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ABSTRACT FULL TEXT FULL-TEXT PDF (2346 KB) CITATION ALERT CITED BY RELATED ARTICLES EXPORT CITATION EMAIL TO A COLLEAGUE RIGHTS/PERMISSIONS [37]Standard image available [38]DOWNLOAD IMAGES NEED REPRINTS? BOOKMARK ARTICLE RR-interval irregularity precedes ventricular fibrillation in ST elevation acute myocardial infarction [39]Miguel E. Lemmert, MD[40]a[41] Corresponding Author Information [42]email address , [43]Mohamed Majidi, MD[44]a, [45]Mitchell W. Krucoff, MD[46]*, [47]Sebastiaan C.A.M. Bekkers, MD[48]a, [49]Harry J.G.M. Crijns, MD, PhD, FHRS[50]a, [51]Hein J.J. Wellens, MD, PhD, FHRS[52]a, [53]Andrzej S. Kosinski, PhD[54]*, [55]Anton P.M. Gorgels, MD, PhD, FHRS[56]a Received 9 August 2009; accepted 15 September 2009. published online 22 September 2009. Background Sudden cardiac arrest is a leading cause of death in industrialized countries, and ischemic ventricular fibrillation (VF) is a frequent cause. Objective The purpose of this study was to determine whether patients with ST elevation myocardial infarction (STEMI) who develop ischemic VF show more overall RR-interval irregularity (RRI) than do STEMI patients without ischemic VF. Methods Ischemic VF was identified in 41 patients from 1,473 digital 12-lead Holter recordings from three separate STEMI studies. Continuous 3-lead and 12-lead electrocardiogram (ECG) snapshots recorded every minute were compared between all ischemic VF patients and 123 random patients without ischemic VF. Time intervals from start of Holter to ischemic VF and equivalent intervals in the controls were used for calculations. ECG variables related to conduction intervals and severity of ischemia were measured using the most ischemic 12-lead ECG. RRI was calculated as the square root of the mean squared differences of successive RR intervals. For RRI, all QRS complexes, including ventricular ectopic beats, were used. Results No baseline differences were observed between the study and control groups, except for male preponderance among ischemic VF patients (90% vs 72%, P = .019). QRS interval, ECG ischemia severity, RRI, and number of ventricular ectopic beats were significantly associated with ischemic VF. Multivariate analysis revealed RRI (odds ratio 1.006, 95% confidence interval 1.001-1.010, P = .016) and ST deviation score (odds ratio 1.073, 95% confidence interval 1.041-1.106, P <.001) as the only statistically significant predictors of ischemic VF. Conclusion In the period before ischemic VF, RRI and ST deviation score are associated with ischemic VF in STEMI patients. These findings could have important pathophysiologic and clinical implications. Keywords: [57]Cardiac arrest, [58]Electrocardiography, [59]Myocardial infarction, [60]Sudden death, [61]Ventricular fibrillation Abbreviations: [62]AUC, [63]area under receiver operating characteristic curve, [64]AV, [65]atrioventricular, [66]ECG, [67]electrocardiogram, [68]HRV, [69]heart rate variability, [70]IQR, [71]interquartile range, [72]ROC, [73]receiver operating characteristic, [74]RRI, [75]RR-interval irregularity, [76]STEMI, [77]ST elevation myocardial infarction, [78]VF, [79]ventricular fibrillation Article Outline o [80]Abstract o [81]Introduction o [82]Methods o [83]Patient population o [84]ECG data o [85]RRI and ventricular ectopic beats o [86]Twelve-lead ECG measurements o [87]Statistical analysis o [88]Results o [89]Baseline characteristics and laboratory values o [90]ECG characteristics o [91]Cutoff values o [92]Discussion o [93]Baseline characteristics o [94]Single 12-lead ECG measurements o [95]Continuous ECG measurements o [96]RRI and total number of ventricular ectopic beats o [97]Heart rate variability o [98]Study limitations o [99]Clinical implications and future research o [100]Conclusion o [101]Acknowledgment o [102]References o [103]Copyright Introduction [104]return to Article Outline Sudden cardiac arrest is one of the leading causes of death in industrialized countries, and ischemic ventricular fibrillation (VF) is one of the most frequent causes.[105]1, [106]2 To date, research aimed at predicting VF has predominantly focused on the postmyocardial infarction stage and nonischemic conditions. Familial history of sudden death recently was demonstrated to be an important risk factor for VF in an ST elevation myocardial infarction (STEMI) population,[107]3 suggesting that genetic factors are involved and that predisposition to ischemic VF differs among patients. Inhomogeneity of intramyocardial conduction velocity plays a role as a substrate for reentrant ventricular arrhythmias and sudden death during acute ischemia.[108]4, [109]5, [110]6, [111]7, [112]8 In the current study, we introduce the novel electrocardiographic (ECG) parameter of overall RR-interval irregularity (RRI), which is measured by taking all QRS complexes into account, irrespective of their origin. A greater RRI could lead to increased inhomogeneity of conduction velocities and refractory periods, facilitating ischemic VF. Using single 12-lead ECGs, our group recently demonstrated longer PR and QRS conduction intervals in first STEMI patients developing ischemic VF.