Autonomic Denervation After the Maze Procedure

LÖNNERHOLM, S., et al .: Autonomic Denervation After the Maze Procedure. The Maze III procedure is a surgical operation for curative treatment of AF. The procedure is extensive, however, with multiple incisions in both atria, and its effects on autonomic regulation of the heart rhythm are not known. This study comprises 17 patients, 10 with paroxysmal AF and 7 with chronic AF, who had no concurrent cardiac disease known to affect heart rate variability (HRV). A 24-hour Holter recording was performed preoperatively and 2 months (early) and 7 months (late) after surgery, for analysis of HRV in the time and frequency domains. Early after the Maze procedure all HRV components were markedly reduced compared to baseline (mean ± 1 SD): SDNN   73 ± 13   versus   148 ± 50   (ms), total power   168 ± 126   versus   560 ± 1567   (ms²), low frequency (LF) power   47 ± 67   versus   826 ± 677   (ms²), high frequency (HF) power   47 ± 40   versus   678 ± 666   (ms²), and LF:HF   1.22 ± 0.9   versus   2.55 ± 1.4   . Late after the Maze procedure all variables were still reduced. Only total power increased significantly between early and late follow-up (   168 ± 126   vs   496 ± 435   ms²). Late after Maze surgery, values of the different HRV components did not differ between the patients with paroxysmal AF and chronic AF. Early after the Maze procedure there is a marked decrease of all HRV components, which is maintained 7 months after surgery, a pattern consistent with denervation of the heart. (PACE 2003; 26[Pt. I]:587–592)     

Mathematical Descriptions of AV Nodal Function Curves in Dogs

Thirty-four anaestheized mongrel dogs subjected to thoracotomy were used to study AV node conduction during atrial pacing at increasing rates. Eplcardial atrial electrodes were used, together with endocavitary recordings of His bundle electrogram. An analysis was made of the repercussions involved in using four different mathematical functions describing nodal conduction; three were nonlinear (exponential and hyperbolic A and B) and one linear. In the case of the first three, the consequences of using a direct nonlinear data-fitting procedure or an indirect procedure by linear transformations of the functions were studied. The exponential and hyperbolic B functions provided the least mean squared residual in quantifying nodal conduction (8.6 ± 10.8 ms² and 10.8 ± 13.9 ms², respectively). The use of nonlinear function transformation into a linear representation caused Joss of precision in the fit to the data in the case of the exponential function (18.3 ± 22.2 ms² versus 8.Q ± 10.8 ms², p < 0.01] and, to a lesser extent, in the case of the hyperbolic B function [12.5 ± 16.4 ms² versus 10.8 ± 13.9 ms², P < 0.05).     

Variable Effects of Physical Training of Heart Rate Variability, Heart Rate Recovery, and Heart Rate Turbulence in Chronic Heart Failure

Background: Heart rate variability (HRV), heart rate turbulence (HRT), and heart rate recovery (HRR), indices that reflect autonomic nervous system (ANS) activity, are outcome predictors in patients with chronic heart failure (CHF). It is not clear, however, whether they reflect the same components of ANS activity. No study has examined the effects of physical training (PT) training on HRV, HRT, and HRR in CHF.
Study Objective: To examine the responses of HRV, HRT, and HRR to a PT program in patients presenting with CHF.
Methods: In 41 patients (mean age = 58.7 ± 10.2 years) in New York Heart Association CHF functional classes II or III, and with a left ventricular ejection fraction <40%, HRV, HRT, and HRR were measured before and after 8 weeks of PT.
Results: The training was clinically effective in all patients. Before versus after PT, standard deviation of all normal RR intervals increased from 107 ± 30 to 114 ± 32 ms (P = 0.047), high frequency increased from 210 ± 227 to 414 ± 586 ms²/Hz (P = 0.02), and the low/high frequency ratio decreased from 1.8 ± 1.55 to 1.1 ± 1.2 (P = 0.002). HRT and HRR did not change significantly after PT.
Conclusions: In patients with CHF, the positive effects of PT were limited to HRV indices, which reflect parasympathetic activity, without significantly changing HRR and HRT. These observations indicate that different mechanisms modulate HRV, HRR, and HRT, which provide complementary information regarding ANS activity. The 8-week PT program failed to completely normalize ANS function.     

