Vasodilator Stress Agents

	Mechanism of action	T 1/2	Administration	Side effects	Contraindications
Adenosine	A2A receptor à direct coronary vasodilation à 3.5- 4 x increased blood flow à stenotic epicardial coronaries will have attenuated hyperemic response. True ischemia may be induced by coronary steal phenomenon.	Secs	140 mcg/kg/min over a 6 min period Minimum time to tracer injection: 2 mins Continue infusion for 2 mins after tracer injection	Nonspecific chest pain: not an indicator of CAD ST depression >1mm: indicative of significant CAD A1 receptor: AV block à does not require termination of infusion A2b receptor: Hypotension A2b and A3 receptors: Bronchospasm Resolve in few seconds (due to extremely short half-life of adenosine)	Asthma with ongoing wheezing 2/3 AV block without a pacemaker SBP <90 mmHg Use of dipyridamole in last 48 hours; aminophylline in 24 hours or caffeine in last 12 hours (pentoxifylline OK) ACS
Regadenoson	A2A receptor à direct coronary vasodilation (lower affinity than adenosine)	2-4 mins	0.4mg/10 ml given as rapid injection followed by saline flush Tracer injection 10-20 secs after	SOB, flushing, headache Most resolve within 15 mins, headaches resolve in 30 mins (Use aminophylline 50-250 mcg infused slowly) Hypotensionѱ	Asthma with ongoing wheezing 2/3 AV block without a pacemaker SBP <90 mmHg Use of dipyridamole in last 48 hours; aminophylline in 24 hours or caffeine in last 12 hours (pentoxifylline OK) ACS
Dipyridamole	Prevents reuptake and deamination of adenosine à indirect coronary vasodilator Dipyridamole induced hyperemia lasts more than 15mins	30-45 mins (liver)	0.56mg/kg IV over 4 mins (142mcg/kg/min) Tracer injection after 3-5 mins	Flushing, chest pain, headaches, dizziness. Resolve in 15-25 mins (Use aminophylline 125-250 mcg infused slowly- should also be used in the presence of ischemic changes after dipyridamole)	Same as adenosine. CAN be used in patients taking oral dipyridamole.
Dobutamine	Direct B1 and B2 stimulation Increase in heart rate, blood pressure and myocardial contractility. Increases regional myocardial blood flow (similar to exercise, less than adenosine). Does not increase venous return (no increase in wall stress)	2 mins	5mcg/kg/min increased at 3 minute intervals to 40mcg/kg/min. Tracer injection at peak dose and continue infusion for 2 mins after	Palpitations, chest pain, headache, flushing, dyspnea (Use esmolol 0.5mg/kg over 1 min)	ACS Hemodynamically significant LVOT obstruction Severe AS Prior h/o VT Aortic dissection/large aortic aneurysm Uncontrolled hypertension B blockers

Ѱ Risk of hypotension higher in patients with autonomic dysfunction, hypovolemia, left main coronary artery stenosis, stenotic valvular heart disease, pericarditis, pericardial effusions, stenotic carotid artery disease with cerebrovascular insufficiency

Other Myocardial Tracers

Rb-82	Ultra short half life	Myocardial perfusion PET scanning
O-15 Water	Free diffusible, uptake directly proportional to blood flow	Best tracer for myocardial blood flow detection PET Scanning
N-13 ammonia		Myocardial perfusion PET Scanning
C-11 acetate	Oxidative substrate	Can be used for both perfusion and metabolism PET Scanning
C-11 palmitate	Fatty acid substrate	Metabolism PET Scanning
FDG	Glucose metabolism	Metabolism PET Scanning
BMIPP (I-123)	Fatty acid	Myocardial ischemic memory imaging (normal myocardium metabolizes fatty acids, during ischemia switches to glucose; if ischemia occurred dark spots on BMIPP imaging, used for detection of ischemia that occurred hours prior. Also, provides viability assessment)
MIBG	Similar to norepinephrine	Sympathetic neuronal imaging for heart failure

PET Perfusion Tracers

	Rb-82	N13 ammonia
T 1/2	75 secs	10 mins
Dose/Injection Rate	20mCi Bolus <30secs BGO/LSO/GSO scanners	10-20mCi Bolus <30secs
Extraction Mechanism	Na/K ATPase pump Extraction decreases with increasing blood flow Can be decreased by hypoxia, acidosis and ischemia	Na/K transporter Passive diffusion
Type of stress used	Pharm stress (short t1/2 of Rb, patient needs to remain still in camera)	Pharm stress
Imaging delay after injection	EF>50%: 70-90secs EF <50%: 90-130 secs	1.5-3mins
Imaging duration	3-6 mins	10-15 mins
Reconstructed pixel size	4 mm	2-3 mm
Organ receiving maximum dose	Kidney	Urinary bladder

