Heterotopic heart transplant: relevance as Bio-VAD in emerging economies

Abstract

Despite the introduction of mechanical circulatory assist systems in India two decades ago, there has not been their wide usage due to two main reasons: (1) economic-financial unaffordability and (2) lack of social support. There have been a number of significant steps taken by the government and by the media for augmenting awareness for organ donation. A sizeable donor pool in India falls into the category of marginal donors, due to a variety of reasons like geographical distances, lack of rapid transport, suboptimal donor management due to the lack of resources, and trained manpower in hospitals where donor harvest is done. Consequently, the usage of the heart as a donor organ is less than 20% in India. There is a lack of statistical data regarding the usage of heterotopic heart transplants, due to the absence of a registry, since the procedure is rarely performed, and comparative results are difficult to obtain due to different subsets of both donors and the recipients. The original papers by Barnard and Cooper cannot be extrapolated in the modern context, as these publications were in the pre-cyclosporin era. Orthotopic heart transplantation (OHT) is a well-established and commonly utilized procedure for patients with end-stage heart failure. Heterotopic heart transplantation (HHT) is a surgical procedure that allows the graft to be connected to the native heart in a parallel fashion to provide a kind of biological biventricular or univentricular (left ventricular support). It was performed first in human beings by Barnard in 1974 [S, J., 49:, Afr, Med, 1975, 303–12].

Background

Despite the introduction of mechanical circulatory assist systems in India two decades ago, there has not been their wide usage due to two main reasons: (1) economic-financial unaffordability and (2) lack of social support. There have been a number of significant steps taken by the government and by the media for augmenting awareness for organ donation. A sizeable donor pool in India falls into the category of marginal donors, due to a variety of reasons like geographical distances, lack of rapid transport, suboptimal donor management due to the lack of resources, and trained manpower in hospitals where donor harvest is done. Consequently, the usage of the heart as a donor organ is less than 20% in India.

There is a lack of statistical data regarding the usage of heterotopic heart transplants, due to the absence of a registry, since the procedure is rarely performed, and comparative results are difficult to obtain due to different subsets of both donors and the recipients. The original papers by Barnard and Cooper cannot be extrapolated in the modern context, as these publications were in the pre-cyclosporin era.

Orthotopic heart transplantation (OHT) is a well-established and commonly utilized procedure for patients with end-stage heart failure. Heterotopic heart transplantation (HHT) is a surgical procedure that allows the graft to be connected to the native heart in a parallel fashion to provide a kind of biological biventricular or univentricular (left ventricular) support. Performed first in a human being by Barnard in 1974 [1], this surgical technique was a useful approach during the pre-cyclosporin era, as it reduced early patient death caused by the high rate of graft failure. However, this indication is no longer relevant, and HHT is mostly used in rare and selected cases, such as patients with fixed pulmonary hypertension (PH; to avoid heart–lung transplantation) or patients with a major donor–recipient body-size mismatch, or a marginal donor heart.

The origins of heterotopic heart transplantation

HHT can be described as a “working” or “non-working model.” The non-working model was mainly used to establish the feasibility of the procedure, for studying surgical sutures and anastomosis and, later, for immunosuppressive therapy that help to prevent graft rejection.

Alexis Carrel (Nobel Prize in Physiology and Medicine 1912) and Charles Guthrie first reported an experimental HHT, where they placed the heart in an ectopic position without removing the native heart [2].

In the 1930s, Franck Mann at the Mayo Clinic [3] recognized rejection of the heterotopic heart in an experimental model.

In the mid-1940s in the Soviet Union, Demikhov and Sinitsyn reported a total of 24 anatomical variants of intrathoracic HHTs by performing a series of 250 canine experiments [4].

Surgical techniques

The current practice is to perform the procedure in the steps described below. To create a working model with a cardiac graft, a connection between the atria is mandatory. Either univentricular or biventricular support is possible depending on the selected technique; however, most of the HHTs are performed using the biventricular model. The main steps of the biventricular model are described underneath [5].

