Stress-Echocardiography in Valvular Heart Diseases: Useful in Theory but Underestimated in Clinical Practice

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1 Home SVCC Area: English - Español - Português Stress-Echocardiography in Valvular Heart Diseases: Useful in Theory but Underestimated in Clinical Practice Miguel H. Bustamante Labarta, MD Echocardiography Section - ICYCC, Fundación Favaloro, Buenos Aires, Argentina Ignorance is the night of the mind, but a night without moon or stars (Confucius) The haemodynamic behavior of regurgitant and stenotic valve lesions is closely related to the changing cardiocirculatory status. Transient variations in heart rate, preload and/or afterload are able to produce significant variations on transvalvular gradients, regurgitant volumes, stroke volumes, etc. These effects are particularly evident in those patients with more severe disease. Echocardiography has widely demonstrated to be an extremely useful tool to assess heart valve disease. Interestingly, the ordinary echocardiographic evaluation of such heart valve conditions that are so dependent on dynamic changes, is commonly and almost exclusively performed under resting conditions. In other words, it is widely recognized and accepted for most cardiologists that the evaluation of heart valve disease under a stress condition offers valuable additional information. Nevertheless, daily practice demonstrates that evaluation of these patients by means of a stress-test (ST) is not a common practice. A simple ST provides information about exercise capacity of patients with stenotic or regurgitant mitral and aortic lesions. This information is very important for choosing the optimal time for surgical treatment. Parameters of left ventricular (LV) function, such as ejection fraction (EF) and end systolic volume (ESV) have also been described as relevant information for determining the need of surgical correction. These data were initially obtained only by means of radionuclide angiography. Stress echocardiography (SE) combines the assessment of dynamic variations of clinical and electrocardiographic parameters, as in a conventional ST, and some other valuable parameters such EF and ESV, as estimated in nuclear medicine studies. Moreover, echocardiography contributes with additional valuable information in regard to cardiac anatomy (cardiac chambers dimensions, wall thickness, structure of valvular apparatus, etc.), function (ventricular performance, regurgitant mechanisms, etc.) and haemodynamic measurements (quantitation of valvular stenosis and regurgitation severity, pulmonary artery pressure, etc.). Therefore, stress-echocardiography offers the possibility of performing an integral assessment of patients with heart valve diseases under both resting and challenged haemodynamic conditions. The stress modality will depend on the type of valvular lesion to be assessed. In most cases, an exercise stress test will be the preferable choice. Dobutamine stress echocardiography (DSE) has the potential to evaluate myocardial contractile reserve in those patients with severe left ventricular dysfunction. This modality is particularly useful for unmasking severe aortic stenosis with low transvalvular gradient at rest. MITRAL REGURGITATION The biggest challenge in the management of asymptomatic (or mildly symptomatic) severe mitral regurgitation (MR) is to determine the optimal time for surgical treatment. It is well known that LV deterioration in these illness frequently develops before the onset of symptoms and even before the

2 evidence of worsening in most of the commonly used resting parameters of anatomy (LV diameters) and function (LV volumes and EF). Leung et al demonstrated the sefulness of preoperative exercise SE in predicting LV dysfunction after mitral valve repair for MR. (1) Seventy-four oligosymptomatic patients with non-rheumatic, non-ischaemic, isolated chronic MR and resting normal LVEF were included in the study. Within multivariate analysis, exercise LVESV resulted predictive of postoperative LV function. A preoperative exercise ESV greater than 25 cm²/m² was the most important predictor of postoperative dysfunction (LVEF < 50%), with a sensitivity and specificity of 83% respectively. Another important finding of these study was that all the patients that increased LVEF > 10% in exercise conserved preoperative values of LVEF after surgery. Resting LVEF was not predictive of postoperative LV systolic function in this population. These results suggest that patients with similar features than the study group that do not show exercise reduction of ESV below 25 ml/cm² and/or increase