- Academic Editor
†These authors contributed equally.
Background: The risk of sudden cardiac death (SCD) after coronary
revascularization in patients with left ventricular (LV) systolic dysfunction has
not been characterized completely. This study aims to evaluate the incidence and
time course of SCD after revascularization in such patients. The determinants of
SCD within 3 months after revascularization were also assessed. Methods:
A cohort study of patients with reduced ejection fraction (EF
Coronary artery disease (CAD) and lower ejection fraction (EF) are two factors associated with sudden cardiac death (SCD) in patients with left ventricular (LV) systolic dysfunction [1]. About 50% of deaths in patients with CAD and LV systolic dysfunction occur suddenly [2, 3]. Attenuating the ischemic state and improving EF with coronary revascularization [4, 5, 6] have been recommended to reduce the risk of SCD [7, 8]. However, the incidence and risk of SCD in patients with CAD and LV dysfunction who underwent coronary revascularization by either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) have not been well-characterized in the literature.
Current guidelines recommend that patients with LV dysfunction undergo a reassessment of EF 3 months after revascularization to evaluate the neccesity for implantable cardioverter defibrillator (ICD) placement [9]. The rationale for waiting 3 months after revascularization is based on the LV function can improve sufficiently to raise the EF to above 35%, and in clinical trials [10, 11], ICD did not achieve the benefit of SCD prevention early after revascularization (i.e., CABG-patch [12], DINAMIT (Defibrillator in Acute Myocardial Infarction Trial) [13], and IRIS (Immediate Risk stratification Improves Survival trial) [14]). However, how the risk of SCD might develop over time after coronary revascularization is uncertain. Therefore, recognizing the distribution of the incidence of SCD over time, especially within 3 months after revascularization, is clinically significant.
Although EF is currently the most widely used and robust clinical risk factor for SCD after myocardial infarction (MI) and has become the basis for determining a patient’s eligibility for ICD therapy [15, 16], EF might be poor at distinguishing between CAD patients who will die suddenly and those who will die of other cardiovascular causes [2, 17]. Studies in patients with CAD and LV dysfunction who underwent coronary revascularization demonstrated that baseline EF was not associated with the subsequent risk of long-term SCD [18, 19]. This might be due to diverse change of EF after revascularization [7, 20] or requirement of combination with other electrical parameters [2]. Identification of patients at risk remains an issue that is not being adequately addressed.
The present study was designed to determine the incidence of SCD during long-term follow-up in patients with both CAD and LV dysfunction after coronary revascularization by either CABG or PCI, to assess how the event rate changes over time after revascularization, and to analyze clinical predictors of SCD within 3 months after revascularization, especially to understand the predictive value of EF.
This was a retrospective cohort study with data generated by Beijing Anzhen
Hospital. The study protocol was approved by the hospital’s ethics committee. We
identified patients’ data with reduced EF (
Baseline demographic, clinical, lab test and angiographic parameters were
collected from medical records of Beijing Anzhen hospital. The preoperative EF
was defined as being measured within 30 days before PCI or CABG. The history of
ventricular tachycardia and/or ventricular fibrillation (VT/VF) was determined by
prior medical record, electrocardiogram, and 24-hour Holter monitor. Patients
with a history of nonsustained VT were also regarded as having a history of
VT/VF. Patinets who experienced VT/VF during the acute phase of MI were not
regarded as having a history of VT/VF. Electrocardiography at discharge from the
index hospitalization for the qualifying procedure was used to diagnose the
presence of bundle branch block. Bundle branch block was considered present when
the QRS duration was
Outcome data were obtained from medical records at Beijing Anzhen Hospital and through telephone follow up. Death was categorized as cardiac and non-cardiac death. Cardiac death was categorized as SCD and non-SCD [8]. Death due to the procedural and/or acute complication of the revascularization was categorized as non-SCD. Death with insufficient information to make a reasonable decision as to the cause of death was categorized as unknown/unclassified death. According to a modified Hinkle-Thaler system [21], SCD was defined as a sudden, unexpected death that was cardiac in origin, which included those who: (1) died suddenly and unexpectedly within 1 hour of cardiac symptoms in the absence of progressive cardiac deterioration; (2) died unexpectedly in bed during sleep; and (3) died unexpectedly within 24 hours after last being seen alive. For this analysis, the outcome was categorized into 3 groups: patients who died of SCD, patients who died of causes other than SCD, and patients who did not die by the end of the study follow-up period.
