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Clinical Ventricular Tachycardia| Volume 4, ISSUE 3, P200-206, March 2023

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Prognostic value of early sustained ventricular arrhythmias in ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention: A substudy of VALIDATE-SWEDEHEART trial

Open AccessPublished:December 22, 2022DOI:https://doi.org/10.1016/j.hroo.2022.12.008

      Background

      Prognostic assessment of ventricular tachycardia (VT) or ventricular fibrillation (VF) in ST-segment elevation myocardial infarction (STEMI) is based mainly on distinguishing between early (<48 hours) and late arrhythmias, and does not take into account its time distribution with regard to reperfusion, or type of arrhythmia.

      Objective

      We analyzed the prognostic value of early ventricular arrhythmias (VAs) in STEMI with regard to their type and timing.

      Methods

      The prespecified analysis of the multicenter prospective Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarctionin Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease evaluated according to Recommended Therapies Registry Trial included 2886 STEMI patients undergoing primary percutaneous coronary intervention (PCI). VA episodes were characterized regarding their type and timing. Survival status at 180 days was assessed through the population registry.

      Results

      Nonmonomorphic VT or VF was observed in 97 (3.4%) and monomorphic VT in 16 (0.5%) patients. Only 3 (2.7%) early VA episodes occurred after 24 hours from symptom onset. VA was associated with higher risk of death (hazard ratio 3.59; 95% confidence interval [CI] 2.01–6.42) after adjustment for age, sex, and STEMI localization. VA after PCI was associated with an increased mortality compared with VA before PCI (hazard ratio 6.68; 95% CI 2.90–15.41). Early VA was associated with in-hospital mortality (odds ratio 7.39; 95% CI 3.68–14.83) but not with long-term prognosis in patients discharged alive. The type of VA was not associated with mortality.

      Conclusion

      VA after PCI was associated with an increased mortality compared with VA before PCI. Long-term prognosis did not differ between patients with monomorphic VT and nonmonomorphic VT or VF, but events were few. VA incidence during 24 to 48 hours of STEMI is negligibly low, thus precluding assessment of its prognostic importance.

      Keywords

      Key Findings
      • Early ventricular arrythmia (VA) is a marker of poor short-term outcomes in patients with ST-segment elevation myocardial infarction, which does not affect long-term prognosis in patients successfully resuscitated and discharged from hospital.
      • The incidence of VA during the second day of ST-segment elevation myocardial infarction is negligibly low, supporting the use of a 24-hour, rather than 48-hour, threshold defining early VA not affecting long-term prognosis.
      • VA that occurs after percutaneous coronary intervention is associated with an increased risk of death compared with VA before percutaneous coronary intervention.

