Transcript Advances in EP Cardiology - For Medical Professionals

Electrophysiology 2011
Taresh Taneja, MD, FACC
Assistant Professor of Medicine
Texas A & M HSC COM
Scott & White Hospital
“The more things change, the more they
stay the same.”
Jean-Baptiste Alphonse Karr
EP 2011
Sudden Cardiac Death
 Cardiac Resynchronization Therapy
 Syncope
 Atrial Fibrillation

Case Vignette
• A 74-year-old man with a history of hypertension and
myocardial infarction that occurred 5 years previously
presents with breathlessness on exertion.
• His current medications include a statin and aspirin.
• On examination, his pulse is 76 beats per minute and
regular, and his blood pressure is 121/74 mm Hg.
• There is jugular venous distention, lateral displacement of
the apex beat, and edema in his lower limbs.
• The lung examination is normal.
• An echocardiogram shows left ventricular dilatation, globally
reduced contractility, and an ejection fraction of 33%.
• How should his case be managed?
Pathophysiology of Systolic Heart Failure
McMurray J. N Engl J Med 2010;362:228-238
Clinical Classifications of Heart Failure Severity
McMurray J. N Engl J Med 2010;362:228-238
Treatment Algorithm for Systolic Heart Failure
McMurray J. N Engl J Med 2010;362:228-238
Telemetry Strip Showing Pause-Independent
Polymorphic Ventricular Tachycardia.
Britton KA et al. N Engl J Med 2010;362:1721-1726.
Sudden Cardiac Death (SCD)
Death from unexpected circulatory arrest,
usually due to cardiac arrhythmia
occurring within an hour of the onset of
symptoms.
Sudden Cardiac Arrest (SCA)- Episode of
resuscitated SCD
Sudden Cardiac Death




Estimates range 200,000 - 450, 000 SCD’s
annually depending on the definition used.
13% of all natural deaths are SCD using the
1 hour definition.
50% of all CHD deaths are sudden.
Overall incidence of SCD 1 to 2/1000
population.
36 cc
Implantable Cardioverter
Defibrillator (ICD)
Secondary Prevention- Multiple studies
have shown a 50% relative-risk reduction
in arrhythmic death and a 25% relativerisk reduction in all-cause mortality.
Patients who die once are more likely to
die again.
Primary Prevention of SCD
• Patients with a history of myocardial
infarction and a reduced ejection fraction
are at increased risk for life-threatening
ventricular arrhythmias.
• Which of these patients are the most
appropriate candidates for implantable
cardioverter–defibrillator (ICD) therapy is
unclear.
Summary of Major Randomized Trials of ICD Therapy
for Primary Prevention of Sudden Death after
Myocardial Infarction
Myerburg R. N Engl J Med 2008;359:2245-2253
Amiodarone or an Implantable CardioverterDefibrillator for Congestive Heart Failure
Gust H. Bardy, M.D., Kerry L. Lee, Ph.D., Daniel B. Mark, M.D., Jeanne E. Poole,
M.D., Douglas L. Packer, M.D., Robin Boineau, M.D., Michael Domanski, M.D.,
Charles Troutman, R.N., Jill Anderson, R.N., George Johnson, B.S.E.E., Steven E.
McNulty, M.S., Nancy Clapp-Channing, R.N., M.P.H., Linda D. Davidson-Ray, M.A.,
Elizabeth S. Fraulo, R.N., Daniel P. Fishbein, M.D., Richard M. Luceri, M.D., John H.
Ip, M.D. and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)
Investigators
N Engl J Med
Volume 352;3:225-237
January 20, 2005
Study Overview




