Complete Revascularization Versus Culprit Lesion Only in Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Disease

JACC: CARDIOVASCULAR INTERVENTIONS

VOL. 12, NO. 8, 2019

ª 2019 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER

Complete Revascularization Versus Culprit Lesion Only in Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Disease A DANAMI-3–PRIMULTI Cardiac Magnetic Resonance Substudy Kasper Kyhl, MD, PHD,a Kiril Aleksov Ahtarovski, MD, PHD,a Lars Nepper-Christensen, MD, PHD,a Kathrine Ekström, MD,a Adam Ali Ghotbi, MD, PHD,a Mikkel Schoos, MD, PHD,a Christoffer Göransson, MD,a Litten Bertelsen, MD,a Steffen Helqvist, MD, DMSC,a Lene Holmvang, MD, DMSC,a Erik Jørgensen, MD,a Frants Pedersen, MD, PHD,a Kari Saunamäki, MD, DMSC,a Peter Clemmensen, MD, PHD, DMSC,b,c Ole De Backer, MD, PHD,a Dan Eik Høfsten, MD, PHD,a Lars Køber, MD, DMSC,a Henning Kelbæk, MD, DMSC,d Niels Vejlstrup, MD, PHD,d Jacob Lønborg, MD, PHD, DMSC,d Thomas Engstrøm, MD, PHD, DMSCa,e ABSTRACT OBJECTIVES The aim of this study was to evaluate the effect of fractional flow reserve (FFR)–guided revascularization compared with culprit-only percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) on infarct size, left ventricular (LV), function, LV remodeling, and the presence of nonculprit infarctions. BACKGROUND Patients with STEMI with multivessel disease might have improved clinical outcomes after complete revascularization compared with PCI of the infarct-related artery only, but the impact on infarct size, LV function, and remodeling as well as the risk for periprocedural infarction are unknown. METHODS In this substudy of the DANAMI-3 (Third Danish Trial in Acute Myocardial Infarction)–PRIMULTI (Primary PCI in Patients With ST-Elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization) randomized trial, patients with STEMI with multivessel disease were randomized to receive either complete FFR-guided revascularization or PCI of the culprit vessel only. The patients underwent cardiac magnetic resonance imaging during index admission and at 3-month follow-up. RESULTS A total of 280 patients (136 patients with infarct-related and 144 with complete FFR-guided revascularization) were included. There were no differences in final infarct size (median 12% [interquartile range: 5% to 19%] vs. 11% [interquartile range: 4% to 18%]; p ¼ 0.62), myocardial salvage index (median 0.71 [interquartile range: 0.54 to 0.89] vs. 0.66 [interquartile range: 0.55 to 0.87]; p ¼ 0.49), LV ejection fraction (mean 58  9% vs. 59  9%; p ¼ 0.39), and LV end-systolic volume remodeling (mean 7  22 ml vs. 7  19 ml; p ¼ 0.63). New nonculprit infarction occurring after the nonculprit intervention was numerically more frequent among patients treated with complete revascularization (6 [4.5%] vs. 1 [0.8%]; p ¼ 0.12). CONCLUSIONS Complete FFR-guided revascularization in patients with STEMI and multivessel disease did not affect final infarct size, LV function, or remodeling compared with culprit-only PCI. (J Am Coll Cardiol Intv 2019;12:721–30) © 2019 by the American College of Cardiology Foundation.

From the aDepartment of Cardiology, Rigshospitalet, Copenhagen, Denmark; bDepartment of Medicine, Nykoebing F Hospital, Nykoebing F and University of Southern Denmark, Odense, Denmark; cUniversity Clinic of Hamburg-Eppendorf, The Heart Centre, Hamburg, Germany; dDepartment of Cardiology, Zealand University, Roskilde, Denmark; and the eDepartment of Cardiology, University of Lund, Lund, Sweden. The Research Foundation of the Department of Cardiology, Rigshospitalet, the Danish Heart Foundation, and the Danish Agency for Science, Technology and Innovation by the Danish Council for Strategic Research supported this study (Eastern Denmark Initiative to Improve Revascularization Strategies grant 09-066994). Dr. Lønborg has

ISSN 1936-8798/$36.00

https://doi.org/10.1016/j.jcin.2019.01.248

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JACC: CARDIOVASCULAR INTERVENTIONS VOL. 12, NO. 8, 2019 APRIL 22, 2019:721–30