[113]9 This finding supports the concept of increased inhomogeneity in conduction velocity and calls upon further elucidation of the concept. Thus, we tested the hypothesis that cardiac rhythm characteristics preceding ischemic VF are different from those in ischemic patients without VF, particularly with regard to the novel ECG parameter RRI. Methods [114]return to Article Outline Patient population A retrospective database consisting of 1,473 24-hour Holter recordings was retrieved from the ECG core laboratory of the Duke Clinical Research Institute (Durham, NC, USA). The database consists of Holter recordings from STEMI patients who were included in three separate safety-efficacy STEMI studies between April 2002 and November 2003. The database includes all analyzable Holter recordings from two cohorts (CASTEMI[115]10 and EMERALD,[116]11 n = 1,031) treated with direct percutaneous coronary intervention and one cohort treated with thrombolytic therapy (RAPSODY, n = 442). All of these patients were older than 18 years, had presented with diagnostic ST elevation on standard ECG, and had symptom duration <= 6 hours. As part of the study protocols, all patients were connected to 24-hour digital 12-lead Holter recorders immediately after hospital admission, prior to any therapeutic intervention in the hospital. For the current study, all 1,473 Holter recordings were examined for ischemic VF. Ischemic VF was defined as irregular undulations of varying shape and amplitude on ECG without discrete QRS or T waves. To ensure the ischemic nature of the VF, only patients with VF that occurred before percutaneous coronary intervention and/or in the presence of persisting ST deviation were included in the study. Patients in whom VF occurred in conjunction with ECG signs of reperfusion were considered to have reperfusion VF rather than ischemic VF and were not included in the study (n = 5). Patients who showed regular monomorphic ventricular tachycardias rather than VF also were excluded from the study (n = 19). Forty-one patients (2.8%) with ischemic VF were identified (study group). For comparison, for each VF patient, three patients without ischemic VF (control group) were selected, only matched for the original study cohort. Selection was done randomly using the statistical software SPSS for Windows (release 12.0.1, SPSS, Inc., Chicago, IL, USA), providing a total of 123 control patients. Clinical descriptors noted include baseline characteristics (gender, age, diabetes mellitus, hypertension, hypercholesterolemia, current smoking, and history of acute myocardial infarction), coronary angiographic data (culprit lesion), and plasma levels of cardiac enzymes. ECG data Holter recordings (DR180+, NorthEast Monitoring, Maynard, MA, USA) consisted of digital 24-hour 3-lead recordings (leads V5, V1, and III), with a complete Mason-Likar 12-lead ECG (calibration 10 mm/mV, speed 25 mm/s) available every minute and featured designated analysis software (Holter 5 LX Analysis version 5.2, NorthEast Monitoring). For each VF patient, the time interval from start of recording to onset of ischemic VF and the equivalent time interval in the three matched controls were used for analysis, disregarding the residual recording time. Computerized labeling of QRS complexes and RR intervals on Holter recordings was reviewed and corrected on a beat-to-beat basis by a trained physician (M.E.L.). RRI and ventricular ectopic beats For this analysis, we introduce RRI as a novel parameter. RRI was calculated using the designated software's capability to calculate heart rate variability (HRV). HRV is the variation in heart rate resulting from sympathetic and vagal influences on the sinus node. HRV disregards all ECG complexes other than sinus beats. Using continuous 3-lead Holter recordings, the software is capable of several HRV measurements within the time domain. Similar to standard HRV measurements, RRI calculations were performed using the three leads of the Holter recordings. Contrary to standard HRV measurements, RRI takes all ECG complexes, irrespective of their origin, into account, including (episodes of) atrial fibrillation or atrial flutter, paced rhythms, and supraventricular and ventricular complexes. To enable RRI measurements by the software, all ECG complexes were manually labeled as sinus beats. Time intervals before onset of ischemic VF frequently were short. Therefore, the square root of the mean squared differences of successive RR intervals method was used because it reflects short-term variations in RR intervals, as previously described in detail.