Dr. Benny J PanakkalSenior ResidentDept. of CardiologyMedical College, Kozhikode

PHARMACOLOGICAL STRESS ECHOCARDIOGRAPHY

Understanding Basic Concepts

Ischemia CascadeThe answer to the Question “Why Echo”

Wall Motion

More Specific

Requires Ischemia

Perfusion Changes

More Sensitive

May occur without producing Ischemia

Low cost

Environment friendly

No ionizing radiation

Equally accurate

Why Echo in comparison to SPECT, PET etc.

Coronary Flow Reserve

Angina with ST-T changes

WITHOUT Wall Motion

Abnormalities

Microvascular Ischemia

• Syndrome X• LV Hypertrophy

Stressors in Stress Testing

Exercise Stress Testing

Treadmill

Most potent

Bicycle

Imaging at Peak Stress and during

each stage of stress

Avoids problem of early resolution of

ischemia

Can accurately measure the time of

onset of ischemia

Prognostically important

Drawbacks

Hyperventilation

Hypercontractility of Normal Walls

Excessive Tachycardia

Excessive chest wall movement

Unable to exercise at all or maximally

Circumvented by Pharmacological

Stressers

Exercise as a StressorPrototype of Demand driven ischemic stress

Situations where Pharmacological Stress is preferred to Exercise Stress

Dipyridamol

Less myocardial dysfunction

More blood flow heterogeneity• Sometimes even

without wall motion abnormalities

• Still supply is sufficient for the demand

More myocardial dysfunction

Less blood flow

heterogeneity

Dobutamine

Adverse Effects and Complications

Protocols

Exercise Stress Test Protocol

Dipyridamol Stress Echo Protocol

Ergonovine Stress Protocol for Coronary Vasospasm

Imaging Equipment and Acquisition

Quad screen FormatNormal response to Exercise, Dobutamine or Pacing Stress Echo

2D imaging

Qualitiy issues

• Failure to image >1 seg (30%)

• Suboptimal visualization (10-15%)

Harmonic imaging

Contrast Echo

Follow a Road

map

• Avoid excessive gain settings

• Same window, Same view for optimal comparison

• Perfect Apical 2-chamber view

Contrast Echo in Stress Echo

LV Opacification by micro bubbles

Improved Wall motion detection

Simultaneous perfusion analysis

Targetted approach to assess wall motion

3D Imaging

Decreased Acquisition periods

Technically easier

Contrast Echo and 3D Imaging

How Contrast Echo improves Endocardial

border defintion

Excessive Gain setting spoiling the Endocardial border definition

Comparing Similar looking but totally different views

TDI or Strain Rate Imaging

QRS to onset of Relaxation = 350 – 400ms

Normally interval decreases by 34% ± 10%

In Ischemia – 12% ± 18%

Speckle Tracking

Diastolic stunning

Lasts longer than wall motion abnormalities

TDI in Stress Echo

Applying Strain Rate Imaging in Stress Echo

Resting

Applying Strain Rate Imaging in Stress Echo

Low dose Dobutamine

Applying Strain Rate Imaging in Stress Echo

High dose Dobutamine

The Do(s) and Don’t(s)

CAD• Diagnosis• Prognosticat

ion

Pre Op risk

assessmen

t

Exertional

dyspnoea

to rule out

cardiac

etiology

Localizing ischemia

Evaluation of valve stenosis severity

Indications of Stress Echo

Special clinical conditions and target endpoints in Stress Echo

• Discordant symptoms and severity of lesion• Rise in contractile

reserve• Exercise induced peak

sytolic pulmonary pressures > 60mm Hg

Regurgitant lesions

Diagnostic and Prognostic value of CFR during Vasodilator testing

Standalone diagnostic criteria: Structural

limitations

Only LAD imaged

LCx and RCA very difficult to image and impractical

Cannot differentiate between microvascular and

macrovascular CAD

Addition of CFR – ↑ Sensitivity, with modest↓

in Specificity

CFR – Flow (High Neg Pred Value)

2D – Function(High Pos Pred Value)

Used in DCMP too!!

Interpretation

Wall motion scoring and attribution to coronary vascular territories

Interpretation of Pharmacological and Exercise Stress Echo

Stress induced myocardial ischemia – Hallmarks

• Worsening of wall motion abnormalities• Development of new wall motion abnormalities

Specific

• Lack of hyperdynamic motion• Beta Blockers• THR not attained

Non-Specific

• Akinetic segment becoming dyskinetic

No meaning

Adjunctive Diagnostic Criteria

LV cavity dilatation

Decreased Global LV systolic function

TVD or Left Main disease

Differential responses to Exercise and Dobutamine Stress Echo

Diagnostic End Points

• Max dose of pharmacological agent

• Achievement of THR• Akinesis of ≥ 2 LV

segements• Severe Chest pain• Obvious ECG

positivity• ≥ 2mm ST shift

Submaximal Non-diagnostic End Points

• Non tolerable symptoms

• Limiting Asymptomatic side effects• Hypertention (BP

> 220/120)• Hypotension (BP

drop > 40mm Hg)• Supraventricular

Arrythmias• Complex Ventricular

Arrythmias• VT• Frequent

polymorphic VPC

Dipyridamol Stress Preferred• Hypertension• Atrial and Ventricular Arrhythmias

Dobutamine Stress Preferred• Conduction disturbances • Bronchospastic diseases• On Xanthine medications• Caffeine containing drinks

