A 34 year old male without a past medical history was diagnosed with cardiogenic shock secondary to coxsackie myocarditis. After stabilization and a thorough workup he was taken for heart transplantation, which he tolerated well. His ICU course was uneventful for the first 3 days, but now he has new onset atrial fibrillation with rapid ventricular response (rate of 130-160 bpm). Amiodarone was prescribed but has thus far had no effect. The patient was then loaded with digoxin, which did not result in any rate control. After some time, the patient’s rhythm changed to a regular, narrow complex tachycardia at a rate of 150 bpm without any notable P-waves, though was otherwise hemodynamically stable and asymptomatic. The on-call provider decided that a trial of adenosine might help clarify a diagnosis of SVT vs A-flutter, and possibly result in an effective cure. After 6 mg of adenosine was administered, the patient’s tachydysrhythmia changed to isolated p-waves without any corresponding ventricular complexes. After 15 seconds the patient appeared grey and lost consciousness, and after 20 seconds of nonconducted p-waves CPR was initiated. 2 minutes later ROSC was achieved, and the patient regained consciousness. He is again in atrial fibrillation, though the rate now ranges from 90-110 bpm.
One of several nuances surrounding postoperative care of the heart transplant is that during implantation of the graft, the innervation of the heart is partially severed. Specifically, the parasympathetic vagal neurons and the intrinsic postganglionic sympathetic nerve fibers traveling from the stellate ganglia to the myocardium are interrupted.
This iatrogenic denervation leads to several physiologic effects that are germane to the intensivist.
- The loss of afferent nerve supply leads to inability of these patients to experience angina. Although almost all transplants have preoperative angiography assessing for baseline coronary disease, in the postoperative period ischemic coronary complications may not manifest with typical chest pain.
- The loss of efferent nerve supply allows a higher resting heart rate compared to non-transplanted patients. The heart rate response to exercise and recovery are both blunted. The heart rate will rise and then recover more slowly.
- Loss of baroreflex has several effects, with the relative lack of tachycardia with hypotension or hypovolemia. Similarly, orthostasis becomes more likely. If a reentrant tachycardia is present, it will not be disrupted by vagal maneuvers.
The denervation also affects the pharmacokinetics of chronotropic medications. In short, indirect autonomic drugs will not work. This includes: digoxin, anticholinesterases, anticholinergics, and ephedrine. Direct sympathomimetics will work effectively, including isoproterenol, norepinephrine, epinephrine, and dopamine.
Transplanted hearts are super sensitive to adenosine, with greater magnitude and duration of sinus pauses when normal doses are applied. Instead of the traditional 6 mg, use of 1.5-3 mg initially is prudent.
This cardiac denervation may not be permanent. Reinnervation following transplant may occur in some but not all recipients and is regionally heterogeneous. It is also time dependent, occurring late after transplant. Sympathetic reinnervation occurs at least 5 to 6 months post transplant, and parasympathetic reinnervation seems to occur over 1 to 3 years.
- Cardiac transplant leads to interruption of the nerve supply to the heart
- These patients cannot feel angina
- They will not have an appropriate heart rate response to hypotension or hypovolemia
- Cardiac medications will have atypical effects, with vagolytics being ineffective and adenosine having exaggerated effects.
- Awad, M., Czer, L. S., Hou, M., Golshani, S. S., Goltche, M., De Robertis, M., … & Kobashigawa, J. A. (2016). Early denervation and later reinnervation of the heart following cardiac transplantation: a review. Journal of the American Heart Association, 5(11), e004070.
- Hunt SA. Current status of cardiac transplantation. JAMA. 1998;280:1692–1698.
- Bengel, F. M., Ueberfuhr, P., Schiepel, N., Nekolla, S. G., Reichart, B., & Schwaiger, M. (2001). Myocardial efficiency and sympathetic reinnervation after orthotopic heart transplantation: a noninvasive study with positron emission tomography. Circulation, 103(14), 1881-1886.\
- Fuentes, F. B., Martínez-Dolz, L., Bonet, L. A., Sánchez-Lázaro, I., Manchón, J. N., Sánchez-Gómez, J. M., … & Sanz, A. S. (2010, October). Normalization of the heart rate response to exercise 6 months after cardiac transplantation. In Transplantation proceedings (Vol. 42, No. 8, pp. 3186-3188). Elsevier.
- Mohanty PK, Thames MD, Arrowood JA, Sowers JR, McNamara C, Szentpetery S. Impairment of cardiopulmonary baroreflex after cardiac transplantation in humans. Circulation. 1987;75:914–921
- Ramakrishna, H., Jaroszewski, D. E., & Arabia, F. A. (2009). Adult cardiac transplantation: a review of perioperative management Part-I. Annals of cardiac anaesthesia, 12(1), 71.
- Ellenbogen, K. A., Thames, M. D., DiMarco, J. P., Sheehan, H., & Lerman, B. B. (1990). Electrophysiological effects of adenosine in the transplanted human heart. Evidence of supersensitivity. Circulation, 81(3), 821-828.
- Bengel FM, Ueberfuhr P, Schiepel N, Nekolla SG, Reichart B, Schwaiger M. Effect of sympathetic reinnervation on cardiac performance after heart transplantation. N Engl J Med. 2001;345:731–738
- Doering LV, Dracup K, Moser DK, Czer LS, Peter CT. Evidence of time‐dependent autonomic reinnervation after heart transplantation. Nurs Res. 1999;48:308–316.