Ragosta - Left Main Disease - Oregon ACC · 6/2/2014 7 Treatment of Left Main Disease Surgery Percutaneous Coronary Intervention Surgery for Management of Left Main Disease 1.CABG

6/2/2014

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Left Main Coronary Disease:Assessment and Treatment for

Imagers, Interventionalists and

Surgeons

Michael Ragosta MD

Director, Cardiac Catheterization Laboratories

Professor of Medicine

University of Virginia Health System

Charlottesville, VA

Disclosure Information

Michael Ragosta MD

The following relationships exist related to this presentation:

Grant support (GS), consultant (C), speakers bureau (SB), stock options (SO), equity interest (EI):

Grant Support: Principal Investigator of EXCEL

Off label use of products discussed in this presentation:

NONE

A Brief History of Left Main Coronary Disease…..

First described in 1912 by Herrick

Recognized as high risk subgroup in 1960’s

Cathing left main disease during 60’s-70’s was

dangerous! (10-15% mortality) Cohen et al Circ 1972 45 Suppl I. I: 57 and Lavine et al AJH 1972;30:791

Early 1970’s: Survival with CABG better than

natural history

Late 1970’s: Trials of medical therapy vs CABG

Gruntzig: Balloon for left main disease in 1978.

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What’s so special about left

main disease?

1. Left main supplies 75% myocardium if right

dominant; 100% if left dominant

2. 4-6% of patients undergoing coronary

angiography

3. Disease is more complex; higher rate of multi-

vessel disease (70-80%)

Some facts about Left Main

Disease Anatomy…

1. Several, very different patterns of left main

involvement (ostial, mid-body, distal

bifurcation)

2. Isolated left main stem disease is rare! (9%)

3. Most patients (70-80%) with left main stem

disease have multivessel disease.

4. That other disease is usually very complex.

The Spectrum of Left Main Disease

ANATOMY

OstialDistal bifurcation/trifurc

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Unprotected Left Main StemExtent of Coexisting CAD

%

Pts

Number of Vessels Diseased

Ragosta et al CCI 2006;67:357–362.

Isolated

Left Main

9%

Unprotected Left Main StemPrevalence of Unfavorable Characteristics for PCI

%

Pts

AnyUnfavorable

Characteristic

Ragosta et al CCI 2006;67:357–362.

Diagnosis of Left Main Disease

1. Non-invasive imaging

2. Coronary angiography

3. Adjuncts to coronary angiography

Intravascular ultrasound

Fractional flow reserve (FFR)

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Non-Invasive Imaging of Left Main Disease

1. Yes, there are findings on stress testing

associated with left main disease

2. No, they are not very specific or helpful.

“High risk” findings also associated with multi-

vessel disease, LV dysfunction.

Concept of “balanced ischemia” might limit

conventional MPI at identifying significant left

main disease

CTA can identify left main disease but…

Coronary Angiography and Left Main Disease

1. Left main is surprisingly difficult to clearly

image on coronary angiography

2. Left main is subject to greatest degree of

observer variability than any other segment (Int J

Cardiol 2007;120:254-61)

Limitations of Coronary Angiography for

Assessment of Left Main Disease

Short segment

Foreshortening

Overlapping vessels

Diffuse disease: what is reference?

Catheter artifacts

Eccentric lesions

Ostial lesions hard to see

Reflux of contrast in aortic sinus

Bifurcation hard to see

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Percent Stenosis is Often Wrong!

In an IVUS study of left main disease:

33% of LM lesions with <30% stenosis had

minimal luminal area by IVUS of < 6 mm2

43% of LM lesions with >50% stenosis had

minimal luminal area by IVUS of > 6 mm2

JACC 2011;58:351-8

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Adjuncts to Coronary Angiography Are Often

Necessary for Optimal Left Main Assessment

1. Fractional Flow Reserve (FFR)• FFR < 0.80 is “significant”

• Can be problematic if disease in LAD/LCX (which

there often is)

2. Intravascular Ultrasound

FFR limited by

downstream disease

JACC Intv 2012;5:697-707

What is a “Significant” Left Main Lesion by IVUS?

