Cindy L. Grines MD FACC FSCAI Hofstra Northwell School of Medicine Chair, Cardiology

Academic Chief of Cardiology, Northwell Health

North Shore University Hospital, Manhasset NY

Multivessel Disease in AMI

Multivessel disease occurs in 40-60% of patients with STEMI, and 70-80% of patients with shock

It confers higher risk of death, reinfarction, stent thrombosis, lack of compensatory hyperkinesis of the non-infarct zone and development of shock

Multiple culprits may be present due to a systemic inflammatory state

Therefore, treatment of non-culprit vessels may be beneficial

The Case for Not Performing Multi-Vessel

PCI during Infarct Angioplasty

Every PCI for every lesion increases the risk (enhanced

thrombotic and inflammatory state during STEMI)

Longer more complex procedures (contrast

nephropathy, hemodynamic instability)

Additional time, cost, more radiation exposure

Non-culprit lesion severity is often exaggerated during

AMI

Follow up angios showed 20% of “significant” lesions were

now less than 50% narrowed (JACC 2002;40:911-6)

FFR negative in 40% of “significant” lesions (Euro Intervention

2010;5:968)

American Guidelines prior to 2015:

PCI should not be performed in a non-

infarct artery (Class III)

Current Guidelines Class IIb

Eur Heart J. Published online August 26, 2017. doi:10.1093/eurheartj/ehx393

ESC STEMI Guidelines 2017

Primary endpoint: Cardiac death, MI or refractory angina

Wald DS et al. NEJM 2013:on-line

91%

77%

Fre

ed

om

fro

m

Pri

mary

Ou

tco

me (

%)

Months

HR 0.35 (95%CI 0.21-0.58)

P<0.001

No. at Risk

Preventive PCI

No Preventive PCI

0

231

6

234

12 18 24 30 36

168

196

144

166

122

146

96

118

74

89

50

67

0

20

40

60

80

100

PRAMI: “Preventative” PCI of Non-culprit Lsns

after Culprit Lesion Primary PCI in STEMI 465 non-shock pts at 5 UK sites with MVD; after successful primary PCI randomized to

NCL PCI of non-LM DS 50-99% stenoses vs. conservative care

600 pts planned; DSMB stopped trial early after 465 pts enrolled (2008-2013)

Complete revasc

Culprit PCI only

PRAMI Results

Criticisms of the PRAMI study

Small sample size and stopped prematurely

Reported “benefits” are too extreme to be real

Non-infarct vessels did not undergo FFR or

QCA – uncertain of severity

Early reinfarction from the nonculprit vessel

missed since enzymes are already elevated

Limited applicability – “we do not treat 50%

lesions or ignore tight lesions”

(68% acute,

32% staged)

ESC 2014

Cv LPRIT Study:

MVD >70% lesion in Non IRA, >2mm diameter

CvLPRIT

Clinical Outcomes (Primary Endpoint) at 12 months

(Per Protocol Population)

Variable IRA Only Multi-vessel

PCI IRA plus N-

IRA

HR (95% CI) P

MACE 28/138 (20.3) 9/136 (6.6) 0.31 (0.15, 0.65) 0.0011

All-cause

mortality

5/138 (3.6) 1/136 (0.7) 0.20(0.02, 1.73)

0.106

Recurrent MI 4/138 (2.9) 2/136 (1.5) 0.50 (0.09, 2.74) 0.418

Heart failure 7/138

(5.1)

3/136 (2.2) 0.43 (0.11, 1.66) 0.207

Repeat Revasc 12/138 (8.7) 3/136 (2.2) .24 (0.07, 0.85) 0.016

Death/MI 14/146 (9.6) 6/150 (4.0)

ESC 2014

PRAGUE-13 Staged PCI at 3-40 days

Primary Composite Endpoint PCI (n=106) Conservative

(n=108)

Hazard ratio

(95% CI)

p-value

All-cause

mortality/non

fatal

MI/stroke

17 (16.0%) 15 (13.9%) 1.35 (0.66-

2.74)

0.407

All-cause

mortality

6 (5.7%) 7 (6.5%) 0.91 (0.30-

2.70)

0.859

Nonfatal MI 11(10.4%) 8 (7.4%) 1.71 (0.66-

4.41)

0.269

Stroke 0 3 (2.8%)

4 (3.8%) periprocedural infarctions in PCI group with good prognosis

PRAGUE-13

Secondary Endpoints Hazard ratio (95% CI) P-value

Hospitalization for unstable angina 0.52 (0.19-1.40) 0.193

Crossover to another treatment group 0.25 (0.09-0.68)

0.006

Revascularization of non-infarct artery 0.51 (0.24-1.11)

0.089

Cardiovascular mortality 01.34 (0.30-6.01)

0.699

All-cause mortality + nonfatal myocardial infarction + hospitalization for unstable angina

1.03 (0.58-1.84)

0.921

All-cause mortality + nonfatal myocardial infarction + revascularization

0.86 (0.53-1.40)

0.538

Hospitalization for heart failure 0.68 (0.11-4.07)

0.672

Cardiovascularmortality + nonfatal myofcardial infarction + revascularization

0.92 (0.56-1.53)

0.754

No non-infarct lesion progressed to myocardial infarction during follow-up.