Evaluation of Direct Respiratory Modulation of the QT Interval Variability

To investigate the direct respiration-mediated vagal modulation of the QT interval variability, spectral analyses of the RTp interval (from the R wave peak to the T wave peak) variability (RTpV) and the RR interval variability (RRV) were performed in 12 subjects with normal ventricular repolarization under three conditions while the respiration frequency was kept at 0.2 Hz: during sinus rhythm, during fixed atrial pacing, and during fixed atrial pacing with autonomic blockade. The cross-spectrum between the RRV and RTpV was quantified by the squared coherence. During sinus rhythm the RRV power spectrum showed two peaks: a broad peak in the low frequency (LF) band and a sharp peak at 0.2 Hz which corresponded to the controlled respiration frequency. The RTpV power spectrum showed corresponding peaks to the RRV peaks in both the LF and high frequency (HF) bands with high coherence (mean maximum values of the squared coherence in the LF band 0.59 ± 0.22, and in the HF band 0.74 ± 0.14). During atrial pacing mean total power of the RTpV decreased from during sinus rhythm (from 16.3 ± 5.6 ms² to 12.9 ± 5.4 ms², P < 0.05) and the RTpV spectral peaks were abolished in both the LF and HF bands concordant with disappearance of the RRV peaks. Autonomic blockade gave no additional change to the RTpV power spectrum independently of the RRV during fixed atrial pacing. The present study suggested that the direct respiration-mediated vagal modulation may not affect the short-term variability of the QT interval in subjects without repolarization abnormality.     

Early Afterdepolarizationlike Activity in Patients with Class IA Induced Long QT Syndrome and Torsades de Pointes

Early afterdepolarizations (EADs) have been linked to the mechanism of torsades de pointes in long QT syndrome. The purpose of this study was to investigate the role of EADs in Class IA induced torsades de pointes. We studied nine patients with Class IA induced torsades de pointes at the time this arrhythmia was present (acute period, n = 7) and after Class IA therapy was discontinued (chronic period, n = 6). ECCs and monophasic action potentials were recorded in both periods. In the chronic period, electrophysiological studies were performed before and after disopyramide infusion. In the acute period, QT_c interval was markedly prolonged (655 ± 32 ms^1/2), and EAD-like activity was recorded in all patients. QT_c interval returned to normal (428 ± 45 ms^1/2) and EAD-like activity disappeared after discontinuation of IA drug. Although, in the chronic period, disopyramide infusion prolonged QT_c interval from 428 ± 48 ms^1/2 to 479 ± 31 ms^1/2 and induced EAD in three of six patients, the degree was not as marked as observed in the acute period. EADs may play an important role in the genesis of long QT and torsades de pointes. Disopyramide infusion in the chronic period could not reproduce marked repolarization ahnormalities and torsades de pointes.     

Time course of effects of cardiac resynchronization therapy in chronic heart failure: benefits in patients with preserved exercise capacity

