chapter  02
40 Pages

CORONARY ARTERY DISEASE (CAD) & MYOCARDIAL INFARCTION

DDX: Aortic dissection; Aortic stenosis; HCM; Secondary ischemia (anemia; hyperthyroidism; arrhythmia); Cocaine; Pericarditis; Myocarditis; Takotsubo; Cardiac syndrome X (Microvascular); Pulmonary embolism; Pneumothorax; Pneumonia; PHT (RV ischemia); Pleurisy; Ruptured esophagus (Boerhaave); Pancreatitis; Cholecystitis; Cholelithiasis; Peptic ulcer (perforated); GERD; Esophageal spasm; Musculoskeletal; Costochondritis; Neck pain; Shoulder tendinitis; Shingles; Psychiatric

O2 DEMAND • HR • Wall stress (preload; afterload) • Contractility

O2 SUPPLY • Coronary perfusion pressure (DBP – LVEDP) • Patent coronary arteries • Blood O2 content

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TWO OBJECTIVES a) Confirm the diagnosis of CAD b) Establish the prognosis of the patient’s CAD

(≤ 1 CHARACTERISTIC) ATYPICAL CHEST PAIN (2 CHARACTERISTICS)

TYPICAL CHEST PAIN (3 CHARACTERISTICS)

M F M F M F

30-39 4 % 2 % 34 % 12 % 76 % 26 %

40-49 13 % 3 % 51 % 22 % 87 % 55 %

50-59 20 % 7 % 65 % 31 % 93 % 73 %

60-69 27 % 14 % 72 % 51 % 94 % 86 %

BAYES’ THEOREM: the predictive value of a test depends on its sensitivity, specificity, and the pretest probability of the disease › The diagnostic value of the test (when it is used to confirm the diagnosis of CAD) is maximal in patients with an intermediate pretest probability of CAD (10-90%)

Se ve

rit y

of is

ch em

ia

Duration of ischemia

Cellular alterations

Relaxation abnormalities

Regional wall motion abnormalities

ST anomalies Angina

G LVEDP

Tissue deformation abnormalities (strain)

Perfusion abnormalities

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SENSITIVITY SPECIFICITY

Stress test 68 % 77 %

MIBI-Stress 88 % 72 %

MIBI-Dipyridamole 90 % 75 %

Stress echocardiography 85 % 81 %

Dobutamine echocardiography 81 % 79 %

Coronary CT angiography 95 % 83 %

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RISK ASSESSMENT DURING NONINVASIVE STRATIFICATION

HIGH RISK (ANNUAL MORTALITY OR MYOCARDIAL INFARCTION > 3%)

• LVEF: < 35% at rest (coronary cause) • LVEF: LV dysfunction during stress with LVEF at peak stress < 45% or H LVEF ≥ 10% • LV dilatation during stress • Stress test: Duke score ≤ -11 • Stress test: ST depression ≥ 2 mm (at low workload or persisting during recovery) or ST elevation or VT/VF on exercise • Echocardiography: regional wall motion abnormality during stress involving ≥ 3 segments and/or ≥ 2 vascular territories • Echocardiography: regional wall motion abnormality occurring at a low dose of Dobutamine (10 μg/kg/min) or at low HR (< 120 bpm) • MIBI: perfusion abnormality at rest involving ≥ 10% of the myocardium (in the absence of a history of MI) • MIBI: perfusion abnormality on stress involving ≥ 10% of the myocardium (or involving ≥ 2 vascular territories) • Agaston score (non-contrast CT): > 400 • Coronary CT angiography: multiple vessel disease (stenosis ≥ 70%) or LMCA involvement (stenosis ≥ 50%)

INTERMEDIATE RISK (ANNUAL MORTALITY OR MI: 1-3%)

• LVEF: 35-49% at rest (coronary cause) • Stress test: Duke score: -10 to +4 • Stress test: ST depression ≥ 1 mm + symptoms on exertion • Echocardiography: regional wall motion abnormality during stress on 1-2 segments (involving 1 vascular territory) • MIBI: perfusion abnormality at rest involving 5 to 9.9% of the myocardium (in the absence of a history of MI) • MIBI: perfusion abnormality on stress involving 5 to 9.9% of the myocardium (involving 1 vascular territory) • Agaston score (non-contrast CT): 100-399 • Coronary CT angiography: 1 vessel with stenosis ≥ 70% (or ≥ 2 vessels with 50-69% stenosis)