of LV in at least 5% should be considered candidates for surgical treatment. Up to date, there is not substantial information on the assessment of patients with rheumatic MR by means of SE. The evaluation of pulmonary systolic pressures under exercise conditions is an appealing option in those controversial cases where symptom status seems not to correlate with the magnitude of the MR. Large increase of systolic pulmonary pressure (SPP) under exercise is an important parameter to take in account when there is doubt about the timing of mitral valve surgery. Selected groups of patients with coronary artery disease (CAD) and unexplained episodes of dyspnea deserve to be assessed by means of a SE in the search of ischaemic MR. It is important to clarify that this special and dynamic way of presentation of MR is certainly infrequent. In fact, the majority of patients with CAD and MR present in a resting Doppler study will show reduction in the magnitude of the valvular insufficiency during SE, even those with positive ischaemic tests. (2) (Figure 1) This reduction in MR magnitude depends on many different phenomenon such as diminished afterload, significant diminution of mitral valve annulus diameter, etc. that occurs during the testing procedure. Fig 1 - The picture on the right shows an isquemic MR during a DSE. Left picture shows a mild MR observed in the resting evaluation. MITRAL STENOSIS Besides a complete resting echocardiographic study, the evaluation of the exercise capacity of a patient with MS by measures of a simple ST is one of the most important prognostic markers of the illness and a valuable tool in the decision of an interventional procedure. Nevertheless, there are particular situations where symptoms are in disagreement with the anatomic and haemodynamic data obtained from echocardiography. An example of this is the case of an asymptomatic patient with severely reduced MVA

3 (MVA), as determined by echocardiographic planimetry and/or pressure half-time (PHT), but unexplained low transvalvular gradient and low SPP. In this situation, SE may be very useful. The evidence of reduced exercise capacity, associated to a significant increase in mean transvalvular gradient and pulmonary pressure (over 15 mmhg and 60 mmhg, respectively) are strongly suggestive of severe MS. This situation may be present in patients with severe MS under a strong diuretic treatment. Thus, transvalvular gradient and pulmonary pressure may be low and symptoms may be absent despite the existence of true severe MS. In agreement with these concepts, Tunick et al reported the utility of the assessment of exercise SPP on clinical decision-making in patients with MS. (3) In this study, those patients with more severe dyspnea and lower exercise capacity presented higher exercise values of SPP. Pitfalls in Doppler estimation of MVA based on the PHT method may be important in particular situations and cardiologists should be aware of it. Thomas et al elegantly described that PHT is mainly related to the atrioventricular compliance. (4,5) This could explain those cases of true severe MS, misinterpreted as mild or moderate as a result of estimating non-severely stenotic MVA because of the presence of a relatively short PHT. In this situation, severe pulmonary hypertension and limiting symptoms are in disagreement with the apparently non severe stenosis. Although it is not frequently assessed, atrioventricular compliance may be non-invasively estimated with echocardiography and may result useful in these selected cases. Scwammenthal et al described in a subgroup of patients with MS that the presence symptoms and pulmonary hypertension despite a relatively large MVA (estimated by PHT) may be secondary to reduced atrioventricular compliance. (6) They demonstrated that there is close correlation between SPP and atrioventricular compliance. According with this, patients with a low atrioventricular compliance were more symptomatic. It has also been recognized that MVA estimated by the PHT method, tends to increase with exercise because of a decrease in atrioventricular compliance. (Fig 2) This causes a shortening in PHT that leads to overestimate the calculated area. (7) (Figure 2) Recently, Firstenberg et al reported validation and pitfalls of PHT method for the estimation of MVA in patients with MS and changes in cardiac output. In this study it was confirmed that in patients with increasing cardiac output, PHT decreased and calculated MVA increased (8) Thus, MVA estimated by the PHT in exercise is not a reliable parameter to discriminate between severe and moderate MS. The continuity equation should be the method of choice for MVA estimation while performing an SE. Fig 2- Resting and exercise mitral flow patterns in a case of mild MS. Resting parameters: Peak gradient: 9.98 mmhg, mean gradient: 3.5 mmhg, PHT: 125 mseg., MVA: 1.76 cm². Exercise parameters: Peak gradient: 28.6 mmhg, mean gradient: 11.9 mmhg, PHT: 104 mseg., MVA: 2.12 cm². In our experience, it is not necessary to perform a classic SE protocol (treadmill or bicycle). A brief and intense exercise performed bed-side or even in supine decubitus on the bed itself, is frequently enough to