      Introduction

      The last several decades demonstrated marked progress in ST-segment elevation myocardial infarction (STEMI) treatment, improving outcomes with early aggressive revascularization and adjunctive antithrombotic treatment. Declining incidence rates and case-fatality rates of ventricular tachycardia (VT) and ventricular fibrillation (VF) in STEMI have been observed in community-based settings.
      • Tran H.V.
      • Ash A.S.
      • Gore J.M.
      • Darling C.E.
      • Kiefe C.I.
      • Goldberg R.J.
      Twenty-five year trends (1986-2011) in hospital incidence and case-fatality rates of ventricular tachycardia and ventricular fibrillation complicating acute myocardial infarction.
      Nevertheless, malignant ventricular arrhythmias (VAs) still contribute to a 4- to 5-fold increase in in-hospital mortality during STEMI
      • Piccini J.P.
      • Berger J.S.
      • Brown D.L.
      Early sustained ventricular arrhythmias complicating acute myocardial infarction.
      ,
      • Bougouin W.
      • Marijon E.
      • Puymirat E.
      • et al.
      Incidence of sudden cardiac death after ventricular fibrillation complicating acute myocardial infarction: a 5-year cause-of-death analysis of the FAST-MI 2005 registry.
      and remain the main cause of sudden death during the prehospital stage.
      • Demirel F.
      • Rasoul S.
      • Elvan A.
      • et al.
      Impact of out-of-hospital cardiac arrest due to ventricular fibrillation in patients with ST-elevation myocardial infarction admitted for primary percutaneous coronary intervention: impact of ventricular fibrillation in STEMI patients.
      In patients successfully resuscitated and discharged from the hospital, early VAs do not appear to influence long-term prognosis.
      • Bougouin W.
      • Marijon E.
      • Puymirat E.
      • et al.
      Incidence of sudden cardiac death after ventricular fibrillation complicating acute myocardial infarction: a 5-year cause-of-death analysis of the FAST-MI 2005 registry.
      ,
      • Mehta R.H.
      • Harjai K.J.
      • Grines L.
      • et al.
      Sustained ventricular tachycardia or fibrillation in the cardiac catheterization laboratory among patients receiving primary percutaneous coronary intervention: incidence, predictors, and outcomes.
      ,
      • Demidova M.M.
      • Smith J.G.
      • Hoijer C.J.
      • Holmqvist F.
      • Erlinge D.
      • Platonov P.G.
      Prognostic impact of early ventricular fibrillation in patients with ST-elevation myocardial infarction treated with primary PCI.
      Prognostic assessment of VAs in STEMI is currently based primarily on categorization of the arrhythmias on early and late based on a 48-hour cutoff time from symptom onset. This cutoff is used to distinguish early VA that do not bear prognostic significance, and late VA that may trigger implantation of an implantable cardioverter-defibrillator. This threshold, however, was set at a time when revascularization using percutaneous coronary intervention (PCI) was not widely implemented as the primary management strategy for STEMI.
      • Newby K.H.
      • Thompson T.
      • Stebbins A.
      • Topol E.J.
      • Califf R.M.
      • Natale A.
      Sustained ventricular arrhythmias in patients receiving thrombolytic therapy: incidence and outcomes. The GUSTO Investigators.
      ,
      • Volpi A.
      • Cavalli A.
      • Santoro L.
      • Negri E.
      Incidence and prognosis of early primary ventricular fibrillation in acute myocardial infarction--results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) database.
      Whether different and possibly shorter cutoff times should be considered for patients undergoing invasive strategy is not known. Moreover, time distribution of VAs during STEMI is more complex than the binary division into early and late arrhythmias. It is plausible to suggest that the prognostic importance of prehospital VAs may not be the same as the importance of VAs occurring during reperfusion or after PCI; however, data on prognostic significance of VA occurring prior to, during, and after PCI are scarce and controversial.
      • Mehta R.H.
      • Harjai K.J.
      • Grines L.
      • et al.
      Sustained ventricular tachycardia or fibrillation in the cardiac catheterization laboratory among patients receiving primary percutaneous coronary intervention: incidence, predictors, and outcomes.
      ,
      • Mehta R.H.
      • Starr A.Z.
      • Lopes R.D.
      • et al.
      Incidence of and outcomes associated with ventricular tachycardia or fibrillation in patients undergoing primary percutaneous coronary intervention.
      • Demidova M.M.
      • Carlson J.
      • Erlinge D.
      • Platonov P.G.
      Predictors of ventricular fibrillation at reperfusion in patients with acute ST-elevation myocardial infarction treated by primary percutaneous coronary intervention.
      • Jabbari R.
      • Risgaard B.
      • Fosbol E.L.
      • et al.
      Factors associated with and outcomes after ventricular fibrillation before and during primary angioplasty in patients with ST-Segment elevation myocardial infarction.
      Until recently, prognostic assessment of VAs did not take into account the type of VA.
      • Mehta R.H.
      • Harjai K.J.
      • Grines L.
      • et al.
      Sustained ventricular tachycardia or fibrillation in the cardiac catheterization laboratory among patients receiving primary percutaneous coronary intervention: incidence, predictors, and outcomes.
      ,
      • Newby K.H.
      • Thompson T.
      • Stebbins A.
      • Topol E.J.
      • Califf R.M.
      • Natale A.
      Sustained ventricular arrhythmias in patients receiving thrombolytic therapy: incidence and outcomes. The GUSTO Investigators.
      ,
      • Mehta R.H.
      • Starr A.Z.
      • Lopes R.D.
      • et al.
      Incidence of and outcomes associated with ventricular tachycardia or fibrillation in patients undergoing primary percutaneous coronary intervention.
      ,
      • Kosmidou I.
      • Embacher M.
      • McAndrew T.
      • et al.
      Early ventricular tachycardia or fibrillation in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention and impact on mortality and stent thrombosis (from the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction Trial).
      Recent data support a differential approach to polymorphic VT or VF (PMVT/VF) and monomorphic VT (MMVT), and indicate a long-term mortality hazard associated with MMVT.
      • Hai J.J.
      • Un K.C.
      • Wong C.K.
      • et al.
      Prognostic implications of early monomorphic and nonmonomorphic tachyarrhythmias in patients discharged with acute coronary syndrome.
      • Liang J.J.
      • Hodge D.O.
      • Mehta R.A.
      • Russo A.M.
      • Prasad A.
      • Cha Y.M.
      Outcomes in patients with sustained ventricular tachyarrhythmias occurring within 48 h of acute myocardial infarction: when is ICD appropriate?.
      • Demidova M.M.
      • Ulfarsson A.E.O.
      • Carlson J.
      • Erlinge D.
      • Platonov P.G.
      Relation of early monomorphic ventricular tachycardia to long-term mortality in ST-elevation myocardial infarction.
      The Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarctionin Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART) was conducted in contemporary settings with a high adherence to guideline-recommended therapies. This was a multicenter, prospective, randomized, registry-based clinical trial in which VA reporting was integrated.
      • Erlinge D.
      • Omerovic E.
      • Frobert O.
      • et al.
      Bivalirudin versus heparin monotherapy in myocardial infarction.
      The design of the VALIDATE-SWEDEHEART trial allows one to overcome the limitations of retrospective studies and prospective studies with selection bias, and based on VALIDATE-VF, we wanted to evaluate the insufficiently elucidated points concerning VAs in STEMI.
      The aim of this prespecified analysis of the multicenter prospective VALIDATE-SWEDEHEART trial was to assess the prognostic value of VAs concerning their type and their timing in STEMI patients treated by primary PCI.

