**6. Risk factors and contraindications**

and quantify the amount of antibodies against surface HLA antigens using a flow cytometry immunofluorescence technique. This method (Luminex) is much more sensitive than the PRA and allows a better assessment of the risk of positive cross-reactivity at the time of HTx and

Patients can be sensitized after pregnancies, blood transfusions, after previous transplantation or after the implant of a ventricular assist device, although sometimes there is no obvious sensitizer event, and it is thought to be due to cross-reactivity between bacterial or viral epitopes and HLAs. In case that the recipient has a ventricular assist device, it is recommended to repeat the PRA and flow cytometry every 2–3 months. If blood transfusions are required, the PRA and flow cytometry should be repeated 2 weeks after the transfusion and each month

The presence of anti-HLA antibodies with high levels of median fluorescent intensity or MFI (units used to quantify antibodies), usually over 3000–5000, depending on the immunology laboratory, is considered potentially cytotoxic. By this technique it is also possible to obtain a calculated PRA (cPRA), which gives the percentage of unacceptable HLAs in the donor population. For example, if the cPRA is 80%, it means that only 20% of all possible donors in this specific population will be compatible with the receptor. Although the cPRA cut-points are not clearly established, some authors consider an absolute contraindication if cPRA is above 50–70%, and thus recommend a desensitization therapy before HTx [47]. In these cases it is also necessary to perform a virtual cross-match at the time of HTx, consisting of the evaluation of anti-HLA receptor antibodies titters relative to the donor HLA. If the virtual cross-match is positive, the risk of hyperacute rejection is very high and the donor organ must not be accepted.

A complete serologic status of the potential recipient should always be obtained before HTx, especially considering previous exposure to cytomegalovirus and Mycobacterium tuberculo-

The human immunodeficiency virus infection with undetectable viral load is not a contraindication to HTx at present, although each case must be assessed individually and retroviral

Patients with chronic hepatitis B infection (defined by the presence of hepatitis B surface antigen) have equal survival rates compared to the rest of the cohort, unless there is significant liver disease. In this setting, liver cirrhosis should be ruled out with biopsy if necessary, and antivirals should be given in order to lower viral load, since there is a risk of reactivation of the disease with immunosuppression after HTx. Similarly, when hepatitis C virus serology is positive, the quantitative viral load and degree of liver disease must be determined. If circulating HCV is detected, the disease is active and antiviral treatment must be prescribed to eliminate the virus. An altered hepatic function, which is not justified by HF, or a liver biopsy

treatment should be adapted to avoid interference with calcineurin inhibitors [48].

with evidence of cirrhosis, should be considered an absolute contraindication [30].

eventual humoral rejection.

22 Heart Transplantation

during 6 months [29].

**5. Infectious evaluation and vaccination**

sis, as it is crucial when defining infectious prophylaxis after HTx.

Absolute contraindications for HTx are progressively diminishing because of the improved treatment strategies both for comorbidities and immunosuppressive therapies after HTx, so nowadays it is preferable to talk about risk factors that increase post-HTx morbidity and mortality than contraindications. According to the latest recommendations from the ISHLT [19] the most important HTx risk factors are classified in **Table 5**. Nonetheless, it is important to especially consider the following:


#### **Absolute contraindications**

• Systemic disease with life expectancy <2 years:

· Active neoplasm (if preexisting, evaluation with an oncology specialist is necessary to stratify the risk of recurrence and establish a time to wait after remission)


#### **Relative contraindications**


[47]. This shows the importance of defining homogeneous criteria to define each stage of classification for HTx waiting list, especially in the setting of emergency. A new more precise

• Continuous infusion of a single high-dose intravenous inotrope or multiple intravenous inotropes, and

• Mechanical circulatory support with significant device-related complications (thromboembolism,

BiVAD: biventricular assist device; ECMO: extracorporeal membrane oxygenation; IABP: intra-aortic balloon pump;

LVAD: left ventricular assist device; RVAD: right ventricular assist device; TAH: total artificial heart.

with continuous hemodynamic monitoring of left ventricular filling pressures

device infection, mechanical failure, or life threatening ventricular arrhythmias)

Maximum time in urgency Grade 0 will be 7 days, once this time has passed the patient will be in Urgency Grade 1.

e.g., Levitronix Centrimag.

Heart Transplant: Current Indications and Patient Selection

http://dx.doi.org/10.5772/intechopen.75507

25

classification for the U.S. is expected to be published in 2018.

**Urgency Grade 0: national (**priority over the rest of grades**)**

.

. • Patients with dysfunctional LTVADd secondary to mechanical dysfunction or thromboembolism.

STVAD: short-term ventricular assist device; LTVAD: long-term ventricular assist device.<sup>a</sup>

**Table 6.** Priority criteria for heart transplant donors in Spain (Adapted from barge et al. [53]).

**Urgency Grade 1: regional (**priority over elective patients in reference zone**)**

• Patients with extracorporeal membrane oxygenation (ECMO) or partial support STVAD for at least 48 hours if

. • Patients with dysfunctional LTVAD secondary to driveline infection, gastrointestinal bleeding or right heart

• Patients with STVAD of complete support<sup>a</sup>

failure.

e.g., BerlinHeart Excor.

**Criteria**

• IABP

• Inpatient TAH • Mechanical ventilation

• Outpatient TAH

Status 2 • Candidates not meeting 1A or 1B criteria Status 7 • Temporarily inactive, most often due to infection

• LVAD, RVAD, or BiVAD for 30 days

Status 1B • Uncomplicated LVAD, RVAD, BiVAD after 30 days have been used.

**Table 7.** Status codes for heart transplantation in U.S. (Source Kittleson et al. [47]).

• Continuous infusion of intravenous inotropes

Status 1A • ECMO

**Elective**

b

c

e

**Status code**

there is no evidence of multi-organ failureb,c

• Patients with a normally functioning external LTVAD<sup>e</sup>

• Patients not included in Grade 0 or Grade 1 categories.

<sup>d</sup>e.g., BerlinHeart Excor, Hearmate II, Heartmate 3, Heartware HVAD.

e.g., Impella CP, Impella 5.0, Tandem Heart.


FEV1 : forced expiratory volume in 1 s; VAD: ventricular assist device; HIV: human immunodeficiency virus; BMI: body mass index.

**Table 5.** Contraindications for heart transplant (Source Sanchez-Enrique et al. [51]).
