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Evaluation of IHD in DM, ESRD, Women, Elderly

DISCLOSURESDISCLOSURESHonorarium Honorarium –– Research and Conferences in Nuclear CardiologyResearch and Conferences in Nuclear Cardiology

BMS, CVT, BMS, CVT, AstellasAstellasInternational Atomic Energy AgencyInternational Atomic Energy Agency

Royalties Royalties –– Publications in Nuclear CardiologyPublications in Nuclear CardiologySpringerSpringer--VerlagVerlag--Nuclear Cardiology and Correlative Imaging: a teaching file,Nuclear Cardiology and Correlative Imaging: a teaching file, NY, 2004NY, 2004LippincottLippincott Williams & Wilkins, Williams & Wilkins, -- Nuclear Medicine teaching FileNuclear Medicine teaching File, 2009, 2009

JoãoJoão V. Vitola, MD, PhDV. Vitola, MD, PhD

Cardiologist and Nuclear Medicine Physician Cardiologist and Nuclear Medicine Physician Quanta Quanta DiagnosticoDiagnostico NuclearNuclear

CuritibaCuritiba -- BrazilBrazil

2005

WHO estimates

2005

2015

100%

WHO estimates

Higher Prevalencein Women

Diabetes Atlas: 2006; DIFDiabetes Atlas: 2006; DIF

World Scenario – 2007Diabetes International Federation

World Scenario – Estimation for 2025Diabetes International Federation

Diabetes Atlas: 2006; DIFDiabetes Atlas: 2006; DIF

Diabetes is Increasing – Mostly in Developing Countries (middle age)

Source WHO

$

Resultado anormal: idade x DM

33% 33%

44%50%

62%

73%

Até 39 40 a 49 50 a 59 60 a 69 70 a 79 80 ou mais

Não diabéticoDiabético

DM, Age and SPECT Abnormalities

%ABNORMAL

(n=10594)(n=10594)

Vitola JV et al , Quanta Database – Curitiba - Brazil

36 yo, ManIDDM, Obese (IMC: 30.1), HTN, High CholesterolDenies Chest Pain

TMTRest ECG – LAHBBruce : 10 minHR: 84 .... 159 (85% = 156 bpm)BP: 130/80 ....180/90 mmHgNo ST segment changesAt peak exercise right should pain, Not LimitingDuke ScoreDuke: exer min – 5x ST – 4x anginaDuke = (+10) – (5x0) – (4x1) = + 6

Clinical Case

Eje Corto

Eje Largo Vertical

Eje Largo Horizontal

Cortes Tomográficos-Referencia

ESV: 70 ml, LVEF: 45%High Risk Findings

Revascularization + Optimized Medical Therapy

Source: Berman JACC 2003; 41(7):1125-33.

Cardiac Mortality in 6,173 Women and Men by Cardiac Mortality in 6,173 Women and Men by Adenosine SPECT ResultsAdenosine SPECT Results

00LowLow

MenMenWomenWomen

Card

iac M

ortal

ityCa

rdiac

Mor

tality

MildlyMildly Mod.Mod. SevereSevere LowLow MildlyMildly Mod.Mod. SevereSevereNonNon--DiabeticDiabetic DiabeticDiabetic

112233445566778899

Giri S, et al. Circulation. 2002

Lowest Survival Rates for Diabetic WomenLowest Survival Rates for Diabetic Women

*P < .05. Extent of ischemia was determined by the number of vascular territories (0, 1, or 2 vessels) involved in the reversible perfusion defect.

≥≥22--vessel vessel ischemia ischemia

11--vessel vessel ischemia ischemia

00--vessel vessel ischemia ischemia

≥≥22--vessel vessel

ischemia ischemia 11--vessel vessel ischemia ischemia

00--vessel vessel ischemia ischemia

77.577.585.085.095.595.597.097.097.597.598.898.8Nondiabetic Nondiabetic womenwomen

60.0*60.0*72.5*72.5*96.596.581.3*81.3*80.0*80.0*99.099.0Diabetic womenDiabetic women85.085.088.088.093.893.895.095.096.596.599.099.0Nondiabetic menNondiabetic men79.079.077.077.086.386.391.391.393.093.093.893.8Diabetic menDiabetic men

Death/MIDeath/MIDeathDeath

Eur Heart J. 2004 Apr;25(7):543-50.

