Arquitectura del Sistema

3.4.1 Mortality

Cumulative survival from date of initial surgical correction as well as the single paper reporting SMRs (Diller et al., 2015) suggest that survival is poorer in patients with a systemic RV versus repaired TOF. This perhaps lends support to the hypothesis that a systemic RV has an innate predisposition to fail prematurely compared to a morphological LV. The reason that CCTGA patients tend to do worse than patients with TGA post-atrial switch can perhaps be explained by the fact that patients with CCTGA often have significant co-existent cardiac lesions, and the papers identified in this review included "all-comers", i.e. it was not possible to express survival purely for patients with CCTGA who did not require any form of additional surgical correction, who would have formed a more natural physiological comparator group to the TGA-atrial switch patients.

With later birth cohorts mortality appeared to decrease, and this is

supported by the fact that surgical repair before 1980 was associated with greater risk on multivariate analysis for both systemic RV and repaired TOF patients (Nollert et al., 1997, Vejlstrup et al., 2015, Cuypers et al., 2014). However this is confounded by the fact that papers did not generally report cumulative survival by surgical era, and dates of initial surgical correction tended to be very broad. Establishing whether there was any social or geographical variation in mortality was beyond the scope of this study, mainly owing to the sheer number of potentially confounding variables. However, it is worth noting that the highest cumulative survival for CCTGA and repaired TOF was reported by centres in East Asia (Park et al., 2010, Chiu et al., 2012, Lim et al., 2010, Miyamura et al., 1993, Okita et al., 1995). Interestingly I found no studies from this region reporting long- term prognosis in TGA-atrial switch, although there were a number of studies reporting outcomes in the Arterial Switch Operation for TGA, and these also demonstrated excellent cumulative survival at well over 90% at up to 20 years post-surgical repair (Lim et al., 2013, Masuda et al., 2001). Finally it is worth noting that only one paper reported mortality as SMR. As described previously, by

86 expressing survival as a function of age rather than time from baseline, one is able to mitigate both the birth cohort effect and also the disproportionate influence of early postoperative mortality. Therefore this method may well be a more accurate way of assessing survival in ACHD patients, and it is surprising that so few centres have adopted this approach.

3.4.2 Morbidity

Morbidity was often not reported, and when it was it was frequently reported in different ways. The commonest way of reporting it was as a cross- sectional "snapshot" at the end of the follow-up period, although for some

outcomes, such as arrhythmia or reintervention, survival analysis was undertaken to ascertain the number of patients who were still free from the outcome of interest at a specified point in time from the original baseline. Furthermore, the morbidity outcomes reported tended to relate to outcomes which are generally easy to ascertain such as repeat surgical intervention, rather than more detailed functional assessment such as data derived from non-invasive imaging regarding e.g. the severity of ventricular dysfunction or valve regurgitation. Data were also lacking for morbidity outcomes such as endocarditis, stroke, venous

thromboembolism, pregnancy, and acquired cardiovascular disease; again these are outcomes where status is difficult to establish as patients may not present to their original cardiac centre when these occur.

A few general themes came across in the analysis however. The proportion of patients experiencing a morbidity outcome in contemporary publications was higher than that reported by the oldest publications, and this was mainly driven by gradual attrition of patients to developing arrhythmia and haemodynamic lesions requiring repeat intervention. On the whole patients with a systemic RV tended to have higher rates of arrhythmia, pacemaker implantation, and repeat intervention than those with TOF.

87 3.4.3 Study limitations

The major limitation of this study is the very heterogeneous nature of the cohorts that were reviewed. Despite the same underlying diagnosis, there may be several subtypes within that condition and a number of different operations which can be performed at the time of initial surgical correction. Patients vary in terms of the presence or absence of other associated congenital abnormalities and genetic syndromes, and they may or may not have had a palliative shunt prior to corrective surgery. Whilst all of these parameters can be reported, it is impossible to adjust for them in a meaningful way when performing a standard survival

analysis (using time from surgical repair as the baseline) due to the relatively small numbers each subgroup. Another important limitation is that the studies reporting outcomes for the longest period of follow up will inevitably reflect the results of surgery performed several decades ago. This means that the survival data will be less relevant to those patients operated upon in a more contemporary era, and perhaps wider reporting of SMRs could avoid this problem. Other important limitations of this study include the lack of reporting of specific morbidity outcomes for each population, a paucity of functional data, the variation in the definition of a particular adverse outcome between different papers (for example one paper may have defined VT as sustained VT requiring treatment whereas another may have included patients experiencing brief runs of asymptomatic VT identified incidentally on an ambulatory ECG), and wide variations in the

proportion of patients for whom morbidity status could be ascertained (sometimes data regarding the presence or absence of arrhythmia was available for less than half of the original cohort). Finally, there was also a degree of selection bias in that by only including papers which included reporting of mortality, it is possible that papers which looked exclusively at a particular morbidity outcome for each diagnosis, for example the need for PVR in TOF, were missed. However this would have added greatly to the complexity of what was already a difficult literature search.

88 3.4.4 Conclusions

Survival is higher in patients with repaired TOF than those with a systemic RV. Only one paper used SMR to assess survival; this valuable technique is thus under-utilised. Morbidity appears to be high, however there were major

differences in the way outcomes were reported, and some outcomes appeared to be significantly under-reported.

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Chapter 4 Long term outcomes in the