Complexities of Stable CADvfustercourse.com/assets/pdfs/ponencia5.pdf · 2019-10-30 · Complexities of Stable CAD Role of PCI vs CABG vs OMT & The Microcirculation MCP BASES OF ATHEROTHROMBOTIC

Molecular (M), Clinical (C) and Population (P)Bases of Cardiovascular Disease and Health

16 and 17 July 2018 / 16 y 17 de julio de 2018Cardona (Barcelona, Spain) – Auditori Valentí Fuster

Complexities of Stable CADRole of PCI vs CABG vs OMT & The Microcirculation

MCP BASES OF ATHEROTHROMBOTIC DISEASE, 2019

2. MCP Bases of Atherothrombotic Disease

5. Challenges of ACS STEMI & NSTEMI

6. Challenges of Stable CAD & Microcirculation

7. Challenges of Acute Stroke & Chronic Carotid Disease

8. Challenges of Thoracic & Abdominal Aortic Diseases

Cardona, July 15, 2019 No Disclosures

Molecular (M), Clinical (C), Population (P)Bases of Cardiovascular Disease and Health, 2019

CABG, PCI, OMT, Microcirculation – 2019Stable Multivessel Coronary Disease

1. Four Questions to be Answered

2. Evolving Concepts of CABG

3. Evolving Concepts of PCI

4. Evolving Optimal Medical Therapy

5. Awareness of the Microcirculation

1). VG Failure – Question to Address?

MY Emmert. Eur Heart J. 2017;38:2029

2).Evolution of Devices – Reaching Limit?

RA Byrne et. al. Lancet 2017; 390: 781

Scaffolds - Late ST/Very Late ST

J Torrado et. al. J Am Coll Cardiol 2018;71:1676

3) Linear Correlation Between the Reduction of LDL-C Levels and the Reduction in MACE in the Main Lipid-Lowering Trials

G Gallone et. al. J Am Coll Cardiol 2018;72:2886

4). Epicardial Coronary Arteries and the Full Coronary Circulation

VR Taqueti et. al. J Am Coll Cardiol 2018;72:2625

(A) Macrocirculation. (B) Macro & Microcirculation







2). Evolution of CABG – Room to Improve

a. CABG vs Stenting

b. IMA & Radial BG

c. On vs Off Pump

d. Dual Antiplatelet Therapy

e. Hybrid Coronary Revascularization

CABG vs Stenting – FREEDOM etc For Diabetic MVD FU 5 yrs.

J Mancini, V Fuster et al. J Am Coll Cardiol 2016; 68:985 –Mortality ?

Survival Curves of Revascularization Strategy in the FREEDOM Follow-On Study

FREEDOM Follow-On Study (ME Farkouh, V Fuster et. al.) J Am Coll Cardiol 2019;73:629

.

18.7%23.7%

Mortality After CABG vs PCI During 5y FU With and Without DM and With LM or MVD

SJ Head, V Fuster et. al. ., Lancet 2018; 391:939 11 RCT, 11,518 Pts

SJ

Stroke After Percutaneous Coronary Intervention VersusCoronary Artery Bypass Grafting

SJ Head, V Fuster et. al. J Am Coll Cardiol 2018;72:386

Diminishing Mortality Gap Between PCI and CABGFor Multivessel Disease From the NY State Registries

S Bangalore. J Am Coll Cardiol 2016;68:996MY Emmert. Eur Heart J. 2017;38:2029

J Nagendran et al. J Am Coll Cardiol 2018;71:819

CABG Improves Outcomes in Patients with Diabetes and LVD

MACCE (EF 35 – 49%) MACCE (EF <35%)

First Treatment Post Index Cath CABG PCI

Infarct Prevention Through Bypass Grafting

T Doenst, H Sigusch et. al. J Am Coll Cardiol 2019;73:964

The majority of infarcts are generated by non–flow-limiting stenoses, but PCI is solely focused on treating flow-limiting lesions. Thus, PCI cannot be expected to significantly limit new infarcts, but CABG may do so through providing flow distal to vessel occlusions.


a. CABG vs Stenting

b. IMA & Radial BG

c. On vs Off Pump



LIMA, Radial Artery, Y Graft Operation Survival Curves – 21 years

AG Royse et. al. J Am Coll Cardiol 2018;72:1332


a. CABG vs Stenting

b. IMA & Radial BG

c. On vs Off Pump



NA Smart et. al. J Am Coll Cardiol 2018;71:983

Long-Term - On-vs Off-Pump CABG:Forest Plot of Mortality Incidence

A Diegeler, W Reents et. al. Circulation. 2019;139:1865

From June 2008 to September 2011, a total of 2539 patients aged ≥75 years were randomly assigned to undergo off-pump or on-pump coronary artery bypass grafting (CABG) at 12 centers in Germany. The primary outcome was all-cause mortality at 5 years. The secondary 5-year outcomes were a composite of death, myocardial infarction, and repeat revascularization. Furthermore, the impact of complete versus incomplete revascularization was assess. The 5-year survival rates and the combined outcome of death, myocardial infarction, and repeat revascularization, as well, were similar after on-pump and off-pump CABG. Incomplete revascularization was associated with a lower 5-year survival rate, irrespective of the type of surgery.