ShouldShould wewe bebe evaluationevaluationasymptomaticasymptomatic DM DM usingusing SPECT as a SPECT as a routineroutine ??

ESTUDIO DIAD ESTUDIO DIAD DDetection of etection of IIschemia in schemia in AAsymptomatic symptomatic DDiabeticsiabeticsN=1123 N=1123 randomizadosrandomizados (test: 561, no test: 562)(test: 561, no test: 562)

•• 22 % 22 % estudiosestudios anormalesanormales = = isquemiaisquemiasilentesilente ((mayoriamayoria ischemia ischemia leveleve).).

•• 6% 6% defectosdefectos severosseveros -- predictorespredictores ::–– GGééneronero MasculinoMasculino (RR 2.5)(RR 2.5)–– DuraciDuracióónn DM (RR 5.2)DM (RR 5.2)–– DisfunciDisfuncióónn AutonAutonóómicamica (RR 5.6)(RR 5.6)

Wackers F et al. Diabetes Care 2004;27:1954-61

ESTUDIO DIAD ESTUDIO DIAD –– 5 years later 5 years later DDetection of etection of IIschemia in schemia in AAsymptomatic symptomatic DDiabeticsiabeticsN=1123 N=1123 randomizadosrandomizados (test: 561, no test: 562)(test: 561, no test: 562)

•• 4.8 y 4.8 y f/uf/u•• Aggressive therapyAggressive therapy according to guidelines for DM therapyaccording to guidelines for DM therapy•• 80% ASA, 80% ASA, StatinsStatins, ACEI + change lifestyle., ACEI + change lifestyle.•• At 3 y,At 3 y, on repeat scan, 80% of initial abnormal SPECTS had become normaon repeat scan, 80% of initial abnormal SPECTS had become normal l (more aggressive (more aggressive txtx), and only 10% had new defects), and only 10% had new defects•• At 5 y,At 5 y, overall, event rate 0.6%/y (low) overall, event rate 0.6%/y (low) –– close follow upclose follow up•• 15 hard cardiac events test group, 17 events no test group (no d15 hard cardiac events test group, 17 events no test group (no difference)ifference)•• RevascRevasc 5.5% test group, 7.8 % no test group5.5% test group, 7.8 % no test group•• Severe defects predicted worse prognosis (only 33 moderate or laSevere defects predicted worse prognosis (only 33 moderate or large rge defects and 2,4% events per year)defects and 2,4% events per year)•• DIAD conclusion: DIAD conclusion: SPECT not indicated in any asymptomatic DM, use SPECT not indicated in any asymptomatic DM, use SPECT if clinical condition changes, aggressive SPECT if clinical condition changes, aggressive txtx in DM leads to low event in DM leads to low event rate.rate.

Wackers F et al. JAMA 2009

The Elderly Population is Increasing

Source: WHO

$

1047260534419Total

6,04%4,48%8,19%

63327136280 ou mais

21,04%18,45%24,58%

22031117108670 a 79

27,54%27,28%27,90%

28841651123360 a 69

27,65%28,86%25,98%

28951747114850 a 59

13,55%15,45%10,95%

141993548440 a 49

4,18%5,48%2,40%

438332106Até 39MasculinoFeminino

TotalSexo

Idade

Vitola JV et al , Quanta Database – Curitiba - Brazil

Prevalence of Elderly undergoing SPECT – special attention

Resultado anormal: idade x sexo

10%

19% 21%

30%

41%

52%

14%

23%

33%

46%

55%

68%

Até 39 40 a 49 50 a 59 60 a 69 70 a 79 80 ou mais

FemininoMasculino

RR 1,5 (CI 1,0-2,2)RR 1,1 (CI 0,9 – 1,3)RR 1,4 (CI 1,2 - 1,7)RR 1,2 (CI 1,0 – 1,5)RR 1,9 (1,3 – 2,7)

P<0.048P<0.611P<0.001P<0.036P<0.001

Age as a Age as a predictorpredictor ofof SPECT SPECT abnormalityabnormalityQuanta Database – Curitiba – Brazil (n=10594)

Elderly patients, age > 75 yo, with normal SPECT, will this translate into lower mortalityrates ?

