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Fragmented QRS complex in patients with implantable cardioverter defibrillator—Prevalence and predisposing factors
Accepted Manuscript Fragmented QRS complex in patients with implantable cardioverter defibrillator—Prevalence and predisposing factors
Anna Kucharz, Piotr Kulakowski PII: DOI: Reference:
S0022-0736(18)30270-X doi:10.1016/j.jelectrocard.2018.07.014 YJELC 52670
To appear in:
Journal of Electrocardiology
Please cite this article as: Anna Kucharz, Piotr Kulakowski , Fragmented QRS complex in patients with implantable cardioverter defibrillator—Prevalence and predisposing factors. Yjelc (2018), doi:10.1016/j.jelectrocard.2018.07.014
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ACCEPTED MANUSCRIPT Fragmented QRS complex in patients with implantable cardioverter defibrillator – prevalence and predisposing factors
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Anna Kucharz1 2, Piotr Kulakowski3 1. Department of Cardiology, Saint Vincent a Paulo Hospital, 81-348 Gdynia, ul.
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Wójta Radtkego 1, Poland
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Warszawskiej 5, Poland – present address
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2. Medical Center Płyta Redłowska, 81-466 Gdynia, ul. Bohaterów Starówki
3. Department of Cardiology, Postgraduate Medical School, Grochowski Hospital, 04-
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073 Warsaw, ul. Grenadierów 51/59, Poland.
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Corresponding author: Anna Kucharz MD
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Address for correspondence: Tel: +48 697263096
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Mail: [email protected]
Declaration of interest: none.
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ACCEPTED MANUSCRIPT Abstract Background. Incidence of fragmented (fQRS) and predisposing factors in patients with implantable cardioverter-defibrillator (ICD) have not yet been established. Aim. To examine incidence of fQRS, associated factors as well as predictive value in
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identifying site of coronary artery disease (CAD).
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Methods. Consecutive patients with ICD. Retrospective analysis of demographic,
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clinical and ECG data.
Results. Of 382 patients, 163 (43%) had fQRS. They had more frequently history of
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MI, Q wave, lower left ventricular ejection fraction and prolonged ECG repolarisation
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indices. The presence of fQRS in more than one ECG localisation was associated with higher number of MI and ICD for secondary prevention. By combining fQRS with
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Q wave location, site of CAD could be predicted (total accuracy 84-95%).
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Conclusions. The fQRS is frequent in patients with ICD, especially those with CAD, more advanced cardiac disease and altered ECG repolarisation. The fQRS may
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improve ECG-based non-invasive identification of the site of CAD.
Key words: fragmented QRS, Q wave, implantable cardioverter-defibrillator.
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ACCEPTED MANUSCRIPT
Introduction Arrhythmic death due to ventricular tachycardia/fibrillation (VT/VF) is the most common type of sudden cardiac death (SCD) in patients with advanced organic heart
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disease [1] . Risk stratification in this population is difficult and currently only the value of left ventricular ejection fraction (LVEF) is taken into account when deciding
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whether to implant cardioverter-defibrillator (ICD) for primary prevention of SCD [1].
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However, specificity of this parameter is low and many patients with ICD do not
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experience appropriate device interventions due to lack of VT/VF occurrence [1]. Clearly, there is a need for new non-invasive parameters to better stratify the risk of
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SCD in these patients.
Recently, fragmentation of the QRS complex (fQRS) has gained considerable
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interest. Fragmented QRS on surface ECG probably represents areas of myocardial
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scarring and conduction disturbances in patients with various cardiac disorders [2]. Some studies have shown that fQRS identifies patients with increased risk of SCD [3]
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[4] [5], however, other papers did not confirm these findings [6]. Currently, the role of fQRS in risk stratification is unknown. Also, the prevalence of fQRS and associated
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factors have not been well established. Accordingly, the aim of our study was to examine the incidence of fQRS in patients with ICD – the group with usually severe cardiac disease and most threatened by VT/VF occurrence. We also sought to evaluate factors associated with the presence of fQRS on surface ECG.
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ACCEPTED MANUSCRIPT Material and methods
Patients. The study included 425 consecutive patients who had undergone implantation of ICD/CRT-D device between 2006 and 2011 at the Cardiology
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Department of Saint Vincent a Paulo Hospital in Gdynia, Poland. All patients had either primary or secondary prevention indications according to the current ESC
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guidelines. All patients had signed informed consent for implantation of the device.
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The study design was approved by the Bioethical Committee of the Centre of Postgraduate Medical Education (number 50PB2014, date 15.07.2014).
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Out of 425 patients, 382 patients had very good quality surface 12-lead ECG,
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amenable for detailed analysis of fQRS, and these subjects formed the study group [7]. We analysed medical records and data related to ICD/CRT-D implantation. Baseline demographic data, history of SCD including type of underlying ventricular
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arrhythmia (VT/VF), presence and extent of coronary artery disease (CAD) or dilated cardiomyopathy (DCM), previous myocardial infarction (MI) (including localisation and number of MI) as well as other clinical conditions (including presence of
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supraventricular arrhythmias, hypertension, diabetes mellitus (DM), chronic
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obstructive pulmonary disease (COPD), previous stroke or transient ischaemic attack (TIA), chronic kidney disease (CKD), peripheral arterial disease (PAD) and thyroid disease) were collected. This group was also evaluated according to the NYHA class and echocardiographic findings including LVEF and LV end-diastolic diameter (LVEDD). In addition, results of pre-implant coronary angiography were examined and classified as left anterior descendent (LAD), circumflex (Cx) or right coronary artery (RCA) disease when there was a > 70% narrowing of vessel lumen.
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ACCEPTED MANUSCRIPT Incomplete revascularisation was defined as the presence of significant narrowing of coronary arteries (>70% or >50% of left main) which were not invasively treated either because the results of stress tests were normal (no stress-induced ischaemia) or because of technical difficulties and/or anatomy which precluded angioplasty
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ECG analysis. We analysed resting 12-lead ECG obtained at the time of ICD
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implantation and measured heart rhythm, heart rate, QRS duration, presence of
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BBB/paced QRS, presence and location of both fQRS and Q wave as well as QT duration and dispersion (QTd). Three sets of ECG leads, corresponding to the
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territories supplied by left descending coronary artery (LAD) (anterior leads V1-V5), circumflex artery (Cx) (lateral leads I, aVL and V6) or right coronary artery (RCA)
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(inferior leads II, III and aVF) were identified.
The fQRS was defined as the presence of an additional R wave (R’) or
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notching in the nadir of the S wave, or the presence of >1 R’ (fragmentation) in 2
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contiguous leads corresponding to a major coronary artery territory, for QRS duration <120ms. Patients with QRS duration ≥120ms were not excluded from the study.
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Fragmented QRS in this subgroup was defined as the presence of >2 notches (at least 1 notch more than typical BBB) or multiple notches of the R wave or >2 notches
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in the nadir of the S wave. Fragmented paced QRS was defined by the presence of >2 R’ or >2 notches in the S wave in 2 contiguous leads [8] [9]. Original ECG recordings with fQRS are presented in Figures 1 and 2. In order to minimise errors in fQRS detection, all ECG tracings were evaluated twice by the principal investigator (AK). All problematic ECG recordings were analysed by both AK and PK, and the final diagnosis (fQRS present or absent) was
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ACCEPTED MANUSCRIPT achieved by joint agreement. Both investigators were blinded to the demographic and clinical data of studied patients.
Statistical analysis. All calculations have been carried out by means of Microsoft Excel spreadsheet and STATISTICA, StatSoft, Inc. ver. 12.0. statistical package
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(data analysis software system). In the statistical description of quantitative data
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classical measures of location such as arithmetic means and median, and measures
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of variation such as standard deviation and range were used. The normality of distribution of the variables and variance equality of a studied feature in groups was
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tested by the use of appropriate Shapiro-Wilk's test and a variance equality test. In order to compare groups in pairs for quantitative data, t-test or Mann-Whitney test
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were used with respect to the type of distribution of the variables tested. In case of multiple group comparisons the Kruskal- Wallis test was used as the non- parametric
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equivalent of one way ANOVA. A stepwise multivariable logistic regression model
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analysis was performed in order to identify variables as independent risk factors for fQRS.
