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Background. To improve acute myocardial infarction (AMI) care in the region 'Hollands-Midden' (the Netherlands), a standardised guideline-based care program was developed (MISSION!). This study aimed to evaluate the outcome of the pre-hospital part of the MISSION! program and to study potential differences in pre-hospital care between four areas of residency. Methods. Time-to-treatment delays, AMI risk profile, cardiac enzymes, hospital stay, in-hospital mortality, and pre-AMT medication was evaluated in consecutive AMI patients (n=863, 61 +/- 13years, 75% male) transferred to the Leiden University Medical Center for primary percutaneous coronary intervention (PCI). Results. Median time interval between onset of symptoms and arrival at the catheterisation laboratory was 150 (interquartile range [IQR] 101-280) minutes. The alert of emergency services to arrival at the hospital time was 48 (IQR 40-60) minutes and the door-to-catheterisation laboratory time was 23 (IQR 13-42) minutes. Despite significant regional differences in ambulance transportation times no difference in total time from onset of symptoms to arrival at the catheterisation room was found. Peak troponin T was 3.33 (IQR 1.23-7.04) mu g/l, hospital stay was 2 (IQR 2-3) days and in-hospital mortality was 2.3%. Twelve percent had 0 known risk factors, 30% had one risk factor, 45% two to three risk factors and 13% had four or more risk factors. No significant differences were observed for AMI risk profiles and medication pre-AMI. Conclusions. This study shows that a standardised regional AMI treatment protocol achieved optimal and uniformly distributed pre-hospital performance in the region 'Hollands-Midden', resulting in minimal time delays regardless of area of residence. Hospital stay was short and in-hospital mortality low. Of the patients, 88% had >= 1 modifiable risk factor. (Neth Heart J 2010;18:408-15.)

Aims To assess the number of patients in daily clinical practice that meets criteria for implantation of an implantable cardioverter defibrillator (ICD) following acute myocardial infarction (AMI) when treated according to an aggressive treatment protocol. Methods and results Patients were treated according to the MISSION! protocol. The protocol encompasses pre-hospital, in-hospital, and outpatient clinical framework for the acute and chronic treatment of AMI patients and the decision making regarding primary prevention of sudden cardiac death (SCD). A total of 676 consecutive AMI patients (78% male, mean age 59 +/-\12 years) treated according to the MISSION! protocol were included in this analysis. Left ventricular ejection fraction at 3 months was 54 +/- 10%. Only 39 (6%) patients met criteria for implantation of an ICD

Aims: To evaluate effects of sirolimus-eluting stents (SES) compared to bare-metal stents (BMS) at stent edges in patients with acute myocardial infarction (AMI). Methods and results: Clinical, angiographic, intravascular ultrasound (IVUS) and virtual histology (VH)-IVUS results were obtained and analysed in 20 SES and 20 BMS AMI patients at the index procedure and at nine months follow-up. Quantitative angiography and IVUS showed a trend toward decreases in mean lumen diameter, vessel volume, minimum lumen area and mean lumen area at both stent edges of BMS, and at the proximal edge of SES. At the distal stent edge, a significant difference between BMS and SES treated patients in mean lumen area was found (Δ-0.8±1.6 mm 2 versus 40.2±0.8 mm 2 respectively, p=0.04). Furthermore, in-stent SES had a larger lumen volume (SES: 167.7±59.2 mm 3 versus BMS: 125.1±43.8 mm 3 ; p=0.02) and less neointima volume (7.3±9.1 mm 3 versus 53.2±35.1 mm 3 ; p

To compare the long-term efficacy and safety of sirolimus-eluting stents (SES) to those of bare-metal stents (BMS) for ST-segment elevation myocardial infarction, outcomes were assessed in 310 patients (mean age age 59 +/- 11 years, 78% men) included in the randomized MISSION! Intervention Study: A Prospective Randomised Controlled Trial to Evaluate the Efficacy of Drug-Eluting Stents Versus Bare-Metal Stents for the Treatment of Acute Myocardial Infarction after a median follow-up period of 38 months. All patients were treated with aspirin (lifelong) and clopidogrel for 1 year after stent implantation. Except for a significant difference between reference vessel diameters (SES 2.76 mm vs BMS 2.92 mm, p = 0.02), there were no significant differences in baseline and angiographic characteristics between the treatment groups (158 SES, 152 BMS). A significant difference between SES and BMS patients for all revascularization end points was found after the first year of follow-up. However, at 3 years of follow-up, although there was still a trend toward better clinical outcomes in SES-treated patients, differences were no longer significant (death 4.4% vs 6.6%, p = 0.41; target vessel related myocardial infarction 2.5% vs 4.6%, p = 0.32; target vessel revascularization 8.9% vs 15.8%, p = 0.06), target lesion revascularization 6.3% vs 12.5%, p = 0.06; and target vessel failure 12.0% vs 19.7%, p = 0.06). Three cases of very late (definite) stent thrombosis were observed in the SES group (1.9%) versus none in the BMS group (p = 0.14). In conclusion, the significant SES benefit (compared to BMS) in patients with ST-segment elevation myocardial infarctions at 1-year follow-up in terms of target vessel revascularizations decreased to some extent because of more similar target vessel revascularization rates during the 2 subsequent years. Rates of death and nonfatal recurrent MI remained comparable. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;106:4-12)

