American Heart Association Update
“Highlights of the AHA”
“Duke at the AHA”
Cardiology Grand Rounds
November 23, 2010
John H. Alexander, MD
Director, Heart Center SBR
Co-Director, DCRI CV Research
John Alexander: Disclosures (2010)
Research Support: Bristol Myers Squibb, CSL Behring,
Medtronic Japan, Merck, NIH, Pfizer, Regado Biosciences
Consulting: Astra Zeneca, Boeringer Ingelheim, Bristol Myers
Squibb, CSL Behring, Medsphere, Novartis, Ortho-McNeilJannsen, Otsuka Pharmaceuticals, Regado Biosciences
Disclosures available:
https://dcri.org/about-us/conflict-of-interest
All Rights Reserved, Duke Medicine 2008
Agenda
• Hot Science
• Duke at the AHA
• Modern Communication
“The grand rounds tomorrow is intended to generate
discussion on how to incorporate the late-breaking science
into our clinical practice. So please join us and prepare to
discuss.” (Tracy Wang, MD - 11/22/10)
All Rights Reserved, Duke Medicine 2008
Hot Science
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ROCKET-AF
EMPHISIS-HF
ASCEND-HF
GRAVITAS
RACE-ER
REVEAL
DEFINE
sdfjaliex
All Rights Reserved, Duke Medicine 2008
Hot Science
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ROCKET-AF
EMPHASIS-HF
ASCEND-HF
GRAVITAS
RACE-ER
REVEAL
DEFINE
sdfjaliex
All Rights Reserved, Duke Medicine 2008
“It is Rocket Science!”
Risk Factors
Study Design
Atrial Fibrillation
Rivaroxaban
20 mg daily
15 mg for Cr Cl 30-49 ml/min
Randomize
Double Blind /
Double Dummy
(n ~ 14,000)
• CHF
At least 2 or
• Hypertension
3 required*
• Age  75
• Diabetes
OR
• Stroke, TIA or
Systemic embolus
Warfarin
INR target - 2.5
(2.0-3.0 inclusive)
Monthly Monitoring
Adherence to standard of care guidelines
Primary Endpoint: Stroke or non-CNS Systemic Embolism
* Enrollment of patients without prior Stroke, TIA or systemic embolism and only 2 factors capped at 10%
Primary Efficacy Outcome
Stroke and non-CNS Embolism
Cumulative event rate (%)
6
5
Event
Rate
Rivaroxaban
Warfarin
1.71
2.16
Warfarin
4
Rivaroxaban
3
HR (95% CI): 0.79 (0.66, 0.96)
2
P-value Non-Inferiority: <0.001
1
0
0
120
240
360
480
600
720
840
3407
3478
2472
2539
1496
1538
960
Days from Randomization
No. at risk:
Rivaroxaban 6958
Warfarin
7004
6211
6327
5786
5911
5468
5542
Event Rates are per 100 patient-years
Based on Protocol Compliant on Treatment Population
4406
4461
634
655
Primary Efficacy Outcome
Stroke and non-CNS Embolism
Rivaroxaban Warfarin
Event
Event
Rate
Rate
On
Treatment
N= 14,171
Rivaroxaban
better
P-value
1.70
2.15
0.79
(0.65,0.95)
0.015
2.12
2.42
0.88
(0.74,1.03)
0.117
N= 14,143
ITT
HR
(95% CI)
Warfarin
better
Event Rates are per 100 patient-years
Based on Safety on Treatment or Intention-to-Treat thru Site Notification populations
Key Secondary Efficacy Outcomes
Rivaroxaban
Warfarin
Event Rate
Event Rate
HR (95% CI)
P-value
4.51
4.81
0.94 (0.84, 1.05)
0.265
Stroke Type
Hemorrhagic
Ischemic
Unknown Type
0.26
1.62
0.15
0.44
1.64
0.14
0.58 (0.38, 0.89)
0.99 (0.82, 1.20
1.05 (0.55, 2.01)
0.012
0.916
0.871
Non-CNS Embolism
0.16
0.21
0.74 (0.42, 1.32
0.308
Myocardial Infarction
1.02
1.11
0.91 (0.72, 1.16)
0.464
All Cause Mortality
Vascular
Non-vascular
Unknown Cause
4.52
2.91
1.15
0.46
4.91
3.11
1.22
0.57
0.92 (0.82, 1.03)
0.94 (0.81, 1.08)
0.94 (0.75, 1.18)
0.80 (0.57, 1.12)
0.152
0.350
0.611
0.195
Vascular Death,
Stroke, Embolism
Event Rates are per 100 patient-years
Based on Intention-to-Treat Population
Primary Safety Outcomes
Rivaroxaban
Warfarin
Event Rate
or N (Rate)
Event Rate
or N (Rate)
HR
(95% CI)
Pvalue
3.60
2.77
1.65
0.82
0.24
3.45
2.26
1.32
1.18
0.48
1.04 (0.90, 1.20)
1.22 (1.03, 1.44)
1.25 (1.01, 1.55)
0.69 (0.53, 0.91)
0.50 (0.31, 0.79)
0.576
0.019
0.044
0.007
0.003
55 (0.49)
84 (0.74)
0.67 (0.47, 0.94)
0.019
Intraparenchymal
37 (0.33)
56 (0.49)
0.67 (0.44, 1.02)
0.060
Intraventricular
2 (0.02)
4 (0.04)
Subdural
14 (0.13)
27 (0.27)
0.53 (0.28, 1.00)
0.051
Subarachnoid
4 (0.04)
1 (0.01)
Major
>2 g/dL Hgb drop
Transfusion (> 2 units)
Critical organ bleeding
Bleeding causing death
Intracranial Hemorrhage
Event Rates are per 100 patient-years
Based on Safety on Treatment Population
Conclusions
 Efficacy:
 Rivaroxaban was non-inferior to warfarin for prevention of
stroke and non-CNS embolism.
