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]