventricular interval (AVI) at rest and during exercise, was studied in 12 patients (age 69 +/- 6 years) with complete AV block and a PEA sensing DDDR pacemakers (Living 1 Plus, Sorin Biomedica). At a mean resting heart rate of 79 +/- 15 beats/min, the mean AVI optimized by PEA versus Doppler echocardiography (echo) were identical (142 +/- 37 vs 146 +/- 26 ms, P = 0.59). During submaximal exercise at a mean heart rate of 134 +/- 6 beats/min, AVI optimized by PEA was 135 +/- 37 ms. Cardiac output at rest, measured by the CO2 rebreathing method, was comparable with AVI determined by echo versus PEA (4.3 +/- 2.9 and 3.7 +/- 2.4 L/min, respectively), and increased to the same extent (8.0 +/- 3.9 vs 8.3 +/- 5.2 L/min) during submaximal exercise. In patients with AV block, AVI automatically set by PEA was comparable with AVI manually optimized by Doppler echocardiography and was associated with comparable exercise induced hemodynamic changes.

Overdrive right atrial pacing has been used to prevent atrial fibrillation, but its efficacy in atrial fibrillation prevention and the patient tolerability and quality of life during high rate pacing remain uncertain. The objective of this study was to test the effects of a consistent atrial pacing algorithm that automatically paced the atrium at 30 ms shorter than the sinus P-P interval for atrial fibrillation prevention. Fifteen patients with sick sinus syndrome implanted with a Thera DR (model 7940 or 7960, Medtronic Inc.) were randomly programmed to rate adaptive dual chamber pacing (DDDR) or DDDR + consistent atrial pacing mode, each for an 8-week study period. The efficacy of consistent atrial pacing was assessed by the number of automatic mode switching and the number of premature atrial complexes. Symptoms and quality of life were assessed by the SF-36 quality of life questionnaire and an atrial fibrillation symptom checklist. The percentage of atrial pacing increased from 57 +/- 32% to 86 +/- 28%. Overall, there was no significant difference in the number of automatic mode switching episodes between DDDR and DDDR + consistent atrial pacing (47 +/- 90 vs 42 +/- 87, P > 0.05), but a significant reduction in premature atrial complexes by 74.7% (P < 0.001). There was no undue increase in atrial rate by the DDDR + consistent atrial pacing mode versus DDDR (63 +/- 13 vs 70 +/- 7 bpm). There was no significant difference in quality of life scores and symptom severity on frequency between the two modes of pacing, but a trend towards a lower frequency of symptoms in the DDDR + consistent atrial pacing mode compared with baseline (29.5 +/- 10.2 vs 25.1 +/- 9.7, P = 0.07). An algorithm that provides consistent atrial overdrive pacing can suppress atrial fibrillation triggering premature atrial complexes without the need to increase the overall atrial rate compared with conventional pacing. The algorithm appears to be well-tolerated, but further studies are needed to address the clinical impact of this atrial fibrillation prevention algorithm.

