Unidirectional valved patches for closure of septal defects in patients with severe pulmonary hypertension

Pulmonary hypertension due to delay in presentation, diagnosis, referral, and surgery for septal defects is not uncommon in the developing world and translates into high morbidity and mortality following open heart surgery to close these defects. Leaving a small atrial communication may not always be effective. Extracorporeal membrane oxygenation and inhaled nitric oxide therapy in the immediate postoperative phase may not be available or may not be financially feasible in many institutions which are economically challenged. Unidirectional valved patch is emerging as a new and effective solution to this problem and promises to make at least the immediate postoperative results more predictable in this subset of patients.


INTRODUCTION
In developing countries, it is not uncommon to encounter patients with ventricular and atrial septal defects who present beyond infancy. [1,2] These patients often have severe pulmonary arterial hypertension (PAH) with a high pulmonary vascular resistance with reversed or bidirectional shunt through a septal defect. Many of these patients are considered to have "borderline operability". The operations to correct these defects are conducted using cardiopulmonary bypass (CPB) that is associated with a systemic inß ammatory response causing release of vasoactive substances (thromboxane A2 and catecholamines), which results in pulmonary vasoconstriction and acute pulmonary hypertension. [3][4][5][6] The resulting pulmonary hypertensive crisis, acute congestive heart failure, and acute respiratory failure are the principal causes of increased morbidity with mortality ranging from 22.7-50%. [7][8][9][10][11][12][13][14][15] To counter these problems, patients require high doses of pharmacologic agents such as phosphodiesterase inhibitors like sildenafil or inhalational nitric oxide to achieve hemodynamic stability in the immediate postoperative phase. In extreme cases, difÞ culty may be encountered in separating these patients from cardiopulmonary bypass and extracorporeal membrane oxygenation (ECMO) support may be required. In industrialized nations, such patients are potential candidates for lung or heart-lung transplantation or aggressive pulmonary vasodilator therapy following closure of septal defects. All currently available pulmonary vasodilators with the exception of sildenaÞ l are very expensive and have limited efÞ cacy. Some of the available agents such as prostacycline and inhaled nitric oxide are difÞ cult to administer on a longterm basis. Elastase inhibitors and gene transfer therapy are still experimental even in the developed world. [16] Despite these strategies the "long-term" survival remains unchanged. [7][8][9][10][11] Therefore, these expensive measures are logistically impractical and are a drain on the meager health resources in developing nations.
A common surgical strategy to improve outcome in these patients consists of leaving behind a small interatrial communication to provide a pop-off during periods of elevated right-sided pressures when the resultant rightto-left shunt through the interatrial communication prevents acute right ventricular failure at the cost of systemic desaturation. The degree of shunting through this communication is unpredictable, and rarely some of these may require percutaneous intervention to close this communication if the pulmonary artery pressures subside and a left-to-right shunt ensues. A fenestration in the patch used to close the defect with a valved mechanism can potentially serve as a pop-off in one direction at the level of the previous shunt (atrial or ventricular septal defect). When the left-sided pressures exceed right-sided pressures, the valve closes and prevents a left-to-right shunt.

Principles
A variety of techniques have been utilized for creating a unidirectional valved patch (UVP). [17][18][19][20][21] The principles of all these techniques essentially remain the same. These patches are designed to function like the fossa ovalis of the atrial septum. During periods of acute elevation of pulmonary artery pressure, opening of the valve allows the blood to fl ow from right to left. This rightto-left shunt prevents acute right ventricular failure from refractory pulmonary artery hypertension and helps in maintaining adequate cardiac output, thereby, reducing the risk of early postoperative death [ Figure  1]. When pulmonary artery pressure gradually falls after operation and pressure gradients between the right and left sides of the circulation normalize, the unidirectional valve closes and prevents a signifi cant left-to-right shunt [ Figure 1].

