Long Inflation at Stent Deployment in Intravascular Ultrasound-Guided Percutaneous Coronary Intervention for Acute Myocardial Infarction

Abstract

Background: There is a substantial risk of slow flow during percutaneous coronary intervention (PCI) for the culprit lesion in acute myocardial infarction (AMI), which can lead to adverse outcomes. We hypothesized that single-step long balloon inflation during stent deployment was associated with a more favorable final Thrombolysis in Myocardial Infarction (TIMI) flow grade. This retrospective study aimed to compare both the final TIMI flow grade and the delta TIMI flow grade in intravascular ultrasound (IVUS)-guided PCI for AMI between patients with long balloon inflation and those with conventional inflation.

Methods and Results: Long inflation was defined as single-step inflation ≥60 s at stent deployment. The primary endpoints were achievement of the final TIMI flow grade 3 and the delta TIMI flow grade, defined as the difference between the initial and final grades. We analyzed 336 AMI patients with attenuation plaque on IVUS, dividing them into a long inflation group (n=50) and a conventional inflation group (n=286). Despite a significantly higher TIMI thrombus grade in the long inflation group (P<0.001), the rate of the final TIMI 3 flow was similar (90% vs. 88.5%; P=1.00). However, the delta TIMI flow grade was significantly greater in the long inflation group (P=0.028).

Conclusions: Single-step long balloon inflation may be a simple and feasible method to achieve optimal final TIMI flow in IVUS-guided PCI for AMI.

Central Figure

Acute myocardial infarction (AMI) is still a life-threatening disease despite the development of primary percutaneous coronary intervention (PCI).^1,2 In primary PCI, final Thrombolysis in Myocardial Infarction (TIMI) flow grade affects the short-term and long-term clinical outcomes in patients with AMI.^3–5 The slow flow phenomenon during PCI for AMI is closely associated with periprocedural myocardial injury, which results in worse clinical outcomes.⁶ Therefore, distal protection devices or thrombus aspiration devices were developed to prevent slow flow in primary PCI.^7–9 However, major guidelines did not recommend either distal protection or routine thrombus aspiration because PCI with those devices did not show the clear clinical benefits compared with PCI without those devices.^10,11

Several studies have suggested that optimizing the stent inflation time might be associated with favorable outcomes.^12–14 In most clinical situations, the stent inflation time is approximately 30 s or less.¹⁵ However, there was no consensus on the stent deployment time. Ma et al. reported that the prolonged stent inflation time of ≥30 s could achieve better final TIMI flow grade than the conventional stent inflation time in PCI for STsegment elevation myocardial infarction (STEMI).¹⁶ Furthermore, long inflation with a perfusion balloon before stent implantation was associated with less in-stent tissue protrusion and better clinical outcomes in PCI for STEMI.¹⁷ Therefore, a long inflation time at stent deployment may result in a favorable final TIMI flow grade. Moreover, the presence of low attenuation plaque in intravascular ultrasound (IVUS) is closely associated with the slow flow phenomenon.^18–20 We hypothesized that single-step long inflation time at stent deployment was associated with better final TIMI flow grade in PCI for AMI with low attenuation plaque.

This study aimed to evaluate the impact of prolonged balloon inflation time during stent deployment on coronary reperfusion outcomes in patients with AMI with low attenuation plaque.

Methods

Study Patients

This was a single-center retrospective observational study at Saitama Medical Center, Jichi Medical University. We reviewed all patients with AMI (both STEMI and non-ST-segment elevation myocardial infarction [NSTEMI]) treated in Saitama Medical Center, Jichi Medical University between September 2021 and August 2024. We included consecutive cases of AMI that met the universal definition of AMI and those that were admitted to the cardiology department in our hospital. The exclusion criteria were: (1) patients without IVUS-guided stent deployment to the culprit lesion of AMI; (2) patients whose culprit of AMI was in-stent restenosis; (3) patients with poor IVUS images; (4) patients without low attenuation plaque; (5) patients without information of stent inflation time; and (6) patients with unclear final TIMI flow grade. The stent inflation time at stent deployment was evaluated in this study. Long inflation at stent deployment was defined as single-step stent inflation ≥60 s. We divided the study population into a long inflation group and a conventional inflation group. Clinical characteristics were compared between the long inflation group and the conventional inflation group. Laboratory data at admission, including hematological parameters (such as white blood cell count and hemoglobin levels) and biochemical tests (such as total protein and serum creatinine levels), were compared between the 2 groups. In-hospital clinical outcomes were acquired from hospital records. The primary endpoints were the achievement of final TIMI flow grade 3 and delta TIMI flow grade, which was defined as the difference between the initial TIMI flow grade and the final TIMI flow grade. This study was conducted in accordance with the Declaration of Helsinki and was approved by the institutional review board of Saitama Medical Center, Jichi Medical University on February 25, 2025 (S24-131), and written informed consent was waived because of the retrospective study design.

PCI Procedure

The procedure was initiated following the administration of unfractionated heparin, and the activated coagulation time was maintained over 250 s during procedures. The choice of PCI devices such as guidewires, balloons, imaging modalities and stents were left to the discretion of the operators. The initial and final TMI flow grades were recorded and assessed based on the results of coronary angiograms. Low attenuation plaque was defined as plaque accompanying backward signal attenuation without dense calcium.²⁰ In brief, we performed pre-dilatation and/or occasionally thrombus aspiration after guidewire insertion to the distal segment of the culprit lesion in AMI. Following pre-dilatation or thrombus aspiration, we performed IVUS and decided whether we should modify the culprit lesion further. The diameter and length of the deployed stent were determined based on the reference vessel diameter and lesion length assessed using IVUS. The duration of stent expansion was left to the discretion of the operators. Moreover, in most cases we evaluated IVUS again to decide whether to add a post-dilatation after stent deployment. The final TIMI flow grade was acquired at the end of PCI procedure.

