Old and New Stress Agent 계명의대 김기식. Ischemic cascade Myocardial ischemia Diastolic dysfunction Regional systolic dysfunction ECG changes Chest pain.
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Ischemic cascade
Myocardial ischemia
Diastolic dysfunction
Regional systolic dysfunction
ECG changesChest pain
StressDipyridamole
Adenosine
ExerciseTM, bicycle
Dobutamine
Arbutamine
Pacing
Sx & sign(angina, BP )
ST (ECG)Perfusion defect
(Thallium, sestamibiContrast echo)
RWMA(Echo)
Metabolic Abnormality
(PET)
Ischemia
Indication pharmacological stress echocardiography
• Inadequate exercise• Left bundle branch block• Paced ventricular rhythm• pre-excitation or conduction abnormality• Medication: beta-blocker, calcium channel blocker• Evaluation of patients very early after MI(<3 days) or angioplasty stent(<2weeks)• Poor image degradation with exercise• Poor patient motivation to exercise
Pharmacologic Stress Agents
Stress agents
Coronary vasodilator
DipyridamoleAdenosinNew agents
Inotropic agents
Dobutamine Arbutamine New agents
Increased vasomotor tone
Reducedflowreserve
Percent contribution to myocardialischemia
ErgonovineHyperventilation
ExerciseHandgripDobutamine
DipyridamolePacing
Conceptual Role of Different Stress test
Dipyridamole
Potent coronary vasodilatorProvoked anginal attack in angina patients
Vasodilation effectinhibition of reuptake of adenosine by the endothelial cell
Coronary blood flow maldistributionReduction of subendocardial blood flow
in stenotic coronary artery
Dipyridamole
Coronary steal phenomenon
Onset and duration of action: prolong
Standard protocol: 0.54 mg/kg for 4 min
High doseprotocol: 0.84mg/kg
Antidote: theophylline
Dipyridamole
Contraindicationactive wheezinghigh degree AV blockhypotension(SBP<90 mmHg)recent use of dipyridamole(<24 hours)
Relative contraindicationHx of reactive airway diseasesick sinus syndromesevere sinus bradycardia
Adenosine
Naturally occuring agentTwo types of receptor
A1: slowing HR and conductionA2: c-AMP
– decrease calcium uptake by SR-- smooth muscle relaxation vasodilation
Half life: 2 seconds need constanr IV infusionRapidly removed from RBC and endothelial cell
Adenosine-protocol
140 mcg/kg/min for 6 min
Theophylline/Caffeine: proto type adenosine receptor antagonist
Adenosine – side effect
Flushng: 37%Dyspnea: 35%GI discomfort: 15%Headache:14%Light-headedness 9%
Most side effect – short-lived and mild
Dobutamine
Mid, late 1980Synthetic catecholamineProminent inotropic actionLess chronotropic action
Beta 1
Beta2/alpha
Dobutamine 2
Myocardial oxygen demand Normal vessel dilatationStenotic vessel: not directly affect
Action: onset – 2 min half life – 2 min: continous IV
Metabolizd by cathechol-o-methyl transferaseExcretion: hepatobiliary system and kidney
Application of Stress Echo Detection and localization of
coronary artery disease Risk stratification after myocardial
infarction Assessment of myocardial viability Evaluation of myocardial reserve
function in non-coronary heart disease
Dobutamine : protocol
Initial dose: 5-10 mcg/kg/min 10 mcg/kg/min every 3-5 min
Maximum dose: 40-50 mcg/kg/min
Suboptimal chronotropic effectadd atropine
Arbutamine
Synthetic catecholamineHemodynamically similat to dobutamine
x10 affinity to beta receptorx 5 lower binding at alpha receptor
Action onset: 1-2 minHalf-life: 8 min
Dose dependant increaseheart rate, cardiac output, LV systolic pressure, DP/DTmean arterial pressure: decrease
Arbutamine II
Increatment of heart rate
Increatment of SBP
Arbutamine
76%
27%
Exercise
72%
36%
Cohen et al
JACC 1995 26:1168
Arbutamine
0
20
40
60
80
100
120
140
SBP-b SBP-p DBP-b DBP-p
Arb Dob
0
20
40
60
80
100
120
140
HR-b HR-p 0
2
4
6
8
10
12
Change of blood pressure heart rate time to peak HR
Korean J Med 2000 58:1013
Arb DobSensitivity 81% 78%Specificity 90% 72%
Arbutamine: side effect
Tremor: 22%Dizziness: 11%Headache: 11%Paresthesia: 7%Arrhythmia: 6%Hypotension: 4%
1997 FDA approval1999 withdraw from the marget
Sensitivity and specificity of exercise and pharmacologic stress test
Sensitivity(%)
Specificity(%)
Dobutamine
71 – 96
66 - 83
Dipyridamole
43 – 74
92 - 100
Exercise
74 – 97
64 - 88
Combined or Acceleraed stress test
Dobtamine + atropineDipyridamole + ExerciseDipyridamole + DobutamineHigh dose dipyridamoleHigh dose dobutamineCombined contrast echo
Accelelated Dobutamine Stress
High dose dobutamine infusion50 mcg/kg/min for 10 min
P-HRSBPdurationdose
Acc
1401696.4320
Stan
14016212.9353
Similar side effect
AJC 86:825
Combined dipyridamole and dobutamine echocardiography
Borges et al. JASE 2000:14 1057
Predicting functional recovery after PTCALow dose Dob(10 mcg/kg/min) + dip(0.28mg/kg)
0102030405060708090
100
Sensitivity Specificity
DipDobDIDOTL
*
**
Ultrasonically measured flow in the critically stenotic LAD and normal LCx of protocol 2 dogs. Left, LAD and LCx flows at rest (solid bars) and during pharmacological stress (hatched bars) with adenosine (250 micro gram *symbol* kg sup -1 *symbol* min sup -1); right, coronary flow responses to WRC-0470 (0.6 micro gram *symbol* kg sup -1 *symbol* min sup -1). LCx flow increased threefold with adenosine and fivefold with WRC-0470. Flow in the critically stenotic LAD did not change with either stress. From: Glover: Circulation, Volume 94(7).October 1, 1996.1726-1732
Figure . Comparison between the decrease in mean arterial pressure produced by adenosine or WRC-0470 in protocol 2 dogs. Solid bars represent mean arterial pressure at rest; hatched bars show pressure during pharmacological stress. Adenosine infusion resulted in a significant hypotensive response (100 to 76 mm Hg), whereas WRC-0470 produced no hypotension. *P < .0001 vs rest; +P = .02 adenosine vs WRC-0470. From: Glover: Circulation, Volume 94(7).October 1, 1996.1726-1732
Inotropic agent for myocardial viabilty
AmrinoneMilinoneEnoximone
Phosphodiesterase inhibitorPotent Inotropic and vasodilating effect
Amrinone stimulation testAmrinone: Not augment myocardial oxygen demandAmrinone 1mg/kg IV over 4 min after CABGObserve change of LVEF: greater than 10% or not
89%
6%
LVEF >10% < 10% JACC 1996 28:1488
ImproveLVEF>10%
Milinone Stress Echo
Milinone: bipyridine inotropic/vasodialor
50 mcg/kg over 10 min IV infusionLV dysfunction + CABGResults:
Akinetic/dyskinetic segmentsSensitivity: 97.8% 97.5%Spcificity: 94.0% 78.8%PP: 92.9% 84.8%NP: 98.2% 96.3%
JASE 2001, 14:668
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