Samin K. Sharma, MD, FACC Director, Clinical and Interventional
Cardiology President Mount Sinai Heart Network Professor of
Medicine Cardiovascular Institute Mount Sinai Hospital, New York
Interventional Cardiology Board Review 2014
Customary ACC/AHA Classification ACC/AHA Guidelines Class
Characteristics I Evidence & general agreement for
usefulness/efficacy IIA Evidence in favor of usefulness/efficacy
IIB Evidence is controversial, usefulness/efficacy less well
established III Not useful/effective, & in some cases may be
harmful Level of evidence Characteristics A (highest rank) Data
derived from multiple randomized trials involving large numbers of
patients B (intermediate) Data derived from limited randomized
trials involving small numbers of patients or from careful analysis
of non- randomized studies C (low rank)Expert consensus
Slide 4
PCI Indications and Outcomes According to Clinical Presentation
For every 100 pts treated with primary angioplasty rather then
thrombolytic therapy, primary angioplasty (when performed without
significant delays) saves approximately how many lives? a.7 B
Slide 5
Thrombolysis Vs. PCI for STEMI Mortality Non-fatal MI
Mortality/re-MI Stroke % Thrombolysis PCI p=0.007 p=0.02 30-Day
Event Rate in 21 Randomized Trials p250250-2500 % of dose in bolus
75% 7% B
Slide 22
Prognostic Value of the Admission ECG in Acute Coronary
Syndromes: GUSTO Trials Savonitto et al. JAMA 1999;281:707 Days
from randomization 30-Day Mortality (%) Kaplan-Meier Estimates of
Probability of Death 6-Month Mortality & Re-MI (%) 6.6% 5.1%
1.7% 8.9% 6.8% 3.4% ST and ST ST Isolated T wave inversion 5.1% ST
and ST ST Isolated T wave inversion 9.1% 9.2% 6.8% 5.4% 8.9%
Slide 23
PCI Indications and Outcomes According to Clinical Presentation
Which of the following trials found no major benefits of routine
early invasive strategy compared to conservative treatment in ACS?
a.COURAGE b.ICTUS c.ACUITY d.TACTICS-TIMI 18 e.FRISC II B
PCI Indications and Outcomes According to Clinical Presentation
A 64 yrs old man has been treated with ASA, a statin, nitrates and
a beta- blocker for stable angina, hypertension and hyperlipidemia.
He successfully controls his DM with diet alone. He recently had
somewhat more frequent angina, and a Thallium stress test revealed
a reversible anterior perfusion defect. Coronary angiography showed
an 80% prox-LAD lesion, 40% circumflex and 40% RCA; LVEF is 55%.
Which of the following options is correct? a.Surgical therapy
offers a survival advantage over medical therapy b.Both PCI and
surgery offer a survival advantage over medical therapy c.Strict
HTN control is not necessary after successful revascularization
d.According to the BARI trial, surgery should offer a survival
advantage over PCI in this pt e.None of the above E
Slide 26
TIMI Risk Score for UA / Non-STEMI Antman et al. JAMA
2000;284:835 % Age 65 years 3 risk factors for CAD Significant
coronary lesion ST segment deviation Severe anginal symptoms Use of
aspirin in last 7 days serum cardiac markers Rate of composite
endpoint Death, MI, UA requiring revasc. 0/1 2 3 4 5 6/7
Characteristics for development of TIMI risk score: No. of risk
factors Test cohort: No. 85 339 627 573 267 66 % 4.3 17.3 32.0 29.3
13.6 3.4 Low Risk Intermed risk High risk
Slide 27
Pathophysiology of ACS: Platelet Activation Vessel wall
Slide 28
% 19% p=NS Clopidogrel (n=1053) Placebo (n=1063) One-Month
& One-Year Composite Endpoint* CREDO Trial (*Death, MI, or
stroke) 27% p=0.02 At 28 days At 1 year At 30 days At 1 year
PCI-CURE Trial (*Death, MI, or urgent TVR) Steinhubl et al. JAMA
2002;288:2411 Mehta et al. Lancet 2001;358:527 Clopidogrel (n=1313)
Placebo (n=1345) 30% p=0.03 16% p=0.03
Slide 29
CURRENT OASIS 7 Trial : A 2x2 Randomized Trial of Optimal
Clopidogrel and ASA Dosing in Pts with ACS Undergoing an Early
Invasive Strategy with Intent for PCI Study Design, Flow and
Compliance Complete Follow-up 99.8% 25,087 ACS Patients (UA/NSTEMI
70.8%, STEMI 29.2%) Planned Early (
Slide 30
CURRENT OASIS 7 : Randomized Trial of Optimal Clopidogrel and
ASA Dosing in Pts with ACS Clopidogrel Double vs. Standard Dose
Major Efficacy Outcomes in PCI Patients Clopidogrel Standard Dose
(n= 8684) Clopidogrel Double Dose (n= 8548) 2.3 % Stent thrombosis
MI Death Stroke Death/MI/Stroke Major Bleed P = 0.002 1.6 2.6 2.0
1.9 0.4 3.9 4.5 P = 0.012 P = 0.68 P = 0.59 P = 0.036 Yusuf et al.