Aims: To evaluate the efficacy of atrial pacing in the suppression of early reinitiation of atrial fibrillation after successful internal cardioversion., Methods and Results: The efficacy of atrial pacing in suppressing early reinitiation of atrial fibrillation was studied in 12 of 45 (29%) patients with early reinitiation of atrial fibrillation after successful cardioversion. These patients were randomized to undergo either repeated defibrillation alone or repeated defibrillation followed by high right atrial pacing at 500 ms in a crossover fashion. In patients with persistent early reinitiation of atrial fibrillation despite atrial pacing at 500 ms and repeated defibrillation, atrial pacing at 300 ms was tested. Lastly, if early reinitiation of atrial fibrillation persisted, administration of intravenous sotalol (1.5 mg. kg(-1)) was tested. Atrial pacing at 500 ms after defibrillation prevented early reinitiation of atrial fibrillation in five of 12 (42%) patients, and was significantly more effective than repeated defibrillation (0/9 patients, 0%, P<0.05). During atrial pacing at 500 ms, the density of atrial premature depolarizations (APDs) was significantly decreased (2.4+/-2.4 APDs. min(-1)vs 16.4+/-9.8 APDs. min(-1), P<0. 05) and the coupling interval of atrial premature depolarization was significantly increased (420+/-32 ms vs 398+/-19 ms, P<0.05) as compared to no pacing. In the remaining seven (58%) patients, atrial pacing at 500 ms failed to prevent early reinitiation of atrial fibrillation, but significantly decreased the density of atrial premature depolarization (3.4+/-2.4 APDs. min(-1)vs 14.2+/-4.8 APDs. min(-1), P<0.05) and delayed the onset of early reinitiation of atrial fibrillation (33+/-17s vs 11+/-11 s, P<0.05). Atrial pacing at 300 ms decreased the coupling interval of atrial premature depolarization as compared to no pacing and during atrial pacing at 500 ms (P<0.05), but without early reinitiation of atrial fibrillation suppression. Administration of intravenous sotalol was effective in preventing early reinitiation of atrial fibrillation in five of seven (71%) patients where pacing failed to suppress early reinitiation of atrial fibrillation., Conclusion: The results of this study suggest that atrial pacing can be useful when combined with transvenous defibrillation in patients with early reinitiation of atrial fibrillation., (Copyright 2000 The European Society of Cardiology.)

Recent studies suggested that distal coronary sinus (CS) pacing may prevent atrial fibrillation (AF) by reducing site dependent intraatrial conduction delay. The aim of this study was to investigate the effect of high right atrial (HRA) and distal CS pacing on local conduction delay in patients with AF. The study population consisted of 10 patients with persistent AF after transvenous atrial defibrillation and 10 control subjects. The local conduction delays along the anterolateral right atrium (RA), in the CS, and at the right atrial septum (RAS), and the incidence of AF in response to an atrial extrastimulus during HRA and distal CS pacing at a drive cycle length of 400, 500, and 600 ms were evaluated. In patients with AF, distal CS and HRA pacing are associated with more prominent and similar extent of conduction delay within the atria, without any significant difference in the dispersion of conduction delay and susceptibility to AF induction (70% vs 60%, P = 0.9). In normal controls, distal CS pacing reduces the conduction delay at the RAS and CS ostium and decreases the dispersion of conduction delay and the propensity for AF induction (0% vs 50%, P = 0.03) compared to HRA pacing. The pacing drive cycle length has no significant effect on conduction delay in patients with AF and normal controls (P > 0.05). Compared to normal controls, patients with AF have significantly longer conduction delay at the RAS and along the anterolateral RA during HRA and distal CS pacing. The result of this study demonstrates that the effect of HRA and distal CS pacing on the local atrial conduction delay in patients with and without AF differ significantly. These patients with AF may have more diffuse atrial anisotropy causing the changes in conduction, and pacing from distal CS in these patients dose not reduce the propensity for AF.

Automatic mode switching (AMS) during atrial fibrillation (AF) in a dual chamber pacemaker is dependent on the accurate detection of an atrial electrogram. As atrial amplitude is often reduced during AF compared with sinus rhythm, this may result in failure of the AMS and a rapid ventricular response. In addition, undersensing of AF may result in competitive atrial pacing that sustains AF. We hypothesize that the use of automatic atrial sensitivity adjustment (ASA) may enhance AF sensing in a dual chamber pacemaker. We studied the AMS response with and without ASA of the Marathon DDDR (model 294-09, Intermedics, Inc.) pacemaker in 10 patients with paroxysmal AF. Intracardiac atrial electrograms during sinus rhythm and induced AF were recorded onto an analog tape recorder. They were replayed into the pacemaker to assess the AMS response at various starting atrial sensitivities from 3.5 to 0.8 mV with ASA activated and without. Atrial amplitude was reduced during AF. The higher the initial atrial sensitivity, the better is the AMS response and the lower the incidence of AF undersensing. The percentage of AMS before ASA ranged from 2.1% at an atrial sensitivity 3.5 mV to 95.6% at highest sensitivity of 0.5 mV (P < 0.05). After 10 minutes of ASA, the AMS response was improved from 1.7% to 50.6% and from 9.5% to 50.9% at starting atrial sensitivities of 3.5 mV and 2.5 mV, respectively (P < 0.05 in both instances). Undersensing during AF was also significantly reduced after ASA from 70% to 10% at a sensitivity of 3.5 mV and from 33.8% to 10.8% at 2.5 mV. There was no increase in oversensing. In four patients with paroxysmal AF with an implanted pacemaker, ASA improved AMS response in patients with a low implant atrial amplitude. In conclusion, efficacy of mode switching and AF sensing are dependent on the programmed atrial sensitivity, which can be enhanced with the use of ASA, particularly when P wave sensing during AF is borderline.