Definition

AMI was defined based on the universal definition.²¹ Myocardial injury was defined as an elevation of serum troponin I levels above the 99th percentile of the upper reference limit.²¹ Diagnostic ST-elevation was characterized as a new ST elevation at the J-point in at least 2 contiguous leads of 2 mm (0.2 mV). Patients with AMI presenting with ST elevation were diagnosed as STEMI.²² In contrast, AMI patients without ST-segment elevation at presentation were defined as NSTEMI.²¹ Hypertension was defined as systolic blood pressure of >140 mmHg, diastolic blood pressure >90 mmHg, or medical treatment for hypertension.²³ Dyslipidemia was defined as a total cholesterol level ≥220 mg/dL, a low-density lipoprotein cholesterol level ≥140 mg/dL, the use of lipid-lowering medication, or a history of dyslipidemia.²³ Diabetes was defined as a hemoglobin A1c level ≥6.5% (National Glycohemoglobin Standardization Program value), the use of antidiabetic medication, or a prior diagnosis of diabetes.²³ The estimated glomerular filtration rate (eGFR) was calculated based on serum creatinine level, age, body weight, and sex using the following formula: eGFR = 194 × Cr^−1.094 × age^−0.287 for males, and eGFR = 194 × Cr^−1.094 × age^−0.287 × 0.739 for females.²⁴ TIMI thrombus grade was defined in accordance with a previous study.²⁵ IVUS findings were evaluated according to the clinical expert consensus document.²⁰ Quantitative coronary angiographic (QCA) analysis was used to determine the reference diameter, lesion length, and minimum diameter from the coronary angiogram.²⁶ In cases of total occlusion, QCA parameters were measured after achieving partial reperfusion (following balloon dilation or thrombectomy). Offline QCA analysis was conducted using Medis Suite 4.0 software (Medis Medical Imaging Systems, Leiden, The Netherlands).

Statistical Analysis

Data are expressed as mean±standard deviation (SD) for normally distributed continuous variables, and median (quartile 1–quartile 3) for non-parametric variables. Categorical variables are presented as numbers (percentage) and compared with a Fisher’s exact test. The Kolmogorov-Smirnov test was performed to determine if the continuous variables were normally distributed. Normally distributed continuous variables were compared between the groups using an unpaired Student t-test. Otherwise, continuous variables were compared using a Mann-Whitney U-test. A P value of <0.05 was considered statistically significant. All analyses were performed using the statistical software SPSS 28.0/Windows (SPSS, Chicago, IL, USA).

Results

From September 2021 to August 2024, a total of 857 patients with AMI were hospitalized in our medical center. AMI patients who underwent primary PCI with stent deployment to the culprit lesion with low attenuation plaque (n=336) were included as the final study population, which was then divided into the long inflation group (n=50) and the conventional inflation group (n=286; Figure 1).

Figure 1.

Study flow chart. The final study population was divided into a long inflation group and a conventional group, according to the inflation procedure at stent deployment. If balloon time was ≥60 s and a single step of inflation, the case was classified into the long inflation group. Cases with other types of stent inflation were classified into the conventional inflation group. AMI, acute myocardial infarction; IVUS, intravascular ultrasound; PCI, percutaneous coronary intervention; TIMI, Thrombolysis in Myocardial Infarction.

Table 1 shows the comparison of patient characteristics between the 2 groups. The long inflation group was significantly younger than the conventional inflation group. The prevalence of STEMI was significantly higher in the long inflation group compared with the conventional inflation group.

Table 1.

Patient Characteristics Between the Long Inflation and Conventional Inflation Groups

	Total population (n=336)	Long inflation group (n=50)	Conventional inflation group (n=286)	P value
Age (years)	72.0 (61.0–80.0)	64.5 (52.7–78.5)	73.0 (62.0–80.2)	0.016
Male sex	268 (79.8)	44 (88.0)	224 (78.3)	0.130
Body mass index (kg/m2)	23.7 (21.4–26.3) [n=335]	24.8 (21.8–27.4)	23.7 (21.3–26.0) [n=285]	0.073
Systolic blood pressure (mmHg)	140 (18–158)	138 (117–149)	141 (118–160)	0.193
Diastolic blood pressure (mmHg)	87 (72–100)	87 (75–103)	87 (72–100)	0.688
Heart rate (beats/min)	80 (65–96)	74 (65–90)	81 (66–97)	0.169
Hypertension	219 (65.2)	30 (60.0)	189 (66.1)	0.424
Dyslipidemia	188 (56.0)	29 (58.0)	159 (5.6)	0.877
Diabetes	152 (45.2)	26 (52.0)	126 (44.1)	0.356
Current smoking	105 (31.3)	17 (34.0)	88 (30.8)	0.741
Hemodialysis	2 (0.6)	0 (0.0)	2 (0.7)	1.00
Previous history of myocardial infarction	23 (6.8)	2 (4.0)	21 (7.3)	0.550
Previous history of PCI	30 (8.9)	2 (4.0)	28 (9.8)	0.281
Previous history of CABG	4 (1.2)	1 (2.0)	3 (1.0)	1.00
Shock status on arrival	60 (17.9)	12 (24.0)	48 (16.8)	0.231
CPA on/before arrival	25 (7.4)	4 (8.0)	21 (7.3)	0.775
Clinical situation on admission				0.011
STEMI	215 (64.0)	40 (80.0)	175 (61.2)
NSTEMI	121 (36.0)	10 (20.0)	111 (38.8)
Killip classification				0.095
1	219 (65.2)	32 (64.0)	187 (65.4)
2	22 (6.5)	4 (8.0)	18 (6.3)
3	33 (9.8)	1 (2.0)	32 (11.2)
4	62 (18.5)	13 (26.0)	49 (17.1)
Left ventricular ejection fraction (%)	47.8 (35.9–60.0)	44.9 (39.0–54.1)	49.5 (35.5–60.7)	0.167
Valvular heart disease	23 (6.8)	4 (8.0)	19 (6.6)	0.760
Medication at admission
ACEi and/or ARB	134 (40.7) [n=329]	16 (32.0)	118 (42.3) [n=279]	0.211
β-blockers	50 (15.2) [n=329]	3 (6.0)	47 (16.8) [n=279]	0.054
Statins	103 (30.6) [n=329]	14 (28.0)	89 (31.6) [n=282]	0.740
Aspirins	51 (15.4) [n=329]	4 (8.0)	47 (16.7) [n=282]	0.139
Thienopyridines	26 (7.8) [n=329]	1 (2.0)	25 (8.9) [n=282]	0.149
Warfarin or direct oral anticoagulants	15 (4.5) [n=329]	2 (4.0)	13 (4.6) [n=282]	1.00
Oral anti-diabetes agents	104 (31.3) [n=329]	17 (34.0)	87 (30.9) [n=282]	0.741
Insulin	15 (4.5) [n=330]	3 (6.0)	12 (4.2) [n=283]	0.479

