PHARMACOLOGICAL STRESS ECHOCARDIOGRAPHY

Dr. Satyam RajvanshiDr. Ram Manohar Lohia Hospital, New

Delhi

OVERVIEW

Physiological Basis ‘Stress’ Methodology Safety & Hazards Protocol Interpretation Applications and Evidence

PHYSIOLOGICAL BASISOF STRESS ECHOCARDIOGRAPHY

Based on fundamental causal relation between induced myocardial ischemia and left ventricular regional wall motion abnormalities (LV-RWMA)

The “Ischemic Cascade”

1930’s – Wiggers and Tenant – showed relationship between systolic contraction and myocardial blood supply

Experimental induction of ischemia - rapid and predictable development of systolic bulging (now called Dyskinesis)

1979 – Mason et al demonstrated earliest proof of concept by echocardiographic imaging of this relation

Studied 13 CAD pts and 11 controls M-mode echo and supine bicycle

exercise Stress induced RWMA seen in 19 of

22 segments supplied by stenotic coronary arteries

1979-80 – Wann et al demonstrated similar findings on early 2D imaging

1980-90 – Improvements in image acquisition

techniques – 2D, 3D Digital acquisition – Reviewing rest and

stress cine loops side by side; eliminating respiratory interference by ECG gated selection of cardiac cycle

ISCHEMIC CASCADE

On Physiological stress - No flow limiting stenosis Demand supply MATCH - increase in

HR; Global ContractilitySystolic wall thickeningEndocardial excursion

Decrease in End Systolic Volume

Hypercontractile response to stress Maybe blunted - Advanced Age

Uncontrolled Hypertension

Beta blocker Absence – usually abnormal

On Physiological stress - with flow limiting stenosis Demand supply MISMATCH - Ischemic Cascade

Parameters overlap Sequence and timing of events may vary

– early or late; may occur simultaneously; may not occur at all

STRESS ECHO

Persistent demand supply MISMATCH Reduction in systolic thickening;

endocardial excursion Regional WMA – Accurate predictor of

regional ischemia – usually occurs prior to ST-T changes, Angina

Elimination of stress Rapid normalization of WMA

Depends on Ischemia severity and durationTypically – Complete recovery 1-2 min.If longer – Stunned myocardium – can rarely last for days!

‘STRESS’ METHODOLOGY

‘STRESS’

Exercise - TreadmillBicycle

(Supine/Upright)

Pharmacological -DobutamineDipyramidole;

Adenosine

Pacing (transesophageal)

Others - Handgrip; Stair step; Ergonovine

Combination modalities

Exercise Stress

Treadmill Stress

Most common form of stress testing Diagnostic and immensely valuable

prognostic information▪ Exercise capacity; BP response; Arrhythmias

Imaging – Just before and immediately after treadmill exercise

Treadmill Stress

False – negative test Main disadvantage Resolution of WMA before imaging

‘Rapid recovery’ variants – unknown causeExercise duration; extent of disease; medical therapy – none predictive

‘Late recovery’ – poor prognostic Severe/Extensive CAD

Bicycle Stress Stationary Bicycle ergometry

Upright Supine / 30º tilt

Greater BP response – WMA at lower HR and workload

Imaging at each stage and at peak workload possible

Disadvantage – Low workload achieved; tolerability

Pharmacological Stress

Dipyridamole

Less myocardial dysfunction

More blood flow heterogeneity• Som

etimes even without wall motion abnormalities

• Still supply is sufficient for the demand

More myocardial dysfunction

Less blood flow heterogeneity

Dobutamine

Choosing the right ‘stress’

Why Pharmacological stress?

