Sudden Cardiac Death - University of Mississippi Medical Center

Sudden Cardiac Death: Who
is at Risk ?
Mark Borganelli, MD
Indications for an ICD
Secondary Prevention
Primary Prevention
Magnitude of SCD
3,000,000 cases per year
worldwide with an overall survival
rate of < 1%
In the US, 450,000 people die
suddenly each year
Only 5 % are successfully
resuscitated
Primary Prevention of SCD in
Ischemic Heart Disease
MADIT
MUSTT
MADIT II
4/10/2013
1

1232 patients
Prior MI (> 4 weeks)
EF

SCD-HeFT Protocol
Inclusion criteria
Placebo n=847 Amiodarone n=845
ICD implant n=829
40 months average follow- up
• Optimize: B, ACE-I, Diuretics
Bardy GH. Chapter Excerpt from Arrhythmia Treatment and Therapy. Woosley RL, Singh SN, editors. Marcel Dekker, 1 st edition. 2000;323-42.
SCD-HeFT Investigators Meeting, August 2001, data from most recent follow-up
4/10/2013
3

Causes of SCD in Young People
Congenital coronary
anomalies
(19%)
HCM
(36%)
Maron BJ et al. Circulation. 1996;94:850-56.
Mildly increased cardiac mass
(10%)
Ruptured aorta 5%
Tunnelled LAD 5%
Aortic stenosis 4%
Myocarditis 3%
Dilated cardiomyopathy
3%
ARVC 3%
MVP 2%
CAD 2%
Other 6%
Hank Gathers and HCM
(hypertrophic cardiomyopathy)
The first sign of trouble came December 9, 1989, in Santa Barbara, California. Six minutes into the second half, Hank Gathers, the All-
American forward for Loyola Marymount, drove to the basket and was fouled. When he went to the foul line, he felt an unusual
sensation. His heart was pounding faster than he had ever noticed. He bounced the ball then launched a shot. He missed. Then, he
collapsed. Coaches and the school's medical personnel immediately rushed to Gathers' side. Within seconds, he rose to his feet and
walked off the court. Yet something was wrong. Drastically wrong.
He was later diagnosed as having an abnormal heartbeat and treated with Inderal, one of a class of beta blocker drugs that inhibits the
effects of adrenaline and smoothes the hearts rhythms. But Gathers detested the drug. He agonized over having to take it. The drug
made him sluggish, moody. His game suffered. He was unable to run the court without getting tired. His shot was off. He'd get woozy
at times. He'd sleep longer.Gathers continually complained to his coaches and doctors about the drug, that the dosage had to be
reduced. They said no. So gradually, Gathers began cutting down on the dosage, and began feeling much better. He also began
skipping some of the required testing. He was playing a risky game.
On the morning of March 4, 1990, Gathers awakes with excitement. LMU is on its way to the West Coast Conference tournament
championship and a NCAA tournament berth. On the court with his best friend, Bo Kimble, LMU's other brilliant player, Gathers
wins the game's opening tip and LMU is off and running, building a huge lead over outmatched Portland State.
There is 13:34 left in the first half and LMU leads 25-13. Suddenly, Gathers falls to the court. The crowd gasps. He tries to get up, but
slumps back to the floor, unable to muster enough strength. Portland's Josh Lowery, standing over Gathers, extends his hand,
attempting to help him up. But Gathers can't acknowledge it. LMU trainer Chip Schaefer flies off the bench. When he arrives, Gathers'
body starts to go into convulsions. Team physicians rush to his side. He has a pulse, but he is unable to comprehend what is
happening. He is removed from the court on a stretcher, and as soon as the medical staff gets outside the gym door, they hook him up
to the school's defibrillator, which was purchased a few months earlier specifically for Gathers, a device that is actually supposed to be
courtside in case he collapses. Taken off court, an external automatic external defibrillator is used to shock the fibrillating heart
Rescue Ambulance 5 of the Los
Angeles Fire Dept. arrives only
seven minutes after Gathers first
collapsed. The rescue vehicle
speeds off to Daniel Freeman
Marina Hospital, two miles away.
Gathers arrives at the hospital
only 24 minutes after he first
collapsed. Emergency personnel
work frantically on him for more
than an hour. Finally, two doctors
emerge from the emergency
Hank suffered from hypertrophic
room. They stonily walk toward
If used < 3 min
Gathers' family and friends.
cardiomyopathy (HCM), a genetic
An AED can
condition where the heart muscle is
They stop. The situation is clear. save over 80%
thickened and is the most common
Suddenly, a woman's shriek of SCA victims
cause of cardiac arrest in the young
pierces the air. "Oh my God.
He's gone. He's gone."
Hypertrophic Cardiomyopathy
Prevalence 1:300 to 1:600
More common in African Americans
More than 100 gene mutations identified
LV outflow obstruction in 30%
Sudden death from ventricular arrhythmia
Most common cause of athlete cardiac sudden
death (under age 35)
4/10/2013
4

