Ann Thorac Surg 2000;69:1858-1863
© 2000 The Society of Thoracic Surgeons
Original articles: Cardiovascular
Right ventricle-sparing heart transplant: promising new technique for recipients with pulmonary hypertension
John A. Elefteriades, MDa,
Costantinos J. Lovoulos, MDa,
George Tellides, MD, PhDa,
Lee J. Goldstein, BSa,
Edward J. Rocco, CCPa,
Spyros G. Condos, PhDa,
Gary S. Kopf, MDa
a Section of Cardiothoracic Surgery, Yale University School of Medicine, New Haven, Connecticut, USA
Address reprint requests to Dr Elefteriades, Section of Cardiothoracic Surgery, Yale University School of Medicine, 121 FMB, 333 Cedar St, New Haven, CT 06510
e-mail: john.elefteriades{at}yale.edu
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Abstract
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Background. Right heart failure remains the leading early cause of mortality after heart transplantation, especially with antecedent pulmonary hypertension. Paradoxically, the discarded recipient right heart, acclimated to pulmonary hypertension, is often stronger than its nonconditioned donor replacement. Heterotopic ("piggy-back") transplantation is plagued by problems related to the retained, dilated, hypocontractile left ventricle (lung compression, systemic emboli, arrhythmias). Were it possible to retain the recipient’s right heart, excising only the left ventricle, this could have important advantages, especially in severe pulmonary hypertension. This report describes such a technique.
Methods and Results. In four transplantation experiments (dogs), right ventricular-sparing transplantation proved technically feasible and hemodynamically successful. Bleeding after excision of the left ventricle was easily controlled. Back-bleeding from the native aortic valve (now open into the pericardial space) was not problematic. All atrial, aortic, and pulmonary arterial connections proved feasible. The preserved recipient right heart of all animals remained in stable sinus rhythm. All recipients were easily weaned from cardiopulmonary bypass, maintaining mean arterial pressures 60 to 110 mm Hg.
Conclusions. This investigation develops a technique for donor right ventricle sparing in cardiac transplantation, demonstrating technical and hemodynamic feasibility. This method holds promise for the unsolved clinical problem of right heart failure after orthotopic heart transplantation with antecedent pulmonary hypertension.
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Introduction
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Pulmonary hypertension remains the Achilles heel of clinical heart transplantation. Right heart failure after transplantation remains the predominant cause of the 10% early mortality still seen after transplantation, even in the current era [1–4]. The donor left ventricle, of course, is much stronger than the recipient left ventricle; this is the reason for the transplantation procedure being performed. Regarding the right ventricles, a paradox exists. The recipient right ventricle has, over time, acclimated itself against the increased afterload of high pulmonary artery pressures resulting from the failing left ventricle. The donor right ventricle, on the other hand, is accustomed only to normal pulmonary artery pressures and can fail easily after transplantation [4, 5]. With regard to the ability to cope with elevated recipient pulmonary artery pressures, the discarded recipient right ventricle is often much stronger than the transplanted donor right ventricle [6]. Even with ß-agonist or phosphodiesterase inhibitor support of the transplanted donor right ventricle and with vasodilatation of the pulmonary arteries with nitrates, nitroprusside, prostaglandins, and inhaled nitric oxide, right heart failure after transplantation can still be irremediable and, frequently, lethal. When mechanical support of the right ventricle needs to be implemented, mortality may approach 50% [7].
Patients with pulmonary artery resistance in the range of 1 to 3 Wood units are optimal candidates for heart transplantation. With pulmonary vascular resistance between 3 and 6 Wood units, patients become high risk. Several studies have shown that patients in this high risk group have an early mortality of 17% to 60% after transplantation [8–10]. Above 6 Wood units, most authorities believe that heart transplantation is contraindicated.
Heterotopic ("piggy back") transplantation allows the entire native heart to be preserved. The presence of the accessory native right ventricle provides valuable assistance to the vulnerable transplanted donor right ventricle. Accordingly, heterotopic transplantation has been used, especially in England and South Africa, for the high risk patient with pulmonary hypertension [6, 11, 12]. However, heterotopic transplantation has not become widely popular, largely due to problems related to the persistent presence of the enlarged, hypocontractile recipient left ventricle [11, 13]. Space problems have been noted, with compression of the left lung by the heterotopic donor heart. Arrhythmias, including ventricular tachycardia and ventricular fibrillation, continue to plague the recipient left ventricle even after heterotopic transplantation. Also, the enlarged, hypokinetic recipient left ventricle continues to be an important source of systemic emboli, which can cause stroke or other ischemic complications. Late postoperative problems after piggy-back transplantation led Losman and colleagues [14] in 1978 to reoperate on 1 patient to partially resect, imbricate, and obliterate the left ventricle.
