Sudden cardiac death in individual with structurally normal hearts.

1. Do You Think You
are SAFE??
Yasmeen Kamal, MBBCh, MSc
Teaching assistant of Cardiovascular Medicine,
Tanta University

2. SCD in structurally Normal
hearts
Sudden death (SD) is defined as an
unexpected natural death occurring
within an hour after the onset of
symptoms. When unwitnessed, SCD
refers to the death of an individual
within 24 hours after being seen
alive and in a normal state of
health.

3. • Nearly 85 % of Sudden deaths are of
cardiac origin.
• 10-15 % of SCD occurs with
structurally normal hearts.
• Mostly in ages below 35 years old.

4. In an autopsy series of 902 cases of SCD (mean
age 38 years), 187 (21 percent) had no
evidence of cardiac pathology that could cause
SCD

6. Long QT

7. Long QT syndrome
In 1950, More than 50 years ago, a family
with concomitant deafness, mutism, and a
peculiar heart disease was described
“Jervell, A.; Lange-Nielsen,”
In 1958, Levine et al. reported a case of an
8-year-old boy who died suddenly after
having been previously diagnosed with
congenital deaf-mutism, attacks of
unconsciousness, and an ECG with a
prolonged QT interval and large T waves.

8. Shortly thereafter, Romano et al. and
Ward published QT prolongation in one
parent and several children from two
different families, all of whom possessed
normal hearing but experienced recurrent
syncope and SD.

9. LQTS can be congenital or acquired
• Congenital LQTS is associated with
mutations in ion channels and/or
associated proteins
• Acquired LQTS is generally associated
with drugs and electrolyte imbalance
(hypokalemia, hypocalcaemia, and
hypomagnesaemia).

10. Diagnosis
QTc values >470 ms for males and
>480 ms for females, representing
approximate 99th percentile values)
Is this enough for diagnosis?

11. the diagnosis of LQTS is established by :
“Schwartz score” of 3.5 without a secondary cause
for QT prolongation
and/or by the presence of a QTc interval 500 ms in
repeated ECGs without a secondary cause forQT
prolongation.
and/or by the presence of a pathogenic variant in
one of the genes known to be associated with LQTS.
Additionally, LQTS can be diagnosed if QTc is between
480 and 499 ms in patients with unexplained syncope
without a secondary cause for QT prolongation and in
the absence of a pathogenic genetic variant

12. Schwarz score was introduced 1993
a quantitative score based on ECG/ Clinical history
and family history.
According to ESC Guidelines of VT/SCD

13. Fig.1 Diagram of the overlap between the genes associated with Brugada syndrome (BrS),
short QT syndrome (SQTS), long short QT syndrome (LQTS) and catecholaminergic
polymorphic ventricular tachycardia (CPVT).Anna Fernández-Falgueras et al,
Biology,2017

14. The three major LQTS-susceptibility genes are KCNQ1,
KCNH2, and SCN5A, and mutations in these genes are
associated with about 75% of patients with a clinical LQTS
diagnosis.
The remaining 16 genes are responsible for nearly 10% of
LQTS cases.

15. The major LQTS genotypes correlates
with specific ST-T wave patterns :
For example:
LQT1: broad-based T wave.
LQT 2 : low-amplitude and notch.
LQT3 has a late-appearing T wave.

16. LQT 1: Broad T waves

17. LQT 2(Bifid T waves)

18. LQT 3 (Prolonged ST segment)

19. Long QT Syndrome
High Risk Features
 Aborted cardiac arrest
 Family history (< 50 y) of cardiac arrest or
unexplained syncope
 History of “seizures” or congenital deafness
 Prolonged QTc ≥500 msec on ECG
 Positive genetic test

21. Short QTc

22. SQTS is a rare channelopathy with an estimated
prevalence of less than 1 in 10,000.
Autosomal-dominant pattern of inheritance.
Currently, genetic alterations associated with
SQTS have been identified in six genes (KCNQ1,
KCNH2, KCNJ2, CACNA1C, CACNB2 and
CACNA2D1).
The most prevalent subtype of SQTS is
associated with gain-of-function mutations in
KCNH2 (SQTS1) that increase current flow
through the channel and shorten the AP
duration and QT interval.

23. Clinical picture :
• QTC < 360 msec
• Cardiac arrest seems to be the most frequent
symptom (up to 40%), Palpitations are a
common symptom (30%), followed by syncope
(25%) and atrial fibrillation (AF), which are
the first symptoms of the disease in up to 20%
of patients.
• Other ECG findings that may facilitate the
correct diagnosis of SQTS such as presence of
tall, peaked, symmetrical, and narrow-based
T waves, prominent U waves ,depression of
PQ segment

26. Brugada Syndrome

27. In 1996, the term “Brugada syndrome” was first used to
define the “right bundle branch block, persistent ST
segment elevation, and sudden death syndrome”
Currently, the global prevalence of Brugada S varies from
five to 20 in every 10,000 individuals, and there is a strong
gender disequilibrium ratio of three to one (male to
female) likely due to the influence of hormones

28. The first manifestation of the disease usually occurs
during rest or sleep likely due to high vagal tone
Three types of ECG have been described (types I, II
and III).
Type I is characterized by ST segment elevation
followed by a negative T wave, with little or no
isoelectric separation, with a “coved morphology”
.