This placebo-controlled study compared the
effect of amiodarone and an implantable
cardioverter-defibrillator (ICD) on mortality
in patients with New York Heart Association
class II or III congestive heart failure (CHF)
Amiodarone had no benefit overall and
slightly increased mortality among patients
with class III CHF
ICD therapy reduced mortality overall, but
the benefit appeared to be restricted to
patients with class II CHF
These important results will broaden the use
of ICD therapy
SCD-HeFT Protocol
DCM + CAD and CHF
EF < 35%
NYHA Class II or III
6-Minute Walk, Holter
R
Placebo N = 847
Amiodarone N = 845
2521 Patients
ICD Implant N = 829
Minimum of 2.5 years follow-up required
45 months average follow-up
Optimized B, ACE-I, Diuretics
Bardy GH. N Engl J Med. 2005;352:225-237.
Kaplan-Meier Estimates of Death from Any Cause
Bardy, G. et al. N Engl J Med 2005;352:225-237
Kaplan-Meier Estimates of Death from Any Cause for
the Prespecified Subgroups of Ischemic CHF (Panel A)
and Nonischemic CHF (Panel B)
Bardy, G. et al. N Engl J Med 2005;352:225-237
Kaplan-Meier Estimates of Death from Any Cause for
the Prespecified Subgroups of NYHA Class II (Panel A)
and Class III (Panel B)
Bardy, G. et al. N Engl J Med 2005;352:225-237
Hazard Ratios for the Comparison of Amiodarone and ICD
Therapy with Placebo in Various Subgroups of Interest
Bardy, G. et al. N Engl J Med 2005;352:225-237
Conclusions

In patients with NYHA class II or III CHF
and LVEF of 35 percent or less, amiodarone
has no favorable effect on survival, whereas
single-lead, shock-only ICD therapy reduces
overall mortality by 23 percent
Incremental Cost-Effectiveness
Cardiovascular Interventions
Incremental Cost per Life-Year Saved
$200,000
Economically
Unattractive
$150,000
$135,000
$120,000
Expensive
$67,000
Borderline
Cost-Effective
$40,750
Cost-Effective
$17,701
Highly
Cost-Effective
$8,461
PTCA
Hypertension
CABG
(chronic CAD,
Therapy
(chronic
severe angina
(diastolic
CAD
1 VD)
95 - 104
mild angina,
mmHg)
3 VD)
End Stage
Renal
Disease
Treatment
Exercise
SPECT
(atypical
angina who
can walk
on treadmill)
Lovastatin
(chol. =
290 mg/dL,
50 yrs old,
male,
no risk
factors)
Carotid
Disease
Screening
(65 yrs old,
male,
no
symptoms)
Routine
Coronary
Angiography
(35 - 84 yrs
old,
low risk MI,
has CHF)
Incremental Cost per Life-Year Saved
Incremental Cost-Effectiveness
ICD, CRT, and CRT-D Therapies
Economically
Unattractive
Expensive
$67,000
$50,000
$28,000
$33,000
Borderline
Cost-Effective
$38,200
Cost-Effective
Highly
Cost-Effective
COMPANION
CRT1
1 Feldman AM.
SCD-HeFT
ICD2
COMPANION
CRT-D1
www.theheart.org. ACC News. March 16, 2005.
Mark DB. www.theheart.org. AHA News. November 11, 2004.
3 Ak-Khatib S. Ann Intern Med. 2005;142:593-600.
4 Larsen G. Circulation. 2002;105:2049-2057.
2
MADIT-II
ICD3
AVID
ICD4
Original Article
Defibrillator Implantation Early after Myocardial
Infarction
Gerhard Steinbeck, M.D., Dietrich Andresen, M.D., Karlheinz Seidl, M.D., Johannes
Brachmann, M.D., Ellen Hoffmann, M.D., Dariusz Wojciechowski, M.D., Zdzisława
Kornacewicz-Jach, M.D., Beata Sredniawa, M.D., Géza Lupkovics, M.D., Franz
Hofgärtner, M.D., Andrzej Lubinski, M.D., Mårten Rosenqvist, M.D., Alphonsus
Habets, Ph.D., Karl Wegscheider, Ph.D., Jochen Senges, M.D., for the IRIS
Investigators
N Engl J Med
Volume 361(15):1427-1436
October 8, 2009
Study Overview
• Implantation of a defibrillator early after
myocardial infarction (MI) in high-risk
patients reduced the risk of sudden cardiac
death, but there was a reciprocal increase in
the risk of nonsudden cardiac death
• Overall mortality was not affected by early
defibrillator implantation, and therefore this
intervention cannot be recommended after
MI in high-risk patients
Baseline Demographic and Clinical Characteristics of the
Patients, According to Study Group
Steinbeck G et al. N Engl J Med 2009;361:1427-1436
Cumulative Risk of Death from Any Cause According to Study
Group
Steinbeck G et al. N Engl J Med 2009;361:1427-1436
Cumulative Risk of Cardiac Death, According to Study Group
Steinbeck G et al. N Engl J Med 2009;361:1427-1436
Conclusion
Prophylactic ICD therapy did not reduce
overall mortality among patients with acute
myocardial infarction and clinical features
that placed them at increased risk
ICD implantation Post Acute MI



