**2. Heterotopic heart transplantation history and current use**

Between 1974 and 1982, Barnard performed 40 heterotopic heart transplants [3]. The first year, second year and five-year survival for heterotopic heart transplantation was 61, 50 and 36%. These survival rates compared well to the orthotopic heart transplant survival from Stanford of 63% at 1 year, 55% at 2 years and 39% at 5 years. The Copeland group from the University of Arizona, during the same time demonstrated 72% 1 and 2-year survival with orthotopic heart transplantation [3].

Bleasdale et al. [4] published the use of 42 consecutive, adult heterotopic heart transplantations in a single center from 1993 to 1999 and compared the outcomes to 303 consecutive orthotopic heart transplants (OHT) during the same time period. Thirty-three (33; 79%) of the heterotopic heart transplant recipients were men; and 26 recipients had ischemic heart disease (62%). In the comparative group of orthotopic heart transplant recipients, 38% had ischemic heart disease and 43% were dilated cardiomyopathy patients. The reasons for using a HHT in these recipients was urgency and need for transplant (36%), pulmonary hypertension of the recipient (55%), donor-recipient size mismatch [donor body surface area (BSA) < 75% of the recipient BSA] (62%); and the native heart was able to be repaired (19%). The patients were followed from 1 to 5 years. The heterotopic heart transplant recipients were older, more often had a donor-recipient size mismatch, and had a higher ischemic time. The ischemic time the HHT group was on average 191 minutes (165–241 minutes) vs. 165 minutes (120–202 minutes) in the orthotopic heart transplant group; which was statistically significant (p = 0.001). The OHT group had a higher 30-day survival of 87 vs. 76% HHT group. The 1-year survival was higher for the OHT group 74 vs. 59%. The three factors that predicted graft failure were: (1) donor recipient size mismatch, (2) donor age, and, (3) the female donor. The donors in the HHT group more often had a size mismatch, were older, and female. Of note, within the HHT group, those who were size matched had a markedly improved 1-year survival 81 vs. 45% (p = 0.02).

Overall, in the Bleasdale et al. [4] study HHT recipients had decreased 1-year survival. The decreased survival was predominantly in patients who had received a donor-recipient mismatched heart. The survival for size matched was comparable to those patients who received an orthotopic heart transplant. In addition, patients with severe and/or fixed pulmonary hypertension benefitted from the HHT; when, these recipients would not have been able to have an OHT.

Newcomb et al. [5] described the use of the heterotopic heart transplant to expand the donor pool in Australia. During a 6-year period from 1997 to 2003, the group performed 20 heterotopic heart transplants and 131 orthotopic heart transplants. The heterotopic heart transplant was used for: (1) fixed pulmonary hypertension (with a pulmonary vascular resistance greater than or equal to 3 Wood units, and a transpulmonary gradient (TPG) greater than or equal to 13 mmHg), (2) donor to recipient weight ratio of less than 0.8, (3) anticipated ischemic time greater than 6 hours, and (4) a marginal donor heart. Marginal donors were described as those that required high inotropic support, had a history of a cardiac arrest or arrhythmia, wall motion abnormalities on the echocardiogram, and/or ischemic changes on the electrocardiogram (EKG). Fourteen of the donor hearts were marginal and had been declined by other centers. Most of the HHT recipients had more than one indication for an HHT.

era when death within 24 hours of the onset of rejection was common. In addition, to the benefits from treatment of acute rejection, the heterotopic heart transplantation technique

Between 1974 and 1982, Barnard performed 40 heterotopic heart transplants [3]. The first year, second year and five-year survival for heterotopic heart transplantation was 61, 50 and 36%. These survival rates compared well to the orthotopic heart transplant survival from Stanford of 63% at 1 year, 55% at 2 years and 39% at 5 years. The Copeland group from the University of Arizona, during the same time demonstrated 72% 1 and 2-year survival with orthotopic

