Presentation on theme: "DR PRADEEP SREEKUMAR SENIOR RESIDENT DEPT. OF CARDIOLOGY GOVT. MEDICAL COLLEGE CALICUT."— Presentation transcript:
DR PRADEEP SREEKUMAR SENIOR RESIDENT DEPT. OF CARDIOLOGY GOVT. MEDICAL COLLEGE CALICUT
Stress echocardiography was introduced in the early 1980s Reliable and cost effective method for both the diagnosis and risk stratification of patients with suspected or known CAD. Use has increased exponentially worldwide and is continuing to expand.
Stress echocardiography may be performed in conjunction with dynamic exercise (treadmill or bicycle). In patients who are unable to exercise, pharmacological agents may be used, such as dobutamine or dipyridamole.
Indications : Diagnosis of ischemia Risk stratification before major non-cardiac surgery, especially vascular After AMI: – Early wall motion abnormality predicts new event. – Remote wall motion abnormality predicts multivessel disease. – Viability of akinetic area: Sustained improvement: Good prognosis Biphasic response: Good prognosis with revascularisation, poor without
Indications : Before PCI / CABG: Significance of stenosis. (NB: only most severe stenosis usually responsive). Viability Assess aortic stenosis with poor LV function. Generally low gradient and low area. With low dose Dobutamine: – Increase in gradient: significant AS, – increase in aortic valve area: poor hemodynamics and non-significant AS.
With any form of stress testing echocardiographic images are first acquired digitally during rest in parasternal and apical views. Subsequently, stress images are acquired during low, intermediate, and peak stress.
Rest and stress images are interpreted for global and regional left ventricular (LV) size, shape, and function. A normal response is when, during stress, the LV size becomes smaller compared to rest, while the shape is maintained and there is increased endocardial excursion and systolic wall thickening
Dobutamine, which is a sympathomimetic agent, is particularly useful in patients with an existing resting wall thickening abnormality. Low doses of dobutamine increases myocardial perfusion, recruits potentially contractile myocardium, and hence increases myocardial contractility in dysfunctional myocardium if there is sufficient contractile reserve (viability).
At high dose, however, dobutamine increases myocardial oxygen demand and in the presence of flow limiting stenosis will result in demand/supply mismatch leading to myocardial ischaemia, resulting in deterioration of regional function (biphasic response). Thus, dobutamine at low doses depicts the presence of myocardial viability, while at high doses uncovers myocardial ischaemia.
Dipyridamole may be used as an alternative to dobutamine but it produces infrequent wall thickening abnormalities even in the presence of significant flow limiting coronary stenosis
Stress echocardiography is based on the fundamental causal relationship between induced myocardial ischemia and left ventricular regional wall motion abnormalities. Mason and colleagues used M-mode echocardiography to study 13 patients with coronary artery disease and 11 age-matched control subjects during supine bicycle exercise
Tennant and Wiggers observed the relationship between systolic contraction and myocardial blood supply to the left ventricle. With the induction of ischemia, these investigators demonstrated the rapid and predictable development of systolic bulging (or dyskinesis). This observation established the link between induced ischemia and transient regional myocardial dyssynergy, recorded echocardiographically as the development of wall motion abnormality after the application of a stressor
In the absence of a flow-limiting coronary stenosis, physiologic stress results in Increase in Heart rate Contractility Systolic wall thickening Endocardial excursion Global contractility Ejection fraction Decrease in end-systolic volume
Blunted in the setting of advanced age hypertension beta-blocker therapy Absence of the hypercontractile state in response to stress should be considered an abnormal response.
In the presence of a coronary stenosis, the increase in myocardial oxygen demand that occurs in response to stress is not matched by an appropriate increase in supply. If the supply-demand mismatch persists, a complex sequence of events known as the ischemic cascade develops.
After the development of a regional perfusion defect, a wall motion abnormality will occur, characterized echocardiographically as a reduction in systolic thickening and endocardial excursion.
The severity of the wall motion abnormality (hypokinesis versus dyskinesis) will depend on several factors like Magnitude of the blood flow change Spatial extent of the defect The presence of collateral blood flow Duration of ischemia. Deterioration in regional wall motion,is a specific and predictable marker of regional ischemia
Once the stressor is eliminated, myocardial oxygen demand decreases and ischemia resolves. Normalization of wall motion may occur rapidly, although typically the complete recovery of normal function takes 1 to 2 minutes-depends on the severity and duration of ischemia.