Data are expressed as median (quartile 1–quartile 3) for non-parametric continuous variables. Categorical variables are presented as n (%). ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CABG, coronary artery bypass grafting; CPA, cardiopulmonary arrest; NSTEMI, non-ST elevation myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST elevation myocardial infarction.

Table 2 shows the laboratory results between the long inflation and conventional inflation groups. The serum hemoglobin level and serum albumin level were significantly greater in the long inflation group than in the conventional inflation group. Peak creatine phosphokinase and creatine phosphokinase myocardial band (CK-MB) levels were significantly higher in the long inflation group than in the conventional inflation group.

Table 2.

Laboratory Results Between Long Inflation and Conventional Inflation Groups

	Total population (n=336)	Long inflation group (n=50)	Conventional inflation group (n=286)	P value
Laboratory data
White blood cell count (/μL)	8,910 (7,122–11,547)	9,305 (7,502–12,052)	8,805 (7,017–11,405)	0.370
Hemoglobin (g/dL)	14.0 (12.8–15.2)	14.8 (13.7–15.8)	13.9 (12.6–15.1)	<0.001
Total protein (g/dL)	6.8 (6.4–7.3)	6.9 (6.3–7.5)	6.8 (6.4–7.2)	0.302
Serum albumin (g/dL)	3.9 (3.5–4.2)	4.0 (3.7–4.6)	3.9 (3.5–4.2)	0.004
Serum creatinine (mg/dL)	0.91 (0.72–1.12)	0.95 (0.72–1.12)	0.91 (0.72–1.12)	0.980
eGFR (mL/min/1.73 m2)	62.1 (45.8–78.9)	63.0 (49.9–85.2)	62.0 (44.5–78.6)	0.280
C-reactive protein (mg/dL)	0.22 (0.10–0.84)	0.18 (0.08–0.61)	0.22 (0.10–0.92)	0.201
B-type natriuretic peptide (pg/mL)	97.0 (28.1–451.2) [n=329]	47.2 (19.6–251.6) [n=49]	104.1 (34.2–516.6) [n=280]	0.026
Total cholesterol (mg/dL)	175 (147–204) [n=335]	178 (142–209)	173 (147–204) [n=285]	0.619
Triglyceride (mg/dL)	101 (71–147) [n=335]	113 (75–150)	99 (70–146) [n=285]	0.327
LDL-cholesterol (mg/dL)	105 (81–134) [n=334]	106 (73–154)	105 (82–132) [n=284]	0.805
HDL-cholesterol (mg/dL)	43 (36–50) [n=333]	42 (34–48) [n=49]	43 (36–51) [n=284]	0.164
HbA1c (%)	6.2 (5.7–6.9) [n=334]	6.3 (5.7–6.9)	6.1 (5.7–6.9) [n=284]	0.799
Peak CPK level (mg/dL)	1,207 (299–2,893)	3,210 (1,055–5,014)	1,041 (257–2,427)	<0.001
Peak CK-MB level (mg/dL)	96 (19–288)	289 (70–444)	75 (17–220)	<0.001
In-hospital mortality	18 (5.4)	5 (10.0)	13 (4.5)	0.162

Data are expressed as median (quartile 1–quartile 3) for non-parametric continuous variables. Categorical variables are presented as n (%). CK-MB, creatine phosphokinase myocardial band; CPK, creatine phosphokinase; eGFR, estimated glomerular filtration rate; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; LDL, low-density lipoprotein.

Table 3 shows the comparisons of coronary angiogram and PCI procedure findings between the 2 groups. The median of the maximum time during stent deployment was significantly different between the 2 groups (60 s in the long inflation group vs. 15 s in the conventional inflation group; P<0.001) The ratio of TIMI thrombus grade of 5 was significantly greater in the long inflation group than in the conventional inflation group. The long inflation group frequently required the support of extracorporeal membrane oxygenation (ECMO) and deployment of durable polymer everolimus-eluting stent compared with the conventional inflation group. The degree of initial TIMI flow grade was significantly worse in the long inflation group than in the conventional inflation group.

Table 3.

Coronary Angiogram and PCI Procedure Findings Between the Long Inflation and Conventional Inflation Groups