[117]12 For the software to perform HRV measurements and thus RRI measurements, a minimum of 5 minutes of recording time is required. The total number of ventricular ectopic beats was counted for each patient, again during the time interval from start of recording to onset of ischemic VF and the equivalent time interval in the control patients. Twelve-lead ECG measurements Our group recently showed significant differences in PR and QRS conduction intervals as well as severity of ischemia between VF patients and control patients. For this reason, similar measurements were made in the current study using the designated software, which features electronic calipers for 12-lead ECGs. For each patient, one 12-lead ECG showing the most pronounced ST-segment deviation was used because these ECGs are expected to be the best representation of ischemia-induced conduction defects. The measurements have been described previously,[118]9 with the difference that, because of the digital ECG data and the accompanying Holter software, the measurements were done using the electronic calipers of the analysis software instead of manually. Statistical analysis Data analysis and case-control randomization were performed using SPSS for Windows (release 12.0.1). Continuous variables are expressed as median and interquartile range (IQR) and categorical variables as percentages. For comparison of continuous variables, a Student's t-test for normally distributed data or a Mann-Whitney test or Wilcoxon signed-rank test for non-normally distributed data was used. For comparison of categorical variables, a Pearson chi-square test or Fisher exact test was used. All statistical tests were two-tailed, and P <.05 was considered significant. ECG characteristics showing a significant univariate relation with the occurrence of VF but lacking multicollinearity (defined as r > 0.4) were included in multivariate logistic regression. Variables were removed stepwise from the model when P was >.10. Variables with P <.05 in the final model were considered independent contributors and are reported in the results. In the final model, tests were done for interactions between main predictors. The predictive accuracy of the final model is reported as the area under the receiver operating characteristic (ROC) curve (AUC). Cutoff values for ECG characteristics by which most VF patients can be correctly classified are identified by applying the Pythagorean theorem to ROC curves, which is a mathematical determination of the cutoff value with the graphically shortest distance to a sensitivity and specificity of 1. Results [119]return to Article Outline Baseline characteristics and laboratory values No statistically significant differences regarding baseline characteristics and laboratory values were found between the VF patients and the controls, except for a significantly higher percentage of males among the VF patients (90% vs 72%, P = .019; [120]Table 1). Table 1. Baseline characteristics of the study population Ischemic VF (n = 41) No ischemic VF (n = 123) P value Age (years) 61 (54-71) 59 (52-71) .54 Male 90 72 .019 Anterior wall infarction 31 29 .84 Culprit artery .32 Left anterior descending branch 20 21 Right coronary artery 77 66 Left circumflex branch 3 13 Comorbidity/risk factor Diabetes mellitus 10 18 .32 Hypertension 39 42 .71 Hypercholesterolemia 33 26 .41 Smoking 38 38 1 Prior myocardial infarction 11 11 1 Original study cohort .30 CASTEMI[121]10 3 97 EMERALD[122]11 3 97 RAPSODY 2 98 Laboratory values Initial CK 1.6 (0.3-10.3) 2.6 (0.7-6.9) .70 Post PCI CK 8.1 (5.6-21.9) 10.1 (5.0-14.5) .75 Initial CK-MB 3.1 (1.7-7.7) 4.2 (0.6-7.6) .77 Post PCI CK-MB 6.9 (2.0-11.0) 8.5 (4.1-13.1) .41 Post PCI troponin-T 50.9 (27.5-74.2) 15.4 (8.2-61.8) 1 Note: Information on the culprit artery was available for 127 patients from the PCI cohorts (CASTEMI and EMERALD). For the thrombolytics cohort (RAPSODY), the distinction between anterior wall infarctions and nonanterior wall infarctions was available. Values are given as median (interquartile range) or percent. CK = creatine kinase; CK-MB = creatine kinase-MB isoenzyme; PCI = percutaneous coronary intervention; VF = ventricular fibrillation. ECG characteristics ECG characteristics are listed in [123]Table 2. All patients were in sinus rhythm, except for six (four VF patients, two controls) with atrial fibrillation, which precluded assessment of sinus rate and PR interval. One VF patient had a paced rhythm during part of the Holter recording. One VF patient and two control patients showed atrioventricular (AV) nodal escape rhythms. Two additional control patients had high-degree AV block. Table 2. ECG characteristics of the study population Ischemic VF (n = 41) No ischemic VF (n = 123) P value Sinus rate (min-1) 74 (62-85) 73 (65-85) .719 PQ (ms) 177 (160-216) 164 (153-181) .055 QRS (ms) 103 (88-115) 93 (83-104) .018 QTc Bazett (ms) 417 (390-446) 414 (396-414) .822 Peak ST deviation (mm) 7 (5-10) 4 (2-7) <.001 Grade of ischemia 3 (2-3) 2 (2-3) .004 No. of leads with ST deviation 10 (9-11) 7 (4-10) <.001 STdev (mm) 36 (26-50) 20 (11-30) <.001 Measuring time (minutes) 29 (16-57) 29 (16-57) N/A