Stunned myocardium is the term applied when functional abnormalities persist after transient ischemia for a longer period. Although a reversible process, stunning may last days or even weeks if the ischemia is severe and prolonged.
Wall Motion Abnormalities at Rest Myocardial Infarction Cardiomyopathy Myocarditis Hibernating myocardium Stunned myocardium Postoperative state Left bundle branch block Hypertension Right ventricular volume/pressure overload
Dobutamine is a synthetic catecholamine that causes both inotropic and chronotropic effects through its affinity for Î² 1, Î² 2, and Î± receptors in the myocardium and vasculature. Because of differences in affinity, the cardiovascular effects of dobutamine are dose dependent, with augmented contractility occurring at lower doses followed by a progressive chronotropic response at increasing doses. Peripheral effects may result in either predominant vasoconstriction or vasodilation, so changes in vascular resistance (i.e., blood pressure) are unpredictable.
The net effect of these interactions is a combined increase in contractility and heart rate with an associated increase in myocardial oxygen demand. If coronary flow reserve is limited, myocardial oxygen demands will eventually exceed supply and ischemia will develop.
The change in venous return that typically accompanies leg exercise is less pronounced with dobutamine. In addition, the autonomic nervous system mediated changes in systemic and pulmonary vascular resistance are different with exercise compared with dobutamine
Heart rate response is less important with dobutamine compared with exercise, and ischemia can often be induced even if target heart rate is not attained. The lower heart rate achieved during dobutamine but produces greater augmentation in contractility. Thus, the two modalities produce ischemia by different mechanisms. As a result, the parameters that define an adequate level of stress are also different.
Digital images are acquired at baseline (these loops are displayed and used as reference throughout the infusion). Continuous electrocardiogram and blood pressure monitoring are established. Dobutamine infusion is begun at a dose of 5 (or 10) µg/kg/min. The infusion rate is increased every 3 minutes to doses of 10, 20, 30, and 40 µg/kg/min. The echocardiogram, electrocardiogram, and blood pressure are monitored continuously. Low-dose images are acquired at either 5 or 10 µg/kg/min (at the first sign of increased contractility).
Atropine 0.5 to 1.0 mg can be given during the mid- and high-dose stages to augment the heart rate response. Mid-dose images are acquired at either 20 or 30 µg/kg/min. Peak images are acquired before termination of the infusion. Post-stress images are recorded after return to baseline. The patient is monitored till return to baseline status
Exceeding target heart rate of 85% age-predicted maximum Development of significant angina Recognition of a new wall motion abnormality A decrease in systolic blood pressure >20 mm Hg from baseline Arrhythmias such as atrial fibrillation or nonsustained ventricular tachycardia Limiting side effects or symptoms
Because of the short half-life of dobutamine, inducible ischemia can be readily reversed through termination of the infusion. In severe cases or when the ischemic manifestations persist, a short-acting intravenous beta-blocker (such as metoprolol or esmolol) is effective. Symptoms palpitations anxiety. Arrhythmias seen include: premature ventricular contractions atrial arrhythmias Nonsustained ventricular tachycardia (3% )of patients
In one series of 1,118 patients referred for dobutamine stress echocardiography, there were no incidents of death, myocardial infarction, or sustained ventricular tachycardia or fibrillation (Mertes et al., 1993).
No absolute contraindications to dobutamine stress testing. Dobutamine echocardiography has been safely performed in patients with recent myocardial infarction, extensive left ventricular dysfunction, abdominal aortic aneurysm, syncope, aortic stenosis, hypertrophic cardiomyopathy, history of ventricular tachycardia, and aborted sudden death. Safe in patients with bronchospastic lung disease.
Unlike dobutamine, Adenosine works by creating a maldistribution phenomenon by preventing the normal increase in flow in areas supplied by stenotic coronary arteries. In more extreme cases, flow may actually be diverted away from abnormal regions (so-called coronary steal), resulting in true ischemia. Adenosine is a potent and short-acting direct coronary vasodilator. Dipyridamole is slower acting and its effects result from inhibition of adenosine uptake.