 Rivaroxaban was superior to warfarin while patients were
taking study drug.
 By intention-to-treat, rivaroxaban was non-inferior to warfarin
but did not achieve superiority.
 Safety:
 Similar rates of bleeding and adverse events.
 Less ICH and fatal bleeding with rivaroxaban.
 Conclusion:
 Rivaroxaban is a proven alternative to warfarin for moderate or
high risk patients with AF.
Stroke or Systemic Embolism
Non-inferiority Superiority
p-value
p-value
Dabigatran 110 vs. Warfarin
<0.001
0.34
<0.001
<0.001
Dabigatran 150 vs. Warfarin
Margin = 1.46
0.50
0.75
1.00
1.25
HR (95% CI)
1.50
# at Risk
Year 0.5
1.0
1.5
2.0
2.5
6015
5900
5771
4666
3006
1420
D150
6076
5958
5817
4735
3080
1451
W
6022
5887
5759
4632
2933
1343
0.02
0.03
D110
0.01
Warfarin
Dabigatran150
Dabigatran110
0.0
Cumulative Hazard Rates
0.04
All Intracranial Bleeding
0
0.5
1.0
1.5
Years
2.0
2.5
Hot Science
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ROCKET-AF
EMPHASIS-HF
ASCEND-HF
GRAVITAS
RACE-ER
REVEAL
DEFINE
sdfjaliex
All Rights Reserved, Duke Medicine 2008
EMPHASIS-HF
EMPHASIS-HF: Major results
Outcome
Eplerenone (%)
Placebo (%)
Adjusted hazard ratio (95%
CI)
p
Cardiovascular death/heart-failure
hospitalization
Cardiovascular death
18.3
25.9
0.63 (0.54–0.74)
<0.001
10.8
13.5
0.76 (0.61–0.94)
0.01
Heart-failure hospitalization
12.0
18.4
0.58 (0.47–0.70)
<0.001
Hospitalization for hyperkalemia
0.3
0.2
1.15 (0.25–5.31)
0.85
NYHA Class II HF (N=2737)
LV EF < 30%
Eplerenone 25-50mg QD vs. Placebo
Hot Science
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ROCKET-AF
EMPHASIS-HF
ASCEND-HF
GRAVITAS
RACE-ER
REVEAL
DEFINE
sdfjaliex
All Rights Reserved, Duke Medicine 2008
“a small phase II trial in the eyes
of someone in the ACS world”
Background
 Acute heart failure is a major health problem responsible for
several million hospitalizations worldwide each year.
 Standard therapy has not changed since 1970s and includes
diuretics and variable use of vasodilators or inotropes.
 In 2001, nesiritide was approved by the FDA to reduce PCWP
and improve dyspnea, based on efficacy at 3 hrs.
 However, in 2005 two meta-analyses raised concerns regarding
the risks of mortality and renal injury.
 Subsequently, an independent panel* was convened by Scios Inc
and recommended that a clinical trial be conducted to definitively
answer the question of nesiritide’s safety and efficacy.
Co-Primary objectives
To assess whether nesiritide vs placebo,
in addition to standard care provides:
• Significant improvement
in self-assessed dyspnea
at 6 or 24 hrs
using 7-point Likert scale
60
Markedly Better
Moderately Better
40
% Subjects
• Reduction in rate of
HF rehospitalization
or all-cause mortality
through Day 30
20
0
Minimally Better
No Change
Minimally Worse
Moderately Worse
20
40
Markedly Worse
Study design and drug procedures
Nesiritide
Acute HF < 24 hrs
from IV RX
24–168 hrs Rx
Placebo
Co-primary
endpoint:
Dyspnea relief
at 6 and 24 hrs
Co-primary
endpoint:
30-day death or
HF rehosp
All-cause
mortality
at 180
days
 Double – blind placebo controlled
 IV bolus (loading dose) of 2 µg/kg nesiritide or placebo
• Investigator’s discretion for bolus
• Followed by continuous IV infusion of nesiritide 0.01 µg/kg/min or placebo
for up to 7 days
 Usual care per investigators including diuretics and/or other therapies as needed
 Duration of treatment per investigator based on clinical improvement
Co-Primary outcome: 30-day all-cause
mortality or HF rehospitalization
P=0.31
Hazard Ratio 0.93 (95% CI: 0.8,1.08)
12
10.1
10
9.4
Placebo
Nesiritide
8
%
6.1
6
4.0
4
6.0
3.6
2
0
30-day Death/HF
Rehospitalization
Risk Diff (95 % CI)
-0.7 (-2.1; 0.7)
30-day Death
-0.4 (-1.3; 0.5)
HF Rehospitalization
-0.1 (-1.2; 1.0)
Co-Primary Endpoint: 6 and 24 hour dyspnea
6 Hours
24 Hours
70
70
P=0.030
60
42.1%
44.5%
50
13.4
15.0
40
40
% Subjects
60
30
20
10
28.7
29.5
0
34.1
32.8
38.6
37.8
22.1
21.2
9.5
8.6
3398
Placebo
3371
Nesiritide
30
20
10
10
30
21.7
20.3
3444
Placebo
3416
Nesiritide
40
50
60
30.4
20
30
40
27.5
0
10
20
% Subjects
50
66.1% P=0.007 68.2%
Markedly Better
Moderately Better
Minimally Better
Minimally Worse
Moderately Worse
Markedly Worse
No Change
Renal Safety
Anytime Through Day 30
>25% decrease eGFR
Placebo
(n=3509)
Nesiritide
(n=3498)
P-value
29.5%
31.4%
0.11
1.0
1.0
0.9
0.9
0.8
0.8
0.7
0.7
0.6
0.5
0.4
0.6
0.5
0.4
0.3
0.3
0.2
0.2
0.1
0.1
0
0
2
4
6
Creatinine (mg/dL)
Nesiritide
Discharge or 10 day Creatinine
Cum Dist
Cum Dist
End of Treatment Creatinine
Placebo
8
0
0
2
4
6
Creatinine (mg/dL)
8
Hypotension
Risk
Difference
(95% CI)
Placebo
(n=3509)
Nesiritide
(n=3498)
Any hypotension
(Through Day 10/discharge)
15.3%
(538)
26.6%
(930)
(9.4 to 13.1)
Asymptomatic Hypotension
12.4%
(436)
21.4%
(748)
9.0
(7.2 to 10.7)
<.001
Symptomatic Hypotension
4.0%
(141)
7.1%
(250)
3.1
(2.1 to 4.2)
<.001
11.3
Pvalue
<.001
Conclusions
 Nesiritide did not reduce the rate of recurrent heart
failure hospitalization or death at 30 days.
