Cardiothoracic Unit, Great Ormond Street Hospital NHS Trust, London WC1N 3JH, UK
* Correspondence to: Professor John E. Deanfield, Department of Cardiothoracic Unit, Great Ormond Street Hospital NHS Trust, Great Ormond Street, London WC1N 3JH, UK. Tel.: +44 207 405 9200x5182; Fax: +44 207 813 8263 (E-mail: macgrm{at}gosh.nhs.uk).
This editorial refers to "Decline in ventricular function and clinical condition after mustard repair for transposition of the great arteries (a prospective study of 2229 years)" by J.W. Roos-Hesselink
Eur Heart J 2004;25:126470
It is now 50 years since the first intra-atrial repair for transposition of the great arteries was reported and the Senning and Mustard operations have transformed the prognosis of this previously fatal condition. The Senning operation has been associated with a lower incidence of late arterial baffle obstruction than the Mustard procedure, but the development of arrhythmia and the progressive decline in the function of the systemic right ventricle has been reported to a comparable degree after both operations. Indeed, these complications have been considered by many to be inevitable and have led to the abandonment of these operations in favour of the more "anatomically correct" arterial switch procedure.
Assessment of the function of the right ventricle in the systemic circulation is of crucial important but has been challenging. There is no easy model for comparison, and no clear criteria of abnormality. Volumetric methods have been the mainstay of right ventricular function estimation but are made difficult by the complex geometry of the right ventricle. Echocardiographic evaluation is often suboptimal, and magnetic resonance imaging and radionuclide ventriculography have a role. Using one or more of these volumetric methods, right ventricular dilatation is almost universal and has been taken to imply right ventricular "failure". Furthermore, it has been implicated as a cause for the frequently reduced exercise capacity even in asymptomatic patients. The relationship between such load dependent changes in right ventricular size and function and clinical outcome is, however, far from clear. Right ventricular dilatation with decreased shortening fraction may merely reflect the "normal" response of the RV to its "abnormal" afterload. In asymptomatic patients after atrial redirection, a fall in stroke volume during exercise or dobutamine infusion has been shown to be due to impaired atrioventricular transport rather than right ventricular contractile failure.1 Similar protocols in patients with congenitally corrected transposition (who have "naturally" occurring systemic right ventricles) have shown a normal stroke volume response.2 The development of new non-invasive relatively load independent indices should enable follow-up of the impact of changes in loading and intrinsic RV contractile function on the clinical course of patients.3
How have patients, now mostly adults, fared after the Mustard and Senning operations? An early peak of "congestive heart failure" has been described. This is not seen in patients who have isolated congenitally corrected transposition in the great arteries. Early failure of the RV may be explained by myocardial damage sustained either pre- or peri-operatively. This explanation is supported by the demonstration of cardiac enzyme release and abnormalities of global and regional cardiac function in unoperated patients with transposition of the great arteries. In short and medium-term follow-up, no significant deterioration of ventricular function indices have been reported, so the evidence that the right ventricle is "doomed to fail" has been lacking. Comparison with congenitally corrected transposition suggest that RV failures are unlikely to occur below 35 years of age in the absence of additional complicating cardiac lesions.4 Long-term serial data describing the fate of the right ventricle supporting the systemic circulation has been sparse in the intra-atrial repair group.
Published in the July issue of the Journal, Roos-Hesslink and colleagues are to be congratulated for their description of the longest prospective study to date, of survival and follow up of 91 patients after a median of 25 years following the Mustard repair of transposition of the great arteries.5 All the operations were performed at a single institution. Detailed follow-up data were available at two cross-sectional stages, at median 14 years and 25 years after surgery. 14-Year survival was 80% and 25 year survival was 77%. Whilst right ventricular function was only assessed subjectively, efforts were made to standardise assessments and control internal errors. Right ventricular function and also the incidence of important tricuspid regurgitation were shown to deteriorate between follow-up periods. Furthermore, exercise capacity and functional status (NYHA class) were also shown to fall. The authors comment that where death occurred, the mode of death changed during the second follow-up from sudden arrhythmic death to death from congestive heart failure, although there were only two deaths and one transplantation in the second period. In addition to deaths, the main endpoint of the study reflects the considerable morbidity, with only 36% of patients enjoying an event-free survival (lack of intervention, heart failure, arrhythmia or sinus node disease). Roos-Hesslink et al., suggest by extrapolation of the data, that a progressive deterioration will continue to be observed in the future, and that many patients after Mustard operation will die or require cardiac transplantation for heart failure in the next decade.5
The mechanism for this late progressive right ventricular failure is still not understood. Recently, myocardial perfusion deficits have been demonstrated both in patients after intra-atrial repairs and with naturally occurring systemic right ventricles. Coronary flow reserve may be reduced in the systemic right ventricles compared to systemic left ventricles, and a correlation between coronary blood flow and exercise tolerance has been demonstrated.6 Right ventricular mass estimation using magnetic resonance imaging has shown marked increase in patients after Mustard operation. Whilst there is a large variability, those patients with a disproportionately increased right ventricular mass are more likely to demonstrate ventricular dysfunction.7 Thus, progressive deterioration in systemic right ventricular function may be related to "mismatch" between myocardial oxygen delivery and requirements. The effects of acquired coronary artery abnormalities as well as changes in the peripheral circulation leading to increased systemic afterload will need careful future study.
How should patients with systemic right ventricle failure be treated? In contrast to adult studies of ischaemic cardiomyopathy, there are no long-term randomized placebo-controlled drug trials. Small-scale studies of angiotensin conversion enzyme inhibition have not shown objective benefit and a small-scale short-term study of the angiotensin receptor antagonist (losartan), demonstrated only small improvements in ejection fraction, tricuspid regurgitation and exercise duration. Prospective multi-centre evaluation of beta-blockers and vasodilator treatment is underway, but the heterogeneous nature of the population will make interpretation difficult. It is easy to understand how vasodilators might be poorly tolerated in a circulation with intrinsically limited ventricular filling, especially in the context of tachyarrhythmia. Patients who are considered for vasodilator therapy should therefore undergo detailed haemodynamic and electrophysiological evaluation.
The place for surgical management of systemic ventricular failure in adults is also controversial. Application of a pulmonary band is a necessary first step to "retrain" the left ventricle to accept the afterload of the systemic circulation if an arterial switch conversion is to considered. Limited success of the retraining process has been observed, however, with older patients being more likely to fail. Left ventricular injury may occur as a result of retraining, and must be avoided if the left ventricle is to take over a lifetime of systemic afterload. Better methods of slow and progressive application of left ventricular afterload and monitoring of the effects of left ventricular health are under evaluation. One observed effect however is the reduction of tricuspid regurgitation during the pulmonary artery banding process by the geometric changes in the position of the interventricular septum. It is possible that some patients, even older patients, would benefit from the application of a pulmonary artery band to reduce tricuspid regurgitation as their definitive palliation.
Long-term prospective protocol-directed follow up, such as that in the study by Roos-Hesselink and colleagues, is essential to assess longitudinal changes in right ventricular haemodynamics and outcome in order to plan future treatment strategies.
Footnotes
doi:
10.1016/j.ehj.2004.03.009
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References
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