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Qualitative data are presented as numbers, proportions, percentages and compared using Chi-square test (according to the number of cases in each compared
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category and/or their expected values, the Pearson’s method, Yates correction, or Fisher’s exact test were used). Sensitivity, specificity, positive and negative predictive value as well as total accuracy were calculated according to standard definitions. In all these calculations the statistical significance level was set at p<0.05.
Results
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ACCEPTED MANUSCRIPT Baseline clinical characteristics are shown in Table 1. The mean age of studied patients was 65.2±11 years and majority were male. Ischaemic aetiology was most common, followed by DCM. All patients had chronic heart failure (CHF) and NYHA class III was the most common stage of CHF. Mean LVEF was significantly reduced. Concomitant diseases included hypertension in more than 50% of patients, followed
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by DM, COPD, PAD and others. Medical treatment included standard agents used in
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patients with CHF and decreased LVEF. Out of antiarrhythmic agents which could
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have influenced QRS complex, amiodarone was by far the most frequent – more than 30% of patients received this drug.
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Details on ECG findings and comparison between wide and narrow QRS
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groups are presented in Table 2. Mean QRS duration in the whole study group was 139 ms±34ms. The prevalence of fQRS was 43%, and the most common location of fQRS were inferior leads (31%), followed by anterior leads and lateral leads. This
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distribution corresponded to the Q wave presence, which was also most frequent in inferior leads. Fragmentation of Q wave, R wave and S wave were noted in 22% to
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49% of patients.
Out of 382 patients included in the study, 209 (54.7%) had prolonged
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(≥120ms) QRS duration. In this subgroup the prevalence of fQRS was significantly higher than in patients with narrow QRS (59% versus 23%, p < 0.0001). In each ECG lead set the incidence of fQRS was higher in patients with wide rather than narrow QRS complex. Also the incidence of fragmented Q, R and S waves was higher in patients with QRS ≥ 120 ms. By definition, the incidence of BBB, IVCD or pacedQRS was significantly higher in patients with wide QRS complex.
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ACCEPTED MANUSCRIPT Comparison between patients with versus without fQRS in the whole study group and in the subgroups with wide and narrow QRS complex is presented in Table 3. In the subgroup with narrow QRS complex, patients with fQRS had more frequently CAD and history of MI, LAD disease, Q wave in anterior leads and incomplete revascularisation. In the subgroup with wide QRS complex, patients with
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fQRS had more often Q wave in inferior leads and greater QTd. In the whole study
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group, patients with fQRS had more frequently ischaemic aetiology, Q wave, lower
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LVEF and more altered ECG repolarisation indices such as QTc and QTd duration. Also QRS width was greater and BBB was more frequent in the fQRS (+) group.
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Comparison of patients with single versus two localisations of fQRS is shown
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in Table 4. Patients with fQRS present in two sets of leads had higher number of MI and more often a history of MI than patients with a single localisation of fQRS. Patients in whom ICD was implanted for primary rather than secondary prevention
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had predominantly fQRS in a single set of ECG leads. Association between the site of CAD and localisation of fQRS in patients with
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ischaemic aetiology is shown in Table 5. There was a significant strong association between LAD disease and the presence of fQRS in anterior leads. There was also a
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significant relationship between Cx disease and fQRS in lateral leads as well as RCA disease and fQRS in anterior leads Association between the site of CAD and localisation of Q wave is shown in Table 6. There was a strong significant association between LAD disease and the presence of Q wave in anterior leads and RCA disease and Q wave in inferior leads. Table 7 shows the accuracy of fQRS, Q wave and combined fQRS and Q wave in identification of the site of CAD disease. Both, fQRS and Q wave performed 8
ACCEPTED MANUSCRIPT better for identification of patients with LAD disease, followed by RCA and Cx disease. Combining fQRS with Q wave increased specificity, positive predictive value and total accuracy of ECG in predicting the site of CAD disease. The results of multivariate analysis are presented in Tables 8 and 9. In the
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group with narrow QRS the LAD disease was the only parameter independently associated with the presence of fQRS. When LAD disease was withdrawn from the
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model the Q wave in anterior leads occurred also independently associated with
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fQRS. In patients with wide QRS, chronic AF and the width of the QRS complex were independent parameters. When the width of QRS was withdrawn from the model, the
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Q wave in inferior leads occurred also independently associated with the presence of
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fQRS.
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Discussion
The main finding of our study is that QRS fragmentation is present in approximately 43% of patients with advanced cardiac disease who are equipped with an ICD and
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occurs more often in individuals with prolonged rather than narrow QRS complex.
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Secondly, there are several significant differences in factors associated with fQRS presence between patients with prolonged versus narrow QRS complex. Thirdly, patients with fQRS visible in more than one set of leads have more frequently remote MI, numerous MI, CAD and history of ventricular arrhythmias requiring ICD implantation (secondary prevention). Fourthly, our study suggests that the presence of fQRS on surface ECG may improve non-invasive prediction of CAD localisation, suggesting which coronary artery is significantly narrowed or blocked.
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ACCEPTED MANUSCRIPT The reported incidence of fQRS varies between the studies. In patients with risk factors referred for cardiology consultation [10] and for coronary angiography [11] fQRS was observed in approximately one third of the population. In a study conducted among ICD patients [12] the prevalence of fQRS was lower (26%) than in our study. In the MADIT II population fQRS was detected in 35% of patients. [3]
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Another study conducted in patients with LV dysfunction showed that 32,5% of
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patients had fQRS [6]. In our study the proportion of patients with fQRS was higher or
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slightly higher than in studies involving patients with cardiac disease. This may be explained by the fact that we included patients with ICD, thus patients with already
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known arrhythmic problem (secondary prevention) or significant cardiac disease (primary prevention) in whom the incidence of arrhythmic markers may be anticipated
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to be high.
The distribution of fQRS among various ECG lead sets was similar to that
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shown in other studies. For example, the MADIT II study found inferior leads as the most frequent site of fQRS [3]. Also in the Finish middle-aged general population inferior leads were the most common site of fQRS and the prevalence of this marker
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was found in 15.7% of all subjects [13]. The fact that inferior leads are the most
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common site of fQRS, regardless of the clinical and demographic characteristics of the studied subjects, suggests that fQRS in inferior leads may not be very specific for identification of subjects with cardiac disease. Our study showed that fQRS is more frequently recorded in patients with wide rather than narrow QRS complex. This may be due to the fact that patients with prolonged QRS tend to have more advanced cardiac disease and more ventricular scarring, providing the substrate for fQRS. Indeed, we found several differences in clinical characteristic between these two subgroups which suggests that patients with 10
ACCEPTED MANUSCRIPT prolonged QRS were sicker. Another possible explanation may be problems with identifying fQRS in patients with BBB although we used modified criteria for fQRS detection in these patients to distinguish between typical ECG changes for BBB and true fQRS in patients with BBB.
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We found that fQRS was associated with CAD rather than DCM. Since fQRS has been shown to be a marker of heterogeneous ventricular activation caused by
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myocardial fibrosis [14] [15], it is not surprising that the prevalence of fQRS is higher
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in patients with CAD and past MI than in patients with less advanced LV injury. Numerous studies have shown the association between the presence of the fQRS
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complexes on ECG and late gadolinium enhancement (LGE) areas on cardiac
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magnetic resonance (CMR) [14] [15]. It has been found to be a marker of a prior MI [8] [9] [16] and poorer collateral circulation [17]. Also complete revascularisation was less common among our patients with fQRS, while larger number of MI correlated
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with fQRS presence in the whole study group. Numerous studies showed association between increased QTd and scar
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tissue and its extent [18] as well as ischemic myocardium [19] in patients with CAD. The QTd also positively correlated with severity of impaired cardiac function [20] and
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was increased in patients without mechanical LV remodelling after CRT-D implantation [21]. To date, no study showed a relationship between fQRS and increase in QT/QTd intervals. Our results suggest that these two parameters may be related and possibly identify patients with greater arrhythmic risk. We found that patients with more diffuse presence of fQRS (more than one set of leads) had more frequently CAD, history of MI and ICD implanted for secondary prevention. This is concordant with the knowledge that the presence of fQRS
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ACCEPTED MANUSCRIPT correlates with the extent of cardiac disease. Thus, the finding of fQRS presence in several sets of leads may be a simple non-invasive marker to identify patients with more severe cardiac disease. Our results are in line with data presented by Tanriverdi et al [22] who showed that prognosis in patients with STEMI was associated with the number of leads with fQRS – the more the leads with fQRS the
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poorer was the outcome. Similar results observed Torigoe [23] et al in patients with
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heart failure and prior MI.