Remodeling in Complete or Culprit-Only PCI

T

ABBREVIATIONS AND ACRONYMS CMR = cardiac magnetic resonance

FFR = fractional flow reserve IQR = interquartile range LV = left ventricular

imely

primary

Thus, the aim of this CMR substudy was to

percutaneous coronary intervention

reperfusion

with

determine if a strategy of fractional flow reserve

(PCI) to reopen the occluded culprit

(FFR)–guided complete revascularization compared

vessel improves outcomes in patients with

with culprit lesion–only PCI in patients with STEMI

ST-segment elevation myocardial infarction

and multivessel disease affects LV function, infarct

(STEMI) (1–4). However, the presence of cor-

size, and LV remodeling and the presence of new

onary stenosis in non-infarct-related arteries

nonculprit MI (periprocedural MI).

(multivessel disease) is observed in approxi-

LVEDV = left ventricular enddiastolic volume

LVEF = left ventricular ejection

mately 45% of patients with STEMI, and controversies regarding handling of noncul-

METHODS

prit disease remain (5). Multivessel disease

This is a substudy of the randomized DANAMI-3-

is an independent predictor of adverse left

PRIMULTI (Third DANish Study of Optimal Acute

systolic volume

ventricular (LV) remodeling (6), impaired

Treatment of Patients with ST-segment Elevation

MI = myocardial infarction

LV ejection fraction (LVEF) (7), increased

Myocardial Infarction: PRImary PCI in MULTIvessel

PCI = percutaneous coronary

mortality, and nonfatal reinfarction (8–11).

Disease) trial (11,21), in which 627 patients with a first

intervention

Whether these poorer outcomes are a result

STEMI, symptom duration #12 h, and multivessel

STEMI = ST-segment elevation

of multivessel disease per se or due to inade-

disease were included to evaluate the clinical effect

myocardial infarction

quate revascularization is unclear. Four ran-

of complete revascularization versus treatment of the

domized studies have shown improved clinical

culprit lesion only (11). STEMI was defined as ST-

outcomes in patients with STEMI with multivessel

segment elevation $0.1 mV in $2 contiguous leads

disease and complete revascularization compared

or newly developed left bundle branch block. Eligible

with treatment of the infarct-related artery only

patients were initially treated with primary PCI of the

(11–14), especially in patients with 3-vessel disease

culprit lesion. Patients with additional angiographic

and severe diameter stenosis in nonculprit vessels (15).

stenosis >50% in 1 or more of the non-infarct-related

SEE PAGE 731

arteries were asked to participate in the DANAMI-3–

fraction

LVESV = left ventricular end-

Therefore, complete revascularization could be a key factor that influences LV function, infarct size and remodeling. However, any supposed benefit from complete revascularization may come at a cost of periprocedural complications related to treatment of nonculprit lesions, including periprocedural myocardial infarction (MI) (type 4a), which is related to adverse outcomes (16). Periprocedural MI is difficult to detect in the acute phase of STEMI, because any increase in cardiac biomarkers may be hidden by the increase in biomarkers related to

PRIMULTI trial. Immediately after the primary PCI procedure, patients were randomly assigned to either FFR-guided complete revascularization or no further revascularization by a web-based computer system (11). Major exclusion criteria included previous contrast media reactions, unconsciousness, cardiogenic shock, and indication for coronary artery bypass grafting (11). The central Danish ethics committee approved the study, which was performed in accordance with the Declaration of Helsinki. This trial is registered at ClinicalTrials.gov (NCT01960933).

the index STEMI. Cardiac magnetic resonance (CMR)

PROCEDURES. Patients

imaging is the method of choice for quantification of

complete revascularization underwent additional

infarct size compared with single-photon emission

FFR-guided coronary angiography of any nonculprit

computed tomography (17–19). CMR allows accurate

stenosis and subsequent PCI procedure if indicated

detection of the location of the infarction and

within 2 days after the index procedure. Complete

assigned

to

FFR-guided

can also detect infarction in the nonculprit myocar-

revascularization was defined as revascularization of

dium (16). Performing CMR scans before and after

all significant coronary lesions in branches with

nonculprit coronary intervention may help detect

reference diameters of 2 mm or larger not located in

periprocedural MI. Also, steady-state free precession

the territory of the culprit lesion. FFR values were

sequences are considered the gold standard for quan-

calculated across the lesions during maximal hyper-

tifying cardiac chamber volumes and function (20).

emia induced by intravenous adenosine infusion

received fees from St. Jude Medical. Dr. Køber has received grants from the Danish Research Foundation. Dr. Engstrøm has received fees from St. Jude Medical, Bayer, Boston Scientific, and AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received October 1, 2018; revised manuscript received January 25, 2019, accepted January 29, 2019.