Objectives: To assess in patients with chronic heart failure the effect of cardiac resynchronization therapy (CRT) over 12 months' follow-up the time course of the changes in functional and neurohormonal indices and to identify responders to CRT.
Methods: Eighty-nine patients (74.1 ± 1 years, left ventricular ejection fraction [LVEF] < 35%), QRS complex duration >150 ms, in stable New York Heart Association (NYHA) class III or IV on optimal medical treatment were prospectively randomized either in a control (n = 45) or CRT (n = 44) group and underwent clinical evaluation, cardiopulmonary exercise testing (CPET), 2D-Echo, heart rate variability (HRV), carotid baroreflex (BRS), and BNP assessments before and at 6- and 12-month follow-up.
Results: In the CRT group, improvement of cardiac indices and BNP concentration were evident at medium term (over 6 months) follow-up, and these changes persisted on a longer term (12 months) (all P < 0.05). Instead CPET indices and NYHA class improved after 12 months associated with restoration of HRV and BRS (all P < 0.05). We identified 26 responders to CRT according to changes in LVEF and diameters. Responders presented less depressed hemodynamic (LVEF 25 ± 1.0 vs 22 ± 0.1%), functional (peak VO₂ 10.2 ± 0.2 vs 6.9 ± 0.3 ml/kg/min), and neurohormonal indices (HRV 203.6 ± 15.7 vs 147.6 ± 10.ms, BRS 4.9 ± 0.2 vs 3.6 ± 0.3 ms/mmHg) (all P < 0.05). In the multivariate analysis, peak VO₂ was the strongest predictor of responders.
Conclusions: Improvement in functional status is associated with restoration of neurohormonal reflex control at medium term. Less depressed functional status (peak VO₂) was the strongest predictor of responders to CRT.     

Abnormal Nocturnal Heart Rate Variability and QT Dynamics in Patients with Brugada Syndrome

Background: In Brugada syndrome (BSY), most of the ventricular arrhythmic events are nocturnal, suggesting an influence of the autonomic nervous system.
Methods: In 46 patients (mean age = 41 ± 14 years, 43 men) with electrocardiograms (ECG) consistent with BSY and structurally normal hearts, we measured heart rate variability (HRV) and QT dynamics (QT/RR slopes) on 24-hour ambulatory ECG. Type 1 BSY-ECG was spontaneous in 23 (50%) and induced in 23 patients.
Results: History of syncope was present in 23 patients (50%). Programmed ventricular stimulation induced ventricular tachyarrhythmias (VTA) in 13 patients (28%). A single patient developed ventricular tachycardia during a mean follow-up of 34 months. Compared to a control group matched for age and sex, HRV was decreased over 24 hours and during nighttime in patients with BSY (SDNN 122 ± 44 vs 93 ± 36 ms, P = 0.0008 and SDANN 88 ± 39 vs 54 ± 24 ms, P < 0.0001). QTend /RR slopes were decreased over 24 hours in patients with BSY (0.159 ± 0.05 vs 0.127 ± 0.05, P = 0.003) and particularly at night (0.123 ± 0.04 vs 0.089 ± 0.04, P = 0.0001). QTend /RR slopes were significantly decreased during nighttime in patients with spontaneous versus provoked BSY-ECG patterns. By contrast, HRV and QT/RR slopes were similar in symptomatic and asymptomatic patients, whether VTA were induced or not.
Conclusions: Patients with a BSY-ECG pattern had lower HRV and QT/RR slopes than control subjects during nighttime. High-risk patients with spontaneous BSY-ECG patterns had the lowest nocturnal QTend/RR slopes. These unique repolarization dynamics might be related to the frequent nocturnal occurrence of VTA in BSY.     

The effects of ryanodine on calcium uptake by the sarcoplasmic reticulum of ischemic and reperfused rat myocardium

Summary— The effects of ischemia and reperfusion on sarcoplasmic reticulum (SR) calcium uptake were measured in crude heart homogenates of rats and were compared to published results for rabbit hearts. Isolated rat hearts ( n = 5 in each group) were Langendorff-perfused at 37 °C and were either kept normally perfused (control group), or submitted to 15 min normothermic ischemia (ischemic group), or reperfused for 10 min after 15 min ischemia (reperfused group). Mechanical function recovered to 50–60% of control after 10 min reperfusion following ischemia. Ca uptake (control V_max; 23.0 ± 2.20 nmol·min⁻¹·mg of protein⁻¹) decreased during ischemia (V_max: 15.7 ± 1.60 nmol·min⁻¹·mg⁻¹) but recovered to control level on reperfusion (V_max: 20.8 ± 2.02 nmol·min⁻¹·mg⁻¹). An increased Ca uptake was obtained when the measurements were carried out in the presence of ryanodine (430 μM) to block Ca leakage through SR Ca-release channels. The relative magnitude of ryanodine effect in the ischemic myocardium (increase: 77.2 ± 18.20%) was more marked than in control (32.0 ± 8.22%) or reperfused myocardium (39.0 ± 10.66%). This result is different from that of rabbit myocardium where similar ryanodine effect is present in all groups (56.7 ± 13.76%, 50.0 ± 13.56% and 54.2 ± 6.88% in control, ischemic and reperfused hearts, respectively) and suggests that a component of cytosolic Ca overload via SR Ca-release channels is present during ischemia in rat, but not in rabbit myocardium.     