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In our study LAD disease was significantly more often present in patients with fQRS. That corresponds with findings from a study conducted in STEMI population
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where fQRS was mostly associated with anterior territory of MI and thus often
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correlated with proximal LAD lesion [24]. Perhaps LAD disease is more than other sites of CAD associated with QRS fragmentation due to being responsible for larger MI causing more visible ECG changes. Results of multivariate analysis confirmed
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that in patients with narrow QRS the presence of fQRS was independently associated with LAD disease.
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In patients with wide QRS complex chronic AF and width of QRS complex were independently associated with fQRS. It may be speculated that both chronic AF
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and wider QRS complex are markers of more advanced cardiac disease in this group of patients which, in turn, is associated with higher prevalence of fQRS. A new finding is that fQRS may improve non-invasive identification of localisation of CAD. When fQRS was added to Q wave then the specificity and total accuracy of ECG in identifying CAD disease increased significantly. The highest values were obtained for Cx disease, however, this finding is limited by the very low number of patients with both fQRS and Q wave present in lateral leads. The accuracy
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ACCEPTED MANUSCRIPT of identification of patients with LAD disease was better than patients with the RCA disease. These findings may be of practical value when analysing standard ECG in patients with CAD. The lack of association between fQRS in inferior leads and localisation of diseased coronary artery (for example, RCA) may be explained by the fact that fQRS in inferior leads may be less specific for the presence of cardiac
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disease because it is present in nearly 16% of healthy subjects [13]. Similar findings
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have been presented by Euybogly et al [25] and Guo R et al [26] who also suggested
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that fQRS in anterior leads may be a non-invasive marker for LAD disease. However, they examined different patient population than in our study.
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Limitations. Our study has several limitations. First, although the total number of
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analysed patients was quite high, the subgroup analysis was in some cases limited by a relatively small number of patients. Second, our study is a retrospective analysis of ECG and associated factors, however, all clinical, echocardiographic and ECG
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data were collected prospectively at the time of patients hospitalisations and clinic visits. Thirdly, the fQRS analysis may be difficult in some ECG tracings. We tried to minimize the risk of false positive or false negative findings by careful inspection of
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ECG tracings, repeated analysis of each ECG recording and resolving all problematic
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tracings by joint agreement (AK and PK). Fourthly, data on recurrent ischaemia were not collected so we were not able to assess the effects of possible ischaemia on fQRS. Finally, Holter ECG or short-term ECG recordings were not available for analysis, therefore, we were not able to assess the relationship between the autonomic tone and fQRS
Conclusions
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ACCEPTED MANUSCRIPT Fragmented QRS detected on surface ECG in ICD recipients is a frequent finding, is associated with etiology (CAD versus DCM), extent of disease, history of MI and duration of QRS. There are several differences in clinical and ECG variables between patients with fQRS and narrow versus prolonged QRS complex. The site of fQRS in a 12 lead ECG corresponds to the diseased coronary artery and may possibly be used
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as a non-invasive marker of the location of CAD.
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ACCEPTED MANUSCRIPT Table 1. Baseline characteristics of the study population.
Parameter
Results
Male gender
319 (83.5%)
Age (years)
65.2 ±10.8
CAD
282 (74.0%)
History of MI
228 (59.7%) 154 (40.6%)
1 4 2
129 (34.0%)
3 5 4
20 (5.3%)
5
1 (0.3%)
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71 (18.7%) 4 (1.1%)
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Number of MI
History of CABG/PCI
186 (48.9%)
Complete revascularisation
194 (63.8%) 107 (28.2%)
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DCM HCM
10 (2.6%) 3 (0.8%)
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ARVD LVEF (%) LVEDD (cm) I II IV
Concomittant diseases Diabetes mellitus Hypertension
4 (2.3%) 44 (11.5%) 112 (29.3%)
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COPD
10 (5.8%) 88 (51.2%)
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III
6.5±3.3 70 (40.7%)
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NYHA class
27.7±10
222 (58.1%) 35 (9.2%)
Stroke/TIA
33 (8.7%)
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Peripheral artery disease Hypothyroidism
14 (3.7%)
Hyperthyroidism
18 (4.7%)
Drugs which may affect QRS Beta blocker
349 (91.8%)
Amiodarone
119 (31.3%)
Sotalol
8 (2.1%)
Calcium channel blockers
39 (10.3%)
Digoxin
66 (17.4%)
Abbreviations: CAD=coronary artery disease; MI=myocardial infarction; CABG=coronary artery bypass grafting; PCI=percutaneous coronary intervention; DCM=dilated cardiomyopathy; HCM=hypertophic cardiomyopathy; ARVD=arrhythmogenic right ventricular disease; LVEF=left ventricular ejection fraction; LVEDD=left ventricular end diastolic diameter; NYHA = New York Heart Association; COPD=chronic obstructive pulmonary disease; TIA=transient ischaemic attack;
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ACCEPTED MANUSCRIPT Table 2. Prevalence of fQRS and other ECG parameters in the whole study group and comparison between patients with QRS < 120 ms versus ≥ 120 ms (p value
QRS < 120 ms, n=172
QRS ≥ 120 ms, n=209
p
fQRS, n (%)
n 163 (42,8%)
39 (22,7%)
124 (59,3%)
<0,0001
fQRS in anterior leads n (%)
77 (20,2%)
18 (10,5%)
59 (28,2%)
<0,0001
fQRS in lateral leads n (%)
26 (6,8%)
8 (4,6%)
18 (8,6%)
0,02131
fQRS in inferior leads n (%)
117 (30,7%)
22 (12,8%)
fragmented Q wave n (%)
83 (21.9%)
24 (13,9%)
fragmented R wave n (%)
185 (48,6%)
63 (36,6%)
122 (58,4%)
<0,0001
fragmented S wave n (%)
102 (26,8%)
26 (15,1%)
76 (36,4%)
<0,0001
Q wave n (%)
227 (59,6%)
93 (54,1%)
134 (64,1%)
0,03494
Q wave in anterior leads n (%)
83 (21,9%)
50 (29,1%)
33 (15,8%)
0,00204
Q wave in lateral leads n (%)
41 (10,7%)
14 (8,1%)
27 (12,9%)
0,17341
Q wave in inferior leads n (%)
100 (26,2%)
59 (34,3%)
41 (19,6%)
0,00139
Q wave in BBB/paced QRS n (%)
62 (16,3%)
(-)
62 (29,7%)
<0,0001
LBBB n (%)
90 (23,6%)
(-)
90 (43,1%)
<0,0001
RBBB n (%)
23 (6,0%)
(-)
23 (11,0%)
<0,0001
IVCD n (%)
76 (19,9%)
(-)
76 (36,4%)
<0,0001
0 (0,0%)
18 (8,6%)
<0,0001
Paced QRS n (%)
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95 (45,4%)
<0,0001
59 (28,2%)
0,00078
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Parameter
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Whole group, n=381
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refers to difference between groups with QRS < 120ms and ≥120ms).
18 (4,7%)
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Abbreviations: LBBB=left bundle branch block; RBBB=right bundle branch block; IVCD=interventricular conduction defect.