Total no. of ventricular ectopic beats 73 (19-268) 19 (2-106) .006 RRI (ms) 132 (100-197) 73 (39-122) <.001 RRI-5 min (ms) 186 (97-237) 44 (22-101) <.001 Values are given as median (interquartile range). RRI = RR-interval irregularity; RRI-5 min = RR-interval irregularity in the last 5 minutes of measuring time; STdev = ST deviation score, the sum of all ST deviations on 12-lead ECG; VF = ventricular fibrillation. With regard to measurements using single 12-lead ECGs, VF patients showed a longer QRS interval [103 ms (IQR 88-115 ms) vs 93 ms (IQR 83-104 ms), P = .018] and a larger amount of ischemia, as measured by peak ST deviation, grade of ischemia,[124]13 total number of leads with ST deviation, and ST deviation score. With regard to continuous ECG measurements, the median measuring time was 29 minutes (IQR 16-57 minutes). Because the requirement of at least 5 minutes of recording time prior to ischemic VF could not be met, the computer software did not allow RRI measurement in three VF patients and subsequently nine control patients. VF patients showed a higher RRI [132 ms (IQR 100-197 ms) vs 73 ms (IQR 39-122 ms), P <.001] and more ventricular ectopic beats [73 (IQR 19-268) vs 19 (2-106), P = .006]. Excluding the recordings with atrial fibrillation from the analysis, did not affect the results regarding the RRI measurements. Logistic regression was applied, with presence of ischemic VF as the dependent variable and variables showing univariate significance (QRS interval, ST deviation score, total number of ventricular ectopic beats, RRI) as the independent variables. Because we recently showed ST deviation score to be an independent predictor of ischemic VF[125]9 and we wanted to correct for multicollinearity between the variables measuring the amount of ischemia, ST deviation score was the only ischemia parameter entered in the logistic regression. This multivariate analysis revealed that only a higher RRI (odds ratio 1.006, 95% confidence interval 1.001-1.010, P = .016) and a higher ST deviation score (odds ratio 1.073, 95% confidence interval 1.041-1.106, P <.001) were independently associated with an increased chance of ischemic VF ([126]Table 3). The interpretation of these odds ratios is that an increase in RRI of 1 ms corresponds to an increased chance of ischemic VF of 0.6%. Table 3. Multivariate analysis of the study population Odds ratio 95% Confidence interval P value RR-interval irregularity (ms) 1.006 1.001-1.010 .016 STdev (mm) 1.073 1.041-1.106 <.001 Area under the receiver operating characteristic curve is 0.835. STdev = ST deviation score, the sum of all ST deviations on 12-lead ECG. For our study population, this means that, based on only RRI measurements, patients who developed VF had a 41.5% (1.006 ^ [132 ms - 73 ms] = 1.415) more chance of doing so than the patients who did not develop VF. Similarly, an increase in ST deviation score of 1 mm implies an increased chance of ischemic VF of 7.3%. The predictive accuracy of this model assessed by the AUC was 0.835. In addition, to examine a fixed and shortest possible time frame prior to ischemic VF, RRI was measured in the last 5 minutes of measuring time. This showed an even more marked difference in RRI between VF and control patients [186 ms (97-237 ms) vs 44 ms (22-101 ms), P <.001]. Multivariate analysis using this RRI of the last 5 minutes yielded an RRI odds ratio of 1.012 (95% confidence interval 1.007-1.018, P <.001), with a predictive model accuracy (AUC) of 0.896 (not shown in [127]Table 3). Of note, measurement of RRI in the last 5 minutes was not possible in 7 VF patients and 27 controls because occasional artifact during this time period in these patients reduced the analyzable recording time to less than the required 5 minutes. Cutoff values Based on the optimal (mathematical) balance between sensitivity and specificity, cutoff values for RRI and the ST deviation score were identified. According to these criteria, the cutoff value for RRI is 110 ms, with sensitivity of 74% and specificity of 75%. The cutoff value for the ST deviation score is 27 mm, yielding sensitivity of 74% and specificity of 70%. Discussion [128]return to Article Outline To the best of our knowledge, this study is the first to show that heart rate irregularity, measured as the novel parameter RRI, plays a significant role preceding ischemic VF on continuous ECG recordings retrieved from a large STEMI database. Baseline characteristics No differences in baseline characteristics were found, except for male preponderance in the VF patients. This is not in accordance with previous research in which no gender difference with regard to ischemic VF or sudden cardiac arrest was found.[129]9, [130]14, [131]15, [132]16, [133]17, [134]18 Our finding could be an observation by chance, due to multiple exploratory tests that in no way are related to any hypothesis tested in this study. Single 12-lead ECG measurements The significantly longer QRS interval and the larger amount of ischemia in the VF patients are in agreement with our previous findings on single 12-lead STEMI ECGs.