Arrhythmia discrimination using hemoglobin spectroscopy in humans.

BACKGROUND: Inappropriate therapies are frequently delivered by implantable cardioverter-defibrillators (ICDs). We have investigated muscle perfusion as a means of augmenting arrhythmia discrimination by using implanted near-infrared spectroscopy. OBJECTIVE: To evaluate hemodynamic stability by monitoring muscle perfusion from within the ICD pocket, in fresh tissue and inside the scar capsule on preexisting ICD generators, during induced cardiac arrhythmias, in humans. METHODS: The sensor was implanted on or under the pectoral muscle, during ICD defibrillation threshold testing. A microvascular oxygenation trend indicator (O2 Index) was computed during 74 induced ventricular fibrillation and 34 normal sinus rhythm episodes in 34 patients and also during 28 atrial and 90 ventricular overdrive pacing episodes as simulations of supraventricular and ventricular tachycardias, respectively. RESULTS: On average, the change in oxygenation, based on the O2 Index, was statistically significant (P <.003) from baseline within 3 seconds following cardiac arrest. An optimized O2 Index, used for detecting the hemodynamic trend, exhibited a decreasing trend during ventricular fibrillation (P <.0001) and was different from that during normal sinus rhythm (P <.0001). The sensitivity for the detection of ventricular fibrillation was 100%, and the specificity for the rejection of normal sinus rhythm was 82% in the presence of scar tissue on the optical sensor. For a 35-mm Hg drop in the mean arterial pressure as the threshold for hemodynamic instability, the specificity for the rejection of hemodynamically stable atrial and ventricular pacing episodes was 93% and 71%, respectively. CONCLUSION: An implantable near-infrared spectroscopic sensor may be useful for hemodynamic monitoring during cardiac arrhythmias to prevent inappropriate therapy.

Intracardiac shunts resulting from transseptal catheterization for ablation of accessory pathways in otherwise normal hearts.

In a series of 14 patients undergoing transseptal catheterization for ablation of left-sided accessory pathways, hydrogen appearance time was used to detect left-to-right shunting after removal of the catheter. Six of the 12 patients who had no evidence of shunt before catheterization had evidence of shunting after the procedure.

Ablation of ventricular tachycardia associated with tetralogy of Fallot: demonstration of bidirectional block.

INTRODUCTION: Ventricular tachycardia is commonly seen in patients following surgical repair for tetralogy of Fallot. The technique of ablation for this arrhythmia is not well defined. METHODS AND RESULTS: In two patients with ventricular tachycardia following surgical repair of tetralogy of Fallot, the traditional indicators for a site for ventricular tachycardia ablation did not yield cure. Based on careful mapping, the circuit was found to involve the isthmus between the outflow tract patch and the tricuspid annulus; linear radiofrequency lesions across this isthmus resulted in cure of ventricular tachycardia. Not only was the tachycardia no longer inducible, but bidirectional block at the line of ablation confirmed interruption of the reentrant circuit. CONCLUSION: A linear radiofrequency lesion was effective in eliminating ventricular tachycardia in both patients. The demonstration of bidirectional block confirms a cure independent of inducibility of ventricular tachycardia.

Determinants of nonthoracotomy biphasic defibrillation.

The clinical variables affecting DFT for ICD systems are not completely determined, especially with regard to biphasic shocking devices. To distinguish which factors correlate with DFT, we examined data from patients who were enrolled in the Ventak P2/Endotak protocol. A total of 284 patients were enrolled in the study. Two patients had a DFT > 25 J and did not receive the device; 154 did not undergo stepdown to failure DFT testing. The remaining 128 patients had formal DFT testing and were suitable for analysis. Variables available for analysis included age, body surface area (BSA), LVEF, gender, lead configuration, primary arrhythmia, primary cardiac disease, and use of cardioactive medication. Data were evaluated using regression analysis, fitting DFT (range, 1-25 J, mean 11 +/- 5 J) as a function of each variable. As a univariate predictor. BSA was found to be significant in predicting DFT, but accounted for only 9% of the total variation on the DFT (P < 0.01, r = 0.3). This study suggests that DFT using a biphasic shocking waveform is modestly in fluenced by the BSA of the patient. Other specific factors, including LVEF, do not predict DFT.