Etiology
Genetic disease with Autosomal-Dominant
inheritance
Familial (inherited) versus Sporadic (de novo
mutation)
Parents transmit the gene to 50% of offspring
Gene mutations code for a sarcomere protein
(most often beta-myosin heavy chain gene,
myosin binding protein C gene, or troponin T
gene).
Synonyms for Hypertrophic Cardiomyopathy
Asymmetrical hypertrophic cardiomyopathy
Asymmetrical hypertrophy of the heart
Asymmetrical septal hypertrophy
Brock's disease
Diffuse muscular subaortic stenosis
Diffuse subvalvular aortic stenosis
Dynamic hypertrophic subaortic stenosis
Dynamic muscular subaortic stenosis
Familial hypertrophic cardiomyopathy
Familial hypertrophic subaortic stenosis
Familial muscular subaortic stenosis
Familial myocardial disease
Functional aortic stenosis
Functional hypertrophic subaortic stenosis
Functional obstructive cardiomyopathy
Functional obstruction of the left ventricle
Functional obstructive subvalvular aortic stenosis
Functional subaortic stenosis
Hereditary cardiovascular dysplasia
Hypertrophic cardiomyopathy
Hypertrophic constrictive cardiomyopathy
Hypertrophic hyperkinetic cardiomyopathy
Hypertrophic infundibular aortic stenosis
Hypertrophic nonobstructive cardiomyopathy
Hypertrophic obstructive cardiomyopathy
Hypertrophic stenosing cardiomyopathy
Hypertrophic subaortic stenosis
Idiopathic hypertrophic cardiomyopathy
Idiopathic hypertrophic obstructive cardiomyopathy
Idiopathic hypertrophic subaortic stenosis
Idiopathic hypertrophic subvalvular stenosis
Idiopathic muscular hypertrophic subaortic stenosis
Idiopathic muscular stenosis of the left ventricle
Idiopathic myocardial hypertrophy
Idiopathic ventricular septal hypertrophy
Irregular hypertrophic cardiomyopathy
Left ventricle muscular stenosis
Low subvalvular aortic stenosis
Muscular aortic stenosis
Muscular hypertrophic stenosis of the left ventricle
Muscular stenosis of the left ventricle
Muscular subaortic stenosis
Muscular subvalvular aortic stenosis
Non-dilated cardiomyopathy
Nonobstructive hypertrophic cardiomyopathy
Obstructive cardiomyopathy
Obstructive hypertrophic aortic stenosis
Obstructive hypertrophic cardiomyopathy
Obstructive hypertrophic myocardiopathy
Obstructive myocardiopathy
Pseudoaortic stenosis
Stenosing hypertrophy of the left ventricle
Stenosis of the ejection chamber of the left ventricle
Subaortic hypertrophic stenosis
Subaortic idiopathic stenosis
Subaortic muscular stenosis
Subvalvular aortic stenosis of the muscular type
Teare's disease
Pathophysiology
Change in sarcomere structure leads to change
in function
Release of growth factors that result in
hypertrophy and fibroblast proliferation
(interstitial fibrosis).
Electrically unstable substrate
- disorganized myocardial architecture (disarray)
- ischemia-related replacement scarring
4/10/2013
5