NEJM 2010;363:930. 2.3 P = 1.00
Slide 31
Biotransformation and Mode of Action of Clopidogrel, Prasugrel,
and Ticagrelor Ticagrelor Prasugrel Clopidogrel Ticagrelor
Prasugrel Clopidogrel Active compound Intermediate metabolite
Prodrug No in vivo biotransformation CYP-dependent oxidation
CYP3A4/5 CYP2B6 CYP2C19 CYP2C9 CYP2D6 Platelet P2Y12 Hydrolysis by
esterase Binding CYP-dependent oxidation CYP2C19 CYP3A4/5 CYP2B6
CYP-dependent oxidation CYP1A2 CYP2B6 CYP2C19 New Players in the
Antiplatelet Therapy Field Ticagrelor, a cyclopentyl
triazolopyrimidine, is rapidly absorbed in the intestine and does
not require further biotransformation for activation. It directly
and reversibly binds to the platelet adenosine diphosphate (ADP)
receptor P2Y12. The half-life of ticagrelor is 7 to 8 hours. The
thienopyridines prasugrel and clopidogrel are prodrugs. Their
active metabolites irreversibly bind to P2Y12 for the platelet's
life span. After intestinal absorption of clopidogrel, it requires
two cytochrome P-450 (CYP) dependent oxidation steps to generate
its active compound. After intestinal absorption of prasugrel, it
is rapidly hydrolyzed, by means of esterases, to an intermediate
metabolite and requires one further CYP- dependent oxidation step
to generate its active compound.
Slide 32
TRITON-TIMI 38 Trial Primary end point: CV death, MI, Stroke
Secondary end points: CV death, MI, Stroke, Recurrent Ischemia CV
death, MI, UTVR Stent thrombosis Safety endpoints: TIMI major
bleeds, life-threatening bleeds Key sub studies: Pharmacokinetic,
Genomic Clopidogrel 300 mg LD/ 75 mg MD ACS (STEMI or UA/NSTEMI)
and Planned PCI Study Design N = 13,600 ASA Double-blind Prasugrel
60 mg LD/ 10 mg MD Median duration of therapy 12 months Wiviott S
et al. NEJM 2007;357:2001
Slide 33
Prasugrel versus Clopidogrel in Patients with Acute Coronary
Syndromes: TRITON Trial Wiviott et al. N Engl J Med 2007;357:2001
Cumulative KaplanMeier Estimates of Primary Efficacy End Point
(death from CV causes, MI or stroke) and Key Safety End Point (TIMI
major bleeding) Primary Efficacy End Points Key Safety End Points
Number at risk Clopidogrel 6795 6169 6036 5835 5043 4369 3017
Prasugrel 6813 6305 6177 5951 5119 4445 3085 15 10 5 0 % 0 30 90
180 270 360 450 Days after Randomization 1.8 12.1 9.9 2.4 138
events 35 events P
CABG Vs. Medical Therapy Trials VACS, ECSS, CASS Results Left
main disease >70% (VACS, ECSS) 3-vessel disease (ECSS, VACS)
3-vessel disease with mild LV dysfunction (CASS, VACS) 2-vessel
disease with one being prox LAD (ECSS) 2 or 3-vessel disease with
high-risk features - ST segment depression - Early positive ETT -
Old age or LVH CABG is superior to medical therapy: No difference
in Q-wave MI and return to work.