Poster Session 2–3: Cardiac Resynchronization Therapy Monday, April 3, 2006, 4:00–5:30pm

Dr. Gabe Bleeker ¹ , Martin Schalij ¹ , Eduard Holman ¹ , Paul Steendijk ¹ , Ernst van der Wall ¹ , Jeroen Bax ^{1   1} Cardiology, Leiden University Medical Center, Leiden, The Netherlands
Background: Cardiac resynchronization therapy (CRT) is beneficial in selected patients with moderate-to-severe heart failure (New York Heart Association (NYHA) class III/IV). Patients with mildly symptomatic heart failure (NYHA class II) are currently not eligible for CRT and potential beneficial effects in these patients are not well studied. Methods: Fifty consecutive patients with NYHA class II heart failure and 50 consecutive NYHA class III/IV patients (control group) were prospectively included. All patients had left ventricular ejection fraction (LVEF) ≤ 35% and QRS duration >120 ms. The effects of CRT in NYHA class II patients were compared to results obtained in the control group. Results: The severity of baseline LV dyssynchrony was comparable between patients in NYHA class II vs NYHA class III/IV (83 ± 49 ms vs 96 ± 51 ms, ns), and resynchronization was achieved in both groups. NYHA class II patients showed a significant improvement in LVEF (from 25 ± 7% to 33 ± 10%, P < 0.001) and reduction in LV end-systolic volume (from 168 ± 55 ml to 132 ± 51 ml, P < 0.001) following CRT, similar to patients in NYHA class III/IV. In addition, only 8% of NYHA class II patients showed progression in heart failure symptoms. Conclusions: CRT has comparable effects in patients with NYHA class II and NYHA class III/IV heart failure in terms of LV resynchronization, improvement in LVEF, and LV reverse remodeling.     

Heart Rate Variability and Sudden Infant Death Syndrome

PERTICONE, F., ET AL.: Heart Rate Variability and Sudden Infant Death Syndrome. The sudden infant death syndrome (SIDS) is the most common cause of death in infancy. The pathophysiological mechanism leading to SIDS is still obscure. In the QT hypothesis, the mechanism must be an arrhythmogenic sympathetic imbalance: the infants die suddenly of cardiac arrhythmia. Recently, it has been suggested that analysis of heart rate variability (HRV), expressed as standard deviation or variance analysis, can provide adequate information on sympathovagal interaction. We studied 150 newborns enrolled in a previous prospective electrocardiographic study to evaluate the predictive value of QT interval for SIDS. We analyzed the ECGs recorded with infants alert on the fourth day of life and after 2 months. For each ECG, the HRV was calculated using the first standard deviation of of RR intervals (ms) measured for 1 minute. The average RR interval was 441 ± 71 ms at the fourth day and 420 ± 39 ms at the second month. The QT_c and HRV mean values were 396 ± 23 and 23 ± 12 ms at the fourth day, 412 ± 19 and 15 ± 7 msec at the second month. Therefore, the SD values of heart rate were correlated with QT_cin order to assess a possible relationship between the two variables. The correlation coefficient and regression equation were: -0.639 and y = 423.67 - 2.18*× (P < 0.002) at the fourth day, -0.146 and y = 418.09 - 0.37*× (NS) at the second month. In conclusion, our data seems to confirm a delayed maturation or impaired fuctioning of the autonomic nervous system in the first weeks of life, reflecting a direct correlation with QT prolongation.     