Kyhl et al.

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Remodeling in Complete or Culprit-Only PCI

(140 m g/kg/min) and stenosis with FFR values of

echo time, 1.4 ms; field of view, 300 to 360 mm; no

#0.80 or >90% visually estimated stenosis consid-

slice gap). Images were obtained 10 min after

ered significant. In a few patients with contraindica-

the administration of 0.1 mmol/kg body weight of

tions

diethylenetriaminepentaacetic

to

intravenous

adenosine,

intracoronary

administration was chosen (80 mg for the right coro-

acid

(0.1

ml/kg;

Gadovist, Bayer Schering, Berlin, Germany). The

nary artery and 160 m g for the left coronary artery).

infarct

All further patient management was in accordance

myocardium

with contemporary international guidelines at the

normal myocardium) on the delayed-enhancement

discretion of the treating physician (11).

short-axis

CMR ACQUISITION AND ANALYSIS. All patients ran-

domized at Rigshospitalet, Copenhagen University Hospital, and without contraindications to CMR underwent baseline CMR scans during the index admission to assess LVEF, LV volumes, acute infarct size, and myocardial area at risk (22–24) and repeat scans 90 days later to assess LVEF, LV volumes, and final infarct size. Patients with available baseline CMR scans were included in the present study. However, patients without available follow-up scans were excluded from the analysis in which both scans (baseline and follow-up) were necessary (i.e., evaluation of remodeling and development of new nonculprit infarctions). All CMR scans were performed on a 1.5-T scanner (Avanto or Espree, Siemens Medical Solutions, Erlangen, Germany). All baseline CMR was performed before any staged PCI procedure. LV volumes and mass were assessed using a steady-state free precession standard cine sequence (slice thickness, 8 mm; no gap; echo time, 1.5 ms; field of view, 300 to 360 mm; phases, 25). Images in the short-axis image plane were obtained covering the entire left ventricle. LV volumes were determined at end-diastole and end-systole using semiautomated endocardial contour detection with papillary muscles included in the blood volume. Stroke volume was calculated as

end-diastolic volume

minus

end-

systolic volume. LVEF was calculated as stroke volume divided by end-diastolic volume. At baseline, the myocardial area at risk was assessed as the

was

size

was (>5

defined SDs

images.

assessed

enhancement

at

above

as

hyperenhanced

the

intensity

Microvascular baseline

on

inversion-recovery

of

obstruction the

delayed-

sequence

on

images obtained 10 min after the administration of diethylenetriaminepentaacetic

acid

(0.1

ml/kg;

Gadovist) (25). Myocardial salvage index was calculated as (area at risk  final infarct size)/area at risk. All images were analyzed by an independent observer blinded to all clinical data, using CVI42 (Circle Cardiovascular Imaging, Calgary, Alberta, Canada), and all analyses were reviewed and finalized by a second observer blinded to all clinical data (26). Assessment of nonculprit MI was performed by 1 observer (K.K.) and approved by 2 other observers (J.L., L.N.-C.) by agreement. Nonculprit MI was defined as the presence of late gadolinium enhancement in a coronary territory clearly remote from the culprit infarction. The culprit territory was defined as the territory supplied by the artery treated with primary PCI during the index procedure. Nonculprit MIs were considered new if they occurred on follow-up CMR but not on baseline CMR. These new nonculprit MIs may be due to de novo plaque rupture (type 1) or periprocedural MI related to nonculprit intervention (type 4a). Interobserver reproducibility has been reported previously from 20 randomly chosen patients and expressed as mean difference (limits of agreement): 0.5% (4%) for acute LVEF and 0.1% (2%) for acute infarct size (26). CMR has high reproducibility for quantification of infarct size, volume, and function and is the method of choice (17–20).

