Abstract
OBJECTIVES
Fragmented QRS (fQRS), related to myocardial fibrosis, is an important prognostic marker of cardiovascular events and mortality. Aortic stenosis (AS), the most frequent valvular heart disease in developed countries, causes myocardial fibrosis due to ventricular pressure overload. The current study aimed to investigate whether fQRS is associated with long-term mortality after isolated surgical aortic valve replacement (SAVR) in patients with severe AS.
METHODS
A total of 289 patients who underwent SAVR for severe AS between May 2009 and January 2020 with interpretable electrocardiogram were included. Patients were divided into 2 groups according to the presence of fQRS. Kaplan–Meier survival analyses were used to detect cumulative survival rates. Univariable and multivariable Cox proportional hazards models were used to determine the predictors of all-cause mortality.
RESULTS
fQRS occurred in 126 (43.5%) patients. A total of 59 (20.4%) patients died over a follow-up period of 54 ± 32 months. All-cause mortality was higher in the fQRS group (23 [14.1%] vs 36 [28.6], log-rank test P = 0.002) in the long term. The presence of fQRS [hazard ratio (HR): 1.802, confidence interval (CI): 1.035–3.135, P = 0.037], electrocardiographic left ventricular strain (HR: 1.836, CI: 1.036–3.254, P = 0.038) and history of stroke or transient ischaemic attack (HR: 3.130, CI: 1.528–6.412, P = 0.002) were independent predictors of all-cause mortality in the multivariable Cox regression model.
CONCLUSIONS
fQRS is associated with a 1.8-fold increase in long-term mortality in patients undergoing isolated SAVR for severe AS. Detecting fQRS in electrocardiograms may provide prognostic information about the long-term outcomes.
Keywords: Aortic stenosis, Aortic valve replacement, Fragmented QRS complex, All-cause mortality
Aortic stenosis (AS) is the most frequent valvular heart disease in developed countries, especially among the older population [1].
INTRODUCTION
Aortic stenosis (AS) is the most frequent valvular heart disease in developed countries, especially among the older population [1]. The most common treatment method used in these patients is surgical aortic valve replacement (SAVR). Long-term survival after SAVR is strongly correlated with the timing of surgery for AS [2]. AS might lead to myocardial fibrosis and infarction because of pressure overload, increased afterload and incremental ischaemia [3]. The transition from pressure overload associated with left ventricular hypertrophy (LVH) to heart failure occurs in clinical follow-up of patients with AS [4]. Long-standing AS, resulting in LVH and diastolic dysfunction, affects postoperative survival [5]. Myocardial fibrosis, which develops during the clinical progress of the disease, is related to poor outcomes [6, 7]. In addition, it was showed that worse clinical outcomes might occur even after SAVR [8, 9].
Fragmented QRS (fQRS) is defined as various RSR’ patterns with or without Q waves in 2 contiguous leads corresponding to a major coronary artery territory. The fQRS is hypothesized to be caused by altered conduction abnormalities because of myocardial fibrosis. The presence of fragmentation of QRS complexes evaluated by standard 12-lead electrocardiography (ECG) is an important prognostic marker of cardiovascular events and mortality [10–12]. In the literature, several studies have investigated the relationship of fQRS with valvular heart disease [13–15]. In addition, detecting fQRS in electrocardiogram may provide prognostic information about the long-term outcome in patients undergoing isolated SAVR for severe AS [13, 14]. The aim of this study is to evaluate the fQRS in patients with severe AS after isolated SAVR and to determine if this indice is related to long-term mortality in these patients.
METHODS
Study population
This retrospective study enrolled 289 AS patients who underwent isolated SAVR between May 2009 and January 2020 in Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital. The hospital database for patients who underwent SAVR operation in our tertiary cardiovascular centre was scanned in detail. As a result of this scan, 1649 patients who underwent SAVR were found. After excluding combined procedures (concurrent valve interventions or coronary artery bypass grafting), a total of 417 patients with isolated SAVR were identified for severe AS. Patients with a moderate–severe paravalvular leak, patient–prosthesis mismatch, history of myocardial infarction or chronic coronary artery disease, chronic inflammatory tissue diseases (Behçet, systemic lupus erythematosus, etc.), active infection, end-stage liver and renal disorders, age <18, malignancies, previous other cardiac surgeries, history of aortic dissection or valve endocarditis and absence of all medical records were excluded from the current study. The data on demographic, laboratory, morbidity and mortality were recruited from medical records and telephone interviews. After the strict exclusion criteria of the study, a total of 289 patients were enrolled in the final analysis. The investigation conforms to the principles outlined in the Declaration of Helsinki. The local ethics committee approved the study (2021–14). Written informed consent was not taken from the patients because of the retrospective and observational design.
