Effects of AV delay and VV delay on left atrial pressure and waveform in ambulant heart failure patients: insights into CRT optimization.

BACKGROUND: We hypothesized that left atrial pressure (LAP) obtained by a permanent implantable sensor is sensitive to changes in cardiac resynchronization therapy (CRT) settings and could guide CRT optimization to improve the response rate. We investigated the effect of CRT optimization on LAP and its waveform parameters in ambulant heart failure (HF) patients. METHODS: CRT optimization was performed in eight ambulant HF patients, using echocardiography as reference. LAP waveform was acquired at each of eight atrioventricular (AV) intervals and five inter-ventricular (VV) intervals. Selected waveform parameters were also evaluated for their sensitivity to CRT changes and agreement with echocardiography-guided optimal settings. RESULTS: Optimal AV and VV intervals varied considerably between patients. All patients exhibited significant changes in waveform morphology with AV optimization. Optimal AV delay determined from echocardiography ranged between 140 ms and 225 ms. Mean LAP tended to be lower at optimal setting 14 ± 3 mmHg compared to shorter (<100 ms) or longer (>160 ms) AV settings (P = 0.16). There were clear trends to smaller peak a-wave (P = 0.11) and gentler positive a-slope (P = 0.15) and positive v-slope (P = 0.09) with longer AV delays. Mean LAP and negative v-wave slope correlated well with echo-guided optimal setting, r = 0.91 (P = 0.001) and 0.79 (P = 0.03), respectively. No significant effects on LAP or waveform were seen during VV optimization. CONCLUSIONS: LAP and its waveform changes considerably with AV optimization. There is good agreement between echo-guided optimal setting and LAP. LAP could provide an objective guide to CRT optimization. (Clinical Trial Registry information: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00632372).

Dynamic ventricular overdrive stimulation in atrial fibrillation: effects on ventricular rate irregularity, ventricular pacing, and fusion beats.

AIMS: In pacemaker patients with preserved atrio-ventricular (AV) conduction, atrial fibrillation (AF) can lead to symptomatic ventricular rate irregularity and loss of ventricular stimulation. We tested if dynamic ventricular overdrive (DVO) as a potentially pacemaker-integrated algorithm could improve both aspects. METHODS AND RESULTS: Different settings of DVO and ventricular-ventricular-inhibited-pacing (VVI) with different base rates were tested in two consecutive phases during electrophysiological studies for standard indications. Mean heart rate (HR), HR irregularity and percentage of ventricular pacing were evaluated. A fusion index (FI) indicative of the proportion of fusion beats was calculated for each stimulation protocol. Dynamic ventricular overdrive from the right ventricular apex was acutely applied in 38 patients (11 females, mean age 62.1 ± 11.5 years) with sustained AF and preserved AV conduction. Dynamic ventricular overdrive at LOW/MEDIUM setting increased the amount of ventricular pacing compared with VVI pacing at 60, 70, and 80 beats per minute (bpm; to 81/85% from 11, 25, and 47%, respectively; P < 0.05). It also resulted in a maximum decrease in interval differences (to 48 ± 18 ms from 149 ± 28, 117 ± 38, and 95 ± 46 ms, respectively; P < 0.05) and fusion (to 0.13 from 0.41, 0.42, and 0.36, respectively; P < 0.05) compared with VVI pacing at 60, 70, and 80 bpm. However, the application of DVO resulted in a significant increase in HR compared with intrinsic rhythm and VVI pacing at 80 bpm (to 97 bpm from 89 and 94 bpm, respectively; P < 0.05). CONCLUSION: Dynamic ventricular overdrive decreases HR irregularity and increases ventricular pacing rate compared with VVI pacing at fixed elevated base rates and spontaneous rhythm. Fusion index might help to refine information on pacing percentages provided by device counters.

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.

The impact of cardiac resynchronization therapy on obstructive sleep apnea in heart failure patients: a pilot study.