Hypertrophic Cardiomyopathy
4/10/2013
6

ICD-HCM Trial:
Arrhythmias Triggering ICD Interventions
VTVF
14%
VT and VF
9%
VT 48%
Bradyarrhythmias = 0
Maron BJ, et al. N Engl J Med. 2000;342:365-373.
Maron BJ, Bonow RO, Cannon RO III, Leon MB, Epstein SE. Hypertrophic cardiomyopathy:
interrelations
of clinical manifestations, pathophysiology, and therapy. N Engl J Med. 1987;316:780-9, 844-
52.
4/10/2013
7

The implantable defibrillator
titanium casing
capacitor(s)
battery
lead(s)
circuitry
header
Hypertrophic Cardiomyopathy
Secondary prevention
Family history of SCD
Unexplained syncope
Age younger than 40
Abnormal BP response to exercise
Severe LVH (particularly if wall > 30mm)
A
B
C
D
Case Presentation
• 22 y/o AAM superstar basketball
player drafted by the Celtics
• Took Bird’s place as the superstar
averaging over 20 points a game
• Had 6 bad dizzy spells over a 4
month period
• Collapsed in a playoff game in 1993
• Team doctor allowed him to
continue to play in the second half
• Taken to a hospital in Boston
afterwards
4/10/2013
8

• Noted to have NSVT on monitor
• Thallium, MR, and cath done
• Cath revealed normal coronaries but there was
clear large apical WMA and perfusion
abnormality
• A panel of 14 cardiologists and EPs met and
recommended to the team that he not play
and consider having an ICD implanted but
they did not talk directly to the patient or the
family
• Team ownership took a neutral position
after originally taking the side of the second
group of doctors
• Two months later while shooting baskets at
Brandeis University he collapsed and died
• Autopsy was performed
• Family was furious and had him transferred
to another local hospital
• MDs there downplayed the abnormalities and
a tilt table test was done and he received the
diagnosis of vasodepressor syncope
• They recommend that he take beta-blockers
and do little activity but at a press conference
the doctors said he could play again
• Sought a third opinion from an EP in
California without clear resolution
4/10/2013
9

Greatness
Reggie “the Jet” Lewis was
drafted by the powerhouse
Boston Celtics in the first
round in 1987.
He averaged over 20 points
a game.
Selected as the Celtic’s team
captain after the retirement
of Larry Bird.
Lewis suffered six dizzy
spells in 4 months before
collapsing during a playoff
game against the Charlotte
Hornets on April 29, 1993.
After he was examined by
the team doctor, he was
allowed to continue to play in
the second half.
Reggie Lewis and Myocarditis
A sad story
Physicians at PBBH developed a
close relationship with Lewis and
his family.
Lewis was prescribed beta
blockers and instructed to do very
little physical activity; however at a
press conference, they stated
Lewis could play again.
Lewis sought a third opinion in
California, but without clear
resolution.
The team ownership took a
neutral position after initially
endorsing the PBBH diagnosis
The family felt abandoned by
the team and all the other
doctors except for the PBBH
group.
Two months later, Lewis
suffered a fatal cardiac arrest
while shooting baskets at
Brandeis on July 27, 1993
His autopsy revealed
extensive scarring of the heart
muscle, consistent with the
original diagnosis.
A sad story
He was hospitalized at Baptist Hospital in
Boston where runs of NSVT were noted.
Work-up included a thallium scan, MR
imaging, and cardiac catheterization.
He was found to have a large apical
perfusion defect but normal coronary
arteries.
A panel of 14 electrophysiologists and
cardiologists reviewed the data in a special
two hour session.
They advised the team not allow Lewis to
play and to consider an ICD, but none of the
panel directly met with Lewis or his family.
A sadder ending:
A sad story
Very upset, the family had Lewis transferred to
Peter Bent Brigham Hospital at midnight by van
Physicians there reviewed but minimized the
abnormalities.
A tilt table test was positive and the diagnosis
was changed to vasodepressor syncope.
Myocarditis
Myocarditis can be produced by a variety of
different disorders, most of them infectious.
Many case are not detected because there are
not significant symptoms, but fatigue and
decreased exercise tolerance can be early
signs.
Chest pains, sudden death, and abnormal
heart beats can be seen as well.
Sometimes obtaining a piece of heart muscle
by way of a biopsy can be helpful in making a
definitive diagnosis.
Myocarditis should be suspected when a
patient, especially a young male, presents with
otherwise unexplained cardiac abnormalities of
new onset. Some may describe recent upper
respiratory infection or recent diarrhea.
Case Presentation
• 20 year old white female basketball
player at the University of
Washington
• Leading scorer for the team
• Rare episodes of dizziness
• Collapsed in her room in late
December 2002 and awakened from
a coma Jan 1 2003 with no sequelae
after being resuscitated with an
external defibrillator
Case Presentation was Kayla Burt Long QT syndrome
4/10/2013
10

