Prognostic Role of Stress Echo

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Stress echocardiography is a widely used method for assessing coronary artery disease, due to the high diagnostic and prognostic value. While inducible ischaemia predicts an unfavourable outcome, its absence is going to be associated with a low risk for future ischemic events.

Stress echocardiography is indicated in cases when exercise testing is unfeasible, uninterpretable, or gives ambiguous result, and when ischaemia during the test is frequently a false positive response, as in hypertensives, patients with left ventricular hypertrophy and women. In these populations stress echo shows a very good profile for prognostic information and accuracy. Stress echocardiography will give us also the opportunity to study myocardial viability that is an aspect very well known as determinant of the prognosis for some revascularization procedures.

Stress echocardiography combines echocardiography with a physical, pharmacological, or electrical stress for assessing the presence, localization, and extent of myocardial ischaemia. Stress-induced wall motion abnormality (WMA) is the early and specific marker of ischaemia, a classical prognosis marker in coronary artery disease. The wide availability of echocardiographic equipment in all medical centres has been a factor of paramount importance for the diffusion of the technique, especially in light of its limited costs and resource consumption, and the prognostic information given by this technique.

Contents

General aspects about prognostic value of stress echo

Quoting Maseri: “Identification of patients with known ischemic heart disease who are at low risk is important, first, because it is reassuring for the patient; second, because in such a group the prognostic accuracy of any diagnostic test becomes very low; third, because it is difficult to demonstrate that even the most aggressive treatments can increase life expectancy when the latter is not reduced appreciably”.

It has been demonstrated that pharmacological[1] or exercise stress echocardiography[2] are capable to allow effective risk assessment in patients with known or suspected coronary artery disease. While the ischaemic or necrotic pattern is associated with markedly increased risk of death or myocardial infarction, a normal test is predictive of a generally favourable outcome particularly in non-diabetic patients.

The ischaemic response can be further stratified with additive stress echo parameters, such as the extent of inducible WMAs and the workload/dose. The higher the WM score and the shorter the ischaemia-free stress time are, the lower will be the survival rate. Particularly appealing is the very high negative predictive value shown by the stress echocardiography in patients with suspected coronary artery disease: a normal exercise echo yields 0.4-0.9% yearly hard event-rate[3], however patients with a normal pharmacologic stress echocardiogram result have a slightly higher event rate. This may be explained by the higher risk status of patients who are unable to perform exercise stress test, as this group tends to be older and with more comorbidities.

Stress echocardiography result can therefore heavily impact on the decision-making process, probably allowing a selective use of invasive procedures, with economical and logistic consequences potentially favourable. Stress echocardiography maintains a high prognostic value also in an angiographically benign subset such as that of single-vessel disease[4]. Furthermore, the result of the stress echo has shown the capability to predict which patient can obtain the maximal beneficial effect by coronary revascularization. In fact, ischaemia at stress echo was the only independent prognostic indicator in medically treated patients among clinical, angiographic, and echocardiographic parameters. Moreover, coronary revascularization was effective in improving the infarction-free survival in subjects with ischaemia but not in those without ischaemia. As for the prognostic implication of the different pharmacological stress modalities, a similar prognostic value has been reported for dobutamine and dipyridamole testing[5]. Anti-ischaemic therapy heavily modulates the prognostic impact of pharmacological stress echocardiography. Inducible myocardial ischaemia in patients on medical therapy identifies the subset of patients at highest risk of death. Conversely, the incidence of death in patients with a negative test off therapy is very low. At intermediate risk are those patients with a negative test on medical therapy or a positive test off medical therapy.

The tables 1 and 2 summarize the parameters further predicting prognosis in a patient who has ischemia (positive test) or not (negative test) during stress echocardiography. [6]

Table 1. Stress echocardiography risk titration of a positive test result

1-year risk (hard events) Intermediate High
(1–3% year) (>10% year)
Dose/workload High Low
Resting EF >50% <40%
Anti-ischemic therapy Off On
Coronary territory RCA/LCx LAD
Peak WMSI Low High
Recovery Fast Slow
Positivity or baseline dyssynergy Homozonal Heterozonal
CFR >2.0 <2.0

CFR, coronary flow reserve; EF, ejection fraction; LAD, left anterior coronary artery; LCx, left circumflex coronary artery; RCA, right coronary artery; WMSI, wall motion score index.

