practical cardiovascular · 2017-01-26 · to my mother marie, my sister eliana, and my beautiful...

Practical Cardiovascular Medicine

Elias B. Hanna, MDAssociate Professor of MedicineAssociate Program Director of Cardiovascular Disease FellowshipAssociate Program Director of Interventional Cardiology FellowshipLouisiana State University School of MedicineUniversity Medical CenterNew Orleans, Louisiana, USA

Practical Cardiovascular Medicine

This edition first published 2017© 2017 by John Wiley & Sons Ltd

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To my mother Marie, my sister Eliana, and my beautiful niece Clara and nephew Marc‐Elias, the constant light in my life

To my mentors and my fellows, and to all those who share my love for cardiology

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Preface, xixAbbreviations, xx

PART 1. Coronary Artery Disease, 1

1. Non‐ST‐Segment Elevation Acute Coronary Syndrome, 1

I. Types of acute coronary syndrome (ACS), 1II. Mechanisms of ACS, 2III. ECG, cardiac biomarkers, and echocardiography in ACS, 3IV. Approach to chest pain, likelihood of ACS, risk stratification of ACS, 4V. Management of high‐risk NSTE‐ACS, 6

VI. General procedural management after coronary angiography: PCI, CABG, or medical therapy only, 9VII. Management of low‐risk NSTE‐ACS and low‐probability NSTE‐ACS, 11VIII. Discharge medications, 11IX. Prognosis, 12

Appendix 1. Complex angiographic disease, moderate disease, 13Appendix 2. Women and ACS, elderly patients and ACS, CKD, 14Appendix 3. Bleeding, transfusion, prior warfarin therapy, gastrointestinal bleed, 15Appendix 4. Antiplatelet and anticoagulant therapy, 16Appendix 5. Differences between plaque rupture, plaque erosion, and spontaneous coronary dissection, 19Appendix 6. Harmful effects of NSAIDs and cyclooxygenase‐2 inhibitors in CAD, 19Questions and answers, 19References, 25

2. ST‐Segment Elevation Myocardial Infarction, 30

1. Definition, reperfusion, and general management, 31I. Definition, 31II. Timing of reperfusion, 31III. ECG phases of STEMI, 32IV. STEMI diagnostic tips and clinical vignettes, 32V. Specific case of new or presumably new LBBB, 33

VI. Reperfusion strategies: fibrinolytics, primary PCI, and combined fibrinolytics–PCI, 34VII. Coronary angiography and PCI later than 24 hours after presentation: role of stress testing, 37VIII. Angiographic findings, PCI, and cellular reperfusion; multivessel disease in STEMI, 38IX. Antithrombotic therapies in STEMI, 39X. Other acute therapies, 40XI. Risk stratification, 41XII. LV remodeling and infarct expansion after MI, 41XIII. Discharge, EF improvement, ICD, 41

2. STEMI complications, 42I. Cardiogenic shock, 42II. Mechanical complications, 45III. Recurrent infarction and ischemia, 47IV. Tachyarrhythmias, 47V. Bradyarrhythmias, bundle branch blocks, fascicular blocks, 49

VI. LV aneurysm and LV pseudoaneurysm, 50VII. Pericardial complications, 51VIII. LV thrombus and thromboembolic complications, 51IX. Early and late mortality after STEMI, 52

Appendix 1. Out‐of‐hospital cardiac arrest: role of early coronary angiography and therapeutic hypothermia, 52Questions and answers, 54References, 59

3. Stable CAD and Approach to Chronic Chest Pain, 65

I. Causes of angina; pathophysiology of coronary flow, 65II. Diagnostic approach, 66

Contents

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III. Silent myocardial ischemia, 68IV. Medical therapy: antiplatelet therapy to prevent cardiovascular events, 70V. Medical therapy: antianginal therapy, 70

VI. Medical therapy: treatment of risk factors, 72VII. Indications for revascularization, 72VIII. CABG, 73IX. PCI, 73X. PCI vs. medical therapy, 74XI. PCI vs. CABG in multivessel disease, 75XII. High‐surgical‐risk patients, 76XIII. Role of complete functional revascularization, 76XIV. Hybrid CABG–PCI, 77XV. Enhanced external counterpulsation (EECP), 77

XVI. Mortality in CAD, 77Appendix 1. Note on outcomes with various surgical grafts, 77Appendix 2. Coronary vasospasm (variant angina, Prinzmetal angina), 79Appendix 3. Women with chest pain and normal coronary arteries, 81Appendix 4. Myocardial bridging, 81Appendix 5. Coronary collaterals, chronic total occlusion, 82Appendix 6. Hibernation, stunning, ischemic preconditioning, 82Questions and answers, 83References, 87

PART 2. Heart Failure (Chronic and Acute Heart Failure, Specific Cardiomyopathies, and Pathophysiology), 93

4. Heart Failure, 93

Definition, types, causes, and diagnosis of heart failure, 941. Definition and types of heart failure, 94

I. Heart failure is diagnosed clinically, not by echocardiography, 94II. After HF is defined clinically, echocardiography is used to differentiate the three major types of HF, 95III. Two additional types of HF, 96

2. Causes of heart failure, 97I. Systolic HF (or HF with reduced EF), 97II. HF with preserved EF, 98III. Right HF, 100

3. Diagnostic tests, 100I. Echocardiography, 100II. BNP, 100III. ECG, 101IV. Coronary angiography and other ischemic workup, 101V. Diastolic stress testing, 102

VI. Endomyocardial biopsy, 102VII. Cardiac MRI, 102

Chronic treatment of heart failure, 1021. Treatment of systolic heart failure, 102

I. Treat the underlying etiology, 102II. Value of revascularization in ischemic cardiomyopathy: STICH trial, 102III. Subsets of patients who are likely to benefit from revascularization: role of viability testing and ischemic testing, 103IV. Drugs that affect survival, 105V. Specifics of drugs that affect survival, 106

VI. Drugs that improve symptoms and morbidity, 110VII. Devices, 112VIII. Other therapeutic measures, 113IX. Prognosis, 113

2. Treatment of HFpEF, 114Acute heart failure and acutely decompensated heart failure, 115

I. Triggers of acute decompensation, 116II. Profiles of acute HF: congestion without low cardiac output, congestion with low cardiac output, 116III. Treatment of acute HF: diagnosis and treatment of triggers, 117IV. Treatment of acute HF: diuretics, cardiorenal syndrome, aggressive decongestion, ultrafiltration, 118V. Treatment of acute HF: vasodilators, 121