LQT1
LQT2
LQT3
Gender + QT +
disease gene
Priori et al 2003
decreasing risk
Torsade de pointes
Rate 200 - 250 bpm
Rhythm Irregular
Recognition Continuously changing QRS morphology
Management of LQTS
β-blockers, exercise restriction in all (controversial in
LQT3)
Sodium channel blocker (mexiletine, ranolazine) in
LQT3 (?)
ICDs in “high-risk” subgroups
Resuscitated from cardiac arrest while compliant
with an effective β-blocker regimen
Resuscitated from cardiac arrest
Age 500?)
Males with LQT3
Family history of SCD is not a marker of high risk
4/10/2013
11

Case Presentation
• 24 year old white male with no prior known
significant medical history
• Developed flu-like illness and high spiking
fevers
• Had dizziness during one of the fever spikes
• Had frank syncope sitting at a desk checking
his e-mail during another fever spike
• ECG revealed classic Type I Brugada
pattern with fever
• Brugada pattern was not seen when fever
was not present
Brugada Syndrome
The Brugada Syndrome
Sudden death (due to VF) often at night; may be especially common in young
SE Asian men (SUDS)
J point elevation in V1-V3 and “RBBB” not always present; exacerbated by Na +
channel block, -blockers; improved by isoproterenol. Syncope/SCD may be
provoked by fever.
Provocation by sodium channel blockers implicated SCN5A.
SCN5A mutations causing loss of I Na function– through multiple mechanisms –
now identified in ~20% of affected subjects. GPD1L mutations identified in a
large kindred.
4/10/2013
12

Brugada Syndrome Mechanisms
Benito Progr Cardiovasc Dis 2008; 51:1-22
ECG in Brugada Syndrome
Brugada Syndrome Management
Benito et al. Progr Cardiovasc Dis 2008;51:1-22.
4/10/2013
13

Catecholaminergic Polymorphic VT
Mutations in genes controlling intracellular calcium
• Autosomal dominant (CPVT1):
Mutations in the ryanodine release channel
(RYR2) Sarcoplasmic Reticulum (SR) Ca 2+
“leak”
Exercise-related PVT
-blockers effective; Ca 2+ channel blockers
are not
• Autosomal recessive (CPVT2)
One large Bedouin kindred
Mutations in calsequestrin (an SR Ca 2+
buffering protein)
Bidirectional VT and Ventricular Fibrillation in CPVT
Human CPVT
RyR2
Knockout
Mouse
Priori, S. G. et al. J. Clin. Invest. 2005;115:2033-2038
CPVT – Exercise Test
Catecholaminergic Polymorphic VT
Take Home Points
1. ECG is essentially normal at rest
2. Exercise induced PVCs with bigeminy –Think CPVT
3. Patients should be restricted from competitive athletics
4. If symptomatic and normal QTc –Think CPVT instead of
“concealed LQT1”
5. RyR2 CPVT (CPVT1) ~ 50 –65% of CPVT
6. 15% SUD/12% SIDS – RyR2 positive
7. CPVT1 is more severe and less responsive to beta blocker
therapy than LQT1
From Ackerman MJ, HRS 2007.
4/10/2013
14

Case Presentation
• 34 y/o former athlete and now
offshore worker
• Presented while running as he runs
3 to 5 miles per day four times per
week
• Severe dizziness and near syncope
• Flagged down car who took him
HOME
• Wife insisted he go to hospital
12-lead ECG Induction of VT
4/10/2013
15

