Search

Cardiac electrogram (EGM) signals and electrophysiologic (EP) characteristics derived from them such as amplitude and timing are central to the diagnosis and therapeutic management of arrhythmias. Bipolar EGMs are often used but possess polarity and shape dependence on catheter orientation contributing to uncertainty. Objective: We describe a novel method to map cardiac activation that resolves signals into meaningful directions and is insensitive to electrode directional effects. Methods: Multielectrode catheters that span 2- and 3-D space are used to derive local electric field (E-field) signals. A traveling wave model of local EGM propagation motivates a new “omnipolar” reference frame in which to understand EGM E-field signals and provide bipolar component EGMs aligned with these anatomic and physiologic directions. We validate the basis of this technology and determine its accuracy using a saline tank in which we simulate physiologic propagation. Results: Omnipole signals from healthy tissue are nearly free of catheter orientation effects and are constrained by biophysics to consistent morphologies and thus consistent measured amplitudes and timings. Using a 3-D EP mapping system, traveling wave treatment, and omnipolar technology (OT) E-field loops, we derived a new and nearly instantaneous means to determine conduction velocity and activation direction. Conclusion: We describe the basis of OT and validate it with ablation and mapping catheters in a saline tank. Finally, we illustrate OT with signals from live subjects. Significance: OT's novel approach with signal processing and real-time visualization allows for a newly detailed characterization of myocardial activation that is insensitive to catheter orientation.

Aims To determine if a software algorithm can use an individualized distance-morphology difference model, built from three initial pacemaps, to prospectively locate the exit site (ES) of ventricular arrhythmias (VA). Methods and results Consecutive patients undergoing ablation of VA from a single centre were recruited. During mapping, three initial pacing points were collected in the chamber of interest and the navigation algorithm applied to predict the ES, which was corroborated by conventional mapping techniques. Thirty-two patients underwent ES prediction over 35 procedures. Structural heart disease was present in 16 (7 ischaemic cardiomyopathy, 9 non-ischaemic cardiomyopathy), median ejection fraction 45% [Interquartile range (IQR) 26]. The remainder had normal hearts. The navigation algorithm was applied to 46 VA (24 left ventricle, 11 right ventricular outflow tract, 5 left ventricular outflow tract, 4 right ventricle, 2 epicardial) and successfully located the site of best pacemap match in 45 within a median area of 196.5 mm2 (IQR 161.3, range 46.6-1288.2 mm2). Conclusions In a diverse population of patients with and without structural heart disease, the ES of VA can be accurately and reliably identified to within a clinically useful target area using a simple software navigation algorithm based on pacemapping.

Introduction: Substrate mapping is evolving as a potential strategy for atrial fibrillation ablation. Defining scar borders and functional boundaries is typically under taken with bipolar electrodes. Catheter orientation affects electrogram (EGM) signal amplitude due to an orientation dependence of bipoles. We developed orientation independent Omnipolar Technology (OT) and compared OT EGM amplitude with traditional bipolar (Bi) methods. Methods: Four anesthetized swine were studied in 6 sessions with a 3D mapping system and a multielectrode OT ablation catheter placed in RA and LA locations in 4 rhythms. With the OT catheter in a stable location, 30 successive atrial beats were acquired. OT electrodes provided bipole (Bi) as well as OT signals along both activation (OTa) and surface normal (OTn) directions. Peak to peak amplitudes (Vpp) of OT and Bi signals were compared for magnitude and consistency. Results: As shown in the table, OT signal amplitudes over all atrial locations and rhythms were greater than traditional bipole amplitudes. The coefficients of variation for signal amplitude over successive cardiac beats were substantially less for OTa and OTn (*p < 0.01 with respect to Bi) than for Bi, reflecting electrode pair orientation effects. Conclusions: Distinct electrogram signals were resolved by OT along physiologic (activation) and anatomic (surface normal) directions. Catheter orientation independent OT signal amplitudes were more self-consistent and reliable than those from orientation dependent bipolar electrode pairs. Omnipolar technology approaches may permit more accurate and specific definition of substrate and thus catheter ablation of arrhythmias.