	Total population (n=336)	Long inflation group (n=50)	Conventional inflation group (n=286)	P value
PCI procedure-related factors
Approach site details				0.237
Radial approach	293 (87.2)	40 (80.0)	253 (88.5)
Brachial approach	1 (0.3)	0 (0.0)	1 (0.3)
Femoral approach	42 (12.5)	10 (20.0)	32 (11.2)
Guiding catheter size				0.848
6Fr	291 (86.6)	43 (86.0)	248 (86.7)
7Fr	44 (13.1)	7 (14.0)	37 (12.9)
8Fr	1 (0.3)	0 (0.0)	1 (0.3)
Index PCI situation				0.064
Elective PCI	100 (29.8)	9 (18.0)	91 (31.8)
Emergent PCI	236 (70.2)	41 (82.0)	195 (68.2)
Temporary pacemaker support	6 (1.8)	0 (0.0)	6 (2.1)	0.597
Intra-aortic balloon pumping usage	22 (6.5)	4 (8.0)	18 (6.3)	0.551
Percutaneous cardiopulmonary support	17 (5.1)	7 (14.0)	10 (3.5)	0.006
Pre-dilatation usage	324 (96.4)	47 (94.0)	277 (96.9)	0.398
Pre-dilatation diameter (mm)	2.00 (2.00–2.00) [n=324]	2.00 (2.00–2.00) [n=47]	2.00 (2.00–2.00) [n=277]	0.130
Pre-dilatation max pressure (atm)	12 (8–14) [n=323]	10 (8–14) [n=47]	12 (8–14) [n=276]	0.263
Post-dilatation usage	195 (58.0)	20 (40.0)	175 (61.2)	0.008
Post-dilatation diameter (mm)	3.00 (2.75–3.75) [n=195]	3.50 (3.00–3.75) [n=20]	3.00 (2.75–3.75) [n=175]	0.377
Post-dilatation max pressure (atm)	20 (16–20) [n=194]	18 (12–20) [n=20]	20 (16–20) [n=174]	0.023
Aspiration usage	13 (3.9)	2 (4.0)	11 (3.8)	1.00
Perfusion balloon usage	17 (5.1)	5 (10.0)	12 (4.2)	0.151
Isosorbide dinitrate administration	252 (75.0)	33 (66.0)	219 (76.6)	0.115
Nicorandil administration	132 (39.3)	23 (46.0)	109 (38.1)	0.347
Nitroprusside administration	47 (14.0)	13 (26.0)	34 (11.9)	0.014
No. deployed stents (n)	1.0 (1.0–1.0)	1.0 (1.0–1.0)	1.0 (1.0–1.0)	0.570
Total stent length (mm)	28.0 (23.0–38.0)	28.0 (23.0–38.0)	28.0 (23.0–38.0)	0.778
Diameter of stent at culprit lesion (mm)	2.75 (2.50–3.00)	3.00 (2.50–3.00)	2.75 (2.50–3.00)	0.003
Length of stent at culprit lesion (mm)	28.0 (23.0–33.0)	28.0 (23.0–33.0)	28.0 (23.0–33.0)	0.569
Details of stent deployed at culprit lesion				0.006
Durable polymer Everolimus eluting stent	271 (80.7)	49 (98.0)	222 (77.6)
Durable polymer Zotarolimus eluting stent	18 (5.4)	1 (2.0)	17 (5.9)
Biodegradable polymer Everolimus stent	36 (10.7)	0 (0.0)	36 (12.6)
Biodegradable polymer Sirolimus stent	10 (3.0)	0 (0.0)	10 (3.5)
Polymer free Biolimus A9 stent	1 (0.3)	0 (0.0)	1 (0.3)
Maximum pressure at stent deployment (atm)	14 (12–16)	14 (12–14)	14 (12–16)	0.693
Maximum inflation time at stent deployment (s)	20 (15–30)	60 (60–60)	15 (15–20)	<0.001
Infarct-related artery				0.099
LMT and/or LAD artery	160 (47.6)	19 (38.0)	141 (49.3)
LCX artery	55 (16.4)	6 (12.0)	49 (17.2)
RCA	121 (36.1)	25 (50.0)	96 (33.7)
Ostial lesion	12 (3.6)	0 (0.0)	12 (4.2)	0.226
Bifurcation lesion	181 (53.9)	23 (46.0)	158 (55.2)	0.282
TIMI thrombus grade				<0.001
1	150 (44.6)	10 (20.0)	140 (49.0)
2	22 (6.5)	3 (6.0)	19 (6.6)
3	18 (5.4)	5 (10.0)	13 (4.5)
4	4 (1.2)	2 (4.0)	2 (0.7)
5	142 (42.3)	30 (60.0)	112 (39.2)
No. injured coronary artery				0.099
1	151 (44.9)	23 (46.0)	128 (44.8)
2	104 (31.0)	10 (20.0)	94 (32.9)
3	81 (24.1)	17 (34.0)	64 (22.4)
Prevalence of chronic total occlusion	44 (13.1)	5 (10.0)	39 (13.6)	0.65
Initial TIMI flow grade				0.039
0	140 (41.7)	30 (60.0)	110 (38.5)
1	28 (8.3)	4 (8.0)	24 (8.4)
2	144 (42.9)	14 (28.0)	130 (45.5)
3	24 (7.1)	2 (4.0)	22 (7.7)

Data are expressed as median (quartile 1–quartile 3) for non-parametric variables. Categorical variables are presented as n (%). LAD, left anterior descending; LCX, left circumflex; LMT, left main trunk; PCI, percutaneous coronary intervention; RCA, right coronary artery; TIMI, Thrombolysis in Myocardial Infarction.

Table 4 shows the comparisons of QCA and IVUS findings between the 2 groups. The prevalence of thrombus on IVUS was significantly greater in the long inflation group than in the conventional inflation group. The percentage area stenosis rate on QCA was significantly larger in the long inflation group than in the conventional inflation group.

Table 4.

QCA and IVUS Findings Between the Long Inflation and Conventional Inflation Groups

	Total population (n=336)	Long inflation group (n=50)	Conventional inflation group (n=286)	P value
QCA findings
Reference diameter (mm)	2.5 (2.1–2.8)	2.5 (2.1–2.9)	2.5 (2.1–2.8)	0.450
Percent stenosis rate (area stenosis; %)	99.4 (97.7–100)	100 (98.2–100)	99.2 (97.6–100)	0.018
Minimum diameter (mm)	0.2 (0.0–0.4)	0.0 (0.0–0.3)	0.2 (0.0–0.4)	0.020
Lesion length (mm)	11.0 (8.8–14.4)	12.3 (8.9–16.2)	10.9 (8.6–14.1)	0.111
Post percent stenosis rate (area stenosis; %)	19.9 (11.8–27.4)	18.7 (15.1–26.8)	20.0 (11.2–27.5)	0.764
Obstruction diameter (mm)	2.5 (2.3–2.8)	2.6 (2.4–2.9)	2.5 (2.3–2.8)	0.170
IVUS findings
Remodeling type				0.947
Positive remodeling	99 (29.5)	14 (28.0)	85 (29.7)
Non-remodeling	230 (68.5)	35 (70.0)	195 (68.2)
Negative remodeling	7 (2.1)	1 (2.0)	6 (2.1)
Plaque type of culprit lesion				0.167
Hypo-echoic plaque	175 (52.1)	31 (62.0)	144 (50.3)
Hyper non-calcification plaque	0 (0.0)	0 (0.0)	0 (0.0)
Hyper calcification plaque	0 (0.0)	0 (0.0)	0 (0.0)
Mixed plaque	161 (47.9)	19 (38.0)	142 (49.7)
Presence of thrombus	146 (43.5)	31 (62.0)	115 (40.2)	0.005
Culprit lesion
External elastic membrane area (mm2)	15.8 (12.4–18.9)	17.5 (14.7–21.2)	15.3 (12.2–18.7)	0.002
Plaque area (mm2)	13.8 (10.7–17.0)	15.5 (12.7–19.2)	13.3 (10.5–16.7)	0.003
Lumen area (mm2)	1.7 (1.6–2.0)	1.9 (1.7–2.2)	1.7 (1.5–2.0)	0.006