Table 2. Stress echocardiography risk titration of a negative test result

1-year risk (hard events) Very Low Low
(<0.5% year) (1–3% year)
Stress Maximal Submaximal
Resting EF >50% <40%
Anti-ischaemic therapy Off On
CFR >2.0 <2.0

CFR, coronary flow reserve; EF, ejection fraction.

Prognostic value of the different stress echo techniques

Exercise Echocardiography

The presence, extent, site, and severity of exercise-induced wall motion abnormalities have a clearly proven prognostic impact, as shown by over 20 studies on 5,000 patients – ranging from patients with normal baseline function to those evaluated early after an acute myocardial infarction, hypertensive subjects or women. The prognostic value of exercise stress echocardiography is high, comparable to other forms of pharmacological(dobutamine or dipyridamole) stress echocardiography and stress single photon emission computer tomography(SPECT).[7]

Among patients who have a normal exercise echocardiogram, the prognosis is favorable and the coronary event rate is quite low. An abnormal stress echocardiogram, defined as a new or worsening wall motion abnormality, substantially increases the likelihood of a coronary event during the follow-up period. This finding, coupled with the presence or absence of resting left ventricular dysfunction and the exercise capacity of the patient, provides a great deal of prognostic information in an individual patient. It has been demonstrated that the prognostic value of exercise echocardiography is incremental over clinical and exercise electrocardiography variables.

In patients evaluated for coronary artery disease, exercise echocardiography and exercise scintigraphy combined with the ECG variable provide comparable prognostic information and can be used interchangeably for risk stratification. Other ancillary markers, beyond regional wall motion, can further stratify the prognosis during exercise echocardiography. In patients with a positive test result the prognosis is more malignant, and in patients with a negative test result the prognosis is less benign, with exercise-induced severe mitral regurgitation or left ventricular cavity dilation. We must take into account that the systematic search of these ancillary markers of ischemia is unfeasible and technically challenging during exercise stress echocardiography, and may shift the focus of imaging away from wall motion, which stands as the cornerstone of diagnosis.

Some groups suggest that peak imaging during treadmill stress is feasible, it is known that peak may have higher sensitivity than post-treadmill exercise echocardiography for the detection of coronary artery disease, its prognostic value was unknown but recently the relative values of peak and post- exercise echocardiography for predicting outcome in patients with known/suspected coronary artery were assessed. The addition of peak exercise echocardiography results to clinical, resting echocardiography, exercise variables, and post- exercise echocardiography provided incremental prognostic information for major cardiac events.[8]

A promising finding, that could modify the current clinical practice guidelines to suggest a bigger use of exercise echocardiography as a substitute of exercise ECG, was shown in a recent study in where the investigators tried to assess the value of exercise echocardiography for predicting outcome in patients with known or suspected coronary artery disease and normal exercise ECG testing. The 5-year mortality and major cardiac event rates were 6.4% and 4.2% in patients without ischemia versus 12.1% and 10.1% in those with ischemia, respectively. The use of exercise echocardiography provides significant prognostic information for predicting mortality and major cardiac events in patients with interpretable ECG and normal exercise ECG testing.[9]

Dobutamine Stress Echocardiography

The presence, timing, site, extent, and severity of dobutamine-induced wall motion abnormalities have a clear prognostic impact, as shown by over 50 studies on over 10,000 patients, including patients with or suspected coronary artery disease, evaluated early after acute myocardial infarction, and patients undergoing major noncardiac vascular surgery.[10] These studies concordantly show that dobutamine stress echocardiography results predict subsequent death, on the basis of coexistent fixed resting wall motion abnormalities, dobutamine dose required to induce ischemia and peak wall motion score index. The prognostic value of dobutamine stress echocardiography is independent and additive to resting echocardiography and exercise electrocardiography, and comparable to dipyridamole echocardiography and stress SPECT.

