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 noninfarct artery (Class III) Current Guidelines Class IIb
ESC STEMI Guidelines 2017 Eur Heart J. Published online August 26, 2017. doi:10.1093/eurheartj/ehx393
Freedom from Primary Outcome (%) 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) Primary endpoint: Cardiac death, MI or refractory angina 100 80 60 40 20 Complete revasc Culprit PCI only 91% 77% HR 0.35 (95%CI 0.21-0.58) P<0.001 No. at Risk Preventive PCI No Preventive PCI 0 0 234 231 6 196 168 12 18 24 30 36 166 144 Months 146 122 118 96 89 74 67 50 Wald DS et al. NEJM 2013:on-line
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
Cv LPRIT Study: MVD >70% lesion in Non IRA, >2mm diameter (68% acute, 32% staged) ESC 2014
CvLPRIT Clinical Outcomes (Primary Endpoint) at 12 months (Per Protocol Population) Variable IRA Only Multi-vessel PCI IRA plus N- IRA HR (95% CI) 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) P 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 All-cause mortality 17 (16.0%) 15 (13.9%) 1.35 (0.66-2.74) 6 (5.7%) 7 (6.5%) 0.91 (0.30-2.70) 0.407 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 All-cause mortality + nonfatal myocardial infarction + revascularization 1.03 (0.58-1.84) 0.921 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
Should All Lesions be Treated? PRAMI:The tightest lesions have the worst outcomes Stenosis Severity and Outcomes Stenosis % No Preventive PCI Primary outcome event Percentage with event 50-74 74 10 14% (10/74) 75-94 130 32 * 23% (32/130) 95-99 27 11 47% (11/27) All 231 53 23% (53/231) * p for trend <0.01
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?
OMPARE-ACUTE
COMPARE-ACUTE FFR of Non-IRA is abnormal in 50% Outcomes based on FFR and management
COMPARE-ACUTE: Primary Outcome
COMPARE-ACUTE Primary Outcome and Components 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
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 (%) All-Cause Mortality 60 50 40 Immediate multivessel PCI 51.5% 43.3% Culprit lesion only PCI 30 20 Number at risk: Culprit lesion only PCI 10 0 Relative risk 0.84; 95% confidence interval 0.72-0.98; P=0.03 0 5 10 15 20 25 30 Days after randomization 344 237 226 211 203 198 193 Immediate multivessel PCI 341 229 197 179 170 166 165
Subgroup Analysis Primary Endpoint 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) 0.25 0.5 1 2 4 Culprit 0 lesion only 1 PCI better 2 3 Multivessel PCI better
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.