Electrocardiography
A 12-lead standard surface ECG (Nihon Kohden Corporation, Cardiofax M Model ECG-1250, Tokyo, Japan), which was performed in the supine position with filtering range 0.15–100 Hz, AC filtering 50 Hz, 25 mm/s and 10 mm/mV, was retrieved from the participants’ records. The last ECGs within 1 week before SAVR were evaluated. All ECG data were scanned and transferred to the main computer system of the hospital. Analyses were performed by a single cardiologist who was blinded to the patients’ data via using the software of Photoshop (Adobe Systems, Inc., San Jose, CA, USA) with ×400% magnification. All parameters were measured for 2 consecutive cycles, and then the average values were obtained. Ventricular rate and pre- and postoperative rhythm were noted. Automatically provided P, QRS and T-wave axis and durations were re-analyzed and were noted. FQRS was defined as different QRS morphologies with varying RSR′ patterns including the presence of an additional R wave (R′), notching in the nadir of the R or S wave, or >1 R′ (fragmentation), the QRS complex with >2 R′ waves or notches in the R or S wave in a wide QRS complex of BBB, paced QRS or premature ventricular complexes in 2 contiguous leads (Fig. 1) [16, 17]. The Sokolow-Lyon index was calculated as the sum of amplitudes of S wave in lead V1 and R wave in lead V5 or V6. The ECG strain was defined as ≥1-mm concave downsloping ST-segment depression with asymmetrical T-wave inversion in the lateral leads (I, aVL, V5, V6) [18].
Figure 1:
Several types of fragmented QRS complexes in 12-lead electrocardiogram.
Echocardiography
All patients underwent two-dimensional and M-mode transthoracic echocardiography using Vingmed CFM 800, Vivid 5 (GE Vingmed Ultrasound AS, Horten, Norway), Vivid 7 Dimension® (GE Vingmed Ultrasound AS N-3190 Horten, Norway) or Philips iE33 (Philips Medical Systems, Andover, Massachusetts) echocardiography devices. In all patients, interventricular septal thickness, left ventricular end-systolic and end-diastolic diameters were measured on the parasternal long-axis view with M-mode echocardiography. LVEF was calculated by using biplane Simpson’s method. Classification of aortic stenosis and aortic insufficiency, pulmonary hypertension, aortic valve area or aortic valve area index, left ventricular mass index (LVMI), mean and maximum transvalvular aortic gradient were defined in accordance with consensus reports and current guideline [19].
End points and follow-up
The primary end point of the study was postoperative all-cause mortality during follow-up of the patients. These follow-up data were confirmed with death records in the National Social Security Institution records.
Statistical analyses
Statistical analyses were performed using the computer software Statistical Package for Social Sciences (IBM SPSS Statistics for Windows, version 21.0 released 2012, IBM Corp., Armonk, NY, USA). The Kolmogorov–Smirnov test was performed to detect the distribution of the variables. Normally distributed variables were presented as mean ± standard deviation, and nonnormally distributed variables were presented as median (25th–75th percentiles). Categorical variables were expressed as number (%). The Student's t-test and Mann–Whitney U-test were used to compare quantitative variables with the normal and non-normal distribution. The Pearson’s chi-square and Fisher exact tests were performed to compare categorical variables where appropriate. Univariable and multivariable Cox proportional hazards models were used to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. We used variables of whom the P-value was <0.10 in the univariable model to generate a multivariable model for the impact of potential confounders on all-cause mortality. We checked the model assumptions in multivariable analyses with log–log Kaplan–Meier plots. Cumulative survival rates were computed using the Kaplan–Meier method and were compared using the log-rank test. A P-value of <0.05 was considered statistically significant.