[135]9 Briefly, in that study we found longer conduction intervals in VF patients that may, depending on the site of the occlusion and amount of ischemia, indicate an inhomogeneity in conduction velocity providing the substrate for ischemic VF. The current study adds a continuous aspect to the period preceding ischemic VF. In a multivariate regression model including continuous ECG measurements, only RRI and the amount of ischemia appear to be independently associated with the occurrence of ischemic VF. Continuous ECG measurements The parameters related specifically to the continuous ECG measurements are RRI and total number of ventricular ectopic beats. RRI and total number of ventricular ectopic beats RRI is a novel and unique ECG parameter that combines into a single parameter the multitude of ECG complexes and rhythms occurring in the acute phase of a STEMI by measuring RRI resulting from all such complexes. Examples of large and small RRIs are shown in [136]Figure 1. [137]View full-size image. [138]View Large Image [139]Download to PowerPoint [140]Standard image available Figure 1. RR-interval irregularity (RRI) in ventricular fibrillation (VF) patient (A) and matched control patient (B). Primarily due to irregular runs of ventricular ectopic beats, the VF patient had an RRI of 257 ms prior to the ischemic VF (red arrow), whereas the control patient had an RRI of 20 ms in the equivalent time interval. Green complexes indicate sinus beats; red complexes indicate ventricular ectopic beats; blue complexes indicate artifact (not used for any calculations). To our knowledge, the only continuous ECG parameter suggested to be associated with ischemic VF occurring in the acute phase of a STEMI is an increased number of ventricular ectopic beats prior to ischemic VF.[141]19 However, the predictive value of these so-called warning arrhythmias has been questioned by other researchers.[142]20, [143]21 In our study population, we were able to reproduce the finding that frequent ventricular ectopic beats represent a harbinger of ischemic VF. These previously reported contradictory results may be explained by our additional finding that the total number of ventricular ectopic beats was not an independent predictor of ischemic VF. RRI was the only independent continuous ECG predictor of ischemic VF, suggesting that the mere presence of ventricular ectopic beats is less important than rhythm irregularity. The manner in which RRI is associated with ischemic VF could be as follows. RRI leads to inhomogeneity in conduction velocity and refractory periods. Beat-to-beat changes in refractoriness, induced by RRI, may become pronounced in ischemic areas due to ischemia-related postrepolarization refractoriness, an effect suggested by our data to be even more pronounced in the final 5 minutes preceding ischemic VF. Subsequent, relatively shortly coupled beats may block or conduct slowly in these areas and instantaneously create a substrate vulnerable to ischemic VF. Shortly coupled beats do not necessarily induce reentry and VF; rather, they set the stage. The finding that the number of leads showing ST deviation was associated with ischemic VF might indicate a role for more widespread myocardial ischemia rather than merely local severity of ischemia. This could add to the heterogeneity of postrepolarization refractoriness. Although not an independent predictor, this concept is supported by a larger region at risk associated with VF found in a previous study using coronary angiography.[144]16 Heart rate variability The RRI measurements were performed using the software's mathematical capabilities to calculate HRV. Although technically possible, actual HRV measurements are not reported here. HRV has been recognized as a marker of the relationship between the autonomic nervous system and cardiac mortality. A decreased HRV has been proposed as a predictor of ventricular arrhythmias and sudden death in different patient populations, mostly consisting of patients in the postmyocardial infarction phase or with nonischemic cardiac diseases.[145]12, [146]22, [147]23, [148]24, [149]25 Most studies attributing a predictive role to HRV were specifically designed to measure this parameter for sufficiently long periods of sinus rhythm in a chronic care setting. The current study relates to a completely different clinical situation, not only because of its acutely ischemic population but also because of the relatively short measuring times with frequent ventricular ectopy. Thus, the clinical meaning of standard HRV measurements would be questionable in our study population. Study limitations The population studied was a selected population because all patients survived until hospital admission. Therefore, whether our findings can be generalized to the situation outside the hospital is not known. The study variables were derived from three separate studies, so possibly the study population was not homogeneous. In spite of this, the association we found between RRI, amount of ischemia, and ischemic VF was very consistent across studies. All patients were derived from STEMI intervention trials who met certain ST-segment criteria for inclusion. Therefore, whether the results are applicable to non-STEMI patients or patients with demand ischemia rather than supply ischemia is not known. Finally, we have no information on use of medication. However, in a previous study we found no influence of any type of medication on development of ischemic VF.