The development of a wall motion abnormality is predicated on the ability to create sufficient maldistribution of regional blood flow to result in an ischemia-induced wall motion abnormality. Compared with dobutamine, these changes are more subtle and short-lived
Redistribution of regional blood flow can occur without an associated wall motion abnormality. Vasodilator stress agents may be better suited to imaging techniques that rely on relative changes in perfusion rather than the development of a wall motion abnormality. Dipyridamole and adenosine have been commonly used with nuclear imaging techniques
Analyzed based on a subjective assessment of regional wall motion, comparing wall thickening and endocardial excursion at baseline and during stress. The rest or baseline echocardiogram is first examined for the presence of global systolic dysfunction or regional wall motion abnormalities. Subtle abnormalities at baseline, such as hypokinesis of the inferior wall, may occur in the absence of coronary artery disease and represent a cause of false-positive results.
Limitation of interpretation is the subjective and nonquantitative nature of wall motion analysis. Calculation of the ejection fraction at rest and during stress, is technical challenging and rarely performed in routine practice. A more practical approach involves the estimation of left ventricular volume changes during stress. The normal response to stress includes a decrease in both end- systolic and end-diastolic volume that can be visually appreciated using side-by-side inspection of images. Failure of the end-systolic size to decrease is an abnormal response. An increase in volume with stress often indicates severe and extensive (i.e., multivessel) disease.
Relies on tissue Doppler imaging to quantify myocardial deformation in response to applied stress. Strain is the change in length of a segment of tissue that occurs when force is applied. Strain rate is how strain changes over time. When assessed using the Doppler technique, strain rate can be measured as the difference in velocity between two points normalized for the distance between them. Strain and strain rate have been examined as objective, quantifiable markers of ischemia during stress testing.
One approach involves determining the myocardial velocity gradient, which is the difference between the systolic velocities of the endocardium versus the epicardium (normalized for wall thickness). Normally, the endocardium has a higher velocity than the epicardium, and this difference is frequently diminished with ischemia
One approach (endorsed by the American Society of Echocardiography) divides the left ventricle into 16 segments and then grades each segment on a scale from 1 to 4 in which 1 normal, 2 hypokinesis, 3 akinesis, 4 dyskinesis. Wall motion is analyzed at baseline, and a wall motion score index is generated according to the formula
Hypokinesis is the mildest form of abnormal wall motion. It is defined as the preservation of thickening and inward motion of the endocardium during systole but less than normal. It has been defined arbitrarily as less than 5 mm of endocardial excursion
Hypokinesis is most likely to be truly abnormal if it is limited to a region or territory that corresponds to the distribution of one coronary artery and is associated with normal (or hyperdynamic) wall motion elsewhere. Tardokinesis – a form of hypokinesis. delayed, sometimes postsystolic, inward motion or thickening.
Akinesis is defined as the absence of systolic myocardial thickening and endocardial excursion. Dyskinesis is the most extreme form of a wall motion abnormality and is defined as systolic thinning and outward motion or bulging of the myocardium during systole. A left ventricular segment that is thin and/or highly echogenic indicates the presence of scar.
Segments that are abnormal at rest and remain unchanged with stress are generally best interpreted as showing evidence of infarction without additional ischemia. Hypokinetic areas that worsen during stress are usually labeled ischemic. These may represent a combination of previous nontransmural infarction and induced ischemia. Segments that are akinetic or dyskinetic at baseline, even if wall motion worsens during stress, are best interpreted as indicating infarction, and the ability to detect additional ischemia in such segments is limited.
An abnormal exercise echocardiogram generally identifies patients at increased risk of cardiac events. The echocardiographic findings that have been correlated with risk include a new wall motion abnormality, rest and exercise wall motion score index, and end-systolic volume response. In most series, echocardiographic evidence of ischemia was the most potent marker of high- risk status and has consistently been a better discriminator than other variables, such as exercise-induced ST-segment depression
Most series applying stress echocardiography to the patient before noncardiac surgery have used dobutamine stress. The majority of patients in the published literature were evaluated before major peripheral vascular surgery and therefore included patients who frequently are unable to exercise. In this high-risk subset, dobutamine stress echocardiography has consistently demonstrated value and the presence or absence of an inducible wall motion abnormality has been the most potent determinant of relative risk. The absence of an inducible wall motion abnormality confers a very favorable prognosis, with a negative predictive value of 93% to 100%.