Continuous variables were expressed as mean
Given the competing risk of SCD and other modes of deaths, cumulative incidence rates for SCD were estimated with the Fine and Gray method [22]. Cumulative incidence function was fitted using a flexible parametric survival model for competing risks with 3 degrees of freedom for time-dependent effects. SCD, other deaths, and all-cause death rate were summarized with cumulative incidence curves for 10 years of follow-up [23]. Cumulative incidence of SCD in the first year after revascularization was separately displayed along with its 95% confidence interval (CI). Incidence rates per month for SCD were reported at 3 months, 3–6 months, 6–12 months, 1–3 years, 3–5 years and 5–10 years after revascularization.
To identify factors associated with the risk of SCD within 3 months after
revascularization, candidate covariates were analyzed in a Cox proportional
hazards model by treating death from other causes as a competing risk [22]. The
crude associations between the candidate predictors and risk of SCD were first
reported by univariate Cox regression. Variables with p values
All statistical analyses were based on 2-tailed tests. Values of p
Among 2852 initially identified patients, 306 had concomitant noncoronary
surgery, 23 had no coronary angiography, and 206 were lost during follow-up. 2317
patients were included in the study, with 1261 (54.4%) undergoing CABG and 1056
(45.6%) undergoinig PCI. There were 1522 (65.7%) patients who were diagnosed
with acute coronary syndromes (ACS), which included 535 (23.1%) with ST-segment
elevation MI, 179 (7.7%) with non-ST-segment elevation MI, and 808 (34.9%) with
unstable angina. There were 795 (34.3%) patients who were diagnosed with stable
angina. The mean age was 66.1 years (Table 1). The preoperative EFs were 36.0%
(4.5%). There was no patient who had ICD before revascularization. There were
971 patinets who had EF reassessed 3 months after revascularization. The
postoperative EFs were 45.3% (11.3%). Among 199 patients whose EFs were
Characteristics | SCD (n = 162) | Other deaths (n = 342) | p value | No death (n = 1813) | p value # |
Age (mean |
70.5 |
72.0 |
0.108 | 64.6 |
|
Male sex, No. (%) | 134 (82.7) | 275 (80.4) | 0.536 | 1511 (83.3) | 0.838 |
Hypertension, No. (%) | 97 (59.9) | 194 (56.7) | 0.504 | 921 (50.8) | 0.027 |
Diabetes, No. (%) | 53 (32.7) | 133 (38.9) | 0.180 | 614 (33.9) | 0.767 |
eGFR (mean |
74.6 |
75.9 |
0.571 | 86.4 (24.6) | |
Cerebral vascular disease, No. (%) | 13 (8.0) | 50 (14.6) | 0.037 | 166 (9.2) | 0.631 |
History of MI, No. (%) | 80 (49.4) | 180 (52.6) | 0.495 | 870 (48.0) | 0.733 |
History of VT/VF, No. (%) | 6 (3.7) | 6 (1.8) | 0.180 | 24 (1.3) | 0.018 |
Atrial fibrillation, No. (%) | 13 (8.0) | 26 (7.6) | 0.868 | 75 (4.1) | 0.022 |
Bundle branch brock (QRSd |
8 (4.9) | 18 (5.3) | 0.878 | 79 (4.4) | 0.730 |
Preoperative EF (mean |
35.1 |
35.2 |
0.787 | 36.3 (4.4) | 0.001 |
ACS, No. (%) | 109 (67.3) | 242 (70.8) | 0.428 | 1171 (64.6) | 0.491 |
*PCI, No. (%) | 75 (46.3) | 128 (37.4) | 0.058 | 853 (47.1) | 0.854 |
Triple-vessel disease, No. (%) | 93 (59.2) | 183 (57.9) | 0.783 | 834 (48.8) | 0.012 |
Left main disease, No. (%) | 14 (8.6) | 36 (10.8) | 0.446 | 117 (6.5) | 0.297 |
Complete revascularization, No. (%) | 89 (54.9) | 186 (56.0) | 0.820 | 1028 (57.2) | 0.582 |
Aspirin, No. (%) | 141 (92.2) | 271 (90.3) | 0.522 | 1703 (94.0) | 0.366 |
Clopidogrel/Ticagrelor, No. (%) | 90 (58.8) | 173 (57.7) | 0.813 | 1030 (56.8) | 0.635 |
ACEi/ARB/ARNI, No. (%) | 74 (48.4) | 125 (41.7) | 0.174 | 803 (44.3) | 0.333 |
b-Blocker, No. (%) | 113 (73.7) | 201 (67.0) | 0.135 | 1444 (79.7) | 0.088 |
MRA, No. (%) | 25 (16.3) | 44 (14.7) | 0.639 | 292 (16.1) | 0.942 |
*CABG was set as reference to PCI.