      Methods

      Study population

      The VALIDATE-SWEDEHEART trial was a multicenter, prospective, randomized, registry-based, controlled, open-label clinical trial aimed at comparing 2 anticoagulation strategies in patients with STEMI or non-STEMI treated by primary PCI. The design and the main results have been published previously.
      • Erlinge D.
      • Omerovic E.
      • Frobert O.
      • et al.
      Bivalirudin versus heparin monotherapy in myocardial infarction.
      ,
      • Erlinge D.
      • Koul S.
      • Eriksson P.
      • et al.
      Bivalirudin versus heparin in non-ST and ST-segment elevation myocardial infarction-a registry-based randomized clinical trial in the SWEDEHEART registry (the VALIDATE-SWEDEHEART trial).
      In brief, patients treated with potent P2Y12 inhibitors (ticagrelor, prasugrel, or cangrelor) before start of the intervention were randomized to receive bivalirudin or heparin during PCI, which was performed predominantly using radial artery access. The primary endpoint was a composite of death from any cause, myocardial infarction (MI), and major bleeding events at 180 days. The trial showed that in patients with acute coronary syndromes undergoing primary PCI, bivalirudin was not superior to heparin with regard to the rate of death, repeat MI, or major bleeding events.
      The VALIDATE-VF substudy included STEMI patients who were enrolled in the VALIDATE-SWEDEHEART trial. This cohort has been already described in prespecified subgroup analysis.
      • James S.
      • Koul S.
      • Andersson J.
      • et al.
      Bivalirudin versus heparin monotherapy in ST-segment-elevation myocardial infarction.
      Baseline patient demographic data, angiographic data, information about medications, and clinical complications were obtained from the SWEDEHEART registry (a nationwide Swedish online registry that reports outcomes of patients hospitalized for acute coronary syndrome or undergoing coronary intervention in Swedish PCI centers). Information on death was obtained from the Swedish National Population Registry.
      Information regarding occurrence of arrhythmias requiring medical intervention during index hospitalization with STEMI was collected in accordance with the core protocol of the VALIDATE study. All patients with registered arrhythmias were selected for source data verification in order to then identify patients who developed hemodynamically unstable, sustained VAs during hospitalization for STEMI, and to obtain information on the arrhythmias’ type and timing. With regard to the type of arrhythmia, all cases of documented arrhythmias during STEMI were classified as follows: (1) no arrhythmia, (2) VF or PMVT, (3) MMVT, (4) undefined shockable rhythm, or (5) other nonshockable rhythm requiring cardiopulmonary resuscitation. MMVT was defined as a regular wide QRS complex tachycardia at a rate >100 beats/min with uniform and stable morphology. PMVT was defined as VT with changing QRS morphology. Only hemodynamically unstable sustained VT or VF were selected for further analysis.
      Timing of arrhythmia was classified as follows: (1) prior to hospital admission; (2) in hospital before PCI; (3) reperfusion arrhythmia; (4) after PCI, but within 24 hours of symptom onset; (5) after PCI within 24 to 48 hours of symptom onset; and (6) after PCI and later than 48 hours from symptom onset, but before discharge from the hospital. Early VAs were defined as VAs occurring at any time within the first 48 hours of STEMI.
      • Newby K.H.
      • Thompson T.
      • Stebbins A.
      • Topol E.J.
      • Califf R.M.
      • Natale A.
      Sustained ventricular arrhythmias in patients receiving thrombolytic therapy: incidence and outcomes. The GUSTO Investigators.
      The research reported in this paper was conducted in accordance with the guidelines outlined in the Declaration of Helsinki. Witnessed oral consent was obtained in all patients followed by providing written informed consent within 24 hours.
      The study was approved by the ethics committee at Lund University.

      Statistical analysis

      Baseline clinical characteristics were presented in comparison between any VA and no VA using Student’s t test or the Mann-Whitney test for continuous variables and either the chi-square test or Fisher’s exact test for categorical variables. Adjusted Cox proportional hazards models were performed to evaluate the association between the presence, type, and timing of VAs with the outcome at 180 days. The primary endpoint was total mortality, the secondary endpoint was cardiovascular mortality.
      All models were adjusted for age, sex, and localization of STEMI. All tests were 2-sided, and P values <.05 were considered significant.

