Minimizing Door-to-Balloon Time Is Not the Most Critical Factor in Improving Clinical Outcome of ST-Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention

Yuan-Chih Ho, MD; Tzu-Hsien Tsai, MD; Pei-Hsun Sung, MD; Yung-Lung Chen, MD; Sheng-Ying Chung, MD; Cheng-Hsu Yang, MD; Shyh-Ming Chen, MD; Chien-Jen Chen, MD; Hsiu-Yu Fang, MD; Chiung-Jen Wu, MD; Hon-Kan Yip, MD

Disclosures

Crit Care Med. 2014;42(8):1788-1796.

Abstract and Introduction

Abstract

Objectives. We tested the hypothesis that, as compared with conventional door-to-balloon, shortened door-to-balloon time would further improve 30-day outcome in ST-elevation myocardial infarction patients undergoing primary stenting.

Design. Retrospective cohort study

Setting. Academic tertiary care hospital with approximately 2600 beds

Patients. Between January 2008 and December 2009, 266 ST-elevation myocardial infarction patients underwent primary stenting with conventional Door-to-baloon were consecutively enrolled as group 1, while 293 ST-elevation myocardial infarction patients underwent primary stenting with shortened door-to-balloon between January 2010 and December 2011 were consecutively enrolled as group 2.

Intervention. Shorten door-to-balloon time.

Measurements and Main Results. The results showed that time from chest pain onset to door did not differ between two groups (p > 0.1), whereas door-to-balloon time was significantly reduced in group 2 compared with that in group 1 (p < 0.0001). The prevalences of successful reperfusion, acute and subacute stent thrombosis, 30-day death or combined endpoint (defined as congestive heart failure ≥ New York Heart Association functional class 3 or 30-d death), and left ventricular function did not differ between two groups (all p > 0.05), whereas the peak creatine phosphokinase level was significantly reduced in group 2 (< 0.05). Further analysis showed that shortening the chest pain-to-reperfusion time to less than 240 minutes was the most important factor in improving left ventricular function (p < 0.001) and 30-day combined endpoint. Multivariate analysis showed that congestive heart failure greater than or equal to New York Heart Association functional class 3, poor left ventricular function, and age (all p < 0.001) along with unsuccessful reperfusion (p = 0.25) were independently predictive of 30-day mortality.

Conclusion. Shortening the duration between chest pain onset and reperfusion to less than 4.0 hours was critical in reducing myocardial necrosis and improving heart function and 30-day mortality.

Introduction

Acute myocardial infarction (AMI) is the leading cause of death in patients hospitalized for cardiovascular disease.^[1–3] Early successful reperfusion using thrombolytic therapy or primary percutaneous coronary intervention (PCI) is the most effective therapeutic strategy adopted to minimize the ischemic insult and infarct size of the myocardium and ultimately improve the overall clinical outcome.^[3–6] A body of evidence from clinical studies has clearly shown that primary PCI is superior to thrombolytic therapy in terms of the time to reperfusion, the rate of achieving a final thrombolysis in myocardial infarction (TIMI)-3 blood flow (i.e., the normal blood flow) in the infarct-related artery, the rate of bleeding complication, the prevalence of recurrent myocardial infarction (MI) and repeated PCI, as well as the preservation of heart function.^[7–11]

Although it is commonly acknowledged that the golden time for primary PCI is less than 12 hours for patients with ST-segment elevation myocardial infarction (STEMI) without cardiogenic shock and less than 18 hours for STEMI patients complicated by cardiogenic shock, it is believed that earlier performance of primary PCI is important in minimizing the ischemic insult and infarct size of the myocardium. Additionally, although the latest guideline (2013 American College of Cardiology Foundation/American Heart Association) recommends that less than 90 minutes of door-to-balloon (DTB) time is acceptable as the management strategy for STEMI using primary PCI,^[12] the guideline strongly emphasizes the importance of shortening the DTB time for primary PCI.^[12]