Dipyridamole Stress Echocardiography

The prognostic value of dipyridamole stress echocardiography based on wall motion abnormalities has been extensively proven, confirmed, and reconfirmed in different subsets of patients with chronic coronary artery disease, recent myocardial infarction, or major noncardiac vascular surgery. The prognostic value has been extensively demonstrated in special patient subsets, including hypertensives, women, elderly patients, patients with left bundle branch block [60], with right bundle branch block and/or left anterior hemiblock, outpatients, patients with single-vessel disease, and in a chest pain unit. Dipyridamole stress results can predict subsequent cardiac death, mainly on the basis of two parameters: peak wall motion score index and dipyridamole time (i.e., the interval between test onset and appearance of obvious dyssynergies).

The prognostic value of dipyridamole stress echocardiography is independent of and additive to simpler clinical and laboratory variables such as resting echocardiography and exercise electrocardiography testing, and it has also been confirmed by prospective large-scale multicenter studies.[11]

The prognostic value has also been evaluated in direct head-to-head comparisons with other forms of stress testing, and it was shown to be similar to dobutamine echocardiography and maybe better than perfusion scintigraphy as some old studies showed. [12] [13] The prognostic information supplied by vasodilator stress echocardiography based on wall motion (functional) imaging has been recently expanded with the systematic use of dual imaging and with combined wall motion and coronary flow reserve imaging. The combination of conventional wall motion analysis with 2D echocardiography and coronary flow reserve with pulsed Doppler flowmetry of the mid-distal left anterior descending artery has been shown to provide an added and complementary power of prognostication in patients with known or suspected coronary artery disease, normal coronary arteries, diabetes, and idiopathic dilated cardiomyopathy. A reduced coronary flow reserve is an additional parameter of severity in the risk stratification of the stress echocardiographic response, whereas patients with a negative test for wall motion criteria and normal coronary flow reserve have a favorable outcome during dipyridamole stress echocardiography.

Adenosine Stress Echocardiography

Data on the prognostic value of adenosine stress echocardiography findings are conspicuously lacking to date. By extrapolation from the wealth of data available with dipyridamole stress echocardiography and from more recent data with adenosine scintigraphy and adenosine magnetic resonance imaging[14], it is reasonable to expect adenosine induced wall motion abnormalities to identify patients expected to have problems in a short time (within months), whereas isolate reduction in coronary flow reserve, without associated wall motion abnormalities, may identify patients with prognosis problems in a long period of follow up (years).

Pacing Stress Echocardiography

Pacing-induced ischemia is also helpful in risk stratification of the patient with known or suspected coronary artery disease.[15]

Ergonovine Stress Echocardiography

Previous research shows significantly higher mortality and event rates with a positive result of ergonovine stress echocardiography in patients with a near normal coronary angiogram or in those with negative stress test results for significant fixed stenosis. These results demonstrate the powerful prognostic implication of a noninvasive ergonovine stress echocardiography in routine daily practice for differential diagnosis of chest pain syndrome and this could be potentially useful even in other clinical situations.[16]

As this test provides an effective and powerful means of risk stratification on the basis of the presence of provocable ischemia in patients with no evidence of significant fixed coronary stenosis, either by direct invasive or noninvasive (by 64-slice computed tomography) coronary angiography or by noninvasive stress testing, consideration of ergonovine stress echocardiography for complete differential diagnosis of mechanisms of myocardial ischemia would be encouraged in various clinical scenarios involving patients with chest pain syndrome, such as patients with angiographically normal coronary arteries and a history of angina at rest, aborted sudden death, flash pulmonary edema, or suspected left ventricular apical ballooning syndrome. But we must highlight that few groups use this approach for diagnosis, and the experience is too limited.