Data are expressed as median (quartile 1–quartile 3) for non-parametric continuous variables. Categorical variables are presented as n (%). IVUS, intravascular ultrasound; QCA, quantitative coronary angiography.

Table 5 shows comparisons of final and delta TIMI flow grade between the 2 groups. The final TIMI flow grade was similarly favorable in both groups. The delta TIMI flow grade was larger in the long inflation group than in the conventional inflation group. In the long inflation group, all cases with an initial TIMI flow grade ≤2 showed improvement in the TIMI flow grade, while all cases with an initial TIMI flow grade of 3 achieved a final TIMI flow grade of 3 (Figure 2). In the conventional inflation group, 9 cases with an initial TIMI flow ≤2 did not show improvement in the TIMI flow grade (Figure 3).

Table 5.

Final and Delta TIMI Flow Grade Between the Long Inflation and Conventional Inflation Groups

	Total population (n=336)	Long inflation group (n=50)	Conventional inflation group (n=286)	P value
Final TIMI flow grade				1.00
0	0 (0.0)	0 (0.0)	0 (0.0)
1	3 (0.9)	0 (0.0)	3 (1.0)
2	35 (10.4)	5 (10.0)	30 (10.5)
3	298 (88.7)	45 (90.0)	253 (88.5)
Delta TIMI flow grade				0.028
0	33 (9.8)	2 (4.0)	31 (10.8)
1	143 (42.6)	15 (30.0)	128 (44.8)
2	44 (13.1)	7 (14.0)	37 (12.9)
3	116 (34.5)	26 (52.0)	90 (31.5)

Categorical variables are presented as n (%) and compared with the Fisher’s exact test. TIMI, Thrombolysis in Myocardial Infarction.

Figure 2.

Delta Thrombolysis in Myocardial Infarction (TIMI) flow grade in the long inflation group. The changes from initial to final TIMI flow grade were as follows. Among patients with an initial TIMI flow grade of 3 (n=2), all maintained a final TIMI flow grade of 3. Similarly, all patients with an initial TIMI flow grade of 2 (n=14) achieved a final TIMI flow grade of 3. Among those with an initial TIMI flow grade of 1 (n=4), 3 patients achieved a final TIMI flow grade of 3, while 1 had a final TIMI flow grade of 2. In the initial TIMI 0 group (n=30), 26 patients achieved a final TIMI flow grade of 3, and the remaining 4 had a final TIMI flow grade of 2. Notably, there were no cases in which the TIMI flow grade worsened from the initial to the final assessment.

Figure 3.

Delta Thrombolysis in Myocardial Infarction (TIMI) flow grade in the conventional inflation group. The transition from initial to final TIMI flow grades was as follows. In the initial TIMI 3 group (n=22), all patients maintained a final TIMI flow grade of 3. In the initial TIMI 2 group (n=130), 122 patients achieved a final TIMI flow grade of 3, while 8 remained at grade 2. Among those with an initial TIMI flow grade of 1 (n=24), 19 achieved a final grade of 3, 4 remained at grade 2, and 1 remained at grade 1. In the initial TIMI 0 group (n=110), 90 patients achieved a final TIMI flow grade of 3, 18 reached grade 2, and the remaining 2 patients had a final grade of 1. Notably, no cases demonstrated a deterioration in TIMI flow grade from the initial to the final assessment.

We conducted the sensitivity analysis using various thresholds for long inflation as ≥30 s, ≥45 s, ≥75 s, and ≥90 s (Supplementary Tables 1–4, respectively). In addition, we compared the TIMI flow grade in patients with an initial TIMI flow grade 0–1 to evaluate the influence of the initial TIMI flow grade. The outcomes were comparable between the long inflation and conventional groups with an initial TIMI flow grade 0–1 (Supplementary Table 5).

Discussion

We included 336 patients with AMI who underwent IVUS-guided PCI for the culprit lesion with low attenuation plaque and classified them into a long inflation group (n=50) and a conventional inflation group (n=286). The prevalence of STEMI was higher in the long inflation group, and the initial TIMI flow grade or TIMI thrombus grade was worse in the long inflation group than in the conventional group. Larger plaque burden area and a greater presence of thrombus on IVUS were frequently detected in the long inflation group than in the conventional inflation group. Furthermore, mechanical support with percutaneous cardiopulmonary support was more frequently used in the long inflation group. The use of percutaneous cardiopulmonary support does not necessarily lead to an improvement in the final TIMI flow grade, whereas the need for cardiopulmonary support often reflects the severity of the patient’s systemic condition.^27,28 Despite the more severe lesion and clinical characteristics, the final TIMI flow grade in the long inflation group was comparable with that in the conventional group. The delta TIMI flow grade was significantly higher in the long inflation group than in the conventional inflation group (P=0.028). An initial TIMI flow grade ≤1 was reported as an independent factor related to a worse final TIMI flow grade.²⁶ Although the initial TIMI flow grade was worse in the long inflation group, the final TIMI flow grade showed no significant difference between the 2 groups. This suggested that long inflation might have a beneficial effect in preserving coronary blood flow, as indicated by the delta TIMI flow grade. These results may support the usefulness of single-step long inflation at stent deployment for the culprit lesion of AMI.