Progression of studied non-infarct lesions was very rare

Stenosis

%

No Preventive

PCI

50-74 74

75-94 130

95-99 27

All 231

Primary

outcome event

10

32

11

53

Stenosis Severity and Outcomes

*

* p for trend <0.01

23% (32/130)

Percentage

with event

14% (10/74)

47% (11/27)

23% (53/231)

Should All Lesions be Treated? PRAMI:The tightest lesions have the worst outcomes

Angiography is not ideal to

determine lesion severity. Should

we perform FFR? If so, when?

FFR and complete revascularization performed 2 days post-MI. 31% had negative FFR

Network Meta-analysis of 10 randomized STEMI trials: No difference in Hard Endpoints, Staging is Preferred

Islam Y. Elgendy et al. JACC interventions 2017;10:315-324

American College of Cardiology Foundation

Do you need to wait 2 days to perform

FFR, or can it be done acutely?

COMPARE-ACUTE

COMPARE-ACUTE FFR of Non-IRA is abnormal in 50%

Outcomes based on FFR and management

COMPARE-ACUTE: Primary

Outcome

COMPARE-ACUTE

FFR-guided

Complete (295)

IRA-only

(590)

Hazard

Ratio

P

Value

MACCE 23 (7.8%) 121 (20.5%) 0.35 <0.001

All-Cause Mortality 4 (1.3%) 10 (1.7%) 0.80 0.70

Cardiac Mortality 3 (1.0%) 6 (1.0%)

Myocardial Infarction 7 (2.4%) 28 (4.7%) 0.50 0.10

Revascularization 18 (6.1%) 103 (17.5%) 0.32 <0.001

Stroke 0 4 (0.7%) NA NA

Primary Outcome and Components

Shouldn’t the sickest patients benefit the

most from complete revascularization?

CULPRIT-SHOCK:

A Randomized Trial of Multivessel PCI in Cardiogenic Shock

Holger Thiele, MD

on behalf of the CULPRIT-SHOCK Investigators

All-Cause Mortality

344 237 226 211 203 198 193

341 229 197 179 170 166 165

Culprit lesion only PCI

Immediate multivessel PCI

Number at risk:

0

10

20

30

40

50

60

0 5 10 15 20 25 30

All

-ca

us

e m

ort

ali

ty (

%)

Days after randomization

Immediate multivessel PCI 51.5%

344 237 226 211 203 198 193

341 229 197 179 170 166 165

Culprit lesion only PCI

Immediate multivessel PCI

Number at risk:

0

10

20

30

40

50

60

0 5 10 15 20 25 30

All

-ca

us

e m

ort

ali

ty (

%)

Days after randomization

Culprit lesion only PCI

Immediate multivessel PCI

Relative risk 0.84; 95% confidence interval 0.72-0.98; P=0.03

51.5%

43.3%

Baseline Variable Multivessel PCI Culprit lesion only PCI Relative Risk

(95% CI)

P Value for

Interaction

Sex

Male 148/266 (55.6) 109/257 (42.4) 0.76 (0.64-0.91) 0.11

Female 41/75 (54.7) 48/86 (55.8) 1.02 (0.77-1.35)

Age

<50 years 3/16 (18.8) 6/17 (35.3) 1.88 (0.56-6.29) 0.24

50-75 years 114/226 (50.4) 82/212 (38.7) 0.77 (0.62-0.95)

>75 years 72/99 (72.7) 70/115 (60.1) 0.84 (0.69-1.01)

Diabetes

No 116/218 (53.2) 93/235 (39.6) 0.74 (0.61-0.91) 0.08

Yes 66/116 (56.9) 59/102 (57.8) 1.02 (0.81-1.28)

Hypertension

No 68/129 (52.7) 65/139 (46.8) 0.89 (0.70-1.13) 0.47

Yes 114/205 (55.6) 88/200 (44.0) 0.79 (0.65-0.97)

Type of infarction

NSTEMI 54/97 (55.7) 45/98 (45.9) 0.82 (0.62-1.09) 0.96

STEMI 128/233 (54.9) 108/237 (45.6) 0.83 (0.69-0.99)

STEMI type

Anterior infarction 59/113 (52.2) 57/108 (52.8) 1.01 (0.79-1.30) 0.07

Non-anterior infarction 48/92 (52.2) 34/97 (35.0) 0.67 (0.48-0.94)

Previous infarction

No 154/281 (54.8) 128/279 (45.9) 0.84 (0.71-0.99) 0.83

Yes 28/53 (52.8) 25/60 (41.7) 0.79 (0.53-1.17)

Coronary artery disease

2-vessel disease 64/124 (51.6) 48/122 (39.3) 0.76 (0.58-1.01) 0.56

3-vessel disease 124/215 (57.7) 109/218 (50.0) 0.87 (0.73-1.03)

Chronic total occlusion

No 146/259 (56.4) 131/267 (49.1) 0.87 (0.74-1.02) 0.26

Yes 43/82 (52.4) 27/77 (35.1) 0.67 (0.46-0.97)

0 1 2 3 4 0.25 0.5 1 2 4

Culprit lesion only PCI better Multivessel PCI better

Subgroup Analysis – Primary Endpoint

STEMI with Multivessel Disease

Multivessel disease = worse outcomes

Recent studies suggest complete

revascularization may be beneficial but:

Benefit may be confined to reduction in ischemia

rather than hard endpoints. Harm in shock pts?

Identification of which lesions benefit (likely

abnormal FFR/iFR or tight stenosis) and the

appropriate timing of PCI is unclear

First do no harm: consider staged PCI to reduce

contrast induced renal failure, allow antiplatelets to

become therapeutic and vasomotion of noninfarct

vessels to “normalize” .