Selective radiofrequency ablation of the "slow" atrioventricular nodal pathway for control of the ventricular response to atrial fibrillation.

In summary, this study reports 2 important findings: (1) AV nodal modification using the conservative protocol we describe reduces long-term success for ventricular rate control during atrial fibrillation but eliminates the incidence of permanent AV block; (2) directed lesions that eliminate clinical AV nodal reentry slow ventricular response to acute atrial fibrillation but are not sufficient to control ventricular response of chronic atrial fibrillation. Further refinement of these techniques may allow an optimal balance between rate control and avoidance of permanent pacing.

Effect of biphasic endocardial countershock on pacing thresholds in humans.

The use of non-thoracotomy endocardial implantable defibrillators with pacing capabilities has increased substantially over the past 2 years. This report demonstrates that the pacing threshold increases in some patients after endocardial defibrillation, and substantiates the practice of using maximal pacing output after endocardial defibrillation.

Diagnosis of ICD lead failure using continuous event marker recording.

Stored electrograms enhance the ability to evaluate therapy episodes in the third-generation implantable cardioverter defibrillator. These electrograms are recorded from either the shocking or rate sensing leads, but not both. As a result, differentiation of certain types of sensing abnormalities may be difficult prior to surgical exploration. We present a case of rate sensing lead failure due to an insulation break. Several minutes of recording of the event marker in the laboratory failed to document any abnormal sensing; the diagnosis was made by recording the event marker on a 24-hour continuous (Holter) monitor. The Holter monitor/event marker combination was of substantial diagnostic value and allowed for a more focused surgical evaluation and treatment.

Relations of the myocardial imaging agents 99mTc-MIBI and 201T1 to myocardial blood flow in a canine model of myocardial ischemic insult.

Myocardial imaging with thallium 201 has proven to be an important clinical procedure to assess the severity of the myocardial ischemic insult. Uptake of 201Tl is related to perfusion to and extraction by intact myocardium. Recently, a newer group of agents based on 99mTc alkyl isonitriles has been developed and appears promising for myocardial imaging. Although the distribution of this new agent has been shown to be related to myocardial perfusion, its dependence on myocardial integrity has not been established. This study compared the distribution of 99mTc-2-methoxy-isobutyl-isonitrile (99mTc-MIBI) with that of 201Tl in a clinically relevant canine model of ischemic insult. Fifteen adult dogs underwent 2 hours of occlusion by left anterior descending coronary artery ligation followed by reperfusion. In one group of dogs, 201Tl and 99mTc-MIBI were administered 5 minutes before 35 minutes of reflow (group 1, n = 5). In the other animals, the agents were given 5 minutes after onset of reflow, and dogs were killed after 10 (group 2, n = 5) and 35 minutes of reperfusion (group 3, n = 5). 99mTc-MIBI activity was significantly correlated with 201Tl activity (r = 0.91, 0.77, and 0.92, for groups 1, 2, and 3, respectively). Both 201Tl and 99mTc-MIBI activities were correlated similarly with blood flow in all models. In groups 1 and 2, 201Tl and 99mTc-MIBI activities correlated directly with microsphere-determined blood flow, whereas in group 3, they correlated inversely. The present study shows that in these models of myocardial ischemic insult, 99mTc-MIBI distribution is closely related to that of 201Tl.

Demonstration of increased myocardial lipid with postischemic dysfunction ("myocardial stunning") by proton nuclear magnetic resonance spectroscopy.