29. Brugada pattern ECG
ST elevation V1-V3
Type 1 (DIAGNOSTIC)
Coved ST elevation ≥ 2mm with negative T wave
sensitivity by moving V2/V3 from 4th to 2nd/3rd intercostal space
Type 2
Saddleback ST elevation ≥ 2mm w/ ST trough ≥ 1mm
Positive/biphasic T wave
Type 3
Coved/saddle ST elevation ≥ 2mm w/ ST trough < 1mm
Also reported in inferior leads and left precordial leads
Some individuals also had SCN5A mutation

30. Approximately 20%–25% of BrS patients are
genetically diagnosed with pathogenic variations
in SCN5A.

31. Brugada Syndrome
Vs
Brugada Pattern

32. Brugada Syndrome
Definition
Type 1 pattern ECG in V1-V3 plus 1 of following:
Pharm conversion to Type 1 from Type 2/3 ECG
Na channel blocker (procainamide, fleicanide, ajmaline)
Documented VF/polymorphic VT
Family history of SCD < 45y
Inducible VT at EP study
Syncope
Nocturnal agonal respirations
ECG pattern only = Brugada pattern ECG but not
Brugada Syndrome

34. The ESC Guidelines

35. Brugada Consensus Conference
Spontaneous Type 1 ECG
ICD (I)
Aborted SCD
ICD (I)
Extracardiac
Cause
absent
Close f/u
Extracardiac
Cause
present
Syncope
Seizure
NAR
Symptomatic
ICD (IIA)
EPS (IIA)
positive
Close f/u
EPS (IIA)
negative
Family Hx
positive
ICD (IIA)
EPS (IIA)
positive
Close f/u
EPS (IIA)
negative
Famil Hx
negative
Asymptomatic
Spontaneous
Type 1 ECG

36. Brugada Consensus Conference
Sodium Channel Blocker Induced Type 1 ECG
ICD (I)
Aborted SCD
ICD (IIA)
Extracardiac
Cause
absent
Close f/u
Extracardiac
Cause
present
Syncope
Seizure
NAR
Symptomatic
ICD (IIB)
EPS (IIB)
positive
Close f/u
EPS (IIB)
negative
Family Hx
positive
Close f/u
Famil Hx
negative
Asymptomatic
Na Channel
Blocker Induced
Type 1 ECG

37. CPVT

38. CPVT is a channelopathy with both autosomal-
dominant and, less frequently, autosomal-
recessiveinheritance patterns.
The first CPVT-associated variants were
identified in 2001 in the gene encoding the
cardiac ryanodine receptor (RYR2)

40. So,
Potential causes of SCD without structural heart diseases can
be due to:
Long QT syndrome
Short QT syndrome
CPVT
Brugada syndrome
Early repolarization syndrome
Idipathic VF
Commotio cordis
WPW and other forms of SVT
VF secondary to PVCs
Familial SCD

41. Early repolarization syndrome

42. In 2008 a higher frequency of early repolarization was
described in 206 survivors of cardiac arrest without
apparent heart disease (31 to 5 percent of controls; p<0.001)
These survivors tended to have increased incidences of
recurrent VF compared with those SCA survivors with normal
hearts and no early repolarization.
Early repolarization ECG pattern is especially common in
athletes, and in these individuals
It is generally benign.
An expert consensus panel does not recommend any specific
treatment for those with early repolarization without SCA.

43. Commotio cordis:
Commotio cordis is defined as sudden cardiac death
secondary to relatively innocent chest wall impact due to
ventricular fibrillation.
Affected patients have No underlying heart disease and
there is no structural damage to the chest wall, thoracic
cavity, or the heart. Early defibrillation of commotio
victims is lifesaving,

44. Idiopathic VF
More commonly referred to as
idiopathic ventricular fibrillation (VF),
this entity is estimated to account for
5 percent of cases of sudden cardiac
death (SCD) with mean age 36 years
with male to female ratio 2.5 : 1

45. To sum up:
• Sudden cardiac death (SCD) refers to the sudden
cessation of cardiac activity with hemodynamic
collapse, often due to sustained pulseless
ventricular tachycardia (VT) or ventricular
fibrillation (VF).
• SCD is the most common cause of cardiovascular
death in the developed world.
• Although the risk of SCD is higher in patients with
structural heart disease, as many as 10 to 15
percent of SCDs occur in individuals with apparently
normal hearts.
• A family history of SCD (in first-degree relatives) in
the absence of apparent structural heart disease is
associated with an increased risk for primary SCD.

46. Patients who experience SCD, particularly young
patients, should undergo an autopsy with particular
attention to the heart to evaluate the presence of
structural heart disease.
In young patients, if there is no clear diagnosis
after autopsy, genetic testing now can yield a
diagnosis in up to one third of young SCD victims
and should generally be performed.

47. Survivors of sudden cardiac arrest (SCA) should
undergo extensive testing to exclude drug or
toxin exposure or underlying structural heart
disease that may have contributed to SCA.
Therapy with an implantable cardioverter-
defibrillator should generally be recommended
in survivors of SCA.

48. In families of victims of unexplained SCD, a general
cardiology evaluation of first- and second-degree
relatives can yield diagnosis of a heritable disease in up
to 40 percent of families.

49. Finally learn to save lives