Catheter-based renal sympathetic denervation exerts acute and chronic effects on renal hemodynamics in swine.

OBJECTIVES: We investigated the acute and chronic effects of catheter-based renal sympathetic denervation (RSD) on renal hemodynamics assessed by average peak velocity (APV), renal blood flow (RBF), renal flow reserve (RFR) and resistive index (RI). BACKGROUND: Sympathetic overdrive is accompanied by impaired RBF, whereas there is no data on the effects of transcatheter RSD on renal hemodynamic balance. METHODS: Before and post-RSD (acutely and after 1 month), in 9 farm swines we measured APV by a 0.014-inch Doppler flow wire placed in the stem of the renal artery under baseline and hyperemic conditions, induced by intrarenal dopamine (50 µg/kg). RFR was calculated as the ratio of hyperemic to basal peak velocity, and RI was estimated as (peak systolic velocity-end-diastolic velocity)/peak systolic velocity. RSD was achieved via the lumen of the main renal artery with a specifically designed catheter connected to a radiofrequency generator according to prespecified algorithm. RESULTS: APV and RBF increased acutely post ablation in all animals, compared to APV and RBF before ablation (61.44 ± 32.6 vs 20.44 ± 6.38 cm/s, p<0.001 and 407.4 ± 335.1 vs 161.1 ± 76.6 ml/min, p=0.003; respectively), whereas RFR and RI were reduced (1.51 ± 0.59 vs 2.85 ± 1.33, p<0.001 and 0.67 ± 0.07 vs 0.74 ± 0.07, p=0.005; respectively). One month post ablation APV and RBF compared to APV and RBF before ablation remained significantly higher whereas RFR and RI remained lower as compared to baseline. CONCLUSIONS: Catheter-based RSD exerts acute and chronic effects on renal hemodynamics in a large animal model. If confirmed in humans RBF parameters may be used as direct markers of successful RSD.

Thoracic spinal cord stimulation improves cardiac contractile function and myocardial oxygen consumption in a porcine model of ischemic heart failure.

BACKGROUND: Prior experimental studies show that thoracic spinal cord stimulation (SCS) improves left ventricular (LV) ejection fraction (LVEF). The mechanism of this improvement in the LV contractile function after SCS and its effects on the myocardial oxygen consumption remains unknown. METHODS AND RESULTS: We performed thoracic SCS (T1-T2 level) followed by 4 weeks of rapid ventricular pacing in 9 adult pigs with ischemic heart failure (HF) induced by myocardial infarction (MI). At 24 hours off-pacing, detailed echocardiogram and invasive hemodynamic assessment were performed to determine LV contractile function and myocardial oxygen consumption. Serum norepinephrine level was measured before and after SCS. SCS was performed on 2 occasions for 15 minutes, 30 minutes apart (recovery) with 50 Hz frequency (pulse width 0.2 millisecond, 90% of motor threshold at 2 Hz output). Echocardiogram revealed significant decrease in LVEF (33.8 ± 1.8% vs 66.5 ± 1.7%, P < 0.01) after induction of MI and HF. Compared with MI and HF, acute SCS significantly increased LVEF and +dP/dt (all P < 0.05). Withdrawal of SCS during recovery decreased +dP/dt, but not LVEF that increased again with repeated SCS. Myocardial oxygen consumption also significantly decreased during SCS compared with MI and HF (P = 0.006) without any change in serum norepinephrine level (P = 0.9). Speckle tracking imaging showed significant improvement in global and regional circumferential strains over the infarcted mid and apical regions, decreased in time to peak circumferential strain over the lateral and posterior wall after SCS, and the degree of intraventricular dyssynchrony during SCS compared with MI and HF (P < 0.05). CONCLUSIONS: In a porcine model of ischemic HF, acute SCS improved global and regional LV contractile function and intraventricular dyssynchrony, and decreased myocardial oxygen consumption without elevation of norepinephrine level.

Attenuation of left ventricular adverse remodeling with epicardial patching after myocardial infarction.