Meta-analysis examining the value of dipyridamole thallium and dobutamine echocardiography before vascular surgery (Shaw et al., 1996), the presence of an inducible wall motion abnormality on echocardiography provided the greatest ability to discriminate between high- and low-risk status
The limitations of the stress ECG in this population have led some investigators to recommend an imaging stress test in most if not all circumstances. Several series have examined the role of both exercise and dobutamine stress echocardiography in this large patient subset. The majority of these studies have demonstrated that wall motion analysis increases both the sensitivity and the specificity of the test. Most series report a sensitivity of 80% to 90% and a specificity of 85% to 90%.
The term viable is commonly used to refer to myocardium that has the potential for functional recovery Refers to either stunned or hibernating myocardium The use of dobutamine echocardiography is based on the observation that viable myocardium will augment in response to adrenergic stimulation, whereas nonviable myocardium will not.
The biphasic response, augmentation at low dose followed by deterioration at higher doses, is most predictive of the capacity for functional recovery after revascularization. Dobutamine echocardiography has been tested in two clinical scenarios. In most series, sensitivity (for predicting functional recovery) has ranged from 80% to 85% with slightly higher specificity (85%-90%). Amount of myocardium identified as viable correlates fairly well with the degree of improvement in global function after revascularization and with long-term outcome. When compared with nuclear techniques, dobutamine echocardiography provides generally concordant results
Nuclear techniques will identify significantly more segments (and patients) as viable. In most series, sensitivity favors nuclear methods, but dobutamine echocardiography is consistently more specific. Thus, all the methods appear to provide a similar positive predictive value. That is, evidence of viability by any of the techniques is predictive of the potential for functional recovery after revascularization. However, the negative predictive value varies widely among the different modalities. In many series, dobutamine echocardiography is favored.
The presence of viability identifies patients in whom revascularization is associated with a significant survival advantage compared with medical management (Fig ). Absence of viability is associated with no significant outcome advantage, whether medical or surgical therapy is implemented. These results were confirmed in a meta-analysis that included more than 3,000 patients studied with either echocardiographic or nuclear methods (Allman et al., 2002). Among patients with viability, surgical revascularization improved prognosis compared with medical therapy. In patients without viability, outcome was similar regardless of treatment. This is in contrast to the results of a multicenter registry in which medically treated patients with viability had a better prognosis than patients without viability (Picano et al., 1998).
The application of contrast echocardiographic techniques to stress testing falls into two distinct categories: left ventricular opacification for border enhancement and myocardial perfusion imaging. The concept of using an intravenous contrast agent to improve left ventricular border detection is predicated on its ability to cross the pulmonary circuit and provide sufficient left-sided chamber opacification
By improving endocardial border detection, the accuracy with which systolic function and wall motion analysis can be ascertained is increased. Studies have confirmed, in properly selected patients, that the use of contrast for left ventricular opacification improves the reproducibility and accuracy of wall motion analysis
A perfusion defect must precede the development of a wall motion abnormality so a method to assess myocardial perfusion should increase the sensitivity of the test to detect ischemia. After intravenous injection, the distribution of the contrast agent parallels blood flow and can be visualized (the contrast effect) as it traverses the microvasculature of the tissue, generating a time- intensity curve. Thus, perfusion can be assessed as a relative change (rest versus stress), a regional difference (e.g., lateral wall versus septum), or more quantitatively based on changes in the rate of flow or blood volume. An echocardiographic test that combines wall motion assessment with the simultaneous ability to evaluate perfusion changes in response to stress would have considerable utility
Stress Echocardiography in Valvular Heart Disease
Exercise testing clearly has no role, and is contraindicated in patients with definite cardiac symptoms or symptoms that are highly suspicious some patients,may ignore or not report mild dyspnea and fatigue, which are difficult to differentiate from the effects of aging or deconditioning. The principal role of exercise testing is to unmask symptoms or abnormal blood pressure responses in patients with AS who claim to be asymptomatic.
Patients with anatomically severe AS and LV systolic dysfunction (ejection fraction <40%) often present with a relatively low-pressure gradient, such as a mean gradient of 30 to 40 mm Hg or less. Difficult to differentiate them from a primary cardiomyopathic process and a thickened but nonstenotic aortic valve producing an outflow murmur-pseudosevere AS
In true severe AS, the small and relatively fixed AVA contributes to an increase in afterload, a decrease in ejection fraction, and a reduction stroke volume. In pseudosevere AS, the predominant factor is myocardial disease, and the severity of AS is overestimated on the basis of AVA because there is incomplete opening of the valve caused by reduction in the opening force generated by the weakened ventricle. .