Evolution and Techniques
In 1995, Zhou et al., [17] fi rst described UVP for closure of ventricular septal defects (VSD) in patients with severe PAH [ Figure 2]. The UVP was constructed from a Dacron patch approximately as large as the size of the defect to be closed. A fenestration about 0.5-1.0 cm in diameter was made in the patch, somewhat off the center. A piece of quadrangular pericardium was attached by suture to the surface of the Dacron patch. The three edges of pericardium were continuously sutured and one edge was left unattached. This unattached edge of pericardium was tailored to provide a small opening, not exceeding 0.5 cm, and appropriate tension was maintained on the pericardial edge so that the valve mechanism is not loose and incompetent. Also, excessive tension was avoided and complete attachment of the pericardium to the Dacron patch was avoided to prevent the valve from losing its effectiveness. The pericardial fl ap valve was placed on the left (systemic) side of the defect.
Novick et al, [18] introduced the fi rst modifi cation [ Figures  1 and 3]. They constructed the UVP from sauvage Dacron (C.R. Bard, Haverhill, MA) and Gore-Tex (W.L. Gore and Assoc, Flagstaff, AZ) cardiovascular patches. After tailoring the patch for primary closure of the VSD, a fenestration was made in the central region of the patch. The weight of the child was used to decide the size of the fenestration. For children weighing 15 kg or less, a 4-mm fenestration was made; for those weighing between 15 and 20 kg, a 5-mm fenestration was made; and for those weighing more than 20 kg, a 6-mm fenestration was made. A separate fl ap valve patch measuring at least 4 mm greater than the diameter of the fenestration was then constructed. This fl ap valve patch was sewn to the superior aspect of the fenestration on the left ventricular side of the VSD patch. Interrupted sutures were placed along one-third of the superior rim of the fl ap valve patch to anchor it to the VSD closure patch. A separate tethering suture was placed inferiorly and tied loosely to approximate the size of the fenestration. The constructed patch was fi nally sewn into place to close the VSD. The important point was that the fenestration was made in the center of the patch for all defects except atrioventricular septal defects (AVSD). In patients with AVSD, the fenestration was placed in the lower third of the patch to prevent the fl ap valve from interfering with left atrioventricular valve excursion. In 2005, they published a modifi ed technique and proposed a fenestration size that was half of the expected aortic annulus diameter for each child. [18] Following this, a separate fl ap patch at least 4 mm larger than the fenestration was constructed and sewn onto the superior margin of the fenestration along onethird of the circumference. A separate tethering stitch was placed at the inferior apex of the fl ap valve and tied loosely over a Hegar dilator that was the same size as the fenestration. This tethering stitch length approximated the diameter of the fenestration. The VSD patch was sewn into place orienting the patch in such a way that the fl ap valve was placed on the left ventricular (LV) side with the fl ap opening towards the LV apex to avoid subaortic obstruction. Novick et al.,[18,19] recommend the use of this technique to improve the quality of life even for those patients who are declared inoperable and in whom alternative therapies for irreversible PAH, like heart-lung transplantation are not an option.
In 2007, Zhang et al, proposed the use of aortic homograft along with the attached mitral leafl et to construct the UVP [ Figure 4]. [20] The aortic valve homograft was opened longitudinally at the commissure between the right and left coronary leafl et. The right and left coronary leafl et were removed but the noncoronary leafl et and anterior mitral leafl et were preserved to form a large aortic patch with the monovalve. A 4-8 mm fenestration was made above the nadir of the noncoronary leafl et. For patients with body surface area (BSA) less than 1 m 2 and with a preoperative saturation of greater than 91%, a 4-mm fenestration was made; a 6-mm fenestration was made if the patient's BSA was less than 1 m 2 and preoperative SaO 2 was less than 91% or the patient's BSA was larger than 1 m 2 and preoperative SaO 2 higher than 91%; and an 8-mm fenestration was made if the patient's BSA was larger than 1 m 2 and preoperative SaO 2 was less than

SK, Talwar S, Airan BA. A simple technique of unidirectional valved patch for closure of septal defects. J Thorac Cardiovasc Surg 2007;134:1357-8. Copyright American association for thoracic surgery and Elsevier)
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91%. The patch was sutured to close the VSD with the noncoronary leaß et facing the left ventricular side and its free edge toward left ventricular outß ow tract.
We have developed a simplified technique at our institution to address the limitations posed by other techniques. This technique is described in detail elsewhere. [21] After inspecting the defect, a patch of knitted polyester fabric (Impra Inc, Tempe, AZ, US), which is the same width as the size of the defect but is approximately one and half times longer than the desired length is selected and a 4-mm fenestration is made into it. The patch is then folded upon itself to achieve adequate dimensions for closure of the septal defect. The ß ap so created by the folding of the patch covers the fenestration and provides a valved mechanism [ Figure 5]. This patch is sutured to the edges of the septal defect so that the ß ap lies toward the left ventricular side in patients with VSD and toward the left atrial side in patients with atrial septal defect (ASD). Care should be taken to orient the ß ap to open downwards toward the LV apex so that it does not produce left ventricular outß ow tract obstruction during systole.