4 unmask a severe MS. Another possible use for exercise SE assessment of mitral flow dynamics is in those patients treated with percutaneous transvenous mitral comissurotomy. Tamai et al described that the reduction in postprocedure resting and exercise transmitral gradient and heart rate correlated with the success of the intervention, represented by the MVA reached after dilatation. (9) A relatively unusual but controversial in its management is MS in pregnant women. In these patients, SE may be useful in predicting the haemodynamic repercussion of the disease in earlier stages of pregnancy. So, the therapeutic management of the patient could be planned earlier. To conclude, SE is certainly not necessary for the assessment of most cases of MS. On the other hand, in this article we have stressed on some different conditions where the dynamic assessment of the patient may be of great value for the decision-making procedure. AORTIC STENOSIS Most patients with severe AS are easily well identified by a conventional echocardiographic study, particularly those presenting with very high transvalvular gradients. However, the diagnosis of severe AS in those patients with severe LV dysfunction and low gradient is still a challenge for the cardiologist. A diminished cardiac output reduces the aortic transvalvular gradient and this becomes an important limitation for determining the severity of AS. Furthermore, although aortic valve area (AVA) estimated by the continuity equation is an useful option, there are some technical aspects limiting the utility of this method. In this scenario it is crucial to define those severely ill patients for whom aortic valve replacement is still the best available therapeutic option. De Filippi et al studied 18 patients with a mean resting AVA of <0.5cm 2 /m 2, mean transvalvular gradient <30mmHg and LV dysfunction. (10) Based on a low dose DSE protocol (maximal dose: 20 mg/kg/min) it was possible to identify three distinct haemodynamic subsets. Patients with non-significant AS who showed an increase in cardiac output and AVA but not in transvalvular gradient. Those with severe AS who evidenced increase in cardiac output and transvalvular gradient but not in AVA. Finally, it was not possible to determine the severity of AS in those individuals without contractile reserve, unable to increase their cardiac output. Yet, the clinical value of detecting this last subset has an important prognostic implication because these patients had a very poor prognosis. (Table 1) The decision of surgical treatment of those patient with severe AS and significant LV dysfunction is still a challenge. In our institution, a group of 19 patients with severe AS without CAD and EF 21 ± 5,4% (12-30), peak pressure gradient: 55 ± 24 mmhg (24-100), mean pressure gradient: 37 ± 16 mmhg (18-60) and AVA area: 0,5± 0,4cm 2 (0,3-08) underwent aortic valve replacement. Hospital mortality was 5,2% (1/19 patients) and follow- up survival at 37 months (mean 13.6±8.3 months) of the remaining patients was 100%. (11) Based on this experience, it is in our opinion that, except for particular cases, patients with severe AS without significant CAD and reduced LVEF should not be excluded from aortic valve

5 replacement, no matter how low ejection fraction and pressure gradients are. AORTIC REGURGITATION Bonow et al. demonstrated that preoperative exercise capacity in symptomatic patients with AR was predictive of postoperative LV function and long-term prognosis after aortic valve surgery. (12) A different issue appears while analyzing EF response to exercise. It has been described that patients who fail to increase LV ejection fraction with exercise tend to have a faster progression to symptoms. It has also been reported that lack of improvement in EF under exercise has a high sensitivity but a low specificity for predicting bad prognosis after aortic valve surgery. It is important to stress on the relative value of assessing exercise EF as a reliable parameter of LV systolic function based on the limitations of the EF as a real expression of myocardial