In both situations, the low-flow state and low- pressure gradient contribute to a calculated AVA that meets criteria for severe AS at rest (1.0 cm 2 ) The resting echocardiogram does not distinguish between these 2 situations
Distinction is essential because patients with true severe AS and poor LV function will generally benefit significantly from AVR. Patients with pseudosevere AS will not and may also have a higher risk of perioperative mortality.
The results of dobutamine stress echocardiography aid in decision making in patients with low-flow aortic stenosis (AS) when dobutamine elicits contractile reserve. Management decisions are more difficult when contractile reserve is absent. Contractile reserve is defined as an increase in stroke volume (SV) 20% using the criteria of Nishimura et al. and Monin et al. When contractile reserve is elicited, patients with true severe AS manifest an increase in transvalvular pressure gradient (P) with a low calculated aortic valve area (AVA).
The main objective of dobutamine stress echocardiography in the context of low-flow AS is to increase the transvalvular flow rate while not inducing myocardial ischemia. Side effects are not infrequent with full-dose dobutamine in unselected patients with normal or moderately reduced LV ejection fraction and can occur in up to 20% of patients with low-flow, low-gradient AS
The dobutamine stress approach is based on the concept that patients who have pseudosevere AS will show an increase in the AVA and little change in the transvalvular gradient in response to the increase in transvalvular flow rate The changes in gradient and AVA during dobutamine stress depend largely on the magnitude of the flow augmentation achieved, which may vary considerably from one patient to another. Therefore, the AVA and gradient are measured at flow conditions that may differ dramatically from one patient to another, and the use of these indexes, which are not normalized with respect to the flow increase, may lead to misclassification of stenosis severity in some patients.
To overcome this limitation, the investigators of the TOPAS (Truly or Pseudo Severe Aortic Stenosis) multicenter study (30) have proposed a new echocardiographic parameter: the projected AVA at a standardized normal flow rate. A projected AVA 1.0 cm 2 is considered an indicator of true severe stenosis.30
Patients identified as having true severe AS and functional reserve, defined as the ability to increase stroke volume with dobutamine by 20% or more (25), have a much better outcome with AVR than with medical therapy (26,27).2526,27 Patients with a lack of LV functional reserve have been shown to have a poor prognosis with either medical or surgical management (25), but as a group they may also benefit from AVR (27,31).2527, Monin JL, Monchi M, Gest V, Duval-Moulin AM, Dubois-Rande JL, Gueret P. Aortic stenosis with severe left ventricular dysfunction and low transvalvular pressure gradients: risk stratification by low dose dobutamine echocardiography J Am Coll Cardiol 2001;37: Monin JL, Quere JP, Monchi M, et al. Low-gradient aortic stenosis: operative risk stratification and predictors for long-term outcome: a multicenter study using dobutamine stress hemodynamics Circulation 2003;108: [
Once true severe AS has been documented, AVR might be reasonable even in the absence of LV functional reserve, although decisions in these high-risk patients must be individualized in the absence of clear guidelines
The other potential role of dobutamine stress echocardiography in patients with AS and impaired LV function is the detection of underlying CAD, because infarcted or hibernating myocardium may be responsible in large part for the contractile dysfunction in many patients. In such patients, revascularization has the potential to improve LV function and clinical outcomes (32,33). However, this situation can represent a diagnostic challenge in patients with AS because multivessel CAD may induce global LV dysfunction, and conversely, regional wall motion abnormalities may occur in the absence of CAD (34).32,3334
lack of contractile reserve on dobutamine stress echocardiography may also be related to LV afterload mismatch, independent of the presence of CAD. These factors may explain why an important proportion of patients with no contractile reserve nonetheless show an improvement in LV ejection fraction after aortic valve replacement with or without revascularization (27). The specificity of stress-induced ST-segment changes and reversible perfusion abnormalities for predicting epicardial coronary artery stenosis is very low in patients with AS because alterations in coronary flow reserve linked to LV hypertrophy and microvascular disease may be present independent of CAD at the epicardial level (35). Thus, in these complex patients coronary angiography (invasive or noninvasive) remains the diagnostic standard.2735