MLA

(mm2)

n Validation Citation

< 7.5 214 Outcomes with deferral JACC 2005;45:204-11

< 5.9 55 Correlated with FFR < 0.75 Circ 2004;110:2831-36

< 4.8 55 Correlated with FFR < 0.80

Note: Korean population

JACC Intv 2011;4:1168-74

< 6.0 351 Outcomes with deferral JACC 2011;58:351-8

MLA < 6.0 mm2 generally

accepted as the cut-off value for

significant left main disease by

IVUS

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Treatment of Left Main Disease

Surgery

Percutaneous Coronary Intervention

Surgery for Management of Left Main

Disease

1. CABG considered the “gold standard”

2. Data comes from ancient and small,

randomized controlled trials

3. Need to understand current outcomes data

regarding surgery for left main stem disease

Randomized Trials of Medical Therapy vs CABG

Left Main Disease

Three trials:

VA Cooperative Study

European Coronary Surgery Study Group

Collaborative Study in Coronary Artery Surgery (CASS)

Enrolled patients in the early 1970’s

VA 1972-1974

CASS 1974-1979

ECSSG 1973-1976

Randomized to CABG or medical therapy

Different enrollment criteria.

CASS excluded significant L main disease

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VA Cooperative

StudyRandomized, angina

>50% stenosis

Medical n = 43

Surgical n = 48Circulation 1982;66:14-22

European Coronary Surgery Study GroupRandomized, mild to moderate angina, >50% stenosis

Medical n = 31; Surgical n = 28Lancet 1982;1173-1180

CASS Registry1492 patients with LM disease, Not randomized

Medical n = 309; Surgical n = 1183Am J Cardiol 1981;48:765-777

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CASS Registry: 15 yr survivalBased on % stenosis of left main

Caracciolo E et al. Circulation 1995;91:2325-2334

Surgery

Medical

Medical n = 25

Surgical n = 26Circulation. 1989;79:1171-1179

CASS Registry

Asymptomatic Patients

Criticisms of This Evidence

1. Very small data sets

2. Angiographic based, 50-70% stenosis group is

problematic

3. Quality of medical therapy was pathetic (66%

on beta blocker, 18% on aspirin, no statins)

4. Surgery group wasn’t optimal either (10% got

IMA)

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Current Outcomes Data with Surgery

Taggart et al JACC 2008;51:885-892

AVERAGE

Time Survival Freedom from

Revasc

30 day 97.6% 99.7%

1 year 93.6% 98.9%

5 year 83% 89%

10 year 64% 76%

Sabik et al Circ 2007;116(Suppl)I:232-239

“Benchmark” Data Regarding Outcomes of

CABG for Left Main Disease

A study of long term outcomes of 3803 patients

with LMCD operated on at the Cleveland Clinic

from 1971-1998

PCI for Left Main Disease:

Balloon Angioplasty

Gruentzig first attempted (unsuccessfully) in 1978 (Lancet 1978;311:263)

First series published in 1989 (Am J Cardiol 1989;64:144-7)

33 elective, unprotected left main POBA

9.1% procedural mortality

36% 3 year survival

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Bare Metal Stents

Lots of non-randomized series and registries in

highly selected patients

Highly variable outcomes depending on

population enrolled

Restenosis was, of course, a problem and was

sometimes associated with sudden death


Drug Eluting Stents

Again, began with lots of non-randomized series

showing good outcomes

Huge selection bias regarding anatomy and

patient characteristics

Evolving randomized trials comparing surgery to

drug eluting stents

The Spectrum of Left Main PCICLINICAL SCENARIOS

“Bailout” procedure due

to complication of cath

Acute MI with an

occluded left main stem

Poor surgical candidate

from comorbid illness

Surgical candidate but

patient refuses surgery

Good operative

candidate

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Unprotected LMCA PCI: Bail-Out IndicationExisting LMCA disease with closure during diagnostic cath

Determining options……..