      Results

      Patient characteristics

      Between June 2014 and September 2016, a total of 3005 STEMI patients were enrolled in the VALIDATE trial. Among 25 sites that participated in the VALIDATE trial, 16 sites agreed to participate in VALIDATE-VF substudy. In total, 2886 patients were included in the VALIDATE-VF substudy. Of those, 97 (3.4%) experienced VF or PMVT, 16 (0.5%) experienced MMVT, 7 (0.2%) had other undefined shockable rhythm, and 31 (1.1%) had nonshockable rhythm requiring cardiopulmonary resuscitation.
      In 108 (90%) patients with life-threatening VAs, VT, VF, or shockable rhythm manifested during the first 24 hours of STEMI, in 3 (2.5%) it manifested during the 24 to 48 hours, and in 9 (7.5%) it manifested after 48 hours. Of the total 120 patients with VT, VF, or shockable rhythm, it occurred before reperfusion in 54 (45.4%) patients and directly after reperfusion in 28 (23.5%) patients, and it occurred after PCI, but during hospital stay in 38 (31%) patients (in 29 patients within the first 48 hours of STEMI, and in 8 patients after the 48-hour cutoff). PMVT/VF was most prevalent before PCI, whereas MMVT was most prevalent after PCI (Figure 1).
      Figure thumbnail gr1
      Figure 1Timing of ventricular tachycardia or ventricular fibrillation (VT/VF) during acute ST-segment elevation myocardial infarction. Data are presented as the percentage of events in each subgroup. Figures in columns indicate the absolute numbers of events in each subgroup. PCI = percutaneous coronary intervention.
      Patients with VA were more likely than patients without VA to have had a history of previous MI, more likely to have been using beta-blockers than patients without VA, and more VA patients smoked than patients without VA (Table 1). Also, patients with VA were more likely than patients without VA to have received cardiopulmonary resuscitation before arrival and mechanical chest compressions with the Lund University Cardiopulmonary Assist System. The 2 groups (with or without VA) did not differ as far as the right coronary artery, left anterior descending artery, or left circumflex artery as the infarct-related artery.
      Table 1Clinical characteristics
      Any VA (n= 120)No VA (n = 2735)Missing (%)P value
      Age, y66.2 ± 10.766.8 ± 11.10.2.527
      Male91 (76.5)1975 (72.2)0.2.324
      BMI, kg/m227.7 ± 4.227.3 ± 5.413.5.360
      Smoker43 (35.8)760 (28.7)3.4.036
      Medical history
      Diabetes18 (15.0)379 (13.9)0.5.682
      Hypertension59 (49.2)1267 (46.7)0.8.425
      Previous MI22 (18.3)328 (12.0)1.5.030
      Previous PCI17 (14.2)310 (11.3)0.2.326
      Previous CABG4 (3.3)68 (2.5)0.2.542
      Previous stroke4 (3.3)85 (3.2)1.2.787
      Renal failure13 (10.8)383 (14.4)2.5.323
      Chronic heart failure79 (3.0)3 (2.6)2.81.000
      Medications at admission
      Beta-blockers15 (12.5)103 (3.8)1.1<.001
      Lipid-lowering therapy33 (27.5)616 (22.8)1.2.192
      Digoxin therapy0 (0.0)6 (0.2)2.61.000
      Time from symptom to PCI, h2.6 (1.8-4.4)3.2 (2.1-5.6)1.8.002
      Infarct-related artery
      RCA36 (30.3)957 (35.0).548
      LAD50 (42.0)1076 (39.3)
      LCx17 (14.3)359 (13.1)
      LM1 (0.8)16 (0.6)
      Graft2 (1.7)20 (1.7)
      CPR before arrival33 (27.7)1 (0.1)1.8<.001
      LUCAS3 (2.5)2 (0.1)0.2.001
      LVEF <40%37 (33)45.2 (18.3)9.7<.001
      Values are mean ± SD, median (interquartile range), or n (%), unless otherwise indicated. The t test, Mann-Whitney test, chi-square test, or Fisher’s exact test or were used.
      BMI = body mass index; CABG = coronary artery bypass grafting; LAD = left anterior descending artery; LCx = left circumflex artery; LM = left main artery; LUCAS = Lund University Cardiopulmonary Assist System; LVEF = left ventricular ejection fraction; MI = myocardial infarction; PCI = percutaneous coronary intervention; RCA = right coronary artery; VA = ventricular arrhythmia.
      In total, 2544 patients had an optimal result of primary PCI, while 336 patients had an impaired flow after PCI. Of those 336 patients, 55 patients had Thrombolysis In Myocardial Infarction (TIMI) flow grade 0, 38 patients had TIMI flow grade 1, and 243 patients had TIMI flow grade 2 after PCI.
      Of the 38 patients with in-hospital VA after PCI (without regard to the 48-hour cutoff), 13 (34%) patients had an impaired flow in the infarct-related artery (TIMI flow grade <3) after PCI, while this was the case in just 11.4% (n = 323 of 2843) of patients without arrhythmias after PCI (P < .001). Three (8%) of the 38 patients with VA after PCI had TIMI flow grade 0 to 1 in the infarct-related artery after PCI, as compared with 90 (11.4%) of 2843 patients without arrhythmias after PCI (P = .115). In log binomial regression, TIMI flow grade <3 was associated with VT or VF after PCI with relative risk 4.10 (95% confidence interval [CI] 2.11–7.98; P < .001) in a univariable analysis and after adjustment for age, sex, and previous MI with an relative risk of 4.54 (95% CI 2.30–8.94; P < .001).

