Abstract
Background
Reperfusion-induced ventricular arrhythmias (VAs) are a common yet under-recognized complication in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Their clinical impact and predictors remain incompletely understood.
Objectives
This study aimed to evaluate the incidence, distribution, risk factors, and prognostic significance of reperfusion-related VAs in a contemporary STEMI population treated with PPCI.
Methods
We retrospectively analyzed 736 STEMI patients who underwent PPCI between 2018 and 2023. Continuous telemetry monitoring was used to detect VAs, including premature ventricular contractions (PVCs), accelerated idioventricular rhythm (AIVR), non-sustained ventricular tachycardia (NSVT), sustained ventricular tachycardia (VT), and ventricular fibrillation (VF). Logistic regression models were applied to identify independent predictors of VA occurrence and assess their association with in-hospital major adverse cardiovascular events (MACE).
Results
VAs were observed in 48.8% of patients, with frequent PVCs (43.7%) and AIVR (18.9%) being the predominant subtypes. Multivariate analysis identified extensive anterior infarction and left anterior descending artery (LAD) involvement as independent predictors of VA development (p = 0.032). The presence of VAs was significantly associated with higher rates of in-hospital MACE, including cardiac death, recurrent myocardial infarction, and urgent target vessel revascularization.
Conclusions
Reperfusion-related VAs are common following PPCI for STEMI and carry a substantial adverse prognostic impact. Early identification of high-risk patients based on infarct characteristics and continuous arrhythmia monitoring is essential to improve clinical outcomes. Further prospective studies are warranted to refine management strategies targeting reperfusion arrhythmias.
Keywords: ST-segment elevation myocardial infarction, Primary percutaneous coronary intervention, Ventricular arrhythmias, Reperfusion injury, Left anterior descending artery
Introduction
Coronary artery disease (CAD) remains a leading cause of global morbidity and mortality, with increasing incidence in developing countries [1]. Among its most severe manifestations is ST-segment elevation myocardial infarction (STEMI), which requires urgent revascularization. Primary percutaneous coronary intervention (PPCI) is the standard of care for STEMI, markedly improving outcomes [2].
Despite its benefits, reperfusion therapy may paradoxically result in myocardial injury—referred to as reperfusion injury—which can lead to serious complications, including ventricular arrhythmias (VAs) [3]. These arrhythmias—such as premature ventricular contractions (PVCs), accelerated idioventricular rhythm (AIVR), non-sustained or sustained ventricular tachycardia (VT), and ventricular fibrillation (VF)—typically occur within hours after reperfusion and are associated with increased early mortality following myocardial infarction (MI) [3, 4]. Reperfusion arrhythmias (RAs) result from sudden changes in myocardial electrophysiology, including adenosine triphosphate (ATP) depletion, calcium overload, potassium shifts, and acidosis, which promote triggered activity and reentrant circuits [5, 6].
Reported incidence of these events varies, with some studies indicating 4–5% [7] and others up to 23% within the first 12 h post-symptom onset [8]. Risk factors include left main coronary artery (LMCA) involvement, elevated creatine kinase, inferior STEMI, right coronary artery (RCA) occlusion, low pre- percutaneous coronary intervention (PCI) thrombolysis and thrombin inhibition in myocardial infarction (TIMI) flow, and Killip class > 1 [5].
The prognostic implications of RAs are debated. Some studies found no association with long-term mortality [7, 9], while others link RAs to increased in-hospital and 30-day mortality [9]. Treatment follows standard VT/VF management using pharmacologic and electrical approaches [2], but preventive strategies remain undefined. Emerging interventions like infarct-related artery (IRA) balloon re-inflation have shown potential for terminating sustained RAs in limited reports [10].
Given these uncertainties and clinical relevance, this study aims to assess the incidence, subtypes, and predictors of reperfusion-related VAs in STEMI patients undergoing PPCI at a tertiary care center, specifically focusing on arrhythmias that occur during the PPCI procedure.