Acute MI-Sudden Cardiac Death paradox
firmly established
SCD post-MI may not be due to arrhythmia
alone
Potential deleterious effect of ICD implantation
and testing
?
Sudden cardiac death after myocardial
infarction in patients with type 2 diabetes
M. Juhani Junttila, MD, Petra Barthel, MD, Robert J. Myerburg, MD, Timo H. Mäkikallio,
MD, Axel Bauer, MD, Kurt Ulm, PhD, Antti Kiviniemi, PhD, Mikko Tulppo, PhD, Juha S.
Perkiömäki, MD, Georg Schmidt, MD and Heikki V. Huikuri, MD
Heart Rhythm
Volume 7, Issue 10, Pages 1396-1403 (October 2010)
DOI: 10.1016/j.hrthm.2010.07.031
Sudden cardiac death after myocardial
infarction in patients with type 2 diabetes



Study population included enrollees in two
prospective post-MI studies: Multiple Risk
Factor Analysis Trial and Improved
Stratification of Autonomic Regulation for Risk
Prediction postinfarction survey program.
3276 acute MI patients
Diabetic vs Non Diabetic patients: Mean Age
64 vs 59 years, 32 vs 22% females, LVEF
49% vs 52, 3 vs CAD 42 vs 30%
Figure 1
Figure 2
Aggregate National Experience With the Wearable
Cardioverter-Defibrillator: Event Rates, Compliance,
and Survival
Chung et al. JACC. 2010;56;194
3,569 patients
Indications: ICD explants (23.4%), VT/VF (16.1%), LVEF
≤ 35% with Recent MI (12.5%), Post-CABG (8.9%),
Nonischemic CM (20.0%), and LVEF> 35% with recent MI
(3.8%)
Actual WCD Use
Chung, M. K. et al. J Am Coll Cardiol 2010;56:194-203
Copyright ©2010 American College of Cardiology Foundation. Restrictions may apply.
Aggregate National Experience With the Wearable
Events While Wearing the WCD
Cardioverter-Defibrillator
Chung, M. K. et al. J Am Coll Cardiol 2010;56:194-203
Copyright ©2010 American College of Cardiology Foundation. Restrictions may apply.
Original Article
An Entirely Subcutaneous Implantable
Cardioverter-Defibrillator
Gust H. Bardy, M.D., Warren M. Smith, M.B., Margaret A. Hood, M.B., Ian G. Crozier,
M.B., Iain C. Melton, M.B., Luc Jordaens, M.D., Ph.D., Dominic Theuns, Ph.D.,
Robert E. Park, M.B., David J. Wright, M.D., Derek T. Connelly, M.D., Simon P. Fynn,
M.D., Francis D. Murgatroyd, M.D., Johannes Sperzel, M.D., Jörg Neuzner, M.D.,
Stefan G. Spitzer, M.D., Andrey V. Ardashev, M.D., Ph.D., Amo Oduro, M.B., B.S.,
Lucas Boersma, M.D., Ph.D., Alexander H. Maass, M.D., Isabelle C. Van Gelder,
M.D., Ph.D., Arthur A. Wilde, M.D., Ph.D., Pascal F. van Dessel, M.D., Reinoud E.
Knops, M.D., Craig S. Barr, M.B., Pierpaolo Lupo, M.D., Riccardo Cappato, M.D.,
and Andrew A. Grace, M.B., Ph.D.
N Engl J Med
Volume 363(1):36-44
July 1, 2010
Locations of the Components of a Subcutaneous
Implantable Cardioverter-Defibrillator In Situ
Bardy GH et al. N Engl J Med 2010;363:36-44
Chest Radiographs and an Electrocardiogram in a Patient Who
Underwent Placement and Testing of a Subcutaneous
Implantable Cardioverter-Defibrillator (ICD)
Bardy GH et al. N Engl J Med 2010;363:36-44
Cardiac Resynchronization
Therapy
Case Vignette