      Prognostic impact of VA

      The in-hospital mortality was 10 times higher in the VA group than in the no VA group (Supplementary Table). The occurrence of VA of any type was associated with increased risk of in-hospital mortality (odds ratio [OR] 7.39; 95% CI 3.68–14.83; P < .001) after adjustment on age, sex, and MI localization. By the end of follow-up, 13 (10.8%) of 120 VA patients died, compared with 77 (2.8%) of 2735 patients without VA (P < .001). Cardiovascular death occurred in 12 (10.0%) patients in the VA group and in 64 (2.3%) patients in the no VA group (P < .001). After discharge, 48 deaths occurred, 36 of which were cardiovascular.
      Compared with patients with no VA, early VA of any type was associated with total mortality and cardiovascular mortality after adjustment for age, sex and localization of MI (Table 2). In patients discharged alive, early VA did not significantly influence either total mortality (HR 0.56; 95% CI 0.77–4.05; P = .656) or cardiovascular mortality (HR 0.74; 95% CI 0.10–5.37; P = .763).
      Table 2Results of Cox regression analysis of association between mortality and the presence and type of ventricular arrhythmias (N = 2855)
      Total mortality (n = 89Cardiovascular mortality (n = 75)
      HR (95% CI)P valueHR (95% CI)P value
      Any VA vs no VA3.59 (2.01–6.42)<.0013.82 (2.08–6.99).001
      PMVT/VF vs no VA4.24 (2.91–8.21)<.0014.57 (2.72–9.20).001
      MMVT vs no VA4.67 (1.14–19.11).0325.58 (1.36–22.96).017
      MMVT vs PMVT/VF1.06 (0.23–5.00).9371.21 (0.25–5.74).815
      HRs were adjusted for age, sex, and MI localization.
      CI = confidence interval; HR = hazard ratio; MI = myocardial infarction; MMVT = monomorphic ventricular tachycardia; PMVT = polymorphic ventricular tachycardia; VF = ventricular fibrillation; VA = ventricular arrhythmia.
      The timing of early VA was associated with the risk of death. Compared with patients without VA, VT or VF before PCI, VT or VF during reperfusion, and VT or VF after PCI were associated with an increased risk of mortality after adjustment for age, sex and MI localization (Table 3, Figure 2). VT or VF after PCI was associated with a further increased risk of death when compared with VT or VF before PCI (Table 3). Taking into account the fact that VT or VF after PCI was often associated with a nonoptimal PCI result, in order to assess the prognostic value of VT or VF after PCI, the Cox proportional model was adjusted not only for age, sex, and MI localization, but also for nonoptimal TIMI flow grade (<3) after PCI; the adjusted Cox proportional hazard of VT or VF after PCI for total mortality was 4.26 (95% CI 1.8–10.08) (P = .001).
      Table 3Results of Cox regression analysis: mortality prediction with regard to timing of ventricular arrhythmias (N = 2855)
      Total mortality (n = 89)Cardiovascular mortality (n = 75)
      HR (95% CI)P valueHR (95% CI)P value
      VA before PCI vs no VA3.14 (1.27–7.78).0133.04 (1.10–8.36).03
      Reperfusion VA vs no VA1.52 (1.14–2.03).0041.59 (1.19–2.13).002
      VA after PCI vs no VA2.61 (1.57–4.34)<.0012.87 (1.72–4.79)<.001
      VA after PCI vs VA before PCI6.68 (2.90–15.41)<.0017.49 (3.12–17.99)<.001
      HRs were adjusted for age, sex, and MI localization.
      CI = confidence interval; HR = hazard ratio; MI = myocardial infarction; PCI = percutaneous coronary intervention; VA = ventricular arrhythmia.
      Figure thumbnail gr2
      Figure 2Kaplan-Meier failure curves: total mortality with regard to arrhythmia timing. PCI = percutaneous coronary intervention; VA = ventricular arrhythmia.
      VA type was not associated with the mortality risk. Two (12.5%) of 16 patients with MMVT and 10 (10.3%) of 97 patients with PMVT/VF died (P = .678). Of those, 2 (12.5%) and 9 (9.3%) patients, respectively (P = .654), died from cardiovascular causes. From the Cox model, neither total mortality nor cardiovascular mortality was associated with arrhythmia type (Table 2, Figure 3).
      Figure thumbnail gr3
      Figure 3Kaplan-Meier failure curves: total mortality with regard to arrhythmia type (nonshockable rhythm excluded). MMVT = monomorphic ventricular tachycardia; PMVT = polymorphic ventricular tachycardia; VA = ventricular arrhythmia; VF = ventricular fibrillation.
      Among patients discharged alive, just 1 patient with PMVT/VF died by end of follow-up (from a cardiovascular cause), while no patients with MMVT died. We were not able to perform survival analysis with regard to the timing or the type of arrhythmia in patients discharged alive because of the small number of events.