hyperintense area using a T2-weighted short-tau

STATISTICAL ANALYSIS. All continuous variables

inversion recovery sequence (slice thickness, 8 mm;

are expressed as mean  SD or median (interquartile

field of view, 300 to 360 mm; inversion time, 180 ms;

range [IQR]) unless otherwise stated. Binomial vari-

repetition time, 2 R-R intervals; time to echo, 65 ms;

ables are expressed as number (percentage), and

no slice gap). A myocardial area was regarded as

differences between proportions were calculated us-

hyperintense when the signal intensity was >2 SDs

ing the chi-square test. Normality of distribution was

above the signal intensity of normal myocardium.

tested visually on a histogram of the residuals and

Hypointense areas within the area at risk were

differences between group means or medians were

included in the area at risk, and hyperintense

assessed using the 2-sided Student’s t-test or the

areas within the normal myocardium were excluded.

Mann-Whitney U test for unpaired samples. A

Final infarct size was assessed in the

culprit

possible interaction between treatment (infarct-

area on follow-up CMR using a delayed enhancement

related artery only vs. complete revascularization)

inversion-recovery sequence (slice thickness, 8 mm;

and multivessel disease (3-vessel disease vs. 2-vessel

723

724

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F I G U R E 1 Trial Flowchart

*Reasons for exclusions are specified in original paper (14). AF ¼ atrial fibrillation; CMR ¼ cardiac magnetic resonance; eGFR ¼ estimated glomerular filtration rate; FFR ¼ fractional flow reserve; STEMI ¼ ST-segment elevation myocardial infarction.

disease), infarct location (anterior vs. nonanterior), or

RESULTS

acute infarct size (greater vs. less than the median infarct size) was evaluated using an analysis of

During the inclusion period, a total of 627 patients

covariance with LV end-systolic volume (LVESV) at

with STEMI with multivessel disease underwent

follow-up. LVEF at follow-up, final infarct size, and

successful

myocardial salvage index were dependent variables.

the

The assumptions for general linear models were

either FFR-guided complete revascularization or

checked. Because this was a substudy, all endpoints

culprit-only treatment. A total of 280 patients

in the present study may be considered secondary,

were included in the present study. Symptom

and thus no power calculation was performed. A p

onset–to–wire time was 188 min (IQR: 128 to 286

value < 0.05 was considered to indicate statistical

min) in the culprit-only group and 170 min (IQR:

significance. All statistical analyses were performed

128 to 283 min) in the complete revascularization

using SPSS Statistics version 20.0 (IBM, Armonk, New

group (p ¼ 0.20). The study flowchart is shown in

York).

Figure 1.

primary

original

study

PCI

and

and

randomized

were

included to

in

receive

Kyhl et al.

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T A B L E 1 Baseline Characteristics

T A B L E 2 Procedural and Discharge Data

Infarct-Related Complete Artery Only Revascularization (n ¼ 136)

(n ¼ 144)

p Value

Mean age (yrs)

61  11

61  11

0.80

Sex Male Female

114 (84) 22 (16)

120 (83) 24 (17)

0.91

16 (12) 57 (42) 68 (50) 7 (5)

8 (6) 45 (31) 86 (60) 2 (1)

0.06 0.06 0.10 0.75

Infarct location Anterior Inferior Posterior

52 (38) 78 (57) 5 (4)

45 (31) 89 (62) 7 (4)

0.51

Triple-vessel disease

46 (34)

46 (32)

0.74

Stenosis on proximal portion of left anterior descending coronary artery

33 (24)

28 (19)

0.33

Medical history Diabetes Hypertension Current smoking Previous myocardial infarction

725

Remodeling in Complete or Culprit-Only PCI

Values are mean  SD or n (%).