Objectives: Our aim was to evaluate the effects of early abciximab administration in the ambulance on immediate, short, and long term outcomes. Background: Early abciximab administration before primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) is recommended in practice guidelines. However, optimal timing of administration remains indistinct. Methods: Within a fixed protocol for PPCI, December 2006 was the cut-off point for this prospective study. A total of 179 consecutive patients with STEMI were enrolled, 90 patients received abciximab bolus in the hospital (in-hospital group), and 89 patients received abciximab bolus in the ambulance (in-ambulance group). Results: The two groups were comparable for baseline and angiographic characteristics. The in-ambulance group received abciximab within the golden period (median 63 min). The infarct related artery (IRA) patency at onset of the PCI was four times higher in the in-ambulance group compared to in-hospital group (odds ratio = 4.9, 95% CI 2.4–10.1). Enzymatic infarct size was smaller in the in-ambulance group (cumulative 48-h CK release 8011 vs. 11267 U/L, P = 0.004). This was associated with higher left ventricular ejection fraction (LVEF) at 90 days post-PPCI measured by myocardial scintigraphy (59% vs. 54%, P = 0.01), and lower incidence of heart failure through a median of 210 days of clinical follow-up (3% vs.11%, P = 0.04). Conclusion: Early abciximab administration in the ambulance significantly improves early reperfusion in STEMI patients treated with PPCI. Moreover this is associated with a smaller infarct size, improved LV function and a lower risk of heart failure on clinical follow-up. © 2009 Wiley-Liss, Inc.

Introduction: Patients with established arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) based on task force (TF) criteria and ventricular tachycardia (VT) are at risk of VT recurrence and sudden death. Data on patients with VT due to right ventricular (RV) scar not fulfilling TF criteria are lacking. The purpose of this study was to assess the long-term arrhythmia recurrence rate and outcome in patients with scar-related right VT with and without a diagnosis of ARVC/D. Methods: Sixty-four patients (age 43.5 ± 15 years, 49 males) presenting with nonischemic scar-related VT of RV origin were studied. Scar was identified by electroanatomical mapping, contrast echocardiography, and/or magnetic resonance imaging (MRI). Patients were evaluated and treated according to a standard institute protocol. Results: Twenty-nine (45%) patients were diagnosed with ARVC/D according to TF criteria (TF+) and 35 (55%) with RV scar of undetermined origin (TF–) at the end of follow-up (64 ± 42 months). Patients were treated with antiarrhythmic drugs, radiofrequency catheter ablation, and/or implantable cardioverter-defibrillator (ICD) implantation. VT recurrence-free survival for TF+ and TF– was 76% versus 74% at 1 year and 45% versus 50% at 4 years (P = ns). Patients with fast index VT (cycle length [CL]≤ 250 ms, n = 31) were more likely to experience a fast VT during follow-up than patients with a slow index VT (CL > 250 ms, n = 33) (61% vs 3%, P < 0.001). Conclusions: Scar-related RV VTs have a high recurrence rate in TF+ and TF– patients. Patients presenting with a fast index VT are at high risk for fast VT recurrence and may benefit most from ICD therapy.

Aims To assess the long-term rate of mortality and the recurrence of potentially life-threatening ventricular arrhythmias in secondary prevention implantable cardioverter defibrillator (ICD) patients and to construct a model for baseline risk stratification. Methods and results Since 1996, all patients with ischaemic heart disease, receiving ICD therapy for secondary prevention of sudden death, were included in the current study. Patients were evaluated at implantation and during long-term follow-up. A total of 456 patients were included in the analysis and followed for 54 ± 35 months. During follow-up, 100 (22%) patients died and ICD therapy was noted in 216 (47%) patients, of which 138 (30%) for fast, potentially life-threatening ventricular arrhythmia. Multivariate analysis revealed a history of atrial fibrillation or flutter (AF), ventricular tachycardia as presenting arrhythmia, and wide QRS and poor left ventricular ejection fraction as independent predictors of life-threatening ventricular arrhythmias. The strongest predictor was AF with a hazard ratio of 2.1 (95% confidence interval 1.3–3.2). On the basis of the available clinical data, it was not possible to identify a group which exhibited no risk on recurrence of potentially life-threatening ventricular arrhythmias. Conclusion Ischaemic secondary prevention ICD recipients exhibit a high recurrence rate of potentially life-threatening ventricular arrhythmias. Factors that increase risk can be identified but, even with these factors, it was not possible to distinguish a recurrence-free group.

