Luc A Piérard, Patrizio Lancellotti

Transcription

1 Valve disease STRESS TESTING IN VALVE DISEASE Lu A Piérard, Patrizio Lanellotti 766 Take the online multiple hoie questions assoiated with this artile (see page 765) AORTIC S Heart 2007; 93: doi: /hrt tress testing is a ornerstone in the evaluation of patients with oronary artery disease and its results are always integrated into any linial deisions. In ontrast, valvular heart disease is usually onsidered stati and its management relies upon resting evaluation only. However, most valve diseases have a dynami omponent. Changes in loading onditions and ontratility during a patient s life may lead to alterations in the severity of lesions, good or poor ventriular ontratile reserve, altered volume-dependent ompliane of heart hambers, and ventriular arterial oupling. Thus, there may be a need for stress testing and imaging in this setting. Exerise testing in partiular an indue symptoms, reveal the dynamis of the valve and the ventrile, and evaluate the hanges in forward output, retrograde flow and pulmonary pressures. The urrent primary role of stress testing in valve disease is to provide an objetive assessment of funtional disability whih is of the utmost importane in patients who often adapt and redue their physial ativity, thus masking their symptoms. The Euro Heart Survey on valvular disease reently showed that stress testing is underused in Europe, or used for inappropriate purposes. 1 The following questions will be addressed for eah of the left valvular heart diseases: How to test: whih stress modality should be used? Whih parameters should be measured and followed in other words, should the valve, the ventrile, or both, be tested? How an the results help in the patient s management? STENOSIS Asymptomati severe aorti stenosis Valve replaement is required in the presene of symptoms and severe aorti stenosis. In suh patients, stress testing is ontraindiated. In ontrast, exerise testing is reommended in asymptomati patients with severe aorti stenosis. Exerise is strongly advoated in the European guidelines 2 and is a grade IIb reommendation in the Amerian College of Cardiology/Amerian Heart Assoiation (ACC/AHA) 2006 guidelines. 3 Stress testing has been shown to be low risk when it is performed in asymptomati patients under strit surveillane. Exerise testing in adults with aorti stenosis has poor diagnosti auray for evaluation of onurrent oronary artery disease. See end of artile for authors affiliations Correspondene to: Professor Lu Piérard, Hôpital Universitaire Sart Tilman, Servie de Cardiologie, CHU Sart Tilman, Liege, Belgique; lpierard@hu.ulg.a.be A symptom-limited exerise test is more physiologi than a dobutamine test and may be performed safely. Treadmill or upright biyle ergometry are the most frequent tests and the hoie is based on individual experiene. Exerise testing should be repeated every 6 months for severe aorti stenosis and every year for moderate aorti stenosis. Supine or semi-supine biyle exerise ould be preferable, beause of a redued risk of haemodynami ollapse in this position. Symptom-limited graded biyle exerise in a semi-supine position on a tilting table allows ontinuous twodimensional and Doppler ehoardiographi examination. Dobutamine stress ehoardiography may be used to assess valve ompliane by plotting effetive orifie area against flow at eah stage of the dobutamine test. 4 Testing should be performed in an appropriately equipped laboratory in the presene of a physiian in order that potential ompliations ould be treated effetively. Whih parameters? Total exerise time, maximum workload, peak heart rate and blood pressure and the reason for stopping the test are reorded.