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ACCEPTED MANUSCRIPT Table 3. Comparison between patients with versus without fQRS in subgroups with QRS duration <120ms, ≥120 ms and in the whole study group (only parameters with significant differences are presented).
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fQRS (-) N=133 92 (69,2%) 68 (51,1%) 12 (10,8%) 76 (67,3%) 31 (23,5%) 42 (31,8%) 74,3±11,8 N=85 153,1±21,8 81,51±56,4 24 (28,2%) 18 (2,2%) 40 (47,1%) N=218 150 (69,4%) 116 (53,7%) 0,83±0,94 119 (55,1%) 70 (32,6%) 18 (8,4%) 70 (32,6%) 28,96±10,24 6,52±4,41 135 (62,5%) 37 (17,1%) 169 (78,6%) 73,17±11,99 458±59,48 494,72±47,59 78,14±47,57 126,41±26,24 32 (14,8%) 6 (2,8%) 6 (2,8%) 204 (94,4%)
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fQRS (+) N=39 34 (89,5%) 27 (69,2%) 10 (33,3%) 15 (48,4%) 19 (48,7%) 4 (10,5%) 70,2±13,1 N=124 170,8±28,5 90,97±54,1 17 (14,0%) 44 (36,4%) 36 (29,0%) N=163 132 (80,0%) 112 (67,5%) 1,05±0,98 108 (66,3%) 30 (18,5%) 44 (27,2%) 37 (22,4%) 26,04±8,49 6,48±0,81 87 (52,4%) 13 (7,8%) 145 (87,3%) 69,3±13,15 495,00±79,34 518,16±65,01 90,78±51,69 156,14±36,20 58 (35,2%) 17 (10,3%) 12 (7,3%) 145 (88,4%)
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Parameter Group with QRS < 120 ms, n=172 CAD History of MI LAD disease Complete revascularisation Q wave in anterior leads DCM HR Group with QRS ≥120 ms n=209 QRS duration (ms) QTd (ms) Q wave in inferior leads Q wave in BBB/stimulated QRS IVCD Whole study group n=381 CAD History of MI Number of MI Q wave Q wave in inferior leads Q wave in BBB/stimulated QRS DCM LVEF (%) LVEDD (cm) Hypertension Chronic AF Sinus rhythm HR (beats/min) QT (ms) QTc (ms) QTd (ms) QRS duration (ms) LBBB RBBB Paced QRS Beta-blocker
Abbreviations: LAD = left anterior descendent artery disease, rest of abbreviations as in Tables 1 and 2.
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P 0,0078 0,0336 0,0049 0,0441 0,0028 0,0058 0,0359 0,0001 0,0228 0,0102 0,0137 0,0061 0,0131 0,0044 0,0232 0,0181 0,0015 0,0000 0,0191 0,0016 0,0075 0,0303 0,0052 0,0176 0,0016 0,0000 0,0001 0,0009 0,0000 0,0000 0,0022 0,0359 0,0268
ACCEPTED MANUSCRIPT Table 4. Comparison between patients with one vs two locations of fQRS (only parameters with significant differences are presented). Numer of locations of fQRS 1 2 p 0.97±1.1 1.86±1.1 0.0317 70.59% 28.57% 0.0495 64.71% 100.00% 0.0694
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Parameter number of MIs primary prevention history of MI
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Table 5. Association between angiographically assessed localization of coronary
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artery disease (occlusion ≥70%, only single vessel disease is included) and fQRS in
fQRS in lateral leads
fQRS in inferior leads
present
12 (44,4%)
0 (0,0%)
5 (18.5%)
absent
44 (17.2%)
16 (6,4%)
72 (28.7%)
0.0022
0.1858
0.1869
3 (25.0%)
3 (25.0%)
4 (33.3%)
absent
53 (19.9%)
13 (4.9%)
73 (27.4%)
p
0.4481
0.0251
0.4359
present
4 (9.3%)
3 (7.0%)
12 (27.9%)
absent
52 (22.0%)
13 (5.5%)
66 (28.0%)
p
0.0371
0.4600
0.5773
p
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CX disease
RCA disease
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present
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fQRS in anterior leads
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LAD disease
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the whole study group.
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ACCEPTED MANUSCRIPT Table 6. Association between angiographically assessed localization of coronary artery disease (occlusion ≥70%, only single vessel disease is included) and Q wave
RCA disease
Q wave nonlocalised
present
16 (59.3%)
4 (14.8%)
10 (37.0%)
2 (7.4%)
absent
39 (15.6%)
24 (9.6%)
p
0.0000
0.2842
0.0630
0.1868
present
3 (25.0%)
3 (25.0%)
2 (16.7%)
2 (16.7%)
absent
52 (19.6%)
25 (9.4%)
62 (23.4%)
40 (15.1%)
p
0.4377
0.1094
0.4482
0.5676
present
9 (20.9%)
5 (11.6%)
22 (51.2%)
6 (13.9%)
absent
46 (19.6%)
23 (9.8%)
42 (17.9%)
37 (15.7%)
0.4426
0.0000
0.4873
0.4894
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54 (21.6%)
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p
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Q wave in inferior leads
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CX disease
Q wave in lateral leads
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LAD disease
Q wave in anterior leads
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in the whole study group.
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40 (16.0%)
ACCEPTED MANUSCRIPT Table 7. Accuracy of fQRS, Q wave and combined fQRS and Q wave in identification of the site of CAD (parameters computed only for patients with a single localisation of CAD)
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LAD disease identification sensitivity specificity NPV PPV ACC fQRS 44% 83% 93% 22% 79% Q wave 59% 84% 95% 29% 82% fQRS+Q 30% 97% 93% 53% 91% Cx disease identification fQRS 25% 95% 97% 20% 92% Q wave 25% 91% 96% 11% 88% fQRS+Q* 0% (NA) 100 % (NA) 96% 0% (NA) 95% RCA disease identification fQRS 26% 72% 85% 14% 65% Q wave 52% 82% 91% 34% 78% fQRS+Q 10% 97% 86% 36% 84% * Sensitivity and positive predictive value for Cx identification not computed due to low number of patients with Q wave and fQRS in lateral leads.
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Abbreviations: NPV=negative predictive value; PPV = positive predictive value, ACC = total accuracy
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fQRS and Q wave location relates to specific coronary artery (LAD – anterior leads, CX – lateral leads, RCA – inferior leads)
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Table 8. Multivariable analysis – factors independently associated with QRS for patients with QRS < 120ms.
LAD disease
Wald
p
OR
CI -95%
CI +95%
8,762
0,003
4,409
11,776
1,651
After withdrawing LAD disease from the model Q wave in anterior 8,208 leads Abbreviations: as in Table 3
0,004
3,398
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7,848
1,472
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Permanent AF QRS duration (ms)
Wald
p
OR
CI -95%
CI +95%
4,221
0,040
2,595
1,045
6,443
18,699
0,000
1,029
1,016
1,043
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Table 9. Multivariable analysis – factors independently associated with QRS for patients with QRS ≥ 120ms.
5,291
After withdrawing QRS width from the model 2,610
1,288
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0,008
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Q wave in 7,085 inferior leads Abbreviations: as in Table 3
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Figure 1. Original example of ECG with fQRS (patient with a significant LAD disease)
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Figure 2. Original example of ECG with fQRS (patient with significant LAD disease)
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Acknowledgements. The authors would like to thank dr Paweł Miękus for his kind agreement to use database of patients implanted with ICD in his department.
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This research did not receive any specific grant from funding agencies in the public,
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commercial, or not-for-profit sectors.