Vitola JV et al , Quanta Database – Curitiba - Brazil

Tempo de sobrevida x perfusãoÓbito Não óbito

Tempo de sobrevida (meses)

Prop

orçã

o acu

mulad

a de s

obre

vida

0,60

0,65

0,70

0,75

0,80

0,85

0,90

0,95

1,00

0 10 20 30 40 50 60 70

p < 0,001

Perfusão normal

Perfusão anormal

Elderly age > 75 yo

Tempo de sobrevida x sexoÓbito Não óbito

Tempo de sobrevida (meses)

Prop

orçã

o acu

mulad

a de s

obre

vida

0,60

0,65

0,70

0,75

0,80

0,85

0,90

0,95

1,00

0 10 20 30 40 50 60 70

p = 0,021

Feminino

Masculino

Vitola JV et al , Quanta Database – Curitiba - Brazil

MALE Gender, still a predictor of higher death rates, age > 75 yo

Resultado anormal: idade x tipo de exame

11%

18%

33%38%

44%

29%

37%

53%58%

37%

56%59%

67%

23%

42%

64%61% 60%

66%

33%

42%

61%61%

Até 39 40 a 49 50 a 59 60 a 69 70 a 79 80 ou mais

ExercícioCombinadoDipiridamolDobutamina

Ancianos que hacen Ejercício como Estrés: Menor chance de anormalidades de perfusión

Vitola JV et al , Quanta Database – Curitiba - Brazil

Elderly patients age > 75 yo, who exercisefor stress, have a lower mortality rate ?

Vitola JV et al , Quanta Database – Curitiba - Brazil

Elderly > 75 yo, overall average mortality rate ~5 % /year(much lower for exercise stress)

Role of LV function measured by Gated-SPECT, as a predictor of death in ElderlyPatients, age > 75 yo ?

PREVALENCE CAD PREVALENCE CAD -- USAUSA

5,510,4

17,4

34,2

51,0

65,270,7

4,60 4,20

13,60

28,90

79,00

48,10

65,20

0102030405060708090

20-24 25-34 35-44 45-54 55-64 65-74 75+Ages

Perc

ent o

f Pop

ulatio

n

MalesFemales

American Heart Association. 2002 Heart and Stroke Statistical Update. 2001

Chronic Heart Failure in the United States. A Manifestation of Coronary Artery Disease

Mihai Gheorghiade, MD; Robert O. Bonow, MD Circulation 1998;97:282-289

CAD68%

non-CAD32%

CAD non-CAD $

Prevalence of Heart Failure by Gender Prevalence of Heart Failure by Gender and Age in the Framingham Studyand Age in the Framingham Study

0,1 0,51,3

3,4

6,6

9,7

0,10,7

1,8

6,26,8

9,8

0

2

4

6

8

10

20-34 35-44 45-54 55-64 65-74 75+Age

patie

nts pe

r 100

perso

ns

WomenMen

Ho, Pinsky, Kannel, Levy. J Am Coll Cardiol 1993; 22:6A

$

Prognostic Significance of Prognostic Significance of 123123II--mmIBG IBG Myocardial Myocardial ScintigraphyScintigraphy in Heart Failure in Heart Failure Patients: Results from the Prospective Patients: Results from the Prospective

MulticenterMulticenter International ADMIREInternational ADMIRE--HF TrialHF Trial

*ADMIRE-HF: AdreView Myocardial Imaging for Risk Evaluation in Heart Failure

Jacobson A et al. ACC, 2009

[123I]mIBG Planar Imaging for Cardiac Assessment

Normal innervation NHYA Class II NYHA Class IVH/M ratio: 2.2 1.7 1.1

Courtesy

Courtesy Prof. Dr. Alia Abd El-Fattah, MDCairo University

Chronic Kidney Disease

www.usrds.org

Stages based on GFR (ml/min/1.73 m2 )� Stage 1: normal (proteinuria, abnormal markers) � Stage 2: 60-89� Stage 3: 30-59� Stage 4: 15-29� Stage 5: < 15 (dialysis or renal failure)