Several previous studies showed the prolonged balloon inflation could achieve an appropriate stent expansion and reduce a stent malapposition, but did not reveal the relationship between the prolonged stent inflation time and the clinical impacts such as achievement of a favorable final TIMI flow grade.^12,14,29,30 These studies suggest that achieving adequate stent expansion might require a very long time (100–200 s).^12,14 Meanwhile, Ma et al. revealed that prolonged balloon inflation during stent deployment was associated with achievement of the favorable final TIMI flow grade and prevention of the slow flow phenomenon, compared with conventional balloon inflation.¹⁶ Although the study defined the prolonged balloon inflation duration as ≥30 s,¹⁶ it might be difficult to have a consensus that ≥30 s inflation is deemed as long inflation based on previous studies.^12,14,29,31 Our study arbitrarily defined ≥60 s inflation as long inflation, because ≥30 s is too short, and 100–200 s is too long for long inflation.

It is important to discuss the reason why single-step long inflation at stent deployment could improve coronary flow. Although the mechanism is not clearly explained, long inflation at stent deployment might work as the long compression toward vulnerable plaque or thrombus. It is reported that long compression by perfusion balloon reduced the risk of plaque protrusion into the stent strut.¹⁷ Therefore, long compression at stent deployment might result in less flow disturbance due to micro-embolization after stent deployment. In conventional stent deployment, we usually repeat inflation and deflation several times.^32,33 The culprit lesion of AMI contains fragile tissue such as lipid deposition with foam cells, cholesterol crystals, and thrombus.^34,35 If the plaques are vulnerable, distal embolization may occur following repeated inflation and deflation. In terms of preventing distal embolization, single-step inflation for 60 s may be better than 2-step inflation for a total of 60 s (i.e., 30 s and 30 s) or 3-step inflation for a total of 60 s (i.e., 20 s, 20 s, and 20 s). In this study, the deployed stent diameter in the long inflation group was significantly larger than that in the conventional inflation group, while incidence of the slow-flow phenomenon remained comparable between the 2 groups. Previous studies have reported that larger stent diameters are associated with a higher risk of slow-flow and worse final TIMI flow grades in the setting of AMI.^18,19 Therefore, the long inflation strategy might be preferable when a large stent was selected for the culprit lesion of AMI.

There may be concerns regarding the safety and feasibility of long balloon inflation at stent deployment. First, we utilized this procedure for the culprit lesions of AMI, which were mostly occluded or semi-occluded. These lesions would have tolerance to myocardial ischemia as compared with non-occluded lesions. Therefore, a balloon inflation duration ≥60 s would be acceptable in terms of safety. The main advantage of long inflation is its simplicity. Long inflation does not require complicated procedures or additional devices such as distal protection devices. The use of additional devices might lead to additional complications.^36–39

Study Limitations

First, as the present study was a single-center retrospective observational study, there is a risk of selection bias. Second, although the study patients were selected from a modest sample size (n=857), the sample size for the long inflation group was small (n=50). Third, the number of patients in the long inflation group (n=50) was approximately 15% of the total study population (n=336). This imbalance hinders generalization of the study results. In addition, we focused on AMI, which included both STEMI and NSTEMI. It may be scientifically more valuable to focus on STEMI (or NSTEMI), because the epidemiological characteristics and plaque pathology are different between STEMI and NSTEMI. However, we did not separate AMI because of the small sample size in the long inflation group. Fourth, the severity of clinical backgrounds in the long inflation group required less isosorbide dinitrate and more nitroprusside than in the conventional inflation group. This difference in vasodilator usage might affect the final TIMI flow grade. Although the delta TIMI flow grade was larger in the long inflation group, the delta TIMI flow grade would be influenced by the initial TIMI flow grades. Since the initial TIMI flow grade in the long inflation group was worse in the long inflation group, the significant difference of the delta TIMI flow grade might be due to the significant difference of the initial TIMI flow grade. In contrast, the final TIMI flow grade was similar despite worse initial TIMI flow grades in the long inflation group. Similar final TIMI flow grades may be more important results for the long inflation strategy than the higher delta TIMI flow grade in the present study. Fifth, since total occlusion was frequently observed in the culprit lesion of STEMI, QCA parameters were measured after the acquisition of some reperfusion. Therefore, these QCA parameters might not reflect the original occlusion length or reference diameter, especially in the long inflation group. Sixth, although we provided peak creatine pkinase (CK) and CK-MB in Table 2, our study population included patients with >24 h of onset of AMI. Therefore, we might not have captured true peak CK and CK-MB in these patients. Seventh, although we did not notice a disadvantage of long inflation during clinical practice, there is a possibility that severe chest pain may occur due to the prolonged ischemia. However, the risk of severe chest pain may be less when long inflation is performed to the culprit lesion of AMI as compared with the culprit lesion of stable angina. Moreover, because 60 s as the cut-off for long inflation was arbitrary, we conducted the sensitivity analysis using a different cut-off for long inflation. The results of each sensitivity analysis showed similar trends compared with the main analysis using 60s, while the number of the long inflation group was very small when using ≥75 s or ≥90 s as a cut-off. Additionally, we should acknowledge that the single-step long inflation technique was developed to prevent slow flow at stent deployment rather than to enhance stent expansion. The single-step long inflation technique might not be a suitable approach when the primary purpose is optimal stent expansion. Furthermore, although the selection of stent types was left to the discretion of operators, a durable polymer everolimus-eluting stent was frequently selected in the long inflation group. The higher prevalence of STEMI and the higher TIMI thrombus grade in the long inflation group might be associated with higher usage of a durable polymer everolimus-eluting stent, partly because of robust evidence for a durable polymer everolimus-eluting stent regarding STEMI and an antithrombotic property.^40–42 Last, we could not perform multivariate analysis because of the insufficient number of the final TIMI flow grade ≤2. Therefore, further studies are required to show the superiority of the long inflation technique over the conventional inflation technique.