2 EDUCATION IN HEART Table 1 Criteria of an abnormal exerise test in patients with asymptomati aorti stenosis Symptoms during exerise: dyspnoea, angina, synope or near synope Fall in blood pressure or,20 mm Hg rise in systoli blood pressure during exerise,80% of normal level of exerise tolerane.2 mm ST segment depression during exerise (horizontal or downsloping, in omparison to baseline, not attributable to other auses) Ventriular arrhythmias The riteria of an abnormal exerise test provided in the European reommendations are listed in table 1. 1 It is essential to reord the development of symptoms arefully, suh as objetive dyspnoea, angina, dizziness or near-synope. When Doppler ehoardiography is obtained during exerise, aorti veloity time integral an be regularly reorded from the same window to assess hanges in mean pressure gradient. The right parasternal window is usually not easily sought in the left lateral yling position. No randomised trial has been onduted in patients with asymptomati severe aorti stenosis. The risk of sudden death is low and is usually onsidered to be lower than the risk of operation. However, the mortality is rather high early after the onset of symptoms or if the patient is on a surgial waiting list. In some patients, symptoms are not identified, espeially in elderly subjets who are rather inative. On the other hand, dyspnoea and hest pain may be non-speifi. Exerise testing an identify a limited exerise apaity and reveal symptoms in many (usually one-third) apparently asymptomati patients. The 1 year prognosis of patients with a normal exerise test is exellent. 5 In ontrast, a positive exerise test predits the onset of a ardia event in a sizeable proportion of patients. 5 7 The development of symptoms during exerise seems to be more preditive than the other riteria of positivity, but this needs to be onfirmed. A >18 mm Hg inrease in mean transaorti pressure gradient predits a higher risk of ardia events and has been shown to provide inremental prognosti information over linial, resting Doppler ehoardiographi and exerise testing. 8 Exertional symptoms are better predited by valve ompliane during dobutamine stress than by resting Doppler parameters, but the linial signifiane of valve ompliane requires further studies. 4 Despite the reommendations to perform exerise testing in patients with asymptomati severe aorti stenosis and the valuable information obtainable by the test, the reent Euro Heart Survey on valvular heart disease revealed that an exerise test was performed in only 5.7% of patients in this setting. 1 Low flow/low gradient aorti stenosis Patients with low gradient aorti stenosis and left ventriular dysfuntion may have a redued aorti valve area beause of inadequate forward stroke volume due to ardiomyopathy relative, non-severe aorti stenosis or may have fixed severe aorti stenosis with afterload mismath. Stress testing is useful to distinguish patients with fixed aorti stenosis from those with relative aorti stenosis. In this setting, a dobutamine hallenge is reommended to determine the absene or the presene and extent of ontratile reserve 3 9 (lass IIa in the ACC/AHA pratie guidelines). A moderate dose of dobutamine should be used in order to obtain the maximal inotropi effet without hronotropi response. Dobutamine is usually started at 5 mg/kg/min and should be inreased to no more than 20 mg/kg/min. The duration of eah stage and the mode of dose inrement at eah step are not standardised; they may vary from 3 5 min and from mg/ kg/min, respetively. Blood pressure and 12 lead ECG need to be arefully monitored, and rash art and personnel trained in ardia resusitation must be present. Criteria for terminating the infusion are the maximal dose, an inrease in heart rate >10 20 beats/min, or an obvious inotropi response. Dobutamine infusion an be oupled with Doppler ehoardiography or with ardia atheterisation. Whatever the method used, the parameters must be arefully and aurately reorded. With Doppler ehoardiography, left ventriular outflow trat and aorti veloity time integrals should be measured for a minimum of three beats in sinus rhythm and up to 10 onseutive beats in atrial fibrillation. In the atheterisation laboratory, simultaneous measurement of left ventriular and aorti pressure is mandatory. Cardia output should preferably be measured by the Fik method whih is more aurate in the presene of a low output. 12 Whih parameters? Aording to the ACC/AHA guidelines, low gradient aorti stenosis is defined by a mean gradient,30 mm Hg and a alulated aorti valve area,1 m 2. 3 However, most published studies have inluded patients with a mean gradient,40 mm Hg. The riteria for dobutamine responsiveness differ among studies. The multientre Frenh study seleted a >20% inrease in forward stroke volume as the ut-off value of ontratile reserve; this equates to a >20% inrease in left ventriular outflow trat veloity time integral, as the outflow trat diameter was assumed to be onstant. 