J.William O'Connell

Effects of long-term right ventricular apical pacing on left ventricular perfusion, innervation, function and histology

OBJECTIVES The purpose of this study was to better understand the effects of long-term right ventricular pacing on left ventricular perfusion, innervation, function and histology. BACKGROUND Long-term right ventricular apical pacing is associated with increased congestive heart failure and mortality compared with atrial pacing. The exact mechanism for these changes is unknown. In this study, left ventricular perfusion, sympathetic innervation, function and histologic appearance after long-term pacing were studied in dogs in an attempt to see whether basic changes might be present that might ultimately be associated with the adverse clinical outcome. METHODS A total of 24 dogs were studied. Sixteen underwent radiofrequency ablation of the atrioventricular (AV) junction to produce complete AV block. Seven of these underwent long-term pacing from the right ventricular apex (ventricular paced group), and nine had atrial and right ventricular apical pacing with AV synchrony (dual-chamber paced group). A control group of eight dogs had sham ablations with normal AV conduction. These dogs had atrial pacing only. Regional perfusion and sympathetic innervation were studied in all dogs by imaging with thallium-201 and [I123]metaiodobenzylguanidine, respectively. The degree of innervation was also determined by assay of tissue norepinephrine levels. Left ventricular function was assessed by radionuclide ventriculography. Cardiac histology was studied with both light and electron microscopy. RESULTS Mismatching of perfusion and innervation in the ventricular paced group was noted, with perfusion abnormalities of both the septum and free wall. Regional [I123]metaiodobenzylguanidine distribution was homogeneous. Tissue norepinephrine levels were elevated in both the ventricular and dual-chamber paced groups compared with the control group. No light or electron microscopic findings were noted in any groups. In the dual-chamber paced group, diastolic dysfunction was noted, with normal systolic function. CONCLUSIONS Ventricular pacing resulted in regional changes in tissue perfusion and heterogeneity between perfusion and sympathetic innervation. Both ventricular and dual-chamber pacing were associated with an increase in tissue catecholamine activity. The abnormal activation of the ventricles via right ventricular apical pacing may result in multiple abnormalities of cardiac function, which may ultimately affect clinical outcome.

Potential added value of three-dimensional reconstruction and display of single photon emission computed tomographic gated blood pool images

BackgroundSingle photon emission computed tomographic (SPECT) acquisition provides potential advantages for blood pool imaging. However, the method has been little applied.MethodsAn improved method of three-dimensional (3-D) reconstruction and display of SPECT equilibrium blood pool scintigrams and related phase data was developed. Dynamic slices and volume-rendered dynamic 3-D images were displayed. Images were viewed from each of 34 solid angles referenced to a sphere surrounding the reconstruction field. Each image pixel was “painted” with intensity-coded regional amplitude and color-coded for its phase angle. The method was applied to evaluate the cardiac anatomy, regional contraction, and related conduction sequence at rest in 17 patients. Twelve had normal left ventricular function including 7 patients with minimal septal preexcitation. Five patients had abnormal left ventricular function, including 2 with left bundle branch block.ResultsSlices contained all of the functional information, but necessary data integration was time-consuming and evaluation of chamber size and anatomy was difficult. Three-dimensional projection images condensed and integrated the data, presenting new vantage points on anatomy, contraction, and conduction not otherwise available in the clinically limited angulations of planar images. This provided excellent visual separation of cardiac chambers with full and increased visualization of right and left ventricular wall motion in all segments compared with the conventional projections acquired clinically (p<0.05). Atria and great vessels were well separated with evident size and function. Phase-angle progression paralleled the electrocardiogram, permitting bypass pathway localization and the direct noninvasive localization of posteroseptal pathways.ConclusionsThe 3-D method permits greater access to and utilization of SPECT blood pool image data. It suggests specific advantages for clinical use.

Usefulness of adenosine in augmenting ventricular preexcitation for noninvasive localization of accessory pathways

Adenosine was administered to test the hypothesis that it would maximize preexcitation and facilitate noninvasive localization of accessory pathways in 22 patients with suspected accessory pathway-mediated tachycardias. Twelve-lead electrocardiograms and 2-dimensional echocardiograms were recorded at baseline and during adenosine-augmented ventricular preexcitation to localize the accessory pathway. Phase analysis was performed on digitized 4-chamber and short-axis views using a first harmonic Fourier transformation. At baseline, 15 patients had manifest preexcitation. In 14 of these patients (93.3%), preexcitation became more prominent after adenosine. Four patients without preexcitation at baseline clearly had it after adenosine. In patients who had preexcitation in response to adenosine, the electrocardiogram correctly identified the accessory pathway locations in 18 of 19 patients at a regional level and was incorrect in 1 of 19 patients. Echocardiographic phase analysis correctly identified the accessory pathway location in all 17 patients, who had technically adequate studies, at a regional level. In conclusion, administration of adenosine accentuates preexcitation, allowing for more accurate electrocardiographic and echocardiographic accessory pathway localization.