contractility. (13,14) The decrease in vascular resistance and shortening in diastolic period during exercise may reduce aortic regurgitant volume. Then, lack of increase or even a decrease in EF may simply be an expression of a significant reduction in diastolic volume and not a real marker of contractile reserve. To date, AR is, maybe, the valvular heart lesion in witch SE offers less diagnostic utility. Nonetheless, it is interesting to discuss about some aspects of the implementation of this technique in such fascinating valvular disease. Early detection of myocardial dysfunction in asymptomatic patients with chronic severe AR and seek of prognostic markers of postoperative outcome are some of the many still unresolved issues. Some echocardiographic parameters of LV function (fractional shortening, end systolic diameter, wall stress, etc.) have been described as prognostic markers of postoperative outcome. Associated to clinical parameters, these measurements are routinely used to decide the optimal time for surgical intervention. Unfortunately, none of these parameters are either highly sensitive or specific in terms of prognostic value. DSE has been demonstrated useful in the evaluation of patients with severe aortic stenosis and LV dysfunction. However, this inotropic agent has not currently been used for the study of patients with AR. The detection of contractile reserve in AR with LV systolic dysfunction by means of analyzing the inotropic response to dobutamine stimulus and its prognostic value after valvular surgery is an attractive field yet to be investigated. In the ICYCC-Fundación Favaloro, 28 patients with chronic severe AR and LV deterioration (EF under 60% - mean value: 39.1±10.5) were prospectively studied with low dose DSE (5 minutes stages of 5, 10 and eventually 15 mg/kg/min) immediately before aortic valve surgery. (15) The goal of this study was to analyze if the effects of dobutamine administration on preoperative LVEF and ESV were predictive of early (first 24 hours) postoperative complications related to pump failure (death, difficulties in cardiopulmonary by-pass weaning and need of mechanical assisted circulation and/or two or more inotropic drugs). Against the original hypothesis, LV response to dobutamine was not predictive of postoperative early complications. Postoperative events only correlated with age and preoperative fractional shortening. Even so, some investigators have reported the utility of DSE in predicting postoperative recovery of LV function in AR. Wahi et al studied 61 patients with asymptomatic or minimally symptomatic AR and not know CAD (16). Exercise EF was evaluated with echocardiography. Patients who showed improved exercise EF were defined as having contractile reserve (CR+). Those without increment of EF were defined as CR-. Thirtyfive patients were medically treated and the remaining 26 patients had surgical treatment. In the medically treated patients, 13 of 21 (62%) with CR+ had preserved EF on follow-up. In the CR- subgroup, 13 of 14 patients had EF deterioration on follow-up (p=0.005). Among the surgery group, 13 showed CR+. All these patients had an increase in EF on follow-up. Of 13 remaining patient with CR-, 10 showed the

6 same or worse EF on postoperative follow-up. Thus, contractile reserve assessed by exercise SE resulted to be a better predictor of postoperative LVF than resting parameters in asymptomatic individuals with chronic AR. In those patients undergoing aortic valve replacement, contractile reserve had a better correlation with resting EF on postoperative follow-up. These findings are encouraging enough to suggest the use of exercise SE in asymptomatic patients with severe AR as a valuable tool in the timing for surgery. In our opinion the helpfulness of SE in AR is an attractive field that still needs to be explored. FINAL CONSIDERATIONS This article does not intend to discover a new way to assess patients with heart valve diseases. Definitively, SE is not the first diagnostic step in the ladder to evaluate cardiac valvular lesions. But, it may become a vital supplementary diagnostic tool, particularly in those controversial cases where timing for clinical-making decisions is crucial. The strong influence of cardiocirculatory dynamic conditions on valvular gradients, regurgitant volumes, stroke volume, pulmonary pressure, symptoms, etc., is one of the reasons that makes the assessment of heart valve diseases so exciting. Therefore, cardiologists would not be pleased of understanding such diverse changing physiopathology just by evaluating patients in resting conditions. Finally, we should understand that SE is not only