10 Other studies have also onsidered hanges in peak aorti veloity, mean pressure gradient, aorti valve area and even wall motion sore. Fixed aorti stenosis with ontratile reserve is haraterised by signifiant inreases in peak veloity and mean gradient without hange in valve area (fig 1). Relative aorti stenosis with ontratile reserve leads to a signifiant inrease in alulated aorti valve area without hange in peak veloity or mean gradient. 13 In patients with low gradient aorti stenosis, the operative risk is well stratified by dobutamine stress haemodynamis. Patients with left ventriular ontratile reserve and fixed severe aorti stenosis have an aeptable operative risk. 10 Valve replaement is reommended in most of these patients and usually leads to improved funtional status and survival. The preise ut-off values for defining ontratile reserve remain unertain

3 EDUCATIONINHEART 768 Rest EF 22.6% DOBU 20 mg/kg/min EF 39.8% LVOT 12.1 m LVOT 17.4 m MPG 23.5 mm Hg PPG 45.3 mm Hg AVA 0.66 m 2 MPG 44 mm Hg PPG 103 mm Hg Figure 1 Two dimensional ehoardiography and Doppler findings in a patient with aorti stenosis and severe left ventriular dysfuntion. Top: Rest reordings suggest severe aorti stenosis with low pressure gradient. Bottom: Dobutamine stress eho reordings showing that depressed left ventriular funtion is related to severe aorti stenosis. In this patient, dobutamine at a dosage of 20 mg/kg/ min indued a 44% (>20%) inrease in stroke volume and a signifiant inrease in transvalvular pressure gradient. The alulated aorti valve area is unhanged. AVA, aorti valve area; EF, ejetion fration; LVOT, left ventriular outflow trat time veloity integral; MPG, mean transaorti pressure gradient; PPG, peak transaorti pressure gradient. AVA 0.67 m 2 In the absene of ontratile reserve, the operative mortality is high but the outome is very poor with medial treatment. Therefore, these patients should not neessarily be denied valve surgery. Operative risk appears to be higher when baseline mean pressure gradient is (20 mm Hg or assoiated oronary artery disease is present. The absene of ontratile reserve does not predit the absene of left ventriular ejetion fration reovery in patients surviving to aorti valvular replaement. 14 Patients with relative or pseudo aorti stenosis should be treated medially and not submitted to valve replaement surgery. AORTIC REGURGITATION Asymptomati patients with severe aorti regurgitation and left ventriular dilation (end-systoli diameter mm) may develop irreversible left ventriular damage while awaiting a deision regarding the need for surgery. Stress testing ould be useful for the early detetion of latent systoli failure (fig 2). When systoli left ventriular dysfuntion is obvious, dynami testing of the left ventrile provides prognosti information. 15 The test may also be helpful when patients with mild to moderate aorti regurgitation present objetive funtional limitation. Although the role of exerise stress testing in aorti regurgitation has not yet been demonstrated, it is onsidered reasonable (lass IIA) in the US guidelines for assessment of funtional apaity and symptomati response in patients with a history of equivoal symptoms (level of evidene: B) or before partiipation in athleti ativities (level of evidene: C). 3 Both exerise and dobutamine stress tests an be performed. Exerise testing provides additional information on exerise performane. Whih parameters? Left ventriular end-diastoli and end-systoli volumes and ejetion fration should be assessed at rest and during the test. Annular systoli veloities and indies of longitudinal funtion ould be measured using tissue Doppler imaging 16 (fig 2). Asymptomati patients with a moderately enlarged left ventrile seondary to severe aorti regurgitation and evidene of latent left ventriular dysfuntion (failure to inrease left ventriular ejetion fration during test) should be onsidered for surgery. MITRAL STENOSIS The asymptomati patient with doumented mild mitral stenosis (mean gradient,5 mm Hg, valve area.1.5 m 2 ) should be followed-up on an annual basis, but does not require further evaluation on the initial work-up. When mitral stenosis is signifiant (valve area (1.5 m 2 ), a haemodynami stress test should be performed, espeially in sedentary patients. This ould also be helpful in patients with apparently mild mitral stenosis but who desribe limiting symptoms suh as dyspnoea. The data regarding the use of stress testing in mitral stenosis are rather limited. Doppler ehoardiography should be used. Dynami exerise is the most physiologi test and an be done by upright treadmill or supine biyle. Dobutamine stress testing may also be performed. 17 The patient should be tested without withdrawal of his or her medial treatment, inluding digoxin and b-bloker.