Chronotropic and inotropic effects of terikalant on isolated, blood-perfused atrial and ventricular preparations of dogs

Summary— We investigated the effects of terikalant, which blocks inward rectifier K⁺ current, on the sinus rate, atrial and ventricular contractile force in the isolated, blood-perfused right atrial and left ventricular preparations of dogs, and the effects of terikalant on the negative cardiac responses to acetylcholine, adenosine or pinacidil (an ATP-sensitive K⁺ channel opener) and on the positive cardiac responses to norepinephrine. Terikalant (1–100 nmol) decreased sinus rate and briefly and slightly increased atrial contractile force in isolated atria. However, terikalant did not increase ventricular contractile force in isolated ventricles. Neither propranolol nor atropine inhibited the positive inotropic and negative chronotropic responses to terikalant, respectively. Terikalant (10 or 30 nmol) did not significantly affect the negative cardiac responses to acetylcholine, adenosine nor pinacidil and the positive responses to norepinephrine. These results suggest that terikalant decreases sinus rate with a small changes in myocardial contractile force and does not affect the cardiac responses to muscarinic and adenosine receptor agonists, ATP-sensitive K⁺ channel openers nor β-adrenoceptor agonists in the dog heart.     

Arrhythmia Risk Prediction in Idiopathic Dilated Cardiomyopathy Based on Heart Rate Variability and Baroreflex Sensitivity

This study examined the relation between heart rate variability (HRV) and baroreflex sensitivity (BRS) and subsequent major arrhythmic events (MAE), defined as sustained VT, VF or sudden death, in 263 patients with idiopathic dilated cardiomyopathy (IDC) in sinus rhythm. The predefined measure of HRV was the standard deviation of all normal-to-normal RR intervals (SDNN) on baseline 24-hour ambulatory ECG. BRS was determined by the phenylephrine method. Over 52 ± 21 months of follow-up, MAE occurred in 38 patients (14%). SDNN at baseline 24-hour ambulatory ECG (106 ± 46 vs 109 ± 45, ns) and BRS (7.9 ± 5.5 vs 7.7 ± 5.3 ms/mmHg, ns) were both similar in patients with versus without MAE during follow-up. In contrast, left ventricular ejection fraction was significantly lower in patients with versus without MAE (24%± 7% vs 31%± 10%, P < 0.019. Conclusions: Neither HRV nor BRS predicted MAE in patients with IDC.     

Strength Duration Curve for Left Ventricular Epicardial Stimulation in Patients Undergoing Cardiac Resynchronization Therapy

Introduction: The strength duration curve has been studied for right ventricular endocardial stimulation. There are differences between left ventricular epicardial and right ventricular endocardial stimulation due to different electrophysiologic properties and different electrode-tissue interface. The strength duration curve for epicardial left ventricular stimulation has not been studied so far.
Methods: One hundred and three patients were studied. The strength duration curves were determined for left ventricular epicardial and right ventricular endocardial stimulation. The studied points were chronaxie, rheobase, and voltage threshold at 0.5 ms. Left ventricular leads Guidant 4512, 4513, 4537, 4538 (unipolar, area 3.5 mm²; Guidant Corp., St. Paul, MN, USA), Medtronic 4193 (unipolar, area 5.8 mm²; Medtronic Inc., Minneapolis, MN, USA), Guidant 4518, 4542, 4543 (bipolar, area 4 mm²), St. Jude Medical (bipolar, area 4.8 mm²; St. Jude Medical, St. Paul, MN, USA), and Medtronic 4194 (bipolar, area 5.8 mm²) were studied.
Results: The Guidant unipolar leads with a distal electrode area of 3.5 mm² had a lower chronaxie than the other studied leads. The left ventricular epicardial and right ventricular endocardial chronaxie for 15 patients with Medtronic left ventricular leads 4194 or 4193 (5.8 mm²) and right ventricular leads 6947 (5.7 mm²) were 0.52 ± 0.36 ms and 0.62 ± 0.46 ms (P > 0.05).
Conclusion: The left ventricular epicardial chronaxie depends on the lead. The left ventricular epicardial chronaxie is similar to the right ventricular endocardial chronaxie for leads with similar electrode stimulation area.     