PATIENT

CHARACTERISTICS

LV Function

Clinical Syndrome

Aortic calcification

Comorbidity

Age

Lungs

Kidneys

Vascular disease

Dementia

Frailty

DAPT

Other

ANGIOGRAPHIC

CHARACTERISTICS

Extent of disease

Quality of targets

Likelihood of successful PCI

Completeness of revascularization

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Patient Selection: Surgical Candidacy

Tools to estimate patient risk:

STS Calculator

Euroscore

Don’t account for variables such as pulmonary

hypertension, cirrhosis of the liver, “porcelain

aorta”.

“Heart Team” approach, similar to those used

for transcatheter valve procedures, should be

applied to left main patients

Patient Selection: The SYNTAX Score

Takes into consideration multiple features:• Dominance

• Number of lesions and segments involved

• Presence of total occlusion, age and features

predicting success

• Nature and presence of disease of trifurcation or

bifurcation

• Aorto-ostial disease

• Severe tortuosity

• Length > 20 mm

• Heavy calcification

• Thrombus

• Diffuse disease

www.syntaxscore.com

What do our Guidelines say about

unprotected left main PCI?

PCI Guidelines

Appropriate Use Criteria

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A Heart Team approach to revascularization is

recommended in patients with unprotected

left main or complex CAD.

Calculation of the STS and SYNTAX scores is

reasonable in patients with unprotected left

main and complex CAD.

Heart Team Approach to

Revascularization Decisions

I IIa IIb III

I IIa IIb III

CABG to improve survival is recommended for patients with significant (≥50% diameter stenosis) left main CAD.

PCI to improve survival is reasonable as an alternative to CABG in selected stable patients with significant LM CAD with: 1) anatomic conditions associated with a low risk of PCI procedural complications and a high likelihood of a good long-term outcome (low SYNTAX score [≤22], ostial or trunk left main CAD); and 2) clinical characteristics that predict an increased risk of adverse surgical outcomes (STS-predicted risk of operative mortality ≥5%).

Revascularization to Improve Survival:

Unprotected Left Main CAD Revascularization

I IIa IIb III

I IIa IIb III

PCI to improve survival is reasonable in patients with UA/NSTEMI when LM is the culprit lesion and patient not eligible for CABG.

PCI to improve survival is reasonable in patients with acute STEMI when LM is the culprit lesion, distal coronary flow is <TIMI 3 and PCI can be performed more rapidly and safely than CABG.

I IIa IIb III

I IIa IIb III

PCI to improve survival may be reasonable in selected stable patients with LM CAD with:

1) anatomy associated with low- intermediate risk of PCI complications and an intermediate to high likelihood of good long-term outcome (SYNTAX score of <33, bifurcation left main)

and

2) clinical characteristics that predict an increased risk of adverse surgical outcomes (COPD, prior stroke, or cardiac surgery; STS-predicted risk of operative mortality >2%).

I IIa IIb III

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PCI to improve survival should not be

performed in stable patients with

significant (≥50% diameter stenosis)

unprotected left main CAD who have

unfavorable anatomy for PCI and who

are good candidates for CABG.

I IIa IIb III

Harm

When is Unprotected Left Main PCI Appropriate?

