Download Short QT Syndrome

Sudden Cardiac Death in
Structurally Normal Heart
Brian D. Le, MD
Presbyterian Hospital
CIVA
Presentation
– HPI-35 yo WM s PMH presents with
exertional syncope
h/o PAF since 18 yrs of age
 Holter- monomorphic isolated PVC’s
 Echo- structurally normal heart

– Meds- no OTC or herbal
– Social- occ. Etoh, no IVDA
– Family History
Sister (31) - dizziness and palpitations
 Sister’s son (6) - cardiac arrest at 8 mo old
after a loud noise with successful DCCV

Gaita et al. Circulation. 2003; 108



A- 35 yo WM c
syncope
B- 31 yo sister,
dizziness and
palpitations
C- 6 yo son, SCD
Sudden Cardiac Death




“Unexpected death from cardiac cause
within a short time (~1 hour of sx) in
a person without prior conditions that
would appear fatal.”
300-400,000 deaths annually (U.S.).
VT/VF account for 80%.
20% have structurally normal hearts.
Wever E, et al. JACC. Vol 43, 2004.
Sudden Cardiac Death



Normal hearts, < 40 years old
< 30% successful resuscitation
reaching hospital
Risk of life-threatening events in
cardiac arrest survivors is 25-40% at
two years
Wever E, et al. JACC. Vol 43, 2004.
Primary Electrophysiologic
Abnormalities







WPW: anterograde BPT ERP <250ms.
Brugada: RBBB w/ST elevation V1-V3
Catecholamine Polymorphic VT: hRyR2.
Long QT: QTc (>440ms), TdP w/long
coupled PVC (600-800ms).
Short-coupled TdP: normal QTc, PVC
w/short coupling (200-300ms).
Short QT syndrome
Idiopathic VF
Brugada’s
Catecholaminergic
Polymorphic VT
Idiopathic VF



A- 35 yo WM c
syncope
B- 31 yo sister,
dizziness and
palpitations
C- 6 yo son, SCD
Evaluation









Physical Exam
Serial ECG’s
Holter
Heart rate variability
QT dispersion
Signal-averaged ECG
Echocardiogram
Cardiac MRI
Electrophysiological Study
QT Interval




Represents ventricular repolarization.
Normal QTc upper limit: 440ms.
Bazett’s formula: QTc = QT/ RR
Rautaharju formula (14,379 pts):
– QTp (ms)= 656/ (1+HR/100)
– QT/QTp x 100% = % QTpredicted.
– 88% of QTp = 2 SD below mean
– Lower limit of nl QT int. = 88% of QTp
QT Interval and SCD

Algra et al. Br.Ht.J. 1993;70:43-8.
– Nested cohort 6693 consecutive pts w/24
ECG.
– F/U 2.5 years in 99.5% of pts.
– End point: QTc correlation w/SCD (104
pts).
– Results:
QTc >= 440ms  2.3 RR of SCD.
 QTc < 400ms  2.4 RR of SCD.

Familial Short QT

Gussak et al. Cardiology 2000;94:99102.
– 3 members of one family; age 17-51 yo.
– Palpitations, sx PAF, syncopeSCD
– All w/ structurally normal hearts.
– All w/ S-QT (260-280ms); QT interval
<80% predicted by Rautaharju method.
Factors That Shorten QT






Increase in heart rate
Hyperthermia
Hypercalcemia
Hyperkalemia
Acidosis
Changes in autonomic tone
Genetic Basis of Short QT

Brugada, Antzelevitch, et al. Circ.
2004;109:30-5.
– Different missense mutations in same
residue codon 588 of KCNH2 (HERG [IKr]).
– Mutations only seen in sQT, and not in
normal relatives.
– Patch clamp models
Heterogeneity of Short QT



Genetic Studies- KCNQ1 gene
mutation G for C, subs. valine for
leucine (IKs)
Mutations negative in 200 unrelated
controlled individuals
Loss of function leadsLQT1
Bellocq et al. Circulation. 109; 2004




KCNJ2, encoding for inwardly
rectifying K channel Kir2.1
Rapid repolarization
SQT3
Loss of function results in LQT7
(Anderson’s disease)
Priori et al. Circ. Res. 2005; 96
Ion Channel Mutations

Loss of Function
Gain of Function

– SCN5A  Brugada
– IKs  LQT1
– IKr  LQT2
1
2
– SCN5A  LQT3
– IKs  Fam. A. Fib.,
Short QT
– IKr  Short QT
Ca > Na
0
Na
4
IKr & IKs
3
Short QT Syndrome Rx

Gaita et al. JACC. 2004;43:1494-9.
– 6 pts. from 2 different families.
– Drugs: Flecainide (IV or oral), Sotalol,
Ibutilide, and Hydroquinidine.
Short QT Rx Results



Flecainide: slight inc. QT due to QRS
prolongation.
Ibutilide & Sotalol: no change in QT
Hydroquinidine:
– 5/6 pts- QTc normalized (290405ms)
– EPS 5/5 pts- inc. VERP, no VF/VT
– F/U 11 mos- 4/6 on hydroquinidine w/o
sx or arrhythmias detected by ICD.
Ventricular ERP
Quinidine



VW Class: Ia (sodium channel blocker)
Blocks: INa, IKr, IKs, Ito, L-type Ca2+,
IK1(in.rect.), & IKATP  QT increase.
Adverse effects: diarrhea, SLE,
thrombocytopenia, hepatitis,
cinchonism (tinnitus/HA), TdP, many
drug interactions 2/2 block of CYP2D6.
ICD


First line therapy
Risk of inappropriate shock deliveryTw oversensing (Schimpf et al. JCE. 14: Dec 2003)
- Ventricular ERP- <150ms - induction of VF
- Atrial ERP- 120ms
Circulation. 2003; 108
Family Tree
49 yo
39 yo
39 yo
8 mo
Circulation. 2003; 108
Schimpf, et al. Heart Rhythm. 2004;2
Summary
Short QT Syndrome







Significantly short QTc <= 300ms.
Tall & peaked T-waves.
Clinical: palpitations, syncope, SCD.
Significant FHX of SCD.
Atrial and ventricular arrhythmias.
Structurally normal hearts.
Treatment: ICD and/or Quinidine.