DISCLOSURES Honorarium – Research / Advisor, Expert Services and Conferences in Nuclear Cardiology

BMS, CVT, Astellas, Lantheus, PPGx, International Atomic Energy Agency

Royalties – Publications in Nuclear Cardiology Springer-Verlag-Nuclear Cardiology and Correlative Imaging: a teaching file, NY, 2004 Lippincott Williams & Wilkins, - Nuclear Medicine teaching File, 2009

João V. Vitola Curitiba

Quantitation in Nuclear Cardiology Influence on Management Decision : Revascularization vs Medical Therapy

joaovitola@quantamn.com.br

• Clinical cases – to ilustrate the relatioship between ischemia and sudden death

• How to segment the LV to quantify extent and severity of ischemia ?

• Quantitation based on perfusion scores (SSS, SDS , SRS) and relation to risk

• LV volumes, LVEF and risk

• Quantitation based on % of LV ischemic and event risk

• Use of quantitation as a measure of success of treatment in clinical trials

Sequence to follow and discuss

51 yo, HTN, obese DM, Fam Hx CAD

NO HISTORY OF CAD

Episodes of chest pain at rest and exercise

Referred for outpatient MIBI

NSR after 3 shocks … cath … 3 vessels .. Tight lesions …surgery !

How much ischemia ?

Very “significant” ischemia ~ enough to induce ST elevation and VTach

Female, 54 yo, obese, atypical chest pain, referred for MIBI

3 min AFTER low workload exercise on the treadmill

Middle Age Women undergoing investigation of suspected CAD

Ischemia Induced Cardiac Arrest Would probably be fatal outside hospital/clinic

OUTCOME – Successful defibrilation, Cath (3 V disease) Surgical revascularization, ALIVE AND WELL

How much ischemia ?

NO HISTORY OF CAD

Sudden death is frequently the first manifestation of CAD

CHALLENGES TO FIGHT CVD MORTALITY

CHALLENGES TO FIGHT CVD MORTALITY

50% of AMI patients die before arriving to the hospital

Mechanisms of death in CAD

• Atherosclerosis : obstructive disease – severe ischemia – ventricular arrythmias – specially if LV dysfunction

• Atherosclerosis : unstable plaques

Changing the paradigm in cardiac risk stratification From : Anatomic and static (Lumen) concept (angio) To : Physiological and Dynamic (FFR, CVR, IVUS, SPECT) From: What % lumen obstruction ? To : How much myocardium at risk ? What % myocardium severely ischemic

Vitola JV (QUANTA database)

Anormalidades de Perfusao

6776

2143

477 65164.55% 20.41% 4.54% 6.20%

010002000

3000400050006000

70008000

Seqüência1Seqüência2

Seqüência1 6776 2143 477 651

Seqüência2 64.55% 20.41% 4.54% 6.20%

Normal Isquemia Fibrose F+I

What results to expect in a nuclear cardiology Laboratory ? Patterns of Perfusion Abnormality

Average Abnormal Rate 35.4%

76%75%

64%63.60%

60.30%53.20%52.30%

39.80%39.20%38.30%

35.40%32.80%

30.50%26.90%

22.60%6.00%

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8

High DukeHx CABG

Hx PCIKnown CAD

DipyridamoleTypical Pain

DiabetesMale Gender

CholesterolSedentary

Mean Abnormal RatePhy Active

Female GenderExercise Test

Low DukeAthletes

Frequency of Abnormal SPECT Depending on Each Variable

Above Average

Vitola JV (QUANTA database, n > 10.000)

• Test result Normal vs Abnormal is not enough • Magnitude of ischemia relates to prognosis • Small vs large, discrete vs severe • Low risk vs high risk ischemia

QUANTIFICATION OF ISCHEMIA NECESSARY TO GUIDE MANAGEMENT

Extent/Severity of Perfusion Defects

Risk

*

*Adjusted or unadjusted

Source: Klocke et al. J Am Coll Cardiol 2003.

Extent/Severity – Ischemia Predicting Death

Source: Klocke et al. J Am Coll Cardiol 2003.

Management based on degree of Ischemia Who Needs Revascularization ? Nuclear is powerful to estimate risk

Quantification in Nuclear Cardiology Scores

Severe LCX Moderate RCA

Extent: number of segments – 1 to 17 Severity: 0 normal 1 mild 2 mod 3 severe 4 absent

SSS 32

Segment Severity 5 4 6 4 11 4 12 4 16 4 4 3 10 3 15 2 3 2 9 2

What is the SSS ?