4 EDUCATION IN HEART Rest EF 54 % Sv 5.4 m/s Exerise EF 51 % Sv 6.1 m/s Delay 60 ms F UP:Aute HF EF 34% Sv 2.4 m/s Figure 2 Ehoardiographi assessment of an asymptomati patient with severe aorti regurgitation. At rest, left ventriular ejetion fration (EF) is normal as well as the peak systoli veloity (Sv) obtained at the level of the septal annulus by tissue Doppler imaging. During exerise, the EF slightly dereases and the inrease in Sv is low suggesting the presene of latent left ventriular dysfuntion. The septolateral delay also severely inreases during the test whih is a marker of dynami left ventriular dyssynhrony. Despite these results, the patient refused surgery. After a few months, she was admitted in aute heart failure (HF). The left ventriular funtion was severely depressed. F UP, follow-up. 769 Whih parameters? Exerise tolerane must be evaluated. Doppler reordings of transmitral and triuspid veloities are obtained allowing measurement of the transmitral gradient and estimation of pulmonary artery systoli pressure during stress (fig 3). If mitral valve morphology is suitable for perutaneous balloon valvotomy, patients who deny symptoms but have objetive signifiant limitation of exerise tolerane may be onsidered for perutaneous valvotomy. This proedure an also be proposed in patients with a valve area.1.5 m 2 who, during exerise, exhibit a transmitral mean gradient.15 mm Hg, pulmonary artery wedge pressure >25 mm Hg, or pulmonary artery systoli pressure.60 mm Hg (lass IIb, level of evidene: C, aording to the ACC/AHA guidelines). 3 When a dobutamine test is performed, the evolution of pulmonary pressure is not helpful. A mean transmitral gradient.18 mm Hg during the test has been shown to be the best ut-off value to predit linial deterioration or the need to operate. 18 MITRAL REGURGITATION Organi mitral regurgitation Asymptomati patients with severe (effetive regurgitant orifie (ERO) area >40 mm 2 ) organi mitral regurgitation are at A Rest MVA 1.21 m 2 B Exerise MPG 28.4 mm Hg MPG 13.8 mm Hg TTPG 37 mm Hg TTPG 89.6 mm Hg Figure 3 Ehoardiographi assessment of an asymptomati patient with mitral stenosis. (A) Rest reordings suggest signifiant mitral stenosis. (B) Exerise reordings show a signifiant inrease in transmitral mean pressure gradient and in transtriuspid pressure gradient. MPG, mean pressure gradient of the transmitral Doppler flow; MVA, mitral valve area; TTPG, transtriuspid pressure gradient.

5 EDUCATIONINHEART 770 inreased risk of ardia events. 19 Some of them might develop signifiant left ventriular dysfuntion after mitral valve repair despite the presene of a normal preoperative resting left ventriular ejetion fration. Stress testing may be useful for unmasking latent left ventriular ontratile dysfuntion and prediting postoperative ejetion fration. 20 The published data are limited. Exerise Doppler ehoardiography is reasonable in asymptomati patients with severe mitral regurgitation to assess exerise tolerane and the effets of exerise on pulmonary artery pressure and mitral regurgitation severity (lass IIa, level of evidene: C). 3 Both post- and per-exerise (treadmill, biyle) imaging an be used. The value of dobutamine stress testing has not yet been investigated, but this mode of testing is not ideal as dobutamine would further redue afterload. Whih parameters? Exertional symptoms must be reorded. Left ventriular enddiastoli volume, end-systoli volume, ejetion fration and transtriuspid pressure gradient (non-invasive estimation of pulmonary artery systoli pressure) should be assessed at rest and during testing. Not all patients with asymptomati severe organi mitral regurgitation are good andidates for early surgery beause of advaned age, omorbidities, or unrepairable valves. In these patients, a more onventional strategy of wathful waiting remains a reasonable option in the absene of latent left ventriular dysfuntion exerise-indued inreases in left ventriular ejetion fration by 4% or left ventriular endsystoli volume index >25 m 3 /m 2 at exerise Eletive surgery might also be proposed in patients with a high likelihood