Exercise stress Drawbacks

Hyperventilation

Hypercontractility of Normal Walls

False negative post stress Imaging Excessive chest wall movement

Unable to exercise at all or maximally

Pharmacological Stress Preferred

Dipyridamol Stress Preferred Hypertension Atrial and Ventricular

Arrhythmias

Dobutamine Stress Preferred Conduction

disturbances Bronchospastic

diseases On Xanthine

medications Caffeine containing

drinks▪ Tea/Coffee/Cola

SAFETY and HAZARDSOF STRESS ECHOCARDIOGRAPHY

Safety of Pharmacological Stress Echo

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

Pharmacological stress is reasonably safe

Physical stress with exercise is probably safer than

pharmacological testing

PROTOCOLDOBUTAMINE STRESS ECHOCARDIOGRAPHY

Dobutamine protocol

End Points to terminate DSE Exceeding THR Development of significant angina or

new RWMA▪ Depending on patients’ clinical status and

presence/extent/severity of WMA Decrease in SBP>20 mmHg from

baseline▪ Depending on patients’ clinical status and LV

function/LVOT gradient Arrhythmias: AF; NSVT Limiting Side effects and Symptoms

Dipyridamol Stress Echo ProtocolDipyridamole protocol

Ergonovine Stress Protocol for Coronary VasospasmErgonovine protocol for Vasospasm

Image Acquisition Traditionally – PLAX, PSAX, A4C, A2C

views Other views maybe used at

discretion of operator By convention – 4 quadrant view of

above 4 views compiled During comparison – Each view side

by side – Rest image (left) and stress image (Right)

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

Excessive Gain setting spoiling the Endocardial border

definition

Comparing Similar looking but totally different views

Quality issues inherent to 2D Echo Suboptimal visualisation (10-15% studies) Inability to visualise >1 segment (upto

30% studies)

Contrast Echo in Stress Echo

LV Opacification by micro bubbles

Improved Wall motion detection

Simultaneous perfusion analysis

Targetted approach to assess wall motion

Contrast Echo and 3D Imaging

Contrast Echo improves

Endocardial border definition

INTERPRETATIONOF STRESS ECHOCARDIOGRAPHY

WMA categorization

Hypokinesis ▪ Mildest WMA▪ Some degree of preserved systolic thickening

and inward endocardial excursion – but less than normal▪ Various definitions

Less than 30% systolic thickeningLess than 5 mm endocardial excursion▪ Distinction from Normal is subtle –

Hypokinesis truly abnormal if corresponds to a coronary territory + normal (or hyperdynamic) motion elsewhere

Akinesis▪ Various definitions

Absence of systolic myocardial thickening and endocardial excursion<10% myocardial thickening▪ Thickening - better measure than endocardial

excursion

Dyskinesis▪ Most extreme WMA▪ Systolic thinning and Systolic outward

motion/bulging

Scar▪ Thin and/or highly echogenic segment▪ Usually akinetic or severely hypokinetic;

maybe diskinetic

Tardokinesis▪ Form of hypokinesis▪ Delayed systolic thickening or inward motion▪ Maybe reported (false) negative▪ To avoid error –

Analyse frame by frameTrim cine loop to include 1st half of systole

Early Relaxation▪ Normal variant – No Ischemia▪ Normal contacting segment in early systole –

relaxes earlier▪ Maybe reported (false) positive▪ To avoid error –

Analyse frame by frameTrim cine loop to include 1st half of systole

Wall motion response to stress Normal

Normal segments with hypercontractility on stress

IschemiaNormal segment with WMA on stress

Prior Nontransmural Infarct with Ischemia

Hypokinetic areas that worsen on stress Infarct/scar

Akinetic/Dyskinetic segment that worsen on stress

Wall motion response to stress Normal segment – unchanged on

stressNeither hypo – nor hyperkineticMaybe abnormal – IschemiaMaybe false positiveCauses of lack of hyperkinesis

Low workloaddelayed post-stress imaging (TMT)Beta blockadeCardiomyopathyElderly females

Wall motion response to stress Hypokinetic segment – improves on

stress Exercise stress

Either reported NormalLocalised abnormality improved by tethering

(adjacent myocardial pull)