      Discussion

      In this prespecified analysis of VA from a registry-based randomized clinical trial based on nationwide data from Sweden, we report a relatively low prevalence of VAs associated with STEMI, 91% of which occurred during the first 24 hours and was strongly associated with in-hospital mortality while not affecting long-term prognosis.
      In our material, almost half (50%) of all VA episodes occurred before PCI, while one-third occurred prior to hospital admission. These ratios are higher than previously reported in other studies: for example, in the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) study, precatheterization VA accounted for just 7.5% (25 of 329) of events; in the French registry of Acute ST-elevation or non-ST-elevation Myocardial Infarction study, the mean time from MI diagnosis to occurrence of VF was 1.8 days (95% CI 1.4–2.2). Our findings can be explained by the broad patient enrollment due to few exclusion criteria as part of a pragmatic registry-based trial. Our study did not exclude the most severe patient categories, such as patients who underwent prehospital resuscitation or arrived at the catheterization laboratory with ongoing mechanical chest compressions with the Lund University Cardiopulmonary Assist System. This may be explained by the difference between our patient population and patient populations selected in other randomized studies.
      In our study, VA occurred after PCI in 31% of patients, which is in agreement with the APEX-AMI study (35%).
      • Mehta R.H.
      • Starr A.Z.
      • Lopes R.D.
      • et al.
      Incidence of and outcomes associated with ventricular tachycardia or fibrillation in patients undergoing primary percutaneous coronary intervention.
      VAs after PCI were associated with impaired TIMI flow grade in the infarct-related artery after PCI, which is in line with earlier findings of the Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28 study on association of VA with impaired myocardial perfusion after fibrinolysis,
      • Gibson C.M.
      • Pride Y.B.
      • Buros J.L.
      • et al.
      Association of impaired thrombolysis in myocardial infarction myocardial perfusion grade with ventricular tachycardia and ventricular fibrillation following fibrinolytic therapy for ST-segment elevation myocardial infarction.
      and also in line with the findings of the APEX-AMI study, which reported the association between postprocedural TIMI flow grade <3 and postprocedural VA.
      • Mehta R.H.
      • Starr A.Z.
      • Lopes R.D.
      • et al.
      Incidence of and outcomes associated with ventricular tachycardia or fibrillation in patients undergoing primary percutaneous coronary intervention.
      Our data indicate that prehospital VA, if successfully cardioverted in a timely manner, in patients admitted for primary PCI is associated with the lowest in-hospital mortality (3.4%), even if compared with VA occurring in hospital before PCI (8%) and reperfusion arrhythmias (10.7%). The risk of mortality related to VA is associated with timing of early VAs, and VAs after PCI are associated with a significantly higher mortality risk than arrhythmias before PCI. These results are in agreement with APEX-AMI findings, which also reported an increased risk of death associated with VA after catheterization end.
      • Mehta R.H.
      • Starr A.Z.
      • Lopes R.D.
      • et al.
      Incidence of and outcomes associated with ventricular tachycardia or fibrillation in patients undergoing primary percutaneous coronary intervention.
      In a contemporary setting, we show that 180-day mortality associated with VA during the first 24 hours after symptom onset is determined by in-hospital mortality, with practically no events reported after discharge from the hospital.
      In the contemporary STEMI cohorts, the incidence of early VA occurring after 24 hours (ie, during 24–48 hours from symptom onset) is extremely low and does not allow sufficient power to statistically assess their association with the long-term outcome. In our data, just 3 patients (0.1% of all included patients; 2.7% of patients with VA) experienced VA during the second day of STEMI, which is in line with previously reported data.
      • Demidova M.M.
      • Smith J.G.
      • Hoijer C.J.
      • Holmqvist F.
      • Erlinge D.
      • Platonov P.G.
      Prognostic impact of early ventricular fibrillation in patients with ST-elevation myocardial infarction treated with primary PCI.
      This number of patients is too low to support the use of a 48-hour threshold for risk stratification with regard to the risk of death and implantable cardioverter defibrillator therapy.
      The prevalence of MMVT in our study (0.5%) was lower than previously reported incidence (2.6%–3%)
      • Hai J.J.
      • Un K.C.
      • Wong C.K.
      • et al.
      Prognostic implications of early monomorphic and nonmonomorphic tachyarrhythmias in patients discharged with acute coronary syndrome.
      ,
      • Hatzinikolaou-Kotsakou E.
      • Tziakas D.
      • Hotidis A.
      • et al.
      Could sustained monomorphic ventricular tachycardia in the early phase of a prime acute myocardial infarction affect patient outcome?.
      ; however, in our study, we only considered MMVT demanding cardioversion and not all sustained MMVT like previous publications did. Recently, we published a single-center study on a similar size study group treated 10 years earlier.
      • Demidova M.M.
      • Ulfarsson A.E.O.
      • Carlson J.
      • Erlinge D.
      • Platonov P.G.
      Relation of early monomorphic ventricular tachycardia to long-term mortality in ST-elevation myocardial infarction.
      The prevalence of MMVT in STEMI patients admitted for primary PCI was 1.5%. The clinical characteristics of patients and the time distribution of MMVT were quite similar in the 2 studies (the single-center study and the current study). PMVT/VF was most prevalent before PCI, while MMVT was most prevalent after PCI. The reason for this phenomenon is likely related to the time needed for an ischemic lesion, to develop, thus creating the arrhythmic substrate late in the course of STEMI. In the single-center study, we showed that early MMVT is associated with a higher risk of all-cause mortality than PMVT/VF. In the current study, both PMVT/VF and MMVT were associated with increased mortality as compared with patients with no VT or VF, but we could not state with certainty that MMVT is associated with greater mortality than PMVT/VF.
      Thus, MMVT is a very rare finding in the acute STEMI population. It occurs mainly after PCI and is associated with a mortality hazard rate similar to VF.