# p values are for the comparison with SCD.
Abbreviations: SCD, sudden cardiac death; eGFR, estimated glomerular filtration rate; MI, myocardial infarction; VT/VF, ventricular tachycardia and/or ventricular fibrillation; QRSd, QRS duration; EF, ejection fraction; ACS, acute coronary syndromes; PCI, percutaneous coronary intervention; CABG, coronary artery bypass graft; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor-neprilysin inhibitor; MRA, mineralocorticoid receptor antagonist.
After a median follow-up of 3.5 years (interquartile range, 2.0–6.4; maximum = 11.6), 504 (21.8%) patients died during this period. Among those, 162 (32.1%) had SCD, and 342 (67.9%) died from other reasons. The median time to SCD was 3.2 years (interquartile range = 1.0–5.3) after revascularization. Causes of death other than SCD included non-SCD (n = 258), non-cardiac causes of death (n = 79), and unclassified death (n = 5). Non-SCD causes of death included: procedural complications (n = 86); acute MI (n = 59); heart failure (n = 87); other reasons (n = 26). Non-cardiac causes of death included: cancer (n = 30); cerebrovascular accident (n = 24); renal dysfunction (n = 5); pneumonia (n = 2); and other non-cardiac reasons (n = 18). Compared with surviving patients without events, patients who died suddenly were significantly older; were more likely to have a history of hypertension, VT/VF or atrial fibrillation; had a lower estimated glomerular filtration rate (eGFR) and preoperative EF; and were more likely to have triple-vessel diseases. The differences between patients who died of SCD and those who died of other causes were much less significantly different (Table 1).
Fig. 1 shows the cumulative incidence of SCD, other deaths and all-cause death as a function of time after revascularization until 10 years. SCD accounted for one-third of all deaths after revascularization. At 1, 5, and 10 years, the cumulative incidence of SCD was 1.79% (95% CI, 1.23–2.34), 6.40% (95% CI, 5.20–7.59), and 14.67% (95% CI, 12.19–17.15), respectively. Fig. 2 shows the cumulative incidence of SCD within 1 year after revascularization, and demonstrates that the highest event rate was in the first 3 months. There were 23 SCDs in the first 3 months representing 14.2% of all patients with SCD in the study. The incidence rates of SCD/month over time after revascularization are reported in Table 2. The SCD/month in the first 3 months after revascularization was 0.37% (95% CI, 0.25–0.56). Among ACS patients, the SCD/month rate in the first 3 months reached 0.47% (95% CI, 0.30–0.74). After 3 months, the risk/month rate decreased to 0.12% (95% CI, 0.06–0.24) and remained relatively stable thereafter. By the end of the follow-up period, the risk/month rate tended to increase numerically, especially for patients with non-ACS, which had a risk/month rate of 0.25% (95% CI, 0.16–0.39).
Cumulative incidence of sudden cardiac death, other deaths and all-cause death after revascularization in patients with coronary artery disease and left ventricular dysfunction.
One-year cumulative incidence of sudden cardiac death after revascularization in patients with coronary artery disease and left ventricular dysfunction. Dashed lines represented 95% confident intervals.