Materials and methods
Study participants
This retrospective study included 736 patients admitted to the Department of Cardiology at Xiangtan Central Hospital between October 2018 and June 2023. All participants were diagnosed with acute STEMI and received PPCI as their initial reperfusion therapy. Patients were eligible if they presented within 12 h of ischemic symptom onset and had ongoing chest pain at the time of admission. However, to ensure a relatively uniform ischemic burden and minimize the confounding impact of prolonged myocardial injury, we included only patients whose total duration of continuous chest pain was more than 30 min but less than 6 h. The diagnosis of STEMI was established based on both electrocardiographic and biochemical markers, following current consensus guidelines [11]. Diagnostic criteria included ST-segment elevation of ≥ 1 mm in two or more contiguous leads on a 12-lead electrocardiogram(ECG) or the presence of new left bundle branch block, accompanied by elevated cardiac troponin T levels (≥ 0.05 ng/mL), as measured using the Roche Diagnostics assay (Basel, Switzerland) [11]. Inclusion criteria were as follows: (1) typical ischemic chest pain persisting for more than 30 min but less than 6 h in total duration; (3) ST-elevation of ≥ 1 mm in anatomically contiguous leads on the initial ECG; and (3) successful completion of PPCI [12]. Patients were excluded if they met any of the following: (1) diagnosis of non-STEMI or unstable angina; (2) history of prior MI; (3) presence of structural heart disease or dilated cardiomyopathy; (4) existing cardiac conduction disturbances (e.g., AV [atrioventricular] block, fascicular block, bundle branch block); (5) permanent pacemaker implantation; (6) need for mechanical ventilation; (7) thyroid dysfunction; (8) contraindications to glycoprotein IIb/IIIa inhibitors (excluded to avoid heterogeneity in periprocedural antiplatelet therapy, which could influence the incidence of reperfusion-related ventricular arrhythmias); (9) inability to provide informed consent for inclusion in the institutional clinical registry (note: all patients undergoing PPCI had provided written informed consent for the procedure, and a waiver of additional consent was granted by the IRB for this retrospective study); (10) poor quality or incomplete ECG/Holter recordings; (11) QRS duration exceeding 120 ms; or (12) terminal illnesses limiting life expectancy (Fig. 1). The study was conducted in alignment with the Declaration of Helsinki (2013 revision) and received approval from the Ethics Committee of Xiangtan Central Hospital (Approval No. X2018083662-1). As this was a retrospective study utilizing de-identified clinical registry data, no additional interventions beyond routine care were performed. All patients undergoing PPCI had previously provided written informed consent for the procedure as part of standard care. For the current retrospective analysis of de-identified registry data, the institutional review board granted a waiver of additional informed consent.
Fig. 1.
Study flowchart PPCI, primary percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction; MI, myocardial infarction; AV, atrioventricular; ECG, electrocardiogram; VA, ventricular arrhythmia;
Clinical parameters
Baseline demographic and clinical information—including age, sex, smoking status, presence of hypertension, diabetes mellitus (DM), dyslipidemia, and a family history of CAD—was retrieved from the hospital’s electronic medical record system. Additional clinical variables recorded included total ischemic time, infarct location, the culprit coronary vessel (left anterior descending artery [LAD], left circumflex artery [LCX], RCA, or LMCA), post-procedural TIMI (thrombolysis in myocardial infarction) flow grade, emergency interventions performed, and arrhythmia classification.
ECG-based infarct localization
Infarct localization was assessed according to the distribution of affected ECG leads. The classification scheme included the following patterns: V1–V4 indicating anteroseptal infarction; V3–V4 for anterior infarction; V1–V6 for extensive anterior involvement; V1–V6 with I and aVL for anterolateral infarction; I and aVL for lateral; II, III, and aVF for inferior; I, II, III, aVF, and aVL for inferolateral; II, III, aVF, V8, and V9 for inferoposterior; II, III, aVF, aVL, V8, and V9 for posterolateral; and II, III, aVF in combination with V3R–V6R for inferior infarction with right ventricular involvement [13].
Arrhythmia monitoring and definitions
Continuous ECG monitoring during PCI was performed using centralized telemetry systems in the cardiac catheterization laboratory. All ECG recordings were stored in digital format and later reviewed independently by two experienced cardiologists to assess the presence and burden of arrhythmias. In cases of reviewer disagreement, a third senior cardiologist adjudicated the final classification. RAs were defined as arrhythmic events occurring after initial restoration of antegrade coronary flow (defined as at least TIMI II flow), but before the end of the PCI procedure. The arrhythmia definitions were as follows [14]: frequent PVCs were defined as more than six premature ventricular contractions per minute, sustained for at least five consecutive minutes during continuous ECG monitoring; AIVR was characterized by a ventricular rhythm ranging from 60 to 125 beats per minute; non-sustained VT (NSVT) was identified as three or more consecutive ventricular beats exceeding 120 bpm and lasting less than 30 s; sustained VT was defined as lasting 30 s or more or requiring therapeutic intervention; and VF was described as disorganized, irregular electrical activity with variable wave amplitudes. This study specifically focused on reperfusion-related arrhythmias observed during the PPCI procedure. Post-PCI arrhythmias occurring during CCU/ward monitoring were not included in this analysis. For subgroup analysis, the ‘VT/VF group’ was defined as patients who experienced either sustained VT or VF during the PPCI procedure.
Peri-procedural management
All patients were administered dual antiplatelet therapy consisting of aspirin (300 mg) combined with a loading dose of clopidogrel, ticagrelor, or prasugrel, along with intravenous heparin (5,000–10,000 U) prior to PCI. The intervention was conducted under activated clotting time (ACT) monitoring, with additional doses of heparin given as necessary to maintain an ACT between 250 and 350 s. In-hospital medical management was conducted in accordance with current guideline-based recommendations [15].
Outcome assessment
In-hospital major adverse cardiovascular events (MACE) were defined as the occurrence of any of the following complications during the hospitalization period—from the time of admission to discharge: cardiac death, MI, acute stent thrombosis, or recurrence of symptoms necessitating urgent repeat target-vessel revascularization (TVR) through either PCI or coronary artery bypass grafting (CABG). All clinical outcomes were classified according to the criteria established by the Academic Research Consortium [16]. Due to the retrospective nature of this study, precise timing of individual adverse events could not be consistently retrieved.
