The history of surgical creation of right ventricle to pulmonary artery continuity could be traced back to the 1960s when Ross et al.1 and Rastelli et al.2 pioneered operations involving implantation of a conduit to connect the right ventricle to the main pulmonary artery in patients diagnosed with PA/VSD. Conduits placed for such purposes were usually on a heterotopic position, rather than the theoretically more hemodynamically efficient orthotopic position like in a normal heart. This led to suggestion that a heterotopically-placed conduit position might negatively affect its function and longevity, which could possibly result in the need for reintervention and ultimately to decreased patient’s overall survival.
Techniques for surgical placement of a conduit on an orthotopic position are more demanding, as enlargement of the RVOT to accommodate the new, larger conduit would be necessary. Sometimes, the size of the newly-enlarged RVOT would still not be compatible to the conduits available, forcing surgeons to implant smaller-than-ideal conduits. Therefore, the technically simpler and more straightforward heterotopic conduit placement seems to be an interesting and more feasible option. However, there has only been a handful of studies directly conducted on this topic regarding the heterotopic conduit position on its longevity and possible negative effects on the patient’s need for reintervention and overall survival. One study3 compared conduit longevity and overall survival of patients at 15 years after placement of conduits on an orthotopic to a heterotopic position. There were no significant differences in both groups. On the other hand, another study4 yielded an opposite result, with patients receiving conduits placed heterotopically having worse reintervention-free survival than those receiving conduits placed orthotopically. The reasons behind these conflicting results had been debated by both authors, stating that in both studies, patients who received conduits placed orthotopically were older and had significantly bigger body sizes, resulting in the possibility to receive larger or “oversized” conduits. Theoretically, an oversized conduit might mitigate the patient’s “outgrowth” process, which would render the conduit relatively too small for the eventual body size.
Conduit type and size, as well as patient’s age at operation, have been thought to have significant effects on conduit longevity5, 8–11. Our results found that there were no associations between younger ages at operation (age less than 15 years) or smaller conduit sizes (diameter less than 20 millimeters) and more conduit dysfunction or worse reintervention-free and overall survival. The reason was that in our study, every patient would have already received an oversized conduit according to BSA (not just numerically large). In our institution, we routinely implanted oversized conduits, albeit no more than + 2SD the ideal size for the corresponding BSA according to the nomogram29. We found that oversized conduits resulted in acceptable reintervention-free and overall survival. We could suggest that placing oversized conduits might in fact be beneficial as we believed that patient “outgrowing” the conduit was a significant risk factor for reintervention. Importantly, large and oversized conduits could be more easily placed on a heterotopic position compared to an orthotopic position, which would otherwise require extensive RVOT enlargement. Limitation regarding smaller homograft sizes availability resulted in the necessity of conduit bicuspidization in some cases. We also found bicuspidization to be a satisfactory solution as none of our patients who received bicuspidized homograft conduits ended up with conduit dysfunction or reintervention.
However, some believed that oversized conduits were associated with higher rate of conduit kinking and narrowing from sternal compression. As a result, these conduits were more prone to turbulent flow, which might increase their wall shear stress and cause earlier deterioration24–26. Coronary compression and pulmonary arteries distortion23 from conduit compression might also occur. This could ultimately result in earlier conduit stenosis. Even that said, we still believed that if conduits were not too oversized and placed on a proper position away from the sternal table, conduit kinking or compression by the sternum could be avoided.
A few studies6, 7 evaluated patients who previously underwent TOF repair during childhood with pulmonary valve regurgitation (PVR). Patients had their regurgitant pulmonary valves replaced either surgically or percutaneously. Their results suggested that pulmonary valve replacement in patients with post-TOF repair PVR resulted in reduced ventricular dimensions and improved ventricular function. Our study also included a significant number of patients with post-TOF repair PVR who underwent secondary pulmonary valve replacement by an orthotopically-placed conduit. In our study, we aimed to compare ventricular dimensions, function, and exercise capacity between patients who had conduits placed orthotopically and heterotopically. Heterotopically placed conduits, which resulted in more turbulent blood flow, might theoretically adversely affect long-term ventricular size and function. However, our results proved the contrary, with both groups yielding similar results. As there were more patients with secondary pulmonary valve replacement in the orthotopic position group than the heterotopic position group, we suspected that the possibly more efficient orthotopic conduit position might be nullified when faced with the fact that this group of patients might already have larger ventricular size and worse cardiac function. These parameters might not improve as well as in patients who had normal or near-normal ventricular size and function before surgery.