Interestingly, we have previously demonstrated that the prevalence of slow or no-reflow phenomenon in patients with STEMI undergoing primary PCI was significantly higher when the duration between chest pain onset and reperfusion was more than 4 hours than that when the duration was less than or equal to 4 hours.^[6] In addition, some previous studies have revealed that only the combination of a short (< 90 min) DTB time and a short chest pain-to-door time was associated with the improvement of clinical outcome.^[13,14] Disappointingly, no further study has been reported. Furthermore, although the guideline and interventional cardiologists often emphasize the critical role of DTB time in STEMI patients undergoing primary PCI, limited data were available to address whether the DTB time of less than 90 minutes would provide additional benefit in STEMI patients undergoing primary PCI.^[14]

The primary PCI program for STEMI patients at Kaohsiung Chang Gang Hospital has started since May 1993. Between May 1993 and April 2009, no specific strategy was adopted for addressing the important issue of DTB time for primary PCI. On the other hand, shortened DTB time has been emphasized as a principal policy for primary PCI in STEMI patients since May 2009. Accordingly, this study tested whether shortened DTB time in our current clinical practice would provide an additional benefit for patients with STEMI undergoing primary PCI.

1 2 3 4

Next Section

Abstract and Introduction
Materials and Methods
Results
Discussion
References

Table 1. Baseline Characteristics of 559 Study Patients.
Variables	Nonemphasized DTB (n = 266)	Emphasized DTB (n = 293)	p
Age (yr)	61.18 ± 11.83	60.37 ± 13.38	0.455
Male gender (%)	84.6 (225)	82.9 (243)	0.576
Diabetes mellitus (%)	33.8 (90)	31.4 (92)	0.539
Hypertension (%)	57.9 (154)	63.8 (187)	0.151
Current smoking (%)	52.3 (139)	47.1 (138)	0.223
Infarction location (%)
Anterior wall	54.9 (146)	53.9 (158)	0.820
Inferior wall	39.5 (105)	42.3 (124)	0.494
Lateral wall	5.6 (15)	3.8 (11)	0.291
Total cholesterol level (mg/dL)	180.4 ± 54.2	167.1 ± 57.9	0.006
Low-density lipoprotein (mg/dL)	110.8 ± 43.5	103.6 ± 45.1	0.056
Fasting sugar (g/dL)	175.7 ± 86.2	184.1 ± 104.9	0.307
Creatinine level (mg/dL)	1.36 ± 1.37	1.50 ± 1.81	0.287
WBC count (×10³)	11.25 ± 4.03	12.1 ± 5.67	0.168
Troponin-I upon presentation (ng/mL)	10.9 ± 34.5	13.6 ± 47.9	0.456
Creatine kinase MB upon presentation (ng/mL)	25.9 ± 60.9	33.9 ± 78.62	0.186
Peak-creatine phosphokinase level (IU/mL)	2,402 ± 2,960	1,699 ± 1,771	0.001

DTB = door to balloon.
Data are expressed as mean ± sd or % (n).