RV Gram: Cardiac MR:
Axial T1-weighted black blood spin-echo images
Transmural fatty replacement of the right ventricular myocardium (RV) and the
right ventricular outflow tract (RVOT)
4/10/2013
16

Anatomy:
Localized or general dilatation of the RV myocardium
associated with thinning of the affected regions
The myocardium is progressively replaced with transmural
fibrous and fatty tissue with scattered residual myocardium
It can also affect the LV
Triangle of dysplasia: Diaphragmatic RV, Infundibulum and
apex.
Recommendations:
Patients with ARVC should NOT participate in
competitive sports
ICD for secondary prevention
ICD for primary prevention if ARVD w/ high risk*
features
Anti-arrhythmics for pts who don’t want or can’t
have an ICD
Pts w/ ARVD + ICD who still have arrhythmias
consider anti-arrhythmic
ARVD Pts + ICD + antiarrhythmics, consider RFA
If anti-arrhythmics to be used consider sotalol or
amiodarone
*Extensive dz, LV involvement, FHx of SCD, unexplained syncope
Transmural fatty
infiltration
Anatomy:
Triangle of dysplasia
Arrhythmogenic Right
Ventricular Dysplasia
Cardiac Arrest
Sustained VT
Unequivocal Syncope
Extensive Myocardial Disease
Frequent NSVT
Family history of SCD
4/10/2013
17

Congenital coronary anomalies
• Anomalous origin of the left main or left anterior
descending coronary artery from the right sinus of
Valsalva is most common
• Cardiac arrest may be the first manifestation
Normal Anomalous
from Cheitlin MD, Circ 1974
Normal Coronary Anatomy
Pete Maravich and Single Coronary
“Pistol” Pete Maravich:
shattering records
•Pete Maravich had a style of
play that was twenty years
ahead of his time
•This gift enabled him to
currently hold every major
NCAA scoring record
•NCAA career record for
most points (3,667 points in
83 games)
•NCAA record for highest per
game average (44.5 ppg)
•NCAA record for most
games over 50 points (28)
Playing guard with
LSU, his father
Maravich was head
coach
“Pistol” Pete Maravich:
the original showtime
•He had a brilliant career with three NBA teams
•NBA All-Rookie Team
•All NBA First Team (‘76, ’77)
•Five-time NBA All-Star ((’73, ’74, ’77, ’78, ’79)
•Led NBA in scoring in 1977 (31.1 ppg)
•Scored 15,948 points (24.2 ppg) in 658 games
•NBA 50th Anniversary All-Time Team (1996)
•NBA Hall of Fame (1987)
•Voted one of the 50 greatest players of all time
•He played for 10
consecutive seasons in
the NBA, but in the end he
collapsed and died at age
40 playing a pickup game
•He was found to have
only one coronary artery
instead of the normal two
•It is suspected that he
died of a terminal
arrhythmia due to this
undiagnosed congenital
heart defect
Patient killer :Congenital Anomaly
•Maravich was born with one coronary artery causing
hypertrophy of the myocardium that was likely the source
of his arrhythmia.
•His defect is reported to occur in less than .1% of the
human population.
•Normal coronary anatomy versus Maravich’s heart
(above).
4/10/2013
18

Case Presentation
• 18 y/o Ole Miss football player
becomes weak and lightheaded at
football practice
• Something is different this time !!
• Difficulty standing up due to weakness
and chest hurts
• Coaches take him immediately to
student health center
• Collapses and full arrest as ECG leads
are being attached
• Immediate defibrillation
Wolff-Parkinson-White Syndrome
SVT
4/10/2013
19

Wolff-Parkinson-White Syndrome Normal AV Conduction
Accessory Pathway in Sinus Rhythm (WPW) AV Reentry Tachycardia
4/10/2013
20

Pre-Excitation Syndromes (WPW)
Surface EKG
P wave
R wave
T wave
Morady F. NEJM 1999
Intracardiac EGM Enlarged View of AV Groove
RF Catheter Site for Left Sided Accessory
Pathway
Atrial Fibrillation with WPW
4/10/2013
21

