Discussion
The patient’s initial presentation of a low serum sodium of 101mmol/L raised the possibility of number of differential diagnoses including syndrome of inappropriate anti diuretic hormone (SIADH), dehydration, congestive heart failure, chronic kidney disease, cerebral- wasting syndrome, psychogenic polydipsia, and beer potomania. Low urine osmolarity and low urine sodium levels excluded dehydration, SIADH and cerebral wasting syndrome as the cause of this patient’s hyponatremia [34]. The patient’s denial of drinking excessive water, also ruled out psychogenic polydipsia. This patient’s noncontributory initial physical examination, along with chest x-ray without any acute intrathoracic process with a normal BNP and renal function essentially ruled out congestive heart failure and renal insufficiency.
His history of alcohol abuse, including clinical presentation of lethargy and disheveled appearance, along with his laboratory work up of low serum osmolarity, urine osmolarity and low urine sodium results and absence of possible explanation, led us to the possibility of beer potomania accounting for the patient’s hyponatremia.
Our eventual working diagnosis of the patient’s hyponatremia was likely related to alcohol, and hence, the patient possibly, had beer potomania evidenced by low urine sodium and severe hyponatremia. This together led to the Status epilepticus our patient experienced. We hypothesize that his severe hyponatremia may have cause the Takotsubo cardiomyopathy (TC), especially in the context of epileptic seizures. The TC evidenced by the absence of coronary artery stenosis on LHC and presence of apical ballooning on ventriculogram and echocardiogram. This was buttressed by a low left ventricular ejection fraction of 30% and its eventual improvement to 55% over a relatively short period of time of a month.
The pathogenesis of TC is not fully understood but the proposed mechanisms include endogenous catecholamine excess, multi-vessel coronary artery vasospasm, and microvascular dysfunction. The most favored mechanism is endogenous catecholamine excess leading to microvascular spasm or dysfunction resulting in myocardial stunning [8]. Others have also discussed a direct toxicity of cardiomyocyte from the large amount of circulating catecholamines [19].
In support of the endogenous catecholamine excess hypothesis, a mouse model showed that a high level of epinephrine had negatively inotropic effect on cardiomyocytes due to a switch from beta-2 adrenoceptor Gs protein signaling to Gi protein signaling. It is speculated that the effect is greatest on the apex of the myocardium because of a higher density of beta-2 adrenoceptors. [20]
Additionally, Ellison et al found that high doses of isoproterenol cause diffuse death of myocytes while sparing cardiac stem cells in rats allowing for rapid recovery of the myocardium. [21]
Akashi et al in another study, reported that TC patients had an increased myocardial 123I-metaodobenzlguanide (123I-MBG) washout rate which indicates an increased norepinephrine release from sympathetic nerve endings or increased clearance of 123I-MBG by extra neural tissues. Ultimately the increased wash out rate correlated to increased plasma norepinephrine levels in TC patients. [22]
There are a few case reports of TC in the setting of moderate to severe hyponatremia described in the body of literature. [10,12,30-33]
Hyponatremia has not been thought to be linked to Takotsubo cardiomyopathy but perhaps may have an indirect causal relationship. The prevailing theory of this indirect causal relationship is a stress induced catecholamine storm causing a direct toxic effect on the myocardium or indirect effect by coronary vasculature constriction. The mechanistic connection is still not clear; however, it has been suggested that hyponatremia could interfere with myocardial inotropy by modifying the cardiomyocytic sodium-calcium exchange pump resulting in myocardial swelling associated with hypotonicity. [10]
Indeed, transient positive inotropic effects on the myocardium were observed in rat hearts, and the degree of positive inotropy correlated with the degree of hyponatremia [11]. There have been cases reported of Takotsubo cardiomyopathy in the setting of “isolated hyponatremia” and it has been suggested that in post-menopausal women presenting with acute coronary syndrome-like symptoms and hyponatremia, Takotsubo cardiomyopathy should be considered within the differential diagnoses. [12]
Takotsubo cardiomyopathy arising as a direct consequence of hyponatremia is an unexplored mechanism for this poorly understood disease process. The prevailing theories for the pathogenesis of TC involves excessive catecholamine action on the myocardium causing stunning either directly or through ischemia by causing multi-vessel epicardial or microvascular spasm. [13]
There has also been a long-recognized connection between TC and stress, particularly strong emotional stress, which suggests that there may be a neurohumoral connection that precipitates TC. Interestingly, TC has been found in cases of subarachnoid hemorrhage and stroke, and neurologists have advanced the idea “neurogenic stunning” to describe this reversible cardiomyopathy in the setting of brain injury in the absence of coronary artery disease [13] Norepinephrine release in the myocardium is increased as a result of hypothalamic ischemia from a subarachnoid hemorrhage, and may be the cause of the myocardial injury observed [14]
Furthermore, this neurogenic stunning effect is dampened when there is a disruption of neural innervation of the myocardium as in diabetes or heart transplant [15]. Neurocardiac lesions also occur in adrenalectomized animals, but to a lesser extent, further strengthening the neurogenic stunning theory. [16]
Although ischemia as a direct cause of TC is still being debated, the dysfunctional myocardium in TC follows a neural rather than vascular distribution, as there is a much higher concentration of adrenergic receptors in areas around myocardial arterioles than in areas adjacent to epicardial coronary arteries. [17]