Histopathologic studies have demonstrated accumulation of lipid droplets in myocardium subjected to greater than or equal to 6 h of ischemic insult. Proton nuclear magnetic resonance (NMR) spectroscopy can provide a noninvasive means to evaluate changes in tissue lipid and, potentially, to characterize the ischemic insult. To determine whether lipids accumulate with a brief ischemic insult, myocardial lipid content was evaluated by 1H NMR spectroscopy of ex-vivo samples from seven dogs in a model of postischemic dysfunction created by 15 min of left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Regional myocardial function was assessed by measuring segment length shortening with use of a pair of ultrasonic crystals placed in the ischemic zone and in the control zone. During the occlusion, all dogs had significant ischemia of the occlusion zone as measured by radiolabeled microspheres (0.08 +/- 0.08 versus 0.88 +/- 0.09 ml/g per min for the control zone), and all dogs developed systolic stretching of the ischemic zone segment. Myocardial lipid content was significantly elevated in the samples from the coronary occlusion zone (p less than 0.02). The increase in lipid signal may result from the ischemia-induced decrease in beta oxidation and resultant accumulation of fatty acyl esters (for example, fatty acids, triglycerides and acylcarnitines). In conclusion, this study shows that myocardium subjected to a brief (approximately 15 min) coronary occlusion followed by 3 h of reperfusion demonstrates a significant increase in NMR-detectable lipid content.

Acute effects of exercise on MR imaging of skeletal muscle in normal volunteers.

Exercise is known to produce changes in the amount and distribution of water in skeletal muscle. Because MR imaging is highly sensitive to changes in water distribution, these changes should be detectable under appropriate imaging conditions. Imaging of the forearms and/or legs was performed in 16 volunteers at 0.35 T, before and after exercise. Exercises included finger flexion and extension, wrist flexion, ankle plantar flexion, and great toe extension. In the case of handgrip exercise, the level of exertion was quantitated. Individual muscles were frequently indistinguishable on preexercise scans. After exercise, active and inactive muscles could be clearly distinguished. For example, in the flexor digitorum profundus, finger flexion resulted in an increase in the image-derived estimate of T1 (T1 postexercise was 1037 +/- 162 msec vs T1 preexercise of 590 +/- 49 msec, p less than .001). T2 also increased (T2 postexercise was 35 +/- 2 msec vs T2 preexercise of 28 +/- 1 msec, p less than .001). Relative spin density also increased (p less than .001). T1, T2, and spin density subsequently decreased with time but were still increased above baseline at 10 min postexercise (p less than .005). Signal changes correlated moderately with the level of exertion (r = .63) and fatigue (r = .45). Vascular occlusion did not prevent intensity changes. Thus, changes in skeletal muscle MR signal intensity occur with exercise and appear to parallel known alterations in water distribution.

Proton nuclear magnetic resonance relaxation times in severe myocardial ischemia.

Contrast produced by differences in regional proton relaxation times (T1 and T2) provides the potential to assess the extent of myocardial infarction using nuclear magnetic resonance (NMR) imaging. Previous laboratory studies have shown that longitudinal (T1) and transverse (T2) relaxation times are prolonged in acute myocardial infarction, and these prolongations have been attributed entirely to increases in tissue water content. The present study seeks to evaluate the relation between both T1 and T2 and regional myocardial perfusion and water content throughout a wide range of blood flow reduction. The left anterior descending coronary artery and collateral vessels supplying a region of the anterior wall of the left ventricle were ligated in 10 dogs for 4 hours until they were killed. Both water proton and bulk proton relaxation times of myocardial samples from ischemic and control zones were measured at 200 and 20 MHz, respectively. Regions of severe ischemia (flow less than 5% of control) demonstrated no significant alteration in T1 compared with nonischemic myocardium. Greatest T1 and T2 elevations were observed in moderately ischemic myocardium (flow = 5 to 50% of control). The water relaxation behavior differed with the severity of the flow reduction and was not totally dependent on changes in water content. These data suggest that relaxation time alterations are more complex than previously reported in myocardial ischemic insult. In the future, using T1 weighted imaging methods, myocardial ischemic insults associated with severe reductions in blood flow would be anticipated to demonstrate a doughnut pattern with an area of abnormal intensity in the peripheral zone surrounding a central ischemic zone with normal intensity.

Proton NMR spectroscopy in myocardial ischemic insult.