Stress echo in special subsets of patients

Hypertensive patients

Arterial hypertension can provoke a reduction in coronary flow reserve through different mechanisms, which may overlap in the individual patient: left ventricular hypertrophy, coronary artery disease and microvascular disease. The diagnostic value of exercise ECG and nuclear techniques has been very disappointing in the hypertensive population, due to high rate of false-positive responses. This reduced coronary flow reserve in the absence of organic coronary artery disease explains this false-positivity. In hypertensive patients, stress echocardiography provides a superior diagnostic specificity than exercise ECG but without differences in sensitivity. The prognostic value of stress-induced wall motion abnormalities is strong and extensively documented in hypertensive patients with suspected coronary artery disease as well as in consecutive cohorts of hypertensive patients. The incremental prognostic value of stress-induced wall motion abnormalities over clinical and exercise ECG findings has also been proven.[17]

Women

The diagnostic specificity of exercise ECG is definitely lower in women than in men. Many explanations for this are available including reduction of coronary flow reserve in syndrome X (mostly affecting female patients), hormonal influences for exercise testing. In contrast, echocardiography combined with exercise or pharmacological agents provides similar sensitivity but a better specificity as compared to exercise ECG. In women the prognostic value of stress echocardiography is high, similar to that in men. In patients with chest pain of unknown origin, a normal test is associated with lower than 1% event-rate at 3 years of follow-up, while an ischaemic test is a strong and independent predictor of future cardiac events. Moreover, stress-induced ischaemia has demonstrated additive prognostic information on top of clinical and exercise ECG data.[18]

Diabetic patients

Exercise ECG is of limited value in diabetic patients because exercise capacity is often impaired by peripheral vascular disease, obesity, and neuropathic disease. In addition, test specificity on ECG criteria is less than ideal due to high prevalence of microvascular and disease hypertension. Stress echocardiography can play a key role in the optimal identification of high-risk diabetic patients, providing similar diagnostic and prognostic information in patients with and without diabetes independently of age. Moreover, stress echocardiography allows effective risk assessment both in diabetics and non-diabetics with intermediate- to high-threshold ischaemic exercise ECG. Nevertheless, the normal test result predicts a less favourable outcome in the diabetic population.[19]

Left bundle branch block

The presence of left bundle branch block makes the ECG uninterpretable for ischaemia and, therefore, a stress imaging would be necessary. The abnormal sequence of left ventricular activation determines increased diastolic extravascular resistance, with lower and slower diastolic coronary flow, accounting for the stress-induced defect often observed by perfusion imaging in patients with normal coronary arteries. In spite of the difficulty posed by abnormal wall motion, stress echocardiography is the best diagnostic option in patients with left bundle branch block. It is more specific than perfusion imaging, and its sensitivity is good, albeit reduced in the left anterior descending territory in the presence of a dyskinetic septum in resting conditions. Moreover, myocardial ischaemia by pharmacological stress echo has a strong and independent power in the prediction of future hard events in left bundle branch block patients, providing a prognostic contribution that is incremental to that of clinical and resting echo findings in the group without previous myocardial infarction.[20]

Non-cardiac vascular surgery

Coronary artery disease is the leading cause of perioperative morbidity and mortality following vascular surgery. Thus, risk stratification before surgery is a major issue, and pharmacological stress echocardiography appears to be the ideal first choice being more feasible than exercise ECG, and less expensive and safer than nuclear scintigraphy. The experience with either dipyridamole or dobutamine indicates that these tests have a very high and comparable negative predictive value (90–100%), allowing a safe surgical procedure.[21] To date, it appears reasonable to perform coronary revascularization before peripheral vascular surgery in the presence of a markedly positive result of stress echocardiography. A more conservative approach, including watchful cardiological surveillance coupled with cardioprotection with beta-blockers, can be adopted in patients with less severe ischaemic response during stress. Risk stratification with stress echocardiography should be probably targeted to patients over 70 years, with current or prior angina, and previous myocardial infarction and heart failure. In other patients, the event rate under beta-blocker therapy is so low that an indiscriminate risk stratification policy with stress echocardiography is probably untenable, as is clearly stated in the last ESC guidelines about pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery.[22]