 Nesiritide reduced dyspnea to a modest degree,
consistent with previous findings but did not meet prespecified protocol criteria for statistical significance at 6
and 24 hours.
 Nesiritide did not affect 30-day all cause mortality nor did
it worsen renal function as had been suggested by prior
meta-analyses of smaller studies.
Hot Science
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ROCKET-AF
EMPHISIS-HF
ASCEND-HF
GRAVITAS
RACE-ER
REVEAL
DEFINE
sdfjaliex
All Rights Reserved, Duke Medicine 2008
GRAVITAS Study Design
Elective or Urgent PCI with DES*
VerifyNow P2Y12 Test 12-24 hours post-PCI
PRU ≥ 230
R
High-Dose Clopidogrel†
clopidogrel 600-mg, then
clopidogrel 150-mg daily X 6 months
Standard-Dose Clopidogrel†
clopidogrel 75-mg daily X 6 months
Primary Efficacy Endpoint: CV Death, Non-Fatal MI, Stent Thrombosis at 6 mo
Key Safety Endpoint: GUSTO Moderate or Severe Bleeding at 6 mo
Pharmacodynamics: Repeat VerifyNow P2Y12 at 1 and 6 months
*Peri-PCI clopidogrel per protocol-mandated criteria to ensure steady-state at 12-24 hrs
†placebo-controlled
All patients received aspirin (81-162mg daily)
GRAVITAS Patient Flow
5429 patients screened with VerifyNow P2Y12
12-24 hours post-PCI
2214 (41%) with high residual
platelet reactivity
(PRU ≥ 230)
Clopidogrel
High Dose
N=1109
Clopidogrel
Standard Dose
N=1105
3215 (59%) without high
residual platelet reactivity
(PRU < 230)
Pharmacodynamics: Effect of SD vs HD Clopidogrel
Standard-Dose
500
P = 0.98
High-Dose
P < 0.001
400
PRU
value
Persistently high
reactivity @ 30
days: 62% vs 40%,
p<0.001
300
200
100
0
N=1105 N=1013 N=940
Post-PCI 30 d
ITT population
6 mo
N=1109 N=1012 N=944
Post-PCI 30 d
6 mo
Primary Endpoint: CV Death, MI, Stent Thrombosis
Observed event rates are listed; P value by log rank test.
Bleeding Events: Safety Population
Severe or life-threatening: Fatal bleeding, intracranial hemorrhage, or bleeding that causes hemodynamic compromise requiring
blood or fluid replacement, inotropic support, or surgical intervention
Moderate: Bleeding that leads to transfusion but does not meet criteria for severe bleeding
P by log rank test; observed event rates listed. HD, high-dose; SD, standard dose
GRAVITAS: Summary
• Compared with standard-dose therapy, high-dose
clopidogrel achieved a modest
pharmacodynamic effect in patients with high
residual reactivity.
• In patients with high residual reactivity measured
after PCI, 6-months of high-dose clopidogrel did
not reduce the rate of cardiovascular death, nonfatal MI, or stent thrombosis and did not increase
GUSTO severe or moderate bleeding.
