Harry J.G.M. Crijns

No difference in cardiac event-free survival between positron emission tomography-guided and single-photon emission computed tomography-guided patient management: a prospective, randomized comparison of patients with suspicion of jeopardized myocardium.

OBJECTIVES We sought to prospectively compare nitrogen-13 (13N)-ammonia/18fluorodeoxyglucose (18FDG) positron emission tomography (PET)-guided management with stress/rest technetium-99m (99mTc)-sestamibi single-photon emission computed tomography (SPECT)-guided management. BACKGROUND Patients with evidence of jeopardized (i.e., ischemic or viable) myocardium may benefit from revascularization, whereas patients without it should be treated with drugs. Both PET and SPECT imaging have been proven to delineate jeopardized myocardium. When patient management is based on identification of jeopardized myocardium, it is unknown which technique is most accurate for long-term prognosis. METHODS In a clinical setting, 103 patients considered for revascularization with left ventricular wall motion abnormalities and suspicion of jeopardized myocardium underwent both PET and SPECT imaging. The imaging results were used in a randomized fashion to determine management (percutaneous transluminal coronary angioplasty [PTCA], coronary artery bypass graft surgery [CABG] or drug treatment). Follow-up for cardiac events (cardiac death, myocardial infarction and revascularization) was recorded for 28 +/- 1 months. The study was designed to have a power of 80% to detect a 20% difference in the event rate between PET- and SPECT-based management. RESULTS Management decisions in 49 patients randomized to PET (12 who had PTCA, 14 CABG and 23 drug therapy) were comparable with 54 patients randomized to SPECT (15 who had PTCA, 13 CABG and 26 drug therapy). In terms of cardiac event-free survival, no differences between PET and SPECT were observed (11 vs. 13 cardiac events for PET and SPECT, respectively; p = NS by the Kaplan-Meier statistic). CONCLUSIONS No difference in patient management or cardiac event-free survival was demonstrated between management based on 13N-ammonia/18FDG PET and that based on stress/rest 99mTc-sestamibi SPECT imaging. Both techniques may be used for management of patients considered for revascularization with suspicion of jeopardized myocardium.

Heart Rate Variability in Patients With Atrial Fibrillation Is Related to Vagal Tone

BACKGROUND Analysis of heart rate variability (HRV) has thus far not been applied in patients with atrial fibrillation, probably because of the presumed absence of any form of patterning of the ventricular rhythm, particularly vagally mediated respiratory arrhythmia. However, such patterning is theoretically conceivable given the function of the atrioventricular node in atrial fibrillation and its susceptibility to autonomic influences. METHODS AND RESULTS Sixteen patients (mean age, 56+/-4 years) with long-term atrial fibrillation on fixed doses of digoxin or verapamil were studied; 12 healthy men in sinus rhythm were used as control subjects. HRV (standard deviation of RR intervals [SD], coefficient of variance [CV], the root-mean-square of successive difference [RMSSD], and low-frequency [LF] and high-frequency power [HF]) was analyzed during 500 RR intervals at baseline, after administration of propranolol (0.2 mg/kg I.V.), and after subsequent administration of methylatropine (0.02 mg/kg I.V.). HRV at baseline and changes in HRV after methylatropine were then related to vagal tone (vagal cardiac control), quantified as the decrease in mean RR after methylatropine. Baseline HRV was higher in the atrial fibrillation group than in the control group; after propranolol, HRV increased in both groups; after methylatropine, HRV neared zero in the control group, whereas it returned to baseline values in the atrial fibrillation group. SD, RMSSD, LF, and HF at baseline were significantly (P<.05) correlated with vagal tone in the control group but also in the atrial fibrillation group (correlation coefficients of .60, .61, .57, and .64, respectively). Even stronger correlations were observed between changes in these parameters after methylatropine and vagal tone, particularly in the atrial fibrillation group (correlation coefficients of .89, .87, .72, and .90, respectively). CONCLUSIONS This study shows that HRV in patients with atrial fibrillation is related to vagal tone.

Continuous vs episodic prophylactic treatment with amiodarone for the prevention of atrial fibrillation : a randomized trial

