Combined heart-kidney transplant improves post-transplant survival compared with isolated heart transplant in recipients with reduced glomerular filtration rate: Analysis of 593 combined heart-kidney transplants from the United Network Organ Sharing Database

There has been significant progress in the field of heart transplantation over the last 45 years. The 1-yr survival rates following heart transplantation have improved from 30% in the 1970s to almost 90% in the 2000s. However, there has been little change in long-term outcomes. This is mainly due to chronic rejection, malignancy, and the detrimental side effects of chronic immunosuppression. In addition, over the last decade, new challenges have arisen such as increasingly complicated recipients and antibody-mediated rejection. Most, if not all, of these obstacles to long-term survival could be prevented or ameliorated by the induction of transplant tolerance wherein the recipient's immune system is persuaded not to mount a damaging immune response against donor antigens, thus eliminating the need for chronic immunosuppression. However, the heart, as opposed to other allografts like kidneys, appears to be a tolerance-resistant organ. Understanding why organs like kidneys and livers are prone to tolerance induction, whereas others like hearts and lungs are tolerance-resistant, could aid in our attempts to achieve long-term, immunosuppression-free survival in human heart transplant recipients. It could also advance the field of pig-to-human xenotransplantation, which, if successful, would eliminate the organ shortage problem. Of course, there are alternative futures to the field of heart transplantation that may include the application of total mechanical support, stem cells, or bioengineered whole organs. Which modality will be the first to reach the ultimate goal of achieving unlimited, long-term, circulatory support with minimal risk to longevity or lifestyle is unknown, but significant progress in being made in each of these areas.

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Heart Transplantation: Challenges Facing the Field

Cardiac tissue engineering offers the prospect of a novel treatment for acquired or congenital heart defects. Previously, our studies have shown a significant mass of vascularized cardiac tissue can be generated using a vascularized tissue engineering chamber approach in nude rats. In this present study, syngeneic rats were investigated as an animal model for cardiac tissue engineering using the arteriovenous loop (AVL) chamber in the presence of a functional immune system. Neonatal cardiomyocytes implanted into the AVL chamber survived and assembled into a contractile flap confirming the basic features we previously showed in growing a cardiac construct. There was no significant loss of the assembled cardiac muscle from immune response. The engineered cardiac muscle flaps (ECMFs) formed were transplanted to the neck vessels of the same animal using a microsurgical technique, and all transplanted tissues remained contractile. The cardiac muscle volume of the control and transplant groups was estimated with histomorphometry using desmin and α-sarcomeric actin immunostaining, and there were no significant differences between the two groups. Finally, utilizing a novel model of transplantation, the ECMFs were transplanted to the heart of a recipient syngeneic rat as a vascularized tissue. The cardiac muscle within the transplanted ECMF was shown to survive and remain contractile for the 4-week post-transplantation period, and importantly, the cardiomyocytes retained the elongated, striated appearance of a mature phenotype. This study demonstrated the proof of concept for transplanting tissue-engineered cardiac muscle as a vascularized cardiac construct.

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Transplantation of Engineered Cardiac Muscle Flaps in Syngeneic Rats

Purpose of reviewWhen it comes to tolerance induction, kidney allografts behave differently from heart allografts that behave differently from lung allografts. Here, we examine how and why different organ allografts respond differently to the same tolerance induction protocol.Recent findingsAllograf

Organ-specific differences in achieving tolerance.

Background Combined heart and kidney transplantation (HKTx) is performed in patients with severe heart failure and advanced renal insufficiency. We analyzed the long‐term survival after HKTx, the i...

Combined Heart and Kidney Transplantation: Clinical Experience in 100 Consecutive Patients.

Different surgical techniques, each with its own advantages and disadvantages, have been used to reverse adverse left ventricular remodeling due to postinfarction left ventricular aneurysm. The most appropriate surgical technique depends on the location and size of the aneurysm and the scarred tissue, the patient's preoperative characteristics, and surgeon preference. This review covers the reconstructive surgical techniques for postinfarction left ventricular aneurysm.

Left Ventricular Reconstruction for Postinfarction Left Ventricular Aneurysm: Review of Surgical Techniques

Background The role of solid multiorgan transplantation remains to be determined. We compared our experience with combined heart-kidney transplantation (HKT) and heart transplant alone (HT), and assessed patient survival rates and freedom from allograft rejection in these two patient groups. Methods We reviewed the clinical outcomes of patients undergoing HKT (n = 30) or HT (n = 440) between June 1992 and March 2009. Baseline patient characteristics, perioperative factors, incidence of rejection, and survival were examined. Results There were no significant differences between the two groups for age, gender, etiology of heart disease, functional class, preoperative left ventricular ejection fraction, end-diastolic diameter, cardiac output, or transplant waitlist status. Patients with HKT had a higher serum creatinine level (P .05 for all comparisons). Conclusions HKT offers excellent survival and similar renal function when compared with HT alone. Patients with end-stage cardiac and renal failure can be considered for HKT.

Survival and allograft rejection rates after combined heart and kidney transplantation in comparison with heart transplantation alone

Objective An updated anesthetic and surgical technique in a rat model of heterotopic heart transplantation is described. Materials and Methods A microsurgical technique via a suprarenal approach was performed, and is described in stepwise fashion, and several technical improvements are compared with previous descriptions. Lewis rats were used as donors and recipients (syngeneic model). Results Factors that affected early surgical outcome included type of anesthetic used; surgeon skill, experience in handling blood vessels, and knowledge of small-animal anatomy; gentle manipulation during the operation; and duration of surgery ( 11 months) with a functioning graft was achieved in all 9 surviving animals. Conclusions Survival was substantially improved with administration of isoflurane anesthesia; surgeon microvascular surgical skills and knowledge of small-animal anatomy, and duration of surgery less than 1 hour. These factors collectively contributed to successful early outcomes after heterotopic heart transplantation in rats, with 90% freedom from morbidity and mortality, and resulted in long-term survival (>11 months) with a functioning graft in a syngeneic model. This heterotopic model in rats is suitable for short- and long-term studies of heart transplantation.

R. Vespignani

Papers

Left Ventricular Reconstruction for Postinfarction Left Ventricular Aneurysm: Review of Surgical Techniques

Survival and allograft rejection rates after combined heart and kidney transplantation in comparison with heart transplantation alone

Heterotopic heart transplantation in rats: improved anesthetic and surgical technique