The scintigraphic characteristics of ventricular pre-excitation through Mahaim fibers with the use of phase analysis.

The phase image pattern of blood pool scintigrams was blindly assessed in 11 patients exhibiting conduction through Mahaim pathways, including 6 nodoventricular and 5 fasciculoventricular. These patterns were compared with the phase image findings in normal subjects, patients with left and right bundle branch block in the absence of pre-excitation and patients with pre-excitation through atrioventricular (AV) connections. In all patients with a Mahaim pathway, the site of earliest phase angle was septal or paraseptal. Phase progression was asymmetric and the pre-excited ventricle demonstrated the earliest mean ventricular phase angle in 10 of 11 patients. This pattern, and the associated ventricular phase difference, appeared to vary from that in normal subjects and in those with a septal AV connection, in whom phase progression is generally symmetric. Scintigraphic phase analysis provided localizing information and presented patterns consistent with Mahaim pathways. Although not able to differentiate among Mahaim pathway subtypes, these phase patterns differed from those in normal subjects, those with right and left lateral free wall pathways and most patients with a septal AV pathway. However, the phase pattern of patients with a Mahaim pathway may not differ from that of patients with a septal AV connection displaying an asymmetric pattern of phase progression, or those with left and right bundle branch block in the absence of pre-excitation. Objective, yet imperfect phase measurements supported these differences. Such image findings may complement the often complex electrophysiologic evaluation of patients presenting with pre-excitation.

Assessment of perfused left ventricular mass in normal, ischemic, and reperfused myocardium by means of single-photon emission computed tomography of technetium-99m isonitrile.

To test the hypothesis that single-photon emission tomography of technetium (Tc) 99m hexakis 2-methoxyisobutyl isonitrile (Tc-MIBI) can accurately measure perfused left ventricular (LV) mass in nonischemic, ischemic, and reperfused myocardium, we acquired Tc-MIBI tomographic images in canines with normally perfused hearts (n = 33) after occlusion of the left anterior descending coronary artery (n = 15), after reperfusion (n = 13), and with subsequent second injection of Tc-MIBI (15 to 18 mCi; n = 12). In all ischemic studies the initial dose of Tc-MIBI (5 to 6 mCi) was injected after coronary artery occlusion but before reflow. Scintigraphic perfused LV mass was calculated from the total voxels demonstrating Tc-MIBI uptake x voxel volume (cm3) x specific gravity of myocardium (1.05 gm/cm3). After being imaged the animals were killed, the left ventricle was weighed, and the risk area was determined by dual perfusion with phthalocyanine blue dye and triphenyltetrazolium chloride (TTC). Perfused LV mass was defined as total LV mass minus the risk area mass. There was good correlation between scintigraphic and morphologic determinations of perfused left ventricular mass in nonischemic hearts (Tc-MIBI left ventricular distribution = 0.84 x left ventricular weight + .20.4, n = 33, r = 0.93, p = 0.0001) and ischemic hearts (Tc-MIBI left ventricular distribution = 0.51 x left ventricular weight + 37.9, n = 15, r = 0.83, p = 0.0001). In animals imaged both before and after reperfusion, scintigraphic determinations of the nonischemic region correlated closely (after-reflow Tc-MIBI distribution = 1.07 x before-reflow Tc-MIBI distribution--8.0, n = 13, r = 0.88, p = 0.0001), indicating that Tc-MIBI does not significantly redistribute into the ischemic zone after reperfusion. After injection of the second dose of Tc-MIBI in acutely reperfused canines, there was good correlation between the distribution mass of Tc-MIBI and the mass of viable myocardium by TTC staining (Tc-MIBI distribution = 0.61 x viable LV mass + 34.2, n = 12, r = 0.77, p = 0.0001). Furthermore, the apparent redistribution of myocardial Tc-MIBI from before and after second injection images correlated with the degree of myocardial salvage by histochemical staining (r = 0.72, p = 0.0082). In conclusion, single-photon emission computed tomography of Tc-MIBI can measure perfused LV mass accurately in both ischemic and nonischemic canine preparations.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiac activation mapping by MRI

To establish cardiac MRI as a tool for noninvasive evaluation of activation patterns, 10 healthy volunteers were examined by cine segmented turboFLASH imaging sequences. Sequence modifications for low signal blood-pool appearance were applied, i.e., bilateral spatial saturation for segmented turboFLASH imaging. Pixelwise calculation of first-harmonic Fourier phase values (displayed as color-encoded maps) reveal either anterior septal or left ventricular free-wall sites as areas of earliest phase spreading towards posterior paraseptal sites in segmented turboFLASH scans. Phase scatter is lower in unsaturated than spatially presaturated segmented turboFLASH studies. Phase standard deviation in areas of endocardial displacement is higher in basal than apical slice positions in these scans. Early results indicate that first-harmonic Fourier phase analysis of cardiac-segmented turboFLASH MRI cine studies may provide a tool for noninvasive studies of cardiac activation sequence.