Conclusions

Despite the more severe lesion characteristics, the final TIMI flow grade was equally favorable in the long inflation group as compared with that in the conventional inflation group. The delta TIMI flow grade was significantly greater in the long inflation group than in the conventional inflation group. The concept of single-step long balloon inflation at stent deployment may be a simple and feasible option to acquire the optimal final TIMI flow grade in IVUS-guided PCI for AMI.

Acknowledgments

The authors acknowledge all staff in the catheter laboratory, cardiology units, and emergency and critical care units in Saitama Medical Center, Jichi Medical University, for their technical support in this study.

Disclosures

K.S. received speaking honorarium from Boston Scientific. This research received no external funding.

IRB Information

The present study was approved by the institutional review board of Saitama Medical Center, Jichi Medical University (reference no. S24-131).

Data Availability

The deidentified participant data will not be shared.

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circrep.CR-25-0141

References

• 1.   Thrane PG, Olesen KKW, Thim T, Gyldenkerne C, Hansen MK, Stødkilde-Jørgensen N, et al. 10-year mortality after ST-segment elevation myocardial infarction compared to the general population. J Am Coll Cardiol 2024; 83: 2615–2625.
• 2.   Seiyama K, Oka A, Miyoshi T, Sudo Y, Takagi W, Ugawa S, et al. Impact of an intensive lipid-lowering therapy protocol on achieving target low-density lipoprotein cholesterol levels in patients with acute coronary syndrome. Circ Rep 2025; 7: 131–138.
• 3.   Murakami T, Sakakura K, Jinnouchi H, Taniguchi Y, Tsukui T, Hatori M, et al. Development of a simple prediction model for mechanical complication in ST-segment elevation myocardial infarction patients after primary percutaneous coronary intervention. Heart Vessels 2024; 39: 288–298.
• 4.   Zachura M, Wilczek K, Janion M, Gąsior M, Gierlotka M, Sadowski M. Long-term outcomes in men and women with ST-segment elevation myocardial infarction and incomplete reperfusion after a primary percutaneous coronary intervention: A 2-year follow-up. Coron Artery Dis 2019; 30: 171–176.
• 5.   Caixeta A, Lansky AJ, Mehran R, Brener SJ, Claessen B, Généreux P, et al. Predictors of suboptimal TIMI flow after primary angioplasty for acute myocardial infarction: Results from the HORIZONS-AMI trial. EuroIntervention 2013; 9: 220–227.
• 6.   Armillotta M, Bergamaschi L, Paolisso P, Belmonte M, Angeli F, Sansonetti A, et al. Prognostic relevance of type 4a myocardial infarction and periprocedural myocardial injury in patients with non-ST-segment-elevation myocardial infarction. Circulation 2025; 151: 760–772.
• 7.   Ikari Y, Sakurada M, Kozuma K, Kawano S, Katsuki T, Kimura K, et al. Upfront thrombus aspiration in primary coronary intervention for patients with ST-segment elevation acute myocardial infarction: Report of the VAMPIRE (VAcuuM asPIration thrombus REmoval) trial. JACC Cardiovasc Interv 2008; 1: 424–431.
• 8.   Ito N, Nanto S, Doi Y, Kurozumi Y, Tonomura D, Natsukawa T, et al. Distal protection during primary coronary intervention can preserve the index of microcirculatory resistance in patients with acute anterior ST-segment elevation myocardial infarction. Circ J 2011; 75: 94–98.
• 9.   Hibi K, Kozuma K, Maejima N, Sonoda S, Endo T, Tanaka H, et al. Long-term clinical outcomes after filter protection during percutaneous coronary intervention in patients with attenuated plaque: 1-year follow up of the VAMPIRE 3 (Vacuum Aspiration Thrombus Reemoval 3) trial. Circ J 2020; 85: 44–49.
• 10.   Lawton JS, Tamis-Holland JE, Bangalore S, Bates ER, Beckie TM, Bischoff JM, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: Executive summary: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2022; 79: 197–215.
• 11.   Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J 2023; 44: 3720–3826.
• 12.   Vallurupalli S, Bahia A, Ruiz-Rodriguez E, Ahmed Z, Hakeem A, Uretsky BF. Optimization of stent implantation using a high pressure inflation protocol. Catheter Cardiovasc Interv 2016; 87: 65–72.
• 13.   Pinton FA, Lemos PA. Inflation time in stent deployment: How long is enough? Catheter Cardiovasc Interv 2016; 87: 73–74.
• 14.   Cook JR, Mhatre A, Wang FW, Uretsky BF. Prolonged high-pressure is required for optimal stent deployment as assessed by optical coherence tomography. Catheter Cardiovasc Interv 2014; 83: 521–527.
• 15.   Saad M, Bavineni M, Uretsky BF, Vallurupalli S. Improved stent expansion with prolonged compared with short balloon inflation: A meta-analysis. Catheter Cardiovasc Interv 2018; 92: 873–880.
• 16.   Ma M, Wang L, Diao KY, Liang SC, Zhu Y, Wang H, et al. A randomized controlled clinical trial of prolonged balloon inflation during stent deployment strategy in primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: A pilot study. BMC Cardiovasc Disord 2022; 22: 30.
• 17.   Nishino M, Egami Y, Nakamura H, Abe M, Ohsuga M, Nohara H, et al. Clinical impact of perfusion balloon for ST-segment elevated myocardial infarction: RYUSEI study. Am J Cardiol 2024; 223: 43–51.
• 18.   Watanabe Y, Sakakura K, Taniguchi Y, Yamamoto K, Wada H, Momomura SI, et al. Determinants of slow flow in percutaneous coronary intervention to the culprit lesion of non-ST elevation myocardial infarction. Int Heart J 2018; 59: 1237–1245.