BACKGROUND: Previous studies suggested that epicardial patch applied to the infarcted site after acute myocardial infarction (MI) can alleviate left ventricular (LV) remodeling and improve cardiac performance; however, the effects of regional epicardial patch on chronic phase of LV remodeling remain unclear. METHODS AND RESULTS: We studied 20 pigs with MI induced by distal embolization and impaired LV ejection fraction (LVEF < 45%) as detected by gadolinium-enhanced cardiac magnetic resonance imaging (MRI). Eight weeks post-MI, all animal underwent open chest procedure for sham surgery (control, n = 12) or patch implantation over the infarcted lateral LV wall (patch group, n = 12). In the patch group, +dP/dt increased and LV end-diastolic pressure decreased at 20 weeks compared with immediately post-MI and at 8 weeks (P < .05), but not in the control group (P > .05). As determined by cardiac MRI, LV end-diastolic and end-systolic volumes increased at 20 weeks compared with 8 weeks in both groups (P < .05). However, the increase in LV end-diastolic volume (+14.1 +/- 1.8% vs. +6.6 +/- 2.1%, P = .015) and LV end-systolic volume (+12.1 +/- 2.4% vs. -4.7 +/- 3.7%, P = .0015) were significantly greater in the control group compared with the patch group. Furthermore, the percentage increase in LVEF (+17.3 +/- 4.9% vs. +4.1 +/- 3.9%, P = .048) from 8 to 20 weeks was significantly greater in the patch group compared with the control group. Histological examination showed that LV wall thickness at the infarct region and adjacent peri-infarct regions were significantly greater in the patch group compared with the control group (P < .05). CONCLUSION: Regional application of a simple, passive synthetic epicardial patch increased LV wall thickness at the infarct region, attenuated LV dilation, and improved LVEF and +dP/dt in a large animal model of MI.

Atrial activation time and pattern of linear triple-site vs. single-site atrial pacing after cardioversion in patients with atrial fibrillation.

AIMS: Multisite atrial pacing has been suggested to be effective in suppressing atrial fibrillation (AF), however, the effect of linear triple-site atrial pacing (LTSP) in humans has not been evaluated. We compared the effects of LTSP to single-site atrial pacing (SSP) on the atrial activation and wavefront propagation pattern in patients with persistent AF. METHODS AND RESULTS: In 10 patients with persistent AF, the effects of LTSP and SSP were evaluated by left atrial (LA) endocardial non-contact multielectrode array mapping and multipolar catheters. LTSP and SSP were delivered from the high right atrium (HRA), the distal coronary sinus (CS), and within the LA at the site showing maximal overlay of low-voltage zones during sinus rhythm and pacing at HRA and CS. Atrial activation time and pattern, P wave duration, and the prevention of AF induced by burst pacing were assessed with these pacing interventions. Compared with SSP, LTSP at the HRA, CS, and LA shortened atrial activation times (183 +/- 24 vs. 174 +/- 24 ms, 186 +/- 29 vs. 166 +/- 28 ms, and 171 +/- 40 vs. 163 +/- 39 ms; P < 0.05, respectively). P wave duration was shorter with LTSP than SSP at all three sites (141.7 +/- 35.1 vs. 146.9 +/- 38.5 ms, 138.1 +/- 34.6 vs. 145.7 +/- 33.7 ms, and 142.7 +/- 33.4 vs. 151.3 +/- 35.1 ms; P < 0.05, respectively). LTSP initially depolarized a larger area than SSP, and produced more uniform and planar wavefront propagation. LTSP prevented the burst-induction of AF during LA pacing in 3 of 10 patients, while SSP was never successful. CONCLUSION: In patients with persistent AF, LTSP provided more rapid and uniform activation of the atria compared with SSP, which was associated with prevention of burst-induction of AF in some patients. Further study is required to determine whether LTSP can modify the substrate of chronic AF, leading to frank AF suppression.