Aims The purpose of this study was to examine, in chronically treated heart failure patients vs control subjects, the influence of neurohumoral activation and aldosterone escape on arterial elastic behaviour, assessed by noninvasive mathematical lumped-parameter modelling of the compliance of the arterial system. Methods and Results Radial arterial pulse waves were recorded non-invasively for 30 s with an arterial tonometer sensor array in 13 chronic heart failure patients (mean age, 59 +/- 2.5 years) in New York Heart Association class II. The patients had been taking digoxin, furosemide, captopril and aspirin for more than 3 months. Thirteen healthy subjects (mean age, 50 +/- 4.0 years) acted as controls. Compliance of the proximal (aorta and major branches, C1) and distal parts (C2) of the circulation were derived from a third order four-element modified Windkessel model which can reproduce arterial pressure waveforms, including both exponential and oscillatory sections. Active renin, angiotensin II and aldosterone levels were determined on venous blood samples in the supine position and after 30 min active standing. There was decreased proximal (C1, 1.51 +/- 0.11 ml . mmHg(-1), P

Autonomic Blockade During Atrial Fibrillation. Introduction: The influence of the autonomic nervous system on the pathogenesis of complex fractionated atrial electrograms (CFAE) during atrial fibrillation (AF) is incompletely understood. This study evaluated the impact of pharmacological autonomic blockade on CFAE characteristics. Methods and Results: Autonomic blockade was achieved with propanolol and atropine in 29 patients during AF. Three-dimensional maps of the fractionation degree were made before and after autonomic blockade using the Ensite Navx® system. In 2 patients, AF terminated following autonomic blockade. In the remaining 27 patients, 20,113 electrogram samples of 5 seconds duration were collected randomly throughout the left atrium (10,054 at baseline and 10,059 after autonomic blockade). The impact of autonomic blockade on fractionation was assessed by blinded investigators and related to the type of AF and AF cycle length. Globally, CFAE as a proportion of all atrial electrogram samples were reduced after autonomic blockade: 61.6 ± 20.3% versus 57.9 ± 23.7%, P = 0.027. This was true/significant for paroxysmal AF (47 ± 23% vs 40 ± 22%, P = 0.003), but not for persistent AF (65 ± 22% vs 62 ± 25%, respectively, P = 0.166). Left atrial AF cycle length prolonged with autonomic blockade from 170 ± 33 ms to 180 ± 40 ms (P = 0.001). Fractionation decreases only in the 14 of 27 patients with a significant (>6 ms) prolongation of the AF cycle length (64 ± 20% vs 59 ± 24%, P = 0.027), whereas fractionation did not reduce when autonomic blockade did not affect the AF cycle length (58 ± 21% vs 56 ± 25%, P = 0.419). Conclusions: Pharmacological autonomic blockade reduces CFAE in paroxysmal AF, but not persistent AF. This effect appears to be mediated by prolongation of the AF cycle length. (J Cardiovasc Electrophysiol, Vol. pp. 766-772, July 2010)

