Nuclear Cardiology and Exercise Stress Testing

, Gaurav A. Upadhyay1, Henry Gewirtz2 and Henry Gewirtz3



(1)
Harvard Medical School Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

(2)
Harvard Medical School, Boston, USA

(3)
Nuclear Cardiology, Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

 



Introduction

Physics, Radiation Safety, and Instrumentation

Stress Testing and Protocols

Induction of Myocardial Ischemia

Detection of Myocardial Ischemia

Image Acquisition, Processing, and Interpretation

Image Acquisition and Processing

Interpretation

Gauging Extent and Severity of Ischemia

Evaluating ECG-Gated SPECT Data

Review of Common Artifacts

Prognosis and Risk Stratification Based on Testing

ACC/AHA Guidelines for Exercise and Myocardial Perfusion Imaging

References


Abstract

Exercise stress testing and radionuclide myocardial perfusion imaging (MPI) are commonly performed in order to provide medical diagnosis of coronary artery disease (CAD) and to assist with risk stratification and clinical management for patients with established CAD. Exercise stress testing also provides an objective, standardized measure of the patient’s functional capacity, which is important prognostically and also an essential component of any cardiac rehabilitation program.

MPI is performed in the context of stress testing determine the presence and extent of myocardial ischemia. Either treadmill exercise or a pharmacologic ‘stress’ with adenosine, regadenoson, or dobutamine is employed. Next, an objective method is utilized to assess the degree of ischemia induced. Commonly used single-photon emission computed tomography (SPECT) MPI tracers include technetium-99m-sestamibi or tetrofosmin, and in some labs thallium-201, for rest imaging. Both of these determine relative regional myocardial flow in order to assess for ischemia. However, positron emission tomography (PET) can assess absolute regional myocardial flow and the availability of new tracers for PET will greatly expand the use of PET for MPI.

This chapter presents a general frame work for MPI stress test selection and also reviews American College of Cardiology (ACC)/American Heart Association (AHA)/American Society of Nuclear Cardiology (ASNC) guidelines and appropriateness criteria regarding indications for such testing.


Abbreviations


ACC

American College of Cardiology

AHA

American Heart Association

Bq

Becquerel

11C

Carbon

CABG

Coronary artery bypass graft surgery

CAD

Coronary artery disease

Ci

Curie

CKD

Chronic Kidney disease

COPD

Chronic obstructive pulmonary disease

CORE

Center of Rotation Error

DBP

Diastolic blood pressure

18F

Fluorine

ECG

Electrocardiogram

EF

Ejection fraction

G

Gray

HR

Heart rate

IC

Internal conversion

IT

Isomeric transition

IVCD

Intraventricular conduction delay

LAD

Left anterior descending

LBBB

Left bundle branch block

LMCA

Left main coronary artery

LV

Left ventricular

LVEF

Left ventricular ejection fraction

MET

Metabolic equivalents of task

MI

Myocardial infarction

mph

Miles per hour

99Mo

Molybdenum

MPI

Myocardial perfusion imaging

13N

Nitrogen

15O

Oxygen

PET

Positron emission tomography

PVC

Premature ventricular complexes

R

Roentgen

RAD

Radiation absorbed dose

82Rb

Rubidium

RMR

Resting metabolic rate

SBP

Systolic blood pressure

SDS

Summed Difference Score

SPECT

Single-photon emission computed tomography

SRS

Summed Rest Score

SSS

Summed Stress Score

ST60/ST80

ST-segment is assessed at the J-point and 60/80 ms

Sv

Sievert

99mTc

Technetium-99m

201TI

Thallium-201

TID

Transit ischemic dilatation

VO2

Estimated oxygen uptake



Introduction


Exercise stress testing and radionuclide myocardial perfusion imaging (MPI) are commonly performed in order to provide medical diagnosis of coronary artery disease (CAD) and to assist with risk stratification and clinical management for patients with established CAD. Exercise stress testing also provides an objective, standardized measure of the patient’s functional capacity, which is important prognostically and also an essential component of any cardiac rehabilitation program.

MPI is performed in the context of stress testing to determine the presence and extent of myocardial ischemia. Either treadmill exercise or a pharmacologic ‘stress’ with adenosine, regadenoson, or dobutamine is employed. Next, an objective method is utilized to assess the degree of ischemia induced. Commonly used single-photon emission computed tomography (SPECT) MPI tracers include technetium-99m-sestamibi or tetrofosmin, and in some labs thallium-201, for rest imaging. All of these determine relative regional myocardial flow in order to assess for ischemia. However, positron emission tomography (PET) can assess absolute regional myocardial flow and the availability of new tracers for PET will greatly expand the use of PET for MPI.

This chapter presents a general frame work for MPI stress test selection and also reviews American College of Cardiology (ACC)/American Heart Association (AHA)/American Society of Nuclear Cardiology (ASNC) guidelines and appropriateness criteria regarding indications for such testing.