Infarct-Related Artery Only

Complete Revascularization

(n ¼ 136)

(n ¼ 144)

p Value

1 (1–1) 1 (1–1) 3.25 (2.71–3.50) 18 (15–23)

2 (1–2) 2 (1–3) 3.00 (2.73–3.50) 35 (18–53)

<0.001 <0.001 0.05 <0.001 0.14

11 (8) 2 (2) 123 (90) 35 (26) 93 (68)

4 (3) 2 (1) 138 (96) 31 (22) 105 (73)

0.41 0.41

Clinical status during admission Killip classes II–IV

4 (3)

5 (4)

0.80

Medical treatment at discharge Antiplatelet drug Aspirin Clopidogrel Prasugrel Ticagrelor Statin Beta-blocker ACE inhibitor or ARB blocker Calcium-channel blocker

135 (99) 10 (7) 108 (79) 16 (12) 135 (99) 124 (91) 57 (42) 16 (12)

140 (97) 11 (8) 108 (75) 24 (17) 144 (100) 131 (91) 55 (38) 11 (8)

0.20 0.93 0.38 0.24 0.30 0.95 0.95 0.24

Percutaneous coronary intervention Arteries treated per patient Implanted stents Stent diameter (mm) Total stent length (mm) Stent type No stenting Bare metal Drug eluting Use of glycoprotein IIb/IIIa inhibitor Use of bivalirudin

Values are median (interquartile range) or n (%).

The baseline scan was performed on day 1

ACE ¼ angiotensin-converting enzyme; ARB ¼ angiotensin II receptor blocker.

(IQR: 1 to 1) after primary PCI in both treatment groups but before the nonculprit intervention in all except 3 patients. Follow-up scans were performed

follow-up, LVEDV increased by 5  17% and LVESV

91 days (IQR: 88 to 94 days) and 93 days (IQR: 89 to

decreased by 7  22% in the group of infarct-related

98 days) after baseline scans in the culprit-only

artery only compared with a 5  16% increase in

group and in the complete revascularization group,

LVEDV and a 6  29% decrease in LVESV in the

respectively. Myocardial remodeling parameters were

group with complete revascularization (p ¼ 0.82 and

not assessable in 41 patients, because there was no

p ¼ 0.99, respectively).

follow-up CMR available for the reasons depicted in Figure 1. By nature of the randomization, PCI procedural

Complete revascularization had no impact on LVESV or LVEF at follow-up or final infarct size across pre-defined subgroups (Table 4). No significant

characteristics differed in number of arteries treated

interaction

per patient, implanted stents, and total stent length as

subgroups and the treatment allocation.

was

present

between

any

of

the

a result of different treatment strategies. All other

Among 239 patients with 2 available CMR scans

baseline characteristics, procedural characteristics,

(baseline and follow-up), the number of new non-

clinical status, and management of patients at

culprit MIs assessed from baseline CMR to follow-up

discharge did not differ between groups (Tables 1

CMR

and 2). Among the patients randomized to complete

complete revascularization than with culprit only

revascularization, 43 (30%) had FFR >0.80 and

(6 [4.9%] vs. 1 [0.8%]; p ¼ 0.12) (Figure 2, Table 3).

was

larger

among

patients

treated

with

thus no further invasive treatment, 5 (3%) had failed revascularization, and 1 (1%) refused further

DISCUSSION

invasive evaluation, leaving 95 (66%) patients to undergo additional revascularization by either PCI

In the present study, FFR-guided complete revas-

(n ¼ 90) or coronary artery bypass graft (n ¼ 5).

cularization compared with culprit lesion–only PCI in

Myocardial area at risk and final infarct size did not

patients with STEMI and multivessel disease did not

differ between the 2 groups (Table 3). At 3-month

affect LV remodeling, function, or infarct extension

CMR follow-up, there were no differences in LVEF,

(Central Illustration). Although not significant, a

LV end-diastolic volume (LVEDV), and LVESV be-

larger number of new nonculprit MIs (not present

tween the 2 groups (Table 3). From baseline to

on

baseline

CMR

performed

before

nonculprit

726

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JACC: CARDIOVASCULAR INTERVENTIONS VOL. 12, NO. 8, 2019 APRIL 22, 2019:721–30

Remodeling in Complete or Culprit-Only PCI

intervention but present on follow-up CMR) was

T A B L E 3 Cardiac Outcomes Evaluated With Magnetic Resonance Imaging

observed among patients treated with FFR-guided

Infarct-Related Artery Only

Complete Revascularization

p Value

Baseline LVEDV (ml) LVESV (ml) LVEF (%) LV mass (g) Area at risk (g) Area at risk (%) Infarct size (%) MVO mass (g) Presence of nonculprit infarction*

(n ¼ 136) 161  36 74  79 52  10 130 (112–153) 44 (31–53) 33 (24–42) 16 (9–25) 0 (0–3.5) 12 (10)

