Download JacobJessenAbstract2016

Title: Antibiotics May Expose Subclinical Long QT Syndrome (IMAGES excluded from
abstract)
Authors: Jessen Jacob, MD, MPH and Scott Sakaguchi, MD
Background:
•
Typical feature of Torsades de Pointes is usually an ectopic ventricular beat
followed by a compensatory pause that is terminated by a sinus beat with
prolonged QT interval and U wave; another ventricular ectopic beat often falls on
the exaggerated U wave of the sinus beat which precipitates TdP (short-long RR
intervals)
•
The two important K+ currents involved in ventricular repolarization are the rapid
delayed rectifier current (Ikr) and slow delayed rectifier current (Iks). Most drugs
block Ikr causing QTc prolongation. Prolonged repolarization allows for early
after depolarization and triggered activity
•
HERG controls the repolarizing current Ikr; mutations in HERG reduce IKr and
thus prolong action potentials in individual cells; drugs that prolong the QT
interval and cause torsade de pointes also block IKr (KCNH2 gene)
•
5 to 10 percent of persons in whom torsade de pointes develops on exposure to
QT-interval–prolonging drugs have mutations associated with the long-QT
syndrome; they may have a subclinical form of the congenital syndrome.
•
Family members with near-normal QT intervals may carry the same mutations in
genes associated with long-QT–syndrome disease as their relatives.
Hospital Course:
•
A 24 year-old man with no significant past medical history presented with
worsening chest discomfort and dyspnea of approximately 4 months duration.
The symptoms began ~ 4 months ago with cough, yellow sputum production,
intermittent fevers and night sweats. The patient endorsed 2 pillow orthopnea
and paroxysmal nocturnal dyspnea.
•
The patient was empirically started on IV Levofloxacin for concern of a
pneumonia. The following morning the patient was found to be unresponsive
•
CPR initiated (~2 minutes), given 1 shock at 200J, IV Magnesium and IV
Amiodarone with ROSC. At ~ 5PM, the pt was once again found to be
unresponsive and pulseless at which time CPR was initiated. The patient was in
polymorphic VT with 1 shock applied at 150J
Imaging:
- excluded from abstract (Cardiac MRI and Electrocardiograms)
Conclusion:
•
Fluoroquinolone and macrolide antibiotics prolong the QT interval through
concentration-dependent blockade of the rapidly activating delayed rectifier
potassium channel (hERG/IKr channel).
•
Antibiotics are weak IKr blockers, and antibiotic-induced TdP or QTc prolongation
in young patients with no high-risk factors (4–6% of the cases) is potentially
unmasking a subclinical disease.