Long-term SurvivalAfter On-pump or Off-pump CABG

A Diegeler, W Reents et. al. Circulation. 2019;139:1865

Four Surgical Methods Of CABG With > Degrees of Aortic Manipulation

MY Emmert. Eur Heart J. 2017;38:2029


a. CABG vs Stenting

b. IMA & Radial BG

c. On vs Off Pump



SVBG 1 Year After CABGTicagrelor + ASA, Ticagrelor Alone, or ASA Alone

In a randomized, multicenter, open-label, clinical trial among 6 tertiary hospitals in China, 1256 patients were identified and 500 were enrolled. Patients were randomized (1:1:1) to start ticagrelor (90 mg twice daily) + aspirin (100 mg once daily) (n=168), ticagrelor (90 mg twice daily) (n=166), or aspirin (100 mg once daily) (n=166) within 24 hours post-CABG. Primary outcome (saphenous vein graft patency 1 year after CABG) was assessed by multislice CTA or coronary angiography. SVBG patency rates 1 year post-CABG were 88.7% with ticagrelor + aspirin; 82.8% with ticagrelor alone; and 76.5% with aspirin alone (p<.001), Five major bleeding (3 with ticagrelor + aspirin; 2 with ticagrelor alone).

Q Zhao et al., JAMA 2018; 319:1677 (China) – Rivaroxaban / ASA Negative

Stable CAD or PAD on Rivaroxaban 2.5 mg/BID Plus ASA 100 mg/d vs ASA 100 mg/d - MACE

COMPASS (A Lamy et. Al). J Am Coll Cardiol 2019;73:121


a. CABG vs Stenting

b. IMA & Radial BG

c. On vs Off Pump



Hybrid Study–Objectives & Targets

•In patients with multi-vessel coronary artery disease -MV-CAD- involving the Left Anterior Descending –LAD- and/or Left Main –LM- arteries.

•2354 patients will be randomized:– PCI with DES, including LAD– HCR - LIMA- to LAD + PCI of non-LAD

Hybrid Study – Primary Endpoint

The occurrence of MACCE, defined as

all-cause mortality, myocardial

infarction (MI), stroke, and repeat

revascularization over a minimum of 5

year follow-up after randomization







3). Evolution of PCI – Room to Improve

a. Scaffolds – Resilience?

b. iFR vs FFR – Taking Over?

c. Wall Shear Stress – Add to FFR?

d. Syntax & FFR For PCI – Worth For CABG?

e. CTA/FFR/Plaque, Taking Over Invasive?

ABSORB II Inv. (DJ Kereiakes et al.) J Am Coll Cardiol. 2017;70:2852

3-Year Outcomes with Everolimus-Eluting Bioresorbable Scaffolds

ABSORB II Inv. (DJ Kereiakes et al.) J Am Coll Cardiol. 2017;70:2852

Time-to First-Event Curves for Definite or Probable Device Thrombosis

Effect of Techniques on Outcomes

GW Stone et. al. J Am Coll Cardiol. 2017;70:2863







iFR vs FFR - Primary Endpoint at 1 Year

iFR SWEDEHEART (M Götberg et. al.) N Engl J Med 2017;376:1813

Primary Endpoint(death from any cause, non-fatal MI, unplanned revasc)

iFR vs FFR - Primary Endpoint at 1 YearPrimary Endpoint

(death from any cause, non-fatal MI, or unplanned revasc)

DEFINE-FLAIR (JE Davies et. al.) N Engl J Med 2017;376:1824







J Am Coll Cardiol 2018;72:1926

In patients with stable CAD and hemodynamically significant lesions, higher WSS in the proximal segments of atherosclerotic lesions is predictive of MI and has incremental prognostic value over FFR.