Tonic block of the Na+ current in single atrial and ventricular guineapig myocytes, by a new antiarrhythmic drug, Ro 22-9194

Summary— Ro 22-9194 reduced the Na⁺ current in the atrial myocytes as well as ventricular myocytes in a tonic block fashion. Ro 22-9194 had a higher affinity to the inactivated state Na⁺ channels (Kd₁ = 3.3 μM in atrial myocytes, Kd₁ = 10.3 μM in ventricular myocytes) than to those in the rested state (Kd_R = 91 μM in atrial myocytes, Kd_R = 180 μM in ventricular myocytes), which indicated that Ro 22-9194 had a higher affinity to the Na⁺ channels in atrial myocytes than in ventricular myocytes. Ro 22-9194 shifted the inactivation curve in the hyperpolarized direction in both atrial and ventricular myocytes. These findings suggest that Ro 22-9194 more strongly inhibited the Na⁺ channel of the atrial myocytes of the diseased hearts with the depolarized membranes potentials than the Na⁺ channels in ventricular myocytes.     

Systematic Comparisons of Electrocardiographic Morphology Increase the Precision of QT Interval Measurement

Decreased intrasubject variability of QTc values is needed to increase the power and reduce the size of the so-called thorough QT studies. One source of QTc variability is the lack of systematic measurements when electrocardiograms (ECG) with closely matching morphologies are not measured in an exactly corresponding way. The inaccuracy can be eliminated by postprocessing of QT measurements by ECG pattern matching. This study tested the effects of pattern matching in ECG measurements in two populations of healthy subjects (n = 48 + 56) and in a population of patients with advanced Parkinson's disease (n = 130) in whom both day-time and night-time data were available. Intrasubject QTc variability was measured by intrasubject standard deviations (SD) of QTc values obtained with manual measurements before and after pattern-matching measurement alignments. In each subject, QT values (n = 230–320) in one drug-free long-term ECG recording were evaluated. The pattern-matching adjustment of the QT measurement decreased the intrasubject QTc variability from 5.2 ± 1.0 to 4.5 ± 1.0 ms (P < 10⁻¹⁴) from 6.4 ± 1.7 to 5.5 ± 1.6 ms (P < 10⁻¹⁰) from 5.6 ± 1.5 to 4.6 ± 1.4 ms (P < 10⁻³⁴) and from 6.1 ± 1.9 to 5.0 ± 1.7 ms (P < 10⁻³³), in the two populations of healthy subjects and in the day-time and night-time recordings of Parkinson's disease patients, respectively. Hence, morphological pattern adjustment of QT interval measurements improves the quality of the QT data with substantial practical implications. Reductions in intrasubject QTc variability were reproducibly found in different populations and thus the technology might be recommended for every thorough QT/QTc study. Noticeable reductions of necessary study size are likely achievable in this way.     