WPW: Atrial Fibrillation Degenerating to Ventricular
Fibrillation
Elimination of Accessory Pathway Function
and Cure of WPW Syndrome
4/10/2013
22

Nonischemic Dilated CM
SCD/HFT Data Unexplained Syncope
If Class II-III CHF &
EF < =35%, then
ICD
IHD EF < 40,>35
Syncope or NSVT
YES
EPS
VT Induced
ICD
Long QT or Brugada
Syncope Asymptomatic
ICD
Medical Individual
And/or ICD Approach
SCD survivor or spontaneous
VT/VF not due to a transient
or reversible cause and cannot
be successfully ablated
IHD EF

Animation – Ventricular
Dysynchrony
Click to Start/Stop
Miracle Trial Conclusions
In NYHA Class III and IV heart failure
patients with ventricular dysynchrony
and with or without an ICD indication,
CRT significantly improves quality of
life, NYHA class, and maximal exercise
capacity (peak VO 2, exercise time)
CRT adds incremental benefit to the
treatment of heart failure
Clinical Consequences of
Ventricular Dysynchrony
Abnormal
interventricular septal
wall motion1 Reduced dP/dt3,4 Reduced pulse
pressure4 Click to Start/Stop
1 Grines CL, Bashore TM, Boudoulas H, et al. Circulation 1989;79:845-853.
2 Xiao, HB, Lee CH, Gibson DG. Br Heart J 1991;66:443-447.
3 Xiao HB, Brecker SJD, Gibson DG. Br Heart J 1992;68:403-407.
4 Yu C-M, Chau E, Sanderson JE, et al. Circulation. 2002;105:438-445.
Conclusions
Reduced EF and CO4 Reduced diastolic
filling time1,2,4 Prolonged MR
duration1,2,4 In NYHA Class III and IV heart failure patients with
ventricular dyssynchrony CRT significantly
improves:
– Quality of life
– NYHA class
– Maximal exercise capacity (peak VO2, exercise time)
CRT adds incremental benefit to the treatment of
heart failure
What About MORTALITY?
4/10/2013
24

COMPANION
Comparison of Medical Therapy, Pacing, and
Defibrillation in Chronic Heart Failure
Published in 2004
Hypothesis: Can CRT decrease morbidity and
mortality in Class III-IV HF patients over drugs
alone?
Patient population: 1,520
Study design: randomized, three arms
– CRT group (no defibrillation)
– CRT-D group
– Conventional therapy group (no device)
Inclusion criteria: NYHA Class III-IV,
LVEF≤35%, QRS ≥ 120 ms
Exclusion criterion: Standard ICD or pacing
indication
COMPANION Conclusions
CRT-D in combination with OPT
reduced the risk of all-cause mortality
by 36% when compared to OPT alone
COMPANION RESULTS
Both CRT and CRT-D decreased the risk of allcause
mortality or first hospitalization for any
reason by about 20% over conventional therapy
CRT-D reduced mortality (p=0.003) by 36%
CRT-P reduced mortality (p=0.059) by 24%
For death from or hospitalization for a CV cause
– CRT reduced risk 25%
– CRT-D reduced risk 28%
For death from or hospitalization for HF
– CRT reduced risk 34%
– CRT-D reduced risk 40%
Indications for the ICD Cardiac
Resynchronization Systems
CRT ICD systems are indicated
for the reduction of HF
symptoms in patients that meet
the following criteria:
– Standard ICD indication
– Moderate to severe heart failure
(NYHA Class III/IV)
– QRS 120 – 130 ms
– LV ejection fraction 35%
– Symptomatic despite stable,
optimal medical therapy
4/10/2013
25

Implant Procedure
Coronary Sinus Angiograms
AP View LAO View
Click to Start/Stop
Implantation of a Biventricular Device
Note visible branches Coronary Sinus Angiograms – Victim of
Anatomy
Varying Patient Anatomy
4/10/2013
26

Venous Anatomy
Lead in Lateral Cardiac Vein
Thank You !!!
AP Position
Lead Placed in Target Vein
LAO View Lateral Coronary Vein Placement
4/10/2013
27