RESULTS
A total of 289 patients [median age: 67 (59–73) years; male: 154], who underwent isolated SAVR, were enrolled in this study. These patients were divided into 2 groups according to the presence of fQRS. Baseline characteristics of the patients are summarized in Table 1. Both groups were balanced in terms of age, gender, hypertension, diabetes mellitus, dyslipidaemia, peripheral artery disease, chronic pulmonary disease, chronic kidney disease, logistic EuroSCORE, atrial fibrillation and anaemia. Patients with fQRS had a higher incidence of the previous stroke or TIA (7 [4.3%] vs 15 [11.9%], P = 0.016). When biochemical and echocardiographic parameters were examined, septum diameter (13 [12–14] vs 14 [12–15], P = 0.010), posterior wall diameter (12 [11–13] vs 13 [12–14], P = 0.002), LVMI (125 [106–146] vs 135 [112–160], P = 0.006), peak aortic gradient (79 [71–94] vs 87 [72–98], P = 0.039) and mean transvalvular aortic gradient (48 [43–57] vs 55 [43–61], P = 0.007) were higher, while aortic valve area (0.80 [0.65–0.90] vs 0.70 [0.60–0.80], P = 0.001) was lower in the fQRS group. Sokolow-Lyon index and the incidence of left ventricle strain pattern in electrocardiogram were significantly higher in the fQRS group (24 [18–30] vs 26 [20–32], P = 0.014; 38 [23.3] vs 55 [43.7], P < 0.001). No dominant variant was observed among the different morphological types of fQRS. The mostly seen morphological types in our study were as follows: (i) R0 waves or a notch in the nadir of the S wave, (ii) R0 waves or a notch in the nadir of the R wave, (iii) 2 or more notches in the R wave and (iv) 2 or more notches in the S wave.
Table 1:
Pre-procedural demographic, clinical and laboratory characteristics of patients
| Patients clinical features | All patients (n = 289) | fQRS (−) (n = 163) | fQRS (+) (n = 126) | P-value |
|---|---|---|---|---|
| Age (years), median (IQR) | 67 (59–73) | 66 (58–73) | 67 (62–73) | 0.32 |
| Female gender, n (%) | 135 (46.7) | 76 (46.6) | 59 (46.8) | 0.97 |
| BMI (kg/m2), mean ± SD | 29 ± 5.2 | 29 ± 5.3 | 29.1 ± 5.1 | 0.79 |
| Clinical presentation, n (%) | ||||
| Angina pectoris | 72 (42.9) | 40 (24.5) | 32 (25.4) | 0.87 |
| Dyspnoea (NYHA 3–4) | 107 (37.7) | 61 (37.4) | 48 (38.1) | 0.91 |
| Syncope | 18 (6.2) | 6 (3.7) | 11 (8.7) | 0.070 |
| Hypertension, n (%) | 176 (60.9) | 98 (60.1) | 78 (61.9) | 0.76 |
| Diabetes mellitus, n (%) | 75 (26) | 48 (29.4) | 27 (21.4) | 0.12 |
| Dyslipidaemia, n (%) | 146 (51.5) | 80 (49.1) | 66 (52.4) | 0.58 |
| Current smoker, n (%) | 69 (23.9) | 32 (19.6) | 37 (29.4) | 0.054 |
| History of stroke or TIA, n (%) | 22 (7.6) | 7 (4.3) | 15 (11.9) | 0.016 |
| Peripheral artery disease, n (%) | 32 (11.1) | 18 (11.2) | 14 (11.1) | 0.99 |
| COPD, n (%) | 62 (21.5) | 31 (19) | 31 (24.6) | 0.25 |
| Chronic kidney disease, n (%) | 38 (13.1) | 21 (12.9) | 17 (13.5) | 0.88 |
| Atrial fibrillation, n (%) | 19 (6.6) | 7 (4.3) | 12 (9.5) | 0.075 |
| Anaemia, n (%) | 89 (30.8) | 46 (28.2) | 43 (34.1) | 0.28 |
