Anesthesia for Noncardiac Surgery After Heart Transplant

The Transplanted Heart and the Cardiovascular System

Before transplantation, patients with advanced HF display varying degrees of systolic or diastolic dysfunction (or both). Whereas the former leads to a decrease in ejection fraction and cardiac output, the latter results in higher filling pressures. The reduction in cardiac output results in a reduction of blood, oxygen, and nutrient supply to end organs, which is only compounded by partial venous congestion. After HT cardiac output improves, and end-organ perfusion is largely restored. However, transplantation does not completely restore the patient to a nonpathologic state.

Anatomic Correlates

Despite the advances made in the management of HF, immunosuppression, and postoperative care, the surgical technique remains largely unchanged from the one described in the 1960s. The donor heart is anastomosed to the native circulation primarily in one of two ways. Biatrial anastomosis, which involves suturing of the native atria to the donor atria, was the standard approach originally and is technically simpler because it preserves the connections to the recipient atrium. The risk of sinus node injury is higher with the biatrial technique, as is the chance of hemodynamic problems associated with altered atrial geometry, size, and flow. Of note, with the biatrial technique, dual p-waves may be seen on the electrocardiogram (ECG) because of activation of native atrial tissue and can sometimes mimic atrial flutter. In addition, the sewing cuff can be seen as a ridge in the atria and can be confused for thrombi or endocarditis. Therefore knowledge of the surgical technique can often be beneficial to avoid misdiagnoses. The biatrial technique has been largely replaced by the bicaval technique. The bicaval technique involves anastomoses at the level of the great vessels—the superior and inferior vena cava—and a line of left atrial tissue encircling the pulmonary vessels. This technique has been associated with a reduction in sinus node dysfunction, tricuspid regurgitation, atrial fibrillation, and atrial dilation after transplant. The bicaval technique has also been shown to confer a small but significant survival advantage compared to the biatrial approach ( Box 6.1 ).

Box 6.1

Heart Transplant Bicaval Technique

• Advantages: reduction in sinus node dysfunction, tricuspid regurgitation, atrial fibrillation, and atrial dilation after transplant; also, small significant survival advantage

• Disadvantage: more complex technique

Reinnervation

The normal heart is innervated by sympathetic and parasympathetic fibers of the autonomic nervous system. Whereas sympathetic innervation to the heart is from the cervical ganglia and upper thoracic (T1–T4) sympathetic chain, branches of the vagus nerves contribute the parasympathetic input. The cardiac plexus, which contains the postganglionic sympathetic and preganglionic parasympathetic fibers, is located at the base of the heart. The autonomic nervous system is also the conduit by which a supply of visceral sensory fibers is supplied to the pericardium. During transplantation, postganglionic neural axons innervating the heart are transected. Within days, cardiac stores of norepinephrine are exhausted, and autonomic influence over the heart ceases. After a variable period of 6 to 12 months, partial reinnervation of the transplanted heart has been shown to occur (see later). However, it remains incomplete and variable for many years after transplant. Thus in the early postoperative period, the transplanted heart is only subject to manipulation via humoral catecholamines.

As a consequence of efferent denervation, sympathetic stimulation and chronotropic responses to exercise, stress, and hypovolemia are not seen. This also includes blunting of baroreceptor responses (e.g., responses to laryngoscopy and intubation). Afferent denervation, on the other hand, impedes vasoregulatory responses by means of the renin-angiotensin axis, and the perception of pain secondary to ischemia (angina) is lost. Transplanted hearts demonstrate a high resting heart rate (90–100 beats/min) without much variability ( Table 6.1 ). Eventually, nerve sprouting occurs, and reinnervation proceeds along the left ventricle into the sinoatrial node and then to the coronaries, in that chronological order. Parasympathetic reinnervation tends to lag behind sympathetic reinnervation; in theory, there could be a state where the transplanted heart could have “unbalanced” autonomic input with sympathetic predominance. With the passage of time, the resting heart rate slows down, and rate variability reappears (see Table 6.1 ). The clinical implications of this pattern of cessation and gradual restoration of neural input to the transplanted heart are many and are discussed later in the text ( Box 6.2 ).