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Highlights
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fQRS is frequent in patients with ICD, mostly in those with CAD and prolonged QRS fQRS presence is associated with remote MI, Q wave, lower LVEF, prolonged QTc and QTd the more the leads with fQRS the greater number of MI and ICD in secondary prevention fQRS in specific ECG localisation predicts the site of coronary artery occlusion combined fQRS and Q wave improve identification of patients with LAD disease
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Anna Kucharz, Piotr Kulakowski PII: DOI: Reference:
S0022-0736(18)30270-X doi:10.1016/j.jelectrocard.2018.07.014 YJELC 52670
To appear in:
Journal of Electrocardiology
Please cite this article as: Anna Kucharz, Piotr Kulakowski , Fragmented QRS complex in patients with implantable cardioverter defibrillator—Prevalence and predisposing factors. Yjelc (2018), doi:10.1016/j.jelectrocard.2018.07.014
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ACCEPTED MANUSCRIPT Fragmented QRS complex in patients with implantable cardioverter defibrillator – prevalence and predisposing factors
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Anna Kucharz1 2, Piotr Kulakowski3 1. Department of Cardiology, Saint Vincent a Paulo Hospital, 81-348 Gdynia, ul.
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Wójta Radtkego 1, Poland
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Warszawskiej 5, Poland – present address
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2. Medical Center Płyta Redłowska, 81-466 Gdynia, ul. Bohaterów Starówki
3. Department of Cardiology, Postgraduate Medical School, Grochowski Hospital, 04-
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073 Warsaw, ul. Grenadierów 51/59, Poland.
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Corresponding author: Anna Kucharz MD
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Address for correspondence: Tel: +48 697263096
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Mail: [email protected]
Declaration of interest: none.
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ACCEPTED MANUSCRIPT Abstract Background. Incidence of fragmented (fQRS) and predisposing factors in patients with implantable cardioverter-defibrillator (ICD) have not yet been established. Aim. To examine incidence of fQRS, associated factors as well as predictive value in
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identifying site of coronary artery disease (CAD).
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Methods. Consecutive patients with ICD. Retrospective analysis of demographic,
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clinical and ECG data.
Results. Of 382 patients, 163 (43%) had fQRS. They had more frequently history of
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MI, Q wave, lower left ventricular ejection fraction and prolonged ECG repolarisation
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indices. The presence of fQRS in more than one ECG localisation was associated with higher number of MI and ICD for secondary prevention. By combining fQRS with
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Q wave location, site of CAD could be predicted (total accuracy 84-95%).
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Conclusions. The fQRS is frequent in patients with ICD, especially those with CAD, more advanced cardiac disease and altered ECG repolarisation. The fQRS may
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improve ECG-based non-invasive identification of the site of CAD.
Key words: fragmented QRS, Q wave, implantable cardioverter-defibrillator.
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Introduction Arrhythmic death due to ventricular tachycardia/fibrillation (VT/VF) is the most common type of sudden cardiac death (SCD) in patients with advanced organic heart
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disease [1] . Risk stratification in this population is difficult and currently only the value of left ventricular ejection fraction (LVEF) is taken into account when deciding
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whether to implant cardioverter-defibrillator (ICD) for primary prevention of SCD [1].
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However, specificity of this parameter is low and many patients with ICD do not
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experience appropriate device interventions due to lack of VT/VF occurrence [1]. Clearly, there is a need for new non-invasive parameters to better stratify the risk of
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SCD in these patients.
Recently, fragmentation of the QRS complex (fQRS) has gained considerable
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interest. Fragmented QRS on surface ECG probably represents areas of myocardial
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scarring and conduction disturbances in patients with various cardiac disorders [2]. Some studies have shown that fQRS identifies patients with increased risk of SCD [3]
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[4] [5], however, other papers did not confirm these findings [6]. Currently, the role of fQRS in risk stratification is unknown. Also, the prevalence of fQRS and associated
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factors have not been well established. Accordingly, the aim of our study was to examine the incidence of fQRS in patients with ICD – the group with usually severe cardiac disease and most threatened by VT/VF occurrence. We also sought to evaluate factors associated with the presence of fQRS on surface ECG.
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ACCEPTED MANUSCRIPT Material and methods
Patients. The study included 425 consecutive patients who had undergone implantation of ICD/CRT-D device between 2006 and 2011 at the Cardiology
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Department of Saint Vincent a Paulo Hospital in Gdynia, Poland. All patients had either primary or secondary prevention indications according to the current ESC
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guidelines. All patients had signed informed consent for implantation of the device.
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The study design was approved by the Bioethical Committee of the Centre of Postgraduate Medical Education (number 50PB2014, date 15.07.2014).
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Out of 425 patients, 382 patients had very good quality surface 12-lead ECG,
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amenable for detailed analysis of fQRS, and these subjects formed the study group [7]. We analysed medical records and data related to ICD/CRT-D implantation. Baseline demographic data, history of SCD including type of underlying ventricular
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arrhythmia (VT/VF), presence and extent of coronary artery disease (CAD) or dilated cardiomyopathy (DCM), previous myocardial infarction (MI) (including localisation and number of MI) as well as other clinical conditions (including presence of
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supraventricular arrhythmias, hypertension, diabetes mellitus (DM), chronic
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obstructive pulmonary disease (COPD), previous stroke or transient ischaemic attack (TIA), chronic kidney disease (CKD), peripheral arterial disease (PAD) and thyroid disease) were collected. This group was also evaluated according to the NYHA class and echocardiographic findings including LVEF and LV end-diastolic diameter (LVEDD). In addition, results of pre-implant coronary angiography were examined and classified as left anterior descendent (LAD), circumflex (Cx) or right coronary artery (RCA) disease when there was a > 70% narrowing of vessel lumen.
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ACCEPTED MANUSCRIPT Incomplete revascularisation was defined as the presence of significant narrowing of coronary arteries (>70% or >50% of left main) which were not invasively treated either because the results of stress tests were normal (no stress-induced ischaemia) or because of technical difficulties and/or anatomy which precluded angioplasty
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ECG analysis. We analysed resting 12-lead ECG obtained at the time of ICD
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implantation and measured heart rhythm, heart rate, QRS duration, presence of
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BBB/paced QRS, presence and location of both fQRS and Q wave as well as QT duration and dispersion (QTd). Three sets of ECG leads, corresponding to the
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territories supplied by left descending coronary artery (LAD) (anterior leads V1-V5), circumflex artery (Cx) (lateral leads I, aVL and V6) or right coronary artery (RCA)
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(inferior leads II, III and aVF) were identified.
The fQRS was defined as the presence of an additional R wave (R’) or
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notching in the nadir of the S wave, or the presence of >1 R’ (fragmentation) in 2
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contiguous leads corresponding to a major coronary artery territory, for QRS duration <120ms. Patients with QRS duration ≥120ms were not excluded from the study.
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Fragmented QRS in this subgroup was defined as the presence of >2 notches (at least 1 notch more than typical BBB) or multiple notches of the R wave or >2 notches
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in the nadir of the S wave. Fragmented paced QRS was defined by the presence of >2 R’ or >2 notches in the S wave in 2 contiguous leads [8] [9]. Original ECG recordings with fQRS are presented in Figures 1 and 2. In order to minimise errors in fQRS detection, all ECG tracings were evaluated twice by the principal investigator (AK). All problematic ECG recordings were analysed by both AK and PK, and the final diagnosis (fQRS present or absent) was
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ACCEPTED MANUSCRIPT achieved by joint agreement. Both investigators were blinded to the demographic and clinical data of studied patients.
Statistical analysis. All calculations have been carried out by means of Microsoft Excel spreadsheet and STATISTICA, StatSoft, Inc. ver. 12.0. statistical package
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(data analysis software system). In the statistical description of quantitative data
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classical measures of location such as arithmetic means and median, and measures
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of variation such as standard deviation and range were used. The normality of distribution of the variables and variance equality of a studied feature in groups was
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tested by the use of appropriate Shapiro-Wilk's test and a variance equality test. In order to compare groups in pairs for quantitative data, t-test or Mann-Whitney test
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were used with respect to the type of distribution of the variables tested. In case of multiple group comparisons the Kruskal- Wallis test was used as the non- parametric
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equivalent of one way ANOVA. A stepwise multivariable logistic regression model
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analysis was performed in order to identify variables as independent risk factors for fQRS.