| Logistic EuroSCORE, median (IQR) | 1.43 (0.91–2.50) | 1.43 (0.9–2.31) | 1.42 (1.02–2.65) | 0.42 |
| Serum creatinine (mg/dl), median (IQR) | 0.83 (0.70–1) | 0.84 (0.73–1) | 0.81 (0.67–1) | 0.46 |
| Haemoglobin (g/dl), median (IQR) | 13.1 (12–14.2) | 13.1 (12.1–14.1) | 13.2 (11.7–14.2) | 0.57 |
| Total cholesterol (mg/dl), mean ± SD | 190 ± 48 | 189 ± 47 | 192 ± 50 | 0.66 |
| HDL-c (mg/dl), median (IQR) | 45 (38–54) | 46 (40–57) | 45 (37–51) | 0.11 |
| LDL-c (mg/dl), mean ± SD | 114 ± 40 | 112 ± 30 | 116 ± 42 | 0.43 |
| Triglyceride (mg/dl), median (IQR) | 123 (88–184) | 122 (86–188) | 126 (88–174) | 0.94 |
| LV ejection fraction (%), median (IQR) | 60 (60–65) | 60 (60–65) | 60 (60–65) | 0.68 |
| LVEDD (mm), mean ± SD | 47.5 ± 5.8 | 47.2 ± 6 | 48 ± 5.5 | 0.24 |
| Septum (mm), median (IQR) | 13 (12–15) | 13 (12–14) | 14 (12–15) | 0.010 |
| Posterior wall (mm), median (IQR) | 12 (11–13) | 12 (11–13) | 13 (12–14) | 0.002 |
| LVMI (g/m2), median (IQR) | 128 (108–152) | 125 (106–146) | 135 (112–160) | 0.006 |
| Mean aortic gradient (mmHg), median (IQR) | 51 (43–60) | 48 (43–57) | 55 (43–61) | 0.007 |
| Maximum aortic gradient (mmHg), median (IQR) | 81 (71–95) | 79 (71–94) | 87 (72–98) | 0.039 |
| AVA (cm2), median (IQR) | 0.75 (0.65–0.85) | 0.8 (0.65–0.9) | 0.7 (0.6–0.8) | 0.001 |
| sPAP >30, n (%) | 81 (28.1) | 39 (24.1) | 42 (33.3) | 0.083 |
| Moderate-severe AR, n (%) | 76 (26.3) | 49 (30.1) | 27 (21.4) | 0.098 |
| LV strain, n (%) | 93 (32.2) | 38 (23.3) | 55 (43.7) | <0.001 |
| Sokolow-Lyon index, (mV), median (IQR) | 24 (18–30) | 24 (18–29) | 26 (20–32) | 0.014 |
| Preoperative BBB, n (%) | 31 (10.7) | 17 (10.4) | 14 (11.1) | 0.85 |
| In-hospital stay (days), median (IQR) | 7 (6-10) | 7 (6 9) | 7 (6–10) | 0.36 |
| Valve type, n (%) | ||||
| Mechanical prosthesis | 132 (45.7) | 79 (48.5) | 53 (42.1) | 0.28 |
| Bioprosthesis | 154 (53.3) | 83 (50.9) | 51 (56.3) | 0.36 |
| Cardiopulmonary bypass time (min), median (IQR) | 105 (77–128) | 106 (80–126) | 102 (74–130) | 0.52 |
| Cross-clamp time (min), mean ± SD | 72.6 ± 30.9 | 72.6 ± 29.2 | 72.6 ± 33 | 0.98 |
| Postoperative complications, n (%) | ||||
| Stroke/TIA | 9 (3.1) | 4 (2.5) | 5 (4) | 0.46 |
| Haemodialysis | 8 (2.8) | 4 (2.5) | 4 (3.1) | 0.71 |
| Atrial fibrillation | 89 (30.8) | 45 (27.6) | 44 (34.9) | 0.18 |
| Permanent pacemaker | 8 (2.8) | 2 (1.2) | 6 (4.8) | 0.069 |
| Cardiac tamponade | 4 (1.4) | 2 (1.2) | 2 (1.6) | 0.80 |
| Major haemorrhage | 10 (3.5) | 3 (1.8) | 7 (5.6) | 0.087 |
| Revision | 13 (4.5) | 8 (4.9) | 5 (4) | 0.70 |
| Myocardial infarction | 2 (0.7) | 2 (1.2) | 0 (0) | 0.21 |
AR: aortic regurgitation; AVA: aortic valve area; BMI: body mass index; COPD: chronic obstructive pulmonary disease; fQRS: fragmented QRS; HDL-c: high-density lipoprotein cholesterol; IQR: interquartile; LDL-c: low-density lipoprotein cholesterol; LV: left ventricle; LVEDD: left ventricle end-diastolic diameter; MI: myocardial infarction; NYHA: New York Heart Association functional capacity; SD: standard deviation: sPAP: systolic pulmonary artery pressure; TIA: transient ischaemic attack.