Hot Science
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ROCKET-AF
EMPHASIS-HF
ASCEND-HF
GRAVITAS
RACE-ER
REVEAL
DEFINE
sdfjaliex
All Rights Reserved, Duke Medicine 2008
Reperfusion of Acute Myocardial
Infarction in Carolina Emergency
Departments – Emergency
Response (RACE-ER) Project
on behalf of RACE Coordinators, Nurses, Physicians,
Paramedics, and Administrators
Objectives
Regional approach to overcoming systematic
barriers
1) Increase reperfusion rate
2) Increase speed of reperfusion
RACE
Pilot
RACE
65 hospitals
2003
2005
2006
RACE - ER
119 hospitals
2007
2008
2009
RACE Hospitals by PCI and
Reperfusion Designation
Primary PCI (21)
Transfer for Primary PCI (52)
Lytics (31)
Mixed (15) (primary PCI if transport readily available
Reperfusion Strategy
Overall population, Eligible Patients
P = 0.0003 for PCI group trend
Use of Pre-hospital 12-lead ECG
(Direct presenters via EMS to PCI Centers)
Transfer Patients: Time to lytic or to device by
designation strategy
Hot Science
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ROCKET-AF
EMPHASIS-HF
ASCEND-HF
GRAVITAS
RACE-ER
REVEAL
DEFINE
sdfjaliex
All Rights Reserved, Duke Medicine 2008
A Randomized, Double-blind,
Placebo-controlled Trial of
Intravenous Erythropoietin in
Patients with ST-Segment Elevation
Myocardial Infarction – Primary
Results of the REVEAL Trial
STEMI n=110
Primary or rescue PCI
TIMI 0-1 flow in IRA
Successful PCI
- Randomize
- Study drug within 4 hrs
IV EPO
Matching saline
placebo
Infarct size in IRA territory 2-6 days by cMRI
Results: Primary endpoint
Mean (SE) infarct size at 2-6 days after study drug admin
25
Infarct Size (%LV)
20
15
EPO
Placebo
EPO vs. placebo
15.8% vs. 15.0%, P=NS
P-value adjusted for age, infarct location,
10
5
0
enrollment phase
Conclusions

These data, coupled with the lack of efficacy
seen in other STEMI trials involving EPO
(REVIVAL-31, HEBE III2), do not support the
hypothesis that EPO favorably impacts outcome
after reperfusion for STEMI

Whether earlier administration or alternate
dosing provides a cardioprotective effect of
EPO in humans remains to be determined
1Ott
I, et. al. Circ:CV Intv 2010
2Voors
AA, et. al. EHJ 2010
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ROCKET-AF
EMPHASIS-HF
ASCEND-HF
GRAVITAS
RACE-ER
REVEAL
DEFINE
sdfjaliex
All Rights Reserved, Duke Medicine 2008
Background: CETP inhibition
Cholesteryl ester transfer protein (CETP) is a plasma protein that catalyzes the transfer
of CE from HDL to apoB-containing lipoproteins (VLDL and LDL-C) in exchange for Trig.
LDL-R
CE
LDL /
VLDL
SR-B1
Liver
FC
X inhibition
CETP
CE
LCAT
Bile
FC
HDL
Free Cholesterol (FC)
in Extrahepatic tissues
Anacetrapib

Orally active, potent, selective CETP inhibitor

Robust lipid efficacy in Phase I-II studies

No effects on blood pressure, electrolytes, and
aldosterone in preclinical and Phase I-II clinical studies

In vitro HDL functional assays: HDL particles isolated
from anacetrapib-treated patients demonstrate preserved
(and possibly enhanced) cholesterol efflux properties

Dose of 100 mg selected based on PK/PD modeling:
minimal dose to achieve maximal effects on HDL and LDL
Study Design
Randomization
Study drug stopped if
LDL-C<25mg/dL during
treatment
1:1 Ratio
• Age: 18-80 years
Anacetrapib 100 mg n=750
• LDL-C @ NCEP
ATPIII goal < 100
mg/dL
12 week
follow-up
R
Placebo n=750
• Statin ± other lipid
modifying therapy
Stable dose-regimen of lipid-modifying therapy
Week
84 88
Visit
16 18
1
Screening
-2
0
6 12 18 24 30 38 46 54
2
3
4
Placebo
Run-in
5
6
7
8
9
Treatment Phase
10 11
62
12
70
13
76
14
80
15
Reversibility
Phase
Effects on LDL-C and HDL-C
LDLC
100
120
100
HDL-C (mg/dL) (SE)
LDL-C (mg/dL) (SE)
80
-39.8% (p<0.001)
60
40
20
0
HDL-C
Anacetrapib
Placebo
BaselineWk 6Wk 12Wk 18Wk 24Wk 30
80
60
40
20
Wk 46
Wk 62
Wk 76
Anacetrapib n = 804 771 716 687 646
604
568
540
Placebo n = 803 759 741 743 735
711
691
666
Study Week
+138.1% (p<0.001)
0
Anacetrapib
Placebo
BaselineWk 6Wk 12Wk 18Wk 24Wk 30
Wk 46
Wk 62
Wk 76
Anacetrapib n = 776 757 718 687 647
607
572
543
Placebo n = 766 761 741 744 736
711
691
666
Study Week
Lipid Parameters
Parameter
LS Mean Percent (95% CI) Placebo-Adjusted
Change from Baseline
Week 24
Week 76
Non-HDL-C
-31.7*
(-33.6, -29.8)
-29.4*
(-31.6, -27.3)
Apo B
-21.0*
(-22.7, -19.3)
-18.3*
(-20.2, -16.4)
Apo A-1
44.7*
(42.8, 46.5)
42.3*
(40.5, 44.1)
TC
13.7*
(12.0, 15.3)
15.6*
(13.8, 17.3)
TG
-6.8
(-9.9, -3.9)
Lp(a)
-36.4
(-40.7, -32.3)
ApoE
29.2*
(24.7, 33.7)
*p<0.001; means for all variables except for triglycerides, lipoprotein(a), for which medians are shown
-5.3
-38.8
35.3*
(-8.9, -1.7)
(-44.5, -33.9)
(30.6, 40.1)
Systolic blood pressure (mmHg)
Anacetrapib had no effect on
BP
22 0
20 0
180
16 0
SBP
140
120
10 0
80
60
40
A= A nac etrapib L
B = Placebo
20
0
Diastolic blood pressure (mmHg)
Baseline
6
12
18
24
140
30
Week
38
46
54
62
70
76
120
100
DBP
80
60
40
20
A= A nacetra pib L
B= Pl ac eb o
0
Baseline
6
12
18
24
30
Week
38
46
54
62
70
76

Anacetrapib treatment had robust effects on HDL-C,
LDL-C, non HDL-C and Lp(a) with sustained effects
over 18 months.

Anacetrapib had an acceptable side-effect profile with
no effects on blood pressure, electrolytes or
aldosterone.

Within the power of the study, anacetrapib did not
exhibit adverse cardiovascular effects seen with a prior
CETP inhibitor

The long term safety and efficacy of anacetrapib will
now be tested in a large clinical outcomes trial.