CONTEXT Amiodarone effectively suppresses atrial fibrillation but causes many adverse events. OBJECTIVE To compare major events in patients randomized to receive episodic amiodarone treatment with those who received continuous amiodarone treatment while still aiming to prevent atrial fibrillation. DESIGN, SETTING, AND PARTICIPANTS A randomized trial of 209 ambulatory patients with recurrent symptomatic persistent atrial fibrillation, conducted from December 2002 through March 2007 at 7 Dutch medical centers. INTERVENTION Patients were randomly assigned to receive either episodic or continuous amiodarone treatment after electrical cardioversion following amiodarone loading. Episodic amiodarone treatment was discontinued after a month of sinus rhythm and reinitiated if atrial fibrillation relapsed (1 month peri-electrical cardioversion). In the continuous treatment group amiodarone was maintained throughout. MAIN OUTCOME MEASURES The primary end point was a composite of amiodarone and underlying heart disease-related major events. The secondary end points were all-cause mortality and cardiovascular hospitalizations. RESULTS After a median follow-up of 2.1 years (range, 0.4-2.5 years), 51 (48%) of those receiving episodic treatment vs 64 (62%) receiving continuous treatment had sinus rhythm (P = .05). There were 85 atrial fibrillation recurrences (80%) among the episodic treatment group vs 56 (54%) in the continuous treatment group (P < .001). No significant difference existed in the incidence of the primary composite end point between each group (37 [35%] episodic vs 34 [33%] continuous; incidence rate difference, 0.2; 95% confidence interval [CI], -10.2 to 10.6). However, there were nonstatistically significant differences in the incidence of amiodarone-related major events (20 [19%] episodic vs 25 [24%] continuous; incidence rate difference, -2.0; 95% CI, -8.7 to 4.6) and underlying heart disease-related major events (17 [16%] episodic vs 9 [9%] continuous; incidence rate difference, 3.6; 95% CI, -1.6 to 8.7). All-cause mortality and cardiovascular hospitalizations were higher among those receiving episodic treatment (56 [53%] vs 35 [34%], P = .02). CONCLUSIONS In this study population, there was no difference in the composite of amiodarone and cardiac major adverse events between groups. However, patients receiving episodic treatment had a significantly increased rate of atrial fibrillation recurrence and a significantly higher rate of all-cause mortality and cardiovascular hospitalizations. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00392431.

AUTOPERFUSION BALLOON VERSUS STENT FOR ACUTE OR THREATENED CLOSURE DURING PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY

Efficacy and major clinical end points were compared in 61 patients treated with a Stack autoperfusion balloon versus 36 patients who received a Palmaz-Schatz stent for acute or threatened closure during coronary angioplasty. The groups were comparable regarding baseline clinical characteristics. Procedural success was achieved in 43 patients (70%) treated with an autoperfusion balloon versus 34 patients (94%) who received a stent (p < 0.02). Emergency bypass surgery was performed in 13 patients (21%) with the autoperfusion balloon versus none of the patients with a stent (p < 0.001). In the stent group, 3 patients (8%) died (p < 0.05); 2 deaths were caused by thrombotic reclosure, and 1 patient died after unsuccessful stent delivery. Subacute reclosure during hospitalization occurred in none of the patients with autoperfusion versus 8 patients with the stent (22%) (p < 0.0002). Therefore, the number of patients with successful stent implantation at discharge decreased to 26 (72%). At 3-month follow-up in all patients with a successful intervention, reclosure or angiographic restenosis (> 50%) occurred in 13 patients with autoperfusion (30%) versus 3 patients with stents (12%) (p = NS). There was no difference in event-free survival during follow-up. Thus, both interventions were equally successful in the treatment of acute and threatened closure. More emergency surgery was performed in the autoperfusion balloon group, whereas a higher subacute reclosure rate was seen in the stent group. At 3-month follow-up, there were no significant differences regarding reclosure, restenosis, and event-free survival.

Hemodynamic effects of iodixanol and iohexol during ventriculography in patients with compromised left ventricular function

A crossover study was performed to compare the hemodynamic effects of the iso‐osmolar contrast agent iodixanol (Visipaque®) 320 mg I/ml to those of the low‐osmolar iohexol (Omnipaque®) 350 mg I/ml. The main hypothesis was that iodixanol and iohexol would affect left ventricular end‐diastolic pressure (LVEDP) to different degrees. In 48 patients with reduced cardiac function (mean ejection fraction 33.4%), one ventricular injection was performed with each contrast medium. Ventricular, aortic and right atrial pressures and heart rate were measured continuously. Cardiac output (using Ficks principle) and systemic vascular resistance were calculated. LVEDP increased with both agents, but significantly less after iodixanol than after iohexol (P < 0.01), also in subgroups of patients in whom baseline LVEDP was severely increased and in whom 3‐vessel disease was present. Immediate changes in variables reflecting vasodilatation were similar with both agents. In conclusion, both contrast agents influenced hemodynamics during ventriculography, but iodixanol had significantly less influence on LVEDP than did iohexol. Cathet. Cardiovasc. Intervent. 50:314–321, 2000.

