Ventricular tachycardia (VT) and ventricular fibrillation (VF) are fatal arrhythmias that could occur in cardiac collapse and are major complications of acute myocardial infarction (AMI) [
The purpose of this study was to investigate the timing of VT/VF occurrences and to compare in-hospital cardiac mortality between patients with VT/VF, which occurred before and within 2 days (48 h) after admission (early VT/VF), and patients with VT/VF, which occurred >2 days after admission (late VT/VF).
From January 2004 to December 2014, 1121 consecutive patients with AMI presented to our institution. Patients were included in these investigations if they were 18 years or older, presented with AMI within 24 hours of their symptom onset, and underwent primary PCI. Definitions of AMI and the standard of care were established according to the latest guidelines at that time. The AMI guideline had been modified in 2008 and 2013 in Japan. It showed there are minor changes; diagnosis of AMI is almost unchanged. The diagnosis of AMI definitions showed as typical lasting chest pain, increase of cardiac enzymes above the normal range, and onset of ST-T changes compatible with myocardial ischemia (ST segment elevation or depression, T-wave inversion) or abnormal Q waves. Emergent coronary angiography (CAG) and primary PCI were performed using standard techniques. Patients were excluded from this study if they received continuous hemodialysis, had asystole or pulseless electrical activity in the emergency room and, thus, were not taken to the catheter laboratory, underwent emergent coronary artery bypass graft surgery, had ventricular septal perforation, had cardiac rupture and required emergent surgery, or had incomplete data. Our study was a retrospective research. Written informed consent to perform the procedure as well as using the data retrospectively as registry was obtained from all patients. This study design was approved by the institutional review board at Tokushukai Group Ethical Committee (Approval Number: TGE00989-024), and it conformed to the Declaration of Helsinki.
We investigated patients who had VT/VF during emergent transportation, in the emergency room or catheter laboratory room, or during hospitalization after primary PCI. Patients with sustained VT/VF received cardiopulmonary resuscitation. Sustained VT was defined as a regular wide-complex tachycardia of ventricular origin, lasting ≥30 seconds or accompanied by hemodynamic compromise requiring electrical cardioversion. VF was defined as irregular waves of inconsistent shape, without distinct QRS complexes, or T-waves. VT or VF was diagnosed using a twelve-lead electrocardiogram or based on electrocardiogram monitoring during chart review. We included patients with sustained VT/VF event before PCI, during PCI and after PCI in VT/VF group. Patients who had only nonsustained VT with stable hemodynamics were not classified as patients with VT/VF; they were included in the non-VT/VF group. We defined cardiac mortality as death due to myocardial ischemia and infarction, cardiac tamponade and worsening heart failure, procedure-related death, valve-related death, sudden or unwitnessed death and death of unknown cause.
Initially, the patients were divided into those with VT/VF and those without VT/VF. Subsequently, patients with VT/VF were further divided into two groups according to the timing of the arrhythmias: patients with VT/VF occurring within 2 days of hospital admission (early VT/VF) and those with VT/VF occurring >2 days after hospital admission (late VT/VF). Patients with episodes of early and late VT/VF were included in late VT/VF group.
Thirty-day cardiac mortality was compared between patients with VT/VF and those without VT/VF. Thereafter, it was compared between the early and late VT/VF groups. Moreover, we also investigated the timing of VT/VF occurrences and in-hospital cardiac death. Finally, we researched the independent predictors for the in-hospital cardiac mortality in patients with VT/VF.