• 19.   Watanabe Y, Sakakura K, Taniguchi Y, Yamamoto K, Wada H, Fujita H, et al. Determinants of slow flow following stent implantation in intravascular ultrasound-guided primary percutaneous coronary intervention. Heart Vessels 2018; 33: 226–238.
• 20.   Saito Y, Kobayashi Y, Fujii K, Sonoda S, Tsujita K, Hibi K, et al. CVIT 2025 clinical expert consensus document on intravascular ultrasound. Cardiovasc Interv Ther 2025; 40: 211–225.
• 21.   Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth universal definition of myocardial infarction (2018). Eur Heart J 2019; 40: 237–269.
• 22.   Kobayashi S, Sakakura K, Jinnouchi H, Taniguchi Y, Tsukui T, Hatori M, et al. Impact of controlled blood pressure and pulse rate at discharge on clinical outcomes in patients with ST-segment elevation myocardial infarction. J Cardiol 2024; 83: 394–400.
• 23.   Watanabe Y, Sakakura K, Taniguchi Y, Adachi Y, Noguchi M, Akashi N, et al. Determinants of in-hospital death in acute myocardial infarction with triple vessel disease. Int Heart J 2016; 57: 697–704.
• 24.   Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 2009; 53: 982–992.
• 25.   Celik T, Balta S, Ozturk C, Kaya MG, Aparci M, Yildirim OA, et al. Predictors of no-reflow phenomenon in young patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Angiology 2016; 67: 683–689.
• 26.   Suzuki N, Asano T, Nakazawa G, Aoki J, Tanabe K, Hibi K, et al. Clinical expert consensus document on quantitative coronary angiography from the Japanese Association of Cardiovascular Intervention and Therapeutics. Cardiovasc Interv Ther 2020; 35: 105–116.
• 27.   Saito Y, Tateishi K, Kobayashi Y. Clinical review of cardiogenic shock after acute myocardial infarction: Revascularization, mechanical circulatory support, and beyond. Circ Rep 2025; 7: 6–14.
• 28.   Choe JC, Lee SH, Ahn JH, Lee HW, Oh JH, Choi JH, et al. Adjusted mortality of extracorporeal membrane oxygenation for acute myocardial infarction patients in cardiogenic shock. Medicine (Baltimore) 2023; 102: e33221.
• 29.   Kawasaki T, Koga H, Serikawa T, Orita Y, Ikeda S, Mito T, et al. Impact of a prolonged delivery inflation time for optimal drug-eluting stent expansion. Catheter Cardiovasc Interv 2009; 73: 205–211.
• 30.   Asano T, Kobayashi Y, Fukushima K, Iwata Y, Kitahara H, Ishio N, et al. Effect of balloon inflation time on expansion of sirolimus-eluting stent. Heart Vessels 2009; 24: 335–339.
• 31.   Hovasse T, Mylotte D, Garot P, Salvatella N, Morice MC, Chevalier B, et al. Duration of balloon inflation for optimal stent deployment: Five seconds is not enough. Catheter Cardiovasc Interv 2013; 81: 446–453.
• 32.   Ann SH, Chung JW, C DEJ, Lee JH, Kim JM, Garg S, et al. Better inflation time of stent balloon for second-generation drug-eluting stent expansion and apposition: An optical coherence tomography study. J Interv Cardiol 2014; 27: 171–176.
• 33.   Skowroński J, Wolny R, Jastrzębski J, Tyczyński P, Szlazak K, Pręgowski J, et al. Impact of the balloon inflation time and pattern on the coronary stent expansion. J Interv Cardiol 2019; 2019: 6945372.
• 34.   Katayama Y, Taruya A, Kashiwagi M, Ozaki Y, Shiono Y, Tanimoto T, et al. No-reflow phenomenon and in vivo cholesterol crystals combined with lipid core in acute myocardial infarction. Int J Cardiol Heart Vasc 2022; 38: 100953.
• 35.   Sato H, Iida H, Tanaka A, Tanaka H, Shimodouzono S, Uchida E, et al. The decrease of plaque volume during percutaneous coronary intervention has a negative impact on coronary flow in acute myocardial infarction: A major role of percutaneous coronary intervention-induced embolization. J Am Coll Cardiol 2004; 44: 300–304.
• 36.   Gutierrez A, Chugh Y, Kostantinis S, Brilakis ES. The perils of buddy wire use with a filterwire. Cardiovasc Revasc Med 2022; 40S: 214–217.
• 37.   Hu S, Wang H, Zhu J, Li M, Li H, Gao D, et al. Effect of intra-coronary administration of tirofiban through aspiration catheter on patients over 60 years with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention. Medicine (Baltimore) 2018; 97: e10850.
• 38.   Porto I, Choudhury RP, Pillay P, Burzotta F, Trani C, Niccoli G, et al. Filter no reflow during percutaneous coronary interventions using the Filterwire distal protection device. Int J Cardiol 2006; 109: 53–58.
• 39.   Kaltoft A, Kelbaek H, Kløvgaard L, Terkelsen CJ, Clemmensen P, Helqvist S, et al. Increased rate of stent thrombosis and target lesion revascularization after filter protection in primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: 15-month follow-up of the DEDICATION (Drug Elution and Distal Protection in ST Elevation Myocardial Infarction) trial. J Am Coll Cardiol 2010; 55: 867–871.
• 40.   Otsuka F, Cheng Q, Yahagi K, Acampado E, Sheehy A, Yazdani SK, et al. Acute thrombogenicity of a durable polymer everolimus-eluting stent relative to contemporary drug-eluting stents with biodegradable polymer coatings assessed ex vivo in a swine shunt model. JACC Cardiovasc Interv 2015; 8: 1248–1260.
• 41.   Sabaté M, Brugaletta S, Cequier A, Iñiguez A, Serra A, Jiménez-Quevedo P, et al. Clinical outcomes in patients with ST-segment elevation myocardial infarction treated with everolimus-eluting stents versus bare-metal stents (EXAMINATION): 5-year results of a randomised trial. Lancet 2016; 387: 357–366.
• 42.   Sabate M, Cequier A, Iñiguez A, Serra A, Hernandez-Antolin R, Mainar V, et al. Everolimus-eluting stent versus bare-metal stent in ST-segment elevation myocardial infarction (EXAMINATION): 1 year results of a randomised controlled trial. Lancet 2012; 380: 1482–1490.