LOW RISK (ANNUAL MORTALITY FROM MI < 1%)

• Stress test: Duke score ≥ +5 (or absence of ST abnormalities and symptoms with exercise achieving 85% of predicted HRmax) • Echocardiography: normal or limited regional wall motion abnormality at rest and unchanged during stress • MIBI: normal or small perfusion defect at rest or on stress involving < 5% of the myocardium • Agaston score (non-contrast CT): < 100 • Coronary CT angiography: absence of stenosis > 50%

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TREATMENT OF RISK FACTORS: g Chapter 9; HTN; Dyslipidemia (statins); DM; Smoking; Exercise program; Target healthy weight; Balanced diet

BB: first-line; antagonist of catecholamine adrenergic receptors; negative inotropic and negative chronotropic agent (G duration of diastole AG coronary perfusion); anti-anginal; antihypertensive; antiarrhythmic › Intrinsic sympathetic activity (ISA): partially beta-agonist at rest

Treatment of risk factors

Noninvasive stratication with high risk factors

Diagnostic coronary angiography (± Revascularization)

Beta-blocker

TNT puff PRN

Long-acting nitrate or CCB

Consider revascularization

Triple therapy (BB; CCB; Nitrates)

Revascularization

Ivabradine; Ranolazine; Nicorandil; Trimetazidine

Consider Neuromodulation / Counterpulsation

Consider transplantation

Cardioprotective treatment: ASA + ACE inhibitor + Statin

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NITRATES: converted into NO in the cell AG intracellular cGMP A smooth muscle relaxation (by decreasing intracellular Ca2+); veinodilatation (H preload); coronary vasodilatation (G perfusion); systemic arterial vasodilatation (H afterload)

CALCIUM CHANNEL BLOCKERS › Dihydropyridines: Nifedipine (★ ACTION); Amlodipine (★ CAMELOT); systemic arterial vasodilatation (H afterload); coronary vasodilatation (G perfusion) › Nondihydropyridines: Verapamil; Diltiazem; negative inotropic and negative chronotropic agent; systemic and coronary arterial vasodilatation

RANOLAZINE (RANEXA): H myocyte calcium overload by INa inhibition; anti-anginal (★ CARISA; ★ ERICA; ★ MERLIN-TIMI 36)

NICORANDIL: 3 mechanisms: A) Opening of potassium channels of ischemic cells (mimics ischemic preconditioning); B) Opening of potassium channels allowing systemic and coronary arterial vasodilatation; C) Similar properties to Nitrates › ★ IONA: Stable CAD; H primary outcome with Nicorandil (cardiovascular mortality - MI - hospitalization)

EXTERNAL COUNTERPULSATION: 35 one-hour treatments for 7 weeks; cuffs on lower limbs that inflate in early diastole and deflate in pre-systole; G collateral circulation and/or angiogenesis and/or improvement of endothelial function › Contraindications: active DVT; PAD; Aortic aneurysm; Aortic stenosis; Aortic regurgitation; Uncontrolled HTN; Decompensated heart failure

No ISA With ISA

Pindolol ***Timolol ***

Propranolol ** Metoprolol **

Bisoprolol **

Esmolol *

Labetalol *

Carvedilol **Nadolol **

Sotalol *

Risk of accumulation in CRF

Atenolol ** Acebutolol *

Selective Alpha and Beta-blockers

No ISA With ISA

* Degree of potency

BETA-BLOCKERS

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ANTI-ANGINAL DOSES ADVERSE EFFECTS

BETA-BLOCKERS

Target resting HR 50-60 bpm Maintenance dose • Metoprolol: 50 - 100 mg bid • Bisoprolol: 2.5 - 10 mg qd • Carvedilol: 3.125 - 50 mg bid • Atenolol: 50 - 100 mg qd • Propranolol LA: 80 - 320 mg qd • Nadolol: 40 - 240 mg qd • Esmolol: Bolus IV 500 μg/kg; infusion 50 - 200 μg/kg/min

Bradycardia - Blocks; Negative inotropic agent (heart failure); Bronchospasm; Depression / Tiredness; Nightmares; Erectile dysfunction; masked symptoms of hypoglycemia (prefer Bisoprolol or Metoprolol); rebound ischemia after sudden discontinuation; Possible exacerbation of PAD or Raynaud or Prinzmetal (unopposed alpha stimulation); G TG and H HDL (nonselective BBs)