We compared continuous variables using Student’s t-test or Mann–Whitney U test. Fisher’s exact test was used for categorical variables. P value < 0.05 was considered statistically significant. Baseline variables in the univariate analysis, with p value < 0.05, were considered in the multivariate analysis, which was performed to determine independent predictors of late VT/VF using a logistic-regression model. In addition, multivariate Cox hazard regression model was constructed to investigate the predictor for in-hospital death. The variables examined in these analyses were over age 75 year of age, onset-to-balloon time, Killip class, creatine phosphokinase (CK)-MB on admission, estimated glomerular filtration rate (eGFR), ejection fraction (EF), peak CK-MB and late VT/VF. In this study, the start of the follow-up was the timing of primary PCI. We defined that long follow-up periods were one year from primary PCI. The long follow-up outcomes adjusted the duration on risk of events with log-rank analysis. Survival curves regarding 30-day cardiac mortality were estimated using the Kaplan-Meier method and survival estimates were also compared using the log-rank test. All statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University) [
From January 2004 to December 2014, 1004 patients with AMI who underwent primary PCI were enrolled. Of these patients, 888 (88%) did not have VT/VF while 116 (12%) had VT/VF during prehospitalization or hospitalization (Figure
Study flow chart. eCABG: emergent coronary bypass graft surgery, HD: hemodialysis, PCI: percutaneous coronary intervention, PEA: pulseless electrical activity, VSP: ventricular septal perforation, VT/VF: ventricular tachycardia or ventricular fibrillation.
Baseline characteristics of patients with VT/VF and those of patients without VT/VF are shown in Table
Baseline characteristics of the patients with VT/VF or no VT/VF and early VT/VF or late VT/VF.
Characteristics | VT/VF (n=116) | No VT/VF (n=888) | p value | Early VT/VF (n=92) | Late VT/VF (n=24) | p value |
---|---|---|---|---|---|---|
Age, y | 70 ± 12 | 70 ± 13 | 0.70 | 69 ± 12 | 77 ± 11 | 0.002 |
Male, n (%) | 85 (73) | 639 (72) | 0.74 | 71 (77) | 14 (58) | 0.074 |
BMI | 22 ± 3.9 | 23 ± 4.0 | 0.81 | 23 ± 4.0 | 24 ± 3.5 | 0.38 |
| ||||||
Hypertension, n (%) | 63 (54) | 515 (58) | 0.37 | 48 (52) | 14 (61) | 0.49 |
Diabetes mellitus, n (%) | 41 (35) | 284 (32) | 0.46 | 32 (35) | 8 (32) | 0.46 |
Dyslipidemia, n (%) | 50 (43) | 442 (52) | 0.20 | 30 (33) | 11 (48) | 0.48 |
Smoking, n (%) | 48 (41) | 400 (45) | 0.48 | 38 (42) | 9 (39) | 1 |
FH of CAD, n (%) | 15 (13) | 142 (16) | 0.41 | 10 (11) | 4 (17) | 0.48 |
prior MI, n (%) | 13 (11) | 80 (9) | 0.50 | 10 (11) | 3 (13) | 0.73 |
prior PCI, n (%) | 20 (17) | 115 (13) | 0.19 | 16 (17) | 4 (17) | 1.00 |
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SBP, mmHg | 118 ± 35 | 135 ± 32 | < 0.001 | 121 ± 37 | 111 ± 29 | 0.27 |
HR, beats/min | 82 ± 29 | 75 ± 21 | 0.004 | 78 ± 27 | 97 ± 30 | 0.004 |
Onset to balloon time, h | 4.5 ± 4.1 | 5.0 ± 4.2 | 0.18 | 3.6 ± 2.6 | 7.8 ± 6.5 | < 0.001 |
Killip class | < 0.001 | 0.63 | ||||
I, n (%) | 40 (34) | 665 (75) | 32 (35) | 8 (33) | ||
II, n (%) | 20 (17) | 106 (12) | 15 (16) | 5 (21) | ||
III, n (%) | 13 (11) | 55 (6.3) | 9 (9.8) | 4 (17) | ||
IV, n (%) | 43 (37) | 51 (5.8) | 36 (39) | 7 (29) | ||
CK, U/L | 506 ± 1052 | 430 ± 922 | 0.41 | 303 ± 478 | 1283 ± 1958 | < 0.001 |
CK-MB, U/L | 50 ± 73 | 43 ± 62 | 0.28 | 38 ± 57 | 95 ± 105 | < 0.001 |
Hb, g/dL | 13 ± 2.3 | 14 ± 2.1 | 0.015 | 14 ± 1.9 | 12 ± 3.3 | 0.007 |
eGFR, ml/min/1.73 m2 | 54 ± 18 | 62 ± 20 | < 0.001 | 58 ± 17 | 40 ± 16 | < 0.001 |
BNP, pg/dL | 328 ± 550 | 172 ± 388 | 0.002 | 250 ± 528 | 619 ± 553 | 0.016 |
EF, % | 47 ± 14 | 55 ± 12 | < 0.001 | 49 ± 13 | 41 ± 17 | 0.019 |
BMI: body mass index, BNP: brain natriuretic peptide, CAD: coronary artery disease, CK: creatine kinase, CK-MB: creatine kinase-MB, EF: ejection fraction, eGFR: estimated glomerular filtration rate, FH: family history, Hb: hemoglobin, HR: heart rate, MI: myocardial infarction, PCI: percutaneous coronary intervention, SBP: systolic blood pressure, VT/VF: ventricular tachycardia or ventricular fibrillation.