(n ¼ 144) 164  40 76  83 50  11 130 (113–145) 42 (31–55) 33 (27–39) 15 (9–25) 0 (0–3) 13 (11)

0.51 0.27 0.31 0.87 0.95 0.89 0.77 0.57 0.88

Follow-up LVEDV (ml) LVESV (ml) LVEF (%) LV mass (g) Infarct size (g) Final infarct size (%) Myocardial salvage index† (%) Presence of nonculprit infarction*

(n ¼ 118) 168  41 72  29 58  9 122 (98–143) 14 (6–24) 12 (5–19) 0.71 (0.54–0.84) 13 (11)

(n ¼ 121) 169  41 74  31 59  9 120 (102–140) 13 (4–22) 11 (4–18) 0.66 (0.55–0.87) 19 (16)

0.79 0.54 0.39 0.84 0.53 0.62 0.49 0.28

(n ¼ 118) 6  26 5  17 –7  19 –7  22 1 (1)

(n ¼ 121) 6  24 5  16 –7  19 –6  29 6 (5)

0.82 0.99 0.99 0.63 0.12

Remodeling LVEDV remodeling (ml) LVEDV remodeling (%) LVESV remodeling (ml) LVESV remodeling (%) Presence of new nonculprit infarction*

complete revascularization. These could be related to periprocedural MI occurring during nonculprit intervention (Central Illustration). In a small exploratory CMR substudy to the PRAMI (Preventive Angioplasty in Myocardial Infarction) study (n ¼ 84) Mangion et al. (27) reported that LV volumes and LVEF were similar between patients randomized to culprit artery–only PCI or preventive PCI. However, there were 4.8% of procedure-related MI in the preventive PCI group versus 0% in the culprit artery–only group. In the PRAMI study, complete revascularization in most cases occurred during the index procedure, whereas in our study complete revascularization was postponed for up to 2 days (14). McCann et al. (28) reported in the CvLPRIT (Complete versus Lesion-only Primary PCI Trial) CMR substudy a 2-fold increase in the presence of multiple MIs following complete revascularization in patients with STEMI and multivessel disease (11% vs. 24%). However, our study adds new knowledge by distinguishing itself from previous studies through several important differences. First, in CvLPRIT the

Values are mean  SD, median (interquartile range), or n (%). *Considers only patients with both baseline and follow-up CMR. †Salvage index ¼ (area at risk [g]  infarct size [g])/area at risk (g). LV ¼ left ventricular; LVEDV ¼ left ventricular end-diastolic volume; LVEF ¼ left ventricular ejection fraction; LVESV ¼ left ventricular end-systolic volume; MVO ¼ microvascular obstruction.

baseline CMR scan was performed before nonculprit revascularization in some patients and after nonculprit revascularization in others. In contrast, in the present study the baseline CMR scan was performed before nonculprit intervention in all patients, and a

T A B L E 4 Subgroup Outcomes Evaluated With Cardiac Magnetic Resonance

follow-up CMR scan was performed approximately

Infarct-Related Artery Only

Complete Revascularization

3 months after nonculprit intervention, allowing

3-vessel disease (n ¼ 75) LVESV follow-up (ml) LVEF follow-up (%) Final infarct size (% LV)

73 (46–90) 59 (49–67) 13 (8–22)

66 (57–85) 59 (51–64) 12 (3–23)

probably related to the intervention (type 4a). Sec-

2-vessel disease (n ¼ 151) LVESV follow-up (ml) LVEF follow-up (%) Final infarct size (% LV)

69 (52–89) 59 (50–65) 12 (4–18)

67 (54–99) 59 (51–64) 11 (6–18)

Anterior (n ¼ 58) LVESV follow-up (ml) LVEF follow-up (%) Final infarct size (% LV)

70 (52–98) 59 (49–65) 15 (6–22)

62 (45–92) 60 (51–67) 11 (6–22)

Nonanterior (n ¼ 197) LVESV follow-up (ml) LVEF follow-up (%) Final infarct size (% LV)

identification of the presence of new nonculprit MI ond, the nonculprit intervention in the present study was FFR guided, which leads to fewer PCIs compared with angiography-guided intervention (29), as used in the CvLPRIT study. Third, nonculprit intervention was performed during the index procedure in a considerable number of patients in the CvLPRIT study, which may be unfavorable compared with staged intervention (30). In our study, it was prespecified that complete revascularization should not 70 (51–89) 59 (52–65) 12 (5–17)