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Qualitative data are presented as numbers, proportions, percentages and compared using Chi-square test (according to the number of cases in each compared
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category and/or their expected values, the Pearson’s method, Yates correction, or Fisher’s exact test were used). Sensitivity, specificity, positive and negative predictive value as well as total accuracy were calculated according to standard definitions. In all these calculations the statistical significance level was set at p<0.05.
Results
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ACCEPTED MANUSCRIPT Baseline clinical characteristics are shown in Table 1. The mean age of studied patients was 65.2±11 years and majority were male. Ischaemic aetiology was most common, followed by DCM. All patients had chronic heart failure (CHF) and NYHA class III was the most common stage of CHF. Mean LVEF was significantly reduced. Concomitant diseases included hypertension in more than 50% of patients, followed
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by DM, COPD, PAD and others. Medical treatment included standard agents used in
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patients with CHF and decreased LVEF. Out of antiarrhythmic agents which could
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have influenced QRS complex, amiodarone was by far the most frequent – more than 30% of patients received this drug.
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Details on ECG findings and comparison between wide and narrow QRS
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groups are presented in Table 2. Mean QRS duration in the whole study group was 139 ms±34ms. The prevalence of fQRS was 43%, and the most common location of fQRS were inferior leads (31%), followed by anterior leads and lateral leads. This
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distribution corresponded to the Q wave presence, which was also most frequent in inferior leads. Fragmentation of Q wave, R wave and S wave were noted in 22% to
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49% of patients.
Out of 382 patients included in the study, 209 (54.7%) had prolonged
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(≥120ms) QRS duration. In this subgroup the prevalence of fQRS was significantly higher than in patients with narrow QRS (59% versus 23%, p < 0.0001). In each ECG lead set the incidence of fQRS was higher in patients with wide rather than narrow QRS complex. Also the incidence of fragmented Q, R and S waves was higher in patients with QRS ≥ 120 ms. By definition, the incidence of BBB, IVCD or pacedQRS was significantly higher in patients with wide QRS complex.
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ACCEPTED MANUSCRIPT Comparison between patients with versus without fQRS in the whole study group and in the subgroups with wide and narrow QRS complex is presented in Table 3. In the subgroup with narrow QRS complex, patients with fQRS had more frequently CAD and history of MI, LAD disease, Q wave in anterior leads and incomplete revascularisation. In the subgroup with wide QRS complex, patients with
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fQRS had more often Q wave in inferior leads and greater QTd. In the whole study
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group, patients with fQRS had more frequently ischaemic aetiology, Q wave, lower
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LVEF and more altered ECG repolarisation indices such as QTc and QTd duration. Also QRS width was greater and BBB was more frequent in the fQRS (+) group.
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Comparison of patients with single versus two localisations of fQRS is shown
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in Table 4. Patients with fQRS present in two sets of leads had higher number of MI and more often a history of MI than patients with a single localisation of fQRS. Patients in whom ICD was implanted for primary rather than secondary prevention
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had predominantly fQRS in a single set of ECG leads. Association between the site of CAD and localisation of fQRS in patients with
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ischaemic aetiology is shown in Table 5. There was a significant strong association between LAD disease and the presence of fQRS in anterior leads. There was also a
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significant relationship between Cx disease and fQRS in lateral leads as well as RCA disease and fQRS in anterior leads Association between the site of CAD and localisation of Q wave is shown in Table 6. There was a strong significant association between LAD disease and the presence of Q wave in anterior leads and RCA disease and Q wave in inferior leads. Table 7 shows the accuracy of fQRS, Q wave and combined fQRS and Q wave in identification of the site of CAD disease. Both, fQRS and Q wave performed 8
ACCEPTED MANUSCRIPT better for identification of patients with LAD disease, followed by RCA and Cx disease. Combining fQRS with Q wave increased specificity, positive predictive value and total accuracy of ECG in predicting the site of CAD disease. The results of multivariate analysis are presented in Tables 8 and 9. In the
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group with narrow QRS the LAD disease was the only parameter independently associated with the presence of fQRS. When LAD disease was withdrawn from the
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model the Q wave in anterior leads occurred also independently associated with
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fQRS. In patients with wide QRS, chronic AF and the width of the QRS complex were independent parameters. When the width of QRS was withdrawn from the model, the
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Q wave in inferior leads occurred also independently associated with the presence of
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fQRS.
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Discussion
The main finding of our study is that QRS fragmentation is present in approximately 43% of patients with advanced cardiac disease who are equipped with an ICD and
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occurs more often in individuals with prolonged rather than narrow QRS complex.
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Secondly, there are several significant differences in factors associated with fQRS presence between patients with prolonged versus narrow QRS complex. Thirdly, patients with fQRS visible in more than one set of leads have more frequently remote MI, numerous MI, CAD and history of ventricular arrhythmias requiring ICD implantation (secondary prevention). Fourthly, our study suggests that the presence of fQRS on surface ECG may improve non-invasive prediction of CAD localisation, suggesting which coronary artery is significantly narrowed or blocked.
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ACCEPTED MANUSCRIPT The reported incidence of fQRS varies between the studies. In patients with risk factors referred for cardiology consultation [10] and for coronary angiography [11] fQRS was observed in approximately one third of the population. In a study conducted among ICD patients [12] the prevalence of fQRS was lower (26%) than in our study. In the MADIT II population fQRS was detected in 35% of patients. [3]
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Another study conducted in patients with LV dysfunction showed that 32,5% of
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patients had fQRS [6]. In our study the proportion of patients with fQRS was higher or
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slightly higher than in studies involving patients with cardiac disease. This may be explained by the fact that we included patients with ICD, thus patients with already
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known arrhythmic problem (secondary prevention) or significant cardiac disease (primary prevention) in whom the incidence of arrhythmic markers may be anticipated
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to be high.
The distribution of fQRS among various ECG lead sets was similar to that
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shown in other studies. For example, the MADIT II study found inferior leads as the most frequent site of fQRS [3]. Also in the Finish middle-aged general population inferior leads were the most common site of fQRS and the prevalence of this marker
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was found in 15.7% of all subjects [13]. The fact that inferior leads are the most
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common site of fQRS, regardless of the clinical and demographic characteristics of the studied subjects, suggests that fQRS in inferior leads may not be very specific for identification of subjects with cardiac disease. Our study showed that fQRS is more frequently recorded in patients with wide rather than narrow QRS complex. This may be due to the fact that patients with prolonged QRS tend to have more advanced cardiac disease and more ventricular scarring, providing the substrate for fQRS. Indeed, we found several differences in clinical characteristic between these two subgroups which suggests that patients with 10
ACCEPTED MANUSCRIPT prolonged QRS were sicker. Another possible explanation may be problems with identifying fQRS in patients with BBB although we used modified criteria for fQRS detection in these patients to distinguish between typical ECG changes for BBB and true fQRS in patients with BBB.
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We found that fQRS was associated with CAD rather than DCM. Since fQRS has been shown to be a marker of heterogeneous ventricular activation caused by
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myocardial fibrosis [14] [15], it is not surprising that the prevalence of fQRS is higher
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in patients with CAD and past MI than in patients with less advanced LV injury. Numerous studies have shown the association between the presence of the fQRS
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complexes on ECG and late gadolinium enhancement (LGE) areas on cardiac
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magnetic resonance (CMR) [14] [15]. It has been found to be a marker of a prior MI [8] [9] [16] and poorer collateral circulation [17]. Also complete revascularisation was less common among our patients with fQRS, while larger number of MI correlated
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with fQRS presence in the whole study group. Numerous studies showed association between increased QTd and scar
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tissue and its extent [18] as well as ischemic myocardium [19] in patients with CAD. The QTd also positively correlated with severity of impaired cardiac function [20] and
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was increased in patients without mechanical LV remodelling after CRT-D implantation [21]. To date, no study showed a relationship between fQRS and increase in QT/QTd intervals. Our results suggest that these two parameters may be related and possibly identify patients with greater arrhythmic risk. We found that patients with more diffuse presence of fQRS (more than one set of leads) had more frequently CAD, history of MI and ICD implanted for secondary prevention. This is concordant with the knowledge that the presence of fQRS
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ACCEPTED MANUSCRIPT correlates with the extent of cardiac disease. Thus, the finding of fQRS presence in several sets of leads may be a simple non-invasive marker to identify patients with more severe cardiac disease. Our results are in line with data presented by Tanriverdi et al [22] who showed that prognosis in patients with STEMI was associated with the number of leads with fQRS – the more the leads with fQRS the
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poorer was the outcome. Similar results observed Torigoe [23] et al in patients with
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heart failure and prior MI.
