Monomorphic Outflow Tract Ventricular Tachycardia: Unique
Presenting Manifestation of Gitelman’s Syndrome
Credits:Subba Reddy Vanga, MD, Chandra Annapureddy, MD, Mazda Biria, MD, Dhanunjaya Lakkireddy, MD FACC*
* Mid America Cardiology @ University of Kansas Hospital, Kansas City, KS. Howard University Hospitals, Washington, DC.
Corresponding Address : Dhanunjaya Lakkireddy MD, FACC, Associate Professor of Medicine, Director,
Center for Excellence in AF & EP Research Bloch Heart Rhythm Center, Mid America Cardiology @ University of Kansas Hospitals, 3901 Rainbow Blvd, Suite G600, Kansas City, KS 66160.
Key Words : Gitelman’s Syndrome, VT.
Outflow Tract Ventricular Tachycardia (OTVT) is typically seen
in young to middle aged people with structurally normal hearts. These
arrhythmias are triggered by emotional or stress factors and that responds to
medications. Electrolyte abnormalities rarely cause ventricular arrhythmia. Gitelman’s
syndrome, a rare autosomal recessive renal disorder causes hypokalemia,
metabolic alkalosis and hypomagnesaemia . This disorder is
often benign with mild clinical symptoms and excellent long-term prognosis. We
present a case of Gitelman’s syndrome with symptomatic OTVT as initial
A 27-year old male presented for
arrhythmia evaluation after multiple ER visits with symptoms of palpitations,
light headedness and near syncope over a period of 2 months. Typical episodes
were spontaneous in onset and were not associated with activity or exercise or
caffeine intake. They lasted from few seconds to few minutes and are associated
with lightheadedness. His past medical history was otherwise unremarkable. His
family history is negative for coronary artery disease or sudden death. His
alcohol and caffeine intake were not significant and he denied tobacco or illicit
drug use. His only medication includes potassium supplements at 20 mEq per day
for documented hypokalemia (Serum K+ 3.1 mEq/L; Normal: 3.5 -5.0
mEq/L) during one of his ER visits. Cardiovascular examination revealed a
normotensive male with regular rhythm and rate without any murmur or clicks. A 12
lead EKG obtained during his initial office visit showed normal sinus rhythm and
QT interval without any obvious pre-excitation or PR prolongation to suggest AV
nodal dysfunction. Patient was sent home on a continuous looping event monitor.
Two weeks later he presented to the
ER with another episode of palpitations with documented sustained VT. He was
found to have hypokalemia (Serum K 2.8mEq/L, Normal: 3.5 – 5.0mEq/L) and
hypomagnesaemia (Serum Mg ++ 0.7 mEq/L; Normal: 1.3 -2.1 mEq/L) during the
work up in the ER and was admitted for further evaluation. On repeat
questioning, he denied diuretic or laxative abuse. Interim review of his
style='font-size:12.0pt;line-height:200%;font-family:"Times New Roman"'>event
monitor showed significant arrhythmia burden which
accounted for more than 14% of his monitored period, with bigeminy, trigeminy,
non sustained and sustained VT. All of his non-sustained and majority of
sustained VT were asymptomatic. ECG obtained during an episode of VT revealed left
bundle branch block morphology with transition in V2/V3 and an inferior axis suggesting
the origin from ventricular outflow tract [Figure 1]. The transition in V2/V3 makes
it difficult to diagnose the origin of VT without an EP study.
Figure 1: 12 lead EKG of the patient with Gitelman's Syndrome showing monomorphic Ventricular tachycardia.