Heart–lung transplantation can be offered to patients with moderate or severe pulmonary hypertension, as the diseased pulmonary vasculature is replaced with the normal vasculature of new lungs. However, donors for heart–lung transplantation are rare, and the procedure has inherent negative long-term sequelae [15]. Heart–lung transplantation, thus, is infrequently applied in the United States.
If it were possible to preserve the self-conditioned right ventricle of the recipient, while excising the enlarged, hypocontractile left ventricle, this could be of great benefit. The presence of the native right ventricle could provide built-in "mechanical" support while the donor right heart accommodates to the extant pulmonary hypertension. The two right hearts could function in parallel. The bulk of the diseased native left ventricle would be removed, allowing space nearly orthotopically for the entire new heart. Furthermore, none of the negative sequelae—space problems, arrhythmias, emboli—that plague the persistent recipient left ventricle in heterotopic transplantation would apply to the right ventricular-sparing transplant.
If such a right ventricular-sparing transplant were feasible, it could render transplantation safer for the patient with moderate pulmonary hypertension and even permit transplantation for the patient with advanced pulmonary hypertension that would otherwise contraindicate transplantation. Also, wider use of the donor pool could be achieved. Currently, surgeons accept only large, usually male, donors for the recipient with moderately severe pulmonary hypertension. With the assistance of the recipient right ventricle, a larger range of donor heart sizes could be used.
Through cadaver and animal experiments, our team has developed such a right ventricular-sparing technique of heart transplantation. We report herein an initial series of feasibility experiments from our laboratory, along with illustrations of the technique.
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Material and methods
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After review and approval by the Yale University Animal Care and Use Committee, surgical experiments were conducted on eight mongrel dogs, weighing 35 to 45 kg. Four dogs served as donors and four as recipients. Donor and recipient operations were carried out simultaneously on side-by-side operating tables. Electrocardiogram, body temperature, arterial blood pressure, pulmonary artery pressure, and arterial blood gases, were monitored and recorded on a strip chart recorder (Electronics for Medicine, Jupiter, FL).
Donor procedure
The donor operation was carried out according to established clinical procedures used at our center for human transplantation. The inferior vena cava was incised initially to prevent right heart dilatation during cardioplegia administration. The vena cavae were transected. The aorta and pulmonary arteries were transected. The pulmonary veins were transected. Donor heart preservation was by aortic root cardioplegia (our institutional standard crystalloid cardioplegia, containing 20 mEq KCl/L at 4°C) and topical hypothermia (ice basin, followed by continuous cold topical irrigation and left atrial instillation during implantation). Implantation was begun immediately after harvest, with no additional ischemic time. The entire superior vena cava (after ligation of the azygos vein) and part of the right subclavian vein were harvested to facilitate later right heart anastomosis. All of the ascending aorta and the aortic arch (after division of the great vessels) were harvested to facilitate later aortic anastomosis. The donor right pulmonary artery was preserved to provide greater length for later anastomosis.
Recipient procedure
The recipient was cannulated with the arterial perfusion cannula in the femoral artery and two venous cannulas, one in the femoral vein and one in the right atrium.
The right ventricular-sparing heart transplantation was performed as follows:
Excision of the recipient left ventricle
The recipient left ventricle was excised 1 cm beyond the interventricular groove, beginning with the anterior wall just left of, and preserving, the left anterior descending coronary artery (Figs 1 and 2). Diagonal coronary arteries were ligated or cauterized, according to size. The incision was carried caudally around the left ventricular apex to the inferior wall. The posterior descending coronary artery was preserved. The main posterolateral branch of the right coronary was divided as it coursed laterally to the posterior surface of the left ventricle in the atrioventricular groove. The coronary sinus was ligated similarly beyond the vein that accompanies the posterior descending coronary artery. The excision of the left ventricle was then carried anteriorly across the base of the left ventricular outflow tract underneath the aortic valve. The left ventricular excision was then completed by transecting the lateral wall of the left ventricle just beyond the atrioventricular groove, just caudal to the mitral valve annulus. The left circumflex coronary artery was ligated, as were the marginal branches, as the left ventricular incision was carried posteriorly. The left ventricle, with the papillary muscles attached, was then removed from the pericardial space after cutting chordal attachments to the mitral valve leaflets. The cut surface of the left ventricle was then oversewn with an over-and-over suture. This accomplished complete hemostasis. No significant bleeding was actually observed through the remaining right ventricular septum itself. This method of excision of the left ventricle spared the right coronary and the posterior descending coronary arteries and the left main coronary and the left anterior descending arteries, thus preserving direct perfusion of the right ventricle through the acute marginal branches of the right coronary artery, the posterior descending coronary artery and its septals, and the left anterior descending artery and its septals (Fig 2).