Donor cardiectomy

This procedure is similar to that used in orthotopic transplantation with minor changes, such as increased length of the superior vena cava (SVC) (obtained by ligating and dividing the azygos vein) and extensive dissection of the ascending aorta and pulmonary arteries. Excision from the donor is then similar to that of orthotopic transplantation.

Donor heart preparation

This is performed in a bowl of cold saline solution. The inferior vena cava (IVC) and right pulmonary veins are over-sewn with a running 5–0 monofilament suture, with care being taken to ensure that coronary sinus drainage is not occluded during the closure of the IVC. The segment of tissue between the left pulmonary veins is excised to create one large orifice into the left atrium (required diameter is 4 cm). The resultant left atrial orifice should be roughly equivalent to the orifice of the native mitral valve. The main pulmonary artery is divided at its bifurcation. A linear incision of 6 cm is made in the posterior wall of the SVC with an extension into the right atrium (RA) to create an adequate right atrial orifice; at least, half the length of this incision must involve the right atrial wall (Fig. 1).

Fig. 1.

Donor heart (posterior view) prepared for implantation. Abbreviations: PA, pulmonary artery; Ao+, aorta; SVC, superior vena cava; LA, left atrium; RA, right atrium; RV, Right ventricle; LV, left ventricle; IVC, inferior vena cava; RPVs, right pulmonary veins

Surgery on the recipient

A median full sternotomy is performed, and a right-sided pleuro-pericardial flap is created, extending this incision over the diaphragm (Fig. 2). Care should be taken to stay 2 cm above the phrenic nerve, and hemostasis should be obtained along the cut edges of the flap at that time. A similar reflection is made superiorly, extending the pleuro-pericardial flap towards the SVC, again taking care not to injure the phrenic nerve. The flap will fall back to the right lung creating a single right pleuro-pericardial space. This is meant to lodge the donor heart which is often small and marginal graft. Cannulation of the recipient for cardiopulmonary bypass is then similar to the orthotopic procedure, except a high aortic or preferably a proximal aortic arch cannulation is ideal. We directly cannulate the SVC and the IVC with metallic angled cannulae. After the recipient’s aorta is cross-clamped, cardioplegic solution is administered. Further increments of cold cardioplegic solution can be infused later during the operation in both the donor’s and recipient’s hearts according to the surgeon’s preference. It is helpful to use modified Bretschneider or Del Nido cardioplegia to avoid repeated infusions. The surgery may also be performed with the recipient heart simply fibrillated, allowing continuous coronary perfusion. Recently, we have stopped using cardioplegia for the native heart altogether.

Fig. 2.

Recipient; reflection of pleuropericardial flap to lie anterior to the hilum of the right lung

Left atrial connection or anastomosis is first performed (Fig. 3)

Fig. 3.

Donor and recipient hearts showing the beginning of the posterior suture line of the left atrial anastomosis

An incision is made, similar to the left atrial approach to mitral-valve surgery, into the recipient’s left atrium, starting at the right superior pulmonary vein and extending inferiorly to the interatrial groove. The donor’s heart is placed into the right thoracic cavity, to lie alongside the recipient’s heart. Anastomosis is initiated at the posterior portion of both left atria using a double-ended 5–0 polypropylene running suture, with both sutures terminating on the anterior edges. Surgeons should be aware that the completed anastomosis will be inaccessible at the end of the operation (covered by the right atrial anastomosis); thus, it is essential to sew with caution to prevent any further bleeding. It is also important to make this connection between both left atria as large as possible to prevent any restriction or stasis in blood flow. The objective at this point is to obtain a common atrium from which blood can enter either via the donor’s or recipient’s left ventricles.

The second anastomosis connects both aortas (Fig. 4)

Fig. 4.