of valve repair and exerise-indued systoli pulmonary arterial pressure.60 mm Hg (lass IIa, level of evidene: C). Ishaemi mitral regurgitation Ishaemi mitral regurgitation is a left ventriular disease and develops in the presene of a struturally normal mitral valve. It results from apial and outward displaement of the papillary musles tethering the mitral leaflets and from a dereased left ventriular generated fore to lose them. The linial importane of ishaemi mitral regurgitation is underestimated, at least partly beause physial examination is insensitive. When present, a systoli murmur is usually soft even when mitral regurgitation beomes severe. Funtional, ishaemi mitral regurgitation varies dynamially in aordane with hanges in loading onditions, annular size and the balane of tethering versus losing fores. 22 Most patients presenting with ishaemi mitral regurgitation have a prior history of myoardial infartion, left ventriular dilation and redued left ventriular ejetion fration. The dynami omponent of ishaemi mitral regurgitation might be tested: in patients with left ventriular systoli dysfuntion who present exertional dyspnoea out of proportion to the severity of resting dysfuntion or mitral regurgitation in patients in whom aute pulmonary oedema ours without an obvious ause for stratifying the risk of mortality and heart failure deompensation in the individual patient before surgial revasularisation in patients with moderate mitral regurgitation. However, stress testing is not yet reommended in this setting by the ACC/AHA 2006 guidelines. Candidates for ombined oronary artery bypass grafting and mitral valve repair should not be seleted by transoesophageal ehoardiography in the operating room beause general anaesthesia results in redued loading onditions and tethering, and thus largely underestimates mitral regurgitation. Similarly, dobutamine stress redues preload, afterload and mitral regurgitation, and is therefore not useful. Dynami exerise testing should be used, ideally, on a dediated exerise table. Whih parameters? Numerous Doppler ehoardiographi variables ould be reorded both at baseline and during exerise and stored for off-line detailed analysis. Left ventriular parameters inlude end-diastoli and end-systoli volumes and ejetion fration, regional wall thikening, and olour-oded Doppler tissue imaging to reonstitute and analyse off-line pulsed-wave Doppler veloity profiles. Mitral valve deformation an be quantitated by measuring the systoli tenting area (the area enlosed between the annular plane and the mitral leaflets in the parasternal long-axis view), displaement of mitral oaptation toward the left ventriular apex (the distane between leaflet oaptation and the mitral annulus plane in the apial four-hamber view) and the distane between the posterior papillary musle and the intervalvular fibrosa in the apial long-axis view. Mitral regurgitation should be quantitated at rest and during exerise (fig 4). The regurgitant jet area is not reproduible and should preferably not be used The PISA (proximal isoveloity surfae area) method is reproduible and reliable if the flow-onvergene region is appropriate. The Doppler method is an alternative in patients with a suboptimal flow-onvergene definition. Regurgitant volumes alulated by the Doppler method are usually slightly larger than those obtained with the PISA method. 24 The results of the two methods may therefore be averaged. The ERO area appears to be the most robust parameter for quantifying mitral regurgitation at rest and during exerise. Systoli pulmonary artery pressure and left ventriular dp/dt an be estimated from the systoli transtriuspid pressure gradient and the steepest inreasing segment of the ontinuous wave Doppler mitral regurgitant jet, respetively. An ERO area >20 mm 2 is onsidered severe and is assoiated with exess mortality. 25 The degree of mitral regurgitation at rest is unrelated to exerise-indued hanges in ERO, 26 whih are related to those in mitral valve deformation (a marker of tethering fore) and to those in left ventriular dyssynergy (an indiator of losing fore).