Courtesy Prof. Dr. Alia Abd El-Fattah, MDCairo University

Circulation 2008;118:2540-2549

Annual CD stratified by presence of ischemia and scar

4.7%

2.2%0.9%0.4%

0%

5.5%

2.2%3.3%

9.6%

11%

3.8%3.4%

0

2

4

6

8

10

12

> 90 (N = 176) 60-89 (N=875) 59-30 (N=511) <30 (N=90)

Normal Scar Ischemia

Cardi

ac de

ath/ye

ar

Estimated GFR

Courtesy Prof. Dr. Alia Abd El-Fattah, MDCairo University

0.150.151.9%1.9%11 (3.6%)11 (3.6%)1%1%15 (2.2%)15 (2.2%)MIMI

0.040.046.2%6.2%37 (12.3%)37 (12.3%)4%4%56 (8.1%)56 (8.1%)All Cause MortalityAll Cause Mortality

0.0010.0012.7%2.7%16 (5.3%)16 (5.3%)0.8%0.8%11(1.6%)11(1.6%)Cardiac DeathCardiac Death

P valueP valueAnnual Annual RateRateTotalTotalAnnual Annual

RateRateTotalTotalOutcomeOutcome

Circulation 2008;118:2540-2549

GFR>60(n=684) GFR<60(n=304)

Unadjusted event rates for Patients With No Defects on MPI (n=664)

Courtesy Prof. Dr. Alia Abd El-Fattah, MDCairo University

0.590.593.8%3.8%23 (7.6%)23 (7.6%)3.3%3.3%24 (6.6%)24 (6.6%)MIMI

<0.001<0.00112.5%12.5%76 (25.3%)76 (25.3%)6.5%6.5%48 (13%)48 (13%)All Cause MortalityAll Cause Mortality

<0.001<0.0019.5%9.5%58 (19.3%)58 (19.3%)4%4%29(8%)29(8%)Cardiac DeathCardiac Death

P valueP valueAnnual RateAnnual RateTotalTotalAnnual RateAnnual RateTotalTotalOutcomeOutcome

Circulation 2008;118:2540-2549

GFR>60(n=364) GFR<60(n=300)

Unadjusted event rates for Patients With Defects on MPI (n=988)

Courtesy Prof. Dr. Alia Abd El-Fattah, MDCairo University

CVD disease mortality trends for males and females CVD disease mortality trends for males and females (United States: 1979United States: 1979--2004). 2004). SSource: NCHS and NHLBI.ource: NCHS and NHLBI.

400

450

500

550

79 80 85 90 95 00 04Years

Deat

hs in

Tho

usan

ds

Males Females

400

450

500

550

79 80 85 90 95 00 04Years

Deat

hs in

Tho

usan

ds

Males Females

Heart disease and stroke AHA statistcs update 2008Circulation, January, 2008

Higher Mortality Rate for Women Following AMIHigher Mortality Rate for Women Following AMI

Gender differences in mortalityGender differences in mortality–– 58% of women who die suddenly from CAD 58% of women who die suddenly from CAD did not have classic warningdid not have classic warningsymptomssymptoms–– 38% of women vs 25% of men will die within 1 year after heart at38% of women vs 25% of men will die within 1 year after heart attacktack–– A higher proportion of A higher proportion of women die of sudden cardiac death prior to hospital women die of sudden cardiac death prior to hospital arrival compared to men (52 % arrival compared to men (52 % vsvs 42 %)42 %)

American Heart Association. Heart Disease and Stroke Statistics—2006 Update.http://www.cdc.gov

Higher Mortality Rate for Women Following AMIHigher Mortality Rate for Women Following AMI

Gender differences in mortalityGender differences in mortality–– 58% of women who die suddenly from CAD 58% of women who die suddenly from CAD did not have classic warningdid not have classic warningsymptomssymptoms–– 38% of women vs 25% of men will die within 1 year after heart at38% of women vs 25% of men will die within 1 year after heart attacktack–– A higher proportion of A higher proportion of women die of sudden cardiac death prior to hospital women die of sudden cardiac death prior to hospital arrival compared to men (52 % arrival compared to men (52 % vsvs 42 %)42 %)