Statistical analysis
Statistical analyses were conducted using SPSS software, version 26.0 (IBM Corp., Armonk, NY, USA). Categorical variables were summarized as frequencies and percentages, with group comparisons performed using either the chi-square test or Fisher’s exact test, as appropriate. Continuous variables were reported as mean ± standard deviation (SD) when data followed a normal distribution, or as median with interquartile range (IQR) when non-normally distributed. For comparisons of continuous data, the independent samples t-test was applied under the assumption of normality; otherwise, the Mann–Whitney U test was utilized. To identify independent predictors of reperfusion-induced ventricular arrhythmias (VAs), a binary logistic regression model was constructed. Variables with P < 0.10 in univariate analysis or deemed clinically relevant based on prior literature were included in the multivariate model. Additionally, to assess whether the occurrence of VAs was independently associated with in-hospital MACE, a separate logistic regression analysis was performed. Results were expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). A two-sided P value < 0.05 was considered statistically significant in all analyses. To assess potential multicollinearity among predictors, variance inflation factor (VIF) analysis was performed. All VIF values were below 5, indicating no significant collinearity.
Results
Baseline clinical characteristics
A total of 736 STEMI patients who underwent PPCI were enrolled in the study, among whom 359 individuals (48.8%) experienced VAs during their hospital stay. The mean age of the cohort was 61.48 ± 11.05 years, with no statistically significant difference observed between the VA and non-VA groups (61.91 ± 12.10 vs. 62.17 ± 11.32 years, P = 0.380). The majority of participants were male (72.6%). The distribution of conventional cardiovascular risk factors—including DM, hypertension, dyslipidemia, and smoking—was comparable between the two groups. Additionally, there were no significant intergroup differences in left ventricular ejection fraction (LVEF), prior cardiovascular history, discharge medication regimens or length of hospital stay (all P > 0.05) (Table 1).
Table 1.
Baseline clinical characteristics
| All (n = 736) | VA group (n = 359) | Without VA group (n = 377) | P value | |
|---|---|---|---|---|
| Age, years | 61.48 ± 11.05 | 61.91 ± 12.10 | 62.17 ± 11.32 | 0.380 |
| Male sex, n (%) | 534 (72.6%) | 256 (71.3%) | 278 (73.7%) | 0.511 |
| BMI, kg/m2 | 24.21 ± 3.16 | 24.2 ± 3.0 | 24.4 ± 3.2 | 0.617 |
| Diabetes mellitus, n (%) | 211 (28.7%) | 111 (30.9%) | 100 (26.5%) | 0.216 |
| Hypertension, n (%) | 451 (61.3%) | 233 (64.9%) | 218 (57.8%) | 0.058 |
| Dyslipidemia, n (%) | 230 (31.2%) | 120 (33.4%) | 110 (29.2%) | 0.244 |
| Previous PCI, n (%) | 114 (15.5%) | 58 (16.2%) | 56 (14.9%) | 0.699 |
| Previous stroke, n (%) | 80 (10.9%) | 35 (9.7%) | 45 (11.9%) | 0.404 |
| Current smoking, n (%) | 352 (47.8%) | 183 (51.0%) | 169 (44.8%) | 0.110 |
| Previous peripheral vascular disease, n (%) | 103 (14.0%) | 44 (12.3%) | 59 (15.6%) | 0.222 |
| LVEF, % | 59.8 ± 7.8 | 59.6 ± 6.9 | 59.9 ± 8.5 | 0.716 |
| Previous atrial fibrillation, n (%) | 56 (7.6%) | 25 (7.0%) | 31 (8.2%) | 0.613 |
| Medication at discharge | ||||
| Aspirin, n (%) | 736(100) | (100) | (100) | - |
| P2Y12 receptor antagonist, n (%) | 721 (98.0%) | 351 (97.8%) | 370 (98.1%) | 0.923 |
| Statin, n (%) | 703 (95.5%) | 341 (95.0%) | 362 (96.0%) | 0.617 |
| ACEI/ARB, n (%) | 662 (89.9%) | 319 (88.9%) | 343 (91.0%) | 0.403 |
| Beta Blocker, n (%) | 632 (85.9%) | 312 (86.9%) | 320 (84.9%) | 0.494 |
| Calcium channel blocker, n (%) | 118 (16.0%) | 61 (17.0%) | 57 (15.1%) | 0.554 |
| Length of hospital stay, days | 7 [5–10] | 7 [5–10] | 7 [5–9] | 0.112 |
Continuous variables were expressed as mean ± SD or median (interquartile range). Categorical variables were expressed as number (percentage)
VA Ventricular arrhythmia, BMI Body mass index, PCI Percutaneous coronary intervention, LVEF Left ventricular ejection fraction, ACEI Angiotensin-converting inhibitor, ARB Angiotensin receptor blocker
Angiographic and electrocardiographic findings
Multivessel CAD was identified in 57.9% of the study population, with no statistically significant difference between the VA and non-VA groups (P = 0.316). However, the distribution of culprit coronary arteries varied significantly between the two cohorts (P = 0.032). The LAD emerged as the most frequently involved culprit vessel and was notably more common among patients in the VA group (63.8%) compared to those in the non-VA group (52.8%). In contrast, RCA-related infarctions were observed more frequently in the non-VA group (30.0% vs. 19.8%).