      Limitations

      Our study has several limitations. Because of the design of the main study (VALIDATE-SWEADHEART study), the follow-up period in our study was limited to 180 days. Due to VALIDATE-SWEADHEART study’s registry-based platform, specific information on implantable cardioverter-defibrillator implantation after MI, the use of wearable cardioverter-defibrillators, and sudden arrhythmic death information was not available for the current study.
      The low incidence of VA and the low outcome event rates, especially in patients with VA within 24 to 48 hours of STEMI, and in the MMVT group did not allow sufficient power to statistically assess their association with the long-term outcome in these subgroups.

      Conclusion

      Early VA is a marker of poor short-term outcomes in patients with STEMI, which does not affect long-term prognosis in patients successfully resuscitated and discharged from hospital. VA after PCI is associated with an increased risk of death compared with VA occurring before PCI. Monomorphic VT is a rare event during STEMI, thus precluding drawing conclusions with regard to its prognostic impact.
      As the incidence of early VA after 24 hours of symptoms appears to be negligibly low, our results support the use of a 24-hour threshold defining VAs that do not affect long-term prognosis.

      Funding Sources

      This study was supported by the Swedish Heart Lung Foundation (# 20180222 to MMD and #20200674 to PPG), by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement, and by donation funds at Skåne University Hospital.

      Disclosures

      The authors have no conflicts to disclose.

      Authorship

      All authors attest they meet the current ICMJE criteria for authorship.

      Patient Consent

      Witnessed oral consent was obtained in all patients followed by providing written informed consent within 24 hours.

      Ethics Statement

      The research reported in this paper was conducted in accordance with the guidelines outlined in the Declaration of Helsinki. The study was approved by the ethics committee at Lund University.

      Acknowledgments

      We thank the patients and staff at all centers participated in VALIDATE-SWEDEHEART trial.