VI. Treatment of acute HF: IV inotropic agents (dobutamine, milrinone, dopamine), 122

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VII. In‐hospital and pre‐discharge use of ACE‐Is and β‐blockers, 122VIII. Treatment of acute HF: O2, non‐invasive ventilatory support (CPAP, BiPAP), intubation, 123IX. Summary: keys to the treatment of acute HF, 123X. Discharge, 124XI. Inability of severe HF to tolerate vasodilatation or hemodialysis, 124XII. Outpatient monitoring of HF and prevention of hospitalization, 124Appendix 1. Management of isolated or predominant RV failure, 125Questions and answers, 127References, 135

5. Additional Heart Failure Topics, 142

1. Specific cardiomyopathies, 142I. Specific dilated cardiomyopathies, 142II. Specific infiltrative restrictive cardiomyopathies, 145

2. Advanced heart failure: heart transplant and ventricular assist devices (VADs), 146I. Stages of HF, 146II. Cardiac transplantation, 146III. Left ventricular assist devices (LVADs), 147

3. Pathophysiology of heart failure and hemodynamic aspects, 149I. LV diastolic pressure in normal conditions and in HF (whether systolic or diastolic), 149II. Definition of afterload, 149III. Cardiac output, relation to preload and afterload, 150IV. LV pressure–volume relationship in systolic versus diastolic failure: therapeutic implications, 151V. Decompensated LV failure: role of heart rate, 152

VI. Mechanisms of exercise intolerance in HF, 153VII. Pressure–volume (PV) loops (advanced reading), 153VIII. Additional features of HF with preserved EF, 153IX. High‐output HF, 154

References, 155

PART 3. Valvular Disorders, 157

6. Valvular Disorders, 157

1. Mitral regurgitation, 158I. Mechanisms of mitral regurgitation, 158II. Specifics of various causes of mitral regurgitation, 158III. Assessment of MR severity, 164IV. Natural history and pathophysiology of organic MR, 164V. Treatment of organic (primary) MR, 165

VI. Treatment of secondary MR (ischemic and non‐ischemic functional MR), 166VII. Treatment of acute severe MR related to acute MI, 167VIII. Percutaneous mitral valve repair using the Mitraclip device, 167

2. Mitral stenosis, 167I. Etiology and natural history, 167II. Diagnosis, 168III. Treatment, 171

3. Aortic insufficiency, 173I. Etiology, 173II. Pathophysiology and hemodynamics, 174III. Diagnosis, 176IV. Natural history and symptoms, 176V. Treatment, 176

4. Aortic stenosis, 178I. Etiology, 178II. Laboratory diagnosis and severity, 179III. Low‐gradient AS with aortic valve area (AVA) ≤1 cm2 and low EF <50%, 181IV. Low‐gradient AS with aortic valve area (AVA) ≤ 1 cm2 but normal EF (paradoxical

low‐flow/low‐gradient severe AS), 181V. Pressure recovery phenomenon, 182

VI. Symptoms, 183VII. Natural history, 183VIII. AS should be differentiated from subvalvular and supravalvular AS in children

or young adults, 183IX. Treatment, 184

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5. Tricuspid regurgitation and stenosis, 186I. Etiology of tricuspid regurgitation (TR), 186II. Natural history of TR, 187III. Treatment of TR, 187IV. Tricuspid stenosis (TS), 187

6. Pulmonic stenosis and regurgitation, 187I. Pulmonic stenosis (PS), 187II. Pulmonic regurgitation (PR), 188

7. Mixed valvular disease; radiation heart disease, 188I. Mixed single‐valve disease, 188II. Multiple valvular involvement (combined stenosis or regurgitation of two different valves), 188III. Radiation heart disease, 189

8. Prosthetic valves, 189I. Bioprosthesis, 189II. Mechanical valve: bileaflet tilting disk (St. Jude) or single‐leaflet tilting disk (e.g., Medtronic‐Hall), 190III. Determinants of valve degeneration and valve thrombosis; anticoagulation guidelines, 190IV. Particular cases: women who wish to become pregnant and dialysis patients, 191V. Echocardiographic follow‐up of prosthetic valves, 191

VI. Complications, 1919. Auscultation and summary ideas, 193

I. Auscultation and other physical findings, 193II. General ideas and workup, 196

Questions and answers, 197References, 206

PART 4. Hypertrophic Cardiomyopathy, 211

7. Hypertrophic Cardiomyopathy, 211

I. Definition and features of HCM, 211II. Natural history and mortality, 213III. Symptoms and ECG, 214IV. Exam, 214V. Invasive hemodynamic findings, 214

VI. Echocardiographic findings, 214VII. Provocative maneuvers, 216VIII. Genetic testing for diagnosis; screening of first‐degree relatives, 216IX. Differential diagnosis of LVOT obstruction, 216X. Differential diagnosis of severe LV hypertrophy, 218XI. Treatment of symptoms, 218XII. Treatment: sudden cardiac death risk assessment and ICD therapy, 220Questions and answers, 221References, 222

PART 5. Arrhythmias and Electrophysiology, 225

8. Approach to Narrow and Wide QRS Complex Tachyarrhythmias, 225

I. The unstable patient (shock, acute pulmonary edema), 225II. Initial approach to any tachycardia, 225III. Approach to narrow QRS complex tachycardias, 226IV. Approach to wide QRS complex tachycardias, 227V. Features characteristic of VT, as opposed to SVT with aberrancy, 228

VI. Features characteristic of SVT with pre‐excitation, 232VII. Role of adenosine in establishing a diagnosis, 233VIII. Differential diagnosis of a wide complex tachycardia on a one‐lead telemetry or Holter monitor strip, 234IX. Various notes, 234X. General management of SVT, 234XI. Non‐tachycardic wide complex rhythms, 235

Questions and answers: Practice ECGs of wide complex tachycardias, 235Further reading, 241

9. Ventricular Arrhythmias: Types and Management, Sudden Cardiac Death, 242

I. Premature ventricular complexes, 242II. Ventricular tachycardia (VT), 243III. Polymorphic ventricular tachycardia, 246

Contents xi

IV. Congenital long QT syndrome (LQT), 248V. Indications for ICD implantation, 249

VI. Specific VTs that should be considered in the absence of obvious heart disease, 251VII. Causes of sudden cardiac death (SCD), 253Questions and answers, 254References, 256Further reading, 257