Differences in infarct localization based on ECG findings were also statistically significant (P = 0.002). Anterior wall infarctions—including anteroseptal (26.5% vs. 19.9%), anterior (11.7% vs. 8.0%), and extensive anterior patterns (13.9% vs. 9.3%)—were more prevalent in the VA group. Conversely, inferior and posterolateral infarctions occurred more commonly in the non-VA group. Furthermore, analysis of TIMI flow grades before and after PPCI revealed a significant difference in pre-procedural TIMI grades between the two groups (P < 0.001), with a higher proportion of patients in the non-VA group exhibiting TIMI 2 or 3 flow prior to intervention. However, post-procedural TIMI flow was uniformly successful across both groups, with over 91% of patients achieving TIMI 3 flow and no significant intergroup difference observed (P = 0.479) (Table 2).
Table 2.
Angiographic and electrocardiogram findings
| All (n = 736) | VA group (n = 359) | Without VA group (n = 377) | P value | |
|---|---|---|---|---|
| Multivessel diseasea, n (%) | 426 (57.9%) | 215 (59.9%) | 211 (56.0%) | 0.3163 |
| Culprit coronary vessel 0.032 | ||||
| LAD, n (%) | 428 (58.2%) | 229 (63.8%) | 199 (52.8%) | |
| LCX, n (%) | 77 (10.5%) | 32 (8.9%) | 45 (11.9%) | |
| RCA, n (%) | 184 (25.0%) | 71 (19.8%) | 113 (30.0%) | |
| OM1, n (%) | 17 (2.3%) | 12 (3.3%) | 5 (1.3%) | |
| Ramus, n (%) | 3 (0.4%) | 2 (0.6%) | 1 (0.3%) | |
| PDA, n (%) | 8 (1.1%) | 4 (1.1%) | 4 (1.1%) | |
| Major D1, n (%) | 7 (1.0%) | 3 (0.8%) | 4 (1.1%) | |
| Major D2, n (%) | 6 (0.8%) | 3 (0.8%) | 3 (0.8%) | |
| LMCA, n (%) | 6 (0.8%) | 3 (0.8%) | 3 (0.8%) | |
| Infarct localization 0.002 | ||||
| V1- V4 (anteroseptal), n (%) | 170 (23.1%) | 95 (26.5%) | 75 (19.9%) | |
| V3- V4 (anterior), n (%) | 72 (9.8%) | 42 (11.7%) | 30 (8.0%) | |
| V1- V6 (extensive anterior), n (%) | 85 (11.5%) | 50 (13.9%) | 35 (9.3%) | |
| V1- V6 with I and aVL (anterolateral), n (%) | 41 (5.6%) | 25 (7.0%) | 16 (4.2%) | |
| I and aVL (lateral), n (%) | 22 (3.0%) | 8 (2.2%) | 14 (3.7%) | |
| II, III, and aVF (inferior), n (%) | 135 (18.3%) | 55 (15.3%) | 80 (21.2%) | |
| II, III, aVF, V8, and V9 (inferoposterior), n (%) | 75 (10.2%) | 30 (8.4%) | 45 (11.9%) | |
| II, III, aVF, aVL, V8, and V9 (posterolateral), n (%) | 73 (9.9%) | 28 (7.8%) | 45 (11.9%) | |
| II, III, aVF with V3R–V6R (inferior + right ventricular), n (%) | 63 (8.6%) | 26 (7.2%) | 37 (9.8%) | |
| Pre- procedural TIMI <0.001 | ||||
| 0, n (%) | 121 (16.4%) | 67 (18.7%) | 54 (14.3%) | |
| 1, n (%) | 160 (21.7%) | 88 (24.5%) | 72 (19.1%) | |
| 2, n (%) | 263 (35.7%) | 118 (32.9%) | 145 (38.5%) | |
| 3, n (%) | 192 (26.1%) | 86 (23.9%) | 106 (28.1%) | |
| Post- procedural TIMI 0.479 | ||||
| 0, n (%) | 3 (0.4%) | 2 (0.6%) | 1 (0.3%) | |
| 1, n (%) | 10 (1.4%) | 6 (1.7%) | 4 (1.1%) | |
| 2, n (%) | 38 (5.2%) | 22 (6.1%) | 16 (4.2%) | |
| 3, n (%) | 685 (93.0%) | 329 (91.6%) | 356 (94.4%) | |
Continuous variables were expressed as mean ± SD. Categorical variables were expressed as number (percentage)
aDefined as the presence of > 50% diameter stenosis in 2 or more major epicardial arteries
VA Ventricular arrhythmia, LAD Left anterior descending coronary artery, LCX Left circumflex coronary artery, RCA Right coronary artery, OM 1 First obtuse marginal artery, PDA Posterior descending artery, Major D1 First diagonal artery, Major D2 Second diagonal artery, LMCA Left main coronary artery, TIMI Thrombolysis and thrombin inhibition in myocardial infarction
Distribution of ventricular arrhythmias
Among the 359 patients who experienced VA, frequent PVCs represented the most common arrhythmic manifestation, observed in 43.7% of cases. This was followed by AIVR (18.9%) and sustained VT (16.2%). VF was identified in 8.1% of patients within the VA group. Instances of combined arrhythmias—such as NSVT co-occurring with AIVR or sustained VT—were relatively infrequent (Fig. 2).