Slide 46
PTCA Vs. Medical (CABG) Therapy Trials ACME, MAAS, GUY Trials
Results Improvement in symptoms Better exercise duration Less
angina & anti-anginals drugs Better quality of life But: Higher
initial cost and cardiac procedures PTCA is superior to medical
therapy: No difference in MI, death or long-term
revascularization.
Slide 47
PTCA Versus CABG Trials Results In-hospital mortality:Slightly
higher in CABG Out of hospital mortality:Slightly higher in PTCA
Overall long-term mortality:Equal, except in diabetics Incidence of
MI:Equal Repeat revascularization:Significantly lower in CABG
Angina class & anti-anginals use:Significantly lower in CABG
Return to work:Earlier in PTCA Cumulative cost:Slightly lower in
PTCA QOL indicatorBetter in CABG
Slide 48
Which of the following statements regarding the trials of PCI
versus CABG is true: A.Diabetics did better with PCI than with CABG
B.CABG has lower MI versus PCI C.CABG has higher restenosis versus
PCI D.PCI is cheaper than CABG Question D
Slide 49
Diabetes and Coronary Revascularization: BARI Investigators 343
patients in BARI had treated diabetes at study entry and were
followed for 5.4 years. BARI Investigators. Circulation 1997 PTCA
n=170 CABG n=173 p Total mortality (%)34.719.10.003 Cardiac
mortality (%) 20.65.80.0003 SVG only n=33 18.2% IMA graft n=140 2.9
p
Balloon Mitral Valvuloplasty Long-term follow-up results Good
results: MVA >2.0 cm 2 ; CI >2.5 5-7 yrs event-free survival
>90% Suboptimal results: MVA 1.5 cm 2 ; CI
Balloon Mitral Valvuloplasty (BMV) Percutaneous Mitral
Commissurotomy (PMC) Procedural success Post-procedure MVA >1.5
cm 2 with 2+ MR
Slide 87
BMV vs. Open Surgical Commissurotomy Reyes et al. NEJM
1994;331:961 Wedge Gradient Exercise pressure (mmHg) duration
(mmHg) (min) BMV Surgery Baseline 1 week 6 months 3 years
HemodynamicsMitral Valve Area MVA (cm 2 ) Baseline and follow-up
results p=0.03 p
Question A young woman is found to have mitral stenosis with
MVA 1.3 cm 2. She is asymptomatic, she has mild mitral and
tricuspid regurgitation; pulmonary artery systolic pressure is
estimated to be 48 mm Hg by Doppler interrogation. Mitral valve
score by echo is 6. You recommend: a.Afterload reduction with
ACE-inhibitors and repeat echo in 1-2 years b.Balloon mitral
valvotomy if the exercise pulmonary artery systolic pressure is
>50 mmHg c.If the exercise pulmonary artery systolic pressure is
>60 mmHg she should undergo surgical mitral valve replacement
because the echo score is >5 and there is mild mitral
regurgitation d.Balloon mitral valvotomy if the exercise pulmonary
artery systolic pressure is >60 mmHg e.Balloon mitral valvotomy
at this point, before the echo score deteriorates with time D
Slide 93
Aortic Stenosis Normal 3-4 cm 2 AS:- mild >1.5 cm 2 -
moderate 1.0-1.5 cm 2 - severe 10% 2.The results are not as good as
TAVR or AVR, but he will have an improved quality of life and 18
month survival. 3.The procedure is typically effective because it
splits open the commissures 4.All of the above Question:
Balloon Valvuloplasty (PBAV) > 10% risk of serious
complication (death [3%], CVA, aortic rupture, AR, vascular injury)
14% 30 day mortality 60% 18 month mortality (similar to those not
undergoing PBAV) 20% event-free 2 year survival
Slide 131
1.The risk of acute PBAV mortality and major morbidity is >
10% 2.The results are not as good as TAVR or AVR, but he will have
an improved quality of life and 18 month survival. 3.The procedure
is typically effective because it splits open the commissures 4.All
of the above Question:
Slide 132
An 88 year old patient with a cardiomyopathy and aortic
stenosis is referred to you for consideration of TAVR. His LV
ejection fraction is 25%, mean gradient 20 mm Hg. It rises to 28 mm
Hg with 40 mcg/kg/min of dobutamine. Valve area is reported as 0.9.