As with patients with AS, exercise testing may elicit symptomatic responses in patients with AR who are apparently asymptomatic based on the medical history, thus identifying candidates for surgery. In addition, pre-operative exercise capacity in patients with AR and LV systolic dysfunction, together with duration of pre-operative LV dysfunction, is helpful in predicting survival and recovery of function after AVR
The observed magnitude of change in ejection fraction or stroke volume from rest to exercise is related not only to myocardial contractile function but also to severity of volume-overload and exercise-induced changes in pre- load and peripheral resistance (1). The validity of stress echocardiography in predicting outcome of patients with asymptomatic AR is limited by the small number of available studies (39,40) compared with the more extensive and consistent experience with exercise radionuclide angiography (41–44). With the sparse data supporting the incremental prognostic value of stress echocardiography, this specific application is not recommended for routine clinical use (1).139,4041–441
In asymptomatic patients with severe MS (mean gradient >10 mm Hg and mitral valve area [MVA] <1.0 cm 2 ), or symptomatic patients with moderate MS (mean gradient of 5 to 10 mm Hg and MVA of 1.0 to 1.5 cm 2 ), the measurement of pulmonary artery pressures (measured from the tricuspid regurgitant velocity) during exercise or dobutamine stress echocardiography can help distinguish those who could benefit from valvuloplasty or valve replacement from those who should be maintained on medical therapy
Patients with reduced atrioventricular compliance show a more pronounced increase in pulmonary arterial pressure during exercise or dobutamine than those with normal compliance Hence, in some patients determined to have only moderate MS at rest, the physiologic effects of heart rate sensitivity and atrioventricular compliance can produce exercise-induced pulmonary hypertension and exertional dyspnea. The resting values of transmitral gradient and pulmonary arterial pressure do not necessarily reflect the actual severity of the disease, stress echocardiography is useful for assesing the severity of MS, assessing its hemodynamic impact, and explaining exercise-induced symptoms.
The current ACC/AHA guidelines have given a Class I recommendation (Level of Evidence: C) for stress echocardiography in patients with MS and discordance between symptoms and stenosis severity (1).1 The threshold values proposed by the ACC/AHA guidelines (1) for consideration for intervention are a mean transmitral pressure gradient >15 mm Hg during exercise or a peak pulmonary artery systolic pressure >60 mm Hg during exercise (Fig. 2).1Fig. 2 In patients with pulmonary artery pressures or valve gradients above these values, percutaneous balloon valvotomy or surgical intervention is recommended, even for patients with apparently moderate MS at rest (1,7,9).1,7,9
Asymptomatic patients with severe MR, exercise stress echocardiography may help identify patients with unrecognized symptoms or subclinical latent LV dysfunction. In symptomatic patients in whom the severity of MR is estimated to be only mild at rest, exercise echocardiography may be useful in elucidating the cause of symptoms by determining whether the severity of MR increases or pulmonary arterial hypertension develops during exercise
worsening of MR severity, a marked increase in pulmonary arterial pressure, impaired exercise capacity, and the occurrence of symptoms during exercise echocardiography can be useful findings for identifying a subset of apparently asymptomatic patients at higher risk who may benefit from early surgery. A pulmonary artery systolic pressure >60 mm Hg during exercise has been suggested as a threshold value above which asymptomatic patients with severe MR might be referred for surgical valve repair (1,8).1,8 This application of stress echocardiography is rated as a Class IIa recommendation.
Stress echocardiography -valuable in confirming or excluding the presence of hemodynamically significant prosthetic valve stenosis or PPM, especially when there is discordance between the patient's symptomatic status and the prosthetic valve hemodynamics measured at rest In contrast to a normally functioning and well-matched prosthesis (including a bileaflet mechanical valve with a localized high gradient at rest), a stenotic prosthetic valve is generally associated with a marked increase in gradient with exercise
A disproportionate increase in transvalvular gradient (>20 mm Hg for aortic prostheses or >12 mm Hg for mitral prostheses) generally indicates severe prosthesis dysfunction or PPM High resting and stress gradients occur more often with smaller (21 for aortic and 25 for mitral) rather than larger- sized prostheses, and mismatched rather than non mismatched prostheses.