Pulmonary hypertension could also affect conduit function. As in our study, the majority of patients receiving RV-to-PA conduit reconstruction were diagnosed with either TOF, PA/VSD, or DORV/PS. These diseases on their own generally resulted in restricted pulmonary blood flow, which would not result in pulmonary vascular obstructive disease (PVOD). Therefore, they might not have negative effects on conduit function and longevity. However, with the rarer diagnosis of TA, which resulted in pulmonary overflow, the results might prove otherwise. Our results did not demonstrate TA to be a potential risk factor for conduit dysfunction, reintervention-free survival, and overall survival. We believed that the reason behind this was that patients with TA generally underwent surgical conduit placement much earlier in life, in which PVOD had not yet developed15, 16. Also, we had very limited number of TA patients in our cohort, which might not be enough to be statistically significant. We also believed that concomitant pulmonary arterioplasty would result in reduction of postoperative pulmonary artery pressure. This should theoretically reduce conduit afterload and therefore resulted in longer conduit dysfunction-free survival.
A few studies12–14, 16–18 compared pulmonary and aortic homograft in terms of reintervention-free and overall survival. Their results suggested that pulmonary homograft use was associated with better reintervention-free and overall survival compared to aortic homograft. They suggested that because aortic homografts had more elastic tissue and tissue calcium content, this would result in more conduit calcification and stenosis. Even though our results did not show pulmonary homograft to be superior in terms of conduit dysfunction-free, reintervention-free, and overall survival, we still preferred pulmonary homograft to be the conduit of choice at our institution. One study12 mentioned that immune process had a more prominent role in causing conduit dysfunction in children than in adults. However, from our results, we found that younger age at operation did not adversely affect conduit longevity, reintervention-free survival, and overall survival. We could suggest that immune process was not a risk factor in determining either conduit longevity or reintervention-free and overall survival.
Decellularized homografts, on the basis that they lacked living cells, would result in less immune reactions and possibly longer conduit durability19, 22. Other studies concentrated on the preservation processes of homografts, including immersing in antibiotic solution21, the now-obsolete irradiation treatment23, and the most commonly used cryopreservation technique. In our hospital, we routinely used cryopreserved homografts supplied by Thai Red Cross Organ Donation Center (Fig. 4). Homografts would be harvested, soaked in 200 milliliters of Roswell Park Memorial Institute (RPMI) 1640 solution, and preserved in 90 milliliters of Medium 199 solution combined with 10 milliliters of 10% dimethyl sulfoxide (DMSO) solution (Thermo Fisher Scientific, Waltham, Massachusetts, USA). They would then be cryopreserved and stored in liquid nitrogen at -196 degrees Celsius, with a shelf life of 5 years. Even with different processing and preservation techniques as compared to others’, we could still obtain reasonably good results from our patients.
Cryopreservation theoretically would result in elimination of living cells in conduits, leaving only the “scaffolding” remaining27. From this aspect, it was implied that immune reaction could not have been the cause of conduit deterioration, as there were no living cells for the immune system to attack. This supported our idea that not immune, but outgrowth process, was the main determinant of conduit longevity. However, one study28 found that most of their patients whose conduits failed were from conduit constriction and shrinking, not from outgrowth process, suggesting that immune process was the main risk factor. Although their results were convincing, we believed that conduit constriction and shrinking could have also been from other factors other than immune process.
Surgical technique-wise for heterotopic conduit implantation, we routinely sutured proximal conduit anastomosis to the right ventricular (RV) epicardium18, not buried deep to the infundibular septum. Even with this technique, which could possibly place the conduit at higher risk of being compressed by the sternum because of its more anterior position, we found that our heterotopically-placed conduits were not associated with worse durability, reintervention-free survival, or overall survival as compared to the orthotopically-placed ones. We could state from our results that the simpler RV epicardial proximal anastomotic suturing technique could be adapted as the outcomes were satisfactory.
We calculated conduit CSA30 indexed to BSA, creating “CSA index” (CSAi), in our study. We believed that this term would be the most accurate in comparing patients with different conduit sizes as they wound have different BSAs. By indexing CSA with BSA, we could obtain a more standardized term corresponding to the individual patient’s BSA for direct comparison rather than conduit diameter or CSA alone. Our aim was to determine if patients whose conduits failed had significantly higher CSAi when compared to patients whose conduits did not. Our results demonstrated that patients in the failure group did not have conduits with significantly higher CSAi implanted compared to those in the non-failure group. This would strongly suggest that implantation of oversized conduits would not result in their reduced longevity or decreased reintervention-free and overall survival, as supported by other findings in our study.