Postoperative management
It has been our practice to start dopamine 5-10 µg/ kg/min, nitroglycerin or nitroprusside 0.5-2 µg/kg/ min, or the phosphodiesterase inhibitor milrinone prior to discontinuation of CPB. Some advocate placing transthoracic pulmonary artery catheters in all patients to monitor pulmonary artery pressures in the postoperative phase. Intraoperative transesophageal echocardiography and postoperative transthoracic echocardiography is used to assess the result of the operation and the degree of shunting across the fenestration. After termination of CPB, moderate hypocarbia is commonly employed in the operating room. Once the patients are fully awake and hemodynamically stable, they are extubated. Upon resuming oral intake, oral angiotensin converting enzyme inhibitor or phenoxybenzamine is started and the inotropes are weaned off. SildenaÞ l may be administered depending upon the institutional protocol. Anticoagulants/aspirin are not administered.
After discharge from the hospital, follow-up consists of clinical examination measurement of SpO 2 using pulse oximetry and trans-thoracic echocardiography at regular intervals to estimate the pulmonary artery (PA) pressure, assess the right ventricular function and demonstrate the degree of right-to-left shunting. Cardiac catheterization is usually not indiacted.

RESULTS
The results obtained with the use of UVP by various groups are summarized in [Table 1]. Two deaths in Zhou's experience [17] were during the learning curve. One patient died due to acute right ventricular failure and another due to respiratory failure. In the initial 18 patients reported by Novick,[18] there were no early deaths and one late death occurred while the child was awaiting detailed evaluation for suspected pulmonary stenosis. In Novick's later experience [19] spread over more than 10 centers around the world, there were seven early deaths. These were due to technical errors (n = 3), pneumonia (n = 2), arrhythmia (n = 1) and hemorrhage following removal of PA line (n = 1). No cause was speciÞ ed for the seven late deaths. However, a trivial right-to-left shunt was still present in four survivors at follow-up (time not speciÞ ed). Postoperative echocardiographic studies revealed persistent PAH in 25 patients and normal pressures in 17 patients. In Zhang's experience of 27 patients, [20] there were two early deaths due to persistent PAH but there were no late deaths. In our own experience with 21 patients, [22] there were no early or late deaths, but our maximum follow-up was only for a period of 18 months. The valved mechanism was always found to work effectively in patients with suprasystemic right ventricular pressures, who needed a pop-off and this was observed on postoperative transthoracic echocardiograms. No patient had a left-to-right shunt when the RV pressure was subsystemic.

Merits and limitations
All the described techniques have their advantages and disadvantages. It is difÞ cult to compare the results of various techniques because of small numbers and heterogeneity of the patient population. These series have included a wide range of patients with diagnosis such as VSD, ASD, AVSD, double outlet right ventricle, total anomalous pulmonary venous drainage, etc. The overall results observed in these series have been gratifying. However, all the earlier techniques have been found to be time consuming. The UVP in these techniques is always constructed after cardioplegic arrest and assessment of the defect as fashioning the patch prior to this may result in improper sizing of the patch. Also, two patches are often required to construct the UVP, a procedure which adds to the ischemia time. In the original description by Novick, one patient died due to left ventricular outß ow tract obstruction due to the movement of the patch necessitating a further modiÞ cation whereby the valve was placed toward the apex of the left ventricle. The technique described by Zhang [20] is innovative, but suffers from the need for a homograft which are costly and in limited supply. To overcome these disadvantages, we devised a new technique [21] that requires the use of only one patch and less than half a minute to fashion. It is safe, effective, and easily reproducible in our early experience. [22] More detailed results with long-term follow up of our technique are awaited.
Unfortunately, in the absence of a randomized study with controls, it is not possible to conclusively demonstrate that a UVP can actually reduce the mortality and improve survival. The magnitude of right-to-left shunt has not been quantiÞ ed in any of these studies. Prospective studies with a detailed evaluation and description of the patients' resting PO 2 before and after surgery, and response to exercise with demonstration of the direction of shunt through the patch using contrast echocardiography may potentially answer questions about the long-tem usefulness and integrity of the valve mechanism. Cardiac catheterization with detailed hemodynamic evaluation can be performed if the patients consent to undergo this procedure.

CONCLUSIONS
The UVP is designed only to tide over the period of hemodynamic instability in patients with septal defects and severe PAH and to provide a safe closure of the septal defects in patients with "border-line operability". Given the present day indications, this approach helps to salvage these patients in the short to mid-term but the long-term effects of this technique on the natural history of patients with long standing severe PAH are unknown.
We have no data to support the use of this technique in patients with established Eisenmenger's syndrome.