The use of single lead for atrial synchronous ventricular (VDD) pacing in patients with high grade atrioventricular (AV) block and normal sinus node function is an acceptable alternative to dual chamber (DDD) pacing. Implantation and follow up procedures are simplified, and cost is usually reduced by more than the cost of an additional atrial lead. With the use of either diagonally arranged dipole or closely spaced ring electrodes, reliable atrial sensing can be achieved using differential atrial amplifier and high atrial sensitivity. Also oversensing is infrequently observed using provocation tests and dynamic recordings, clinical undersensing is unusual and minimized by programming to the highest atrial sensitivity. However, as atrial pacing is not possible, loss of AV synchrony and rate response may occur for unrecognized or progressive sinus node disease and lower rate limit. The development of single lead dual chamber pacing system may overcome this limitation. Recent studies have demonstrated that atrial pacing can be effective either with the use of a special pacing lead configuration or via floating atrial electrode with a novel stimulation method. Overlapping biphasic impulse (OLBI) can reduce atrial pacing threshold. Early clinical experience suggested that this new pacing method can provide effective and reliable atrial pacing with a relatively low incidence of diaphragmatic pacing. Thus the problem of atrial sensing is solved with a single pass lead but further long term evaluation is required to assess the efficacy and feasibility of new instrumentation for single lead dual chamber pacing.

Automatic mode switching (AMS) prevents tracking of paroxysmal atrial fibrillation (AF) in dual chamber pacing. The correct detection of AF can be affected by the programmed atrial sensitivity (AS). We prospectively studied the relationship between AS, AF undersensing, and AMS, using unfiltered bipolar intracardiac atrial electrograms recorded from 17 patients during sinus rhythm (SR) and in AF. Overall, 780 rhythms were recorded and replayed onto three dual chamber pacemaker models using different AMS algorithms (Thera DR 7940, Marathon DDDR 294-09, and Meta DDDR 1254), and the ventricular responses were measured. AS was randomly programmed in steps from the highest available AS to half of the mean atrial P wave amplitude (PWA), and the percentage of appropriate AMS responses (defined as a ventricular pacing rate at the expected AMS mode) were recorded. AMS efficacy was related to the programmed AS settings in an exponential manner. At low AS settings, a higher percentage of tests were associated with absence of, or with intermittent AMS and tracking of AF, whereas at higher AS, oversensing of noise during SR occurred. An optimal AS measured approximately 1.3 mV, representing about one-third of the PWA measured during SR, although oversensing of SR and undersensing of AF continued to occur in 14% of tests and time, respectively, due to the high variation in PWA during AF. Thus, a fixed AS cannot eliminate AF undersensing without inviting noise oversensing, suggesting the need for automatic adjustments of AS, or the use of a rate-limiting algorithm to prevent rate oscillation during intermittent AF sensing. In conclusion, AMS functions of existing pacemakers were significantly limited by the undersensing of AF and oversensing of noise. Proper adjustment of the AS is important to enable effective AMS during AF.