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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