A opção de programação rate drop response (resposta à queda de freqüência) previne a hipotensão ortostática em pacientes idosos, portadores de marcapasso e com incompetência cronotrópica? / Transient overdrive pacing upon standing prevents orthostatic hypotension in elderly pacemaker patients with chronotropic incompetence

Introdução: pacientes idosos, portadores de marcapasso e com incompetência cronotrópica (IC) podem apresentar hipotensão em posição ortostática (HO). Objetivo: determinar se o aumento transitório da freqüência cardíaca, por meio da opção de programação rate drop response (resposta à queda da freqüência cardíaca), previne...

Transient overdrive pacing upon standing prevents orthostatic hypotension in elderly pacemaker patients with chronotropic incompetence.

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.

Estimation of the optimal VV delay by an IEGM-based method in cardiac resynchronization therapy.

Determination of the optimal interventricular (VV) delay in cardiac resynchronization therapy currently relies on costly, time-consuming echocardiographic (ECHO) methods. This study evaluated the performance of a new intracardiac electrogram (IEGM)-based VV method compared to the aortic velocity time integral (AVTI) method of VV delay optimization. The study included two patient groups. Eleven patients enrolled by a single center in the Rhythm II ICD trial underwent prospective comparisons of the AVTI at the VV interval determined by the IEGM VV method versus the maximum AVTI at the echocardiographically determined optimal VV delay. In 61 patients enrolled in the RHYTHM VV trial, the same testing methods were compared retrospectively. In the prospective study, the maximum AVTI by the ECHO-based method (24.3 +/- 7.9 cm), was closely correlated with maximum AVTI by the IEGM-based method (23.9 +/- 7.9 cm; concordance correlation coefficient = 0.99; 95% confidence, lower limit of 98%. Likewise, in the retrospective analysis, the ECHO-determined maximum AVTI (22.1 +/- 8.2 cm) was similar to that determined by the IEGM-based method (20.9 +/- 8.3 cm; concordance correlation coefficient = 0.98; 95% confidence, lower limit of 97%).

Blood pressure response to transition from supine to standing posture using an orthostatic response algorithm.

Upon standing from a supine position, the normal response is an increase in heart rate to maintain blood pressure (BP). In patients with chronotropic incompetence, heart rate may not increase upon standing, and they may experience orthostatic hypotension (OH). We evaluated a new orthostatic response (OSR) pacing algorithm that uses an accelerometer signal to detect sudden activity following prolonged rest to trigger a 2 minutes increase in pacing rate to 94 bpm. Ten recipients of DDDR pacemakers which contain the OSR compensation algorithm (mean age = 77 +/- 9 years, 8 women) with sick sinus syndrome (n = 6) or atrioventricular block (n = 4) were studied. In all patients BP was measured before and 0.5, 1, 1.5, 2, and 3 minutes after standing at their programmed base rate. A 20 mmHg fall in systolic BP upon standing was observed in five patients (OH patients), while the other five were considered non-OH patients. The measurements were repeated with the OSR algorithm turned on. Mean BP was defined as 1/3 systolic BP + 2/3 diastolic BP. Baseline heart rate was significantly slower in OH patients (62 +/- 2 bpm) than non-OH patients (71 +/- 7 bpm, P < 0.05). In OH patients mean BP increased significantly upon standing (P < 0.05 for all comparisons) with the algorithm ON instead of decreasing with the algorithm OFF, at 1 minute (+3.4 vs -10.3 mmHg), 1.5 minutes (+7.0 vs -4.9 mmHg), 2 minutes (+1.6 vs -6.7 mmHg), and 3 minutes (+2.5 vs -8.5 mmHg). These preliminary results suggest that the OSR algorithm maintains BP upon standing in patients with OH.

Evaluation of the atrial evoked response for capture detection with high-polarization leads.