Box 6.2

The Transplanted Heart and the Autonomic Nervous System

• Postganglionic neural axons innervating the heart are transected during transplant.

• The newly transplanted heart is only subject to manipulation via humoral catecholamines.

• Reinnervation can occur within 6–12 months posttransplant.

Filling Patterns

The filling pressures of an immediate posttransplant heart are significantly elevated. The elevated filling pressures are likely related to ischemic myocardial injury, rejection, volume overload, or a preexisting pulmonary vascular abnormality. Over time, this transitions to a mild rightward shift on the Frank-Starling curve during rest. However, circulating brain natriuretic peptide (BNP) levels are elevated even with normal hemodynamic parameters, suggesting some atrial stretch. The filling pressures, which are significantly elevated immediately after transplant, typically never fully return to normal, suggesting a mild restrictive physiology. Donor recipient size mismatch, increased afterload in the form of hypertension, and rejection are all proposed mechanisms. Often the end result is an abrupt rise in left ventricular filling pressures in response to fluid challenges, which makes these patients prone to pulmonary and systemic venous congestion. Mild rejection does not affect function significantly, although both systolic and diastolic function are adversely affected when rejection reaches severe proportions. Overall, this calls for caution with fluid challenges in the face of hypotension and vigilance toward volume status under anesthesia.

Exercise Response

Compared with their own pretransplant status, the exercise capacity of HT recipients shows improvement, but it is still reduced compared with that of healthy control participants. In healthy persons, withdrawal of vagal tone at the onset of exercise results in an initial increase in heart rate, which then results in an increased cardiac output. In HT recipients, the heart rate increase is slower, and the maximal heart rate achieved is lower (see Table 6.1 ). During exercise, an initial increase in cardiac output results from an increase in stroke volume and preload, but later during exercise, improved contractility and heart rate augmentation from circulating catecholamines take over. This neurohumoral response is exaggerated in HT recipients and may represent compensation for denervation. In addition, elevated pulmonary resistance and impairment in skeletal muscle function contribute to the reduction in maximal exercise capacity in HT recipients. HF in the pretransplant period, chronic oxygen debt, and steroid use generally lead to muscle fiber atrophy in this patient population. However, exercise training can result in a restoration of muscle mass, strength, and endurance after transplant. In a variety of clinical situations, exercise tolerance has been successfully used as a predictor of a patient's ability to undergo the stress of anesthesia and surgery. It is no different for a transplant recipient presenting for noncardiac surgery.

Receptors and Drug Response

An increase in the number and the sensitivity of β-adrenergic receptors is present posttransplant. As a consequence, the transplanted heart demonstrates augmented responses to directly acting β-adrenergic antagonists. Resting coronary blood flow increases because of an absence of sympathetic tone. However, serotonin hypersensitivity (likely related to endothelial damage) causes decreased flow reserve in the transplanted heart. Abnormalities of response to endothelium-derived vasodilators such as substance P and acetylcholine have been noted, although the response to non–endothelium-derived vasodilators such as adenosine and dipyridamole is preserved. As previously noted, coronary demand-supply mismatch does not result in ischemic pain or angina in transplanted patients, so surveillance is required to identify coronary vasculopathy, which results in ischemia, even in the absence of symptoms.

Complications After Transplantation

Although rejection, infection, and cancer all come to mind as common complications posttransplant, the total list of complications is fairly long. In fact, surviving recipients have hypertension (97%), severe renal insufficiency (14%), hyperlipidemia (93%), diabetes (39%), and angiographic coronary allograph vasculopathy (CAV) (52%) by 10 years postcardiac transplantation. Many of these have a profound impact on outcomes in the perioperative period and the delivery of an anesthetic.