Dobutamine stressMay indicate VIABILITY – potential for

revascularization

Wall motion response to stress Hypokinetic segment – improves on

stress

Wall motion scoring and Attribution to coronary vascular territories

16 or 17 segment models Both endorsed by ASE 17 segment model includes Apical cap

More compatible with nuclear imaging views

Wall motion score index (WMSI) WMSI = Sum of all segments’

scoreNo. of segments scored

WMSI generated at baseline and at peak stress

On stress, hyperkinesis is given 1 scoring

Normal WMSI = 1

Normal study = WMSI of 1 at both baseline and stress

No Ischemia = No increase in stress WMSI from baseline

Abnormal Baseline WMSI (>1)Resting Abnormality present

Any increase in WMSI on stressIncrease in Extent/Severity of

WMA

This approach – Systematic; standardized; quantitative reporting despite subjective analysis; allows comparison between studies

Contents of Stress Echo Report

APPLICATIONS OF STRESS ECHOCARDIOGRAPHY

Localization of Coronary lesions Sensitivity – MV-CAD > SV-CAD

In SV-CAD – LAD > RCA > LCX

Due to variable distribution – Difficult to differentiate RCA from LCX territory

Correlation with Symptoms and ECG For CAD detection

WMA more sensitive and specific than

either Symptoms or ST segment changes

WMA without symptomsPAINLESS ISCHEMIAIschemia in absence of ST changes

and symptoms – less extensive (than with these)

ST segment changes without WMALow risk group (eg. young women)Strong evidence against CAD

Mod-high risk group (ST changes likely to be reliable; or with symptoms)Consider False negative stress echo

To answer this….

Ryan et al 1993

In generalMost cases – Stress ECG and ECHO agree!

If they disagree - Usually Echo is t0 be believed! (More sensitive and specific)

- If markedly positive stress ECG, esp with symptoms – Do not ignore!

Detection of CAD

Overall sensitivity 72-96% (similar to exercise stress echo)

Resting RWMA – highly predictive of CADExtent rather than presence important(Including such patients increases sensitivity)

False –ve MC cause - HTNConcentric

remodelling

Sensitivity – MV-CAD > SV-CAD In SV-CAD – LAD > RCA > LCX Due to variable distribution – Difficult

to differentiate RCA from LCX territory

In contrast,Anterior or Posterior circulation (LCA or RCA) differentiation – highly accurate!

Overall specificity 75-90% Normalcy rate – 92-100%

(Likelihood of normal stress echo in pts with very low pretest risk)

Also, Normal stress echo in known CAD – Prognosis Favourable

False +ve Stress echo (Nonischemic causes of WMA)

LBBB – MC cause – Maybe rate dependent Marked hypertensive response (afterload mismatch)Nonischemic CardiomyopathyPulmonary HTN

Comparison with SPECT-MPI

Comparison with SPECT-MPI High degree of concordance – 87% In general

Nuclear MPI – more sensitiveStress echo – more specific (Exercise & Dob-stress similar)

Metaanalysis (Fleischmann et al, 1998)

Stress echo similarly sensitive, more specific, more cost-effective than SPECT!

Prognostic value in CAD

Exercise-Stress has more robust data compared to Dob-Stress

Normal Ex-stress echo (in Intermediate-High pretest risk groups)Event free survival at 1,2,3 yrs – 99%, 98%, 97% Predictors of event – Age; Low achieved workload; Angina; LVHPost stress WMSI – linearly relates to CVE rate

(Mc Cully et al, 1998)

Positive Ex-stress Echo with Negative TMT(Intermediate risk patients)Relatively common – 16.7%High risk of CVE

(Bouzas Mosquera et al, 2009)(Marwick et al, 1997)

Event rates after Dob-stress echo – higher than Ex-stress

Normal Dob-stress echo – more modest event free survival than normal Ex-stress

Patients referred for Dob-stress – relatively worse prognosis at baseline – inability to exercise itself an ominous sign!