Initial Experience with 1.5-mm2 High Impedance, Steroid-luting Pacing Electrodes

In this human study, 21 atrial and 62 ventricular 1.5-mm² unipolar steroid-eluting pacing electrodes were implanted in 64 patients. Pacing thresholds, lead impedance, and sensing measurements were measured via pacemaker telemetry within 24 hours postimplont, and at 1, 2, 3, 4, 6, 12. 24. and 52 weeks. Acute pacing impedances measured via a pacing systems analyzer were 1,039 ± 292 (atrial) and 1,268 ± 313 ohms (ventricular). A10%-15% decline in the mean telemetered atrial and ventricular pacing impedances was observed at 1 week, but thereafter remained stable. Acute pacing thresholds at 0.5 ms were 0.5 ± 0.3 V (atrial) and 0.4 ± 0.1 V (ventricular). Filtered P and B wave amplitudes were 3.7 ± 2.3 mV and 14.9 ± 5.9 mV, respectively. In 21 patients, no complications related to the atrial electrode were observed. Of 62 patients with ventricular electrodes, 4 patients (6%) experienced complications and required surgical intervention. On these, causative factors included micro-dislodgment (l patient), and perforation (l patient). Sudden unexplained exit block occurred late (> 6 weeks) in two patients. In the remainder of patients, pacing thresholds and sensed electrogram amplitudes remained stable throughout the 52-week follow-up period. Conclusions: The- present study validates that smaller surface (i.e., 1.5 mm²) steroid- eluting electrode designs offer excellent pacing and sensing performance with significantly higher pacing impedances. Although questions remain as to the cause of late exit block in two patients in this series, this relatively small surface electrode design offers promise toward achieving greater pacing efficiency and a theoretical 13%-16% (minimum) enhancement in permanent pacemaker longevity.     

Value of Heart Rate Variability to Predict Ventricular Arrhythmias in Recipients of Prophylactic Defibrillators with Idiopathic Dilated Cardiomyopathy

GRIMM, W., et al. : Value of Heart Rate Variability to Predict Ventricular Arrhythmias in Recipients of Prophylactic Defibrillators with Idiopathic Dilated Cardiomyopathy. This study investigated the relation between heart rate variability (HRV) measured as standard deviation of normal to normal RR intervals (SDNN) on baseline 24-hour ambulatory electrocardiogram (ECG) and subsequent appropriate implantable cardioverter defibrillator (ICD) interventions in 70 patients with idiopathic dilated cardiomyopathy (IDC) in whom ICDs were implanted prophylactically in the presence of a low left ventricular ejection fraction (LVEF). During   43 ± 26   months of follow-up, 26 of 70 (37%) study patients with IDC received one or more appropriate ICD interventions for sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) documented by electrograms stored in the ICD. Mean SDNN at ICD implant was   94 ± 33 ms   . No difference was found between patients with   (90 ± 25 ms)   versus without   (96 ± 37 ms)   appropriate ICD interventions for VT or VF during follow-up. Multivariate Cox regression analysis of baseline clinical characteristics including age, gender, LVEF, NYHA functional class, nonsustained VT on Holter, history of syncope, left bundle branch block, baseline medication and HRV revealed LVEF as the only significant predictor of arrhythmia. These findings do not support the use of HRV measured as SDNN on 24-hour ambulatory ECG to select patients with IDC for prophylactic ICD therapy. (PACE 2003; 26[Pt. II]:411–415)     

Electrical Atrial Remodeling Assessed by Monophasic Action Potential and Atrial Refractoriness in Patients with Structural Heart Disease

The present study was performed to assess the effect of induced atrial fibrillation (AF) on atrial monophasic action potentials (MAPs) and atrial refractory period (ERP) in patients with structural heart disease. An electrode MAP catheter was placed in the right atrium to continuously measure atrial potential duration (APD₉₀) in 13 patients (coronary artery disease, 10 patients; dilated cardiomyopathy, 2 patients; hypertrophic cardiomyopathy, 1 patient) without spontaneous AF episodes. AF was induced by rapid atrial stimulation (300–1500/min). If sinus rhythm returned within 10 minutes, AF was reinduced. The atrial ERP was measured during atrial pacing at a basic cycle length of 550 ms before AF induction and after its conversion. Results: The mean atrial ERP and the atrial APD₉₀ before AF was 242 ± 34 ms and 256 ± 23 ms, respectively. ERP and APD_go shortening was observed after 3 minutes of AF. After 11 ± 0.5 min (10 min 20 s-13 min 10 s) of AF, ERP and APD₉₀ reached their minimal values of 72%± 13% and 71%± 10% of baseline, respectively. ERP and APD₉₀ returned to their initial values within 10 minutes after conversion of AF. A tendency toward longer duration of consecutive AF episodes and facilitation of their induction was observed. Conclusion: The present study confirms that short episodes of AF modify the electrophysiological properties of the atria in humans. In patients with structural heart disease, induced atrial fibrillation shortens the atrial ERP as well as the atrial APD₉₀. The changes were reversible within 10 minutes after arrhythmia termination.     