Aortic anastomosis. In Bio-LV assist configuration, the PA is anastomosed to RA and in Bio-BiVAD PA, anastomosis is done with interposition graft

The proper length of the donor’s ascending aorta is determined by temporary inflation of the lungs. If the donor aorta is left too long it will cause collapse or atelectasis of right lower lobe of the lung. An end-to-side anastomosis is performed using a side-biting clamp applied to the right side of the recipient’s ascending aorta and a continuous suture using 5–0 polypropylene. Keeping the donor aorta short helps to rotate the donor heart to the anterior part of the right chest, thereby reducing compression of the right lung.

The pulmonary artery connection is completed

The donor’s main artery is often not long enough, and a 22-mm Dacron graft will be needed to avoid any tension or distortion (Fig. 5).

Fig. 5.

Completed procedure with the graft in parallel circuit to the native heart

The rest of the operation is similar to that for orthotopic transplantation: rewarming, release of both snares, cautious and long de-airing maneuvers with a patient placed in the Trendelenburg position, and discontinuation of the cardiopulmonary bypass.

Before closure of the chest, it is recommended to fully ventilate both lungs to ensure the expansion of the right lung and its lower lobe, which has been compressed by the donor’s heart during the operation [5].

For left-ventricular support alone, the heart is similarly placed in the right chest, and both left atria are first connected as described above. The aorta is then connected to the recipient’s ascending aorta. Both vena cava are tied and, in order to create a shunt for the coronary sinus, the pulmonary artery is sutured end-to-side to the recipient’s RA. This is a “biologic left ventricular assist transplant” (bio-LVA) and it does not directly support the right ventricle (RV) [6].

In orthotopic transplantation, high recipient vascular resistance (> 7 Wood units in an adult) is a contraindication to cardiac transplantation. Whereas in bio-LVA implantation, as in left ventricular assist device (LVAD) implantation, recipient right ventricular failure is a contraindication, but high pulmonary resistance in the absence of recipient right ventricular failure is not.

A new technique of HHT with direct PA anastomosis [7]

Owing to the inherent problems of the classic technique, we described a modified technique which affords several advantages as biological biventricular assist.

The current technique for heterotopic cardiac transplantation in patients with high pulmonary vascular resistance entails the interposition of a Dacron conduit between the native and donor pulmonary artery (PA) as it is not possible for the donor PA to reach the recipient PA (Fig. 5). The original technique of Barnard and Losman was abandoned due to intractable arrhythmias. Da Silva et al. [8] proposed an anastomosis between the donor main PA and the inferior margin of the recipient right PA.

We describe a technique of direct PA anastomosis between the anterior surface of the recipient right PA and the donor left PA, an in end-to-side fashion after closing the donor right PA with suture. We believe that this technique confers an excellent anatomic orientation, thereby reducing the chances of the kinking and torsion of the anastomosis.

Surgical technique (Fig. 6)

Fig. 6.

A new technique of HHT with direct pulmonary artery anastomosis. AO, aorta; IVC, inferior vena cava; LA, left atrium; LPA, left pulmonary artery; LPV, left pulmonary vein; RA, right atrium; RPA, right pulmonary artery; RPV, right pulmonary vein; SVC, superior vena cava

We used this technique first in a 48-year-old male patient of end-stage ischemic cardiomyopathy with prior multiple percutaneous coronary interventions and cardiac resynchronization therapies. The calculated pulmonary vascular resistance was 7.1 Woods unit and the systolic PA pressure was 82 mmHg with a systemic pressure of 95/50 mm of Hg. The patient’s severe PH precluded orthotopic transplantation.

Donor heart preparation

After standard donor cardiectomy, the ostia of the right pulmonary veins and the right PA were closed. The IVC was not closed, and nor was a posterior opening made in the SVC-RA junction of the donor heart for a cavo-atrial anastomosis.