According to the timing of VT/VF occurrence, 92 patients had early VT/VF (79%) and 24 patients had late VT/VF (21%). Their baseline characteristics are shown in Table
Angiographic findings in patients with early and late VT/VF are shown in Table
Angiographic findings of the patients with early VT/VF or late VT/VF.
Characteristics | Early VT/VF (n=92) | Late VT/VF (n=24) | p value |
---|---|---|---|
LMT, n (%) | 7 (7.6) | 1 (4.2) | 0.12 |
LAD, n (%) | 40 (43) | 8 (33) | |
LCX, n (%) | 4 (4.3) | 5 (21) | |
RCA, n (%) | 41 (45) | 10 (42) | |
Multivessel disease, n (%) | 36 (39) | 15 (63) | 0.063 |
CTO, n (%) | 5 (5.4) | 2 (8.3) | 0.63 |
| |||
Grade 0, n (%) | 74 (80) | 19 (79) | 1 |
Grade I, n (%) | 4 (4.3) | 1 (4.2) | |
Grade II, n (%) | 7 (7.6) | 2 (8.3) | |
Grade III, n (%) | 7 (7.6) | 2 (8.3) | |
| |||
Grade 0, n (%) | 1 (1.1) | 0 | 0.54 |
Grade I, n (%) | 2 (2.2) | 0 | |
Grade II, n (%) | 7 (7.6) | 4 (17) | |
Grade III, n (%) | 82 (89) | 20 (83) | |
Aspiration, n (%) | 78 (72) | 20 (83) | 0.78 |
IABP, n (%) | 49 (53) | 13 (54) | 0.82 |
PCPS, n (%) | 16 (17) | 3 (13) | 0.76 |
CTO: chronic total occlusion, IABP: Intra-aortic balloon pumping, LAD: left anterior descending coronary artery, LCX: left circumflex coronary artery, LMT: left main trunk, PCPS: percutaneous cardiopulmonary support, RCA: right coronary artery, TIMI: thrombolysis in myocardial infarction, VT/VF: ventricular tachycardia or ventricular fibrillation.
The clinical outcomes of patients with early and late VT/VF are shown in Table
Clinical outcomes of the patients with early VT/VF or late VT/VF.
Characteristics | Early VT/VF (n=92) | Late VT/VF (n=24) | p value |
---|---|---|---|
Peak CK U/L | 4362 ± 4060 | 4817 ± 4170 | 0.63 |
Peak CK-MB U/L | 321 ± 308 | 433 ± 544 | 0.20 |
Length of hospital stay, days | 16 ± 29 | 25 ± 15 | 0.15 |
In-hospital recurrent MI, n (%) | 2 (2.2) | 1 (4.2) | 0.51 |
In-hospital stroke, n (%) | 1 (1.1) | 1 (4.2) | 0.37 |
In-hospital cardiac mortality, n (%) | 22 (24) | 14 (58) | 0.002 |
In-hospital noncardiac mortality, n (%) | 3 (3.2) | 2 (8.3) | 0.28 |
Recurrent MI at 1 year, n (%) | 2 (2.2) | 1 (4.2) | 0.63 |
Stroke at 1 year, n (%) | 3 (3.3) | 0 (0) | 0.58 |
All-cause mortality at 1 year, n (%) | 26 (28) | 17 (71) | < 0.001 |
Cardiac mortality at 1 year, n (%) | 22 (24) | 14 (58) | < 0.001 |
CK: creatine kinase, CK-MB: creatine kinase-MB, MI: myocardial infarction, VT/VF: ventricular tachycardia or ventricular fibrillation.