68 (56–97) 59 (51–64) 11 (4–18)

be performed during the acute phase but within a well-defined time interval; hence, the lesions could be evaluated better for ischemia. Fourth, the infarct

Acute IZ < median (n ¼ 113) LVESV follow-up (ml) LVEF follow-up (%) Final infarct size (% LV)

54 (45–75) 64 (60–67) 5 (1–8)

59 (44–68) 62 (58–66) 5 (2–9)

Acute IZ > median (n ¼ 113) LVESV follow-up (ml) LVEF follow-up (%) Final infarct size (% LV)

77 (59–97) 55 (48–59) 17 (13–24)

85 (67–109) 52 (47–60) 18 (14–24)

Values are median (interquartile range). No significant differences were observed, and no interaction was present. IZ ¼ infarct zone; other abbreviations as in Table 3.

size in the CvLPRIT study was very small compared with most STEMI populations, thus leading to risk for the inclusion of low-risk patients. In the present study, nonculprit MI was rare in both treatment groups but more frequent following complete revascularization. However, because this difference was nonsignificant, it should be interpreted with caution. Also, these subclinical MIs detected by CMR are rare, and their clinical importance is unknown (11).

Kyhl et al.

JACC: CARDIOVASCULAR INTERVENTIONS VOL. 12, NO. 8, 2019 APRIL 22, 2019:721–30

Remodeling in Complete or Culprit-Only PCI

F I G U R E 2 Multivessel Disease

A representative case of periprocedural myocardial infarction. The patient underwent primary percutaneous coronary intervention (PCI) of the right coronary artery (RCA). In a staged manner, the patient underwent PCI of a nonculprit diagonal lesion during same admission. (A,B) baseline T2-weighted and delayed-enhancement images showing edema and late enhancement in the inferior wall after ST-segment elevation myocardial infarction with RCA as the culprit lesion. (C) In the same patient, delayed enhancement was performed after 3 months, showing infarct in both the inferior and anterior myocardium, most likely caused during the PCI of the nonculprit diagonal lesion.

Clinically detected periprocedural MI was very un-

patients with multivessel disease could indicate a

common in the parent study. Nevertheless, the

generally more pronounced inflammatory response

benefit of complete revascularization in patients with

and increased wall stress in these patients or non-

STEMI and multivessel disease must be counter-

culprit ischemia from arteries subtending viable but

balanced against an inherent risk for periprocedural

suffering myocardium. However, neither the present

MI. However, because periprocedural MI is rare and

study nor the CvLPRIT study found any association of

their clinical importance unknown, further large

complete revascularization with infarct size, LV

clinical studies are warranted to assess the true

function, or remodeling compared with an infarct-

impact of complete revascularization in patients with

related artery–only strategy (28). As mentioned

STEMI and multivessel disease on clinical outcomes.

earlier, there are some important differences between

Multivessel disease in patients with STEMI is associ-

the present study and the CvLPRIT study making

ated with adverse late (6-month follow-up) LV

these 2 studies complementary.

dilatation and lower LVEF (6,7,9). Patients with

The

lack

of

an

association

between

CMR-

STEMI and multivessel disease are also at increased

based parameters and treatment strategy may be

risk for development of congestive heart failure after

explained by several factors. First, clinical results

PCI (31) and have higher mortality rates than patients

from the DANAMI-3–PRIMULTI trial showed benefit

with single-vessel disease (8–10). In an autopsy study

from

the presence of multivessel disease in patients with

ischemia-driven revascularization (11), which is not

STEMI was associated with an increased amount of

necessarily related to myocardial performance rep-

apoptosis in the remote (noninfarcted) myocardium

resented by LVEF, LV remodeling, or infarct size.

compared with that in patients with single-vessel

Second, the second CMR scan was performed 90 days

disease (32). Apoptosis in the remote myocardium of

after the initial procedure in our study, which might

complete

revascularization

primarily

on

727

728

Kyhl et al.

JACC: CARDIOVASCULAR INTERVENTIONS VOL. 12, NO. 8, 2019

Remodeling in Complete or Culprit-Only PCI

APRIL 22, 2019:721–30

C E N T R A L IL L U ST R A T I O N Schematic Illustration of the Study Outline and Main Results

Kyhl, K. et al. J Am Coll Cardiol Intv. 2019;12(8):721–30.