Recipient operation

After a standard cardiopulmonary bypass, right-sided pleuro-pericardial reflection was divided to create space for the donor heart in the right pleural cavity. The recipient SVC was transected near the RA, its lower stump was sutured, and its upper stump was laterally mobilized, which exposed the right PA. A left atrial incision was made medially to the right superior pulmonary vein and extended in the interatrial groove. The donor heart was placed in the right side of the chest, and the 2 left atria were sutured in a position that allowed the donor left PA to easily reach the recipient right PA. The anterior surface of the recipient right PA was opened and a cobra hood posterior slit was made on the donor left PA, almost extending to the main PA, and a direct anastomosis was achieved without tension. This was followed by an end-to-end donor/recipient SVC anastomosis and then an end-to-side anastomosis of the donor IVC to the recipient IVC as low as possible, allowing the lower body venous return of the recipient to reach the donor RA. The donor ascending aorta, which is usually long, was anastomosed as distally as possible in the recipient ascending aorta to create space and access to the PA anastomosis in case of bleeding. We believe that the method herein expounded has certain merits. The technique can prevent the theoretic complications of a PA prosthetic graft such as compression, infection, thrombosis, fibrosis, and difficulty in sternal closure. Moreover, achieving a bicaval anastomosis seems to have dual advantages. The first advantage on the SVC side is that the closure of the recipient cardiac end unloads the dysfunctional native heart and endomyocardial biopsy is facilitated because the SVC anastomosis leads the bioptome forceps easily to the donor RV. The other positive point on the IVC side is the sharing of lower body blood and burden between the recipient and donor heart.

Post-operative care

Once cardiopulmonary bypass is discontinued and all vent sites are closed, careful hemostasis is obtained and protamine is administered. Hemodynamics are assessed with echo and pulmonary artery catheter.

Pacing wires are placed on the RA and RV of each heart. Electrocardiographic (EKG) tracings show the non-synchronous contractions of the hearts. Donor and recipient surface EKGs may be obtained from the temporary pacing wires to better isolate the two EKG tracings, but this does not eliminate the tracing from the other heart. As an external pacemaker, temporary electrodes are placed in the RA of both hearts and in the RV of the transplanted heart, enabling a synchronized cardiac pacing through a sequential pacemaker, connecting the atrial poles to the atrial electrodes of the native heart (of higher frequency) and the atrial electrodes of the transplanted heart to the ventricular poles of the pacemaker. Thus, the pacemaker senses the P-wave of the native heart and, after an adjustable pause, stimulates the atrium of the transplanted heart, producing synchronized beats of both hearts, in the same logical sequence as of the intra-aortic balloon which is important in optimizing the cardiac output in the first few 6–8 postoperative days. After discharge from the intensive care unit (ICU) and the removal of epicardial wires of the pacemaker, there was no more electrical synchronization between the two hearts; however, a spontaneous tendency to an equalization of the heartbeats is expected, which could be attributed to the lower adrenergic stimulation provided by an improved cardiac output, due to the implanted piggyback heart. Post-operative course was smooth. Echocardiography of donor heart showed good biventricular function and no change in ejection fraction of native heart and no intra-cardiac thrombus. The electrocardiogram (Fig. 7) showed typical dual heartbeats, chest X-ray (Fig. 8) showed no right lower lobe atelectasis, and a follow-up magnetic resonance imaging (Fig. 9) showed a good configuration of native and donor hearts. At 6-month follow-up, transjugular endomyocardial biopsy was performed which showed no rejection. Due to direct donor to recipient SVC anastomosis, it was easy to enter the right heart.

Fig. 7.

Electrocardiogram of patient with heterotopic heart transplant

Fig. 8.

Chest X-ray of a patient with heterotopic heart transplant

Fig. 9.

Magnetic resonance imaging of heterotopic heart transplant

Documentation of adequate native right ventricular function is important immediately after discontinuation of cardiopulmonary bypass and continuously in the early post-operative period. Much of the management is like management of a patient with a left ventricular assist device with an emphasis on not overloading the RV.