American Heart Association. Heart Disease and Stroke Statistics—2006 Update.http://www.cdc.gov

MORTALIDAD HOSPITALARIA POSTMORTALIDAD HOSPITALARIA POST--INFARTO AGUDO DE MIOCARDIOINFARTO AGUDO DE MIOCARDIO

n: 95 mujeres diabéticasn: 88 varones diabéticos

Svage et al. Am J Cardiol 1.988; 62: 665

MORTALIDAD HOSPITALARIA

Women Ischemic Syndrome Evaluation :The Changing Paradigm of CAD detection in Women

Gulati M et al Adverse cardiovascular outcomes in women with nonobstructive coronary artery disease: A report from the Women’s Ischemia Syndrome Evaluation study and the St James Women Take Heart Project. Arch Intern Med. 2009;169:843-850.

0.00819.1%9.1%3.9%SecondaryCompositeEndpoint

0.00216.0%7.9%2.4%PrimaryCompositeEndpoint

0.748.2%3.0%2.1%All-CauseMortality

0.824.4%1.5%0.6%Cardiovascular Death

0.0045.2%2.4%1.0%Stroke

0.0025.6%3.3%0.3%Hospitalizationfor CHF

0.313.9%0.9%0.7%MI

AdjustedP Valuea,b

NonobstructiveCAD

(WISE, n = 222)

Normal Coronary Arteries

(WISE, n = 318)

Asymptomatic(WTH,n =1,000)

Outcome Data on Symptomatic Women with NonObstructive CAD on Cath

Life tables for WHO member states, Geneva, Word Health Organization , 2006http://www.who.int/whosis/database/life_tables.cfm

Country Men WomenRussia 59 72India 62 64Brazil 68 75China 71 74Argentina 72 78Cuba 75 79USA 75 80Canada 78 83Italy 78 84Australia 79 84Japan 79 86

Women die later

DeathsDeaths From CVD by Age and GenderFrom CVD by Age and Gender

050.000

100.000150.000200.000250.000300.000

<45 45-64 65-84 >84Ages

Deat

hs in

Tho

usan

ds

CVD: Males CVD: Females

Anderson RN. National Vital Statistics Reports. 2002

Women die later …

CAD – is it different in women compared to men ?• Clinical Presentation – atypical symptoms• Macro vc microcirculatory disease – endothelial Dx• At time of diagnosis more diffuse disease – not so much epicardial• Outcomes in subgroups of women worse – DM, blacks, smokers• Outcomes following AMI

Elderly Female, ischemic changes on ECG during adenosine infusion

From Vitola and Delbeke. Nuclear From Vitola and Delbeke. Nuclear Cardiology and Correlative Imaging: Cardiology and Correlative Imaging: A Teaching File. SpringerA Teaching File. Springer--VerlagVerlag, , 2004, Case 4.72004, Case 4.7

Thomas GS. J Nucl Cardiol 2007:14;136-8.

Nuclear Cardiac Imaging Nuclear Cardiac Imaging –– 3 decades of solid data3 decades of solid dataChallenges exist but we are moving on the right directionChallenges exist but we are moving on the right direction50% reduction in mortality in 3 decades50% reduction in mortality in 3 decades

2.5% yearly decrease in

mortality from heart disease

•• ObesityObesity andand DM DM willwill contributecontribute to to increasedincreased CVD CVD mortalitymortality worldwideworldwide

•• PreventionPrevention ofof CAD is CAD is essentialessential

•• ImagingImaging cancan bebe usedused to to assessassess riskriskandand guideguide managementmanagement costcosteffectivellyeffectivelly

•• WideWide variationvariation underunder andand over over utilizationutilization ofof technologytechnology –– regional regional differencesdifferences -- GDP GDP butbut alsoalso InformationInformation

•• ConsideringConsidering increasingincreasing costscosts --essentialessential to to rationalizerationalize investigationinvestigationandand managementmanagement

Confronting the Epidemics of CVD Worldwide:Time to Stop and Think About Cardiac Care

Imaging Utilization in 2009

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