Note: P value for recurrent MI, stroke, all-cause mortality, and cardiac death were analyzed by log-rank test.
The factor associated with an increased risk of late VT/VF was onset-to-balloon time after multivariable adjustment with a significant level of p< 0.05 in Table
Multivariable adjustment of risk factors of late VT/VF.
OR | 95% CI Lower | 95% CI Upper | p value | |
---|---|---|---|---|
Age | 1.12 | 0.906 | 1.380 | 0.30 |
HR | 1.02 | 0.983 | 1.050 | 0.35 |
Onset to balloon time | 2.03 | 1.01 | 4.080 | 0.047 |
CK-MB | 1.01 | 0.984 | 1.030 | 0.64 |
Hb | 0.423 | 0.216 | 0.827 | 0.012 |
eGFR | 0.847 | 0.741 | 0.968 | 0.015 |
BNP | 0.998 | 0.995 | 1.000 | 0.064 |
EF | 0.994 | 0.916 | 1.080 | 0.88 |
BNP: brain natriuretic peptide, CI: confidence interval, CK-MB: creatine kinase-MB, EF: ejection fraction, eGFR: estimated glomerular filtration rate, HR: heart rate, OR: odds ratio, VT/VF: ventricular tachycardia or ventricular fibrillation.
The independent predictors for in-hospital cardiac death-Cox regression model.
OR | 95% CI Lower | 95% CI Upper | p value | |
---|---|---|---|---|
Age >=75 years | 1.397 | 0.532 | 3.667 | 0.50 |
Onset to balloon time | 0.987 | 0.898 | 1.084 | 0.78 |
Killip class | 1.484 | 1.017 | 2.165 | 0.04 |
EF | 0.986 | 0.959 | 1.015 | 0.34 |
eGFR | 0.986 | 0.950 | 1.024 | 0.46 |
Peak CK-MB | 1.001 | 1.000 | 1.002 | 0.03 |
Late VT/VF | 3.436 | 1.115 | 10.59 | 0.03 |
CI: confidence interval, CK-MB: creatine kinase-MB, EF: ejection fraction, eGFR: estimated glomerular filtration rate, OR: odds ratio, VT/VF: ventricular tachycardia or ventricular fibrillation.
The Kaplan-Meier curve demonstrated the cardiac survival rate in the patients with VT/VF compared with those patients without VT/VF during a 30-days (Figure
Clinical outcomes regarding cardiac survival rate between patients without VT/VF and those with VT/VF during the 30-day period. Notes: log-rank test p <0.001 for comparisons between patients without VT/VF and those with VT/VF. VT/VF: ventricular tachycardia or ventricular fibrillation.
Clinical outcomes regarding cardiac survival rate among patients without VT/VF, those with early VT/VF, and those with late VT/VF during the 30-day period. Notes: log-rank test p <0.001 for comparisons between patients without VT/VF and those with early VT/VF, those without VT/VF, and those with late VT/VF, and between those with early VT/VF and those with late VT/VF. VT/VF: ventricular tachycardia or ventricular fibrillation.
In early VT/VF group (92 patients), fifty-one patients had the occurrences of VT/VF before PCI, 33 patients had the occurrences of VT/VF during PCI, and 8 patients had the occurrences of VT/VF after PCI within 48 hours after admission. Eighty-nine patients with VT/VF (77%) had the timing of VT/VF occurrences within 24 h of admission. Of these, 13 patients had the occurrence of VT/VF within 1 hour from onset. The frequency of late VT/VF was high between the 6th and 10th days of hospitalization (Figure
Timing and frequency of late VT/VF. VT/VF: ventricular tachycardia or ventricular fibrillation.