Acute and late stent malapposition (SM) after bare-metal stents (BMS) and sirolimus-eluting stents (SES) in ST-segment elevation myocardial infarction patients were studied.Stent thrombosis may be caused by SM after primary percutaneous coronary intervention in ST-segment elevation myocardial infarction patients.Post-procedure and follow-up intravascular ultrasound data were available in 184 out of 310 patients (60%; 104 SES, 80 BMS) included in the MISSION! Intervention Study. To determine the contribution of remodeling and changes in plaque burden to the change in lumen cross-sectional area (CSA) at SM sites, the change in lumen CSA (follow-up minus post-lumen CSA) was related to the change in external elastic membrane CSA (remodeling) and change in plaque and media CSA (plaque burden).Acute SM was found in 38.5% SES patients and 33.8% BMS patients (p = 0.51), late SM in 37.5% SES patients and 12.5% BMS patients (p0.001). Acquired SM was found in 25.0% SES patients and 5.0% BMS patients (p0.001). Predictors of acute SM were reference diameter (SES: odds ratio [OR] 3.49, 95% confidence interval [CI] 1.29 to 9.43; BMS: OR 28.8, 95% CI 4.25 to 94.5) and balloon pressure (BMS: OR 0.74, 95% CI 0.58 to 0.94). Predictors of late SM were diabetes mellitus (SES: OR 0.16, 95% CI 0.02 to 1.35), reference diameter (BMS: OR 19.2, 95% CI 2.64 to 139.7), and maximum balloon pressure (BMS: OR 0.74, 95% CI 0.55 to 1.00). Change in lumen CSA was related to change in external elastic membrane CSA (R = 0.73, 95% CI 0.62 to 0.84) after SES implantation and to change in plaque and media CSA (R = -0.62, 95% CI -0.77 to -0.46) after BMS implantation. After SES implantation, acquired SM was caused by positive remodeling in 84% and plaque reduction in 16% of patients.Acute SM was common after SES and BMS stent implantation in ST-segment elevation myocardial infarction patients. After SES implantation, late acquired SM is common and generally caused by positive remodeling.

Our purpose was to evaluate the efficacy and safety of drug-eluting stents in the setting of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI).There is inconsistent and limited evidence about the efficacy and safety of drug-eluting stents in STEMI patients.A single-blind, single-center, randomized study was performed to compare bare-metal stents (BMS) with sirolimus-eluting stents (SES) in 310 STEMI patients. The primary end point was in-segment late luminal loss (LLL) at 9 months. Secondary end points included late stent malapposition (LSM) at 9 months as determined by intravascular ultrasound imaging and clinical events at 12 months.In-segment LLL was 0.68 +/- 0.57 mm in the BMS group and 0.12 +/- 0.43 mm in the SES group with a mean difference of 0.56 mm, 95% confidence interval 0.43 to 0.68 mm (p0.001). Late stent malapposition at 9 months was present in 12.5% BMS patients and in 37.5% SES patients (p0.001). Event-free survival at 12 months was 73.6% in BMS patients and 86.0% in SES patients (p = 0.01). The target-vessel-failure-free survival was 84.7% in the BMS group and 93.0% in the SES group (p = 0.02), mainly because of a higher target lesion revascularization rate in BMS patients (11.3% vs. 3.2%; p = 0.006). Rates of death, myocardial infarction, and stent thrombosis were not different.Sirolimus-eluting stent implantation in STEMI patients is associated with a favorable midterm clinical and angiographic outcome compared with treatment with BMS. However, LSM raises concern about the long-term safety of SES in STEMI patients.

Serial Reevaluation for ARVD/C. Introduction: Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is based on a set of criteria proposed by the International Task Force (TF) for Cardiomyopathies in 1994. To fulfill these criteria, presence of both electrocardiographic and anatomical abnormalities must be assessed with ECG and imaging techniques, respectively. This may be difficult in patients with early/mild forms of the disease as detectable structural abnormalities may still be absent. We evaluated in which patients presenting with right ventricular tachycardia (VT) serial reevaluation for ARVD/C is indicated. Methods and Results: Sixty consecutive patients (41 men, mean age 40±15 years) were evaluated by the TF criteria for possible ARVD/C because of presentation with a left bundle branch block (LBBB) VT, representing 1 minor criterion. The presence on the ECG of a T-wave inversion beyond lead V2 (1 minor), right precordial QRS prolongation (1 major), or an epsilon wave (1 major) was assessed together with the visualization of severe regional/global right ventricle dysfunction (1 major) or mild segmental dilatation/regional hypokinesia (1 minor) by standard imaging techniques. Initially, 22 (37%) patients were diagnosed as having ARVD/C. After 47±39 (range 6-146) months, 23 initially TF-negative patients were reevaluated because of recurrent symptoms, with 12 (52%) additional patients now meeting the TF criteria. Eleven of these 12 (92%) patients presented initially with ECG abnormalities only, but developed structural abnormalities on imaging at follow-up. Conclusion: ECG abnormalities may precede structural abnormalities warranting serial reevaluation for ARVD/C in initially TF-negative patients presenting with LBBB VT with only ECG abnormalities.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a heart muscle disorder characterized pathologically by fatty or fibrofatty replacement and electrical instability of the right ventricular myocardium. Clinical manifestations include structural and functional malformations (fatty infiltration, dilatation, aneurysms) of the right ventricle, ECG abnormalities, and presentation with ventricular tachycardias with left bundle branch block pattern or sudden death. The disease often is familial with an autosomal inheritance. The typical hallmarks of ARVD/C are distributed in the so-called "triangle of dysplasia." The functional and morphologic characteristics are relevant to clinical imaging approaches such as contrast angiography, echocardiography, radionuclide angiography, ultrafast computed tomography, and cardiovascular magnetic resonance imaging. Evident forms of the disease are straightforward to diagnose based on a series of diagnostic criteria proposed by the International Task Force for Cardiomyopathy. However, the diagnosis of early and mild forms of the disease often is difficult. Treatment is directed toward preventing life-threatening ventricular arrhythmias in which radiofrequency ablation and implantable defibrillators play an increasing role. Despite new diagnostic and therapeutic approaches in ARVD/C, uncertainties about the etiology of the disease, the genetic basis, the appropriate diagnosis and therapy, and the clinical course of patients with ARVD/C have resulted in several registries to increase our knowledge of this intriguing disease.