AutoCapture based on the evoked response can be confounded by electrode polarization. In this study, polarization was measured in human subjects who had chronic atrial leads. The aim of the study was to determine whether electrode polarization can be measured using a time integral atrial evoked-response integral (AERI) of the negative portion of the atrial paced ER evoked-response signal and to determine whether high-polarization atrial leads unsuitable for AutoCapture can be identified a priori. Atrial intracardiac-electrogram (IEGM) signals from 39 patients with implanted pacemakers were recorded and analyzed. The signals were recorded during conventional atrial-threshold searches. A total of 221 atrial-capture thresholds were recorded, ranging from 0.25 to 2.75 V with a mean of 0.79 V. Each evoked response was evaluated using the AERI in a 36 ms window following the 0.4 ms atrial stimulus. The polarization was estimated as a linear function of stimulus voltage using the evoked-response signal integral of captured beats identified on the IEGM. The 221 threshold-search datasets were obtained using leads with eight different electrode materials. Polarization could be measured using AERI as a function of stimulus voltage. Furthermore, this polarization measure can be used to identify high-polarization leads, which are ill suited for the atrial AutoCapture algorithm.

Impedance cardiography for atrioventricular interval optimization during permanent left ventricular pacing.

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.

Autocapture enhancements: unipolar and bipolar lead compatibility and bipolar pacing capability on bipolar leads.

Beat-by-beat Autocapture maximizes device longevity by minimizing stimulus amplitude while assuring patient safety. Currently, Autocapture permits use of only bipolar leads. The authors have devised a detection method that operates with unipolar and bipolar leads and covers all pacing and sensing combinations (but bipolar pace and sense simultaneously). This new detection method for unipolar sensing uses the integral of the negative portion of the unipolar evoked response as a robust capture detection feature. When using bipolar leads, the method provides the flexibility of bipolar or unipolar pacing. In this study, unipolar ventricular intracardiac electrograms (EGMs) were recorded in 71 patients, 73.7 +/- 9.9 years of age; 9 with high polarization, 62 with low polarization. High polarization had polished platinum or activated carbon electrodes. Low polarization had TiN, platinized platinum, or IrOx electrodes. The intracardiac EGMs were recorded 544 +/- 796 days after implant. The pacemakers performed an automatic capture threshold test while the intracardiac EGM signals were recorded in a programmer. These digitized signals were saved for off-line analysis. The unipolar evoked response was calculated at up to six (depending on capture threshold) pacing voltages and the polarization integral at 4.5 V and at loss of capture. An automatic calibration algorithm determined if the signal-to-noise ratio was adequate for Autocapture operation. Autocapture was possible with 60 of 62 of the low polarizations, and with 6 of 9 of the high polarizations. The average values form the data collected were: average unipolar evoked response--4.1 +/- 2.1 mV, average peak negative voltage--10.0 +/- 3.7 mV, average polarization 0.3 +/- 0.34 mV, and average signal-to-noise ratio (unipolar evoked response/ polarization) 38 +/- 71. In all cases the algorithm correctly determined the appropriateness of using Autocapture with the electrodes tested and the unipolar evoked response threshold to be used.

Atrial evoked response integral for automatic capture verification in atrial pacing.

Beat-by-beat Autocapture is currently limited to operation in the ventricle with bipolar leads. The authors investigated the integral of the negative-going portion of the atrial evoked response integral (AERI) as a potential resource for verification of atrial capture. Intracardiac electrogram signals were collected from 59 patients (ages 67.8 +/- 15.1 years) with bipolar, low polarization atrial leads. The signals were collected over a mean period of 6.1 months (minimum 4 days) after lead implantation. St. Jude Medical Affinity pulse generators were used to perform automatic capture threshold tests while the electrogram signals were recorded by a Model 3510 programming device. These signals were transferred to a personal computer in digital form for later analysis. The AERI was calculated at each programmable pacing voltage until capture was lost. The difference between the polarization integral at loss of capture and evoked response integral with successful capture was sufficient to justify enabling the atrial Autocapture feature in 53 of 59 patients in whom bipolar pacing and unipolar sensing was performed. The authors developed a calibration routine to identify automatically those patients in whom atrial Autocapture could be programmed On, based on the polarization integral at loss of capture, the estimated maximum polarization integral, and the AERI. Preliminary analysis indicated that the AERI is a practical resource for beat-by-beat atrial capture detection when used with low polarization leads.