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Fig 2. Isolation of coronary blood supply. The right ventricular-sparing transplant preserves the right coronary artery and the posterior descending coronary artery, and the left main coronary artery and the left anterior descending, thus maintaining direct perfusion of the right ventricle through the acute marginal branches of the right coronary artery, the posterior descending coronary artery and its septals, and the left anterior descending and its septals.
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Closure of the aortic valve
We found that the aortic valve remained competent after excision of the left ventricle. Of course, the bottom of the valve was now open to the free left ventricular cavity. Nonetheless, no blood whatsoever was seen regurgitating through the valve, despite the performance of the operation with the heart perfused and beating without cross-clamp application. Because of the potential for significant bleeding from even trace aortic insufficiency in the human clinical setting, the aortic valve was closed in these animal experiments, either by a pericardial patch across the left ventricular outflow tract or by direct suture of the aortic valve leaflets (Fig 3). Both methods were effective. The aortic cross-clamp was applied, with antegrade cardioplegic arrest of the retained right ventricle, for this aortic valve closure.
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Fig 3. Cut edge after removal of the left ventricle. A continuous suture achieves hemostasis of the cut ventricular edge. The aortic valve has been oversewn to prevent regurgitation into the pericardial space.
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Left atrial anastomosis
The donor left atrium was prepared by incising between the pulmonary veins to produce a single circular left atrial opening, as in routine clinical practice. This donor left atrial opening was then anastomosed to the recipient heart remaining after the excision of the left ventricle, as described previously. In addition to the excision described, the posterior left ventricular wall and the posterior mitral valve leaflet were excised, opening into the anterolateral portion of the left atrium. This atrial incision was then carried cephalad into the left atrial appendage to match the size of the donor left atrial cuff. This incision into the left atrial appendage raised the ultimate position of the implanted donor heart anteriorly, permitting easier great vessel anastomosis later in the procedure. The left atrial anastomosis was performed by suturing the donor left atrial opening to the recipient left atrial cuff and then running the suture line anteriorly to incorporate the anterior mitral valve annulus and leaflet. The leaflets and annulus together made a secure ring of strong, fibrous material for the anterior aspect of the anastomosis (Fig 4). As the left atrial anastomosis proceeded, the donor heart was lowered into the pericardial cavity.
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Fig 4. Left atrial anastomosis. The posterior mitral annulus has been excised, providing entry to the recipient left atrium (LA). This incision is continued toward the left atrial appendage. The donor left atrial opening is anastomosed to the left atrial free wall posteriorly and to the mitral valve annulus and anterior leaflet anteriorly. The annulus and leaflet from a strong fibrous ring for suture placement. (LV = left ventricular; RA = right atrium; SVC = superior vena cava.)
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Aortic anastomosis
The donor aorta was anastomosed end-to-side to the recipient aorta in a convenient location above the aortic valve (Fig 5). This anastomosis was done under side-biting control of the ascending aorta. Donor heart perfusion was resumed as soon as this anastomosis was released. Thus, the donor ischemic interval was minimal, involving only the left atrial and aortic anastomoses. (A Dacron conduit was used for length when necessary to extend the donor aorta to reach the recipient.)
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Fig 5. Completed right ventricular-sparing heart transplant. The entire donor heart fits nearly orthotopically in the space left behind by excision of the left ventricle (LV). Space should be even more ample in the clinical setting of advanced left ventricular dilatation. (Ao = aorta; PA = pulmonary artery; LA = left atrium; RA = right atrium; RV = right ventricle.)
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Right heart connections
The inferior vena cava of the donor heart was closed by running suture. The donor superior vena cava was anastomosed to the recipient right atrial appendage (with an interposition Dacron graft, if necessary) (Fig 5). This anastomosis permitted inflow from the recipient venous circulation to the donor right heart. Subsequently, the donor pulmonary artery was anastomosed end-to-side to the main pulmonary artery of the recipient in a convenient location above the pulmonic valve. This connection established continuity for donor right ventricular outflow to the recipient pulmonary circulation.
A single dose of steroid medication (500 mg Solumedrol; Upjohn, Kalamazoo, MI) was administered before aortic unclamping to prevent early rejection. No other immunosuppressive medications were given. The dog was weaned from cardiopulmonary bypass, with inotropic support as required, hemodynamic measurements taken, and the animal euthanized 30 minutes after termination of bypass. All composite recipient–donor heart preparations were excised and subjected to gross postmortem inspection.
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Results
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In all four transplant procedures, the right ventricular-sparing heart transplantation was able to be accomplished. The operation proved technically feasible in all respects: - The left ventricle was able to be excised alone.
- Hemostasis from the cut free wall of the left ventricle was easily achieved by the continuous suture.
- Donor aortic valve hemostasis and exclusion were able to be achieved.
- Bleeding from the septal wall was minimal.
- Blood flow to the right ventricle was preserved, with maintained visible, normal-appearing contraction of the right ventricle, without ventricular fibrillation.