Background Zones of slow conduction facilitate reentry, the major mechanism of ventricular tachycardia (VT) after myocardial infarction (MI). Identification of these zones during sinus rhythm (SR) is desirable for radiofrequency (RF) catheter ablation of VT. Local conduction velocity may correlate with electrogram duration. Objectives The purpose of this study was to revise the definition of normal electrogram characteristics and to reevaluate the significance of low-amplitude, long-duration electrograms recorded during SR to select RF catheter ablation sites in patients with VT. Methods Electroanatomic mapping was performed during SR in 10 control patients with normal left ventricles (LVs) and in 10 patients with stable VT after MI. From the controls, reference values for electrogram amplitude, duration (first peak to last peak distance), and fragmentation (positive deflection) were derived. In patients after MI, areas with signals exceeding these values were annotated and related to successful ablation sites. Results Ninety-five percent of normal LV electrograms were ≥1.0 mV and ≤28 ms (range 5–39 ms) and all had ≤4 deflections. Based on these results, cutoff values were set at 1 mV, four deflections, and 40 ms. In infarcted hearts, 653 electrograms (44%) were 4 deflections and restricted to circumscribed areas. Twenty-seven of 28 targeted VTs remained noninducible after RF catheter ablation within these areas, resulting in 86% sensitivity and 94% specificity for low-amplitude, long-duration electrograms predicting successful ablation sites. Conclusion Identification of successful RF target areas during SR in patients with VT is feasible with high sensitivity and specificity using a mapping strategy based on voltage and duration criteria.

Cardiac resynchronization therapy (CRT) is a recently introduced therapeutic option for patients with severe heart failure and intraventricular conduction disturbances. However, it is estimated that 20% to 30% of patients may not respond to CRT. Patients with ischemic cardiomyopathy (IC) may respond less favorably to CRT compared with patients with idiopathic dilated cardiomyopathy (IDC). Accordingly, the beneficial effects of CRT were evaluated in 2 subsets of patients (IC and IDC). Seventy-four patients with end-stage heart failure, New York Heart Association (NYHA) class III or IV, left ventricular (LV) ejection fraction35%, QRS120ms, and left bundle branch block received a biventricular pacemaker. At baseline and 6 months after implantation these parameters were evaluated: NYHA class, Minnesota quality-of-life score, QRS duration, and 6-minute walking distance. LV ejection fraction and severity of mitral regurgitation were assessed before and 6 months after CRT using 2-dimensional echocardiography. Long-term follow-up and hospitalization rates were obtained up to 2 years. Of the 74 patients, 46% (n = 34) had IC and 54% (n = 40) IDC. At 6 months follow-up all clinical parameters, QRS duration, LV ejection fraction, and mitral regurgitation improved significantly in both groups. Long-term (2-year) follow-up showed a survival rate of 87.5% for patients with IDC and 88.3% for patients with IC. The percentages of responders to CRT (defined as an improvement in NYHA classor=1 grade) were comparable in both groups (65% vs 71%). Therefore, the underlying etiology of heart failure (IC vs IDC) was not related to the response to CRT.

The aim of this study was to evaluate the effect of a systematic screening/treatment protocol on outcome in patients after aborted sudden death.Patients after aborted sudden death are at high risk for recurrent events. In this regard, systematic screening is mandatory to reveal the underlying etiology, to detect and subsequently treat reversible causes, and to establish patient-tailored antiarrhythmic treatment.A total of 417 consecutive patients after aborted sudden death due to ventricular arrhythmias underwent echocardiography and coronary angiography. In the presence of coronary artery disease and myocardial ischemia, using stress-rest myocardial perfusion imaging/exercise testing, subsequent revascularization was performed. Patients without ischemic heart disease were further evaluated with magnetic resonance imaging, contrast echocardiography, right ventricular angiography and/or flecainide/ergonovine testing. After these diagnostic steps, final antiarrhythmic therapy was based on the outcome of electrophysiologic testing.The majority of patients had ischemic heart disease (n = 300, 72%). After screening, 78 (78 of 300, 26%) patients underwent revascularization. In 69% of patients, ventricular arrhythmias were inducible during electrophysiologic testing. Therapy consisted of implantable defibrillators in 301 (72%) patients, antiarrhythmic drugs in 239 (57%) patients, and catheter ablation in 58 (14%) patients. During 5-year follow-up, only 3 (1%) patients died suddenly. The 5-year survival rate was 82%; of 39 deaths, 10 (26%) patients died due to non-cardiac disease and 26 (67%) due to heart failure.Screening and treatment of patients after aborted sudden death according to a standardized protocol resulted in1% arrhythmic deaths during 5-year follow-up. The majority of patients died of heart failure, stressing the importance of optimizing medical and surgical therapy and screening.

