Editorials
“Treat-and-Repair” Strategy for Atrial Septal Defect and Associated Pulmonary Arterial Hypertension
2016 Volume 80 Issue 1 Pages 69-71
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2016 Volume 80 Issue 1 Pages 69-71
While there has not been a definite consensus for the treatment of adult patients with unrepaired congenital heart disease (CHD) and associated pulmonary arterial hypertension (CHD-PAH), drugs for PAH (PAH-drugs) have been widely used and have shown their usefulness in CHD-PAH conditions, including Eisenmenger syndrome.
Article p 227
In this issue of the Journal, Kijima et al1 demonstrate the efficacy of medical treatment (“treat”) with PAH-drugs before initiating the closure of an atrial septal defect (ASD) in patients with open ASD-associated PAH (ASD-PAH). Transcatheter ASD closure (“repair”) was performed when the pulmonary vascular resistance (PVR) and the pulmonary–systemic blood flow ratio (Qp/Qs) were <8 Wood and ≥1.5, respectively. The researchers show the procedural safety of the transcatheter ASD closure and report an improvement in the WHO functional capacity (WHO-FC) of the patients after closure. Various criteria2–4 for ASD closure have been recommended (Table). However, Myers et al expressed suspicions about the long-term benefits of a “treat-and-repair” strategy.2 Because definite criteria do not exist, the “treat-and-repair” strategy has to be reasonably applied to current patients. The Figure shows an algorithm that I propose for understanding the reasonable application of this strategy.
| Year Major Recommendations | Disease | Criteria (Class I) for Operability |
|---|---|---|
| 2014 Mayer et al2 | CHD | · PVRI <6 WU·m2, PVR/SVR <0.3 |
| · PVRI 6–9 WU·m2, PVR/SVR 0.3–0.5, vasoreactivity (+) | ||
| 2013 ACC/AHA Guideline for PH3 | CHD | · PVR(I) <2.3 WU (4.6 WU·m2) |
| 2012 JCS Guidelines for PH | ASD | · Qp/Qs >1.3, PVRI ≤14 WU·m2 |
| · Rp/Rs <0.5 | ||
| · Rp/Rs 0.5–0.8, vasoreactivity (+)/lung biopsy | ||
| 2010 ESC Guidelines for ACHD4 | ASD | · PVR <5 WU |
| Major Concerns on ASD Closure in Patients With Open ASD-PAH | ||
| 1. Perioperative risks | ||
| · Acute PH crisis | ||
| · Acute decompensation of LV | ||
| · Acute decompensation of RV | ||
| 2. Postoperative risks in the chronic phase | ||
| · Residual PAH controllability | ||
| · Right ventricular failure | ||
ACC/AHA, American College of Cardiology/American Heart Association; ACHD, adult congenital heart disease; ASD, atrial septal defect; CHD, congenital heart disease; ESC, European Society of Cardiology; JCS, Japanese Circulation Society; PAH, pulmonary arterial hypertension; PH, pulmonary hypertension; PVRI, PVR index=PVR×body surface area (BSA); Rp, pulmonary vascular resistance (PVR); Qp, pulmonary blood flow; Qs, systemic blood flow; Rs, systemic vascular resistance (SVR); WU, Wood unit.
Algorithm of the “treat-and-repair” strategy for patients with open ASD-PAH. The process of the algorithm is simply explained in the text, except for the threshold values of PVR and estimated mPAP as criteria for “Repair,” which are determined from the linear relationship of PVR/mPAP with right ventricular ejection fraction (RVEF) (=0.4) in patients with chronic thromboembolic pulmonary hypertension (data not shown). ASD, atrial septal defect; mPAP, mean pulmonary arterial pressure; PAH, pulmonary arterial hypertension; PVD, pulmonary vascular disease; PVR, pulmonary vascular resistance.
There are 2 intrinsic problems under consideration in order to reasonably apply the “treat-and-repair” strategy.
1. What is the key information for deciding to perform ASD closure?
2. What are the concerns about ASD closure?
To date, we have searched for triggers that suggest operability as noted in the Table. Before PAH-drugs became available, ASD-PAH caused by reversible pulmonary vascular disease (PVD) was thought to be closed, although there were no definite indicators for the reversibility of PAH/PVD. Even the information obtained from an invasive lung biopsy is limited because it does not represent the histology of the whole lung. Yamaki’s score, the index of PVD (IPVD),5 has the same problem and another potential bias–some operable patients had been misinterpreted as inoperable. Also, we should keep in mind that IPVD used no data from patients treated with PAH-drugs.