Effects of streptokinase during acute myocardial infarction on the signal-averaged electrocardiogram and on the frequency of late arrhythmias

Although a number of studies have shown that the incidence of late potentials is lower after thrombolytic therapy, it is not known whether this is paralleled by fewer arrhythmic events during long-term follow-up. In patients with first acute myocardial infarction, filtered QRS duration was significantly shorter when treated with streptokinase (95 +/- 11 ms, n = 53) than when treated with conventional therapy (99 +/- 12 ms, n = 77, p < 0.05). The low-amplitude signal (D40) was shorter after thrombolysis (28 +/- 11 vs 33 +/- 12 ms, p < 0.02). Terminal root-mean-square voltage did not differ significantly (41 +/- 24 vs 35 +/- 23 microV). Irrespective of treatment, late potentials were predictive in the complete group (n = 171) for arrhythmic events during follow-up (13 +/- 6 months, range 6 to 24) (hazard ratio 7.7, p < 0.02, Cox proportional-hazards survival analysis), but treatment (streptokinase vs conventional) did not significantly affect outcome when added to the model. It is concluded that thrombolysis prevents the development of late potentials. However, this study does not confirm the hypothesis that prevention of late potentials leads to a decrease in arrhythmic events.

Late potentials, QTc prolongation, and prediction of arrhythmic events after myocardial infarction

In a series of 171 consecutive survivors of acute myocardial infarction, the predictive value of late potentials and QTc prolongation was prospectively assessed. QT intervals were measured in lead V2, corrected QT (QTc) was calculated using Bazetts equation (cut-off value 440 ms). Late potentials were considered to be present when all of the three signal-averaged electrocardiographic variables were abnormal (i.e. QRS > 114 ms, D40 > 38 ms, and V40 < 20 microV). Complete follow-up was obtained (mean 13 +/- 6 months, range 6-24 months). Six percent of the patients had an arrhythmic event (i.e. sustained ventricular tachycardia or sudden death). The relative risk of late potentials for arrhythmic events was 7.7 (P < 0.02). The relative risk of QTc > 440 ms was 1.1 (NS). In a multivariate analysis, the addition of QTc prolongation did not significantly improve the prognostic value of late potentials alone. It is concluded that late potentials are predictive of arrhythmic events after myocardial infarction, but the presence of concomitant QTc prolongation does not worsen the prognosis.

Prediction of Lesion Size Through Monitoring the 0°C Isothermic Period Following Transcatheter Cryoablation

A prototype steerable 8.5F bipolar catheter fitted with a feedback thermocouple was tested in 7 anaesthetized pigs (30 kg) guided by the electrocardiogram in order to modify the AV nodal and His-Purkinje system conductive properties. Thermal energy was delivered by a pressurized N2O tank (>650 psi) via a cardiac cryo unit (Spembly, Hampshire, UK) into the catheter wherein gas expands resulting in a tip temperature as low as−70± 2°C within 10 seconds. Cryoablation under fluoroscopic and electrocardiographic guidance was applied at distinct sites in both ventricles for 60 or 120 seconds. After a follow-up period of 6 weeks, the ablation lesions found were well demarcated with small margins of hypertrophy of myocardial cells. With respect to lesion volume variability (8–207 mm3) and geometry, a relationship between the 0°C isothermic period and cryolesion volume was found. Results of an in vitro model corroborated this relationship. Therefore, an isothermic period probably can predict the lesion size and its geometry in terms of lesion depth. This potential therapeutic mode of transcatheter cryoablation deserves further investigation.

Electrophysiologic and antiarrhythmic effects of intravenous bisoprolol in atrioventricular nodal reentry tachycardia

Abstract Beta-blockade may be useful in the termination and prevention of atrioventricular nodal reentry tachycardia (AVNRT). An electrophysiologic study was performed in 9 patients (4 men and 5 women; mean ± SD age, 56 ± 16 years) with documented AVNRT before and after the intravenous administration of 5 mg of bisoprolol. In 5 of the 9 patients, AVRNT was terminated by bisoprolol, and AVNRT could no longer be induced in 6 of the 9 patients. Bisoprolol significantly prolonged the Wenckebach cycle length but did not affect fast pathway refractoriness or atrioventricular (AV) nodal conduction time during sinus rhythm or various paced cycle lengths up to 430 milliseconds. Conversely, it significantly prolonged the mean atrium-His bundle (AH) interval during AVNRT from 244 ± 65 milliseconds to 320 ± 64 milliseconds. These observations suggest that the effects of bisoprolol on the AV node, primarily at short cycle lengths, are rate dependent. Due to AH prolongation, mean tachycardia cycle length significantly increased from 313 ± 58 milliseconds to 378 ± 50 milliseconds, but there was no difference in the relative amount of prolongation between responders (60.8 ± 26 ms) and nonresponders (64.6 ± 37 ms). Bisoprolol appears to be useful in the termination and prevention of AVNRT during programmed electrical stimulation studies. Its effects on the AV node are use dependent.

DIFFERENCES BETWEEN HS-TROP T AND NT-PROBNP AS PREDICTORS FOR CARDIOVASCULAR OUTCOMES IN PATIENTS WITH PERMANENT ATRIAL FIBRILLATION: DATA FROM THE RACE II STUDY

High-sensitive troponin T (hs-Trop T) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) are important clinical markers and could be useful to assess cardiovascular (CV) outcomes in patients with permanent atrial fibrillation (AF). Of 543 (88%) of the total 614 patients randomized