Recently, the authors have developed a protocol that invokes gradual autonomic changes by incremental tilt. For each tilt angle, heart rate (HR) and the normalized low-frequency (0.07-0.14 Hz) heart rate variability power (LF) are computed. Linear regression of LF on HR allows assessment of the sympathovagal transition (SVT). After 5 to 8 months, the authors repeated the measurements in young healthy males (n=17), and assessed the reproducibility of the supine HR and LF (HR/sub supine/ and LF/sub supine/), HR and LF at 50/spl deg/ tilt (HR/sub tilt/ and LF/sub tilt/), and of the range and position of the sympathovagal transition (SVT/sub range/, SVT/sub position/) by computing the coefficient of variation (CV), the relative error (RE), and the reliability coefficient (RC). HR/sub supine/ reproduced best (CV=4%, RE=8%, and RC=96%), followed by SVT/sub position/, HR/sub tilt/, LF/sub supine/, LF/sub tilt/, and SVT/sub range/ (CV=35%, RE=25%, and RC=48%). It is concluded that HR and SVT/sub position/ reproduce much better than LF. The remarkable lack of reproducibility of SVT/sub range/ suggests that the size of the sympathovagal transition range is a dynamic autonomic feature within subjects. >

Magnetic resonance imaging (MRI) of the heart precludes dynamic exercise. Therefore, stress MRI is accomplished by pharmacological stimulation, e.g., by the synthetic adrenergic agent dobutamine. With dobutamine stress, an autonomic defense (a shift of the sympathovagal balance towards vagal predominance) is to be expected. To assess this, the authors measured heart rate (HR) and the percentage 0.07-0.14 Hz low-frequency heart rate variability (LF) in 9 male patients (mean/spl plusmn/SD age 60.6/spl plusmn/8.6 years), 3 with one-, 3 with two-, and 3 with three-vessel disease, during control and dobutamine stress MRI. As the PQ-intervals were sometimes varying, we derived LF from PP-intervals (LF-P) as well as from QQ-intervals (LF-Q). With dobutamine, HR increased significantly (paired t-test, P >

The relationship between the QT interval and the preceding RR interval is often described by a simple formula with 1 or 2 parameters like, e.g., Bazett's correction formula or an exponential formula. These formulas may perform adequately in large groups of people, but not in individuals. The authors describe an incremental head-up tilt protocol to obtain QT intervals at a large range of different heart rates in individuals within 3 hr under minimal changes in conditions. The resulting QT-RR relationship is complex and differs for each individual, but all curves share some common characteristics.

The authors studied 34 young healthy male subjects (age 26.2/spl plusmn/3.5 yrs) in supine position, measuring heart rate (HR) in 3 six-minute episodes. Prior to the first episode, the subjects were supine for stabilization during 20 minutes. Prior to the second episode, a venous needle was introduced in the left underarm. Prior to the third episode, complete autonomic blockade was accomplished by metoprolol and atropine. The sympathovagal balance before and after needling was computed by division of HR in episodes 1 and 2 by HR in episode 3 (the intrinsic heart rate). Needling caused a significant decrease in the sympathovagal balance from 0.71/spl plusmn/0.09 (range 0.50 to 0.89) to 0.68/spl plusmn/0.10 (range 0.49 to 0.91). The average decrease was -0.03/spl plusmn/0.04, range -0.11 to +0.04. This study demonstrates that intravascular instrumentation has a major autonomic impact; which imposes a methodological problem on invasive autonomic studies. >

Heart rate variability (HRV) analysis is commonly used to assess sympathetic or vagal tone, or the sympathovagal balance (SVB). Thorough validation, however, is lacking. According to the Rosenblueth-Simeone model, heart rate (HR) equals m/spl middot/n/spl middot/HR/sub 0/ (m=sympathetic factor, n=vagal factor, HR/sub 0/=intrinsic heart rate); m, n, and HR/sub 0/ can be determined by two-stage autonomic blockade. SVB is defined as m/spl middot/n. The current study aims at validating HRV measures with values of m, n, and m/spl middot/n. The authors analyzed the ECG of 21 healthy males (ages 24.9/spl plusmn/3.0 yrs) in three 5-min episodes. In episode 1 they computed HR, and the following HRV measures: SDNN, CV, pNN50, and the absolute and relative spectral powers VLF (0.01-0.05 Hz), HF (0.05-0.15 Hz), and HF (0.15-0.40 Hz). Prior to episodes 2 and 3 complete sympathetic and vagal blockade was instituted, respectively, for measurement of m, n, and HR/sub 0/. Linear correlations between m, n, m/spl middot/n, and all HRV measures, were computed. For all HRV measures the authors also determined the maximal mean performance (MMP; averaged sensitivity and specificity) to discriminate high from low values of m, n, and m/spl middot/n. Significant correlations >0.43 or 0.75 were found for n vs. HR (MMP=0.76), SDNN (MMP=0.80), CV (MMP=0.76), and pNN50 (MMP=0.76), and for m/spl middot/n vs. SDNN (MMP=0.80), CV (MMP=0.76), and pNN50 (MMP=0.76). These results demonstrate that time domain HRV measures superiorly rank the subjects on vagal tone or SVB. However, performance is weak. Therefore, reconsideration of current HRV interpretation seems to be indicated. >