JACC 2012;59:857-81

Attractive features:

• proximal location

• large diameter vessel

High risk/Unattractive features:

• large vascular territory

• potential cardiovascular collapse with ischemia

• often involves bifurcation or ostium

• presence of other CAD not treatable by PCI

• restenosis

• stent thrombosis likely a fatal event

Unprotected Left Main PCI

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Left Main PCI

Few randomized controlled trials in the modern era comparing PCI to CABG

Major trials:

SYNTAX

LEMANS

PRECOMBAT

Boudriot et al

EXCEL trial (completed enrollment)

Meta Analysis of Existing Trials Comparing PCI

to CABG (n=1611)

PCI CABG p value

1 year MACCE 14.5% 11.8% 0.11

Death 3.0% 4.1% 0.29

MI 2.8% 2.9% 0.95

CVA 0.1% 1.7% 0.013

TVR 11.4% 5.4% <0.001

Capodanno et al J Am Coll Cardiol 2011;58:1426-32

No difference in death or MI

Less stroke with PCI

Less repeat revascularization with CABG

Meta Analysis of Existing Trials Comparing PCI

to CABG (n=1611)

Capodanno et al JAm Coll Cardiol 2011;58:1426-32

1 Year

MACCE

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Complexity and extent of

disease AND the ability to

achieve complete

revascularization is an

important determinant of

outcome with PCI versus

CABG

Capodanno, D. et al. J Am Coll Cardiol Intv 2009;2:731-738

Score < 34Score > 34

Importance of the SYNTAX Score in Determining

Outcome for PCI versus CABG

Capodanno, D. et al. J Am Coll Cardiol Intv 2009;2:731-738

Relationship Between SYNTAX Score and Ability

to Achieve Complete Revascularization with PCI

versus CABG

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The SYNTAX Trial

• Largest trial of PCI vs CABG in

complex, multi-vessel disease

including left main disease.

• Left main subset consisted of 705

patients

PPPP=0.12=0.12=0.12=0.12

31.031.031.031.0%%%%

0000

Cumulative Event Rate (%)




25252525

50505050

Months Since AllocationMonths Since AllocationMonths Since AllocationMonths Since Allocation

<1 year

13.7% vs 15.8%

P=0.44

1-2 years

7.5% vs 10.3%

P=0.22

2-3 years

5.2% vs 5.7%

P=0.78

3-4 years

6.4% vs 8.3%

P=0.35

36.936.936.936.9%%%%

TAXUSTAXUSTAXUSTAXUS (N=357)(N=357)(N=357)(N=357)CABGCABGCABGCABG (N=348)(N=348)(N=348)(N=348)

MACCE to 5 YearsLeft Main Subset

4-5 years

5.9% vs 5.5%

P=0.82

0000 12121212 6060606024242424 36363636 48484848

Serruys PW et al. Lancet 2013;381:629Serruys PW et al. Lancet 2013;381:629Serruys PW et al. Lancet 2013;381:629Serruys PW et al. Lancet 2013;381:629––––38383838

PPPP=0.12=0.12=0.12=0.12 PPPP=0.53=0.53=0.53=0.53 PPPP=0.03=0.03=0.03=0.03 PPPP=0.10=0.10=0.10=0.10 PPPP<0.001<0.001<0.001<0.001

MACCE to 5 YearsLeft Main Subset

Event rate (%)

Event rate (%)

Event rate (%)

Event rate (%)

TAXUS (n=357)TAXUS (n=357)TAXUS (n=357)TAXUS (n=357)CABG (n=348)CABG (n=348)CABG (n=348)CABG (n=348)


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TAXUSTAXUSTAXUSTAXUS (N=135)(N=135)(N=135)(N=135)

CABGCABGCABGCABG (N=149)(N=149)(N=149)(N=149)CABG PCI

p

value

Death 14.1% 20.9% 0.11

CVA 4.9% 1.6% 0.13

MI 6.1% 11.7% 0.13

Death,

CVA or

MI22.1% 26.1% 0.40

Revasc 11.6% 34.1% <0.001

LM DiseaseLM DiseaseLM DiseaseLM Disease

MonthsMonthsMonthsMonths

MACCE (%)

MACCE (%)

MACCE (%)

MACCE (%)