Follow-up data and clinical outcomes are displayed in Table 2. A total of 59 (20.4%) patients died over a follow-up period of 54 ± 32 months. There was no significant difference in hospital and 30-day mortality. All-cause mortality was higher in the fQRS group (23 [14.1%] vs 36 [28.6], log-rank test P = 0.002) in the long term (Fig. 2). There was no significant difference in terms of postoperative complications.
Table 2:
Comparison of clinical outcomes according to the presence of fragmented QRS
| Parameter | All patients (n = 289) | fQRS (−) (n = 163) | fQRS (+) (n = 126) | P-value |
|---|---|---|---|---|
| Follow-up period (months), mean ± SD | 54 ± 32 | 55 ± 30 | 51 ± 35 | 0.25a |
| In-hospital mortality, n (%) | 5 (1.7) | 1 (0.6) | 4 (3,2) | 0.93b |
| 30-Day mortality, n (%) | 7 (2.4) | 2 (1.2) | 5 (4) | 0.53b |
| Total mortality, n (%) | 59 (20.4) | 23 (14.1) | 36 (28.6) | 0.002 b |
fQRS: fragmented QRS; SD: standard deviation.
Student's t-test was used to compare variables.
Log-rank test was used to compare mortality rates.
Values with p<0.05 were accepted as significant and are shown as bold in the table.
Figure 2:
Long-term survival according to the presence of fragmented QRS.
Univariable and multivariable Cox regression analyses were used to determine the independent predictors of all-cause mortality in SAVR patients. Clinical presentation with syncope (HR: 2.454, CI: 1.112–5.417, P = 0.026), diabetes mellitus (HR: 1.816, CI: 1.076–3.066, P = 0.026), history of stroke or transient ischaemic attack (HR: 3.491, CI: 1.806–6.748, P < 0.001), cardiopulmonary by-pass time (HR: 1.007, CI: 1.002–1.012, P = 0.008), cross-clamp time (HR: 1.010, CI: 1.002–1.017, P = 0.015), electrocardiographic left ventricular strain (HR: 2.165, CI: 1.298–3.611, P = 0.003) and presence of fQRS (HR: 2.208, CI: 1.307–3.730, P = 0.003) were associated with all-cause mortality in univariable analyses. We generated a multivariable cox regression model with the variables with a P-value of <0.10 in univariable analyses. The presence of fQRS (HR: 1.802, CI: 1.035–3.135, P = 0.037), electrocardiographic left ventricular strain (HR: 1.836, CI: 1.036–3.254, P = 0.038) and history of stroke or transient ischaemic attack (HR: 3.130, CI: 1.528–6.412, P = 0.002) were independent predictors of all-cause mortality in the multivariable Cox regression model (Table 3).