      Appendix. Supplementary data

      References

        • Tran H.V.
        • Ash A.S.
        • Gore J.M.
        • Darling C.E.
        • Kiefe C.I.
        • Goldberg R.J.
        Twenty-five year trends (1986-2011) in hospital incidence and case-fatality rates of ventricular tachycardia and ventricular fibrillation complicating acute myocardial infarction.
        Am Heart J. 2019; 208: 1-10
        • Piccini J.P.
        • Berger J.S.
        • Brown D.L.
        Early sustained ventricular arrhythmias complicating acute myocardial infarction.
        Am J Med. 2008; 121: 797-804
        • Bougouin W.
        • Marijon E.
        • Puymirat E.
        • et al.
        Incidence of sudden cardiac death after ventricular fibrillation complicating acute myocardial infarction: a 5-year cause-of-death analysis of the FAST-MI 2005 registry.
        Eur Heart J. 2014; 35: 116-122
        • Demirel F.
        • Rasoul S.
        • Elvan A.
        • et al.
        Impact of out-of-hospital cardiac arrest due to ventricular fibrillation in patients with ST-elevation myocardial infarction admitted for primary percutaneous coronary intervention: impact of ventricular fibrillation in STEMI patients.
        Eur Heart J Acute Cardiovasc Care. 2015; 4: 16-23
        • Mehta R.H.
        • Harjai K.J.
        • Grines L.
        • et al.
        Sustained ventricular tachycardia or fibrillation in the cardiac catheterization laboratory among patients receiving primary percutaneous coronary intervention: incidence, predictors, and outcomes.
        J Am Coll Cardiol. 2004; 43: 1765-1772
        • Demidova M.M.
        • Smith J.G.
        • Hoijer C.J.
        • Holmqvist F.
        • Erlinge D.
        • Platonov P.G.
        Prognostic impact of early ventricular fibrillation in patients with ST-elevation myocardial infarction treated with primary PCI.
        Eur Heart J Acute Cardiovasc Care. 2012; 1: 302-311
        • Newby K.H.
        • Thompson T.
        • Stebbins A.
        • Topol E.J.
        • Califf R.M.
        • Natale A.
        Sustained ventricular arrhythmias in patients receiving thrombolytic therapy: incidence and outcomes. The GUSTO Investigators.
        Circulation. 1998; 98: 2567-2573
        • Volpi A.
        • Cavalli A.
        • Santoro L.
        • Negri E.
        Incidence and prognosis of early primary ventricular fibrillation in acute myocardial infarction--results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) database.
        Am J Cardiol. 1998; 82: 265-271
        • Mehta R.H.
        • Starr A.Z.
        • Lopes R.D.
        • et al.
        Incidence of and outcomes associated with ventricular tachycardia or fibrillation in patients undergoing primary percutaneous coronary intervention.
        JAMA. 2009; 301: 1779-1789
        • Demidova M.M.
        • Carlson J.
        • Erlinge D.
        • Platonov P.G.
        Predictors of ventricular fibrillation at reperfusion in patients with acute ST-elevation myocardial infarction treated by primary percutaneous coronary intervention.
        Am J Cardiol. 2015; 115: 417-422
        • Jabbari R.
        • Risgaard B.
        • Fosbol E.L.
        • et al.
        Factors associated with and outcomes after ventricular fibrillation before and during primary angioplasty in patients with ST-Segment elevation myocardial infarction.
        Am J Cardiol. 2015; 116: 678-685
        • Kosmidou I.
        • Embacher M.
        • McAndrew T.
        • et al.
        Early ventricular tachycardia or fibrillation in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention and impact on mortality and stent thrombosis (from the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction Trial).
        Am J Cardiol. 2017; 120: 1755-1760
        • Hai J.J.
        • Un K.C.
        • Wong C.K.
        • et al.
        Prognostic implications of early monomorphic and nonmonomorphic tachyarrhythmias in patients discharged with acute coronary syndrome.
        Heart Rhythm. 2018; 15: 822-829
        • Liang J.J.
        • Hodge D.O.
        • Mehta R.A.
        • Russo A.M.
        • Prasad A.
        • Cha Y.M.
        Outcomes in patients with sustained ventricular tachyarrhythmias occurring within 48 h of acute myocardial infarction: when is ICD appropriate?.
        Europace. 2014; 16: 1759-1766
        • Demidova M.M.
        • Ulfarsson A.E.O.
        • Carlson J.
        • Erlinge D.
        • Platonov P.G.
        Relation of early monomorphic ventricular tachycardia to long-term mortality in ST-elevation myocardial infarction.
        Am J Cardiol. 2022; 163: 13-19
        • Erlinge D.
        • Omerovic E.
        • Frobert O.
        • et al.
        Bivalirudin versus heparin monotherapy in myocardial infarction.
        N Engl J Med. 2017; 377: 1132-1142
        • Erlinge D.
        • Koul S.
        • Eriksson P.
        • et al.
        Bivalirudin versus heparin in non-ST and ST-segment elevation myocardial infarction-a registry-based randomized clinical trial in the SWEDEHEART registry (the VALIDATE-SWEDEHEART trial).
        Am Heart J. 2016; 175: 36-46
        • James S.
        • Koul S.
        • Andersson J.
        • et al.
        Bivalirudin versus heparin monotherapy in ST-segment-elevation myocardial infarction.
        Circ Cardiovasc Interv. 2021; 14e008969
        • Gibson C.M.
        • Pride Y.B.
        • Buros J.L.
        • et al.
        Association of impaired thrombolysis in myocardial infarction myocardial perfusion grade with ventricular tachycardia and ventricular fibrillation following fibrinolytic therapy for ST-segment elevation myocardial infarction.
        J Am Coll Cardiol. 2008; 51: 546-551
        • Hatzinikolaou-Kotsakou E.
        • Tziakas D.
        • Hotidis A.
        • et al.
        Could sustained monomorphic ventricular tachycardia in the early phase of a prime acute myocardial infarction affect patient outcome?.
        J Electrocardiol. 2007; 40: 72-77