Introduction: Pacemapping (PM) is an established method for localising the site of origin (SO) of ventricular arrhythmias (VA). Currently, there is no system to indicate where subsequent PM will result in a better match to the clinical VA. We investigated the relationship between the change in ECG and distance between PM points and developed a novel navigation algorithm which was tested prospectively. Methods: Digitised ECGs and Cartesian catheter coordinates were extracted from prospectively collected PM points across the endocardial (endo) surface of both ventricles and epicardial (epi) where possible, along with geometry from a 3D mapping system used in patients who underwent ablation of VA. Using custom software, a similarity metric was calculated using the root mean square error sum (RMSE) for each ECG between pairs of PM points (myocardial voltage > 0.5 mV) and plotted against Euclidian distance and linear regression through origin performed to examine the distance similarity relationship (DSR). For the navigation concept, custom 3D mapping software was developed to run in parallel with the EnSite Velocity System (St Jude Medical, MN). For each study, a patient specific DSR was created initially from 3 widely spaced PM points and RMSE calculated between the VA and PM points. Using the DSR, the distance between VA and each PM point was extrapolated and visualised as 3 overlapping circles converging on a target superimposed on the 3D geometry (Figure). If the target was large, the PM point furthest away was substituted with a PM point predicted to be closest to the VA and this process repeated iteratively until the target area reduced to a minimum. Results: From Oct 11-Jun 14, we enrolled 64 patients, 43 Male, median age 56 (IQR 26) who underwent 70 procedures (40 VE, 30 VT, 65 Endo, 5 Epi approach). 30 had normal hearts (NH), 19 ICM and 15 NICM. Median LVEF was 55% (IQR 22). A total of 861 PM points were analysed (mean 12.3±4.4 PM points per patient). Distance and ECG similarity were strongly correlated, median correlation coefficient R 0.937 (IQR .044). There was no difference in strength of correlation or gradient of the slope between scarred vs NH or between NH vs ICM vs NICM. We performed real time SO prediction on 25 prospectively enrolled patients (18 male; age 52±15 yrs; median LVEF 57% (IQR 15); 15 VE, 10 VT; 11 NH, 4 IHD, 10 NICM; Epi approach in 3). SO prediction was performed on 32 distinct VA (12 LV, 4 LVOT, 3 RV, 11 RVOT, 2 Epi LV). The system correctly identified the SO (as identified by conventional means) in 31/32 instances with a mean target area of 208±185mm2 range (40-708mm2) requiring 7±3 PM to build the relationship. In one case, the system correctly identified the area of best PM match but was discordant with activation mapping. Conclusion: There is a strong linear relationship between change in ECG morphology and distance using PM points from myocardium >0.5 mV that does not appear to be significantly different between scar and non-scar aetiologies. Using this novel system, it is possible to correctly identify a clinically useful target area in real time to identify the SO of VA in patients with structural heart disease and normal hearts. Further work is needed to confirm its usefulness in VA of epicardial origin. ![Graphic][1] [1]: /embed/inline-graphic-1.gif

Arterial compliance measurements using intraarterial pulse contour analysis and a modified Windkessel model were carried out in 19 patients with isolated systolic hypertension (or = 160/or = 90 mm Hg) and compared to measurements in 29 patients with essential hypertension (diastolic blood pressure [BP]or = 95 mm Hg) and 47 normotensive control subjects. Arterial capacitive compliance was significantly lower in isolated systolic hypertension than in essential hypertension (P.0002) and significantly lower in essential hypertension than in normotensive control subjects (P.0001). Although the isolated systolic hypertension group was older than the essential hypertension group, the reduction of capacitive compliance in isolated systolic hypertension persisted even when comparison was made with a more nearly age-matched group of essential hypertension. In contrast, oscillatory compliance was reduced similarly in isolated systolic hypertension and essential hypertension compared to normotensive control subjects (P.0001). Although pulse pressure was greater in isolated systolic hypertension than in essential hypertension, only a weak correlation (r = -0.34) existed between pulse pressure and capacitive compliance. These data indicate that both essential hypertension and isolated systolic hypertension patients exhibit comparably abnormal structure or tone of the small vessels that are the site of oscillations or reflections in the arterial vasculature. In isolated systolic hypertension there is a profound reduction in large artery or capacitive compliance that accounts for the increase in systolic BP and decrease in diastolic BP. This abnormality cannot be accurately assessed by pulse pressure alone.

Abstract —The objective of this study was to evaluate age-related changes in pulsatile arterial function. Aging alters arterial pulsatile function and produces consistent changes in the pressure pulse contour. A reduced systemic arterial compliance that can be derived from analysis of the pulse contour is regarded as the best clinical index of impaired pulsatile arterial function and may mark the presence of early vascular damage. We analyzed intra-arterial brachial artery waveforms in 115 healthy normotensive volunteers (83 men, 32 women) and radial artery waveforms obtained with the use of a calibrated tonometer device in 212 healthy volunteers (147 women, 65 men). A computer-based assessment of the diastolic pressure decay and a modified Windkessel model of the circulation were used to quantify changes in arterial waveform morphology in terms of large artery or capacitive compliance, oscillatory or reflective compliance in the small arteries, inertance, and systemic vascular resistance. Large artery compliance and oscillatory compliance correlated negatively with age for both invasive and noninvasive groups ( r =−0.50 and r =−0.55; r =−0.37 and r =−0.66; P