Fig. 2.
Distribution of various ventricular arrhythmia types in patients who developed VAs during PPCI for STEMI. Frequent PVCs were the most prevalent (43.7%), followed by AIVR (18.9%), sustained VT (16.2%), VF (8.1%), and combined arrhythmias such as NSVT with AIVR (7.0%) and NSVT with sustained VT (6.1%) VA, ventricular arrhythmia; PVC, premature ventricular contraction; NSVT, non-sustained ventricular tachycardia; Sustained VT, sustained ventricular tachycardia; VF, ventricular fibrillation; AIVR, accelerated idioventricular rhythm; PPCI, primary percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction;
In-Hospital adverse outcomes
The incidence of in-hospital MACE was significantly greater in the VA group compared to the non-VA group (15.0% vs. 4.5%, P < 0.001). In particular, the VA group exhibited higher rates of cardiac death (3.9% vs. 0.8%, P = 0.005), MI (13.4% vs. 2.7%, P < 0.001), and TVR (9.2% vs. 2.4%, P = 0.001). All differences were statistically significant, highlighting a worse in-hospital prognosis among patients who experienced VAs (Table 3). To further elucidate the prognostic impact of arrhythmia subtypes, we stratified the VA group (n = 359) into VT/VF (defined as sustained VT or VF; n = 95) and non-VT/VF (n = 264) subgroups. The incidence of in-hospital MACE was significantly higher in the VT/VF group compared to the non-VT/VF group (25.3% vs. 11.4%, P < 0.001). Additionally, cardiac death (8.4% vs. 2.3%, P = 0.012), myocardial infarction (23.2% vs. 9.8%, P = 0.002), and TVR (14.7% vs. 7.2%, P = 0.029) occurred more frequently in patients with VT/VF. There was no significant difference in acute stent thrombosis between the two groups (P = 0.763) (Table 4).
Table 3.
In-hospital outcomes
| All (n = 736) | VA group (n = 359) | Without VA group (n = 377) | P value | |
|---|---|---|---|---|
| In-hospital MACE, n (%) | 71 (9.6%) | 54 (15.0%) | 17 (4.5%) | < 0.001 |
| Cardiac death, n (%) | 17 (2.3%) | 14 (3.9%) | 3 (0.8%) | 0.005 |
| MI, n (%) | 58 (7.9%) | 48 (13.4%) | 10 (2.7%) | < 0.001 |
| TVR, n (%) | 42 (5.7%) | 33 (9.2%) | 9 (2.4%) | 0.001 |
| Acute stent thrombosis, n (%) | 6 (0.8%) | 3 (0.8%) | 3 (0.8%) | 0.998 |
Categorical variables were expressed as number (percentage)
VA Ventricular arrhythmia, MACE Major adverse cardiovascular event, TVR Target-vessel revascularization, MI Myocardial infarction
Table 4.
Analysis of In-hospital outcomes in VA patients (VT/VF vs. Non-VT/VF)
| All (n = 359) | VT/VF (n = 95) | Non-VT/VF (n = 264) | P value | |
|---|---|---|---|---|
| In-hospital MACE, n (%) | 54 (15.0%) | 24 (25.3%) | 30 (11.4%) | < 0.001 |
| Cardiac death, n (%) | 14 (3.9%) | 8 (8.4%) | 6 (2.3%) | 0.012 |
| MI, n (%) | 48 (13.4%) | 22 (23.2%) | 26 (9.8%) | 0.002 |
| TVR, n (%) | 33 (9.2%) | 14 (14.7%) | 19 (7.2%) | 0.029 |
| Acute stent thrombosis, n (%) | 3 (0.8%) | 1 (1.1%) | 2 (0.8%) | 0.763 |
Categorical variables were expressed as number (percentage)
VA Ventricular arrhythmia, VT Ventricular tachycardia, VF Ventricular fibrillation, MACE Major adverse cardiovascular event, TVR Target-vessel revascularization, MI Myocardial infarction
Predictors of ventricular arrhythmia
Univariate logistic regression analysis identified anterior infarct patterns—particularly extensive anterior infarction (OR(odds ratio) = 1.626, 95% CI(confidence interval): 1.466–2.771, P < 0.001)—and involvement of the LAD as the culprit vessel (OR = 1.125, 95% CI: 1.082–1.289, P < 0.001) as significant predictors of VA occurrence. Upon multivariate adjustment, both extensive anterior infarction (OR = 3.736, 95% CI: 1.227–8.665, P = 0.001) and LAD-related infarction (OR = 2.326, 95% CI: 1.322–3.564, P < 0.001) remained independently associated with an increased risk of VA (Table 5). VIF analysis revealed no significant multicollinearity between these variables (all VIFs < 5).
Table 5.