Table 2. Clinically Relevant Variables, Echocardiography Findings, Angiographic Results, and 30-Day Clinical Outcomes Among 559 Patients.
Variables	Nonemphasized DTB (n = 266)	Emphasized DTB (n = 293)	p
Killip scores (mean ± sd)			0.962
≥ score 3 (%)	24.1 (64)	24.2 (71)
≤ score 2 (%)	75.9 (202)	75.8 (222)
Cardiogenic shock (%)	14.3 (28)	15.7 (46)	0.640
Congestive heart failure (mean ± sd)^a	0.89 ± 1.23	0.95 ± 1.41	0.236
≥ NYHA Fc-3 (%)	13.9 (37)	15 (44)	0.710
≤ NYHA Fc-2 (%)	86.1 (229)	85 (249)	0.710
Intra-aortic balloon pump support (%)	15.8 (42)	15 (44)	0.800
Extracorporeal membrane oxygenator implantation (%)	3 (8)	2 (6)	0.468
Chest pain onset to emergency room	150 (72–260)	128 (59–245)	0.113
Door-to-puncture time (min)	74 (55–101)	42 (30–61.5)	<0.001
Puncture to first balloon inflation (min)	18 (13–25)	15 (10–21)	<0.001
Door-to-reperfusion time < 60 min (%)	11.7 (31)	51.9 (152)	<0.001
Multivessel disease (%)	59 (157)	64.5 (189)	0.183
Left main obstructive disease (%)	7.9 (21)	7.2 (21)	0.745
Initial TIMI flow			0.227
≥ TIMI-2 (%)	32.3 (86)	27.6 (81)
≤ TIMI-1 (%)	67.7 (180)	72.2 (212)
Final TIMI flow			0.291
TIMI-3 flow (%)	94 (251)	96.2 (282)
≤ TIMI-2 flow (%)	5.6 (15)	3.8 (11)
Pre-PCI stenosis (%)	94.12 ± 9.21	94.09 ± 9.68	0.975
Pre-PCI MLD (mm)	0.17 ± 0.28	0.18 ± 0.31	0.782
Pre-PCI RLD (mm)	3.02 ± 0.70	3.05 ± 0.61	0.783
Post-PCI residual stenosis (%)	15.53 ± 8.56	14.98 ± 12.52	0.545
Post-PCI MLD (mm)	2.78 ± 0.66	2.76 ± 0.58	0.602
Post-PCI RLD (mm)	3.26 ± 0.57	3.27 ± 0.59	0.789
Thrombectomy (%)	62.8 (167)	51.9 (155)	0.018
PercuSurge distal protection (%)	51.9 (138)	24.1 (71)	<0.001
Primary stenting (%)
Bare metal stent	89.5% (238)	69.3% (203)	<0.001
Drug-eluting stent	10.5% (28)	30.7% (90)	<0.001
Final TIMI-3 flow in drug-eluting stent (%)	92.9 (26 of 28)	98.9 (89 of 90)	0.077
Final TIMI-3 flow in bare metal stent (%)	94.5 (225 of 238)	95.1 (193 of 203)	0.801
Acute or subacute stent thrombosis (%)	1.1 (3)	1 (3)	0.905
Left ventricular ejection fraction (%)	56.81 ± 16.42	56.48 ± 18.16	0.822
30-d mortality (%)	4.1 (11)	5.5 (16)	0.465
30-d combined endpoint^b (%)	18 (48)	16.7 (49)	0.680

DTB = door to balloon, NYHA Fc = New York Heart Association Functional Classification, TIMI = thrombolysis in myocardial infarction, PCI = percutaneous coronary intervention, MLD = minimal lumen diameter, RLD = reference lumen diameter.
^aDefined as congestive heart failure ≥ NYHA Fc-3.
^bDefined as the 30-d composite occurrence of major adverse clinical outcomes, including advanced congestive heart failure or 30-d death.
Data are expressed as mean (range) or % (n).

Table 3. Determined the Impact of Various Shortening Door-to-Balloon Timing on Offering the Benefit for the Patients Among 559 Patients.
Variables	Door-to-Balloon Time ≤ 30 (n = 36)	Door-to-Balloon Time > 30 (n = 523)	p
Door-to-balloon time ≤ 30 vs > 30 min
30-d mortality (%)	8.3 (3)	4.6 (24)	0.311
Final TIMI flow ≤ 2 (%)	2.8 (1)	4.8 (25)	0.581
Advanced CHF ≥ 3 (%)^a	22.2 (8)	14 (73)	0.173
Combined endpoint (%)^b	25 (9)	16.8 (88)	0.210
Variables	Door-to-Balloon Time ≤ 45 (n = 88)	Door-to-Balloon Time > 45 (n = 471)	p
Door-to-balloon time ≤ 45 vs > 45 min
30-d mortality (%)	5.7 (5)	4.7 (22)	0.685
Final TIMI flow ≤ 2 (%)	4.5 (4)	4.7 (22)	0.959
Advanced CHF ≥ 3 (%)^a	14.8 (13)	14.4 (68)	0.935
Combined endpoint (%)^b	15.9 (14)	17.6 (83)	0.697
Variables	Door-to-Balloon Time ≤ 60 (n = 183)	Door-to-Balloon Time > 60 (n = 376)	p
Door-to-balloon time ≤ 60 vs > 60 min
30-d mortality (%)	4.9 (9)	4.8 (18)	0.946
Final TIMI flow ≤ 2 (%)	3.8 (7)	5.1 (19)	0.518
Advanced CHF ≥ 3 (%)^a	14.8 (27)	14.4 (54)	0.902
Combined endpoint (%)^b	15.3 (28)	18.4 (69)	0.371