NITRATES

• Sublingual: 0.4 mg/puff every 5 min x 3 • Patch: 0.2 - 0.8 mg/h; 8:00 a.m. to 8:00 p.m. • Isosorbide 5-mononitrate (Imdur): 30 to 240 mg qd • Isosorbide dinitrate: 10 - 40 mg tid • IV: 5 - 200 μg/min

Headache; Flushing; Hypotension; Tolerance (prevention by 12-hour period without TNT each day); Methemoglobinemia; Interaction with PDE5 inhibitors; Avoid in the presence of aortic stenosis or HCM

DIHYDROPYRIDINE CCBS

• Nifedipine SR (long-acting): 30 - 60 - 90 mg qd • Amlodipine: 2.5 - 10 mg qd

Headache; Faintness; Hypotension; Flushing; Leg edema

NONDIHYDROPYRIDINE CCBS

Diltiazem • PO: 30 - 90 mg tid-qid • CD: 120 - 360 mg qd • Bolus: 0.25 mg/kg IV • Infusion: 5 - 15 mg/h Verapamil • PO: 80 - 120 mg tid-qid • SR: 120 - 480 mg qd • Bolus: 0.075 - 0.15 mg/kg

Block; Bradycardia; Heart failure (negative inotropic agent); Hypotension; Flushing; Headache; Leg edema; Drug interactions

IVABRADINE • 5 to 7.5 mg bid Bradycardia; Phosphenes

NICORANDIL • 10-20 mg bid Ulcers; Nausea; Hypotension; Headache; Weakness; Flushing

TRIMETAZIDINE • 20 mg tid or 30 mg bid Nausea; Vomiting; Parkinsonism

RANOLAZINE • 500 to 1000 mg bid Drug interactions; Nausea; Weakness; G QT (but H delayed after-depolarizations)

2 OBJECTIVES a) Improve quantity of life (prognosis) b) Improve quality of life (symptoms)

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FACTORS AFFECTING THE PATIENT’S PROGNOSIS a) Markers of high risk on noninvasive stratification b) Significant ischemia (> 10% of LV) c) LV dysfunction d) Anatomical extent of CAD / Number of vessels involved

SYNTAX score ≤ 22 SYNTAX score 23-32 SYNTAX score ≥ 33

Similar primary outcome with CABG and PCI G adverse events with PCI G adverse events with PCI

(consider PCI if SYNTAX ≤ 22)

High-risk anatomy

LMCA > 50%

3vessel

disease

Persistent angina unresponsive to

medical treatment

Proximal LAD

stenosis

2-or 3vessel with H LVEF

Improve survival (quantity of life) Improve symptoms (quality of life)

INDICATIONS FOR REVASCULARIZATION IN STABLE CAD

Angiographic lesion characteristics

Heart team • SYNTAX score • STS score • Comorbidities • Patient preference

3-vessel disease Predominant LMCA DM + ≥ 2-vessel

SYNTAX ≤ 22

SYNTAX > 22

SYNTAX ≤ 22

SYNTAX > 32

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DIFFERENTIAL DIAGNOSIS OF ELEVATED TROPONIN

• Infarction • Heart failure • Bradyarrhythmia or Tachyarrhythmia • Myocarditis • Pulmonary embolism • Aortic valve disease • Myocardial contusion • Takotsubo • Infiltrative cardiomyopathy • HCM • Hypertensive crisis

• Aortic dissection • Coronary vasospasm • Endothelial dysfunction without CAD • PCI • Cardiac surgery • Balloon valvuloplasty • ECV / Defibrillation • Electrophysiological ablation • Graft rejection • Sepsis • Renal failure

• Significant PHT • Severe anemia • Respiratory failure • Intense physical exercise • Cardiotoxic chemotherapy • Cardiotoxins • Subarachnoid hemorrhage • Acute brain syndrome • Rhabdomyolysis • Body burn (> 30% BSA) • Scorpion venom

Myocarditis

Moderate MI; Myocarditis;

Takotsubo; Shock; Pulmonary embolism

Small MI Myocarditis; Takotsubo; Shock;

Pulmonary embolism; Heart failure...