Sudden Cardiac Death in Structurally Normal Heart

1
Sudden Cardiac Death in Structurally Normal Heart

• Brian D. Le, MD
• Presbyterian Hospital
• CIVA

2
Presentation

• HPI-35 yo WM s PMH presents with exertional
  syncope
• h/o PAF since 18 yrs of age
• Holter- monomorphic isolated PVCs
• Echo- structurally normal heart
• Meds- no OTC or herbal
• Social- occ. Etoh, no IVDA
• Family History
• Sister (31) - dizziness and palpitations
• Sisters son (6) - cardiac arrest at 8 mo old
  after a loud noise with successful DCCV

Gaita et al. Circulation. 2003 108
3

• A- 35 yo WM c syncope
• B- 31 yo sister, dizziness and palpitations
• C- 6 yo son, SCD

4
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.
5
Sudden Cardiac Death

• Normal hearts, lt 40 years old
• lt 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.
6
Primary Electrophysiologic Abnormalities

• WPW anterograde BPT ERP lt250ms.
• Brugada RBBB w/ST elevation V1-V3
• Catecholamine Polymorphic VT hRyR2.
• Long QT QTc (gt440ms), TdP w/long coupled PVC
  (600-800ms).
• Short-coupled TdP normal QTc, PVC w/short
  coupling (200-300ms).
• Short QT syndrome
• Idiopathic VF

7
Brugadas

8
Catecholaminergic Polymorphic VT

9
Idiopathic VF
10

• A- 35 yo WM c syncope
• B- 31 yo sister, dizziness and palpitations
• C- 6 yo son, SCD

11
Evaluation

• Physical Exam
• Serial ECGs
• Holter
• Heart rate variability
• QT dispersion
• Signal-averaged ECG
• Echocardiogram
• Cardiac MRI
• Electrophysiological Study

12
QT Interval

• Represents ventricular repolarization.
• Normal QTc upper limit 440ms.
• Bazetts formula QTc QT/ RR
• Rautaharju formula (14,379 pts)
• QTp (ms) 656/ (1HR/100)
• QT/QTp x 100 QTpredicted.
• 88 of QTp 2 SD below mean
• Lower limit of nl QT int. 88 of QTp

13
QT Interval and SCD

• Algra et al. Br.Ht.J. 19937043-8.
• 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 gt 440ms ? 2.3 RR of SCD.
• QTc lt 400ms ? 2.4 RR of SCD.

14
Familial Short QT

• Gussak et al. Cardiology 20009499-102.
• 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 lt80
  predicted by Rautaharju method.

15
Factors That Shorten QT

• Increase in heart rate
• Hyperthermia
• Hypercalcemia
• Hyperkalemia
• Acidosis
• Changes in autonomic tone

16
Genetic Basis of Short QT

• Brugada, Antzelevitch, et al. Circ.
  200410930-5.
• 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

17
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
18

• KCNJ2, encoding for inwardly rectifying K channel
  Kir2.1
• Rapid repolarization
• SQT3
• Loss of function results in LQT7 (Andersons
  disease)

Priori et al. Circ. Res. 2005 96
19
Ion Channel Mutations

• Loss of Function
• SCN5A ? Brugada
• IKs ? LQT1
• IKr ? LQT2

• Gain of Function
• SCN5A ? LQT3
• IKs ? Fam. A. Fib., Short QT
• IKr ? Short QT

20
Short QT Syndrome Rx

• Gaita et al. JACC. 2004431494-9.
• 6 pts. from 2 different families.
• Drugs Flecainide (IV or oral), Sotalol,
  Ibutilide, and Hydroquinidine.

21
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.

22
Ventricular ERP
23
(No Transcript)
24
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.

25
ICD

• First line therapy
• Risk of inappropriate shock delivery- Tw
  oversensing (Schimpf et al. JCE. 14 Dec 2003)

26
- Ventricular ERP- lt150ms - induction of VF -
Atrial ERP- 120ms
Circulation. 2003 108
27
Family Tree
49 yo
39 yo
39 yo
8 mo
Circulation. 2003 108
28
Schimpf, et al. Heart Rhythm. 20042
29
SummaryShort QT Syndrome

• Significantly short QTc lt 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.