Treat and repair strategy in cardiac shunts with moderate to severe pulmonary arterial hypertension – Is it a feasible solution?

Pulmonary arterial hypertension (PAH) associated with a systemic-to-pulmonary shunt comprises a broad spectrum of patients ranging from very mild elevation of pulmonary pressures in the context of increased pulmonary flow from the systemic-to-pulmonary shunt to others with established vasculopathy and severe elevations in pulmonary pressures and pulmonary vascular resistance (PVR). While management of the extremes of the spectrum is usually straightforward (closure if mild PAH and non-closure if very severe PAH, especially if low pulmonary-to-systemic blood flow [Qp/Qs] and resting systemic desaturation), decision on whether to close the defect or not might be particularly challenging in patients with moderate elevations in pulmonary pressures and PVR. In these borderline cases, the ‘treat and repair’ strategy has been proposed and attempted with promising results.1-3 ‘Treat’ refers to first administer PAH-targeted drugs during at least 3-6 months to reduce PAH to then ‘repair’ the defect by fenestrated closure to diminish part of the volume overload from the shunt, provided specific haemodynamic requirements are met. This strategy is only recommended for atrial septal defects (ASD) in the current ESC and AHA Guidelines for the Management of Adult Congenital Heart Disease, and overall, evidence is scarce and with limited data regarding the haemodynamic profile and its change after treatment, and derived clinical outcomes.4

Akagi et al present data from 25 patients with atrial or ventricular septal defect (VSD) and PAH with PVR ≥5 Wood units eligible for the ‘treat and repair’ strategy, of which 20 underwent successful repair and 5 remained unrepaired.5 Cardiac catheterisation was performed at baseline, after administering PAH-targeted drugs and after closing the cardiac defect. Criteria for defect closure were lenient, allowing repair in patients with PVR <6 Wood units, a Qp/Qs ≥1.3, and resting saturations ≥90% on reassessment after PAH-targeted therapy. No data on exercise such as exercise desaturation or parameters from cardiopulmonary exercise testing or exercise haemodynamics were taken into consideration to decide whether defect closure was feasible.

When comparing the repaired and non-repaired populations there were significant differences between them, since the non-repaired cohort seem to be Eisenmenger-like patients: although there were no data on haemoglobin, these patients had low mean baseline resting saturations (86±4%) and mean Qp/Qs <1 (0.8±0.2). In this cohort, PAH-targeted drugs led to a very mild decrease in pulmonary pressures and a mild increase in Qp/Qs to an absolute value of just 1±0.7, with PVR remaining prohibitively elevated (18±4 Wood units). Nevertheless, the repaired cohort also had severe PAH even after treatment with PAH-targeted drugs with a mean PVR 4.8±2.2 Wood units. Interestingly, and contrarily to the non-repaired group, in the repaired cohort there was a greater decrease in pulmonary pressures (53±13 to 43±20), but specially a significant augmentation of the Qp/Qs (1.5±0.6 to 2.4±1.3), in relation to an underlying vasoreactive pulmonary vasculature. This behaviour with PAH-targeted therapy applied especially to ASDs, since in VSDs pulmonary pressures and Qp/Qs did not change significantly after treatment with PAH-targeted drugs and defects were repaired with a mean PVR of 9.0±1.3 Wood units. The authors explain that these patients with VSD underwent defect closure due to a positive response in the vasoreactive test during cardiac catheterisation. It should be highlighted that only 1 from 18 ASDs and 3 from 7 VSDs closures were fenestrated. There is no information regarding whether the fenestrae remained open during follow-up.

Follow-up data from this study are also interesting. PAH-targeted therapy did not decrease after reparation, on the contrary, the number of patients on dual or triple combination therapy increased during a median follow-up of ~3 years. Although there is no explanation from the authors of the reasons to increase treatment, it could have been related to clinical worsening of the patient due to progression of the disease, ‘despite’ closure of the defect. From a haemodynamic perspective, pulmonary pressures decreased during follow-up, in repaired ASDs due to a reduction in the Qp/Qs but with a net increase in PVR, while in repaired VSDs the decrease in pulmonary pressures was greater and accordingly PVR also decreased significantly. These differences in haemodynamic responses during follow-up possible respond to pathophysiological differences in pulmonary vascular remodelling in each type of defect, and to PAH in patients with ASD resulting from the addition of a second hit (ASD) to an individual (genetically) predisposed to the development of PAH.   
One strength of the study, despite the small sample size, are the data on outcomes at 20 years of follow-up. Despite the data presented on haemodynamics of repaired patients, there was no death or lung transplantation among them, while there were 3 events (2 deaths from PAH, 1 lung transplantation) in the non-repaired cohort starting after 8 years of follow-up. These data should be interpreted with a word of caution, since non-repaired patients represent a population with a more advanced disease, and accordingly it may take longer for repaired patients to have an adverse outcome. Additionally, an increase in PAH-targeted drugs was observed during follow-up in repaired patients possibly to underlying disease progression, although it is remarkable that no patient from this group died or received transplantation during 20 years of follow-up.

To conclude, PAH associated with a systemic-to-pulmonary shunt remains a very challenging entity where there is definitely no universal solution of treatment, but rather a tailored individual management after detailed multimodal assessment should be provided. The ‘treat and repair’ strategy might be a valid option in carefully selected patients, but attention should be given to the different clinical, functional, imaging and hemodynamic parameters as a whole and to their evolution with treatment with PAH-targeted drugs. Further studies are warranted to better delineate the profile of patients with PAH associated with a systemic-to-pulmonary shunt who might benefit from defect closure and to better understand the differences between PAH associated with ASD versus VSD, and accordingly whether there is need for specific management for each entity.