10. Atrial Fibrillation, 258

I. Predisposing factors, 258II. Types of AF, 259III. General therapy of AF, 259IV. Management of a patient who acutely presents with symptomatic AF, 261V. Peri‐cardioversion management and long‐term management after the acute presentation, 262

VI. Decisions about long‐term anticoagulation, role of clopidogrel, role of triple therapy, 262VII. Special situation: atrial fibrillation and heart failure, 264VIII. Special situation: atrial fibrillation with borderline blood pressure, 265Appendix 1. Antiarrhythmic drug therapy (indications and examples), 265Appendix 2. Catheter ablation of atrial fibrillation, surgical ablation, AV nodal ablation, 267Appendix 3. INR follow‐up in patients receiving warfarin; new anticoagulants, 268Appendix 4. Bridging anticoagulation in patients undergoing procedures and receiving warfarin, 270Appendix 5. Management of elevated INR values, 270Appendix 6. A common special situation: AF and symptomatic pauses (sinus or AF pauses) or bradycardia, 271Appendix 7. DC cardioversion in patients with a slow ventricular response, 271Appendix 8. AF occurring post‐cardiac surgery and AF related to acute transient triggers, 271Appendix 9. Brief asymptomatic runs of AF seen on telemetry or device interrogation, 272Questions and answers, 272References, 274Further reading, 277

11. Atrial Flutter and Atrial Tachycardia, 278

I. Atrial flutter, 278II. Focal atrial tachycardia, 281III. Multifocal atrial tachycardia (MAT) (or chaotic atrial tachycardia), 284IV. Ectopic atrial rhythm, 285

Questions and answers, 285References, 287Further reading, 287

12. Atrioventricular Nodal Reentrant Tachycardia, Atrioventricular Reciprocating Tachycardia, Wolff–Parkinson–White Syndrome, and Junctional Rhythms, 288

I. Sinus tachycardia, 288II. Atrioventricular nodal reentrant tachycardia (AVNRT), 288III. Atrioventricular reciprocating tachycardia (AVRT) and Wolff–Parkinson–White (WPW) syndrome, 291IV. Junctional escape rhythm and accelerated junctional rhythm (or non‐paroxysmal junctional tachycardia), 299

Questions and answers, 301Further reading, 302

13. Bradyarrhythmias, 304

I. AV block, 304II. Sinus bradyarrhythmias, 312III. Bundle branch blocks, bifascicular and trifascicular block, 315


14. Permanent Pacemaker and Implantable Cardioverter Defibrillator, 320

I. Indications for permanent pacemaker implantation, 320II. Types of cardiac rhythm devices, 320III. Pacemaker intervals, 324IV. Leads, 327V. Systematic PM/ICD interrogation using the programmer, 328

VI. Pacemaker troubleshooting, 329VII. Perioperative management of PM and ICD (during any surgery), 333

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VIII. Differential diagnosis and management of the patient who presents with ICD shock(s), 333IX. Evidence and guidelines supporting various pacing devices, 334

Questions and answers: Cases of PM troubleshooting, 338References, 344

15. Basic Electrophysiologic Study, 346

I. General concepts; intracardiac electrograms, 346II. AV conduction abnormalities, 346III. Sinus node assessment, 348IV. Ventricular vs. supraventricular tachycardia, 348V. Dual AV nodal pathways, 348

VI. AVNRT, 349VII. Accessory pathway, orthodromic AVRT, antidromic AVRT, 349VIII. Atrial flutter, 351IX. Inducible VT, 352X. Mapping for ablation, 353

Further reading, 357

16. Action Potential Features and Propagation: Mechanisms of Arrhythmias, Antiarrhythmic Drugs, 358

I. Action potential, 358II. Action potential propagation and mechanisms of arrhythmias, 358III. General mechanism of action of antiarrhythmic agents, 361IV. Modulated receptor hypothesis and use dependence, 363V. Concept of concealed conduction, 364

VI. Specific examples of drugs, 364VII. Amiodarone toxicity, 365VIII. Effect on pacing thresholds and defibrillation thresholds, 365Further reading, 365

PART 6. Pericardial Disorders, 367

17. Pericardial Disorders, 367

1. Acute pericarditis, 368I. Causes of acute pericarditis, 368II. History and physical findings, 368III. ECG findings, 368IV. Echocardiography, 368V. Myopericarditis and perimyocarditis, 369

VI. Treatment, 3692. Tamponade, 370

I. Definition, 370II. Pathophysiology and hemodynamics, 370III. Diagnosis: tamponade is a clinical diagnosis, not an echocardiographic diagnosis, 371IV. Echocardiographic findings supporting the hemodynamic compromise of tamponade, 371V. Role of hemodynamic evaluation, 372

VI. Special circumstances: low‐pressure tamponade, tamponade with absent pulsus paradoxus, regional tamponade, 372VII. Effusive–constrictive pericarditis, 373VIII. Treatment of tamponade, 373

3. Pericardial effusion, 373I. Causes of a pericardial effusion with or without tamponade, 373II. Management of asymptomatic effusions and role of pericardiocentesis, 374III. Note on postoperative pericardial effusions (after cardiac surgery), 375IV. Note on uremic pericardial effusion, 376

4. Constrictive pericarditis, 376I. Causes, 377II. Pathophysiology and hemodynamics, 377III. Hemodynamic findings in constrictive pericarditis and differential diagnosis of constrictive pericarditis:

restrictive cardiomyopathy, decompensated RV failure, COPD, 379IV. Practical performance of a hemodynamic study when constrictive pericarditis is suspected, 381V. Echocardiographic features of constrictive pericarditis, and differentiation between constrictive pericarditis

and restrictive cardiomyopathy, 381VI. Physical exam, ECG findings, BNP, pericardial thickness (CT/MRI), 382VII. Transient constrictive pericarditis, 383VIII. Treatment, 383

Contents xiii

Questions and answers, 384References, 386Further reading, 387

PART 7. Congenital Heart Disease, 389

18. Congenital Heart Disease, 389

1. Acyanotic congenital heart disease, 389I. Atrial septal defect (ASD), 389II. Patent foramen ovale (PFO), 393III. Ventricular septal defect (VSD), 394IV. Patent ductus arteriosus (PDA), 396V. Coarctation of the aorta, 397