[150]9 Furthermore, it is more likely that medications such as beta-blocking agents would influence RR-interval duration rather than RRI. In this regard, it should be noted that there was no difference in sinus rate between VF patients and control patients. However, it should be taken into account that the current database of Holter recordings prior to ischemic VF is unique in its size and possibly the best available. Clinical implications and future research The results of this study are important for a better understanding of ischemic VF. Moreover, it provides simple variables with possible implications for clinical use. There is an increased need for monitoring high-risk cardiac patients outside the hospital setting, and the development of monitoring devices with alarm features has been advocated by our group and others.[151]26, [152]27, [153]28 When incorporated within the algorithms of arrhythmia sensing devices, a warning predictor of ischemic VF could lead to improved early identification of individuals at risk. The predictive accuracy of 0.835 by multivariate analysis was high ([154]Table 3). This indicates that RRI and the ST deviation score may be useful as predictors of ischemic VF in STEMI patients. The cutoff value for RRI is 110 ms, with sensitivity of 74% and specificity of 75%. The cutoff value for the ST deviation score is 27 mm, yielding sensitivity of 74% and specificity of 70%. Because false-positive identification of STEMI patients at risk for ischemic VF is preferable to false-negative failure to identify, it could be speculated that different (ranges of) cutoff values with higher sensitivities at the cost of lower specificities should be chosen. Sensitivities of (approximately) 80% and 90% and corresponding cutoff values for RRI and the ST deviation score are shown in [155]Figure 2, [156]Figure 3. [157]View full-size image. [158]View Large Image [159]Download to PowerPoint [160]Standard image available Figure 2. Sensitivity and specificity for all cutoff values for RR-interval irregularity (RRI). [161]View full-size image. [162]View Large Image [163]Download to PowerPoint [164]Standard image available Figure 3. Sensitivity and specificity for all cutoff values for the ST deviation score (STdev). This study was aimed at STEMI patients who suffer from supply ischemia. One could speculate whether the results can be extrapolated to patients suffering from demand ischemia due to a severe stenosis. In that case, RRI could play a similar role in these patients, leading to ischemic VF (e.g., during exercise or diminished blood supply during sleep). Because the majority of sudden cardiac arrests occurs outside the hospital, a warning predictor of ischemic VF could be useful in patients with known coronary artery disease. The model proposed in the current study could serve as an ischemia model that could be used in future research studying patients who are potential victims of ischemic VF due to demand ischemia. Such populations are currently being studied by our group. Conclusion [165]return to Article Outline Overall RRI and the amount of ischemia are suggested to be useful predictors of ischemic VF occurring in the acute phase of STEMI. Acknowledgments [166]return to Article Outline We thank W.R. Dassen, PhD, for statistical advice. 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Real-time detection and alerting for acute ST-segment elevation myocardial ischemia using an implantable, high-fidelity, intracardiac electrogram monitoring system with long-range telemetry in an ambulatory porcine model. J Am Coll Cardiol. 2006;11:2306-2314. [201]a Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands [202]* Duke University Medical Center/Duke Clinical Research Institute, Durham, North Carolina, USA [203]Corresponding Author Information Address reprint requests and correspondence: Dr. Miguel E. Lemmert, Maastricht University Medical Center, Department of Cardiology, PO Box 5800, 6202 AZ Maastricht, The Netherlands This research was supported by an unrestricted grant from Philips Healthcare, Seattle, Washington. PII: S1547-5271(09)01043-1 doi:10.1016/j.hrthm.2009.09.024 © 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved. [204]View previous. 12 of 28 [205]View next. [206]Copyright © 2010 Elsevier, Inc. 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