Predicting the Risk of Sudden Cardiac Death Leon Glass Isadore Rosenfeld Chair in Cardiology, McGill University, Montreal, Quebec
Predicting the Risk of Sudden
Cardiac Death
Leon Glass
Isadore Rosenfeld Chair in
Cardiology, McGill University,
Montreal, Quebec
Patents describing algorithm are
licensed to Medtronic • Medtronic Reveal XT™ ICM
Offers Important Insights into Patients’ Irregular Heart Rhythms, Including Atrial Fibrillation
• MINNEAPOLIS – Feb. 11, 2009 – Medtronic, Inc. (NYSE: MDT) today announced the commercial availability of its Reveal XT™ Insertable Cardiac Monitor (ICM) in the United States, along with the nation’s first implant of the new device.
The revolutionary Reveal LINQ™
Insertable Cardiac Monitoring System
is designed to help your doctor quickly
diagnose and treat irregular heartbeats
that may be related to unexplained
fainting.
• “Given the desirability of accurate risk
stratification [for sudden cardiac death]
and the long history of research in this
area, it is important to understand why the
field is not further advanced.” Jeffrey
Goldberger et al. Circulation 2011
Key Questions
• Laboratory: Understand complex rhythms
and transitions between rhythms in model
cardiac systems?
• Clinical: What therapies are available?
• Clinical: Who is at high risk for
tachyarrhythmic sudden cardiac death?
Dynamics in chick heart
cells – transitions
to reentrant dynamics
Thanks to my colleague
Alvin Shrier
Chaos in periodically stimulated
heart cells
(Guevara, Glass, Shrier Science ,1981)
Predict chaos based on
1D circle maps determined
from resetting experiments.
Resetting depends on phase
of stimulus.
Spiral waves in cardiac tissue -
role in atrial and ventricular
tachycardias?
• Theoretical predictions – Wiener and
Rosenblueth, Krinski, Winfree et al.
• Experimental observations – Jalife,
Witkowski and many others subsequently
density
a glycyrrhetinic acid
0 mm 5 mm 10 mm
high
periodic periodic burst
mid
periodic burst burst
low
irreg.burst irregular irregular
(Bub, Glass, Shrier, PRL 2005)
R=3, q=0.35
R=1.8, q=0.35
Target patterns (‘periodic’)
bursting
Cellular automata model – pacemakers,
heterogeneity, fatigue, connectivity
Spiral formation in tissue culture
with a central obstacle
Quail et al., Physical Review Letters 2014
Key Questions
• Laboratory: Understand complex rhythms
in model cardiac systems?
• Clinical: What therapies are available?
• Clinical: Who is at high risk for
tachyarrhythmic sudden cardiac death?
Implantable Cardioverter Defibrillators (ICD)
reduce the incidence of sudden death due to rapid
arrhythmias
But it is difficult to assess which patients will benefit from an ICD
Cheney's change-out: Vice president's ICD replaced
July 30, 2007 Steve Stiles
Washington, DC - Vice President Dick Cheney's implantable
cardioverter-defibrillator (ICD) was replaced Saturday at George Washington
University Hospital, news outlets reported over the weekend, citing a statement
made by his deputy press secretary Megan McGinn. There were no
complications, and the vice president emerged from the hospital about four
hours after he entered, according to the reports.
The procedure had been scheduled after a check of the device during the vice
president's annual physical last month showed the battery was nearing the end
of its lifetime. The device was implanted in 2001 and, according to the vice
president's office, on no occasion did it deliver a shock. The lead system
wasn't replaced.
Cheney's cardiovascular health history is one of the world's most publicly
documented. As reported over the years by heartwire and news outlets virtually
everywhere, it includes four heart attacks before he became vice president, a
CABG, two PCIs, and an episode of deep venous thrombosis on a recent
international tour.
Re: Cost of ICD
Last year when I was in the hospital,
I was told it would cost $30,000 for the ICD
and the procedure.
We lost count at $100,000 for the complete hospitalization.
I am thankful I was able to pay my insurance premiums.
From the internet
Key Questions
• Laboratory: Understand complex rhythms
in model cardiac systems?
• Clinical: What therapies are available?
• Clinical: Who is at high risk for
tachyarrhythmic sudden cardiac death?
Analysis of arrhythmias in people
• Risk stratification for sudden cardiac death
• First analyze mechanisms of arrhythmia in
individual patients (this is NOT commonly
done now)
What is the mechanism of this rhythm?
16 year old boy who had an atrial septal
defect corrected at a young age who
fainted on the lunch line in a school
cafeteria. Does he have a high risk for
SCD?
Rules of Pure Parasystole Count the number of sinus beats between PVCs beats. In this sequence: (1) there are 3 integers; (2) one is odd; (3) the sum of the two smaller is one less than the largest.
Glass, Goldberger, Belair (1986)
Heartprint from a patient who had sudden cardiac death - Record 47 -
PhysioBank’s Sudden Cardiac Death Database
Potassium channel defects
• Long QT due to repolarization defects
• Possibility for early afterdepolarizations
leading to PVCs and inducing tachycardia
• Rule of “bigeminy” – bigeminal patterns
tend to perpetuate. Possible reason –
following a PVC there is a compensatory
pause leading to a longer recovery time
and long QT with a PVC
New Indices for Risk Assessment
• The coupling interval (short versus long)
• The maximum value of the NIB
• Examine data from the CARISMA study –
(data from patients who have had a heart
attack and who have poor cardiac
function)
(Lerma, Ghanem, Gorelick, Glass, Huikuri,
2013)
• “Given the desirability of accurate risk
stratification [for sudden cardiac death]
and the long history of research in this
area, it is important to understand why the
field is not further advanced.” Jeffrey
GOLDBERGER et al. Circulation 2011
• Possible Reasons : (i) impossible; (ii) the
wrong people are studying the problem;
(iii) the data concerning arrhythmias is not
good enough; (iv) new strategy needed –
mechanisms in individual patients.
Acknowledgments
Collaborators: Michael Guevara, Alvin Shrier, Glen Ward, Ary Goldberger, Jacques Bélair, Hiroyuki Ito, Verena Schulte-Frohlinde, Taishin Nomura, Eugene Stanley, Plamen Ivanov, Gil Bub, Hortensia González, Yoshihiko Nagai, Katsumi Tateno, Kevin Hall, Jacques Billette, David Christini, Claudia Lerma, Chiu Fan Lee, Ben Steinberg, Alex Hodge, Min-Young Kim, Bart Borek, Alex Gorelick, Raja Ghanem, Heikki Huikuri, TK Shajahan, Thomas Quail, Manli Marquez
Funding Sources: NSERC, CIHR, MITACS, NIH (National Resource for Complex Physiologic Signals), Canadian Heart and Stroke Foundation, Medtronic