TIMI = thrombolysis in myocardial infarction, CHF = congestive heart failure.
^aDefined as CHF ≥ New York Heart Association Functional Class 3.
^bDefined as the 30-d composite occurrence of major adverse clinical outcomes, including advanced CHF or 30-d death.
Data are expressed as % (n).

Table 4. Benefit of Variable Durations From Chest Pain Onset to Reperfusion for ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention.
Variables	Pain Onset to First BT ≤ 240 Min (n = 263)	Pain Onset to First BT > 240 Min (n = 296)	p
Duration ≤ 240 vs > 240 min
CPK (IU/mL)	1,730 ± 1,907	2,315 ± 2,795	<0.001
LVEF (%)	57.9 ± 18.1	55.4 ± 16.6	0.095
30-d death (%)	3.8 (10)	5.7 (17)	0.285
Combined endpoint (%)^a	14.1 (37)	20.3 (60)	0.053
Variables	Pain Onset to First BT ≤ 180 Min (n = 158)	Pain Onset to First BT > 180 Min (n = 401)	p
>Duration ≤ 180 vs > 180 min
CPK (IU/mL)	1,636 ± 1,937	2,199 ± 2,588	0.014
LVEF (%)	58.7 ± 17.2	55.8 ± 17.3	0.078
30-d death (%)	2.5 (4)	5.7 (23)	0.112
Combined endpoint (%)^a	13.3 (21)	19 (76)	0.111
Variables	Pain Onset to First BT ≤ 120 Min (n = 66)	Pain Onset to First BT > 120 Min (n = 493)	p
>Duration ≤ 120 vs > 120 min
CPK (IU/mL)	1,791 ± 2,411	2,073 ± 2,433	0.376
LVEF (%)	60.9 ± 15.2	56.1 ± 17.5	0.003
30-d death (%)	1 (1.5)	5.3 (26)	0.181
Combined endpoint (%)^a	10.6 (7)	18.3 (90)	0.123

BT = balloon time, CPK = creatine phosphokinase, LVEF = left ventricular ejection fraction.
^aDefined as the 30-d composite occurrence of advanced congestive heart failure or 30-d death.
Data are expressed as mean ± sd.

Table 5. Univariate Analysis of Predictors for 30-Day Mortality.
Variables	OR	95% CI	p
Advance congestive heart failure ≥ 3^a	35.275	12.873–96.66	<0.001
Final thrombolysis in myocardial infarction flow ≤ 2	12.023	4.648–31.101	<0.001
Age	1.073	1.037–1.110	<0.001
Left ventricular ejection fraction	0.931	0.913–0.949	<0.001

OR = odds ratio.
^aDefined as congestive heart failure ≥ New York Heart Association Functional Class 3.

Table 6. Multiple Stepwise Logistic Regression Analysis of Predictors for 30-Day Mortality.
Variable	OR	95% CI	p
Advance congestive heart failure ≥ 3^a	19.398	5.764–65.279	<0.001
Final thrombolysis in myocardial infarction flow ≤ 2	6.006	1.255–28.737	0.025
Age	1.081	1.031–1.133	<0.001
Left ventricular ejection fraction	0.948	0.923–0.974	<0.001