Bleasdale et al. [4] published the use of 42 consecutive, adult heterotopic heart transplantations in a single center from 1993 to 1999 and compared the outcomes to 303 consecutive orthotopic heart transplants (OHT) during the same time period. Thirty-three (33; 79%) of the heterotopic heart transplant recipients were men; and 26 recipients had ischemic heart disease (62%). In the comparative group of orthotopic heart transplant recipients, 38% had ischemic heart disease and 43% were dilated cardiomyopathy patients. The reasons for using a HHT in these recipients was urgency and need for transplant (36%), pulmonary hypertension of the recipient (55%), donor-recipient size mismatch [donor body surface area (BSA) < 75% of the recipient BSA] (62%); and the native heart was able to be repaired (19%). The patients were followed from 1 to 5 years. The heterotopic heart transplant recipients were older, more often had a donor-recipient size mismatch, and had a higher ischemic time. The ischemic time the HHT group was on average 191 minutes (165–241 minutes) vs. 165 minutes (120–202 minutes) in the orthotopic heart transplant group; which was statistically significant (p = 0.001). The OHT group had a higher 30-day survival of 87 vs. 76% HHT group. The 1-year survival was higher for the OHT group 74 vs. 59%. The three factors that predicted graft failure were: (1) donor recipient size mismatch, (2) donor age, and, (3) the female donor. The donors in the HHT group more often had a size mismatch, were older, and female. Of note, within the HHT group, those who were size matched had a markedly improved 1-year survival 81 vs. 45% (p = 0.02).

Overall, in the Bleasdale et al. [4] study HHT recipients had decreased 1-year survival. The decreased survival was predominantly in patients who had received a donor-recipient mismatched heart. The survival for size matched was comparable to those patients who received an orthotopic heart transplant. In addition, patients with severe and/or fixed pulmonary hypertension benefitted from the HHT; when, these recipients would not have been able to

Newcomb et al. [5] described the use of the heterotopic heart transplant to expand the donor pool in Australia. During a 6-year period from 1997 to 2003, the group performed 20 heterotopic heart transplants and 131 orthotopic heart transplants. The heterotopic heart transplant was used for: (1) fixed pulmonary hypertension (with a pulmonary vascular resistance greater than or equal to 3 Wood units, and a transpulmonary gradient (TPG) greater than or equal

allows selected recipients with pulmonary hypertension to receive a transplant.

**2. Heterotopic heart transplantation history and current use**

heart transplantation [3].

124 Heart Transplantation

have an OHT.

In the study of Newcomb et al. [5], the heterotopic heart transplant recipients were significantly older (mean 58 years vs. 47.1 years for OHT); the donors were also significantly older (mean age 45.2 years vs. 34.5 years for OHT). The ischemic time was also much higher for the HHT recipients; 366 minutes vs. 258 minutes for OHT. The intensive care unit and the total length of the hospital stay was higher for HHT recipients; though, not statistically significant. The study demonstrated lower survival for heterotopic heart transplant recipients compared to orthotopic heart transplant recipients in the same time period; though, the survival benefit for OHT recipients disappeared when they performed a subgroup analysis for the recipients who had elevated pulmonary artery pressures. The study demonstrates the successful use of the heterotopic heart transplant. The survival in HHT recipients were not as good as in those of OHT recipients because of the HHT technique was more often used in marginal donors and more high-risk recipients. Marginal donor hearts may not have performed as well in OHT recipients. Furthermore, high risk recipients have decreased survival expectations especially with the use of a marginal donor heart.

Boffini et al. [6] described their single center experience with the heterotopic heart transplant; and, found the HHT to be comparable to OHT. HHT was used between in 1985–2003, in 12 patients [(1.7%) of the all the heart transplant performed during that time]. The 1-year and 5-year survival was 92 and 64% respectively. These results demonstrated when the HHT technique is used in the usual recipient risk patient, the outcomes can be effective and acceptable for recipients. The HHT technique was used for body size mismatch in 11 patients and 1 recipients for a marginal donor heart.

In addition to donor-recipient size mismatch, elevated pulmonary vascular resistance (PVR), and, fixed pulmonary hypertension are also indications for HHT. Vassileva et al. [7] reviewed 18 recipients with fixed pulmonary vascular resistance who received a HHT with the donor pulmonary artery anastomosed to the recipient right atrium. The indications were (1) PVR > 6 units/m<sup>2</sup> , (2) transpulmonary gradient (TPG) > 15 mmHg, or, (3) pulmonary artery (PA) systolic pressure > 60 mmHg. All of the recipients had some degree of pulmonary hypertension, and, 8 of the patients had a restrictive cardiomyopathy. Twelve of the patients were New York Heart Association class III or IV; the remaining six were in the hospital with continuous inotropic support, and, one was intubated. The mean aortic cross clamp time was 58 minutes and a mean ischemic time of 122 minutes. The follow-up right heart catheterizations demonstrated a progressive decrease in the pulmonary artery pressures after transplant with a mean systolic pulmonary artery pressure of 29 mmHg, a TPG of 10 mmHg, and, a PVR of 3.7 units/m<sup>2</sup> . The group concluded that the HHT technique was a valuable option for patients with elevated, and/or, fixed pulmonary artery pressures, and, elevated pulmonary vascular resistance.