• 30,000 patients with occlusive arterial disease
in North America, Europe and Asia
• Background LDL-lowering with atorvastatin
• Randomized to anacetrapib 100 mg vs. placebo
• Scheduled follow-up: 4 years
• Primary outcome: Coronary death, myocardial
infarction or coronary revascularization
www.revealtrial.org
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ROCKET-AF
EMPHASIS-HF
ASCEND-HF
GRAVITAS
RACE-ER
REVEAL
DEFINE
●
sdfjaliex
All Rights Reserved, Duke Medicine 2008
PI3K Regulates 2-Adrenergic
Receptor Stimulated EGFR
Transactivation
Kevin M. Alexander, Supachoke Mangmool, Chetan
B. Patel, Kunhong Xiao, and Howard A. Rockman
Duke University Medical Center
Durham, NC
β-AR Mediated EGFR Transactivation
Noma et. al. (2007) J. Clin. Invest. and Engelhardt (2007) J. Clin. Invest.
PI3K is Required for 2AR
Mediated EGFR Transactivation
β2AR stable HEK-293 cells
EGFR Phosphorylation
Src Activity
 Both the lipid and protein kinase activity of PI3K are necessary
for 2AR mediated EGFR transactivation.
 PI3K protein kinase activity appears to lead to Src activation.
PI3K is Required for 2AR-EGFR
Complex Formation
Fluorescence Resonance Energy Transfer (FRET)
PI3K
Inhibition
Quantification of Src Phosphorylation Using
Stable Isotope Labelling with Amino Acids in
Cell Culture (SILAC)
Grow two populations of HEK-293 cells expressing HA-Src and β2AR
“Light” medium
“Heavy” medium
L-Arg
L-Lys HCl
[13C6, 15N2 ]-L-Lys HCl (+8)
[13C6, 15N4]-L-Arg (+10)
LY + ISO
ISO
Mix, IP, trypsin digest, and IMAC phosphopeptide enrichment
Phosphopeptide analysis by LC-MS
Relative Abundance
100
Extracted Ion
Chromatogram
(XIC)
Light
Heavy
0
Measure area under the curve
Sites of Src Phosphorylation by PI3K
SH3
SH2
PI3K Regulates β2AR Stimulated EGFR Transactivation
Function of PI3K in β2AR stimulated EGFR transactivation
1. Formation of PIP3
2. Src phosphorylation
Agenda
• Hot Science
• Duke at the AHA
• Modern Communication
All Rights Reserved, Duke Medicine 2008
Duke At the AHA
•
•
•
•
•
An Award
Presentations
Fellow Presentations
LBCT & LBSS
The Duke Reception
All Rights Reserved, Duke Medicine 2008
Award
• Dr. Victor Dzau receives the 2010 Research
Achievement Award at the AHA Opening
Sessions
All Rights Reserved, Duke Medicine 2008
Duke Presentations
All Rights Reserved, Duke Medicine 2008
Duke Presentations
•
•
•
•
•
•
Saturday November 13th
Sunday November 14th
Monday November 15th
Tuesday November 16th
Wednesday November 17th
Total
All Rights Reserved, Duke Medicine 2008
5
23
57
52
18
155
Duke Fellow Presentations (5)
Gerald Bloomfield
Studying Non-Communicable
Cardiovascular Diseases in sub-Saharan
Africa: One Fellow's Journey
Todd Kiefer, Lawrence Park,
Christophe Tribouilloy, Claudia
Cortes, Riccardo Utilli, Andrew
Wang
Heart Failure Complicating Infective
Endocarditis: An Analysis of In-Hospital
Mortality from the International
Collaboration on Endocarditis Prospective
Cohort Study
Prediction of In-Hospital Major Bleeding
Among Patients With Acute Myocardial
Infarction: Results From 90,273 Patients in
the Acute Coronary Treatment Intervention
Outcomes Network Registry&#174;- Get
With the Guidelines&#8482; (AR-G)
Are We Targeting the Right Economic
Metric for Heart Failure? Association of
Hospital 30-Day Heart Failure Readmission
Rates and Total Inpatient Days
Is Bleeding Risk Augmented With Acute
Therapies Across Increasing INR Levels
Among NSTEMI Patients on Home
Warfarin Therapy?
Robin Mathews, Eric D. Peterson,
Anita Y. Chen, Tracy Wang, Chee T.
Chin, Gregg C. Fonarow,
Christopher P. Cannon, Matthew T.
Roe, Karen P. Alexander
Robb D. Kociol, Li Liang, Adrian F.
Hernandez, Lesley H. Curtis, Paul
A. Heidenreich, Clyde W. Yancy,
Gregg C. Fonarow, Eric D. Peterson
Sumeet Subherwal, Eric D.
Peterson, Anita Y. Chen, Richard G.
Bach, Brian F. Gage, Deepak L.