Radiotracers: Thallium and Technetium

	Thallium 201	Technetium 99m (Sestamibi/ Cardiolite, Tetrofosmin/Myoview)
	Potassium analog; monovalent cation	Lipid soluble, cationic
Preparation	Cyclotron	Generator (eluted from Mo 99m)
Half life	73.1 hours	6 hours (therefore larger doses can be given resulting in higher counts, less scatter and less tissue attenuation)
Decay	Electron capture to Hg-201/ X rays	Isomeric transition/ Gamma ray emission
Energy release	68-80 keV	140 keV
First pass extraction	High (85%)	Lower (55%)
Pharmacodynamics	Active membrane transport in to the myocyte through Na/K pumps Rapid clearance from intravascular space	Diffuses in to cells- no active uptake Uptake depends on blood flow Enters mitochondria due to transmembrane energy potentials (mitochondria à negatively charged membrane)
Myocardial extraction coefficient	Highest: 85% (peak concentration 10 mins after injection)	65% (S) 54% (T)
Redistribution	Mono-exponential  (depends on initial tracer concentration in the myocyte and myocardial blood flow) washout that starts 10-15 mins after injection	Negligible washout therefore no redistribution
Clearance	Kidneys	Hepatobiliary system (tetrofosmin clears liver earlier than sestamibi)
Dose administered	2.5-4 mCi	10-20 mCi: sestamibi 5-33 mCi: tetrofosmin
Whole body radiation dose	0.68 rad	0.5 rad
Whole body effective dose	6.3mSv/mCi of Tl-201 injected	0.3mSv/mCi of Tc 99m injected
Collimator	GAP/ LEAP	High Resolution (LEHR)
Imaging protocol	Exercise/Pharm Stress àTh-201 injection à 10-15mins àImaging (stress) à 2-4 hours à Imaging (rest/redistribution)	1 day protocol: Patient at rest à  Tc injection à 45 mins à Imaging à -Exercise Stress à Tc injection (2-3 times higher dose) à15-20 mins àImaging -Pharm stress à Tc injection (2-3 times higher dose) à 45mins à Imaging 2 day protocol*: Stress imaging on day 1; rest imaging on day 2 (if needed)
Time to imaging Rest/ resdistribution: Pharmacologic stress: Exercise:	2.5- 4 hours after stress 10-15 mins 10-15 mins	45-60 mins (S)/ 30-45 mins (T) 60 mins (S)/ 45 mins (T) 15-20 (S)/ 10-15 mins (T)
Limitations	Low energy emission, therefore: -More image attenuation (especially obese patients) -Longer imaging times	Short shelf life: must be ordered everyday/ twice a day
Clinical uses	CAD diagnosis Viability assessment	CAD diagnosis: sharper images LV function
Minimum number of counts	100 counts/ pixel	200 counts/pixel
Minimum number of projections	32	60-64

*2-day protocol used in BMI >30; female patients where significant breast attenuation in expected

Stable Ischemic Heart Disease Guidelines: Summary

Stable Ischemic Heart Disease Guidelines: Summary

 

Revascularization to improve mortality:

- Left Main >50% (CABG Class I, PCI Class IIa)- CASS, VA Co-op Study, MASS II

- 3 vessel disease or pLAD and one other (CABG, Class I)- CASS, VA Co-op Study, MASS II

- 2 major coronary arteries with significant ischemia (CABG, Class IIa)

- LVSD 35-50% EF when viable myocardium present (Class IIa)

- SCD in presumed ischemia related VT (CABG/PCI, Class I)

Revascularization options:

- CABG vs BMS: 

o No difference at 5 years, single or multi-vessel disease

o Procedural stroke CABG>PCI

o Angina relief CABG>PCI

o Repeat revascularization PCI>CABG

 

- CABG vs DES

o MACE and mortality: PCI>CABG at 3 years in higher syntax scores >22 (<22, no difference)

Special groups

- Left main (selected patients- ostium or trunk)

o Mortality, MI and stroke at 1 and 2 years, PCI=CABG (syntax >33, higher mortality)

o TVR at 1, 2 and 3 years, PCI>CABG

- PLAD

o (PCI =CABG) >medical therapy

- LV systolic dysfunction

o LVEF <35%, CABG = GDMT at 5 years- STICH

- Diabetes

o Survival: CABG >PCI – BARI, FREEDOM

o Revascularization: PCI>CABG - SYNTAX

Medical therapy of angina:

- Beta blockers

o For patients with PAD/ Prinzmetal’s angina: labetalol/carvedilol (alpha adrenergic blocking) or nebivolol (direct vasodilator)

- CCBs: verapamil or diltiazem

- Long acting nitrates

- Ranolazine: contraindicated in significant hepatic impairment. 500mg BID max dose with diltiazem and verapamil. Increases plasma concentration of simvastatin 2 fold.