0000 12121212 24242424

50505050

0000

25252525

4848484836363636 60606060

MACCE to 5 Years by SYNTAX Score Tercile LM Subset High Scores ≥33

46.546.546.546.5%%%%

29.7%29.7%29.7%29.7%

PPPP=0.003=0.003=0.003=0.003

Serruys PW et al. Lancet 2013;381:629–38

CABG PCIp

value

Death 15.1% 7.9% 0.02

CVA 3.9% 1.4% 0.11

MI 3.8% 6.1% 0.33

Death,

CVA or

MI19.8% 14.8% 0.16

Revasc 18.6% 22.6% 0.36

LM DiseaseLM DiseaseLM DiseaseLM Disease

TAXUSTAXUSTAXUSTAXUS (N=221)(N=221)(N=221)(N=221)

CABGCABGCABGCABG (N=196)(N=196)(N=196)(N=196)

31.331.331.331.3%%%%

32.1%32.1%32.1%32.1%

Months Since AllocationMonths Since AllocationMonths Since AllocationMonths Since Allocation





0000 12121212 24242424

50505050

0000

25252525

4848484836363636 60606060

PPPP=0.74=0.74=0.74=0.74


MACCE to 5 Years by SYNTAX Score Tercile LM Subset Low to Intermediate Scores (0-32)

What have we learned?• Complexity and extent of disease is an

important determinant of outcome in PCI vs

CABG debate.

• High SYNTAX score (>33) does better with

CABG

• Data suggests less risk of stroke and lower

mortality with PCI for low-intermediate

SYNTAX score (<33).

• Studies not designed or powered to definitely

answer this question

• Thus, there is clinical equipoise regarding

choice of revascularization for SYNTAX score

<33.

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EXCEL Trial

R

Clinical follow-up:1 mo, 6 mo and yearly through 5 years

EXCEL: Study Design

3600 pts with unprotected left main disease

SYNTAX score ≤32

Consensus agreement by heart team

Yes

(N=2600)

No

(N=1000)

Enrollment

registry

PCI (Xience Prime)

(N=1300)

CABG

(N=1300)

@ 165 international sites

EXCEL: Inclusion Criteria

• Clinical and anatomic eligibility for both PCI and CABG by heart team consensus

• Silent ischemia, stable angina, unstable angina or recent MI

• Significant LM disease by heart team consensus

- Angiographic DS ≥70%, or

- Angiographic DS ≥50% to <70% with

- a markedly positive noninvasive study, and/or

- IVUS MLA <6.0 mm2, and/or

- FFR <0.80

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EXCEL: Principal Exclusion Criteria

• Prior PCI within 1 year, or prior LM PCI anytime

• Prior CABG anytime

• Need for any cardiac surgery other than CABG

• Additional surgery required within 1 year

• Unable to tolerate, obtain or comply with dual antiplatelet therapy for 1 year

• Non cardiac co-morbidities with life expectancy <3 years

• Left main RVD <2.25 mm or >4.5 mm

EXCEL: Principal Exclusion Criteria

• The presence of any condition(s) which leads the surgeon to believe that clinical equipoise is not present (i.e. the subject should not be treated by CABG, but rather should be managed with PCI or medical therapy

• The presence of any condition(s) which leads the Interventionalist to believe that clinical equipoise is not present (i.e. the subject should not be treated by PCI, but rather should be managed with CABG or medical therapy

EXCEL: Principal Endpoints• Primary endpoint: Death, MI, or stroke at 3 years

Powered for sequential noninferiority and

superiority testing

• Major secondary endpoints (powered):

1. Death, MI, or stroke at 30 days

2. Stroke at 30 days

3. Unplanned repeat revascularization for

ischemia at 3 years

• Additional secondary endpoint (powered):

1. Death, MI, stroke or unplanned

revascularization for ischemia at 3 years

• Quality of life and cost-effectiveness assessments:

At baseline, 1 month, 1 year, 3 years and 5 years

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EXCEL Case Review

Left Main PCI

DP is a 65 year old woman with chest, neck

and arm pain…..

History

• 65 year old smoker with prior IMI and

DES to RCA

• Reports a one week history of chest

tightness and presented with

prolonged, left sided chest pain.