Table 3:
Univariable and multivariable Cox proportional hazard models of all-cause mortality
| Variables | Univariable analyses |
Multivariable analyses |
||
|---|---|---|---|---|
| HR (95% CI) | P-value | HR (95% CI) | P-value | |
| Age | 1.023 (0.999–1.048) | 0.063 | 1.016 (0.990–1.043) | 0.23 |
| Male gender | 1.158 (0.688–1.948) | 0.58 | ||
| BMI | 0.982 (0.935–1.032) | 0.47 | ||
| Clinical presentation | ||||
| Angina pectoris | 0.795 (0.430–1.473) | 0.47 | ||
| Dyspnoea (NYHA 3–4) | 1.160 (0.689–1.952) | 0.58 | ||
| Syncope | 2.454 (1.112–5.417) | 0.026 | 0.969 (0.392–2.393) | 0.95 |
| Hypertension | 1.080 (0.633–1.842) | 0.78 | ||
| Diabetes mellitus | 1.816 (1.076–3.066) | 0.026 | 1.541 (0.893–2.658) | 0.12 |
| Dyslipidaemia | 0.937 (0.562–1.564) | 0.80 | ||
| Current smoker | 1.064 (0.592–1.912) | 0.84 | ||
| Congestive heart failure | 1.708 (0.776–3.763) | 0.18 | ||
| Chronic kidney disease | 0.998 (0.452–2.205) | 0.99 | ||
| Peripheral artery disease | 1.476 (0.726–3.003) | 0.28 | ||
| COPD | 1.399 (0.796–2.457) | 0.24 | ||
| History of stroke/TIA | 3.491 (1.806–6.748) | <0.001 | 3.130 (1.528–6.412) | 0.002 |
| Atrial fibrillation | 1.320 (0.527–3.304) | 0.55 | ||
| Anaemia | 1.575 (0.932–2.659) | 0.089 | 1.357 (0.774–2.378) | 0.29 |
| Logistic EuroSCORE | 1.127 (0.976–1.302) | 0.10 | ||
| LV ejection fraction | 0.983 (0.954–1.014) | 0.24 | ||
| LVEDD | 0.996 (0.956–1.038) | 0.86 | ||
| Septum | 0.960 (0.864–1.068) | 0.46 | ||
| LVMI | 0.998 (0.991–1.005) | 0.53 | ||
| Mean aortic gradient | 0.992 (0.973–1.011) | 0.39 | ||
| Peak aortic gradient | 0.997 (0.985–1.010) | 0.67 | ||
| AVA | 0.939 (0.686–1.285) | 0.70 | ||
| Moderate-severe aortic regurgitation | 0.893 (0.503–1.586) | 0.70 | ||
| Creatinine | 0.752 (0.258–2.191) | 0.60 | ||
| Hemoglobin | 0.921 (0.818–1.037) | 0.17 | ||
| Cardiopulmonary bypass time | 1.007 (1.002–1.012) | 0.008 | 1.003 (0.990–1.016) | 0.65 |
| Cross-clamp time | 1.010 (1.002–1.017) | 0.015 | 1.007 (0.988–1.026) | 0.47 |
| In hospital stay | 1.034 (0.989–1.080) | 0.14 | ||
| LV strain | 2.165 (1.298–3.611) | 0.003 | 1.836 (1.036–3.254) | 0.038 |
| Sokolow-Lyon index | 1.008 (0.975–1.042) | 0.65 | ||
| Preoperative bundle brunch block | 0.926 (0.502–1.706) | 0.80 | ||
| Fragmented QRS | 2.208 (1.307–3.730) | 0.003 | 1.802 (1.035–3.135) | 0.037 |
AVA: aortic valve area; BMI: body mass index; CI: confidence interval; COPD: chronic obstructive pulmonary disease; HR: hazard ratio; LV: left ventricle; LVEDD: left ventricle end-diastolic diameter; LVMI: left ventricular mass index; NYHA: New York Heart Association functional capacity; TIA: transient ischaemic attack.
Values with p<0.05 were accepted as significant and are shown as bold in the table.
DISCUSSION
In this study, we evaluated the effect of fQRS on the long-term mortality of patients with severe AS who underwent isolated SAVR. The 3 major findings of the current study are: (i) mortality was higher in patients with fQRS, (ii) History of stroke/TIA, left ventricular strain, higher LVMI and echocardiographic findings of severe AS were associated with fQRS in patients undergoing isolated SAVR and (iii) LV strain, history of stroke and presence of fQRS were independent predictors of total mortality during the follow-up.
LVH is a physiological adaptation mechanism to reduce stress on the ventricular wall and maintain cardiac output within normal limits. Nevertheless, LVH, which occurs in AS in the long term, causes myocardial degeneration with the excessive increase of wall stress and myocardial fibrosis with the effect of the relative ischaemia. These changes occur primarily in the subendocardial layer, causing interstitial fibrosis and then myocardial tissue to transform into fibrous tissue in advanced stages [20–22]. Hence, several symptoms, including dyspnoea, angina and syncope, occur due to impaired systolic and diastolic function of the LV. For all the reasons described above, it appears that myocardial fibrosis is associated with a poor prognosis in AS patients [23–25]. Previously, Milano et al. [26] reported that myocardial fibrosis in these patients negatively affected the clinical status, and long-term survival after SAVR was lower in patients with myocardial fibrosis. Moreover, another study indicated that myocardial fibrosis was associated with reduced survival in 10-year follow-up in patients treated with SAVR due to severe AS [27].