Arterial compliance, defined as a change in dimension in response to a given change in stress, is becoming an increasingly important clinical parameter. Related concepts, such as distensibility, elasticity, and stiffness, and more traditional concepts such as resistance, afterload, and impedance need to be differentiated from compliance, although they are frequently (inappropriately) used interchangably. Many studies cannot differentiate between compliance changes due to a drug's effect on blood pressure and those due to a drug's effect on vessel wall integrity. This differentiation is important because a more physiologic therapy, one that benefits pulsatile and nonpulsatile flow, should be of greater clinical benefit than a therapy that only lowers blood pressure. A number of methods have been used to estimate compliance, but to date there is no generally agreed-on best method. There also are no longitudinal studies that relate abnormal compliance and drug effects to outcome. Nonetheless, patients at risk from a variety of disease states, such as hypertension, diabetes mellitus, and hypercholesterolemia, may benefit from earlier recognition of abnormal compliance. Earlier recognition may lead to interventions that would reduce their risk. This review includes a discussion of compliance and related estimates of blood vessel function and attempts to summarize the data currently available regarding the effects of cardioactive drugs on arterial compliance.

Consistent changes in the arterial pulse contour are found with aging and disease states that impair the compliance characteristics of blood vessels that buffer pulsatile phenomena in the arterial tree. We assessed whether vascular adaptation in structure or tone of blood vessels associated with long-term cigarette smoking would influence steady state or pulsatile hemodynamics at a preclinical stage.We analyzed intraarterial brachial artery waveforms in 35 healthy long-term cigarette smokers and 32 nonsmoking control subjects matched for age and gender. The diastolic pressure decay was segmented into two components: an exponential decay that reflects the compliance characteristics of the large arteries and an oscillatory diastolic waveform generated principally by pulse-wave reflections from small arteries and arterioles.Resting heart rate was higher in smokers than nonsmokers, mean +/- SD (66 +/- 9 versus 60 +/- 10; P0.05). Systolic, diastolic, and mean arterial pressures were lower in smokers compared with nonsmokers (P0.01 for all). No differences in cardiac output, large artery compliance, or systemic vascular resistance estimates where apparent between groups. A decrease in the amplitude and duration of the diastolic wave, produced by peripheral pulse-wave reflections in the arterial system, was found in smokers compared with nonsmokers (0.04 +/- 0.02 versus 0.7 +/- 0.03; P0.001).Quantitative changes in the arterial waveform were found in long-term smokers compared with nonsmoking control subjects. The altered arterial wave shape marks the presence of abnormal structure or tone in the peripheral vasculature that affects pulsatile arterial function. This measure of vascular injury is detectable at a preclinical stage and may relate to the subsequent risk of morbid events in chronic smokers and aid in clinical risk stratification.

Endothelial injury is a central feature of vascular disease induced by cigarette smoking and may act as a precursor for future atherosclerosis. Using forearm occlusion plethysmography, we studied the vascular responses to methacholine (an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator) infused into the brachial artery of 35 long-term cigarette smokers and 16 nonsmoking subjects. NG-monomethyl-L-arginine (L-NMMA), a stereospecific inhibitor of nitric oxide production, was used to inhibit synthesis of nitric oxide in the endothelium. The reactive hyperemic response at peak and during recovery to the temporary interruption of forearm blood flow was also compared between groups. Smokers had elevated carboxyhemoglobin levels compared with nonsmokers (5.1 +/- 2.1% vs 0.8 +/- 0.4%; p0.001). No differences were found in the peak or late hyperemic responses between groups. In smokers, the incremental infusions of methacholine and sodium nitroprusside increased forearm blood flow from 3.6 +/- 1.2 to 12.9 +/- 9.0 ml.min-1 x 100 ml-1 and from 4.0 +/- 1.5 to 9.3 +/- 4.0 ml.min-1 x 100 ml-1, respectively, compared with 3.2 +/- 1.0 to 13.5 +/- 5.6 ml.min-1 x 100 mL-1 and from 2.9 +/- 0.7 to 8.6 +/- 4.2 ml.min-1 x 100 ml-1 in nonsmoking subjects (p = NS). L-NMMA (4 mumol/min for 5 minutes) significantly reduced forearm blood flow in both smokers and nonsmokers from 4.1 +/- 1.4 to 3.4 +/- 1.2 ml.min-1 x 100 ml-1 and 3.8 +/- 0.7 to 2.3 +/- 0.5 mL.min-1 x 100 ml-1, respectively (p0.01 for both); and the decrement in forearm blood flow in nonsmokers was significantly greater than that recorded in smoking subjects (p0.05). In this study, long-term cigarette smokers exhibited an impairment in basal, but not stimulated, nitric oxide-mediated vasodilation.