High Wall Shear Stress Predicts MI

A Kumar et. al. J Am Coll Cardiol 2018;72:1926

Incremental Prognostic Value of Prox. WSS Over FFRfor Vessel-Related Myocardial Infarctionc

A Kumar et. al. J Am Coll Cardiol 2018;72:1926







J Am Coll Cardiol 2018;72:2732 J Am Coll Cardiol 2018;72:2826







Case Example of Typical NoninvasiveImaging Results

RS Driessen, P Knaapen et. al. J Am Coll Cardiol 2019;73:161 - PACIFIC TRIAL

In total, 505 of 612 (83%) vessels could be evaluated with FFRCT which showed a diagnostic accuracy, sensitivity, and specificity of 87%, 90%, and 86% on a per-vessel basis. FFRCT. showed higher diagnostic performance than standard coronary CTA, SPECT, & PET for vessel-specific ischemia

Comparison of Risk Reclassification Noninvasive vs Invasive Functional SYNTAX Score

C Collet, PW Serruys et. al. J Am Coll Cardiol 2018;71:2756

Evidence supporting the noninvasive FSS in patients with multivessel CAD is scarce. The CTA-SS was calculated in patients with 3-vessel CAD included in the SYNTAX II. The noninvasive FSS was determined by including only ischemia-producing lesions (FFRCT ≤0.80). The noninvasive FSS was feasible in 80%. Calculation of the noninvasive FSS is feasible and yielded similar results to those obtained with invasive pressure-wire assessment..

CTA - Plaque Characteristics and Physiological Stenosis Severity as Prognostic in CAD

JM Lee, BK Koo, T Akasaka et. al. J Am Coll Cardiol 2019;73:2413

A total of 772 vessels (299 patients) evaluated by both coronary CTA and FFR were analyzed. The presence and number of HRPC were assessed using coronary CTA images. The risk of vessel-oriented composite outcome or VOCO (a composite of vessel-related ischemia-driven revascularization, vessel-related MI, or cardiac death) at 5 years was compared.

Comparison of VOCO Among Groups Classified According to FFR-Guided Treatment and HRPC

JM Lee, BK Koo, T Akasaka et. al. J Am Coll Cardiol 2019;73:2413

Coronary Plaque Characteristics at CTA

MC Williams, ED Nicol et. al. J Am Coll Cardiol 2019;73:291

(A) positive remodeling, (B) low-attenuation plaque, (C) spotty calcification, and (D) the “napkin ring” sign

Perivascular FAI Analysis Around Epicardial Coronary Vessels

CRISP-CT (EK Oikonomou, S Achenbach, C Antoniades et. Al). Lancet 2018; 392: 929

CABG, PCI, OMT, Microcirculation – 2019Stable Multivessel Coronary Diseas






4). Evolution of OMT – Room to Improve

a. Low Compliance – Polypill for 2ary Prev.?

b. DAPT – Boring but Moving

c. Platelet Inhibitors + A/C – PCSK9i - SGLT2

CNIC- Polypill, 2ary Prevention.

Am. H J 2011;162:811 Semin.Thor.Cardiov.Surg 2011;23:24JACC, 2014; 64:2071BMC Phrmac. Toxic. 2017;18:10 Approved in 45 Countries

FOOD INTERACTION

PHARMACOKINETIC INTERACTION WITH ASPIRIN

PHARMACOKINETIC INTERACTION WITH

SYMVASTATIN

PHARMACOKINETIC INTERACTION WITH RAMIPRIL

PHARMACODYNAMIC INTERACTION WITH ASPIRIN

PHARMACODYNAMIC INTERACTION WITH

SYMVASTATIN

PHARMACODINAMIC INTERACTION WITH RAMIPRIL

BIO-EQUIVALENCE

ASA, Statin, ACE-Inhibitor

ArgentinaBrazilParaguayItalySpain

FOCUS 1 & 2

FREEDOMAETNA-DIABETESSECURE-EC 2015

HOPE-3-NEJM 2016;374:2032 – Polypill for 1ary Prevention ?





PRECISE-DAPT Score and Complex PCI

PRECISE-DAPT (F Costa, M Valgimigli et. al.) J Am Coll Cardiol 2019;73:2596

Complex PCI was defined as ≥3 stents implanted and/or ≥3 lesions treated, bifurcation stenting and/or stent length >60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high (≥25) or nonhigh (<25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT.

Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT.

PRECISE-DAPT Score and Complex PCI

PRECISE-DAPT (F Costa, M Valgimigli et. al.) J Am Coll Cardiol 2019;73:2596





COMPASS. N Engl J Med 2017;377:1319 - < Mortality

Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better CV outcomes but more major bleeding events than those assigned to aspirin alone. (Rivaroxaban (5 mg twice daily) alone did not result in better CV outcomes than aspirin alone and resulted in more major bleeding events).

