ABSTRACT
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...