Adding contrast perfusion echo to Dob-stress echo – increases prognostic value

3-year vent free survival

Normal wall motion + Normal perfusion 95%Normal wall motion + Abnormal perfusion82%Abnormal wall motion + perfusion 68%

(Tsutsui et al, 2007)

Stress Echo Post InfarctionUsually resting RWMA present ‘Normal’ response – Hyperdynamic wall

motion in all regions remote from infarct

Goal – identify ‘Ischemia at a distance’Inducible ischemia and/or MV-CADAll these are High-risk groupsResting RWMA (high risk)Low achievable workload (higher risk)Inducible ischemia (highest risk cohort) – according to extent

Dob-Stress Echo post MIInducible ischemia on echo – better CVE risk predictor than angiographic MV-CAD

Patients recovering from MI Normal DSE – conservative

management reasonableDSE +ve – CAG warranted

(Carlos et al, 1997)

Pre-Op risk assessment

Risk of Perioperative CVENo inducible ischemia – 93-100% NPV Inducible Ischemia – 7-33% PPVResting RWMA – much lower PPV than inducible ischemia; almost similar to ‘normal’

DSE has better NPV than SPECT Risk not only confined to

perioperative period, but upto 3 yrs

Question of Myocardial ViabilityVIABLE Myocardium

Hypokinetic/Akinetic myocardium that has the potential for functional recovery – Stunned or Hybernating

Resting echoMore severe the WMA – less likely the viabilityThin and scarred – less likely the viability

Dob-stress Echo Principle

‘Viable’ myocardium – contractility augments on Beta-adrenergic stimulation

‘Non-viable’ myocardiam – no augmentation

‘Biphasic’ responseMost predictive of functional recovery after revascularization

‘Sustained improvement’ or ‘No change’Correlate with Non-viability – lack of improvement after revascularization

Post MI and ICMP For functional recoveryDSE – sensitivity 80-85%specificity 85-90%yHighest PPV & NPV for functional recovery

SPECT/PET – Higher sensitivity; identify more viable segments Less specific; identified segments need not necessarily regain function

Stress Echo in Valvular disease MS of borderline severity – when

symptoms do not match the objective evidence – (Supine Bicycle ergometry is best)

Dynamic MR

Low Output/Low Gradient Severe AS

Principle - Increase in flow rate will normally cause increase in valve area

Dobutamine – Low to mid dose5 to 20 ug/kg/min

‘True’ Severe AS Area <1 sq.cmLVOT/AV peak jet velocity ratio unchanged

‘Pseudosevere’ AS/CardiomyopathyArea increases to > 1 sq.cm (Moderate AS)LVOT/AV peak jet velocity ratio decreases (LVOT jet velocity increases but AV jet velocity decreases)

AVA = CSA-LVOT x (TVI-LVOT/TVI-AV)

Diastolic Stress Echo

Diastolic dysfunction – early and sensitive marker for ischemia; maybe more quantitativeImpaired myocardial relaxation Post-systolic shortening – ‘Ischemic Memory’Increase in E/e’ ratio on exerciseStrain imaging

Less reproducibleNot yet standardized

Take Home Message

Pharmacological stress echo is a safe, informative, cost-effective, special investigation with varied indications

Further research needed to make this versatile investigation even more relevant for diagnostic and prognostic purpose

THANK YOU

TDI or Strain Rate ImagingQRS to onset of Relaxation = 350 – 400ms

Normally interval decreases by 34% ± 10%

In Ischemia – 12% ± 18%

Speckle TrackingDiastolic stunning

Lasts longer than wall motion abnormalities

TDI in Stress Echo

Applying Strain Rate Imaging in Stress EchoResting

Applying Strain Rate Imaging in Stress EchoLow dose Dobutamine

Applying Strain Rate Imaging in Stress EchoHigh dose Dobutamine

CAD• Diagn

osis• Progn

ostication

Pre Op risk

assessment

Exertional

dyspno

ea to

rule out

cardiac

etiology

Localizing ischemia

Evaluation of valve stenosis severity

Indications of Stress Echo