Bhatt, Stephen D. Wiviott, Jeffrey
B. Washam, Matthew T. Roe, Karen
P. Alexander, Tracy Y. Wang
All Rights Reserved, Duke Medicine 2008
Early Career: Global
Cardiovascular Research
Training, Opportunities and
Experiences
Valvular Heart Disease:
Diagnosis, Pathophysiology and
Medical Management II
Best of AHA Specialty
Conferences Poster Session:
QCOR 2010
Best of AHA Specialty
Conferences Poster Session:
QCOR 2010
Atrial Fibrillation/Arrhythmias:
Epidemiology, Quality of Care
and Outcomes
Duke Fellow Presentations (9)
Chee Tang Chin, John C Messenger, Lisa
A Kaltenbach, Michael A Kutcher, H
Vernon Anderson, Matthew T Roe, Tracy Y
Wang
Comparison of Acute Coronary
Syndrome Patients Undergoing
Percutaneous Coronary Intervention for
Previously Stented versus De Novo
Culprit Lesions: Insights from the
National Cardiovascular Data Registry
CathPCI Registry
7118 - Pre-Treatment With
Thienopyridines Reduces The Amount of
Myonecrosis in Acute Coronary
Syndrome Patients Invasively Managed:
Insights from the CHAMPION trials
Sergio Leonardi, Amanda Stebbins,
Renato D Lopes, Yuliya Lokhnygina,
Deepak L Bhatt, Gregg W Stone, Michael A
Lincoff, Harold L Dauerman, C. Michael
Gibson, Harvey D White, Keyur Parick,
Luis Gruberg, Howard C Herrmann, Brent
T McLaurin, Shaun Goodman, Robert A
Harrington, Kenneth W Mahaffey
Kevin M Alexander, Supachoke
15645 - Phosphoinositde 3-Kinase
Mangmool, Chetan B Patel, Kunhong Xiao, Regulates &#946;2-Adrenergic Receptor
Howard A Rockman
Stimulated Epidermal Growth Factor
Receptor Transactivation
Thomas T Tsai, John C Messenger, J
19884 - Contemporary Risk of Follow-up
Matthew Brennan, Uptal D Patel, David
Adverse Events in Older Patients with
Dai, Robert Piana, Kevin J Anstrom, Eric L Chronic Kidney Disease and Dialysis
Eisenstein, Rachel S Dokholyan, Eric D
Undergoing Percutaneous Coronary
Peterson, Pamela S Douglas
Interventions: A Report from the Merged
NCDR CMS Registry
All Rights Reserved, Duke Medicine 2008
Acute Coronary Syndromes
and Percutaneous Coronary
Intervention: Quality of Care
and Outcomes
What's New in the
Treatment of Patients with
Acute Coronary
Syndromes?
Vascular Signaling
The Role of Comorbidities
in Cardiovascular Disease
Duke Fellow Presentations (14)
Jonathan P Piccini, Bradley G.
Hammill, Moritz F. Sinner, Paul N.
Jensen, Adrian F. Hernandez,
Susan R. Heckbert, Emelia J.
Ben, Lesley H. Curtis
Robin Mathews, Anita Y Chen,
Chee T Chin, Tracy Y Wang,
Kevin L Thomas, Matthew T Roe,
Eric D Peterson
Chee Tang Chin, Robert V Kelly,
Mauricio G Cohen, Marc Cohen, J
Richard Trout, Gregg W Stone,
Jan T Christenson, Robert J
Freedman Jr, Ramachandra C
Reddy, Debra Joseph, E Magnus
Ohman
Sergio Leonardi, L. Kristin
Newby, E. Magnus Ohman, Paul
W Armstrong
Zubin J Eapen, Shelby D Reed,
Lesley H Curtis, Adrian F
Hernandez, Eric D Peterson
All Rights Reserved, Duke Medicine 2008
Incidence of Atrial Fibrillation and Associated
Mortality among Medicare Beneficiaries from
1993 to 2007
Epidemiology and Outcomes
in Atrial Fibrillation
Short- and Long-term Outcomes Among Black
vs. White Patients with Non-ST-segment
Elevation Myocardial Infarction
Diagnosis and Outcomes
The Impact of Anticoagulation During Intra-Aortic
Balloon Counterpulsation Pump Placement on
In-Hospital Outcomes in 18,875 Patients
Undergoing Cardiac Revascularization
Heart Failure: Pacing and
Other Therapeutic Devices
Lack of Implementation of ESC/ACC Definition of
Myocardial Infarction in Contemporary
Randomized Clinical Trials
Do Heart Failure Disease Management Programs
Make Financial Sense Under a Bundled Payment
System?
From Acute Thrombotic to
Chronically Occluded
Coronary Arteries
Heart Failure: Disease
Management, Quality of
Care, Anemia
Duke Fellow Presentations (18)
Rajendra H Mehta, Jonathan P
Piccini, James T Tcheng, Martin
Fahy, Roxana Mehran, Gregg W
Stone, On Behalf of HORIZONS-AMI
Investigators
Robin Mathews, Eric D. Peterson,
Shuang Li, Matthew T. Roe,
Stephen D. Wiviott, Jorge F.
Saucedo, Elliott M. Antman, Tracy
Y. Wang
J. Matthew Brennan, Eric D
Peterson, Yue Zhao, Sean O'Brien,
Rachel Dokholyan, Pamela S
Douglas, Fred H Edwards
Jonathan P. Piccini, Jennifer A.
White, Rajendra H. Mehta, Sana M.
Al-Khatib, Pierluigi Tricoci, Charles
V. Pollack Jr, Gilles Montalescot,
Frans Van de Werf, C. Michael
Gibson, Robert A. Harrington, L.