He is symptomatic with minimal exertion. Based on which one of the
following would you decide to have him undergo transapical TAVR:
1.He has severe mitral regurgitation 2.He has concentric
calcification in the ascending aorta. 3.His iliac arteries have a
minimal diameter of 5 mm bilaterally. 4.You elect not to have him
undergo TAVR. Question:
Slide 133
Low gradient Aortic Stenosis Group 1 - Severe AS with resultant
severe LV dysfunction and inability to generate gradient Group 2 -
Moderate aortic stenosis and underlying cardiomyopathy
Slide 134
Increase transvalvular flow Dobutamine, nitroprusside,
isoproterenol, exercise In patients with severe stenosis
disproportionate rise in gradient Differentiating severity of
stenosis low gradient patients Minimal change in valve area if
orifice size fixed 0.6 2.0
Slide 135
How dobutamine stress echocardiography can help in
decision-making in patients with low-flow aortic stenosis Pibarot
etn al., J Am Coll Cardiol 2012;60:1845
Slide 136
Kodali et al., N Engl J Med 2012;366:1686 Multivariable
Predictors of Mortality
Slide 137
1.He has severe mitral regurgitation 2.He has concentric
calcification in the ascending aorta. 3.His iliac arteries have a
minimal diameter of 5 mm bilaterally. 4.You elect not to have him
undergo TAVR. Question: The key to this question is the very modest
rise in gradient despite dobutamine. Thus this is likely a
cardiomyopathy with moderate aortic stenosis. A concentrically
calcified ascending aorta is a contraindication to aortic
cross-clamping and surgical aortic valve replacement. 5 mm femoral
arteries are too small to accommodate the 22 and 24F sheaths used
in transfemoral TAVR, but not to transapical TAVR. Severe mitral
insufficiency raises the overall risk of aortic valve replacement,
more so with AVR than TAVR. However, this patient does not meet
criteria for either TAVR or aortic valve replacement based on his
hemodynamic assessment.
Slide 138
A 80 year old patient undergoes TAVR and has an excellent
result except for a mild paravalvular leak. When speaking with the
family afterward: 1.You mention the leak and reassure them that it
is mild. 2.You do not mention the leak since it is present in
almost all TAVRs 3.You explain that the leak is potentially
important and may be associated with lower overall survival than
patients with trace or no paravalvular leak 4.You explain that you
will do percutaneous closure of the paravalvular leak as indicated
by the guidelines Question:
Slide 139
Kodali et al, N Engl J Med 2012;366:1686 Severity of
Paravalvular Leak: None or Trace vs. Mild to Severe
Slide 140
1.You mention the leak and reassure them that it is mild. 2.You
do not mention the leak since it is present in almost all TAVRs
3.You explain that the leak is potentially important and may be
associated with lower overall survival than patients with trace or
no paravalvular leak 4.You explain that you will do percutaneous
closure of the paravalvular leak as indicated by the guidelines
Question: Paravalvular leak is typically the result of undersizing
of the aortic prosthesis. Other causes relate to the placement of a
circular object in a non-circular and frequently irregular
calcified orifice. The three year results of PARTNER IA show a
higher mortality in patients with even mild paravalvular leak than
those with trace or none. There is limited experience with
percutaneous paravalvular leak closure in this setting hence no
guidelines.
Slide 141
Complex Coronary Lesions Question: PCI is planned on a 67 year
old man with ESRD and left main with triple vessel coronary
disease. Syntax score is calculated at 30 and left ventricular
systolic function is markedly depressed. Compared with support
using an IABP, the use of an Impella device would be associated
with a.Lower mortality b.Lower myocardial infarction c.Lower repeat
revascularization d.Higher stroke rate
Slide 142
Complex Coronary Lesions The PROTECT II Trial: Impella 2.5 vs.
IABP in High Risk PCI
Slide 143
Complex Coronary Lesions In- and Out-of-Hospital Hierarchical
Outcomes Intent-to-Treat Population ONeill et al., Circulation
2012;126:1717
Slide 144
Complex Coronary Lesions Question: PCI is planned on a 67 year
old man with ESRD and left main with triple vessel coronary
disease. Syntax score is calculated at 30 and left ventricular
systolic function is markedly depressed. Compared with support
using an IABP, the use of an Impella device would be associated
with a.Lower mortality b.Lower myocardial infarction c.Lower repeat
revascularization d.Higher stroke rate