A 55-year-old man who had had an anterior-wall
myocardial infarction six months previously is
admitted with an exacerbation of congestive heart
failure.
An electrocardiogram shows sinus rhythm with a
left bundle-branch block; an echocardiogram
demonstrates a left ventricular ejection fraction of
25 percent.
He is treated with furosemide, lisinopril, and
carvedilol.
However, during an office visit three months later,
he reports persistent shortness of breath with mild
exertion.
He is referred to a cardiologist, who recommends
implantation of a biventricular pacemaker.
The Cardiac Conduction System and Biventricular Pacing
Jarcho J. N Engl J Med 2006;355:288-294
The Cardiac Conduction System and
Biventricular Pacing
In patients with a LBBB, conduction of the wave
of depolarization in the left ventricle is
markedly altered, proceeding from the anterior
septum through the left ventricular
myocardium to the inferior and lateral left
ventricular walls- left ventricular contraction is
dyssynchronous, mechanically inefficient with
decreases in left ventricular ejection farction
and cardiac output.
CRT- The Evidence
Trial
Patients
Age
(yrs)
LVEF
MetaAnalysis
1,634
63-66
21-23% 37-69%
158-176 54-87% 23%
65
22%
158
COMPANION 1,520
CAD
56%
QRS
(ms)
LBB
71%
MR▼
24%
1520 patients, NYHA III/ IV, QRS  120 ms, EF  35%
RANDOMIZED
Optimal medical therapy vs. OMT + cardiac resynchronization
pacemaker vs. OMT + cardiac resynchronization defibrillator
CRT Indications


Class I- EF ≤ 35%, QRS ≥ 0.12 sec, SR,
NYHA III/ Ambulatory Class IV + OMTCRT±ICD
Class IIA- EF ≤ 35%, QRS ≥ 0.12 sec, AF,
NYHA III/ Ambulatory Class IV + OMTCRT±ICD
Original Article
Cardiac-Resynchronization Therapy for the
Prevention of Heart-Failure Events
Arthur J. Moss, M.D., W. Jackson Hall, Ph.D., David S. Cannom, M.D., Helmut Klein,
M.D., Mary W. Brown, M.S., James P. Daubert, M.D., N.A. Mark Estes, III, M.D.,
Elyse Foster, M.D., Henry Greenberg, M.D., Steven L. Higgins, M.D., Marc A. Pfeffer,
M.D., Ph.D., Scott D. Solomon, M.D., David Wilber, M.D., Wojciech Zareba, M.D.,
Ph.D., for the MADIT-CRT Trial Investigators
N Engl J Med
Volume 361(14):1329-1338
October 1, 2009
Kaplan-Meier Estimates of the Probability of Survival Free of Heart Failure
Moss AJ et al. N Engl J Med 2009;361:1329-1338
Conclusion
CRT combined with ICD
decreased the risk of heartfailure events in relatively
asymptomatic patients with a
low ejection fraction and wide
QRS complex
MADIT-CRT
Editorial- Mariell Jessup, MD