Kristin Newby
All Rights Reserved, Duke Medicine 2008
Prognostic Significance of Post-Procedural
Sustained Ventricular Tachycardia or
Fibrillation in Patients Undergoing Primary
Percutaneous Coronary Intervention: Insights
from the HORIZONS AMI Trial
Under-utilization of Emergency Medical
Service Transport Among Contemporary
Patients with ST Elevation Myocardial
Infarction: Findings from the National
Cardiovascular Data Registry ACTION - Get
With The Guidelines
Predictors of Bioprosthetic Aortic Valve
Failure: Results in 73,616 Patients from the
Society of Thoracic Surgeons (STS) Adult
Cardiac Surgery National Database
Sustained Ventricular Tachycardia and
Ventricular Fibrillation are Infrequent Events
but are Associated with Increased Arrhythmic
and All-cause Death Following Non-STSegment Elevation Acute Coronary Syndromes
From Acute Thrombotic to
Chronically Occluded
Coronary Arteries
From Acute Thrombotic to
Chronically Occluded
Coronary Arteries
Cardiac Surgery: Valvular
Heart Disease (Not Including
Percutaneous Valves) IV
Noninvasive Arrhythmia
Testing/Risk Assessment
Duke LBCT & LBSS
• Late Breaking Clinical Trials
– ROCKET-AF
– ASCEND-HF
• Late Breaking Sciences Sessions
– RACE-ER
– REVEAL
All Rights Reserved, Duke Medicine 2008
“The Duke Reception”
Sponsors
Duke Heart Center
Duke Division of Cardiology
Duke Clinical Research Institute
Interviews at the DCRI Reception
Networking
Current Faculty & Fellows
Heart Center, Division, DCRI Staff
Former Fellows
Academic & Industry Collaborators
All Rights Reserved, Duke Medicine 2008
All Rights Reserved, Duke Medicine 2008
Agenda
• Hot Science
• Duke at the AHA
• Modern Communication
All Rights Reserved, Duke Medicine 2008
All Rights Reserved, Duke Medicine 2008
44 Shows Broadcast in Real
Time
Duke TV Temporarily Shut
Down for “Internet Abuse”
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15 13:55
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All Rights Reserved, Duke Medicine 2008
Dr. Hisao Ogawa reviews: ROCKET-AF and RELY, A Japanese Perspective in Japanese.
Dr. Robert Harrington, Dr. Robert Califf, Dr. C. Michael Gibson present: AHA 2010 wrap-up.
Dr. Robert Califf, Dr. Manesh Patel, Dr. Kenneth Mahaffey, and Dr. Keith Fox discuss: Stroke
Prevention Using the Oral Direct Factor Xa Inhibitor Rivaroxaban Compared with Warfarin in
Patients with Nonvalvular Atrial Fibrillation (ROCKET-AF).
Dr. Matthew Price presents: Standard Versus High-Dose Clopidogrel According to Platelet
Function Testing After PCI: Results of the GRAVITAS Trial.
Dr. Robert Califf, Dr. Adrian Hernandez, Dr. Christopher O'Connor and Dr. Randy Starling
discuss: Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Dr.
Clyde Yancy presents ASCEND: Historical perspective, implications for patients Failure Trial
(ASCEND-HF).
Dr. Anthony Furlan and Dr. Duane Pinto discuss: CLOSURE I Trial: A Prospective,
Multicenter, Randomized Controlled Trial to Evaluate the Safety and Efficacy of the
STARFlex Septal Closure System Versus Best Medical Therapy in Patients with a Stroke or
Transient Ischemic Attack due to Presumed Paradoxical Embolism through a Patent
Foramen Ovale.
All Rights Reserved, Duke Medicine 2008
Dr. Renato Lopes, Dr. Alexandre Quadros, Dr. Antonio Carlos Carvalho and Dr. Roberto
Giraldez: AHA wrap-up in Portuguese.
Dr. Hisao Ogawa and Dr. Yoshihiko Saito: An AHA 2010 wrap-up in Japanese.
Professor Murray Esler and Dr. Duane Pinto discuss: Symplicity HTN-2: International,
Multicenter, Prospective, Randomized, Controlled Trial Of Endovascular Selective Renal
Sympathetic Denervation For The Treatment Of Hypertension.
Dr. Jonathan Piccini and Dr. Duane Pinto discuss: Sustained Ventricular Tachycardia and
Ventricular Fibrillation Are Infrequent Events but are Associated with Increased Arrhythmic
and All-Cause Death Following Non-ST-Segment Elevation Acute Coronary Syndromes.
Dr. Stephen Nicholls and Dr. Ravi Karra discuss the results of the ASSERT study, the first
major clinical trial of an oral agent inducing Apo A1 synthesis: A new approach to HDL
raising and CV risk modification.
Dr. Magnus Ohman and Dr. C. Michael Gibson discuss LVADs: Improving Outcomes.
Dr. Matthew Brennan and Dr. C. Michael Gibson discuss: Anticoagulation Following
Bioprosthetic Aortic Valve Replacement.
All Rights Reserved, Duke Medicine 2008
Dr. Christopher Granger, Mayme Roettig, RN, MSN, and Dr. Ravi Karra discuss: Mission
Lifeline Update 2010.
Dr. Peter Kowey provides and expert opinion on ROCKET AF and RELY.
Dr. Robert Harrington presents: Beyond 2010, The Future of Antithrombic Therapy - Old
Agent Replacement, Combination Therapy, and the Impact of Generics.
Dr. Kristin Newby and Dr. Duane Pinto discuss: An EARLY-ACS Update.
Dr. Chistopher Cannon presents: Primary Results of the DEFINE trial: Determining the
EFficacy and Tolerability of CETP INhibition with AnacEtrapib.
Dr. Peter Kowey discusses: Efficacy And Safety Of Prescription Omega-3-Acid Ethyl Esters
(P-OM3) For The Prevention Of Recurrent Symptomatic Atrial Fibrillation (AF).
Dr. Magnus Ohman reviews: TRILOGY: An Update.
Dr. Karen Alexander and Dr. Duane Pinto describe: The Coming Tsunami: Cardiovascular
Disease in the Elderly.
All Rights Reserved, Duke Medicine 2008
Dr. Tracy Wang and Dr. Duane Pinto discuss: Under-Utilization of Emergency Medical
Service Transport Among Contemporary Patients with ST-Elevation Myocardial Infarction –
Findings from the National Cardiovascular Data Registry ACTION, Get with the Guidelines.