• History of hypertension, carotid

disease and dyslipidemia

Coronary Angiography: RCA

Ostial RCA

Prior stents

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Coronary Angiography: LCAOstial

LM

Coronary Angiography: LCA

Ostial LAD lesion

OM lesion

IVUS

Ostial LAD MLA = 3.6 mm2

Ostial LM MLA = 3.7 mm2

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SYNTAX

SCORE =28

Enrolled in

EXCEL

Randomized

to PCI

Ramus/OM Stenting

LAD Stenting

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Left Main Stenting

Final Kissing Balloons

Final Angiogram: LCA

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Final Angiogram: RCA

Issues in Unprotected Left Main Stenting

Technical aspects

Management of bifurcation

Staging if multi-vessel disease

Need for Hemodynamic Support

Choice of Stents (does not seem to matter)

Adjunctive Pharmacology

Role of IVUS

Follow-up

Bifurcation Strategies

• The bifurcation is involved in over 50% of LM

cases.

• PCI of bifurcation associated with high risk of

MACE as compared to ostial/mid shaft lesions (JACC Intv 2013:6:1242-9)

• Optimal strategy is not yet known. Most favor

a “provisional stent” strategy (JACC Intv 2014;7:255-63).

• If 2 stent strategy used, “Double-kissing-

crush” technique has lower rate of TVR and

ST than “Culotte” technique (JACC 2013;61:1482-8)

• Need proper RCT to answer this important

question.

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Double Kissing Crush Technique

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From Fajadet J and Chieffo A. Eur H J 2012;33:36-50

Need for Support

Devices available for support of high risk PCI

IABP

IMPELLA

TANDEM

Not needed for most Left Main PCI cases. Need

based on:

LV function

Hemodynamic status (LVEDP, CO etc)

Status of the RCA

Anticipated ischemic time with PCI

Complexity of intervention

Unsupported, left main PCI

Balloon

Inflated

Here

Consider

New Career

Here

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Baseline

With TANDEM Heart

Unprotected,

complex left main

PCI with occluded

RCA and EF 20%

Adjunctive Pharmacology

Stent thrombosis would likely be a

fatal event in the left main setting.

How long to treat with dual anti-

platelet therapy? (ISAR-LEFT MAIN

data is reassuring regarding late stent

thrombosis)

Should we be assessing platelet

inhibition?

Role of IVUS Imaging

Optimizes sizing

Determines involvement of the side branches

Assesses ostial coverage and identifies stent

apposition/expansion.

Should be done in all cases.

3 year freedom

from

IVUS No IVUS p value

MACE (overall) 88.7% 83.6% 0.04

MACE (distal LM) 90% 80.7% 0.03

Stent thrombosis 0.6% 2.2% 0.04

JACC Intv 2014;7:244-54

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Surveillance Post-PCI of Left Main

Disease

Optimal surveillance during follow-up is unclear.

Symptoms? Stress test? Angiography?

Concern about asymptomatic restenosis and

risk of sudden death led many to advocate

routine angiography at 2-6 months.

However, this strategy has not been shown to

predict outcome so now classified as Class III

indication in the guidelines.

SUMMARY: Left Main PCI

Patients with left main disease often have complex,

coexisting coronary disease.

Patient selection is important. Value of heart team

approach, assessment based on STS and SYNTAX

scores.

Currently, PCI is of uncertain appropriateness in

operative candidates with low-moderate SYNTAX score

and is INAPPROPRIATE in operative candidates with

high SYNTAX score. EXCEL trial designed to shed more

light on low-moderate SYNTAX score patients.

PCI of left main requires skill with management of ostial

lesions, bifurcation techniques, support devices and

IVUS.

Documents

Ragosta - Left Main Disease - Oregon ACC · 6/2/2014 7 Treatment of Left Main Disease Surgery Percutaneous Coronary Intervention Surgery for Management of Left Main Disease 1.CABG