Time interval after revascularization | Person-month | SCD event, n | Incidence rate per month, % (95% CI) | |
Total Cohort | 3 Months | 6221 | 23 | 0.37 (0.25–0.56) |
3–6 Months | 5998 | 7 | 0.12 (0.06–0.24) | |
6–12 Months | 11,709 | 9 | 0.08 (0.04–0.15) | |
1–3 Years | 41,333 | 37 | 0.09 (0.06–0.12) | |
3–5 Years | 25,095 | 34 | 0.14 (0.10–0.19) | |
5–10 Years | 26,874 | 50 | 0.19 (0.14–0.25) | |
ACS patients | 3 Months | 4037 | 19 | 0.47 (0.30–0.74) |
3–6 Months | 3897 | 3 | 0.08 (0.02–0.24) | |
6–12 Months | 7583 | 8 | 0.11 (0.05–0.21) | |
1–3 Years | 26,989 | 25 | 0.09 (0.06–0.14) | |
3–5 Years | 16,181 | 21 | 0.13 (0.08–0.20) | |
5–10 Years | 19,181 | 31 | 0.16 (0.11–0.23) | |
Non-ACS patients | 3 Months | 2184 | 4 | 0.18 (0.07–0.49) |
3–6 Months | 2101 | 4 | 0.19 (0.07–0.51) | |
6–12 Months | 4126 | 1 | 0.02 (0.00–0.18) | |
1–3 Years | 14,344 | 12 | 0.08 (0.05–0.15) | |
3–5 Years | 8915 | 13 | 0.15 (0.08–0.25) | |
5–10 Years | 7693 | 19 | 0.25 (0.16–0.39) |
Abbreviations: SCD, sudden cardiac death; CI, confidence interval; ACS, acute coronary syndrome.
Baseline variables associated with SCD within 3 months are reported in Table 3.
In the univariate analysis, history of VT/VF, history of hypertension, and
triple-vessel CAD were associated with increased SCD risk. Bundle branch block
with QRS duration of
Variables | Univariate analysis | Multivariate analysis | ||
HR (95% CI) | p value | HR (95% CI) | p value | |
Age in 5 years increments | 0.99 (0.82–1.19) | 0.908 | ||
Male sex | 0.48 (0.20–1.16) | 0.103 | ||
Hypertension | 2.58 (1.02–6.54) | 0.046 | 2.25 (0.88–5.75) | 0.091 |
Diabetes | 0.83 (0.34–2.01) | 0.673 | ||
eGFR in 5 mL/min increments | 0.98 (0.91–1.06) | 0.649 | ||
Cerebral vascular disease | 0.90 (0.21–3.84) | 0.887 | ||
History of MI | 1.38 (0.60–3.05) | 0.445 | ||
History of anterior MI | 1.48 (0.58–3.76) | 0.407 | ||
History of VT/VF | 6.18 (1.41–27.07) | 0.016 | 5.55 (1.33–23.19) | 0.019 |
Atrial fibrillation | 0.86 (0.12–6.33) | 0.879 | ||
Bundle branch block (QRSd |
3.30 (0.98–11.08) | 0.054 | 3.39 (1.00–11.50) | 0.050 |
Preoperative EF in 5% increments | 0.98 (0.62–1.55) | 0.935 | ||
ACS | 2.48 (0.85–7.29) | 0.098 | 2.61 (0.91–7.46) | 0.074 |
Triple-vessel disease | 3.56 (1.32–9.57) | 0.012 | 3.90 (1.38–11.05) | 0.010 |
Left main disease | 1.99 (0.59–6.71) | 0.265 | ||
PCI* | 0.60 (0.25–1.41) | 0.241 | ||
Complete revascularization | 0.49 (0.21–1.13) | 0.094 | 0.80 (0.34–1.90) | 0.612 |
Aspirin | 0.73 (0.28–1.87) | 0.510 | ||
Clopidogrel/Ticagrelor | 0.83 (0.33–2.05) | 0.682 | ||
ACEi/ARB/ARNI | 1.58 (0.55–4.54) | 0.393 | ||
b-Blocker | 0.63 (0.20–2.02) | 0.441 | ||
MRA | 0.39 (0.05–2.95) | 0.359 |
*CABG was set as reference to PCI. SCD, sudden cardiac death; eGFR, estimated glomerular filtration rate; MI, myocardial infarction; VT/VF, ventricular tachycardia and/or ventricular fibrillation; QRSd, QRS duration; EF, ejection fraction; ACS, acute coronary syndromes; PCI, percutaneous coronary intervention; CABG, coronary artery bypass graft; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor-neprilysin inhibitor; MRA, mineralocorticoid receptor antagonist; HR,hazard ratio; CI, confidence interval.