Univariable and multivariable logistic analyses to predict ventricular arrhythmia
| Univariate Analysis | Multivariate Analysis | |||||
|---|---|---|---|---|---|---|
| Variables | OR | 95% CI | P value | OR | 95% CI | P value |
| Age | 1.302 | 0.640–3.179 | 0.455 | |||
| Male sex | 1.672 | 0.836–3.626 | 0.073 | |||
| Diabetes mellitus | 1.233 | 0.737–3.824 | 0.327 | |||
| Hypertension | 1.234 | 0.737–2.837 | 0.843 | |||
| Previous PCI | 1.622 | 0.737–2.827 | 0.528 | |||
| Previous stroke | 1.624 | 0.729–4.521 | 0.178 | |||
| Previous atrial fibrillation | 1.410 | 0.736–1.730 | 0.631 | |||
| LAD | 1.125 | 1.082-1. 289 | <0.001 | 2.326 | 1.322-3. 564 | <0.001 |
| LCX | 1.023 | 0.445–2.335 | 0.602 | |||
| RCA | 1.138 | 0.720–2.001 | 0.534 | |||
| Ramus | 1.355 | 0.941–2.011 | 0.146 | |||
| PDA | 1.037 | 0.551–4.221 | 0.933 | |||
| LMCA | 2.153 | 1.142–4.152 | 0.022 | 3.441 | 0.204–16.829 | 0.346 |
| V1- V4 (anteroseptal) | 1.054 | 1.032–1.064 | 0.037 | 1.186 | 0.151–11.533 | 0.893 |
| V3- V4 (anterior) | 2.323 | 1.640–5.737 | 0.001 | 2.531 | 0.682–3.521 | 0.640 |
| V1- V6 (extensive anterior) | 1.626 | 1.466–2.771 | <0.001 | 3.736 | 1.227–8.665 | 0.001 |
| V1- V6 with I and aVL (anterolateral) | 1.527 | 0.251–6.211 | 0.643 | |||
OR Odds ratio, CI Confidence interval, PCI Percutaneous coronary intervention, LAD Left anterior descending coronary artery, LCX Left circumflex coronary artery, RCA Right coronary artery, PDA Posterior descending artery, LMCA Left main coronary artery
Multivariate analysis of predictors for In-Hospital MACE
Logistic regression analysis was performed to identify independent predictors of in-hospital MACE. As shown in Table 6, the occurrence of ventricular arrhythmias was significantly associated with an increased risk of MACE in both univariate (HR = 1.847, 95% CI: 1.155–2.953, P = 0.018) and multivariate analyses (HR = 2.173, 95% CI: 1.031–4.667, P = 0.021). Other variables, including LAD involvement and extensive anterior infarction, did not remain significant in the multivariate model (P > 0.05).
Table 6.
Univariable and multivariable logistic analyses to predict In-hospital MACE
| Univariate Analysis | Multivariate Analysis | |||||
|---|---|---|---|---|---|---|
| Variables | HR | 95% CI | P value | HR | 95% CI | P value |
| VA occurrence | 1.847 | 1.155–2.953 | 0.018 | 2.173 | 1.031–4.667 | 0.021 |
| Age | 1.008 | 0.561–1.811 | 0.977 | |||
| Male sex | 1.251 | 0.695–2.246 | 0.455 | |||
| Hypertension | 1.065 | 0.588–1.929 | 0.833 | |||
| LAD involvement | 2.072 | 1.168–3.674 | 0.012 | 1.122 | 0.623–2.012 | 0.704 |
| Extensive anterior infarct | 1.125 | 0.626–2.022 | 0.693 | |||
MACE Major adverse cardiovascular event, CI Confidence interval, HR Hazard ratios, VA Ventricular arrhythmia, LAD Left anterior descending coronary artery
Discussion
In this study, we conducted a comprehensive evaluation of the incidence, distribution, and clinical significance of reperfusion-related ventricular arrhythmias (VAs) in STEMI patients treated with PPCI. The principal findings are summarized as follows: (1) High VA incidence: Approximately 48.8% of patients developed VAs during hospitalization, with frequent PVCs and AIVR representing the predominant arrhythmia subtypes. (2) Relationship with infarct localization and culprit artery: Anterior wall infarctions and LAD involvement were more frequently observed in patients who experienced VAs compared to those who did not. (3) Adverse impact on in-hospital outcomes: The presence of VAs was significantly correlated with increased rates of in-hospital MACE, including cardiac death, myocardial infarction, and TVR. (4) Independent predictors of VA: Multivariate logistic regression analysis identified both extensive anterior infarction and LAD-related lesions as independent risk factors for VA occurrence during hospitalization. (5) Independent prognostic impact of VA: A separate multivariate model revealed that VA occurrence was independently associated with an increased risk of in-hospital MACE, including cardiac death and revascularization.