Risco baseado na quantificação - SPECT

0.3 0.50.8

2.72.3

2.92.4

4.2

0

1

2

3

4

5Cardiac DeathMI

Hachamovitch Circ 1998;97:535-543

Mildly Abnormal

Moderately Abnormal

Severely > 13 Abnormal

Normal < 4 2,946 884 455 898

Summed Stress Perfusion Score

What to Report in This Study in a descriptive way ?

What to Report in This Study ?

Sestamibi, exercise, Bruce, 134 bpm, 6.5 minutes, Severe, Extensive, AS + Apical, Proximal LAD territory, Hipokinesia from stress, stunning-CLEAR MESSAGE of HIGH RISK

LV function – quantitation parameters and risk estimations

Adenoex, 5 min on Bruce, peak HR 93 spm (on meds), denied chest pain.

AMI 6 years in the past, treated with primary PTCA

AKINESIA REMODELED LV LVEF 25 % (nl > 50%) EDV 235 ml (nl 101 ml) ESV 176 ml (nl 44 ml)

Stunning

Scar from prior MI

Hibernation

63 yo man, physician, had sudden death while playing tennis MPI 24 months prior to his death

% Ischemic Myocardium: (Stress TPD-Rest TPD) • < 5%: Minimal (“No Ischemia”) • 5.0%-9.9%: Mild • ≥10%: Moderate-to-Severe Significant Reduction in Ischemia: • ≥5% Reduction in Ischemic Myocardium*

% Ischemic Myocardium Total Perfusion Deficit (TPD)

Source: Slomka et al. J Nucl Cardiol 2005;12:66-77

Defect Extent

TPD Lower Nl Limit

Defect Severity

TPD: Quantitative Measure of Defect Extent & Severity

< 2.5 SD

log

Haza

rd R

atio

0

1

2

3

4

5

6

% Total Myocardium Ischemic 0 12.5% 25% 32.5% 50%

Medical therapy

Revascularization *

*

*P<0.001

Source: Hachamovitch et al. Circulation. 2003;2900-2907.

10,627 patients 146 Cardiac death 492 All cause mortality

Risk of Cardiac Death & Ischemic Burden

Post-SPECT Therapeutic Decisions

OMT (n=155) PCI + OMT (n=159)

8.6% 8.1%

(6.9%-9.4%)

8.2% 5.5%

(4.7%-6.3%)

Shaw L et al, circ, 2008

COURAGE - Randomization based on anatomy NOT ischemia Only Sub study used nuclear quantification (n=314)

Help us understand why PCI did no reduce mortality in the entire study but only subgroups

p=0.001

(n=68) (n=37)

32.4%

16.2%

Deat

h or

MI R

ate (

%)

Sub study COURAGE – nuclear

ISCHEMIA Trial International Study of Comparative Health Effectiveness with Medical and Invasive Approaches NIH funding 97 millhões US PIs – David Maron, Nashville Judith Hochman, NYC

•8,000 stable CAD patients • 3-6 yr. F/U for events*

*CV Death, MI, hosp for ACS, CHF

How would you manage the following patients in 2012 ?

Ischemia trial , perhaps results by 2018 ~ 2020 ?

Habibian R, Delbeke D, Martin W, Sandler M, Vitola JV Cardiovascular Imaging, in Nuclear Medicine Teaching File, 2009

Male, 53 yo Atypical pain

stress Calcium score: 10 / Duke Intermediate

Eixo Curto

Eixo Longo Vertical

Eixo Longo Horizontal

Cortes Tomográficos-Referência

Post 1 stent LAD

Risk > 3%/ y Risk< 1%/y

Habibian R, Delbeke D, Martin W, Sandler M, Vitola JV Cardiovascular Imaging, in Nuclear Medicine Teaching File, 2009

Severe ischemia > 10% of LV

Habibian R, Delbeke D, Martin W, Sandler M, Vitola JV Cardiovascular Imaging, in Nuclear Medicine Teaching File, 2009

Male 61 yo Dispnea on exertion, Atypical Pain

> 10% severe ischemia

Eixo Curto

Eixo Longo Vertical

Eixo Longo Horizontal

Cortes Tomográficos-Referência

Post CABG – 0 % ischemia

Habibian R, Delbeke D, Martin W, Sandler M, Vitola JV Cardiovascular Imaging, in Nuclear Medicine Teaching File, 2009

Sudden death is frequently the first manifestation of CAD NUCLEAR Imaging is useful to provide quantification of ischemia and risk assessment Define high risk subgroups – who will benefit from revascularization Define low risk subgroups – who will benefit from prevention and medical therapy ISCHEMIA trial will be an important prospective randomized trial based on % ischemia

CONCLUSIONS

Thank you

joaovitola@quantamn.com.br

CURITIBA