VI. Other anomalies, 3972. Cyanotic congenital heart disease, 398

I. Pulmonary hypertension secondary to shunt, 398II. Tetralogy of Fallot, 399III. Ebstein anomaly, 401

3. More complex cyanotic congenital heart disease and shunt procedures, 401I. Functionally single ventricle and Fontan procedure, 401II. Transposition of great arteries (TGA), 403III. Other anomalies, 404


PART 8. Peripheral Arterial Disease, 409

19. Peripheral Arterial Disease, 409

1. Lower extremity peripheral arterial disease, 409I. Clinical tips, 410II. Clinical classification of PAD: critical limb ischemia, acute limb ischemia, atheroembolization, 411III. Diagnosis of PAD, 413IV. Medical therapy of PAD, 414V. Revascularization for PAD, 414

VI. Notes on the technical aspects of surgical and percutaneous therapies, 416VII. Management of acute limb ischemia, 418VIII. Management of lower extremity ulcers, 418

2. Carotid disease, 418I. Assessment of carotid stenosis, 418II. Medical therapy of carotid stenosis, 419III. Revascularization of asymptomatic carotid stenosis, 419IV. Revascularization of symptomatic carotid stenosis, 419V. Main risks of CEA and carotid stenting, 420

VI. CEA versus carotid stenting, 420VII. Carotid disease in a patient undergoing CABG, 420VIII. Subtotal and total carotid occlusions, 420

3. Renal artery stenosis, 421I. Forms of renal artery stenosis, 421II. Screening and indications to revascularize renal artery stenosis, 421III. Notes, 422


20. Aortic Diseases, 428

I. Aortic dissection, 428II. Thoracic aortic aneurysm, 432III. Abdominal aortic aneurysm, 436

References, 437

PART 9. Other Cardiovascular Disease States, 439

21. Pulmonary Embolism and Deep Vein Thrombosis, 439

1. Pulmonary embolism, 439I. Presentation of pulmonary embolism (PE) and risk factors, 439II. Probability of PE, 440

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III. Initial workup, 440IV. Specific PE workup, 440V. Submassive PE, pulmonary hypertension, and thrombolysis, 442

VI. PE and chronic pulmonary hypertension, 443VII. Acute treatment of PE, 443VIII. Duration of anticoagulation, 444IX. Thrombophilias, 445X. PE prognosis, 445

2. Deep vein thrombosis, 445I. Types, 445II. Diagnosis, 445III. Treatment, 446

3. Immune heparin‐induced thrombocytopenia, 446I. Incidence, 446II. Diagnosis, 446III. Treatment, 446


22. Shock and Fluid Responsiveness, 449

1. Shock, 449I. Shock definition and mechanisms, 449II. Goals of shock treatment, 450III. Immediate management of any shock, 450

2. Fluid responsiveness, 452Appendix. Hemodynamic equations, transfusion, and miscellaneous concepts, 454References, 455

23. Hypertension, 456

1. Hypertension, 456I. Stages of hypertension, 456II. Causes of HTN, 456III. Treatment of HTN: goals of therapy, 458IV. Treatment of HTN: timing, first‐line drugs, compelling indications for specific drugs, 458V. Resistant HTN, 459

VI. Peripheral vs. central aortic pressure: therapeutic implications, 460VII. Antihypertensive drugs, 460VIII. Other considerations in therapy, 464

2. Hypertensive urgencies and emergencies, 465I. Definitions, 465II. Treatment of hypertensive emergencies, 465III. Treatment of hypertensive urgencies, 466IV. Causes and workup, 467V. Specific situations, 467


24. D yslipidemia, 472

I. Indications for therapy, 472II. Notes on LDL, HDL, and triglycerides, 473III. Drugs: LDL‐lowering drugs, 473IV. Drugs: TG/HDL‐treating drugs and lifestyle modification, 474V. Metabolic syndrome, 475

VI. Diabetes, 475VII. Elevated hs‐CRP (high‐sensitivity C‐reactive protein test) ≥2 mg/l, 475VIII. Chronic kidney disease (CKD), 475IX. Causes of dyslipidemia to consider, 475X. Side effects of specific drugs: muscle and liver intolerance with statins, fibrates,

and niacin, 475Questions and answers, 476References, 477

Contents xv

25. Pulmonary Hypertension, 479

I. Definition, 479II. Categories of PH, 479III. Two tips in the evaluation of PH, 481IV. Hypoxemia in patients with PH, 481V. Diagnosis: echocardiography; right and left heart catheterization, 481

VI. Treatment, 482Questions and answers, 484References, 486

26. Syncope, 488

I. Neurally mediated syncope (reflex syncope), 488II. Orthostatic hypotension, 489III. Cardiac syncope, 490IV. Other causes of syncope, 490V. Syncope mimic: seizure, 490

VI. Clinical clues, 491VII. Diagnostic evaluation of syncope, 491VIII. Tilt table testing, 494IX. Indications for hospitalization, 494X. Treatment of neurally mediated syncope, 495


27. Chest Pain, Dyspnea, Palpitations, 499

1. Chest pain, 499I. Causes, 499II. Features, 500III. Management of chronic chest pain, 501IV. Management of acute chest pain, 501

2. Acute dyspnea, 502I. Causes, 502II. Notes, 503III. Management, 503

3. Palpitations, 504I. Causes, 504II. Diagnosis, 504

References, 505

28. Infective Endocarditis and Cardiac Rhythm Device Infections, 507

1. Infective endocarditis, 507I. Clinical diagnosis, 507II. Echocardiography: timing and indications, 507III. Organisms, 508IV. Morphology, 508V. Anatomical complications, 508

VI. Indications for valvular surgery and special situations, 5082. Cardiac rhythm device infections, 511

I. Organisms and mechanisms of infection, 511II. Diagnosis, 511III. Diagnosis in patients with bacteremia but no local or TEE signs of infection, 511IV. Management, 511

References, 513

29. Preoperative Cardiac Evaluation, 514

I. Steps in preoperative evaluation, 515II. Surgical risk: surgery’s risk and patient’s risk, 515III. CARP and DECREASE V trials, 516IV. Only the highest‐risk coronary patients require revascularization preoperatively, 516V. Preoperative percutaneous revascularization, 516

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VI. Surgery that needs to be performed soon after stent placement, 517VII. Preoperative β‐blocker therapy, 517VIII. Other interventions that improve outcomes, 517IX. Severe valvular disease, 517X. Perioperative hypertension, 518XI. Preoperative management of patients with pacemakers or ICDs, 518


