Samin K. Sharma, MD, FACC Director, Clinical and Interventional Cardiology President Mount Sinai...

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

2002- 71% 2003- 75% 2004- 78% 2005- 83% 2006- 85% 2007- 84% 2008- 85% 2009- 86% 2010- 88% 2011- 90% 2012- 88% 2013- 86%

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

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

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

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%

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

Recent Randomized Trials of ACS Conservative Early Intervention % p=0.025 Primary Endpoints: Death, Re-MI, & Re- hospitalization p=0.32 p=0.001 p=0.04 TACTICS* INTERACT** RITA-3*** ISAR-COOL** ICTUS*** (n=2210) (n=746) (n=1810) (n=410) (n=1200) *At 6 mths, ** At 30-days, ***At 1-year 18.6 Cons. Inter. All Combined 14.6 25% NNT=25 P=0.001 p=0.33

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

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

Pathophysiology of ACS: Platelet Activation Vessel wall

% 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

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 (

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

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.

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

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.

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.

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

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

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

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

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:

Aortic Valvuloplasty Mechanisms + Commissural stretching - Commissural splitting + Calcification cracking

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

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:

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:

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

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

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

Kodali et al., N Engl J Med 2012;366:1686 Multivariable Predictors of Mortality

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.

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:

Kodali et al, N Engl J Med 2012;366:1686 Severity of Paravalvular Leak: None or Trace vs. Mild to Severe

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.

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

Complex Coronary Lesions The PROTECT II Trial: Impella 2.5 vs. IABP in High Risk PCI

Complex Coronary Lesions In- and Out-of-Hospital Hierarchical Outcomes Intent-to-Treat Population ONeill et al., Circulation 2012;126:1717

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

Samin K. Sharma, MD, FACC Director, Clinical and Interventional Cardiology President Mount Sinai...

Documents

Transcript of Samin K. Sharma, MD, FACC Director, Clinical and Interventional Cardiology President Mount Sinai...