High incidence of ventricular arrhythmias
In our cohort of STEMI patients undergoing PPCI, VAs were observed in 48.8% of cases, a rate that surpasses previously reported figures ranging from 4–23% [5]. This discrepancy is likely attributable to the routine use of continuous telemetry monitoring, which enhances the detection of transient arrhythmic events during mechanical reperfusion [17]. Although this method improves sensitivity for arrhythmia identification, it may also lead to an overestimation of incidence when compared to studies utilizing less intensive monitoring protocols [17]. Among the arrhythmias detected, AIVR and frequent PVCs were the most prevalent, consistent with findings from large registries reporting AIVR in approximately 42–50% of STEMI patients receiving reperfusion therapy [17–19]. The genesis of AIVR is typically linked to enhanced abnormal automaticity within ischemia–reperfusion zones, driven by intracellular calcium overload and increased sympathetic stimulation [20]. In contrast, frequent or complex PVCs are considered markers of heightened myocardial electrical instability and have been independently associated with an increased risk of sudden cardiac death (SCD) [5]. Notably, the Cardiac Arrhythmia Suppression Trial (CAST) demonstrated that pharmacologic suppression of PVCs using traditional antiarrhythmic agents paradoxically led to increased mortality [21]. Over time, the arrhythmia burden was observed to decline following reperfusion, reflecting the gradual resolution of ionic and metabolic derangements [17, 18]. Therefore, distinguishing benign arrhythmias such as AIVR from potentially life-threatening ones like complex PVCs and sustained VT is essential for optimizing individualized treatment strategies [5].
Ventricular arrhythmia mechanisms and risk stratification
Post-reperfusion VAs can be broadly classified according to their underlying electrophysiological mechanisms. AIVR is generally considered benign and transient, frequently observed in association with successful myocardial reperfusion [10, 20]. In contrast, frequent PVCs and NSVT—particularly when occurring at a rate exceeding 10 episodes per hour—may reflect underlying myocardial electrical instability [17, 22]. Sustained VT or VF is strongly linked to a significantly elevated risk of mortality [9, 17]. Recent genetic studies have identified polymorphisms in ion channel genes, such as SCN5A and KCNQ1, as well as gap junction proteins like connexin-43, as modulators of individual susceptibility to ischemia-related arrhythmias [23]. These findings contribute to the development of personalized strategies for arrhythmic risk prediction following acute myocardial infarction (AMI). Accordingly, a risk stratification model informed by mechanistic insights—incorporating arrhythmia subtype, infarct characteristics, early electrocardiographic findings, systemic inflammatory status, and genetic predisposition—may enhance early identification of high-risk patients and support more tailored preventive interventions.
Infarct localization and culprit vessel
Anterior wall STEMI involving the LAD was found to be significantly associated with the occurrence of VAs [5]. Occlusion of the LAD affects a substantial portion of the myocardium, promoting the formation of macro-reentrant circuits within infarct border zones [5, 17]. In contrast, inferior STEMI, most often resulting from RCA occlusion, is more commonly associated with conduction abnormalities such as bradyarrhythmias and AV block [17, 24]. This association arises from the RCA’s predominant role in supplying the sinus and AV nodes [24]. Although inferior infarctions are linked with conduction disturbances, the presence of robust collateral circulation may limit the extent of ischemic injury and thereby reduce the risk of VA development [17]. Notably, multivariate analyses have indicated that infarct localization—particularly anterior versus inferior distribution—serves as a stronger predictor of VA occurrence than the culprit vessel itself [9, 17]. Podolecki et al. reported that anterior infarctions are more likely to lead to delayed-onset VAs beyond 48 h, whereas inferior infarcts tend to provoke early but transient arrhythmic events [9]. From a mechanistic perspective, large anterior infarcts contribute to heterogeneous scar formation, slowed myocardial conduction, and increased dispersion of refractoriness [17]—electrophysiological conditions that collectively enhance the substrate for sustained VA.
Impact on In-Hospital outcomes
The occurrence of VAs during hospitalization was significantly linked to adverse short-term clinical outcomes, including cardiac death, recurrent MI, and the need for urgent TVR [19, 25]. Among these, sustained VT and VF were particularly detrimental, often resulting in hemodynamic instability requiring immediate therapeutic intervention [25]. As reported in previous studies [9, 17], early-onset RAs—occurring within the first 48 h—were primarily associated with increased in-hospital mortality, whereas VAs emerging beyond 48 h correlated with poorer outcomes at both 90 days and one year.
The Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial demonstrated that patients developing sustained VA within 48 h had an in-hospital mortality HR of 1.56 (p = 0.03) compared to those without VAs [26]. Additionally, early transient arrhythmias, such as AIVR or isolated PVCs, may not substantially affect prognosis when managed appropriately [9, 18, 19, 27]. In contrast, sustained VT or VF often signifies ongoing myocardial electrical instability and is associated with markedly worse clinical outcomes [9, 17]. Although early reperfusion therapy plays a critical role in salvaging ischemic myocardium, it may paradoxically precipitate arrhythmic episodes due to abrupt ionic shifts and heightened sympathetic stimulation [17]. Therefore, even in the context of successful PPCI, vigilant monitoring and timely management of post-RAs remain essential to improving clinical outcomes.
In addition to descriptive comparisons, our multivariate logistic regression analysis demonstrated that the occurrence of VAs was an independent predictor of in-hospital MACE. This finding remained significant even after adjusting for age, sex, infarct localization, hypertension, and LAD involvement, underscoring the prognostic significance of arrhythmia beyond its role as a reperfusion phenomenon. Our results highlight that VA is not merely a transient electrophysiological event but also a marker of increased myocardial vulnerability and hemodynamic compromise.