30. Miscellaneous Cardiac Topics: Cardiac Masses and Tumors, Pregnancy, HIV and Heart Disease, Cocaine and the Heart, Chemotherapy and Heart Disease, Chest X‐Ray, 521

1. Cardiac masses, 522I. Differential diagnosis of a cardiac mass, 522II. Cardiac tumors; focus on atrial myxoma, 522

2. Pregnancy and heart disease, 523I. High‐risk cardiac conditions during which pregnancy is better avoided, 524II. Cardiac conditions that are usually well tolerated during pregnancy, but in which careful cardiac evaluation

and clinical and echo follow‐up are warranted 524III. Cardiac indications for cesarean section, 525IV. Mechanical prosthetic valves in pregnancy: anticoagulation management, 525V. Peripartum cardiomyopathy (PPCM), 525

VI. Cardiovascular drugs during pregnancy, 526VII. Arrhythmias during pregnancy, 526VIII. MI and pregnancy, 526IX. Hypertension and pregnancy, 527

3. HIV and heart disease, 527I. Pericardial disease, 527II. HIV cardiomyopathy, 527III. Pulmonary hypertension (PH), 527IV. CAD, 527

4. Cocaine and the heart, 527I. Myocardial ischemia, 527II. Other cardiac complications of cocaine, 528

5. Chemotherapy and heart disease, 528I. Cardiomyopathy, 528II. Myocardial ischemia, 529

6. Chest X‐ray, 529I. Chest X‐ray in heart failure, 529II. Various forms of cardiomegaly, 530III. Left atrial enlargement; aortic dilatation, 531IV. Lateral chest X‐ray, 532V. Chest X‐ray in congenital heart disease, 532


PART 10. Cardiac Tests: Electrocardiography, Echocardiography, and Stress Testing, 537

31. Electrocardiography, 537

I. Overview of ECG leads and QRS morphology, 537II. Stepwise approach to ECG interpretation, 540III. Rhythm and rate, 541IV. QRS axis in the limb leads and normal QRS progression in the precordial leads, 543V. P wave: analyze P wave in leads II and V

1 for atrial enlargement, and analyze PR interval, 544

VI. Height of QRS: LVH, RVH, 546VII. Width of QRS. Conduction abnormalities: bundle brunch blocks, 548VIII. Conduction abnormalities: fascicular blocks, 551IX. Low QRS voltage and electrical alternans, 553X. Assessment of ischemia and infarction: Q waves, 554XI. Assessment of ischemia: ST‐segment depression and T‐wave inversion, 557XII. Assessment of ischemia: differential diagnosis of ST‐segment elevation, 567XIII. Assessment of ischemia: large or tall T wave, 573XIV. QT analysis and U wave, 574XV. Electrolyte abnormalities, digitalis effect and digitalis toxicity, hypothermia, PE, poor precordial

R‐wave progression, 577

Contents xvii

XVI. Approach to tachyarrhythmias, 582XVII. Approach to bradyarrhythmias: AV block, 585XVIII. Abnormal automatic rhythms that are not tachycardic, 587XIX. Electrode misplacement, 588

Appendix 1. Supplement on STEMI and Q‐wave MI: phases and localization, 589Appendix 2. Spread of electrical depolarization in various disease states using vector illustration, 594Questions and answers, 595References, 598Further reading, 601

32. Echocardiography, 602

1. General echocardiography, 602I. The five major echocardiographic views and the myocardial wall segments, 602II. Global echo assessment of cardiac function and structure, 602III. Doppler: mainly assesses blood flow direction (→ regurgitation), timing, and velocity, 612IV. Summary of features characterizing severe valvular regurgitation and stenosis, 623V. M‐mode echocardiography is derived from 2D echo, 624

VI. Pericardial effusion, 624VII. Echocardiographic determination of LV filling pressure and diastolic function, 628VIII. Additional echocardiographic hemodynamics, 630IX. Prosthetic valves, 634X. Brief note on Doppler physics and echo artifacts, 637

2. Transesophageal echocardiography (TEE) views, 639Further reading, 648

33. Stress Testing, Nuclear Imaging, Coronary CT Angiography, 649

I. Indications for stress testing, 649II. Contraindications to all stress testing modalities, 650III. Stress testing modalities, 650IV. Results, 651

Appendix 1. Mechanisms of various stress modalities, 656Appendix 2. Nuclear stress imaging, 657Appendix 3. Coronary CT angiography, 660References, 663Further reading, 664

PART 11. Cardiac Tests: Invasive Coronary and Cardiac Procedures, 665

34. Angiographic Views: Coronary Arteries and Grafts, Left Ventricle, Aorta, Coronary Anomalies, Peripheral Arteries, Carotid Arteries, 665

I. Right coronary artery, 665II. Left coronary artery, 666III. Coronary angiography views. Recognize the angle of a view: LAO vs. RAO, cranial vs. caudal, 667IV. Coronary angiography views. General ideas: cranial vs. caudal views, 667V. Coronary angiography views. General ideas: foreshortening and identifying branches, 670

VI. Left coronary views, 670VII. Right coronary views, 679VIII. Improve the angiographic view in case of vessel overlap or foreshortening: effects of changing

the angulation, effects of respiration, and vertical vs. horizontal heart, 681IX. Saphenous venous graft views, 682X. LIMA‐to‐LAD or LIMA‐to‐diagonal views, 684XI. Left ventriculography, 685XII. Aortography for assessment of aortic insufficiency, 688XIII. Coronary anomalies, 688XIV. Lower extremity angiography, 691XV. Carotid angiography, 696


35. Cardiac Catheterization Techniques, Tips, and Tricks, 700

I. View for the engagement of the native coronary arteries: RAO vs. LAO, 700II. Design of the Judkins and Amplatz catheters, 700III. Engagement of the RCA, 700IV. How to gauge the level of the RCA origin in relation to the aortic valve level, 703V. What is the most common cause of failure to engage the RCA? What is the next step?, 704

xviii Contents

VI. JR4 catheter engages the conus branch. What is the next step?, 704VII. Left coronary artery engagement: general tips, 704VIII. Management of a JL catheter that is sub‐selectively engaged in the LAD or LCx, 706IX. Specific maneuvers for the Amplatz left catheter, 706X. If you feel that no torque is getting transmitted, what is the next step?, 706XI. Appropriate guide catheters for left coronary interventions, 706XII. Appropriate guide catheters for RCA interventions, 708XIII. Selective engagement of SVGs: general tips, 709XIV. Specific torque maneuvers for engaging the SVGs, 709XV. Appropriate catheters for engaging SVGs, 711