Dr. Sara Pasquali and Grendel Burrell discuss: The Impact of Intensive Care Unit Structure
on Post-operative Outcomes Following Congenital Heart Surgery: Analysis of a Multiinstitutional Database.
Dr. Jennifer Li, Dr. C. Michael Gibson, and Grendel Burrell discuss: Lessons from Pediatric
Cardiovascular Drug Trials.
Dr. Dominick Angiolillo presents: Commentary on GRAVITAS.
Dr. Christopher Granger and Dr. Ravi Karra discuss: Reperfusion of Acute Myocardial
Infarction in Carolina Emergency Departments - Emergency Response (RACE-ER) Project.
Bradi Granger RN, PhD and Dr. Ravi Karra discuss: The Duke Translational Nursing Institute.
Dr. Otavio Berwanger and Dr. Duane Pinto discuss: Acetylcystein for the Prevention of
Contrast-Induced nephropaThy (ACT) Trial: a Pragmatic Multicenter Randomized Trial to
Evaluate the Efficacy of Acetylcysteine for the Prevention of Renal Outcomes in Patients
Undergoing Coronary and Vascular Angiography.
All Rights Reserved, Duke Medicine 2008
Dr. Christoph Kaiser and Dr. Duane Pinto discuss: The BASKET PROspective Evaluation
Examination (BASKET PROVE): Late Cardiac Clinical Death and Myocardial Infarction
Associated With Late Stent Thrombosis in Large Vessel Stenting After 1st or 2nd Generation
Drug-eluting Compared to Bare-metal Stents.
Dr. William Weintraub and Dr. Ravi Karra discuss: Top 100 Vocabulary Project.
Dr. Richard Becker and Dr. Ravi Karra discuss: Pathways in Anticoagulation: What's Most
Efficacious, Safest.
Karen Pieper and Dr. Duane Pinto present: Insights from Plato: Proton Pump Inhibitor Use Is
Likely a Marker for, Rather than a Cause of, a Higher Risk of Cardiovascular Events.
Dr. Thomas Povsic and Dr. Duane Pinto discuss: A Prospective RADAR Pharmacokinetic
and PharmacodynamicSubstudy: Pegnivacogin (RB006), a Direct Factor IXa Inhibitor,
Results in Consistent and Near Complete Inhibition of Factor IX Activity in Patients with
Acute Coronary Syndromes.
Dr. Sunil Rao and Dr. Ravi Karra discuss: The Primary Results of the REVEAL Trial: A
Randomized Placebo Controlled Trial of Intravenous Erythropoietin to Reduce Infarct Size
After ST-Segement Elevation Myocardial Infarction.
All Rights Reserved, Duke Medicine 2008
Dr. Kristin Newby and Dr. Duane Pinto discuss: MURDOCK Study Progress and
Substudies.
Dr. Keith Aaronson and Dr. Duane Pinto discuss: Evaluation of the Heartware HVAD Left
Ventricular Assist Device System for the Treatment of Advanced Heart Failure: Results of
the ADVANCE Bridge to Transplant Trial.
Dr. James Daubert and Dr. Duane Pinto discuss: QTc Prolongation During Therapeutic
Hypothermia: Does it Deserve Attention?
Dr. David Cohen and Dr. Duane Pinto discuss: PARTNER Trial (Cohort B): Health-Related
Quality of Life After Transcatheter Aortic Valve Implantation vs. Non-Surgical Therapy
Among Inoperable Patients With Severe Aortic Stenosis.
Dr. Karen Alexander discusses: Frail Older Adults at Risk for Loss of Independence
Following MI.
Dr. Kenneth Ellenbogen and Dr. Duane Pinto discuss: SMART AV: Comparison of AV
Optimization Methods Used in Cardiac Resynchronization Therapy (CRT).
Dr. Deepak Voora and Dr. Duane Pinto discuss: A Whole Blood RNA Signature Accurately
Classifies Multiple Measures of Platelet Function on Aspirin in Healthy Volunteers and
Highlights a Common Underlying Pathway.
All Rights Reserved, Duke Medicine 2008
Dr. James Januzzi and Dr. Duane Pinto discuss: PROTECT: Use of NT-proBNP Testing to
Guide Heart Failure Therapy in the Outpatient Setting.
Dr. Chris O'Connor, Dr. Randy Starling, and Dr. Clyde Yancy provide historical perspective
and discuss the results/implications for ASCEND.
Dr. Christopher O'Connor and Dr. Zubin Eapen discuss Duke's Presence at AHA, What's
Happening, What to Expect.
Dr. Rob Califf talks with Dr. Zubin Eapen about a Cardiology Fellow's Perspective from AHA
2010.
All Rights Reserved, Duke Medicine 2008
All Rights Reserved, Duke Medicine 2008
Daily
Heart Line Memos
From Chris & Marti
All Rights Reserved, Duke Medicine 2008
Post-Test Question
Question: What was the most important advance by
Duke Heart Center faculty or fellows from the AHA?
Answer Options:
• ROCKET-AF
• ASCEND
• RACE-ER
• The Duke Cardiology Fellows Blog
• DUKE-TV
All Rights Reserved, Duke Medicine 2008
Post-Test Question
Question: What was the most important advance by
Duke Heart Center faculty or fellows from the AHA?
Answer Options:
• ROCKET-AF
• ASCEND
• RACE-ER
• The Duke Cardiology Fellows Blog
• DUKE-TV
All Rights Reserved, Duke Medicine 2008
Thank You!
Have a Happy Thanks Giving!
Cardiology Grand Rounds
November 23, 2010
John H. Alexander, MD
Director, Heart Center SBR
Co-Director, DCRI CV Research