Proton NMR methods can monitor mobile lipids (e.g., fatty acids and glycerides) in intact tissue. Lipids play a major role in cardiac energy production, and elevated levels of myocardial lipids have been reported following an ischemic insult. The present study examines the potential of high-resolution 1H NMR spectroscopy to monitor lipid alterations 24 h following coronary occlusion in dogs, and to correlate these finds with regional myocardial blood flow (RMBF) measured by radiolabeled microspheres. The dogs were killed, and samples of excised myocardium were studied by high-resolution 1H NMR spectroscopic analysis using solvent suppression in combination with the Hahn spin-echo pulse sequence. Mobile lipids levels in myocardium with moderate blood flow reduction (28.6 +/- 7, integral values, arbitrary units; flow 5-50% of control) were significantly elevated compared to the mobile lipid levels in control myocardium (5.3 +/- 8, P less than 0.001) and in myocardium with severe flow reduction (7.2 +/- 10, P less than 0.001; flow less than 5% of control). The mobile lipids in myocardium with severe flow reduction were not elevated significantly relative to control tissue. As anticipated, depression in the level of creatine paralleled the microsphere determined degree of ischemia, i.e., compared to control (9.0 +/- 3); creatine levels were moderately decreased with flows 5-50% of control (5.5 +/- 4, P less than 0.001) and markedly decreased with flows less than 5% of control (1.0 +/- 2, P less than 0.001). This study suggests that high-resolution 1H NMR spectroscopy may be used to evaluate alterations in myocardial lipid levels following an ischemic insult.(ABSTRACT TRUNCATED AT 250 WORDS)

Adriamycin cardiotoxicity and proton nuclear magnetic resonance relaxation properties.

Present noninvasive techniques to detect Adriamycin (doxorubicin) cardiotoxicity rely on assessment of myocardial function rather than direct observation of change in tissue character. Proton nuclear magnetic resonance imaging may provide a unique means of characterizing the myocardium. The relaxation properties T1 and T2 are related to certain biophysical properties of tissue such as water, lipid, and macromolecular content and have considerable impact on the intensity observed in nuclear magnetic resonance images. In a model of chronic Adriamycin cardiotoxicity in rats, T1 values of excised hearts were elevated, relative to control, in rats with histologic evidence of chronic cardiotoxicity (651 msec vs 622 msec, p less than 0.05) and more so in rats with gross evidence of toxicity or heart failure (668 msec, p less than 0.005). No significant change in T2 was observed. This T1 prolongation increases as disease worsens, whereas water concentration did not change significantly. The results suggest that predictable prolongation in T1 occurs in association with cardiotoxicity. In conclusion, proton nuclear magnetic resonance imaging methods could provide a new means for assessing Adriamycin cardiotoxicity.

Monitoring the bioenergetics of cardiac allograft rejection using in vivo P-31 nuclear magnetic resonance spectroscopy.

Monitoring human cardiac allograft rejection is currently accomplished by endomyocardial biopsy. Available noninvasive methods for identifying rejection have lacked the necessary sensitivity or specificity, or both, for routine clinical application. In vivo phosphorus-31 (P-31) nuclear magnetic resonance (NMR) spectroscopy has been used for monitoring phosphorus metabolism in both animal models and humans. In the present study this technique was employed as a noninvasive means to assess the bioenergetic processes that occur during cardiac allograft rejection in a rat model. Brown Norway rat hearts were transplanted subcutaneously into the anterior region of the neck of Lewis rat recipients (allografts). Control isografts employed Lewis donors and recipients. Phosphocreatine to inorganic phosphate (PCr/Pi), phosphocreatine to beta-adenosine triphosphate (PCr/ATP beta), beta-adenosine triphosphate to inorganic phosphate (ATP beta/Pi) ratios and pH of the transplanted hearts were monitored using surface coil P-31 NMR spectroscopy (at 4.7 tesla) daily for 7 days. To allow recovery from the compromise induced by the surgical procedure, the measurements obtained on day 2 were taken as a baseline. PCr/Pi was unchanged or increased in the isografts but decreased continually in allografts, with the difference becoming significant by day 4 when compared with levels in day 2 allografts (p less than 0.005) and by day 3 when compared with levels in the isograft group (p less than 0.05). PCr/ATP beta in isografts did not change throughout the study; however, allografts demonstrated a significant decrease as early as day 3 (p less than 0.01), although a significant difference between isografts and allografts did not become manifest until day 4 (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)