BACKGROUND: Cardiac resynchronization therapy (CRT) has been shown to improve cardiac function and reduce Cheyne-Stokes respiration but has not been evaluated in patients with obstructive sleep apnea (OSA). In this pilot study, we investigated the impact of both CRT and CRT plus increased rate pacing in heart failure (ie, congestive heart failure [CHF]) patients with OSA. We hypothesized that through increased cardiac output CRT/pacing would reduce obstructive events and daytime symptoms of sleepiness. METHODS: Full polysomnograms were performed on CHF patients who were scheduled for CRT, and those patients with an apnea-hypopnea index (AHI) of > 5 events per hour were approached about study enrollment. Patients had a pre-CRT implant baseline echocardiogram and an echocardiogram a mean (+/- SEM) duration of 6.6 +/- 1.4 months post-CRT implant; polysomnography; and responded to the Minnesota Living with Heart Failure questionnaire, the Epworth sleepiness scale, and the Functional Outcomes of Sleep Questionnaire. An additional third polysomnography was performed combining CRT with a pacing rate of 15 beats/min above the baseline sleeping heart rate within 1 week of the second polysomnography. Assessments for the change in cardiac output during the polysomnography were performed using circulation time to pulse oximeter as a surrogate. RESULTS: Twenty-four patients were screened, and 13 patients (mean age, 68.6 years; body mass index, 28.7 kg/m(2)) had evidence of OSA. The mean AHI decreased from 40.9 +/- 6.4 to 29.5 +/- 5.9 events per hour with CRT (p = 0.04). The mean baseline ejection fraction was 22 +/- 1.7% and increased post-CRT to 33.6 +/- 2.0% (p < 0.05). The reduction in AHI with CRT closely correlated with a decrease in circulation time (r = 0.89; p < 0.001) with CRT. Increased rate pacing made no additional impact on the AHI or circulation time. CRT had a limited impact on sleep architecture or daytime symptom scores. CONCLUSIONS: CRT improved cardiac function and reduced the AHI. Reduced circulatory delay likely stabilized ventilatory control systems and may represent a new therapeutic target in OSA.

Time Course of Subsequent Shocks After Initial Implantable Cardioverter-Defibrillator Discharge and Implications for Driving Restrictions.

IMPORTANCE: Although guidelines recommend driving restrictions for 3 to 6 months after appropriate implantable cardioverter-defibrillator (ICD) shocks, contemporary data to support these recommendations are lacking. OBJECTIVE: To define the time course of subsequent shocks after an initial ICD discharge. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of a nationwide cohort of 14 230 ICD recipients enrolled in a remote monitoring program. Participants underwent ICD implantation from October 1, 2008, to December 31, 2013, and experienced at least 1 shock. The risk of driving after an ICD shock was estimated using the risk for harm (RH) formula, and an annual RH of less than 5 events per 100 000 ICD recipients was deemed safe. The likelihood of loss of consciousness associated with an ICD shock was estimated using a cautious value of 32% and an estimate of 14% based on contemporary data. Data were extracted and analyzed from December 17, 2014, to October 31, 2015. MAIN OUTCOMES AND MEASURES: Time course of subsequent shocks after an initial ICD discharge. RESULTS: Of 73 503 ICD recipients who underwent remote monitoring, 14 230 (19.4%) experienced at least 1 ICD shock and were included in this analysis (10 870 men [76.4%]; 3360 women [23.6%]; median age at device implantation, 68 years; interquartile range [IQR], 60-76 years). The cumulative incidence of receiving a second shock was 14.5% (IQR, 13.9%-15.1%) at 1 month and 28.7% (IQR, 27.9%-29.5%) at 6 months. The time from implantation to initial shock had an inverse association with the likelihood of receiving a second shock (lowest quartile of time at 6 months, 31.6% [95% CI, 30.2%-33.2]; highest quartile of time at 6 months, 25.3% [95% CI, 23.8%-26.9%]). The number of ICD therapy zones was also significantly associated with the incidence of a second shock (1 therapy zone, 20.8% [95% CI, 19.4%-22.3%] at 3 months to 51.5% [95% CI, 48.5%-53.7%] at 3 years; 3 therapy zones, 26.9% [95% CI, 24.8%-29.0%] at 3 months to 57.3% [95% CI, 54.1%-60.5%] at 3 years). When a likelihood of loss of consciousness of 32% associated with an ICD shock was used, the RH while driving fell below the accepted threshold at 4 to 6 months after an initial shock. However, when a contemporary estimate for loss of consciousness associated with an ICD shock of 14% was used, the RH fell below the threshold at 1 month after an initial shock. CONCLUSIONS AND RELEVANCE: In this large cohort of ICD recipients, the incidence of a second shock after an initial ICD discharge was lower than previously reported and depended on several programmed ICD variables. These data, with future research to derive contemporary estimates of the likelihood of fatality resulting from an ICD shock while driving, should support the development of evidence-based guidelines for driving restrictions in ICD recipients.

Acute and chronic performance evaluation of a novel epicardial pacing lead placed by percutaneous subxiphoid approach in a canine model.