The authors addressed the question wether differences in fitness are associated with differences in sympathetic tone, vagal tone, or sympathovagal balance, expressed in the Rosenblueth-Simeone factors m, n, and their product m/spl middot/n. They also determined whether fitness related differences in heart race variability (HRV) are associated with differences in autonomic tone or sympathovagal balance. They measured HRV, heart rate (HR), and, with autonomic blockade, the intrinsic HR and the Rosenblueth-Simeone factors in 21 low fit (mean/spl plusmn/SD age 27.5/spl plusmn/3.4 yrs; VO/sub 2/-max 50 ml/spl middot/kg/sup -1//spl middot/min/sup -1/, mean/spl plusmn/SD 57.6/spl plusmn/5.5 ml/spl middot/kg/sup -1//spl middot/min/sup -1/) healthy male subjects. HR and the intrinsic HR differed significantly between the low and high fit groups, but the sympathetic and vagal tone, and the sympathovagal balance were not significantly different. All time- and absolute frequency-domain HRV measures differed significantly. Linear regression of HR, intrinsic HR, sympathetic tone, vagal tone, sympathovagal balance, and the time- and frequency-domain HRV measures on VO/sub 2/-max values of all 44 subjects yielded significant correlations for resting HR, intrinsic HR, standard deviation of inter-beat-intervals, coefficient of variation, percentage of successive inter-beat-intervals differing more than 50 ms, respiratory sinus arrhythmia, and the very low frequency spectral HRV power. All correlations were below 0.50 (

Localization of target sites for radiofrequency catheter ablation (RFCA) is facilitated by the identification of abnormal electrograms at specific endocardial sites. With new 3-D electro-anatomical mapping systems such as the CARTO/sup TM/ system and the Real-time Positioning Management System/sup TM/ (RPM) the 3-D position of EP catheters can be visualized and recorded Detailed information about anatomical structures can only be obtained by standard imaging modalities, such as ventricular angiography. Combination of information obtained from the 3-D mapping systems with angiographic image information would therefore greatly enhance the applicability of these systems. In patients referred for ventricular tachycardia, the XYZ-coordinates of the ablation catheter positions, were obtained with the RPM system, and visualized in 3-D space. In addition, biplane angiographic images were obtained in these patients to confirm the geometric findings of the mapping system, and to display the ablation locations superimposed on the angiographic images. Analysis of the mapping and angiography data revealed that it is not feasible to create an accurate 3-D representation of a heart chamber based on two angiographic projections. Therefore, fusion of mapping data and angiographic images was not possible as planned. However, new ideas are presented that may make this fusion possible in the near future.

Voltage differences might be used to distinguish normal atrial tissue from abnormal atrial tissue. This study was aimed at identifying lowest voltage areas in patients with atrial tachycardia after surgical correction of congenital heart disease and to evaluate if identification of these areas in diseased hearts facilitates selection of critical conduction pathways in reentrant circuits as target sites for catheter ablation. Ten patients (four men, age 39 +/- 15 years) with normal sized atria and atrioventricular reciprocating tachycardia (control group) and ten patients (5 men, 32 +/- 7 years) with congenital heart disease and postoperative atrial tachycardia (CL 281 +/- 79 ms) referred for radiofrequency catheter ablation were studied. Mapping and ablation was guided by a three-dimensional electroanatomic mapping system (CARTO) in all patients. In the control group, voltage maps were constructed during sinus rhythm and during tachycardia to evaluate the voltage distribution. The amplitude of bipolar signals was 1.90 +/- 1.45 mV (0.11-8.12 mV, n = 660) during sinus rhythm and 1.45 +/- 1.66 mV (0.12-5.83 mV, n = 440, P < 0.05) during atrioventricular reciprocating tachycardia. In the study group, the amplitude of 1,962 bipolar signals during tachycardia was 1.01 +/- 1.19 mV (0.04-9.40 mV), which differed significantly from the control group during tachycardia (P < 0.0001). No significant difference in the tachycardia cycle length was found (P < 0.05) between the control and study groups. As the lowest voltage measured in normal hearts was 0.1 mV, this value was used as the upper limit of the lowest voltage areas in the patients with congenital heart disease. These areas were identified by detailed voltage mapping and represented by a gray color. Activation and propagation maps were then used to select critical conduction pathways as target sites for ablation. These sites were characterized by fragmented signals in all patients. Ablation resulted in termination of the tachycardia in eight (80%) of ten patients. Complications were not observed. Identification of the lowest voltage areas using a cut-off value of 0.1 mV in congenital heart disease patients with postoperative atrial reentrant tachycardia facilitated the selection of critical conduction pathways as target sites for ablation.

Three-Dimensional Reai-Time Position Management. Introduction: Precise localization of target sites for radiofrequency catheter ablation (RFCA) of arrhythmias is hampered by the relative inaccuracy of X-ray localization procedures. This study evaluated the efficacy of a three-dimensional (3D) real-time position management system in guiding RFCA procedures in patients. Methods and Results: Patients (n = 30, age 59 ± 20 years) referred for ablation of either atrial flutter (n = 10), ventricular tachycardia (n = 15), or accessory pathways (n = 5) were studied. The real-time position management system uses ultrasound ranging techniques to track the position of an ablation catheter relative to two multitransducer reference catheters, positioned in the right atrium or coronary sinus and the right ventricle. Each catheter contains three or four ultrasound transducers. The distance between the transducer(s) is determined hy calculating the time necessary for an ultrasound pulse to reach other transducers, assuming the speed of sound in blood is 1,550 m/sec. The proximal His bundle was marked at the beginning and the end of the procedure as an electrical landmark to verify reproducibility. After identification of target sites, the position of each lesion created with the ablation catheter was marked. Successful ahlation was achieved in 94% of the patients. The distance between the location of the proximal His hundle as marked at the beginning and at the end of the procedure was 2.0 ± 1.2 mm (range 1.5 to 3.5). Conclusion: The new 3D real-time position management system facilitated RFCA procedures as it allowed accurate and reproducible 3D tracking of the mapping and ablation catheter.