6 EDUCATION IN HEART Rest ERO 19 mm 2 TA 5.2 m 2 TA ERO 41 mm 2 Exerise TA 6.8 m 2 TA Figure 4 End-systoli stop frame images and proximal flow-onvergene region at rest and during exerise in a patient with hroni posterior myoardial infartion and funtional mitral regurgitation. Top: At rest, the systoli tenting area (TA) is enlarged and mitral regurgitation is moderate. The olour M-mode reveals a harateristi pattern of the proximal flow onvergene zone with early and late systoli peaks and a mid-systoli derease in the PISA (proximal isoveloity surfae area) radius. Bottom: During exerise, the severity of mitral regurgitation inreases greatly. The proximal flow onvergene zone beomes larger and the radius is nearly onstant throughout systole. ERO, effetive regurgitant orifie area. 771 Dynami funtional mitral regurgitation usually develops in the absene of transient indued ishaemia. An exerise-indued inrease in mitral regurgitation is larger in patients who stop their exerise test beause of dyspnoea as ompared to those who stop beause of fatigue. 29 Parallel inreases in ERO and pulmonary pressures haraterise patients Stress testing in valve disease: key points Most valvular heart diseases have a dynami omponent Exerise testing, exerise ehoardiography and dobutamine stress ehoardiography are the most frequent stress modalities Exerise testing is reommended in asymptomati severe aorti stenosis. A normal exerise test predits good short term (1 year) outome In symptomati patients with low gradient aorti stenosis, dobutamine stress ehoardiography should be performed to distinguish relative from fixed aorti stenosis. Patients with fixed aorti stenosis, but without ontratile reserve by dobutamine stress testing, have a high operative mortality ompared with patients with ontratile reserve In patients with mitral stenosis, the severity of exeriseindued inreases in mean pressure gradient and estimated pulmonary pressures an help in deision making Post-exerise ehoardiography helps to identify patients operated for severe organi mitral regurgitation who are at risk of postoperative left ventriular dysfuntion. They are haraterised by a larger left ventriular end-systoli volume index and a low ontratile reserve Ishaemi mitral regurgitation is harateristially dynami. Exerise-indued hanges in effetive regurgitant orifie (ERO) area are not preditable by any measurement made at rest A large inrease in ERO area is assoiated with a high risk of mortality and of deompensated heart failure with systoli heart failure who may develop aute pulmonary oedema. 30 An inrease in ERO >13 mm 2 during exerise is assoiated with both mortality and hospital admission for worsening heart failure. Patients who exhibit a sizeable derease in ERO beause of reruitable ontration of the basal left ventriular segments have a good long-term prognosis. Patients with severe funtional mitral regurgitation at rest and dynami mitral regurgitation should reeive optimal medial treatment, inluding an angiotensin-onverting enzyme (ACE) inhibitor and a b-bloker that an ontribute to reverse left ventriular remodelling and redution in mitral regurgitation. When the QRS width is enlarged (.120 ms) and signifiant left ventriular dyssynhrony is demonstrated, patients will benefit from ardia resynhronisation therapy whih autely dereases mitral regurgitation and its dynami omponent, and might ontribute to long-term reverse remodelling and further redutions in mitral regurgitation. In patients who need surgial revasularisation, the role of mitral valve surgery in the presene of mitral regurgitation remains ontroversial. Combination treatment involving bypass and mitral ring annuloplasty and speifi subvalvular approahes might be proposed if the ERO is >20 mm 2 and/or if a >13 mm 2 inrease in ERO develops with exerise, but this strategy needs to be tested prospetively. INTERACTIVEMULTIPLECHOICEQUESTIONS This Eduation in Heart artile has an aompanying series of six EBAC aredited multiple hoie questions (MCQs). To aess the questions, lik on BMJ Learning: Take this module on BMJ Learning from the ontent box at the top right and bottom left of the online artile. For more information please go to:

7 EDUCATIONINHEART 772 Please note: The MCQs are hosted on BMJ Learning the best available learning website for medial professionals from the BMJ Group. If prompted, subsribers must sign into Heart with their journal s username and password. All users must also omplete a one-time registration on BMJ Learning and subsequently log in (with a BMJ Learning username and password) on every visit.... Authors affiliations Lu Piérard, Faulté demédeine, Université de Liège, Chef de Servie, Servie de Cardiologie, CHU Sart Tilman, Liege, Belgique P Lanellotti, Responsable de l Unité de Soins Intensifs Cardiologiques, CHU Sart Tilman, Liege, Belgique In ompliane with EBAC/EACCME guidelines, all authors partiipating in Eduation in Heart have dislosed potential onflits of interest that might ause a bias in the artile REFERENCES 1 Iung B, Baron G, Buthart EG, et al. A prospetive survey of patients with valvular heart disease in Europe: the Euro Heart Survey on valvular heart disease. 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