Physics, Radiation Safety, and Instrumentation


A basic background in nuclear physics and radiation is essential for better understanding of nuclear cardiology, and in order to provide protection for oneself and others from radiation.

A.

Basic nuclear physics



  • Background: Radionuclides commonly used for SPECT myocardial perfusion imaging include technetium-99m ( 99m Tc) and thallium-201 ( 201 TI). Positron emission tomography (PET) utilizes Rubidium (82Rb), oxygen (15O), nitrogen (13N), carbon (11C), and fluorine (18F) to label a wide variety of tracer molecules in order to assess myocardial blood flow and metabolism. In addition, PET can reveal important information about molecular signaling and responses of the myocardium to pathological states as ischemia and heart failure (HF). In sharp contrast to SPECT imaging, which can assess relative differences in tracer distribution, PET is capable of absolute quantitative measurement of myocardial tracer content. Thus PET can differentiate between normal and abnormal regions of the heart with better accuracy and allows direct quantitative comparison between patients.


  • Commonly used tracers (Table 8-1)


    Table 8-1
    Tracers commonly used for myocardial perfusion imaging













































    Radionuclides
    Generation
    Half-life
    Gamma rays/x-rays (keV)
    Myocardial Extraction fraction (%)
    Comments

    SPECT

    Technetium-99m ( 99m Tc)-Sestamibi
    On-site generator
    6 h
    140 (ideal photopeak)
    60
    Most commonly used for medical procedures

    Thallium-201 ( 201 TI)
    Cyclotron
    73 h
    80
    75
    Active, Na/K ATPase-dependent

    PET

    Rubidium (82Rb)
    Cyclotron
    76 s
    511
    60
    Greater spatial and temporal resolution compared with SPECT

    Absolute quantization of myocardial blood flow possible

 

B.

Radiation Exposure, Units, and Dose Limits



  • Radiation exposure



    • In the United States, ionizing radiation from medical procedures make up almost 50 % of radiation exposure, while in other parts of the world, natural background comprises the majority of radiation exposure.


    • The linear no-threshold model: there is a linear dose response relationship in future risk of cancer but any exposure to ionizing radiation, can induce a future risk of malignancy.


  • Units of radiation dose



    • Radiation exposure: ionizing radiation concentration in air, measured in Roentgen (R)


    • Absorbed dose: how much is absorbed in a specific tissue, measured in radiation absorbed dose (RAD) or Gray (Gy). Gy  =  100 RAD


    • Effective dose: equivalent whole body dose taking into consideration the organ irradiated, usually used in assessing risk of radiation, measured in Sievert (Sv) or radiation equivalent dose (REM). Sv  =  100 REM


  • Average effective radiation dose in common cardiac procedures (Table 8-2)


    Table 8-2
    Average effective radiation dose in common cardiac procedures [43]








































    Procedure
    Average effective dose (mSv)

    CXR, posteroanterior
    0.02

    CXR, posteroanterior and lateral
    0.1

    CT coronary calcium score
    3

    Coronary angiogram
    7

    CT chest
    8

    Nuclear cardiac stress test (Rest/Stress Tc-99m-MIBI exam)
    15–20

    Cardiac (dose is tracer and protocol dependent:stress only 30 mCi 13-N-ammonia)
    2.5

    CTA, pulmonary embolism protocol
    15

    Coronary angioplasty or stent
    15

    CT coronary angiogram (with current 128 slice CT and dedicated coronary protocol)
    2–5


  • Radiation Dose Limits



    • Guiding principle: ALARA – As Low As Reasonably Achievable.


    • Three factors to achieve this goal



      • Decrease time.


      • Increase distance: Radiation exposure diminishes in an inverse square relative to distance from radiation source.


      • Use shielding


    • Non-occupational dose limit: 5 mSv per year


    • Occupational dose limit: 50 mSv per year

 


Stress Testing and Protocols



Induction of Myocardial Ischemia






  • Exercise



    • Types of exercise testing: commonly treadmill or bicycle. Arm ergometry or rowing machine available.


    • Subject preparation



      • Medications:



        • Diagnosis of CAD: negative inotropic medications, particularly β-blockers are usually held so that a maximal heart rate (HR) response may be achieved.


        • Known CAD, ischemic threshold or efficacy of antianginal therapy: take usual cardiovascular medications


    • Exercise protocols



      • Standard Bruce Protocol: the most widely used and validated protocol. A multi-stage test in which successive stages increase estimated oxygen uptake (VO2) and myocardial demand [1]



        • Stage I is roughly equivalent to four metabolic equivalents of task


      • Modified Bruce Protocol : in assessment of patients soon after myocardial infarction (MI) or in those who are elderly or sedentary [2]. The protocol adds two stages prior to Stage I of the Standard Bruce Protocol:


      • Other protocols include the Cornell, Naughton and Balke protocols, all of which offer the ability to begin at a lower workload and assess at more stages.