Ideally, some native left ventricular function will allow pulsatile flow through the native aortic valve, but most of the left-sided cardiac output is through the bio-LVA. Left-sided filling pressure is reduced as is the PA pressure by the normally functioning donor heart. PH may diminish or persist over time, just as with LVAD support. Inotropes, vasopressors, vasodilators, antiarrhythmic agents, and volume replacement are used, as they would be in an orthotopic recipient. Close monitoring of central venous pressure, cardiac output, and pulmonary and systemic vascular resistance is necessary for adequate management. Immunosuppression and cardiac biopsy should be done in accordance with institutional protocols. Yearly coronary angiograms of the donor are advised. We found computed tomography (CT)-angio scanning helpful but inadequate for documenting coronary artery vasculopathy.

A heterotopic transplantation in Bio-LVA configuration may be well suited for:

1. Patients with left ventricular failure in the absence of right ventricular failure (examples include ischemic cardiomyopathy, restrictive left ventricular disease, and some cases of idiopathic cardiomyopathy)

2. Patients with high pulmonary arterial pressure and resistance but normal central venous pressure and absence of right ventricular failure

3. Patients that are candidates for long-term LVAD support, but lack financial or psychosocial support, which is rampant in developing countries like ours.

4. Donor heart size is judged to be too small for an orthotopic heart transplant, especially in Indian donor female patients

5. “High risk” donor heart for problems related to the donor or from prolonged ischemic time; this may be due to either suboptimal donor management or greater geographical distances in transportation with a lack of robust travel connections.

Thus, HHT might increase the donor pool allowing more smaller hearts to be transplanted. It might also make transplantation possible in some patients who are currently not selected either because of recipient PH or psycho-social contraindications to LVAD support.

Discussion

HHT has many potential advantages. The initial intention of Barnard and colleagues was that the HHT might give assistance in the cases of severe acute rejection where it may maintain circulation. Indeed, the residual myocardial function of the remaining native heart may be life-saving in the cases of acute failure of the graft. However, the availability of cyclosporine in 1983 resulted in its decreased utility, and OHT became the configuration of choice. Nowadays, major improvements in mechanical circulatory support, including extracorporeal life support, allow us to deal with early acute graft failure as a bridge to recovery or a bridge to decision. However, these measures are not financially feasible in developing countries like India, where the escalating costs of additional devices may not be borne by the relations HHT has been reported to be advantageous for recipients with irreversible elevated pulmonary resistance [9], although one should also consider heart–lung transplantation or implantation of an LVAD, which are not practical in Indian scenario.

HHT may be considered in the cases of a significant donor-recipient size mismatch. HHT also allows the use of marginal donor hearts that may otherwise be wasted.

However, there are several recognized complications of heterotopic graft placement: an early post-operative compression of the right middle and right lower lobes of the lung by the donor’s heart, leading to atelectasis, infection, and impaired ventilation. An aggressive bronchoscopy to clear secretions should be done. Ventricular arrhythmias have been reported in HHT [10]. Reduced exercise capacity has been also observed in HHT recipients compared with patients after orthotopic transplantation, possibly due to the competitive contraction of the two hearts. Indeed, the donor’s left ventricle may generate a high afterload to the failing recipient’s left ventricle. However, counter-pulsation of the two hearts is possible by linking [11, 12] them with cardiac synchronization therapy, which can improve overall hemodynamics.

In patients with ischemic cardiomyopathy, the recurrence of angina in the post-transplantation period can be problematic. Although concomitant coronary artery bypass grafting can be performed.

By leaving the often dilated, diseased native heart in place, thrombo-embolic events may occur at an increased rate. Long-term anticoagulation is then recommended. Another disadvantage of using the heterotopic configuration is the added complexity and prolonged duration of the operation.

In conclusion, the unaffordability issue of left ventricular assist devices in developing countries coupled with a suboptimal donor heart can potentially open a possibility of performing heterotopic heart transplantation. In our experience, the modified technique described offers several advantages and may be considered in suitable conditions.

Funding

Nil

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical compliance/ethics committee approval

Not applicable.

Human and animal rights

Not applicable.

Informed consent

Informed consent was obtained from all the patients and relations.