The baseline characteristics of patients who underwent CABG and those who underwent PCI are compared in Supplementary Table 1. The predictors of SCD for CABG patients and those for PCI patients were explored. Among CABG patients, a history of VT/VF (HR, 9.51; 95% CI, 1.10–82.50; p = 0.041) was predictive of SCD in the multivariate analysis (Supplementary Table 2). Among PCI patients, a history of VT/VF (HR, 5.05; 95% CI, 1.13–38.62; p = 0.038), bundle branch block (HR, 6.24; 95% CI, 1.34–29.04; p = 0.020), and triple vessel disease (HR, 4.40; 95% CI, 1.06–18.27; p = 0.041) were predictive of SCD (Supplementary Table 3).
In the present study, we report three main findings. First, in patients with CAD
and EF
In the Multicenter Unsustained Tachycardia Trial (MUSTT) [24], patients with
documented CAD, EF
The incident rate per month over different time intervals after
revascularization indicated the extreme risk of SCD within 3 months after
revascularization, especially for patients with ACS. Similar results had been
reported in the STICH tial [19] and VALIANT (Valsartan in Acute Myocardial
Infarction Trial) [25]. In the STICH trial, patients enrolled had chronic
ischemic heart disease. The SCD/month rate at 1 month, 1–3 months, 3–6 months,
6–12 months, 1–3 years and 3–5years was 0.35%, 0.43%, 0.26%, 0.14%,
0.14%, and 0.11%, respectively. In the VALIANT trial, patients with acute MI
complicated by heart failure, LV systolic dysfunction (EF
It is recommended that patients with left ventricular dysfunction undergo a
reevaluation of EF 3 months after revascularization for deciding whether to do
ICD implantation or not [16]. This interval may allow LV to recover the EF from
revascularization. However, the risk of SCD in this period was greatest. Early
acute MI also constitutes a period of particularly high risk of death from
arrhythmia [25, 26]. The effectiveness of early ICD implantation was explored by
the Defibrillator in Acute Myocardial Infarction Trial (DINAMIT) [13] and
Immediate Risk-stratification Improves Survival (IRIS) trial [14]. ICD was
implanted 6 to 40 days or 5 to 31 days after acute MI, respectively. All the
patients had EF
In the present study, a history of VT/VF or bundle branch block was a protential
predictor for SCD in the first 3 months after revascularization. Bundle branch
block, including both left and right bundle branch blocks, was a powerful and
independent predictor of SCD in patients with reduced EF [28] and acute MI [29].
Electrical dispersion of ventricular depolarization and conduction delay, as
manifested by QRS prolongation, reflect severity of electrical dysfunction.
Bundle branch block with QRS duration
The present study had several limitations. (1) This was an observational study
from a single center and thus might have selection bias. (2) An accurate estimate
of SCD incidence requires prospective ascertainment of cases. Studies that have
used a retrospective death certificate-based method to identify cases of SCD are
likely to overestimate [30, 31]. (3) There were 13 patients with ICD implantation
during the follow-up, but we did not have data on ICD shocks or aborted sudden
cardiac arrest. However, these data were unlikely to have affected the present
findings because of their uses were minimal in this cohort. (4) The medical
treatments for SCD prevention were underutilized. Both prescripton rate and
target-dose achievement did not align with the treatment consensus for SCD
prevention, especially for patients who underwent CABG treatment. There were
97.1% who did not achieve the target dose of
For patients with CAD and LV systoclic dysfunction who underwent coronary revascularization, SCD accounted for one-third of all deaths. The event rate of SCD was the highest during the first 3 months after revascularization, especially in patients with a history of VT/VF or coronary triple vessel disease. Preoperative EF did not predict the short-term risk of SCD, this underscores the importance of cardiac function surveillance of patients after revascularization.
The data are available from the corresponding author upon request.
JHL and BJB conceived the concept of the study and supervision. SPW and YL contributed to the design of the research. SPW, YL, YCL, SJC, SYL, ZZ, XYG and MG were involved in data collection and analysis. SPW and YL wrote the original draft. All authors edited and approved the final version of the manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.
This study was approved by the ethics committee of the Beijing Anzhen Hospital (No. 2021004X). Because this was a retrospective cohort study, written informed consent from the patients was waived. The study conforms with World Medical Association Declaration of Helsinki.
We express our gratitude to all participated staffs for completing the CRISIS Project (Coronary Revascularization In Patients with Ischemic Heart Failure and Prevention of Sudden Cardiac Death).
This research received no external funding.
The authors declare no conflict of interest.
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