Although previous studies have suggested that aging results in an increase in vascular stiffness, diseases that increase in prevalence with advanced age may have confounded the results of some of this past research. The purpose of this investigation was to determine whether aging per se results in reduced arterial compliance by using animals that are resistant to atherosclerosis and do not develop hypertension or hyperlipidemias with advanced age. We evaluated systemic and regional (femoral) arterial compliance in older (110 ± 8 months old) and in younger (27 ± 2 months old) female beagle dogs by using a computer-based assessment of the diastolic decay of arterial pressure waveforms and a modified Windkessel model of the circulation. Although systemic arterial pressure was very similar in both age groups, cardiac output was 29% lower ( p = 0.03) and systemic vascular resistance was 24% higher ( p = 0.02) in the older dogs. Moreover, there was an age-related reduction in systemic arterial compliance, derived both from the exponential decay in the arterial pulse (C 1 ) ( p = 0.05) and that derived from the oscillatory component of the diastolic pulse wave (C 2 ) ( p = 0.04). By contrast, although femoral vascular resistance was 25% higher in the older dogs ( p = 0.04), regional (femoral) vascular compliance measured after femoral arterial occlusion was also 25% reduced but was not significantly changed with age ( p = 0.14). These results demonstrate that systemic arterial compliance is reduced with age in dogs, extending this finding to animals without age-related diseases that frequently occur in older human beings. Regional compliance, evaluated in the isolated femoral vascular bed, also tends to be reduced with age, but variability in this parameter in dogs reduces the significance of this finding.

Abstract A noninvasive technique has been developed and validated for calculating capacitive and oscillatory systemic arterial compliance with the use of pulse wave analysis and a modified Windkessel model. Application of the technique to subjects with hypertension, postmenopausal women with symptomatic coronary artery disease, and appropriate control subjects has confirmed a reduction of oscillatory compliance in the disease states and an increase in capacitive and oscillatory compliances in response to vasodilator drugs. This method should be useful in screening subjects for early evidence of vascular disease and in monitoring the response to therapy.

To evaluate the effects of cigarette smoking on endothelial function, we examined forearm vascular responses to the intra-brachial infusion of methacholine (MC), NG-monomethyl-L-arginine (L-NMMA) and sodium nitroprusside (SN) in 36 smokers (S) and 11 non-smoking (NS) control subjects. Values are presented as means ± standard deviation. The mean age of S (42 ± 7 years) was similar to NS (43 ± 11 years). Blood glucose, total and HDLcholesterol and serum fibrinogen concentrations were not different between groups. S had elevated carboxyhemoglobin levels compared with NS (5.1 ± 2.5% vs, 1.1 ± 0.3%, P l 0.001). The incremental infusions of MC increased forearm blood flow (FBF) (ml/100 ml/min) from 3.6 ± 1.2 to 12.7 ± 8.9 in S and from 3.1 ± 0.8 to 14.7 ± 7.5 in NS (p = NS). SN increased FBF (ml/100 ml/min) ml/min) from 3.7 ± 1.4 to 9.0 ± 4.7 in S and from 2.8 ± 0.3 to 8.4 ± 47 in NS (p = NS). L-NMMA reduced FBF (m11100 mllmin) more (p = 0.03) in NS (3.9 ± 0.5 to 2.2 ± 0.7) than in S (4.1 ± 1.5 to 3.3 ± 1.2) but did not attenuate the dose response curves to MC infusion in either group. Conclusion Chronic cigarette smoking appears to impair basal but not stimulated release of endothelium-derived nitric oxide from the forearm vasculature.