References

  1. Cortigiani L, Bigi R, Sicari R, Landi P, Bovenzi F, Picano E. Prognostic value of pharmacological stress echocardiography in diabetic and mondiabetic patients with known or suspected coronary artery disease. J Am Coll Cardiol 2006; 47:605–10. [1]
  2. Marwick TH, Case C, Vasey C, Allen S, Short L, Thomas JD. Prediction of mortality by exercise echocardiography: a strategy for combination with the duke treadmill score. Circulation 2001; 103:2566–71. [2]
  3. 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.[3]
  4. Cortigiani L, Picano E, Landi P, Previtali M, Pirelli S, Bellotti P, et al. Value of pharmacologic stress echocardiography in risk stratification of patients with single-vessel disease: a report from the Echo-Persantine and Echo-Dobutamine International Cooperative Studies. J Am Coll Cardiol 1998; 32:69–74.[4]
  5. Pingitore A, Picano E, Varga A, Gigli G, Cortigiani L, Previtali M, et al. Prognostic value of pharmacological stress echocardiography in patients with known or suspected coronary artery disease: a prospective, large scale, multicenter, head-to-head comparison between dipyridamole and dobutamine test. J Am Coll Cardiol 1999; 34:1769–77. [5]
  6. Sicari R, Nihoyannopoulos P, Evangelista A, Kasprzak J, Lancellotti P, Poldermans D, Voigt JU, Zamorano JL, European Association of Echocardiography. Stress Echocardiography Expert Consensus Statement: European Association of Echocardiography (EAE) (a registered branch of the ESC). Eur J Echocardiogr 2008;9:415 – 437.[[6]]
  7. Olmos LI, Dakik H, Gordon R, Dunn JK, Verani MS, Quiñones MA, Zoghbi WA. Long-term prognostic value of exercise echocardiography compared with exercise 201Tl, ECG, and clinical variables in patients evaluated for coronary artery disease. Circulation. 1998;98:2679-86. [7]
  8. Peteiro J, Bouzas-Mosquera A, Broullón FJ, Garcia-Campos A, Pazos P, Castro-Beiras A. Prognostic value of peak and post-exercise treadmill exercise echocardiography in patients with known or suspected coronary artery disease. Eur Heart J. 2010;31:187-95.[8]
  9. Bouzas-Mosquera A, Peteiro J, Alvarez-García N, Broullón FJ, Mosquera VX,García-Bueno L, Ferro L, Castro-Beiras A. Prediction of mortality and major cardiac events by exercise echocardiography in patients with normal exercise electrocardiographic testing. J Am Coll Cardiol. 2009;53:1981-90. [9]
  10. Marcovitz PA, Shayna V, Horn RA, Hepner A, Armstrong WF. Value of dobutamine stress echocardiography in determining the prognosis of patients with known or suspected coronary artery disease. Am J Cardiol. 1996;78:404-8. [10]
  11. Sicari R, Landi P, Picano E, Pirelli S, Chiarandà G, Previtali M, Seveso G, Gandolfo N, Margaria F, Magaia O, Minardi G, Mathias W; EPIC (Echo Persantine International Cooperative); EDIC (Echo Dobutamine International Cooperative) Study Group. Exercise-electrocardiography and/or pharmacological stress echocardiography for non-invasive risk stratification early after uncomplicated myocardial infarction. A prospective international large scale multicentre study. Eur Heart J. 2002;23:1030-7. [11]
  12. Pasquet A, D’Hondt AM, Verhelst R, et al. Comparison of dipyridamole stress echocardiography and perfusion scintigraphy for cardiac risk stratification in vascular surgery patients. Am J Cardiol 1998; 82:1468–1470. [12]
  13. Van Daele ME, McNeill AJ, Fioretti PM, et al. Prognostic value of dipyridamole sestamibi single-photon emission computed tomography and dipyridamole stress echocardiography for new cardiac events after an uncomplicated myocardial infarction. J Am Soc Echocardiogr 1994;7:370–380. [13]