Patients with confirmed ST-segment elevation myocardial infarction (STEMI) and multivessel disease were randomized to complete or culprit lesion–only revascularization. Baseline and follow-up cardiac magnetic resonance allowed us to assess final infarct size, myocardial salvage, left ventricular function, and left ventricular remodeling. FFR ¼ fractional flow reserve.

Kyhl et al.

JACC: CARDIOVASCULAR INTERVENTIONS VOL. 12, NO. 8, 2019 APRIL 22, 2019:721–30

Remodeling in Complete or Culprit-Only PCI

be too early to detect a significant difference in LV

between patients excluded and included for CMR in

remodeling, a process that continues over time.

the Online Tables 1 and 2. The excluded patients had

However, infarct size measured by late gadolinium

more comorbidities, more often had proximal left

enhancement CMR appears to be dynamic within a

anterior descending coronary artery lesions, and

shorter time. Infarct size assessed on CMR rapidly

were more clinically unstable at admission. Inter-

decreases after the first week but remains almost

pretation of the present results should therefore bear

constant from 30 days to 1 year after the infarction

in mind this potential bias. Another limitation could

(33,34). The shrinkage of infarct size is both a

be the time point of the follow-up CMR, as 3 months

remodeling phenomenon of the infarct and due to

may be too soon to detect a difference in LV

a larger distribution volume of gadolinium in the

remodeling.

acute phase in both necrotic and damaged myocytes and edema (33–36). Because infarct size seems to

CONCLUSIONS

be stable after 1 month, it appears reasonable to measure the final infarct size after 3 months. Adverse

In this substudy of the DANAMI-3–PRIMULTI trial,

ventricular remodeling is highly related to both

complete FFR-guided complete revascularization of

infarct size and myocardial salvage index (22,37). The

patients with STEMI and multivessel disease did

infarct size modulates both the amount of LV

not affect final infarct size in the culprit territory,

remodeling and its time course (38). Large infarctions

LVEF, or LV remodeling compared with culprit-only

with severe areas of akinesia or dyskinesia seem

PCI.

to remodel continuously over time, whereas the remodeling process in patients with smaller infarcts is

ADDRESS

complete after a few months (38,39). Third, the ter-

Kyhl,

FOR

CORRESPONDENCE:

ritories of the non-infarct-related arteries might be

Blegdamsvej 9, 2100 Copenhagen, Denmark. E-mail:

too small compared with the culprit area at risk. In

[email protected].

Department of

Dr.

Kasper

Cardiology, Rigshospitalet,

this study, revascularization was allowed in significant coronary lesions in branches with a reference

PERSPECTIVES

diameter of 2 mm. However, there was no interaction in LVESV, LVEF, final infarct size, or myocardial salvage in patients with 2- and 3-vessel disease. Fourth, in the modern era, STEMI treatment is

WHAT IS KNOWN? Studies indicate improved clinical outcomes of complete revascularization compared with culprit lesion–only PCI.

effective and associated with a low mortality rate. However, infarct size and adverse remodeling may

WHAT IS NEW? We found no benefit in final infarct size,

still affect progression to heart failure. Because LVEF,

myocardial salvage, LV function, or LV remodeling from

infarct size, and LV remodeling were comparable

complete revascularization in patients with STEMI and

between the treatment groups in the present study,

multivessel disease compared with culprit-only PCI.

the long-term development of heart failure is probably not affected by complete revascularization.

WHAT IS NEXT? Periprocedural MI is rare and their clinical

However, other mechanism such as prevention of

importance unknown, so further large clinical studies are war-

long-term clinical MI may be at play.

ranted to assess the true impact of complete revascularization in

STUDY

LIMITATIONS. We

had a relatively large

number of patients not undergoing CMR, which could

patients with STEMI and multivessel disease on clinical outcomes.

have biased the results. We included a comparison

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KEY WORDS acute myocardial infarction, cardiac function, cardiac remodeling, cardiovascular magnetic resonance, complete revascularization, culprit lesion, primary percutaneous coronary intervention, randomization, randomized study, STsegment elevation myocardial infarction

A PPE NDI X For supplemental tables, please see the online version of this paper.