To further investigate arrhythmic heterogeneity, we performed a subgroup analysis comparing VT/VF with non-VT/VF patients. The VT/VF group had significantly higher in-hospital MACE, cardiac death, MI, and TVR. These results indicate that VT/VF confers substantially greater prognostic risk than other arrhythmic subtypes. These findings advocate for more vigilant monitoring, early identification, and potentially preemptive anti-arrhythmic strategies in patients exhibiting VA during hospitalization.
While certain types of VAs, such as AIVR and isolated PVCs, are typically regarded as benign and self-limiting, our findings indicate that the overall occurrence of VAs during PPCI remains a clinically meaningful event. These arrhythmias may serve as markers of underlying myocardial vulnerability and electrical instability, rather than merely epiphenomena. The identification of reperfusion-related VAs enables clinicians to recognize patients at higher risk for adverse outcomes and may help guide intensified monitoring and individualized care strategies—even in cases where immediate treatment for the arrhythmia itself is not warranted. We acknowledge that reperfusion-related VAs encompass a heterogeneous spectrum, both in terms of electrophysiological mechanisms and prognostic implications. While our primary analysis treated all VAs as a composite category, this may obscure meaningful clinical differences between benign arrhythmias (e.g., AIVR, isolated PVCs) and malignant ones (e.g., sustained VT, VF). The subgroup results from VT/VF vs. non-VT/VF further reinforce the prognostic gradient among arrhythmias. We recognize that future prospective studies should incorporate stratification by arrhythmia subtype and timing to enhance risk prediction models and optimize care.
Predictive factors for VA occurrence
In our multivariate analysis, extensive anterior infarction and LAD involvement were identified as independent predictors of in-hospital VAs. This finding is consistent with prior studies, which also reported no consistent association between conventional risk factors and early RAs [17]. Interestingly, patients with a history of prior revascularization procedures such as PCI or CABG exhibited a lower incidence of in-hospital VAs [9]. This protective effect may be attributed to improved collateral circulation, ischemic preconditioning, and routine administration of secondary preventive therapies, including beta-blockers and ACE inhibitors. Furthermore, elevated inflammatory markers—such as high C-reactive protein levels and leukocytosis at admission—have emerged as significant independent predictors of VA, supporting the hypothesis that systemic inflammation contributes to myocardial electrical instability [17]. Electrocardiographic abnormalities, particularly prolonged QRS duration (> 120 ms) and notable ST-segment deviations, have also been implicated in increased susceptibility to early VAs following PPCI [9, 17]. Collectively, these findings suggest that infarct extent, coronary artery involvement, inflammatory status, and early ECG characteristics form an integrated risk profile for identifying patients at elevated risk for reperfusion-related VAs.
Limitations
This study has several limitations that should be acknowledged. First, this was a retrospective, single-center study with a relatively small sample size, which may limit the generalizability of the findings. Second, although continuous telemetry monitoring enabled sensitive detection of VAs, transient and asymptomatic arrhythmic episodes might still have been missed. Third, only reperfusion-related arrhythmias occurring during the PPCI procedure were systematically recorded; arrhythmias that occurred after the procedure (i.e., late VAs) were not included, which may have led to underestimation of the total VA burden. Fourth, while we discussed the potential role of mechanical interventions such as balloon re-inflation, no direct procedural data regarding these strategies were available in the present cohort, limiting the strength of our conclusions. Finally, inflammatory biomarkers, cardiac magnetic resonance imaging, and genetic profiling were not routinely performed, which restricted a more comprehensive assessment of arrhythmic risk stratification. Additionally, all RAs were analyzed as a composite endpoint without stratification by subtype or timing, which may reduce the precision of prognostic interpretation. Future studies should consider a more granular approach. Moreover, post-PCI cardiac arrest and ventricular arrhythmias requiring treatment were not separately categorized as individual MACE components due to the retrospective design and limitations in the consistency of documentation. This may have resulted in underreporting of clinically meaningful events.
Conclusions
In conclusion, VAs occurred in nearly half of STEMI patients undergoing PPCI, with accelerated idioventricular rhythm and frequent premature ventricular contractions being the most common manifestations. The occurrence of VAs was significantly associated with anterior wall infarction patterns and LAD involvement, and was independently predicted by extensive anterior infarction. Importantly, the presence of RAs during hospitalization was linked to a higher incidence of MACE. These findings emphasize the need for meticulous arrhythmic monitoring, early risk stratification, and individualized management strategies during and after PPCI to improve short-term outcomes in STEMI patients. Future prospective studies with larger cohorts and extended follow-up are warranted to validate these observations and further explore the optimal management of reperfusion-related arrhythmias.
Acknowledgements
Not applicable.
Clinical trial number
Not applicable.
Authors' contributions
X.W. and L.W. had the idea for the paper, reviewed and edited it critically for important intellectual content. H.B.H. and H.H. performed the literature search and analysis. X.W., M.X.W., L.W., Z.L. and H.H. substantially contributed to the conception of the paper, drafted and critically revised the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.
Funding
No funding was received for this study.
Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
The present research was carried out in accordance with the tenets mentioned in the Helsinki Declaration and was approved by the Ethical Board of Xiangtan Central Hospital (approval number: X2018083662-1). Prior to the commencement of the research, our team obtained written informed consent from each patient.
Consent for publication
Not applicable. No individual patient data will be reported.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.