• Tea• Coffee• Cola

Contents of Stress Echo Report

Statistics, StudiesThe Comparison

Exercise Stress Echo

Dobutamine Stress Echo

VT 1.4% 4%

VF 1 2

SVT and AF are more common than VT/VF

Single Centre Analysis ( >50,000 studies ) – Mayo Clinic

Sensitivity Specificity

Stress Echo 85% 88%

Stress SPECT 85% 81%

Diagnostic Accuracy - Overall

SVD DVD TVD

Stress Echo 58% 86% 94%

Stress SPECT 61% 86% 94%

Sensitivities in CAD subtypes

Pellikka PA: Stress echocardiography for the diagnosis of coronary artery disease: Progress towards quantification. Curr Opin Cardiol 20:395, 2005.Armstrong WF, Zoghbi WA: Stress echocardiography: Current methodology and clinical applications. J Am Coll Cardiol 45:1739, 2005

Cardiac Event : Cardiac Death, Non-fatal MI, Coronary Revascularization

Normal Stress Echo – Event Rate < 3% (0.9% per person years of follow up)

Predictors of Cardiac Event (TMT)

Low effort tolerance

LVH

Advancing Age

Stress Echo as a Prognostic Indicator

Mayo Clinic Study comprising 1325 patients

HR

Diabetes 1.9

Previous MI 2.4

Increase or No change in LV systolic size

1.6

Predictors among patients with Good Effort Tolerance and Abnormal Stress Echo –Event Rate was 2% per person year follow up

Kane GC, Hepinstall MJ, Kidd GM, et al: Safety of stress echocardiography supervised by registered nurses: Results of a 2-year audit of 15,404 patients. J Am Soc Echocardiogr 21:337, 2008

Among patients with a High Pretest Probability for CAD – cardiac event rate

At 1 yr At 3 yra

Normal Stress Echo 2% 4%

Abnormal Stress Echo

17% 25%

Elhendy A, Mahoney DW, Burger KN, et al: Prognostic value of exercise echocardiography in patients with classic angina pectoris. Am J Cardiol 94:559, 2004

Ischemic Threshold Event Rate

< 60% THR 43%

≥ 60% THR 9%

No Ischemia 0%

Dobutamine Stress Echo in Preop Evaluation and Prognostication

A Mayo clinic study of 530 patients

Accuracy of different approaches for diagnosis of CAD with Stress Echo

Hoffmann R, Lethen H, Marwick T, et al. Standardized guidelines for the interpretation of dobutamine echocardiography reduce interinstitutional variance in interpretation. Am J Cardiol. 1998;82:1520–1524.

Dip

yrid

amol

vs

Dob

utam

ine

Stre

ss E

cho

Dipyridamol vs Exercise Stress Echo testing

Dipyridamol vs Exercise Stress Echo testing

Sensitivity Specificity Accuracy

SVD MVD GLOBAL

Dipyridamol 66 81 72 92 77

Exercise 72 90 79 82 80

Meta analysis of major trials comparing Dipyridamol with Exercise Stess Testing

3D Echo in Stess Testing

Prognostication

Metz LD, Beattie M, Hom R, Redberg RF, Grady D, Fleischmann KE. The prognostic value of normal exercise myocardial perfusion imaging and exercise echocardiography: a meta- analysis. J Am Coll Cardiol 2007; 49:227–37

Prognostic value of normal stress echoNormal test – Annual risk of Death = 0.4% – 0.9%

Prognostic Value of Inducible Myocardial Ischemia

Stress Echo Titration of a Negative Test

Prognostic Value of Inducible Myocardial Ischemia

Biphasic Response is the single most important response in predicting improvement in LV function in patients with LV dysfunction undergoing revascularization

72% vs <15%

Safety Data

Safety of Pharmacological Stress Echo

Physical stress with exercise is probably safer than

pharmacological testing

Lattanzi F, Picano E, Adamo E, Varga A. Dobutamine stress echocardiography: safety in diagnosing coronary artery disease. Drug Saf 2000; 22:251–62.Varga A, Garcia MA, Picano E. International Stress Echo Complication Registry. Safety of stress echocardiography (from the International Stress Echo Complication Registry). Am J Cardiol 2006;98:541–3

Safety of Pharmacological Stress Echo

Special SubsetsValvular Heart Disease

Cut Offs for DiagnosisContractile Reserve – 20% of stroke volume

Valve area improvement to differentiate true from Pseudostenosis – 0.2%Asymptomatic Sev AS, mean gradient rise on exercise - > 20 mmHg

Special SubsetsNon Cardiac Surgery

Cytokine response

Catecholamine Surge

Hemodynamic stress

Vasospasm

Reduced Fibrinolytic

activity

Platelet activation

Hyper-coagulability

Perioperative Stress Response

High risk categoryIntermediate risk category with Poor functional capacity

• Age < 70 yrs• β blocker

therapy suffices

• Age > 70 yrs• Revasculariza

tion

Peripheral Vascular Disease

• Stress Echo positivity does not always mean Revascularization

Left main or 2 vessel disease

• Only indication for revascularization

Others

• β blockers and Statins

When to perform Pharmacological Stress Echo in the context of Perioperativerisk stratification

Special SubsetsEmergency Department

Randomized muticenter trial - Italy

99% Neg predictive value to

r/o ACS

Still has drawbacks

Patients with negative stress test had early

readmission with ACS

Special SubsetsMyocardial Viability Assessment

Viable

Thickness ≥ 6mm

Scarred

Thinned Echodense

Diagnostic Accuracy comparison for Myocardial Viability AssessmentMetanalysisBax et al. 2001

Bax JJ, Poldermans D, Elhendy A, et al. Sensitivity, specificity, and predictive accuracies of various noninvasive techniques for detecting hibernating myocardium. Curr Probl Cardiol. 2001;26:142–186

Examples

Detection of Myocardial Ischemia – Apical wall thickness, improves at low dose but deteriorates and high dose dobutamine stress echo.

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