a synonym of dynamic assessment of patients with CAD but also an open window to the comprehension of some other cardiac diseases. REFERENCES 1. Leung DY, Griffin BP, Stewart WJ, Cosgrove DM 3rd, Thomas JD, Marwick TH. Left ventricular function after valve repair for chronic mitral regurgitation: predictive value of preoperative assessment of contractile reserve by exercise echocardiography. J Am Coll Cardiol 1996 Nov 1;28(5): Heinle SK, Tice FD, Kisslo J. Effect on dobutamine stress echocardiography on mitral regurgitation. J Am Coll Cardiol 1995;25: Tunick PA, Freedberg RS, Gargiulo A, Kronzon I. Exercise Doppler echocardiography as an aid to clinical decision making in mitral valve disease. J Am Soc Echocardiogr 1992;5: Thomas JD, Weyman AE. Doppler mitral pressure half-time: a clinical tool in search of theoretical justification. J Am Coll Cardiol 1987;10(4): Thomas JD, Wilkins GT, Choong CY, Abascal VM, Palacios IF, Block PC et al. Inaccuracy of mitral pressure half-time immediately after percutaneous mitral valvotomy. Dependence on transmitral gradient and left atrial and ventricular compliance. Circulation 1988;78(4): Scwammenthal E, Vered Z, Agranat O, Kaplinsky E, Rabinowitz B, Feinberg MS. Impact of atrioventricular compliance on pulmonary artery pressure in mitral stenosis: an exercise echocardiographic study. Circulation 2000;102: Braverman AC, Thomas JD, Lee RT. Doppler echocardiographic estimation of mitral valve area during changing haemodynamic conditions. Am J Cardiol 1991;68(15): Firstenberg MS, Prior DL, Greenberg NL Wahi S, Pasquet A, Garcia MJ et al. Effect of cardiac output on mitral valve area in patients with mitral stenosis: validation and pitfalls of the pressure half-time method. J Heart Valve Dis 2001;10: Tamai J, Nagata S, Akaike M, Ishikura F, Kimura K, Takamiya M et al. Improvement in mitral flow dynamics during exercise after percutaneous transvenous mitral comissurotomy. Non-invasive evaluation using continuous wave Doppler technique. Circulation 1990;81: defilippi CR, Willett DL, Brickner E, Appleton CP, Yancy CW, Eichhorn EJ et al. Usefulness of dobutamine echocardiography in distinguishing severe from non severe valvular aortic stenosis in patients with depressed left ventricular function and low transvalvular gradients. Am J Cardiol 1995;75: Casabe H, Stutzbach P, Guevara E, Gomez C, Machain A, Favaloro M et al. Outcome of aortic valve replacement in patients with severe aortic stenosis without significant coronary artery disease and severely depressed left ventricular function. J Am Coll Cardiol 2000; 35(Suppl A): Bonow RO, Borer JS, Rosing DR, Henry WL, Pearlman AS, McIntosh CL et al. Preoperative exercise capacity in symptomatic patients with aortic regurgitation as a predictor of postoperative left ventricular function and long-term prognosis. Circulation 1980;62(6): Borer JS, Bacharach SL, Green MV, Kent KM, Henry WL, Rosing DR et al. Exercise-induced left ventricular dysfunction in symptomatic and asymptomatic patients with aortic regurgitation: assessment with radionuclide

7 cineangiography. Am J Cardiol 1978;42(3): Boucher CA, Kanarek DJ, Okada RD, Hutter AM, Strauss HW, Pohost GM. Exercise testing in aortic regurgitation: Comparison of radionucleide left ventricular ejection fraction with exercise performance at the anaerobic threshold and peak exercise. Am J Cardiol 1983;52: Bustamante Labarta M, Miranda A, Perrone S, Comtesse D, Favaloro RR, Stutzbach P et al. Insuficiencia aórtica severa con disfunción ventricular: Parámetros basales del Eco-Doppler versus test de Eco-Dobutamina en la predicción de complicaciones de la cirugía valvular. Rev Arg Cardiol 1999;67(Suppl 3): Wahi S, Haluska B, Pasquet A, Case C, Rimmerman CM, Marwick TH. Exercise echocardiography predicts development of left ventricular dysfunction in medically and surgically treated patients with asymptomatic severe aortic regurgitation. Heart 2000;84: Top Your questions, contributions and commentaries will be answered by the lecturer or experts on the subject in the Echocardiography list. Please fill in the form (in Spanish, Portuguese or English) and press the "Send" button. Question, contribution or commentary: Name and Surname: Country: address: Send Erase Top 2nd Virtual Congress of Cardiology Dr. Florencio Garófalo Steering Committee President fgaro@fac.org.ar fgaro@satlink.com Dr. Raúl Bretal Scientific Committee President rbretal@fac.org.ar rbretal@netverk.com.ar Dr. Armando Pacher Technical Committee - CETIFAC President apacher@fac.org.ar apacher@satlink.com Copyright Argentine Federation of Cardiology All rights reserved This company contributed to the Congress