BACKGROUND: Endovascularly implanted leads risk vascular injury and endocarditis, and can be difficult to locate in desired positions for LV pacing. We evaluated the acute and long-term stability, electric performance and histopathology of a percutaneously placed intrapericardial lead (IPL). METHODS AND RESULTS: Twelve adult mongrel dogs underwent defibrillator implants incorporating IPLs. Successful uncomplicated percutaneous implantation of an IPL was achieved in all. Early fluoroscopic shift noted with 3 of 6 of the initial version IPL-1 was not seen with the modified IPL-2. Mean±95% confidence interval bipolar capture threshold at 0.5-ms pulse width for the IPL increased from 0.69±0.14 V at implant to 1.50±0.34 V (P=0.003) at 12 weeks. The 12-week thresholds were higher for IPL compared with right ventricular endocardial leads (0.75±0.33 V; P=0.001) but not different compared with coronary sinus leads (1.33±0.58 V; P=0.994). IPL impedance increased from 742±46 Ω at implant to 1066±207 Ω at 12 weeks (P=0.007). R-wave amplitude at 12 weeks was 8.37±1.52 mV. There was no important phrenic nerve stimulation from IPL pacing. Histopathology in 8 animals showed adequate adhesion of the electrodes or mesh to the epicardium without damage to underlying vasculature. There was no evidence for late pericardial inflammation or effusion. CONCLUSIONS: The IPL demonstrated adequate stability of position and acceptable electric parameters without chronic pericardial inflammation in this canine model and offers a potential alternative to endocardial pacing leads.

Identification of transmural necrosis along a linear catheter ablation lesion during atrial fibrillation and sinus rhythm.

BACKGROUND: Determining whether a linear catheter radio frequency (RF) ablation lesion is transmural may be difficult, especially during atrial fibrillation. We hypothesized that changes in pacing thresholds and electrogram amplitude during atrial fibrillation and sinus rhythm could be used to assess whether a radiofrequency ablation resulted in transmural necrosis. METHODS: A hexapolar, linear, RF ablation catheter was positioned between the caval veins in the right atrium of seven sheep. Pacing thresholds and electrogram amplitudes during atrial fibrillation and sinus rhythm were measured before and after the application of RF energy. Sites along the linear lesion were assessed histologically. RESULTS: The electrogram amplitude in atrial fibrillation decreased significantly more at transmural sites (unipolar recording: 33 +/- 11% transmural vs. 22 +/- 13% non-transmural, p < or = 0.01; bipolar recording: 62 +/- 9% transmural vs. 43 +/- 15% non-transmural, p < or = 0.01). The electrogram amplitude in sinus rhythm decreased significantly more at transmural sites (unipolar recording: 49 +/- 18% transmural vs. 15 +/- 20% non-transmural, p < 0.001; bipolar recording: 63 +/- 17% transmural vs. 42 +/- 19% non-transmural, p = 0.002). The pacing threshold increased significantly more at sites with transmural necrosis (unipolar: increased by 378 +/- 103% transmural vs. 207 +/- 93% non-transmural, p < 0.001; bipolar: 370 +/- 80% transmural vs. 259 +/- 60% non-transmural, p < 0.001). CONCLUSIONS: The amplitude of the atrial electrogram from an ablation catheter can be used to discriminate areas with transmural necrosis from those without transmural necrosis during either atrial fibrillation or sinus rhythm. Termination of atrial fibrillation may not be necessary to estimate the histologic characteristics of an ablation lesion.

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.

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.

Reduction of the internal atrial defibrillation threshold with balanced orthogonal sequential shocks.

INTRODUCTION: The aim of this study was to determine the atrial defibrillation threshold (ADFT) of a first shock across the standard right atrium (RA) to distal coronary sinus (dCS) configuration followed by a second shock along the atrial septum with a standard sequential waveform (the second shock leading edge equaled the first shock trailing edge) and a balanced sequential waveform (the leading edges of both shocks were equal). METHODS AND RESULTS: In nine sheep atrial fibrillation was induced with acetyl-beta-methylcholine and burst pacing. A catheter was placed with electrodes in the dCS, proximal coronary sinus (pCS), and RA. A J-shaped catheter was positioned with an electrode at Bachmann's bundle (BB) while another catheter was positioned with an electrode in the superior vena cava (SVC). The ADFTs of six single- and dual-pathway configurations were determined with single, standard sequential, or balanced sequential shocks. The ADFT of the RA-->dCS configuration (0.86 +/- 0.27 J, 159 +/- 29 V, 2.42 +/- 0.36 A) was significantly reduced when followed by an SVC-->pCS (0.58 +/- 0.17 J, 112 +/- 20 V, 1.64 +/- 0.39 A) or a BB-->pCS shock (0.64 +/- 0.16 J, 119 +/- 18 V, 1.81 +/- 0.38 A) with standard sequential shocks. With balanced sequential shocks, the peak voltage and current ADFTs were further significantly reduced (85 +/- 11 V and 1.24 +/- 0.21 A for second shock SVC-->pCS, and 93 +/- 13 V and 1.38 +/- 0.27 A for second shock BB-->pCS). CONCLUSION: The ADFT of the standard RA-->dCS shock is significantly reduced when followed by a second shock along the atrial septum delivered between electrodes in the pCS and either SVC or BB and ADFT is further reduced with balanced sequential shocks.

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...