A comparison of the effects of IGF-I and insulin on glucose metabolism, fat metabolism and the cardiovascular system in normal human volunteers

Abstract. The metabolic and cardiovascular effects of recombinant human IGF-I were compared to insulin in six normal subjects. Subjects were studied twice and intravenously received an infusion of [6,6-²H₂]glucose (0–480 min) and in random order either IGF-I 20μg kg^-1 h^-1 (43.7 pmol kg^-1 min^-1) or insulin 0.5 mU kg^-1 min^-1 (3.4 pmol kg^-1 min^-1) with an euglycaemic clamp. One subject was withdrawn following a serious adverse event. During the IGF-I infusion glucose appearance rate (Ra) decreased from 1.79 ± 0.13 at baseline (150–180 min) to 0.35 ± 0.26 mg kg^-1 min^-1 ( P < 0.01) at 360min, and glucose utilization rate (Rd) increased from 1.79 ± 0.28 to 4.17 ± 0.84 mg kg^-1 min^-1 ( P < 0.01). There was no change in free fatty acids (FFA) and an increase (percentage change from pre-infusion mean) in cardiac output + 37.3%± 9% ( P < 0.01), heart rate + 13%± 2% ( P < 0.01) and stroke volume + 21%± 7% ( P < 0.05). During the insulin infusion glucose Ra decreased from 1.89 ± 0.13 to 0.34 ± 0.33 mg kg^-1 min^-1 ( P < 0.01) and FFA from 0.546 mmoll^-1 to 0.198 mmoll^-1 ( P < 0.01), glucose Rd increased from l.89 ± 0.18 to 5.41 ± l.47mg kg^-1 min^-1 ( P < 0.01) and there were no significant changes in the cardiovascular variables.     

Influence of Duration of Rapid Ventricular Pacing on Ventricular Refractoriness in the Presence of Propafenone and Lidocaine

Propafenone and lidocaine have a rate dependent negative dromotropic effect on intraventricular conduction. We investigated the use dependent actions of propafenone and lidocaine on intraventricular conduction in isolated guinea pig hearts perfused by the method of Langendorff. Of primary interest was how the number of stimuli of the conditioning train (S1) might influence the ventricular effective refractory period (VERP) when refractoriness is assessed at a high pacing rate. Propafenone (0.3 μM) and lidocaine (50 μM) caused a comparable prolongation of the intraventricular conduction time during sinus rhythm. During ventricular pacing in the presence of propafenone an abrupt decrease of the pacing cycle length (220 to 120 ms) resulted in an initial peak of rate dependent prolongation of the QRS interval that subsequently decreased to a stable steady-state level. Lidocaine also induced a rate dependent increase of the intraventricular conduction time up to a steadystate level. The time constant, characterizing the changes of the intraventricular conduction time after shortening the ventricular pacing cycle length from 220 to 120 ms was significantly (P < 0.01) longer in the presence of propafenone (τ= 31 ± 4 beats; mean ± SEM; n = 11) than for lidocaine (τ= 3 ± 1; n = 10). Both drugs caused the greatest increase of tbe VERP when the number of conditioning stimuli (S1, interstimulus interval = 120 ms) was in the range of their respective time constant. However, when the number of conditioning stimuli was further increased, VERP progressively diminished. These effects may be explained by a shortening of the action potential during high rates that results in a decreased binding of propafenone to Na⁺ channels and by the direct shortening of repolarization period by lidocaine (Class IB drug).