We present herein the case of a heart-transplanted patient with short-lived recurrent episodes of generalized weakness. The initial cardiac follow-up consisted of coronary angiograms, Holter monitoring, and cardiac ultrasounds; only high-burden atrial fibrillation was observed. Finally, the realized EEG identified central hypoxia with a high-degree AV block as the etiology. We decided to implant a single-chamber ventricular pacemaker, and no further episodes were observed in follow-up.
As mentioned above, late-onset AV blocks in patients with orthotopic heart transplantation are rare, and their pathophysiology is not well understood. The diagnosis is often difficult because of its primarily intermittent presentation [8]. Studies have shown that the incidence of AV blocks requiring implantation of a pacemaker at any time is 7.5%, with 3.3% occurring in the first 3 months after transplantation, while only 2.1% are late-onset high-degree AV blocks [2, 8].
Cardiac rejection has also been well demonstrated as a cause of AV blocks, especially in the acute phase (< 3 months) post transplant due to the involvement of the conduction system. To our knowledge, infiltration of the conducting system has never been documented in chronic rejection (> 3 months) [9,10,11].
The most common cause of later death after heart transplantation is graft coronary artery disease with chronic coronary insufficiency with repercussions on the conduction system, which was not the case in our patient with healthy coronaries [9, 10].
The cause of late-onset AV blocks is not yet known. Studies do not point to any correlation with the operation time, the donor’s age, or the age of the transplanted heart [8]. Due to the age of the transplanted heart, a fibrotic process is most probably the primary origin.
Diagnostic work-up was not straightforward in our case. Initially, we suspected low blood flow caused by decreased cardiac output due to the paroxysmal atrial fibrillation bradycardia. We, therefore, decided on cardiac Holter monitoring. Indeed, an arrhythmia caused the recurrent short-lived episode of generalized weakness.
In literature, only two similar high-degree AV blocks have been diagnosed during EEG, a third-degree and a second-degree type Mobitz II. In those cases, the profound cerebral hypoxia provoked a convulsive seizure [12].
Typical central nervous system complications after solid-organ transplantation include immunosuppressor-induced neurotoxicity, central nervous system infections, cerebrovascular disease, and different types of epileptic seizures, which are usually tonic–clonic with focal onset or primarily generalized [13, 14]. The incidence of epileptic seizures depends on the transplanted organ and reaches between 2% and 20% after orthotopic heart transplantation [14]. Mostly, they appear in the early period after transplantation and are due to cerebral ischemia secondary to perioperative hemodynamic instability or due to metabolic disorders [14, 15]. Patients with end-stage heart failure before transplantation may have chronically decreased brain perfusion, making them particularly vulnerable to encephalopathy and, consequently, seizures [14]. However, most epileptic seizures are provoked by the immunosuppressive treatment, especially calcineurin inhibitor treatment such as cyclosporin or tacrolimus. Above all, abrupt increase in the dosing of immunosuppressive medication or abnormally high blood levels favor seizure provocation. Other immunosuppressive treatments including antiproliferative treatments such as mycophenolate mofetil or azathioprine or corticosteroids are much less likely to provoke epileptic seizures [13]. Calcineurin-inhibitor-triggered epileptic seizures may be explained by the inhibition of the gamma-aminobutyric acid system leading to increased and potentially synchronized neuronal transmission and hence to an epileptic seizure [14].
The diagnosis of seizures in transplant patients is no different from that in other patients suffering from epileptic fits, and this applies also largely to the treatment goals, given the absolute necessity for long-term immunosuppression. However, special attention must be paid to drug–drug interactions, enzyme induction, or tolerability. Newer antiepileptic drugs have a more favorable adverse effect profile and fewer drug interactions than older drugs. A specialist should always be consulted when prescribing or adapting antiepileptic drugs in patients with solid-organ transplantation [13].
We considered a primary epileptic cause in the initial differential diagnosis of our patient. However, the clinical presentation was not typical for focal with secondary generalization or focal to bilateral tonic–clonic seizures (no post-ictal phase, no loss of urine or stool, and no bitten tongue). Primary generalized or nonmotor seizures (“absence seizures”) could be considered but would be rather unlikely given the first manifestation at age > 50 years.
Nevertheless, EEG is a simple, noninvasive investigation that can help in the diagnostic workup, especially in atypical clinical situations. However, EEG should not be systematically performed in all patients with transient loss of consciousness and syncope because only 1–2 % of EEGs show potentially epileptic potentials. Meanwhile, the cost for one diagnostic-relevant EEG is up to US $33,000 [16, 17]. Our patient suffered from recurrent episodes of presyncope, subjectively perceived as short-lived generalized weakness and sometimes associated with falls. There was no complete syncope with evident loss of consciousness, as seen in more sustained bradyarrhythmia due to a high-degree AV block. It is possible that our patient did not suffer from typical vasovagal episodes because of a transplanted and hence vagally denervated heart.
Most syncopes are described in the context of tachyarrhythmias such as ventricular tachycardia or fibrillation [18]. The patient’s symptoms typically appear within 10 seconds after the arrhythmia and are sometimes followed by transient electrocerebral silence [7]. Most published studies about bradycardia-associated cerebral hypoxia due to cerebral hypoperfusion demonstrate that they are induced by ocular compression, carotid sinus massage, or intentional transitional deactivation of an automatic implantable cardioverter–defibrillator [7].