    • Test termination and adequacy



      • Test termination: based on perceived exertion, anginal symptoms, electrocardiogram (ECG) assessment, and clinical symptoms [3]



        • Absolute indications for terminating exercise testing include (from the 2001 AHA Exercise Standards for Testing and Training) [3]:



          • ST-segment elevation (>1.0 mm) in leads without diagnostic Q-waves


          • Drop in systolic blood pressure (SBP) of >10 mmHg from baseline, despite an increase in workload, when accompanied by other evidence of ischemia


          • Moderate-to-severe angina that is intolerable


          • Central nervous system symptoms (e.g., ataxia, dizziness, or


          • near-syncope)


          • Signs of poor perfusion (cyanosis or pallor)


          • Sustained ventricular tachycardia (VT)


          • Technical difficulties in monitoring ECG or SBP


          • Subject’s desire to stop


        • Relative indications for terminating exercise testing [3] include:



          • ST or QRS changes such as excessive ST depression (>2 mm of horizontal or downsloping ST-segment depression) or marked axis shift


          • Drop in SBP of >10 mmHg from baseline, despite an increase in workload, in the absence of other evidence of ischemia


          • Increasing chest pain


          • Fatigue, shortness of breath, wheezing, leg cramps, or claudication


          • Arrhythmias in addition to sustained ventricular tachycardia, others, such as multifocal premature ventricular complexes (PVC), triplets of PVCs, supraventricular tachycardia, heart block, or bradyarrhythmias


          • General appearance of exhaustion or poor tissue perfusion


          • Hypertensive response (SBP  >  250 mmHg or diastolic blood pressure (DBP)  >  than 115 mmHg)


          • Development of bundle-branch block or intraventricular conduction delay (IVCD) that cannot be distinguished from VT


      • Adequate if the patient can achieve at least 85 % of her or his maximal predicted HR [4]



        • Maximal predicted HR  =  220 – age (in years)


        • Peak double product or rate pressure product (RPP)  =  HR×SBP



          • RPP of apparently healthy males (n > 700; ages 25–54) was between 25,000 (10th percentile) and 40,000 (90th percentile) [3]


    • Contraindications to exercise stress testing (Table 8-3)


      Table 8-3
      Contraindications to exercise testing













































      Absolute

      Acute MI (within 2 days)

      High-risk unstable angina

      Uncontrolled cardiac arrhythmias

      Severe aortic stenosis

      Uncontrolled symptomatic HF

      Acute pulmonary embolus or pulmonary infarction

      Acute aortic dissection

      Acute myocarditis or pericarditis

      Unstable patient for non-cardiac reason

      Patient is unable to give consent

      Relative

      Left main coronary stenosis

      Moderate stenotic valvular heart disease

      Electrolyte abnormalities

      Severe arterial hypertension

      Significant arrhythmias

      Hypertrophic cardiomyopathy and other forms of outflow tract obstruction

      High-degree atrioventricular block

      Mental or physical impairment leading to inability to exercise adequately




      • Exercise stress testing is associated with a small risk of death (0.5 per 10,000), MI (3.6 per 10,000) and serious arrhythmia (4.8 per 10,000) [3].


      • When the patient is unable to exercise or ECG will be uninterpretable for ischemia (e.g.; LBBB, LVH, WPW), pharmacological stress testing is employed. In patients unable to exercise long term prognosis may be somewhat worse, due to the fact that inability to exercise is a marker of poorer functional status [5].


  • Vasodilators



    • Background: induce coronary vasodilatation and hyperemia. Regional flow differences between diseased (less hyperemic) and normal vessels (more hyperemic) are visualized as perfusion defects using MPI


    • Vasodilator stress agents: adenosine, regadenoson and dypridamole are the most commonly used agents in the US [6],



      • Adenosine: is an endogenously present purine nucleoside molecule which produces dose-dependent myocardial hyperemia through activation of adenonsine A2A receptors in the coronary vasculature [7]



        • Mechanism: nonselective agonist of A1, A2A, A2B, A3, and A4 receptors (throughout the body) with half-life of  <  10 s


        • Side effects: flushing, headache, nausea, mild fall in arterial blood pressure (BP), bradyarrhythmia, bronchospasm, and transient A-V block including complete heart block


        • Protocol: IV adenosine at140 μg/kg/min for 5–6 min. Radiotracer is injected after 2–3 min of infusion.


      • Regadenoson: recently approved selective A2A agonist [8]



        • Mechanism: high affinity selective A2A agonism, peak of 1–4 min and half-life of 30 min


        • Side effects: similar to adenosine but at lower overall incidence than for adenosine.