- All anastomoses were able to be constructed hemostatically. The "reach" from all structures to their anastomotic counterparts was feasible (with interposition Dacron grafts as necessary). With experience, the interposition grafts became unnecessary.
- The donor heart fit well in the space remaining after removal of the recipient left ventricle. The left lateral pericardium was incised to permit a comfortable lie. No undue compression or atelectasis of the lung was observed.
All four recipients were able to be weaned from cardiopulmonary bypass with only mild support with epinephrine. Mean arterial blood pressure at termination of bypass ranged from 60 to 110 mm Hg. All animals sustained hemodynamics well for the duration of the experiment. The donor and recipient ventricles beat vigorously in parallel, but not in synchrony. No pacing of either donor or recipient hearts was required.
In the fourth experiment, pulmonary hypertension was created after weaning bypass by mechanically occluding 75% of the distal recipient pulmonary artery (by clamp, beyond the end-to-side anastomosis). Systolic blood pressure decreased from 115 to 105 mm Hg and remained stable at that level, without visual evidence of strain of either right ventricle.
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Comment
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Right ventricular failure after cardiac transplantation in the face of antecedent pulmonary hypertension remains a serious cause of early mortality and a persistent clinical problem despite developments in pharmacologic support of right ventricular function and pharmacologic manipulation of pulmonary vascular resistance. Even temporary mechanical assistance of the right ventricle after transplantation is usually not lifesaving in these circumstances. The irony in this problem is that the conditioned right ventricle that the patient had before the operation was stronger than the new transplanted one.
The experiments reported in this laboratory investigation develop a procedure for heart transplantation that permits the recipient right heart to remain in place. Only the recipient left ventricle is excised. This results in a preparation with two right hearts (donor and recipient) functioning in parallel and a single (donor) left heart (Fig 6).
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Fig 6. Schematic diagram of connections and flow patterns in right ventricular-sparing heart transplantation. (Ao = aorta; PA = pulmonary artery; LA = left atrium; LV = right ventricle; RA = right atrium; RV = right ventricle; D = donor; R = recipient.)
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These experiments demonstrate that such a technique is anatomically and physiologically feasible and technically achievable. These experiments demonstrate that the resulting heart preparation is capable of functioning well physiologically in vivo.
We have shown that the left ventricle can be excised alone. The open-ended aortic valve is not a problem once oversewn. Septal bleeding is not a problem. The free edge of the transected left ventricle is easily controlled by a continuous suture. All anastomoses are feasible. The right ventricle maintains an organized contraction despite the absence of its normal neighbor. The right ventricle does not fibrillate with the preservation of the left anterior descending artery, the right coronary artery, and the posterior descending coronary artery. The two right hearts function well physiologically in parallel.
An added benefit of this technique is that the ischemic time for the donor heart is minimized, as only two anastomoses—left atrium and aorta—need to be done before reperfusion of the donor heart. The right-sided anastomoses are done subsequently.
We contemplated not connecting the donor right heart to the recipient right heart, so that the donor right heart would need to pump only its own coronary sinus return. This is another option. We believe that it was preferable to do the right atrial connection, however, so that both right hearts could contribute to pumping blood to the lungs.
We believe that the technique reported holds significant promise for the clinical dilemma of heart transplantation in the face of elevated pulmonary vascular resistance. We hope that this procedure may have a beneficial impact on the mortality of transplantation under these circumstances. This technique may allow greater flexibility in selection of donor hearts, perhaps eliminating the need to "oversize" for pulmonary hypertension. The right ventricular-sparing heart transplantation may even permit clinical transplantation of patients currently thought to have levels of pulmonary vascular resistance that contraindicate transplantation.
As this was a feasibility study only, there are limitations of the work reported. The animals were sacrificed after stable hemodynamics were confirmed. Survival experiments would be important to demonstrate continued good physiologic function. These studies were carried out in normal animals, not in a chronic pulmonary hypertension model. An experimental model incorporating pulmonary artery banding or a chemically induced simulation of the clinical scenario of human chronic pulmonary hypertension would be instructive. Further experiments are required to detail the physiologic interrelation of the two right ventricles, in terms of valve function and flow patterns of the parallel right heart systems over time in normal and pulmonary hypertension models. Echocardiographic or crystal models need to investigate the physiologic function of the right ventricle bereft of its normal left ventricular neighbor; there may be significant consequences when the septal wall becomes a "free" wall.
Despite these limitations, this method of transplantation provides hope for progress in the unsolved problem of right heart failure after orthotopic heart transplantation in the face of antecedent pulmonary hypertension.
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Footnotes
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This article has been selected for the open discussion forum on the STS Web site: http://www.sts.org/section/atsdiscussion/
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References
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Accepted for publication December 28, 1999.
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Abstract
Introduction