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In our study LAD disease was significantly more often present in patients with fQRS. That corresponds with findings from a study conducted in STEMI population
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where fQRS was mostly associated with anterior territory of MI and thus often
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correlated with proximal LAD lesion [24]. Perhaps LAD disease is more than other sites of CAD associated with QRS fragmentation due to being responsible for larger MI causing more visible ECG changes. Results of multivariate analysis confirmed
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that in patients with narrow QRS the presence of fQRS was independently associated with LAD disease.
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In patients with wide QRS complex chronic AF and width of QRS complex were independently associated with fQRS. It may be speculated that both chronic AF
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and wider QRS complex are markers of more advanced cardiac disease in this group of patients which, in turn, is associated with higher prevalence of fQRS. A new finding is that fQRS may improve non-invasive identification of localisation of CAD. When fQRS was added to Q wave then the specificity and total accuracy of ECG in identifying CAD disease increased significantly. The highest values were obtained for Cx disease, however, this finding is limited by the very low number of patients with both fQRS and Q wave present in lateral leads. The accuracy
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ACCEPTED MANUSCRIPT of identification of patients with LAD disease was better than patients with the RCA disease. These findings may be of practical value when analysing standard ECG in patients with CAD. The lack of association between fQRS in inferior leads and localisation of diseased coronary artery (for example, RCA) may be explained by the fact that fQRS in inferior leads may be less specific for the presence of cardiac
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disease because it is present in nearly 16% of healthy subjects [13]. Similar findings
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have been presented by Euybogly et al [25] and Guo R et al [26] who also suggested
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that fQRS in anterior leads may be a non-invasive marker for LAD disease. However, they examined different patient population than in our study.
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Limitations. Our study has several limitations. First, although the total number of
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analysed patients was quite high, the subgroup analysis was in some cases limited by a relatively small number of patients. Second, our study is a retrospective analysis of ECG and associated factors, however, all clinical, echocardiographic and ECG
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data were collected prospectively at the time of patients hospitalisations and clinic visits. Thirdly, the fQRS analysis may be difficult in some ECG tracings. We tried to minimize the risk of false positive or false negative findings by careful inspection of
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ECG tracings, repeated analysis of each ECG recording and resolving all problematic
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tracings by joint agreement (AK and PK). Fourthly, data on recurrent ischaemia were not collected so we were not able to assess the effects of possible ischaemia on fQRS. Finally, Holter ECG or short-term ECG recordings were not available for analysis, therefore, we were not able to assess the relationship between the autonomic tone and fQRS
Conclusions
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ACCEPTED MANUSCRIPT Fragmented QRS detected on surface ECG in ICD recipients is a frequent finding, is associated with etiology (CAD versus DCM), extent of disease, history of MI and duration of QRS. There are several differences in clinical and ECG variables between patients with fQRS and narrow versus prolonged QRS complex. The site of fQRS in a 12 lead ECG corresponds to the diseased coronary artery and may possibly be used
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as a non-invasive marker of the location of CAD.
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ACCEPTED MANUSCRIPT Table 1. Baseline characteristics of the study population.
Parameter
Results
Male gender
319 (83.5%)
Age (years)
65.2 ±10.8
CAD
282 (74.0%)
History of MI
228 (59.7%) 154 (40.6%)
1 4 2
129 (34.0%)
3 5 4
20 (5.3%)
5
1 (0.3%)
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0
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71 (18.7%) 4 (1.1%)
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Number of MI
History of CABG/PCI
186 (48.9%)
Complete revascularisation
194 (63.8%) 107 (28.2%)
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DCM HCM
10 (2.6%) 3 (0.8%)
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ARVD LVEF (%) LVEDD (cm) I II IV
Concomittant diseases Diabetes mellitus Hypertension
4 (2.3%) 44 (11.5%) 112 (29.3%)
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COPD
10 (5.8%) 88 (51.2%)
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III
6.5±3.3 70 (40.7%)
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NYHA class
27.7±10
222 (58.1%) 35 (9.2%)
Stroke/TIA
33 (8.7%)
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Peripheral artery disease Hypothyroidism
14 (3.7%)
Hyperthyroidism
18 (4.7%)
Drugs which may affect QRS Beta blocker
349 (91.8%)
Amiodarone
119 (31.3%)
Sotalol
8 (2.1%)
Calcium channel blockers
39 (10.3%)
Digoxin
66 (17.4%)
Abbreviations: CAD=coronary artery disease; MI=myocardial infarction; CABG=coronary artery bypass grafting; PCI=percutaneous coronary intervention; DCM=dilated cardiomyopathy; HCM=hypertophic cardiomyopathy; ARVD=arrhythmogenic right ventricular disease; LVEF=left ventricular ejection fraction; LVEDD=left ventricular end diastolic diameter; NYHA = New York Heart Association; COPD=chronic obstructive pulmonary disease; TIA=transient ischaemic attack;
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ACCEPTED MANUSCRIPT Table 2. Prevalence of fQRS and other ECG parameters in the whole study group and comparison between patients with QRS < 120 ms versus ≥ 120 ms (p value
QRS < 120 ms, n=172
QRS ≥ 120 ms, n=209
p
fQRS, n (%)
n 163 (42,8%)
39 (22,7%)
124 (59,3%)
<0,0001
fQRS in anterior leads n (%)
77 (20,2%)
18 (10,5%)
59 (28,2%)
<0,0001
fQRS in lateral leads n (%)
26 (6,8%)
8 (4,6%)
18 (8,6%)
0,02131
fQRS in inferior leads n (%)
117 (30,7%)
22 (12,8%)
fragmented Q wave n (%)
83 (21.9%)
24 (13,9%)
fragmented R wave n (%)
185 (48,6%)
63 (36,6%)
122 (58,4%)
<0,0001
fragmented S wave n (%)
102 (26,8%)
26 (15,1%)
76 (36,4%)
<0,0001
Q wave n (%)
227 (59,6%)
93 (54,1%)
134 (64,1%)
0,03494
Q wave in anterior leads n (%)
83 (21,9%)
50 (29,1%)
33 (15,8%)
0,00204
Q wave in lateral leads n (%)
41 (10,7%)
14 (8,1%)
27 (12,9%)
0,17341
Q wave in inferior leads n (%)
100 (26,2%)
59 (34,3%)
41 (19,6%)
0,00139
Q wave in BBB/paced QRS n (%)
62 (16,3%)
(-)
62 (29,7%)
<0,0001
LBBB n (%)
90 (23,6%)
(-)
90 (43,1%)
<0,0001
RBBB n (%)
23 (6,0%)
(-)
23 (11,0%)
<0,0001
IVCD n (%)
76 (19,9%)
(-)
76 (36,4%)
<0,0001
0 (0,0%)
18 (8,6%)
<0,0001
Paced QRS n (%)
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95 (45,4%)
<0,0001
59 (28,2%)
0,00078
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Parameter
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Whole group, n=381
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refers to difference between groups with QRS < 120ms and ≥120ms).
18 (4,7%)
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Abbreviations: LBBB=left bundle branch block; RBBB=right bundle branch block; IVCD=interventricular conduction defect.
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ACCEPTED MANUSCRIPT Table 3. Comparison between patients with versus without fQRS in subgroups with QRS duration <120ms, ≥120 ms and in the whole study group (only parameters with significant differences are presented).