CRT benefit solely driven by a 41% reduction in risk
of first heart failure event, since mortality not
influenced.
In CRT trials with symptomatic patients, 29 patients
need to be treated for 6 months, 13 patients for 2
years and 9 patients for 3 years to prevent 1 death.
MADIT CRT enrolled patients with stage C and NOT
stage B (truly asymptomatic).
MADIT CRT- treat 12 patients to prevent 1 heart
failure hospitalization
Cardiac Resynchronization- Effect of
Bundle Branch Block




Analyzed the results of MADIT-CRT
1820 patients, NYHA I/II, LVEF≤ 30%, QRS
≥130 ms, on optimal medical therapy
1281 LBBB, 228 RBBB, 308 IVCD
Hazard ratios for the primary end-point of
death or heart failure event were significantly
lower in the LBBB patients than in the nonLBBB patient.
Zareba et al. JACC 2011
Cardiac Resynchronization In Hypertrophic
Obstructive Cardiomyopathy



Biventricular pacing was attempted in 12
severely symptomatic HOCM patients and
was successful in 9 patients.
Functional capacity and QOL improved
NYHA class decreased from 3.2±0.4 at
baseline to 1.4±0.5 at 1 year with a reduction
in the LV gradient from 74±23 mmHg at
baseline to 28±17 mmHg at 1 year.
Berruezo et al. Heart Rhythm 2011
US Registry of Sudden Death in
Athletes




Healthy young competitive athletes assembled
over 27 years, 1,866 died suddenly (or survived
cardiac arrest).
Sudden death were due to cardiovascular
disease in 56% and 82% occurred with
physical exertion.
HCM – 36% and congenital coronary
anomalies- 17%
Pre-participation screening with history, PE and
EKG did not impact the rate of sudden death.
Maron et al. Circ. 2009;119:1085
US Registry of Sudden Death in
Athletes
US Registry of Sudden Death in
Athletes
Pathophysiology of Commotio Cordis
Maron B, Estes N. N Engl J Med 2010;362:917-927
Syncope
Transient loss of consciousness due to transient
global cerebral hypoperfusion characterized by
rapid onset, short duration, and spontaneous
complete recovery.
www.escardio.org/guidelines
www.escardio.org/guidelines
www.escardio.org/guidelines
www.escardio.org/guidelines
Original Article
Lenient versus Strict Rate Control in Patients with
Atrial Fibrillation
Isabelle C. Van Gelder, M.D., Hessel F. Groenveld, M.D., Harry J.G.M. Crijns, M.D.,
Ype S. Tuininga, M.D., Jan G.P. Tijssen, Ph.D., A. Marco Alings, M.D., Hans L.
Hillege, M.D., Johanna A. Bergsma-Kadijk, M.Sc., Jan H. Cornel, M.D., Otto Kamp,
M.D., Raymond Tukkie, M.D., Hans A. Bosker, M.D., Dirk J. Van Veldhuisen, M.D.,
Maarten P. Van den Berg, M.D., for the RACE II Investigators
N Engl J Med
Volume 362(15):1363-1373
April 15, 2010
Study Overview
• This clinical trial of outcomes in patients
with atrial fibrillation showed that lenient rate
control (resting heart rate, <110 beats per
minute) was not inferior to strict rate control
(resting heart rate, <80 beats per minute)
• On the basis of the results, strict rate control
may be abandoned as a therapeutic
strategy in many patients with permanent
atrial fibrillation
Cumulative Incidence of the Composite Primary Outcome and Its Components during the 3-Year
Follow-up Period, According to Treatment Group
Van Gelder IC et al. N Engl J Med 2010;362:1363-1373
Kaplan-Meier Estimates of the Cumulative Incidence of the
Primary Outcome, According to Treatment Group
Van Gelder IC et al. N Engl J Med 2010;362:1363-1373
Conclusion
• In patients with permanent atrial
fibrillation, lenient rate control is as
effective as strict rate control and is
easier to achieve
Thromboemblic Risk in Atrial
Fibrillation
www.escardio.org/guidelines
www.escardio.org/guidelines
www.escardio.org/guidelines
www.escardio.org/guidelines
www.escardio.org/guidelines
AF guidelines update 2011Dabigatran