COMPASS ( SJ Connolly , S Yusuf et. al.) Lancet 2018; 391: 205

Primary Efficacy & Safety OutcomesLow Dose Ribaroxaban in Stable CAD and PVD

Inhibition of PCSK9 Via Monoclonal Antibody Blocking Plasma PCSK9 & siRNA Blocking PCSK9 Transcription

RS Rosenson et. al. J Am Coll Cardiol 2018;72:314

ODYSSEY OUTCOMES Mean Cumulative Functions for Nonfatal Cardiovascular Events

ODYSSEY OUTCOMES (M Szarek, G Steg et. al.) J Am Coll Cardiol 2019;73:387

Changes After SGLT2 Inhibition

TA Zelniker et. al. J Am Coll Cardiol 2018;72:1845

Summary of the Published SGLT2 Inhibitor Cardiovascular Outcomes Trials

SR Das et. al. J Am Coll Cardiol 2018;72:3200

Cardiorenal Benefits of SGLT2i In Different Patient Populations

S Verma et. al. Lancet 2019;393:3

Summary of the GLP-1RACardiovascular Outcomes Trials

SR Das et. al. J Am Coll Cardiol 2018;72:3200







J Am Coll Cardiol 2018;72:2625 - J Am Coll Cardiol 2018;72:2642

5). Awareness of the Microcirculation

a. Definition of an Extensive Network

b. Measurements – Fixed vs Dynamic

c. Classification of No Stenosis Angina

Normal Structure and Function of the CoronaryMacrocirculation and Microcirculation


Abnormal Structure and Function of the CoronaryMacrocirculation and Microcirculation






STRENGTHS AND LIMITATIONS OF SELECT DIAGNOSTICTECHNIQUES FOR THE EVALUATION OF CMD

Accuracy Reproducibility Threshold

Noninvasive*PET ++++ ++++ CFR <2CMR +++ +++ MPRI <2Doppler Echo ++ +++ CFVR <2

Invasive*CFR ++++ ++++ <2.3IMR ++++ +++ >25 U

VR Taqueti, MF DiCarli. JACC 2018; 72:2625

*

Women With S & S of Ischemia With No Obstructive CAD Role of Coronary Reactivity Testing

A AlBadri, NB Merz, B Ahmed et. al. J Am Coll Cardiol 2019;73:684

Women (n=224) with non obstructive CAD and with signs and symptoms of ischemia. At angiography non endothelial microvascular reactivity increased by IC adenosine (FR or velocity change) and epicardialreactivity by IC NTG (CSA). Endothelial microvascular reactivity and epicardial reactivity by IC-Ach.





Subendocardial ischemia, diffuse epicardial narrowing and adequate microvascular that is not recognized by standard imaging or may be associated with impaired subendocardial perfusion due to aortic stenosis or LVH and shorted diastolic perfusion time of tachycardia.

Overlooked stenosis, occlusions of secondary branches not seen on angiogram, increasingly common for stent-caged branches.

Diffuse microvascular dysfunction, with low CFR and CFC associated with risk factors, subclinical coronary atherosclerosis, endothelial dysfunction, or from inflammatory disease, sarcoid, etc.

Nonischemic cardiac pain mechanisms, aberrant adenosine A1 receptors or other nonischemic cardiac mechanisms.

KL Gould, NP Johnson. JACC 2018; 72:3643

Classification of No Stenosis Angina

The Retinal Microcirculation & Early CV Effectsof Several Cardiometabolic Disorders

ME Hall et. al. Circ Res. 2019;124:1692

Impaired Retinal Vessel Dilation Predicts Mortality in End-Stage Renal Disease

In the multicenter prospective observational ISAR study, data on dynamic retinal vessel analysis were available in a subcohort of 214 dialysis patients (mean age, 62.6 ± 15.0; 32% women). Microvascular dysfunction was quantified by measuring maximum arteriolar dilation and maximum venular dilation (vMax) of retinal vessels in response to flicker light stimulation. Our results provide the first evidence that impaired retinal venular dilation is a strong and independent predictor of all-cause mortality Dynamic retinal vessel analysis may be a novel diagnostic tool to optimize CV risk stratification in end-stage renal disease and other high-risk cardiovascular cohorts.

R Günthner, C Schmaderer et al. Circ Res 2019; 124:1796., (Munich, Germany)

Future For PCI / CABG – OMT ADHERENCE

SCAAR (ML Fokkema et.al.) JACC 2013;61:1222 - Swedish Registry Diab.Trialists’ Collab. – 2015 - FREEDOM, BARI 2D, COURAGE

PCI

CABG

OMT







2. MCP Bases of Atherothrombotic Disease

5. Challenges of ACS STEMI & NSTEMI

6. Challenges of Stable CAD & Microcirculation

7. Challenges of Acute Stroke & Chronic Carotid Disease

8. Challenges of Thoracic & Abdominal Aortic Diseases

Cardona, July 15, 2019 No Disclosures

Molecular (M), Clinical (C), Population (P)Bases of Cardiovascular Disease and Health, 2019

Documents

Complexities of Stable CADvfustercourse.com/assets/pdfs/ponencia5.pdf · 2019-10-30 · Complexities of Stable CAD Role of PCI vs CABG vs OMT & The Microcirculation MCP BASES OF ATHEROTHROMBOTIC