Page 1585 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

1104 PART 10: The Surgical Patient

Arrhythmia: Heart transplant is frequently complicated by arrhythmias cellular and humoral immune response in addition to atherosclerosis.
secondary to structural abnormalities at the sinoatrial node, parasympa- Effective prevention can be achieved with lipid-lowering therapy with
thetic and sympathetic denervation posttransplant, and heterogeneous statins and possibly mTOR inhibitors and diltiazem. Statins have been
partial sympathetic reinnervation. The mechanism for arrhythmia is shown to have a favorable impact on outcome through preventing and
secondary to complete cardiac denervation following biatrial or bicaval minimizing the severity of CAV. Some literature comparing mTOR
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anastomosis, potential ischemia of the sinoatrial (SA) node, and enlarge- inhibitors to antiproliferative agents suggest a reduction in CAV with
ment of the atria. Loss of parasympathetic innervation leads to the mTOR inhibitors 139,140 ; however, given the reports of impaired wound
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absence of the suppressive effect on the SA node. Conversely, loss of healing, anemia, thrombocytopenia, hyperlipidemia, and renal dysfunc-
sympathetic innervation results in a blunting of stress-induced elevation tion associated with the mTOR inhibitors, their early use posttransplant
in heart rate. While the heart does undergo partial sympathetic rein- may be problematic until further research is available. These drugs
nervation, it is often heterogeneous. Interestingly, bicaval anastomosis are currently not approved for this indication posttransplant. There
appears to be associated with less incidence of arrhythmias perhaps currently exists some debate surrounding the usefulness of diltiazem
due to the preservation of the normal atrial anatomy and function, after transplant in the prevention of CAV. For localized disease, per-
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thus minimizing trauma at the level of the sinoatrial node. Myocardial cutaneous coronary intervention should be performed if amenable to
scarring, altered cardiac anatomy, heterogeneous innervation, transplant interventions in those who have clinically significant discrete lesions.
coronary artery disease, and rejection can all manifest as arrhythmias. Retransplantation would be an alternative option in those with diffuse
Due to the loss of parasympathetic innervations, these patients have triple vessel disease, decreased ventricular function and symptoms if
minimal response to atropine or digoxin. no contraindications exist. Screening PRAs are performed on all heart
Atrial fibrillation and atrial flutter occur in 20% of patients posttrans- transplant candidates prior to transplantation in an attempt to identify
plant. It has been associated with a higher mortality posttransplant their risk of rejection and facilitate steps to minimize its occurrence.
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primarily in the group with late atrial fib/flutter (>30 days). Risk factors High PRA could significantly decrease the chance of a compatible donor
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for the development of the arrhythmia include older donor and recipient or increase the risk of unavoidable mismatches. Given the absence of
age. Persistent tachyarrhythmias should raise suspicion of acute rejec- international standards, each transplant center has a defined threshold
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tion. Antiarrhythmic management posttransplant needs to take into con- of antibody levels above which they deem an unacceptable risk of rejec-
sideration drug interactions with immunosuppression and the variability tion. A PRA level >10% is often deemed a significant allosensitization
in response given the denervation of the posttransplanted heart. and is often the threshold to consider instituting desensitized therapies.
Rejection: Though immunosuppressive regimens have minimized epi- Desensitization therapies include a combination of IV immunoglobu-
sodes of acute rejection, this complication still is responsible for 7% of lin, plasmapheresis, rituximab, and in some cases splenectomy. The
deaths within the first 30 days of the procedure. Most episodes of acute strategies employed are center specific and determined based on
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rejection are asymptomatic and are diagnosed on routine endomyocardial the patients’ individual risk and results of the cross match. 142
biopsy. When symptoms are present, they are often nonspecific and may Reperfusion Injury: Prolonged ischemic time resulting in reperfusion
include fever, malaise, hypotension, congestive heart failure, or reduced injury can range from a transient time period to 12 to 24 hours post-
exercise tolerance and fatigue. Consequently, surveillance for rejection transplant. Cold ischemic times greater than 5 hours are associated with
through the use of endomyocardial biopsy has become standard practice. reperfusion injury, greater risk of allograft dysfunction, and death. This
When performed by an experienced operator, this procedure is associated often manifests as shock or LV systolic dysfunction posttransplant. The
with a morbidity of less than 1% and a procedure-related mortality of causes of post-operative left ventricular systolic failure are provided in
less than 0.2%. 136,137 The most concerning complication of this procedure Table 115-16.
is cardiac perforation with acute pericardial tamponade or injury to the
tricuspid valve. Typically biopsies (with multiple sampling) are performed ■ INFECTIOUS COMPLICATIONS
every week for the first 4 weeks, every 2 weeks for the next 6 weeks, With significant advancements in transplant technique, immunosup-
monthly for the next 3 to 4 months, and then every 3 months until the end pression, and graft survival, infection remains one of the most significant
of the first year. After that time, it is reduced to three to four times per year complications posttransplantation. Prior to the transplant procedure, it
in the second year and one to two times per year after that. 115 is important to know whether or not the transplant recipient has been
Once rejection is diagnosed histologically, imaging to assess cardiac
function should be obtained (using two-dimensional echocardiography exposed to common infections that can cause serious morbidity in the
postoperative period when immunosuppressive therapies are instituted.
or multiple-gated acquisition nuclear scanning). Mild rejection in the Patients are routinely screened for antibodies to CMV, Epstein-Barr
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absence of cardiac dysfunction is usually treated conservatively with an virus (EBV), herpes viruses, HBV, HCV, human immunodeficiency virus
increase in the dose of immunosuppressive agents. If moderate rejec- (HIV), Toxoplasma, and tuberculosis exposure via skin testing. In an
tion or left ventricular dysfunction is present, the episode of rejection is immunosuppressed recipient who has been previously exposed, many of
treated using high-dose pulsed steroids with or without cytolytic therapy these infections can be reactivated. Alternatively, a naïve recipient may
(antithymocyte globulin or OKT3). Repeat endomyocardial biopsy be transplanted with an organ from a seropositive donor. The most pro-
should always be performed to assess the response to therapy. found period of immunosuppression often occurs approximately 4 weeks
Chronic rejection in the cardiac allograft typically manifests as posttransplantation when immunosuppressive agents maximally inhibit
aggressive and premature coronary artery disease. This complication the T-cell immunity defense. Given the immunosuppressed status of the
usually develops months to years after the procedure. In contrast to the
more familiar causes of coronary artery disease, transplant-associated
coronary artery disease is generally more diffuse, involving all the vessels
of the heart including the arteries, veins, and great vessels. Because TABLE 115-16 An Approach to Left Ventricular Systolic Dysfunction Posttransplant
the allograft is denervated, classic angina only develops in a minority Late LV dysfunction (weeks-years
of patients, and coronary artery disease more typically presents with Early LV dysfunction (days posttransplant) posttransplant)
“angina-equivalent” symptoms such as dyspnea. Accelerated CAD has
a significant impact on mortality posttransplant. Over 50% cardiac Hyperacute rejection Acute rejection
transplants develop transplant CAD by 5 years. Transplant CAD, also Reperfusion injury Acute myocarditis (T. Gondii, CMV)
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known as cardiac allograft vasculopathy (CAV), is the leading cause of Suboptimal donor heart Nonspecific allograft dysfunction
death in the first posttransplant year. Accelerated plaque formation may
occur because of sustained or recurrent inflammatory response due to Allograft coronary artery disease

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