Class I

Dabigatran is useful as an alternative to warfarin
for the prevention of stroke and systemic
thromboembolism in patients with paroxysmal to
persistent AF and risk factors for stroke or
systemic embolization who do not have a
prosthetic heart valve or hemodynamically
significant valve disease, severe renal failure
(creatinine clearance < 15 ml/min) or advanced
liver disease (impaired baseline clotting function).
Level of evidence B
www.escardio.org/guidelines
Catheter ABlation versus
ANtiarrhythmic Drug Therapy in
Atrial Fibrillation (CABANA) Trial
Mayo Clinic Rochester
Duke Clinical Research Institute
National Heart Lung and Blood Institute
Future of AF--ATRIA Study
Projected Number of Adults with AF in the U.S.
7
6
5
Upper scenarios based on
sensitivity analyses
Lower scenarios based on
sensitivity analyses
4
Millions
3
2
1
0
1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050
Year
Go et al: JAMA 285:2370, 2001
Impact of Atrial Fibrillation on Mortality in
Framingham Study
55-74 Years Old
80
Dead (%)
60
Men AF
Women AF
Men no AF
Women no AF
75-94 Years Old
80
60
40
40
20
20
0
0
0 1 2 3 4 5 6 7 8 9 10
Follow-up (yr)
Benjamin et al: Circ 98:946, 1998
0 1 2 3 4 5 6 7 8 9 10
Follow-up (yr)
CABANA Trial Inclusion Criteria
Subjects must meet all of the following criteria
• Have documented AF episodes 1 hour in duration; with 2
episodes over 4 months with ECG documentation of 1 episode or at
least 1 episode of AF lasting >1 week
• Warrant active therapy beyond simple ongoing observation
• Be eligible for catheter ablation and 2 sequential rhythm control
and/or 3 rate control drugs
• Be 65 yr of age, or <65 yr with 1 of the following risk factors for
stroke
Hypertension
Diabetes
Congestive heart failure (including systolic or diastolic heart failure)
Prior stroke or TIA
LA size >5.0 cm (or volume index 40 cc/m2)
EF 35
CABANA Trial
Primary Objective and Hypothesis
The treatment strategy of percutaneous left atrial catheter
ablation for the purpose of eliminating atrial fibrillation
(AF) is superior to current state-of-the-art medical
therapy with either rate control or rhythm control drugs
for reducing total mortality (primary endpoint) and
decreasing the composite endpoint of total mortality,
disabling stroke, serious bleeding, or cardiac arrest (key
secondary endpoint) in patients with untreated or
incompletely treated AF warranting therapy
Design of the CABANA Study
Atrial fibrillation
Eligible for ablation and/or drug
therapy
65 yr of age
<65 yr w/ 1 CVA risk factor
R
Drug Rx & AC
• Rate control
• Rhythm Rx
1° ablation &
AC
• PV isolation
• Adjunctive
Follow-up
60 months
Descriptive analysis
• NSR vs AF impact
• w/ w/o heart disease
• AF type – (paroxysmal;
persistent; long-standing
persistent)
• CT/MR image analysis
• ECG/EGM analysis
CABANA Sites International Approach
Canada
10
UK
10
U.S.
90
Asia
5
Australia
NZ
5
South
Am
5
Europe
30