Arrhythmogenic right ventricular dysplasia (ARVD) is a heart muscle disorder of unknown cause that is characterized pathologically by fibrofatty replacement of the right ventricular myocardium. Clinical manifestations include structural and functional malformations of the right ventricle, electrocardiographic abnormalities, and presentation with ventricular tachycardias with left bundle branch pattern or sudden death. The disease is often familial with an autosomal inheritance. In addition to right ventricular dilatation, right ventricular aneurysms are typical deformities of ARVD and they are distributed in the so-called “triangle of dysplasia”, i. e., right ventricular outflow tract, apex, and infundibulum. Ventricular aneurysms at these sites can be considered pathognomonic of ARVD. Another typical hallmark of ARVD is fibrofatty infiltration of the right ventricular free wall. These functional and morphologic characteristics are relevant to clinical imaging investigations such as contrast angiography, echocardiography, radionuclide angiography, ultrafast computed tomography, and magnetic resonance imaging (MRI). Among these techniques, MRI allows the clearest visualization of the heart, in particular because the right ventricle is involved, which is usually more difficult to explore with the other imaging modalities. Furthermore, MRI offers the specific advantage of visualizing adipose infiltration as a bright signal of the right ventricular myocardium. MRI provides the most important anatomic, functional, and morphologic criteria for diagnosis of ARVD within one single study. As a result, MRI appears to be the optimal imaging technique for detecting and following patients with clinical suspicion of ARVD.

UNLABELLED Homografts and stentless xenografts are increasingly used in aortic valve surgery. Echocardiography technicians and cardiologists have to know what they will find when performing an echo-Doppler examination in patients who received a stentless valve. We therefore evaluated echocardiographic images of 74 patients who received a Freestyle stentless bioprosthesis with three techniques and a follow-up of 2 years in two high-volume hospitals. Of the patients studied, 81% were operated using the subcoronary technique, 12% using the root-inclusion technique, and 7% using the full-root technique. RESULTS Transvalvular gradients across the stentless valves were low: 8.0 mmHg when implanted with the subcoronary technique, 8.2 +/- 5.1 mmHg using the root-inclusion technique, and 6.5 mmHg using the full-root technique. Trivial aortic insufficiency (grade 1) was observed in 10.7% of the patients (8.9% for the subcoronary technique, 13% for the root-inclusion technique, and 0% for the full-root technique). When the bioprosthesis was implanted using the subcoronary technique or the root-inclusion technique, the prosthesis was placed inside the recipient aortic root. Using these techniques, a lumen between the double layer of the xenograft and the aortic wall could be observed. With the root-replacement technique, the porcine root became the most proximal part of the ascending aorta. As the native aortic wall was removed, in most cases, no double lumen could be observed with imaging of the ascending aorta.

Intravascular instrumentation may induce syncope or presyncope. It is not known whether asymptomatic subjects also have autonomic reactions, albeit concealed. We addressed this issue by studying 44 healthy young male subjects of various levels of fitness, ranging from inactivity to athletic [mean maximal oxygen uptake was 49.1 (SD 10.7) ml*kg(-1)*min(-1), range 28.7-71.9 ml*kg(-1)*min(-1)]. The autonomic response to venous cannulation was quantified by measuring heart rate before cannulation (HR(1)), after cannulation (HR(2)), and after complete pharmacological autonomic blockade (HR(0) = the intrinsic heart rate). The sympathovagal balance before and after cannulation was computed as HR(1)/HR(0) and HR(2)/HR(0), respectively. The group means of heart rate and sympathovagal balance decreased significantly (paired Student's t-test P0.01) from 62.5 to 59.9 beats*min(-1), and from 0.71 to 0.68, respectively. The maximal decrease in heart rate was 8.8 beats*min(-1), and in the sympathovagal balance was 0.11. Our study demonstrated that the asymptomatic subjects responded to intravenous instrumentation with a concealed autonomic reaction. Thus, from our findings it would seem that intravenous instrumentation interferes with measurements relating to autonomic nervous system activity.