Several imaging tools, including cardiac MRI, are used to show myocardial fibrosis. These methods may be expensive, difficult to access, require specialized equipment. Hence, there is a need for cheaper and easily accessible daily methods. The use of ECG findings in this regard is being investigated because of its easy applicability and cost. One of the most important findings of these is the presence of fQRS. The fQRS as a non-invasive prognostic marker on resting ECG has been associated with alternation of myocardial activation due to myocardial scar and/or fibrosis [17]. The primary mechanism in the pathophysiology of fQRS is the depolarization problem in tissues that do not function electrically due to fibrosis [16]. This dysfunction creates variation by reflecting on QRS complexes in ECG. Moreover, it has been previously determined that fQRS is related to the severity of aortic stenosis and predicts complications that may develop after the treatment [14]. Recently, Gulsen et al. [13] have reported that fQRS was associated with mortality after transcatheter aortic valve replacement in patients with severe AS. In the present study, similar to the results of their study, in patients with fQRS, both mortality was higher, and the presence of fQRS was an independent predictor of total mortality during follow-up.
Although its physiopathology remains debated, previous studies showed that ECG strain is associated with an advanced hypertrophic response to AS with mid-wall fibrosis [28]. The prognostic value of the LV strain, including mortality and morbidity, has been reported in several previous studies with patients with AS [28–30]. Previously, Al-Hijji et al. indicated that ECG strain is an independent predictor of long-term mortality post-TAVI. Besides, Coisne et al. have recently shown that LV strain was a predictor of ventricular myocardial damage in a large cohort of patients with severe AS undergoing SAVR, and fQRS was common in this patient population [31]. Based on these results, ECG strain has been linked to excess cardiovascular morbidity and mortality in patients with AS. This is consistent with our observation that fQRS is a predictor of mortality after SAVR in patients with severe AS.
Stroke is a catastrophic cause of morbidity in patients with severe AS undergoing interventional treatment [1,2,13]. Previously, Gulsen et al. [13] evaluated 116 patients who underwent TAVI, and it was found that the presence of a history of stroke was associated with mortality. Besides, these results have been confirmed by large-scale studies in patients who underwent SAVR [19]. Similar to these results, stroke was an independent predictor of total mortality in the 54 ± 32-month follow-up of patients who underwent SAVR in our study. To the best of our knowledge, this is the first study to demonstrate that fQRS predicts total mortality in patients undergoing isolated SAVR during long-term follow-up.
Limitations
The retrospective design of the study is the main limitation. Selection bias and unmeasured confounders may affect the results due to the nature of retrospective studies. However, our findings are consistent with previous studies. Second, the sample size was small; hence, further prospective studies with larger cohorts may be needed to confirm the results. Lastly, we included only isolated SAVR patients. The results cannot be generalized to concomitant coronary artery bypass surgery and the other valve surgeries with SAVR.
CONCLUSIONS
In conclusion, the current data suggest that fQRS on a standard 12-lead ECG is a simple tool that may provide valuable information for risk stratification of the patients undergoing isolated SAVR for AS.
Conflict of interest: none declared.
Author contributions
Cafer Panç: Conceptualization; Data curation; Investigation; Methodology; Project administration; Writing—original draft. Arda Güler: Formal analysis; Investigation; Resources; Visualization. Arda Can Doğan: Data curation; Formal analysis; Resources; Software. Recep Gülmez: Conceptualization; Data curation; Funding acquisition; Investigation; Validation; Visualization. Ahmet Güner: Writing—review & editing. Ömer Çelik: Conceptualization; Formal analysis; Supervision; Validation; Visualization; Writing—review & editing.
Reviewer information
Interactive CardioVascular and Thoracic Surgery thanks Thomas Kuntze, Olaf Wendler and the other, anonymous reviewer(s) for their contribution to the peer review process of this article.
ABBREVIATIONS
- AS
Aortic stenosis
- CI
Confidence interval
- ECG
Electrocardiography
- fQRS
Fragmented QRS
- HR
Hazard ratio
- LVH
Left ventricular hypertrophy
- LVMI
Left ventricular mass index
- SAVR
Surgical aortic valve replacement
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