XVI. Engagement of the left internal mammary artery graft, 712XVII. Left ventricular catheterization, 713XVIII. Engagement of anomalous coronary arteries, 714XIX. Specific tips for coronary engagement using a radial approach, 714XX. Damping and ventricularization of the aortic waveform upon coronary engagement, 717XXI. Technique of right heart catheterization, 718

36. Hemodynamics, 720

I. Right heart catheter, 720II. Overview of pressure tracings: differences between atrial, ventricular, and arterial tracings, 720III. RA pressure abnormalities, 720IV. Pulmonary capillary wedge pressure (PCWP) abnormalities, 720V. LVEDP, 725

VI. Cardiac output and vascular resistances, 726VII. Shunt evaluation, 727VIII. Valvular disorders: overview of pressure gradients and valve area calculation, 729IX. Dynamic LVOT obstruction, 733X. Pericardial disorders: tamponade and constrictive pericarditis, 735XI. Exercise hemodynamics, 736

Appendix 1. Advanced hemodynamic calculation: a case of shunt with pulmonary hypertension, 737Questions and answers: Additional hemodynamic cases, 738References, 740

37. Intracoronary Imaging, 741

1. Intravascular ultrasound (IVUS), 741I. Image basics, 741II. Plaque types, 744III. Basic IVUS measurements, 746IV. Interpretation of how a severe stenosis may look mild angiographically, yet severe by IVUS;

significance of lesion haziness, 748V. Endpoints of stenting, 748

VI. Assessment of lesion significance by IVUS, 748VII. Assessment of left main by IVUS, 749

2. Optical coherence tomography (OCT), 749References, 751Further reading, 751

38. Percutaneous Coronary Interventions and Complications, Intra‐Aortic Balloon Pump, Ventricular Assist Devices, and Fractional Flow Reserve, 752

I. Major coronary interventional devices, 752II. Stent thrombosis, restenosis, and neoatherosclerosis, 754III. Peri‐PCI antithrombotic therapy, 756IV. Complex lesion subsets, 756V. Sheath management, 757

VI. Post‐PCI mortality and coronary complications, 758VII. Femoral access complications, 760VIII. Renal, stroke, and atheroembolic complications, 761IX. Intra‐aortic balloon pump (IABP) or intra‐aortic balloon counterpulsation, 762X. Percutaneous LV assist device: Impella and TandemHeart, 765XI. Extracorporeal membrane oxygenation (ECMO), 767XII. Fractional flow reserve (FFR), 767


Index, 775

xix

You should learn solely in order to create. For willing is creating.Friedrich Nietzsche, Thus Spoke Zarathustra

Work without ceasing. If you remember in the night, “I have not done what I ought to have done,” rise up at once and do it. Believe to the end, even if all men went astray and you were left the only one faithful.

Fyodor Dostoevsky, The Brothers Karamazov

Practical Cardiovascular Medicine is a comprehensive yet practical review of all fields of cardiovascular medicine. It addresses various cardiac diseases and presentations using both pathophysiology and clinical evidence, and expands from basic concepts to advanced ones. It should therefore prove useful to experienced physicians as well as trainees. In fact, there is a particular emphasis on the knowledge gaps of cardi-ologists and cardiology fellows. Organizing fellowship conferences and working with cardiology and interventional cardiology fellows has helped me perceive common deficiencies and focus on them.

Colleagues who read the book will find that it provides them with an in‐depth understanding that translates into better patient man-agement. My aim has also been to improve on pre‐existing knowledge of pathophysiology and clinical trials. The book follows a compre-hensive yet easy, practical, and illustrated flow. To facilitate learning, bottom‐line approaches are consistently provided throughout the 38 chapters. There is an extra emphasis on concepts that are frequently misunderstood by practitioners.

Throughout, I have tried to answer daily, practical questions that may not be addressed in any other book. Even classic topics, such as ST‐segment elevation myocardial infarction, heart failure, arrhythmias, atrial fibrillation, cardiac catheterization, or electrocardiography are discussed from a different, fresh, and contemporary viewpoint. The book is comprehensive, and many of its chapters could even stand alone as separate books.

In order to consolidate the understanding of complex topics, review questions with detailed answers are provided at the end of clinical chapters, mainly in a clinical vignette format (approximately 400 questions overall). The book will serve cardiologists and cardiology fellows, but will also be valuable to internists, internal medicine residents, and all professionals caring for patients with cardiovascular disease. I have written this book in an effort to embrace the magic and evolving depths of cardiovascular diseases. It is written with love, and with the hope of improving patients’ outcomes.

Elias B. HannaAugust 2016

Preface

xx

3D three‐dimensionalAAD antiarrhythmic drugAAA abdominal aortic aneurysmABI ankle–brachial indexACC American College of CardiologyACCP American College of Chest PhysiciansACE‐I angiotensin converting enzyme inhibitorACS acute coronary syndromeACT activated clotting timeADHF acutely decompensated heart failureADP adenosine diphosphateAF atrial fibrillationAflutter atrial flutterAHA American Heart AssociationAI aortic insufficiencyAIVR accelerated idioventricular rhythmAM acute marginalANA antinuclear antibodiesAo aortaAoV aortic valveAP accessory pathwayAP anteroposterior viewARB angiotensin‐II receptor blockerARDS acute respiratory distress syndromeARVC arrhythmogenic right ventricular cardiomyopathyARVD arrhythmogenic right ventricular dysplasiaAS aortic stenosisASD atrial septal defectAT anterior tibial arteryAT atrial tachycardiaAT1 receptor type receptor of angiotensin 2AT2 receptor type 2 receptor of angiotensin 2AT III antithrombin IIIIAV atrioventricularAV block atrioventricular blockAVA aortic valve areaAVNRT atrioventricular nodal reentrant tachycardiaAVR aortic valve replacementAVRT atrioventricular reciprocating tachycardiaBBB bundle branch blockBiPAP bilevel positive airway pressureBiV biventricularbiVAD biventricular assist deviceBMS bare‐metal stentBNP brain natriuretic peptideBP blood pressurebpm beats per minutesBSA body surface areaBUN blood urea nitrogenCa calciumCABG coronary artery bypass graftingCAD coronary artery diseaseCBC complete blood countCCB calcium channel blockersCEA carotid endarterectomyCIA common iliac artery