Regarding the perioperative risks (Table), acute decompensation of the left ventricle (LV) sometimes occurs because of diastolic dysfunction during the adjustment process of a small LV that has been compressed by the right ventricle (RV); however, this is usually transient and controllable. The most critical situation would be acute RV failure caused by an acute pulmonary hypertensive (PH) crisis. Although an acute PH crisis may be inducible under the additional stresses of hypoxia, acidosis, or surgical procedures, its prediction or complete avoidance can be difficult, particularly during surgical repair using a cardiopulmonary bypass. With the less invasive percutaneous procedure, PH crises are less likely to occur or can even be predicted before releasing the Amplatzer device from the catheter.
The postoperative risks (Table) are much more critical. ASD closure is performed if the residual PAH is controllable and PVD is reversible. However, there is still not any definite evidence of the controllability of residual PAH or the reversibility of PVD after ASD closure. Specialists in CHD and/or pulmonary hypertension have argued that residual PAH mimics the pathophysiology of IPAH,2,6 which has a worse prognosis than Eisenmenger syndrome; therefore, ASD closure leading to IPAH pathophysiology should not be performed if significant PAH persists.2,6 However, in the PAH-drug era, their effectiveness is similar in the treatment of both residual PAH and IPAH. Therefore, the data on the medical treatment of IPAH could guide the treatment of residual PAH. The data from the treatment of patients with IPAH at 1 Japanese center showed an outstandingly good prognosis and hemodynamic improvement as compared with other countries.7,8 All the Japanese patients with IPAH whose mPAP was reduced to below 42.5 mmHg with PAH-drugs survived for 10 years.8 This may be caused by the aggressive combination and titration of PAH-drugs in order to reach (sub-)normalization of mPAP. This process is quite common in Japan because medical insurance covers the cost, which is in contrast to the guidelines for PH or the medical insurance regulations in Western countries. With these results, if the estimated residual mPAP (=PVR×Qs+mean pulmonary capillary wedge pressure) is below 42.5 mmHg, it is possible that the residual PAH after ASD closure will be controllable, leading to a ≥10-year lifespan. Further studies will be necessary to confirm this theoretical strategy.
Despite the similarities between residual PAH and IPAH, the resultant RV dysfunction differs much between them. The duration and amount of volume overload by the L–R shunt before PAH onset and the age of PAH onset are very important in determining the preconditioning (dilatation process) of an individual RV with personal/genetic factors; this leads to a specific adaption process as a (hypertrophic) reaction to the pressure overload from PAH. The effect of a small L–R shunt through a restrictive ASD is negligible in relation to preconditioning; this shunt may even play a protective role in a failed RV as a reverse (R–L) shunt reducing preload for RV and maintaining preload for LV. Therefore, the shunt does not need to be closed. When a large L–R shunt is observed (eg, Qp/Qs >1.5–2), the existence of a nonrestrictive ASD with mild–moderate PAH and functional compensation of the dilated RV can be imagined. Therefore, residual PAH and RV function are likely manageable after ASD closure. The most difficult case is an open ASD-PAH that has a certain level of L–R shunting with/without a mild R–L shunt through a nonrestrictive ASD (eg, Qp/Qs=1–1.5); this is associated with moderately increased PVR and impaired RV function with reduced diastolic compliance. RV dysfunction may initially progress to volume overload and then to pressure overload, and RV dysfunction may be more severe and complicated than that in IPAH, which is afterload (pressure)-dependent and reversible after PAH is fully controlled,9 or after lung transplantation.10 Here, a treatment challenge with one PAH drug (“treat”) is very useful. The response of the RV and PVR to the challenge (“treat”) could direct the decision for ASD closure (“repair”) (Figure). It is important to precisely evaluate RV function using cardiac magnetic resonance imaging (cMRI) before and during the challenge (“treat”). Until the challenge (“treat”) exerts a substantial reduction in PVR (and mPAP), ASD closure (“repair”) will not be indicated and the challenge would still be “treat-without-repair” as for Eisenmenger syndrome. This challenge (“treat”) can be utilized in all situations with the possible reversibility of PAH/PVD.
The “treat-and-repair” strategy makes sense if we understand that “treat” is the method used to determine if the patient’s case is operable. During and after the “treat-and-repair” process, it is important to monitor hemodynamics and RV function. For the same reason, data collection from patients who have already been treated in accordance with the recommendations will help clarify the pathophysiology of ASD-PAH and associated RV dysfunction. The first step in the prompt construction of better guidelines would be a retrospective/registry study, rather than a prospective study, that collects the results from the “treat and/or repair” process.
A.Y. has received lecture fees from Actelion Pharmaceuticals Japan.