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CE
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fQRS (-) N=133 92 (69,2%) 68 (51,1%) 12 (10,8%) 76 (67,3%) 31 (23,5%) 42 (31,8%) 74,3±11,8 N=85 153,1±21,8 81,51±56,4 24 (28,2%) 18 (2,2%) 40 (47,1%) N=218 150 (69,4%) 116 (53,7%) 0,83±0,94 119 (55,1%) 70 (32,6%) 18 (8,4%) 70 (32,6%) 28,96±10,24 6,52±4,41 135 (62,5%) 37 (17,1%) 169 (78,6%) 73,17±11,99 458±59,48 494,72±47,59 78,14±47,57 126,41±26,24 32 (14,8%) 6 (2,8%) 6 (2,8%) 204 (94,4%)
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fQRS (+) N=39 34 (89,5%) 27 (69,2%) 10 (33,3%) 15 (48,4%) 19 (48,7%) 4 (10,5%) 70,2±13,1 N=124 170,8±28,5 90,97±54,1 17 (14,0%) 44 (36,4%) 36 (29,0%) N=163 132 (80,0%) 112 (67,5%) 1,05±0,98 108 (66,3%) 30 (18,5%) 44 (27,2%) 37 (22,4%) 26,04±8,49 6,48±0,81 87 (52,4%) 13 (7,8%) 145 (87,3%) 69,3±13,15 495,00±79,34 518,16±65,01 90,78±51,69 156,14±36,20 58 (35,2%) 17 (10,3%) 12 (7,3%) 145 (88,4%)
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Parameter Group with QRS < 120 ms, n=172 CAD History of MI LAD disease Complete revascularisation Q wave in anterior leads DCM HR Group with QRS ≥120 ms n=209 QRS duration (ms) QTd (ms) Q wave in inferior leads Q wave in BBB/stimulated QRS IVCD Whole study group n=381 CAD History of MI Number of MI Q wave Q wave in inferior leads Q wave in BBB/stimulated QRS DCM LVEF (%) LVEDD (cm) Hypertension Chronic AF Sinus rhythm HR (beats/min) QT (ms) QTc (ms) QTd (ms) QRS duration (ms) LBBB RBBB Paced QRS Beta-blocker
Abbreviations: LAD = left anterior descendent artery disease, rest of abbreviations as in Tables 1 and 2.
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P 0,0078 0,0336 0,0049 0,0441 0,0028 0,0058 0,0359 0,0001 0,0228 0,0102 0,0137 0,0061 0,0131 0,0044 0,0232 0,0181 0,0015 0,0000 0,0191 0,0016 0,0075 0,0303 0,0052 0,0176 0,0016 0,0000 0,0001 0,0009 0,0000 0,0000 0,0022 0,0359 0,0268
ACCEPTED MANUSCRIPT Table 4. Comparison between patients with one vs two locations of fQRS (only parameters with significant differences are presented). Numer of locations of fQRS 1 2 p 0.97±1.1 1.86±1.1 0.0317 70.59% 28.57% 0.0495 64.71% 100.00% 0.0694
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Parameter number of MIs primary prevention history of MI
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Table 5. Association between angiographically assessed localization of coronary
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artery disease (occlusion ≥70%, only single vessel disease is included) and fQRS in
fQRS in lateral leads
fQRS in inferior leads
present
12 (44,4%)
0 (0,0%)
5 (18.5%)
absent
44 (17.2%)
16 (6,4%)
72 (28.7%)
0.0022
0.1858
0.1869
3 (25.0%)
3 (25.0%)
4 (33.3%)
absent
53 (19.9%)
13 (4.9%)
73 (27.4%)
p
0.4481
0.0251
0.4359
present
4 (9.3%)
3 (7.0%)
12 (27.9%)
absent
52 (22.0%)
13 (5.5%)
66 (28.0%)
p
0.0371
0.4600
0.5773
p
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CX disease
RCA disease
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present
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fQRS in anterior leads
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LAD disease
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the whole study group.
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ACCEPTED MANUSCRIPT Table 6. Association between angiographically assessed localization of coronary artery disease (occlusion ≥70%, only single vessel disease is included) and Q wave
RCA disease
Q wave nonlocalised
present
16 (59.3%)
4 (14.8%)
10 (37.0%)
2 (7.4%)
absent
39 (15.6%)
24 (9.6%)
p
0.0000
0.2842
0.0630
0.1868
present
3 (25.0%)
3 (25.0%)
2 (16.7%)
2 (16.7%)
absent
52 (19.6%)
25 (9.4%)
62 (23.4%)
40 (15.1%)
p
0.4377
0.1094
0.4482
0.5676
present
9 (20.9%)
5 (11.6%)
22 (51.2%)
6 (13.9%)
absent
46 (19.6%)
23 (9.8%)
42 (17.9%)
37 (15.7%)
0.4426
0.0000
0.4873
0.4894
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54 (21.6%)
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p
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Q wave in inferior leads
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CX disease
Q wave in lateral leads
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LAD disease
Q wave in anterior leads
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in the whole study group.
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40 (16.0%)
ACCEPTED MANUSCRIPT Table 7. Accuracy of fQRS, Q wave and combined fQRS and Q wave in identification of the site of CAD (parameters computed only for patients with a single localisation of CAD)
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LAD disease identification sensitivity specificity NPV PPV ACC fQRS 44% 83% 93% 22% 79% Q wave 59% 84% 95% 29% 82% fQRS+Q 30% 97% 93% 53% 91% Cx disease identification fQRS 25% 95% 97% 20% 92% Q wave 25% 91% 96% 11% 88% fQRS+Q* 0% (NA) 100 % (NA) 96% 0% (NA) 95% RCA disease identification fQRS 26% 72% 85% 14% 65% Q wave 52% 82% 91% 34% 78% fQRS+Q 10% 97% 86% 36% 84% * Sensitivity and positive predictive value for Cx identification not computed due to low number of patients with Q wave and fQRS in lateral leads.
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Abbreviations: NPV=negative predictive value; PPV = positive predictive value, ACC = total accuracy
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fQRS and Q wave location relates to specific coronary artery (LAD – anterior leads, CX – lateral leads, RCA – inferior leads)
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Table 8. Multivariable analysis – factors independently associated with QRS for patients with QRS < 120ms.
LAD disease
Wald
p
OR
CI -95%
CI +95%
8,762
0,003
4,409
11,776
1,651
After withdrawing LAD disease from the model Q wave in anterior 8,208 leads Abbreviations: as in Table 3
0,004
3,398
20
7,848
1,472
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Permanent AF QRS duration (ms)
Wald
p
OR
CI -95%
CI +95%
4,221
0,040
2,595
1,045
6,443
18,699
0,000
1,029
1,016
1,043
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Table 9. Multivariable analysis – factors independently associated with QRS for patients with QRS ≥ 120ms.
5,291
After withdrawing QRS width from the model 2,610
1,288
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0,008
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Q wave in 7,085 inferior leads Abbreviations: as in Table 3
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Figure 1. Original example of ECG with fQRS (patient with a significant LAD disease)
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Figure 2. Original example of ECG with fQRS (patient with significant LAD disease)
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ACCEPTED MANUSCRIPT
Acknowledgements. The authors would like to thank dr Paweł Miękus for his kind agreement to use database of patients implanted with ICD in his department.
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This research did not receive any specific grant from funding agencies in the public,
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commercial, or not-for-profit sectors.
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ACCEPTED MANUSCRIPT coronary artery disease severity. Rev Port Cardiol. 2017; 36:89-93 DOI: 10.1016/j.repc.2016.07.008 [26] Guo R., Li Y., Xu Y., Tang K., Li W. Significance of fragmented QRS complexes for identifying culprit lesions in patients with non-ST-elevation myocardial infarction: a
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Highlights
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fQRS is frequent in patients with ICD, mostly in those with CAD and prolonged QRS fQRS presence is associated with remote MI, Q wave, lower LVEF, prolonged QTc and QTd the more the leads with fQRS the greater number of MI and ICD in secondary prevention fQRS in specific ECG localisation predicts the site of coronary artery occlusion combined fQRS and Q wave improve identification of patients with LAD disease
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