Abbreviations

Abbreviations xxi

CK creatine kinaseCK‐MB creatine kinase MBCKD chronic kidney diseaseCHF congestive heart failureCO cardiac outputCOPD chronic obstructive pulmonary diseaseCPAP continuous positive airway pressureCRP C‐reactive protein testCRT cardiac resynchronization therapyCT computed tomographyCTA computed tomography angiographyCTI cavotricuspid isthmusCTO chronic total occlusionCTPH chronic thromboembolic pulmonary hypertensionCVP central venous pressureCW continuous wave DopplerCYP 450 cytochrome P450CXR chest X‐rayDAD delayed afterdepolarizationDBP diastolic blood pressureDC cardioversion R‐wave synchronized direct‐current cardioversionDCM dilated cardiomyopathyDES drug‐eluting stentDHP dihydropyridine (calcium channel blocker)dP/dt delta pressure/delta time (sharpness of rise in pressure over time)DTI direct thrombin inhibitorDTS Duke treadmill scoreDVT deep vein thrombosisEAD early afterdepolarizationECG electrocardiogramecho echocardiogramECMO extracorporeal membrane oxygenationED emergency departmentEF ejection fractionEIA external iliac arteryEP electrophysiologicalERO effective regurgitant orificeESC European Society of CardiologyESR erythrocyte sedimentation rateESRD end‐stage renal diseaseFFR fractional flow reserveFiO

2 fraction of inspired oxygenFMD fibromuscular dysplasiaGFR glomerular filtration rateGI gastrointestinalGPI glycoprotein IIb–IIIa inhibitorHb hemoglobinHbA1c glycosylated hemoglobinHCM hypertrophic cardiomyopathyHCTZ hydrochlorothiazideHDL high‐density lipoproteinHF heart failureHFpEF heart failure with preserved ejection fractionHFrEF heart failure with reduced ejection fractionHIT heparin‐induced thrombocytopeniaHIV Human immunodeficiency virusHOCM hypertrophic obstructive cardiomyopathyHR heart ratehs‐CRP high sensitivity C‐reactive protein testHTN hypertensionIABP intra‐aortic balloon pumpICD implantable cardioverter defibrillatorICU intensive care unit

xxii Abbreviations

INR international normalized ratioIV intravenous or intravenouslyIVC inferior vena cavaIVC‐ isovolumic contractionIVCT isovolumic contraction timeIVR isovolumic relaxationIVRT isovolumic relaxation timeIVUS intravascular ultrasoundJVD jugular venous distensionJVP jugular venous pressureK potassiumLA left atriumLAA left atrial appendageLAFB left anterior fascicular blockLAD left anterior descending arteryLAO left anterior obliqueLBBB left bundle branch blockLCx left circumflex coronary arteryLDL low‐density lipoproteinLHC left heart catheterization and coronary angiogramLIMA left internal mammary arteryLLSB left lower sternal borderLM left mainLMWH low‐molecular‐weight heparinLPFB left posterior fascicular blockLUSB left upper sternal borderLV left ventricle or left ventricularLVAD left ventricular assist deviceLVEDD left ventricular end‐diastolic diameterLVEDP left ventricular end‐diastolic pressureLVEF left ventricular ejection fractionLVESD left ventricular end‐systolic diameterLVH left ventricular hypertrophyLVOT left ventricular outflow tractMAP mean arterial pressureMAT multifocal atrial tachycardiaMET metabolic equivalent of taskmph miles per hourMI myocardial infarctionMR mitral regurgitationMRA magnetic resonance angiographyMRI magnetic resonance imagingMS mitral stenosisMV mitral valveMV O

2 mixed venous oxygen saturationMVA mitral valve areaMVP mitral valve prolapseMVR mitral valve replacementNa sodiumNO nitric oxideNSAID non‐steroidal anti‐inflammatory drugNSTEMI non‐ST‐segment elevation myocardial infarctionNSVT non‐sustained ventricular tachycardiaNT pro‐BNP amino‐terminal pro‐brain natriuretic peptideNTG nitroglycerinNYHA New York Heart AssociationOCT optical coherence tomographyOM obtuse marginal branch of the left circumflexP pressurePA pulmonary arterial or pulmonary arteryPA O2 pulmonary arterial oxygen saturationPAC premature atrial complexPaCO2 partial pressure of carbon dioxide in arterial bloodPAD peripheral arterial disease

Abbreviations xxiii

PAH pulmonary arterial hypertensionPAI plasminogen activator inhibitorPaO2 arterial oxygen pressurePaO2 alveolar oxygen pressurePCI percutaneous coronary interventionPCSK9 Proprotein convertase subtilisin/kexin type 9PCWP pulmonary capillary wedge pressurePDA patent ductus arteriosusPDA posterior descending artery branch of the right coronary artery or left circumflexPE pulmonary embolismPEA pulseless electrical activityPET positron emission tomographyPFO patent foramen ovalePFT pulmonary function testingPH pulmonary hypertensionPHT pressure half‐timePISA proximal isovelocity surface areaPJRT permanent junctional reciprocating tachycardiaPLB posterolateral ventricular branches of the right coronary artery or left circumflexPM pacemakerPMBV percutaneous mitral balloon valvuloplastyPMT pacemaker‐mediated tachycardiaPND paroxysmal nocturnal dyspneaPOTS postural orthostatic tachycardia syndromePPD purified protein derivative for Mycobacterium tuberculosisPPI proton pump inhibitorPPM patient/prosthesis mismatchPR pulmonic regurgitationPS pulmonic stenosisPT posterior tibial arteryPTT partial thromboplastin timePV loop pressure–volume loopPV O

2 pulmonary venous oxygen saturationPVARP post‐ventricular atrial refractory periodPVC premature ventricular complexPVR pulmonary vascular resistancePW pulsed wave DopplerQp pulmonary blood flowQs systemic blood flowQTc corrected QT intervalRA right atriumRAAS renin‐angiotensin‐aldosterone systemRAO right anterior obliqueRAS renal artery stenosisRBBB right bundle branch blockRCA right coronary arteryRHC right heart catheterizationRIMA right internal mammary arteryrPA reteplaserpm revolutions per minuter‐tPA recombinant tissue plasminogen activatorRUSB right upper sternal borderRV right ventricle/ventricularRVAD right ventricular assist deviceRVEDP right ventricular end‐diastolic pressureRVH right ventricular hypertrophyRVOT right ventricular outflow tractSA sinoatrialSA O