        • Protocol: Regadenoson is administered as a single bolus of a pre-filled intravenous syringe of 0.4 mg (in 5 mL) over 10 s. The radiotracer is subsequently injected before the end of the first minute after infusion


      • Dipyridamole: produces coronary hyperemia by impairing the cellular reuptake of adenosine [9]



        • Mechanism: inhibits nucleoside transporter and causes an accumulation of adenosine in the interstitial space. It has a substantially longer half-life than adenosine or regadenoson.


        • Side effects: similar to those of adenosine and regadenoson, but usually longer lasting


        • Protocol: infused at 0.56 mg//kg over 4 min. The radionuclide tracer is injected 7–9 min after initiation. Aminophylline is also required 1–2 min after radiotracer in order to reverse effects


    • Subject preparation



      • Medications: aminophylline is used as an antidote to adenosine, regadenoson, and dipyridamole, and cannot be used within the 24 h preceding the test with vasodilator compounds (Table 8-4)


        Table 8-4
        Contraindications for pharmacological stress testing
































        Adenosine/Regadenoson/Dipyridamole
        Dobutamine

        Severe asthma, chronic obstructive pulmonary disease (relative contraindication for regadenoson)
        Unstable angina

        SBP  <  90
        Recent MI (within 1–3 days)

        HR  <  40 bpm
        SBP  <  90

        Xanthines: e.g., caffeine, tea, dark chocolate, aminophylline or theophylline within 24 h of testing
        SBP  >  200

        High degree atrioventricular block/sick sinus syndrome
        Significant history of ventricular tachyarrhythmias

        Less than 2 days after MI
        Severe aortic stenosis

        Hypertrophic cardiomyopathy

        Large aortic aneurysm or aortic dissection


    • Contraindications: patients at a greater chance for suffering the known side effects to vasodilator agents (Table 8-4)


  • Dobutamine



    • Background: inotropic/chronotropic stimulation with synthetic catecholamine, when exercise or vasodilator-stressing is not feasible or is contraindicated [10].


    • Mechanism: β-1 adrenoreceptor agonist (increase inotropy and chronotropy) but also with β-2 effects (can cause hypotension). Atropine can also be added to achieve target HR.


    • Side effects: arrhythmia is common. Nonsustained VT and sustained atrial fibrillation are not uncommon among patients with history of left ventricular dysfunction. Hypotension, angina, nonspecific chest pain, and dyspnea also occur in a minority of patients. Headache, paresthesias, and nausea have also been reported


    • Protocol: dobutamine infusion is escalated in scheduled doses, beginning with 5–10 μg/kg per min, up to 40 μg/kg with attention to maximal HR. Indications to terminate dobutamine infusion are similar as to those for exercise stress testing.


    • Subject preparation: All β-blocking medications must be held for a 24–48 h period


    • Contraindications: in patients in whom enhanced contractility, increased dP/dT are harmful and patients who are at high risk of side effects (Table 8-4)


Detection of Myocardial Ischemia






  • Electrocardiogram



    • Background: a broad spectrum of ECG changes during exercise are considered normal. Myocardial ischemia, in particular, manifests on the ECG stress testing with ST segment changes


    • Physiologic ECG changes with stress [3]



      • P-wave: magnitude increases, particularly in the inferior leads


      • PR segment: shortens and slopes downward, particularly in the inferior leads. The ‘Ta wave,’ or repolarization of the atrial p-wave is thought to drive the downward sloping of the PR segment


      • QRS complex: a decrease in the R-wave amplitude is noted in the apical leads (V5, V6), associated with an increasing S-wave depth


      • J-point depression: The J-point (or J-junction) is depressed during exercise, ­particularly in the apicolateral leads (V4-V6). This is felt to be due to atrial ­repolarization (i.e., the ‘Ta’ wave) and often leads to ‘upsloping’ ST depressions of <2 mm


      • T-wave: decrease in T-wave amplitude seen in early in exercise, resolves within 1 min into recovery


    • Baseline ECG abnormalities which make it difficult to diagnose ischemia from ECG (Table 8-5)


      Table 8-5
      Baseline ECG abnormalities which make it difficult to diagnose ischemia from the electrocardiogram

















      Complete LBBB

      Preexcitation syndrome

      Left ventricular hypertrophy

      Digoxin therapy

      Greater than 1 mm of resting ST-segment depression

      Electronically paced ventricular rhythm


    • Abnormal ECG responses during stress testing (See Fig. 8-1)

      A306999_1_En_8_Fig1_HTML.jpg


      Figure 8-1
      Abnormal and borderline ECG changes during exercise stress testing (Courtesy of Dr. Hanna Gaggin) (a) ST Segment Patterns (b) Measurement of ST Segment Depression


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Jul 13, 2016 | Posted by in CARDIOLOGY | Comments Off on Nuclear Cardiology and Exercise Stress Testing

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