The relationship between early or late VT/VF and in-hospital cardiac death was demonstrated in Figure
Timing and frequency of in-hospital cardiac death. VT/VF: ventricular tachycardia or ventricular fibrillation.
This study compared the timing of VT/VF occurrences in patients with AMI who underwent primary PCI and 30-day cardiac mortality between patients without VT/VF, those with early VT/VF, and those with late VT/VF. The main findings of this study are as follows: (1) the timing of VT/VF occurrences had two peaks, i.e., within 2nd day and around 8 days after admission and (2) patients with late VT/VF had a very poor prognosis compared to that of patients without VT/VF and patients with early VT/VF.
Of 1004 patients with AMI who were hospitalized within 24 h of AMI symptom onset and underwent primary PCI, 12% had VT/VF in this study. Previous AMI registry data, including the APEX-AMI and HORIZONS-AMI trials, demonstrated that VT/VF incidence in the acute phase of AMI was higher in our study (APEX-AMI 5.7% and HORIZONS-AMI 5.2%) [
Furthermore, our study showed that the 30-day mortality rate of patients without VT/VF vs. patients with early VT/VF vs. patients with late VT/VF was 3.9% vs. 24% vs. 58% and that VT/VF was significantly associated with high 30-day mortality. These findings are acceptable in daily clinical practice and were reported in various studies [
According to a previous report, early VF is triggered by acute ischemia in combination with an elevated sympathetic tone due to total coronary artery occlusion [
Hence, the pathophysiology of VT/VF in the two groups was different. Even if reperfusion therapy was successful, in cases of long onset-to-balloon time, careful management using electrocardiogram monitoring is necessary, considering the low survival rate of patients with late VT/VF. Although
Our study was a retrospective, nonrandomized, single-center research. In addition, the number of patients who had late VT/VF was relatively small. We could not provide more detail on the types of VT/VF, such as fast, slow, monomorphic, or polymorphic. Our study could not distinguish between VT and VF regarding prognosis. It was difficult to distinguish between the patients with VT and those with VF completely because these types of arrhythmia were overlapping in almost all cases. Previous large scale studies such as HORIZONS-AMI Trial [
In this study, the timing of VT/VF had two peaks, and late VT/VF was strongly related to the timing of the secondary peak of in-hospital cardiac death. Careful management of patients with late VT/VF is crucial because they have a very poor prognosis.
(1) The retrospective research data used to support the findings of this study have been deposited in the Department of Cardiology and Catheterization Laboratories, Shonan Kamakura General Hospital Repository.
The authors declare that there are no conflicts of interest.
All authors listed meet the authorship criteria according to the latest guidelines of the International Committee of Medical Journal Editors. Takuma Takada designed the study, analyzed data, and wrote the initial draft of the manuscript. Koki Shishido contributed to analysis and interpretation of data. Koki Shishido, Noriaki Moriyama, Futoshi Yamanaka, Saeko Takahashi, and Shigeru Saito assisted in the preparation of the manuscript. Takahiro Hayashi, Shohei Yokota, Hirokazu Miyashita, Hiroaki Yokoyama, Takashi Nishimoto, Tomoki Ochiai, Noriaki Moriyama, Kazuki Tobita, Shingo Mizuno, Futoshi Yamanaka, Masato Murakami, and Yutaka Tanaka have contributed to data collection and interpretation and critically reviewed the manuscript. Koki Shishido, Takahiro Hayashi, Shohei Yokota, Hirokazu Miyashita, Hiroaki Yokoyama, Takashi Nishimoto, Tomoki Ochiai, Noriaki Moriyama, Kazuki Tobita, Shingo Mizuno, Futoshi Yamanaka, Masato Murakami, Yutaka Tanaka, Saeko Takahashi, and Shigeru Saito have read and approved the final version of the manuscript and agreed to be accountable for all aspects. All authors performed percutaneous coronary intervention and obtained informed consent for the patients in this study.
We thank the patients and Moeko Takada, who is a staff of the clinical laboratory department at our hospital, for her enormous help with the data collection.