**5. Preventive strategies after heart transplantation**

The immunosuppressive regimen varies mainly according to the postoperative period and the diagnosis of type of rejection (**Table 3**). The rejection can be classified according to **Table 4** and graded according to pathologic findings.

The most common classification of immunosuppressive regimen is induction, maintenance, and treatment of rejection.

Endomyocardial biopsy remains the gold standard for the diagnosis of rejection. However, post-transplant rejection surveillance using endomyocardial biopsies has been decreasing over time due to the low number of positive biopsies in the era of calcineurin-inhibitor and mycophenolate-base immunosuppressive regimens.

So the emphasis is the use of noninvasive methods for surveillance of rejection, which has been increased. **Table 5** shows the main noninvasive methods for surveillance of rejection.

The immunosuppressive regimens are used to prevent rejection; however, it is difficult to balance between rejections and avoid the side effects of the drugs as well as infection and malignancy.

3. Treatment of rejection

#### **Table 3.**

*Types of immunosuppressive regimens according to the posttransplant period.*

<sup>1.</sup> Induction therapy (early postoperative period)

<sup>2.</sup> Maintenance regimen (prevent rejection)

Hyperacute rejection (humoral)

Acute rejection (cellular or humoral)

Chronic rejection (CAV coronary allograft vasculopathy)

Mixed rejection (cellular and humoral)

**Table 4.**

*Types of rejection.*


#### **Table 5.**

*Noninvasive rejection monitoring.*

Oyer et al. reported in 1983 the use of cyclosporine, as immunosuppressive drug for heart transplantation with improvement in survival. Since then, many regimens have been used to prevent rejection as well as renal insufficiency and posttransplant lymph proliferative diseases.

#### **5.1 Induction therapy**

The immune reactivity and the risk of rejection are high in the early postoperative period so the immunosuppressive regimens have the highest intensity after the procedure. This is one of the reasons that many centers use induction therapy and maintenance drugs with high target blood levels. Induction therapy is performed using antilymphocyte antibodies for specific epitopes on the surface of lymphocytes. The induction also allows delayed initiation of nephrotoxic drugs and weaning of glucocorticoid regimens.

The drugs that have been use for induction are interleukin-2 receptor antagonists and antilymphocyte antibodies (polyclonal antithymocyte antibodies and monoclonal antilymphocyte antibodies include alemtuzumab).

Interleukin-2 receptor antagonists are a monoclonal antibody that binds to the IL-2 receptor of T lymphocytes, blocking binding of IL-2 to the receptor complex so it inhibits IL-2-mediated T lymphocyte proliferation.

*Strategies for Prevention and Management of Heart Transplant Rejection DOI: http://dx.doi.org/10.5772/intechopen.114145*

Polyclonal antilymphocyte antibodies act directly against human T-cell antigens. This causes a depletion of T lymphocytes.

According to the recent ISHLT update guidelines, induction with polyclonal antibody may be beneficial in patients with a high risk of renal dysfunction when used with intent to delay or avoid the use of a CNI (Class IIa, Level of Evidence B) [2].

In pediatric population, the use of IL-2 antagonist or polyclonal antibody induction is beneficial over corticosteroids (CS) only induction and is also recommended when CS-sparing or avoiding therapies are applied (Class II, Level of Evidence B) [2].