Orthostatic defense is commonly validated with a 60 ° to 80 ° head-up tilt test, addressing the step response rather than the response to permanent orthostasis. During the initial phase of tilt, neural factors predominate, while later, the slower humoral factors fade in. It has been demonstrated that, during adaptation of the circulatory system to the standing conditions, overshoot and undershoot occur. These oscillations hamper straight-forward interpretation of a tilt test, and may contribute to the inconclusiveness of current studies regarding the aging of orthostatic defense. Gradual, progressive, orthostatic load testing seems a valuable alternative. We used a novel, incremental, head-up tilt protocol (0 ° to 80 °, 13 increments) to impose graded orthostatic stress on 46 healthy young adult men (mean age ±SD 25 ± 3 years), ana on 16 healthy late middle-aged men (60 ± 4 years), while recording the electrocardiogram and the blood pressure. A first-order estimate of the heart rate range associated with the sympathovagal transition was made by combined analysis of heart rate and heart rate variability trends. We observed similar responses in heart rate, heart rate variability, and blood pressure. Supine heart rate (61 ± 8 vs 61 ± 7 beats/min), heart rate at the maximal tilt angle (86 ± 13 vs 84 ± 12 beats/min), sympathovagal transition (112 ± 82 vs 111 ± 76 beats/min), percent increase of the rate-pressure product (49 ± 23% vs 43 ± 20%), and the slope of the linear regression of the mean blood pressure on the sine of the tilt angle (8.7 ± 8.3 vs 9.2 ± 7.1 mm Hg) did not differ significantly. We conclude that aging, per se, does not impair orthostatic defense under gradually increasing orthostatic stress.

In the avian heart the right and left atrioventricular (AV) valves not only exhibit their own special anatomical characteristics, but they also are in close proximity to the conduction system. The right AV valve is a single, spiral plane of myocardium, in remarkable contrast to the fibrous structure characteristic of the mammalian tricuspid valve. A ring of Purkinje tissue encircles the avian right AV orifice and connects to the muscular valve. The chicken has no crista supraventricularis, its right AV valve serving that function as well as opening and closing the right AV orifice. The left AV valve consists of three leaflets instead of the two typical of mammalian hearts. Its anterior and posterior leaflets are small; its large aortic (medial) leaflet merges with the bases of both the left and noncoronary cusps of the aortic valve by fibrous tissue, resembling that of the mammalian heart. However, unlike in mammals, there is a slim cylinder of continuous myocardium coursing parallel to this fibrous junction. This unusual arc of myocardium in the chicken serves to complete an entire subaortic ring of myocardium and is thus potentially capable of constricting the outflow tract of the chicken's left ventricle. The middle bundle branch connects with both the muscle arch and the AV Purkinje ring. Thus the myocardium in or near both AV valves (and the left ventricular outflow tract) in the chicken heart is so arranged that it may receive direct early activation from the conduction system. ©1993 Wiley-Liss, Inc.

To identify the effect of myocardial ischemia on systemic neurohormones and vascular resistance, 32 untreated, normotensive patients with coronary artery disease underwent incremental atrial pacing until angina. Arterial and coronary venous lactate and arterial values of catecholamines and angiotensin II were determined at control, at maximal pacing rates, and at 1, 2, 5 and 30 minutes after pacing. Based on pacing-induced ST-segment depression (≥0.1 mV) or myocardial lactate production, or both, patients were selected as ischemic (n = 25) or nonischemic (n = 7). Baseline clinical and hemodynamic data were comparable. During pacing, chest pain was similar (20 ischemic vs 7 nonischemic patients). Also, hemodynamic measurements were comparable, except for contractility, which did not improve, and left ventricular end-diastolic pressure, which significantly increased in ischemic patients. Moreover, during ischemia arterial pressures increased significantly (13%) and systemic resistance increased from 1,470 ± 60 (control) to 1,632 ± 76 dynes · s · cm−5 5 minutes after pacing (p < 0.05) in ischemic but not in nonischemic patients. Pacing did not affect neurohormones in nonischemic patients. In contrast, norepinephrine in ischemic patients increased significantly from 1.7 ± 0.2 (control) to 2.6 ± 0.3 (maximal pacing) and to 3.0 ± 0.4 nmol/liter (1 minute after pacing), whereas angiotensin II levels increased from 6.2 ± 1.4 (control) to 9.3 ± 2.1 pmol/liter (1 minute after pacing, p < 0.05). Epinephrine only increased during maximal rates (0.9 ± 0.1 vs 0.6 ± 0.1 nmol/liter at control, p < 0.05). Thus, myocardial ischemia activates circulating catecholamines and angiotensin II, accompanied by systemic vasoconstriction. Because the latter may amplify ischemia, modulation of this neuroendocrine stimulation may be of therapeutic value.

Heart Rate Variability (HRV) is an important prognostic indicator, particularly in post-infarction patients. Moreover, it can be noninvasively measured. However, it has recently been suggested that Baroreflex Sensitivity (BRS) might be a better prognostic indicator than HRV. The explanation of the predictive power of both these parameters is that they reflect cardiac vagal tone, known to influence the electrical stability of the heart. The authors present a method of measuring BRS which is completely noninvasive. Moreover, the authors have compared HRV and BRS in their ability to provide an indication of cardiac vagal tone.

With the purpose of investigating joint heart rate and heart rate variability changes, the authors studied two groups of young normal subjects with a 10-min (group 1) and 30 min (group 2) lower body negative pressure (LBNP) protocol. In both studies LBNP was applied two times, the first episode at a -15 mmHg and the second episode at a -40 mmHg level. All subjects in the first study completed the protocol. However, the protocol of the second study had to be aborted several times because of presyncopal symptoms during -40 mmHg LBNP. The question of what might have caused these symptoms is addressed. >

The use of advanced imaging modalities for early determination of infarct size is limited in daily practice and therefore, it would be of particular use to estimate infarct size and prognosis by troponin (cTnT). The value of peak and serial 6h high-sensitive (hs) cTnT for estimation of infarct size