His biochemistry panel also showed metabolic
alkalosis. In the absence of diuretic use and GI losses, it triggered further
workup which demonstrated hypocalciuria. His urinary prostaglandins were
normal. Plasma renin-activity, aldosterone and cortisol levels were in the
upper normal range. Patient had a Thiazide test which demonstrated a blunted
diuretic response to thiazide diuretic with lower than the normal (2.2%) fractional
chloride clearance . These findings were suggestive of
Gitelman’s syndrome. H is 2D-Echocardiogram was normal
and cardiac MRI ruled out arrhythmogenic right ventricular dysplasia. His
arrhythmia improved with intravenous electrolyte replacement alone and hence an
electrophysiology study was not undertaken. He required 80 mEq of potassium, 2
grams of magnesium supplements every day and spironolactone was added to
maintain his serum potassium and magnesium levels within normal range. Patient remained
asymptomatic on oral electrolyte supplementation alone and 24-Hour Holter
monitor demonstrated less than 10 premature ventricular contractions without
arrhythmia at one year follow up.
syndrome, also called as familial hypokalemia-hypomagnesemia, is a autosomal
recessive disorder resulting from a gene (SLC12A3) defect that encodes the
renal thiazide-sensitive sodium-chloride co-transporter [1, 3, 4]. Secondary to this defect, the
biochemical abnormalities closely mimic chronic thiazide diuretic abuse characterized
by hypokalemic metabolic alkalosis with significant hypomagnesemia and low
urinary calcium excretion. The differential diagnosis of Gitelman's syndrome
includes Barter's syndrome and Hereditary Magnesium loosing nephropahthy . Barter's syndrome is not associated with hypomagnesemia and
hypocalcuria while the magnesium loosing nephropathy does not present with
hypokalemia. The diagnosis is made on clinical symptoms and biochemical
abnormalities. Although genetic testing is available, it is not recommended
because of excellent long-term prognosis of this syndrome. Gitelman's syndrome
typically manifests during adolescence and adulthood with symptoms of fatigue,
muscle weakness, cramps, and tetany from hypomagnesemia. Acute fluid and
electrolyte losses such as dehydration, vomiting or diarrhea can exaggerate or
precipitate these symptoms. Gitelman's Syndrome is hereditary, no other first
degree relatives of this patient had electrolyte abnormalities.
The mechanism of arrhythmogenesis in Gitelman's syndrome is not
clear. Chronic hypokalemia can predispose but not sufficient to generate a
symptomatic ventricular arrhythmia. Electrocardiographic
abnormalities were studied in Barter's syndrome patients who have predominantly
hypokalemia . Electrocardiograms demonstrated prolongation
of QT interval and frequent premature ventricular contractions were noted in 2
patients on Holter monitor. No arrhythmia was documented. Another study
specifically looking at cardiac workup in Gitelman's syndrome, found out that
QT interval is often prolonged but 24 hour Holter, treadmill exercise,
echocardiographic data was unchanged . Similar changes in
QT interval were reported from other study without any documentation of
Magnesium deficiency can potentially result in torsades-de-pointes
and cardiomyopathy . Similarly VT was documented in a
patient with Magnesium deficiency 
. A rare case of exercise induced VT in
Gitelman's syndrome was that disappeared with electrolyte replacement was
reported . In another case report VT in a patient with
Gitelman's syndrome did not respond to electrolyte replacement but required
multiple antiarrhythmic medications and ICD therapy .
Rarely this syndrome can present as sudden cardiac death .
Autonomic system imbalance can cause arrhythmia and this patient did not
demonstrate any signs or symptoms suggestive of such problem. It is unlikely
that this patient had a concurrent idiopathic monomorphic OTVT because the
arrhythmia was suppressed with simple electrolyte replacement alone.
contraction might have probably precipitated the arrhythmia in this patient
whose substrate was modified from chronic electrolyte imbalance.
Recent study supports the role of
microvascular dysfunction and myocardial perfusion abnormalities as triggering
factors precipitating malignant ventricular arrhythmias in the context of
chronic hypokalemia usually present in Gitelman's syndrome patients .
imbalance is an easily correctable cause that could be the potentially
precipitate or exaggerate an arrhythmia. Every effort should be taken to
correct hypokalemia and hypomagnesemia early in the management of an
arrhythmia. Rare causes of electrolyte disorders should be kept in differential
diagnosis in such cases as these problems will recurs if not treated
appropriately. Gitelman's syndrome, a rare cause of hereditary hypokalemic,
hypomagnesemic metabolic alkalosis is gaining recognition for its association
with cardiac arrhythmia.
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