  14. Jahnke C, Nagel E, Gebker R, Kokocinski T, Kelle S, Manka R, Fleck E, Paetsch I. Prognostic value of cardiac magnetic resonance stress tests: adenosine stress perfusion and dobutamine stress wall motion imaging. Circulation. 2007;115:1769-76. [14]
  15. Biagini E, Schinkel AF, Elhendy A, Bax JJ, Rizzello V, van Domburg RT, Krenning BJ, Schouten O, Branzi A, Rocchi G, Simoons ML, Poldermans D. Pacemaker stress echocardiography predicts cardiac events in patients with permanent pacemaker. Am J Med. 2005;118:1381-6. [15]
  16. Song JK, Park SW, Kang DH, Hong MK, Lee CW, Song JM, Kim JJ, Park SJ. Prognostic implication of ergonovine echocardiography in patients with near normal coronary angiogram or negative stress test for significant fixed stenosis. J Am Soc Echocardiogr. 2002;15:1346-52. [16]
  17. Cortigiani L, Coletta C, Bigi R, Amici E, Desideri A, Odoguardi L. Clinical, exercise electrocardiographic, and pharmacologic stress echocardiographic findings for risk stratification of hypertensive patients with chest pain. Am J Cardiol 2003; 9:941–5. [17]
  18. Dodi C, Cortigiani L, Masini M, Olivotto I, Azzarelli A, Nannini E. The incremental prognostic value of stress echo over exercise electrocardiography in women with chest pain of unknown origin. Eur Heart J 2001; 22:145–52. [18]
  19. Cortigiani L, Bigi R, Sicari R, Rigo F, Bovenzi F, Picano E. Comparison of the prognostic value of pharmacologic stress echocardiography in chest pain patients with versus without diabetes mellitus and positive exercise electrocardiography. Am J Cardiol 2007; 100:1744–9. [19]
  20. Bouzas-Mosquera A, Peteiro J, Alvarez-García N, Broullón FJ, García-Bueno L, Ferro L, Pérez R, Bouzas B, Fábregas R, Castro-Beiras A. Prognostic value of exercise echocardiography in patients with left bundle branch block. JACC Cardiovasc Imaging. 2009;2:251-9. [20]
  21. Beattie WS, Abdelnaem E, Wijeysundera DN, Buckley DN. A meta-analytic comparison of preoperative stress echocardiography and nuclear scintigraphy imaging. Anesth Analg 2006; 102:8–16. [21]
  22. . Task Force for Preoperative Cardiac Risk Assessment and Perioperative Cardiac Management in Non-cardiac Surgery; European Society of Cardiology (ESC),Poldermans D, Bax JJ, Boersma E, De Hert S, Eeckhout E, Fowkes G, Gorenek B,Hennerici MG, Iung B, Kelm M, Kjeldsen KP, Kristensen SD, Lopez-Sendon J, Pelosi P, Philippe F, Pierard L, Ponikowski P, Schmid JP, Sellevold OF, Sicari R, Van den Berghe G, Vermassen F.European Heart Journal 2009;30:2769–2812 [22]

Further reading and external links

  • Picano E. Stress Echocardiography, 5th ed. Heidelberg: Springer-Verlag, 2009. [[23]]
  • Lauro Cortigiani, Eugenio Picano. Stress echocardiography. The EAE Textbook of Echocardiography, 1st ed.Oxford University Press,2011.[[24]]
  • Sicari R, Nihoyannopoulos P, Evangelista A, Kasprzak J, Lancellotti P, Poldermans D, Voigt JU, Zamorano JL, European Association of Echocardiography. Stress Echocardiography Expert Consensus Statement: European Association of Echocardiography (EAE) (a registered branch of the ESC). Eur J Echocardiogr 2008;9:415 – 437.[[25]]
  • Pellikka PA, Nagueh SF, Elhendy AA, Kuehl CA, Sawada SG; American Society of Echocardiography. American Society of Echocardiography recommendations for performance, interpretation, and application of stress echocardiography. J Am Soc Echocardiogr 2007; 20:1021–41. [[26]]
  • Peteiro J, Bouzas-Mosquera A.Exercise echocardiography.World J Cardiol. 2010 Aug 26;2(8):223-32.[[27]]
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