2 systemic arterial oxygen saturationSAM systolic anterior motionSaO2 arterial oxygen saturationSBE subacute bacterial endocarditisSBP systolic blood pressureSCD sudden cardiac death

xxiv Abbreviations

SIRS systemic inflammatory response syndromeSFA superficial femoral arterySNRT sinus node reentrant tachycardiaSPECT single photon emission computed tomography (nuclear imaging)SQ subcutaneouslySTEMI ST‐segment elevation myocardial infarctionSTS Society of Thoracic SurgeonsSV stroke volumeSVC superior vena cavaSVG saphenous venous graftSvO2 mixed venous oxygen saturationSVR systemic vascular resistanceSVT supraventricular tachycardiaTAA thoracic aortic aneurysmTdP torsades de pointesTEE transesophageal echocardiogramTGA transposition of great arteriesTIA transient ischemic attackTID transient ischemic dilatationTR tricuspid regurgitationTSH thyroid stimulating hormoneTTE transthoracic echocardiogramUA unstable anginaUFH unfractionated heparinVAD ventricular assist deviceV/Q scan lung ventilation/perfusion scanVF ventricular fibrillationVLDL very‐low‐density lipoproteinVp velocity of propagationVSD ventricular septal defectVSR ventricular septal ruptureVT ventricular tachycardiaVTI velocity‐time integralWPW Wolff–Parkinson–White

Practical Cardiovascular Medicine, First Edition. Elias B. Hanna. © 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.

1

Non‐ST‐Segment Elevation Acute Coronary Syndrome1

I. Types of acute coronary syndrome (ACS) 1

II. Mechanisms of ACS 2

III. ECG, cardiac biomarkers, and echocardiography in ACS 3

IV. Approach to chest pain, likelihood of ACS, risk stratification of ACS 4

V. Management of high‐risk NSTE‐ACS 6

VI. General procedural management after coronary angiography: PCI, CABG, or medical therapy only 9

VII. Management of low‐risk NSTE‐ACS and low‐probability NSTE‐ACS 11

VIII. Discharge medications 11

IX. Prognosis 12

Appendix 1. Complex angiographic disease, moderate disease 13

Appendix 2. Women and ACS, elderly patients and ACS, CKD 14

Appendix 3. Bleeding, transfusion, prior warfarin therapy, gastrointestinal bleed 15

Appendix 4. Antiplatelet and anticoagulant therapy 16

Appendix 5. Differences between plaque rupture, plaque erosion, and spontaneous coronary dissection 19

Appendix 6. Harmful effects of NSAIDs and cyclooxygenase‐2 inhibitors in CAD 19

Questions and answers 19

Part 1 CoroNAry Artery DISeASe

I. Types of acute coronary syndrome (ACS)A. Unstable anginaUnstable angina is defined as any of the following clinical presentations, with or without ECG evidence of ischemia and with a normal troponin:

• Crescendo angina: angina that increases in frequency, intensity, or duration, often requiring a more frequent use of nitroglycerin• New‐onset (<2 months) severe angina, occurring during normal activities performed at a normal pace• Rest angina• Angina occurring within 2 weeks after a myocardial infarction (post‐infarction angina)

B. Non‐St‐segment elevation myocardial infarction (NSteMI)A rise in troponin, per se, is diagnostic of myocardial necrosis but is not sufficient to define myocardial infarction (MI), which is myocardial necrosis secondary to myocardial ischemia. Additional clinical, ECG, or echocardiographic evidence of ischemia is needed to define MI.

In fact, MI is defined as a troponin elevation above the 99th percentile of the reference limit (~0.03 ng/ml, depending on the assay) with a rise and/or fall pattern, along with any one of the following four features: (i) angina; (ii) ST‐T abnormalities, new LBBB, or new Q waves on ECG; (iii) new wall motion abnormality on imaging; (iv) intracoronary thrombus on angiography.1 NSteMI is defined as MI with-out persistent (>20 min) ST‐segment elevation.

Isolated myocardial necrosis is common in critically ill patients and manifests as a troponin rise, sometimes with a rise and fall pat-tern, but frequently no other MI features. Also, troponin I usually remains <1 ng/ml in the absence of underlying CAD.2,3

2 Part 1. Coronary Artery Disease

A rise or fall in troponin is necessary to define MI. A fluctuating troponin or a mild, chronically elevated but stable troponin may be seen in chronic heart failure, myocarditis, severe left ventricular hypertrophy, or advanced kidney disease. While having a prognostic value, this stable troponin rise is not diagnostic of MI. Different cutoffs have been used to define a relevant troponin change, but, in general, a troponin that rises above the 99th percentile with a rise or fall of >50–80% is characteristic of MI (ACC guidelines use a less specific cutoff of 20%; 50–80% cutoff is more applicable to low troponin levels <0.1 ng/ml).4

C. St‐segment elevation myocardial infarction (SteMI)STEMI is defined as a combination of ischemic symptoms and persistent, ischemic ST‐segment elevation.1,5 For practical purposes, ischemic symptoms with ongoing ST‐segment elevation of any duration are considered STEMI and treated as such. The diagnosis may be retrospec-tively changed to NSTEMI if ST elevation quickly resolves without reperfusion therapy, in <20 minutes.

II. Mechanisms of ACSA. true ACS is usually due to plaque rupture or erosion that promotes platelet aggregation (spontaneous or type 1 MI). This is followed by thrombus formation and microembolization of platelet aggregates. In NSTEMI, the thrombus is most often a platelet‐rich non‐occlusive thrombus. This contrasts with STEMI, which is due to an occlusive thrombus rich in platelets and fibrin. Also, NSTEMI usually has greater collateral flow to the infarct zone than STEMI.

As a result of the diffuse inflammation and alteration of platelet aggregability, multiple plaque ruptures are seen in ~30–80% of ACS cases, although only one is usually considered the culprit in ACS.8 This shows the importance of medical therapy to “cool down” the diffuse process, and explains the high risk of ACS recurrence within the following year even if the culprit plaque is stented.8

Occasionally, a ruptured plaque or, more commonly, an eroded plaque may lead to microembolization of platelets and thrombi and impaired coronary flow without any residual, angiographically significant lesion or thrombus.

B. Secondary unstable angina and NSteMI (type 2 MI). In this case, ischemia is related to severely increased O2 demands (demand/supply mismatch). The patient may have underlying CAD but the coronary plaques are stable without acute rupture or thrombosis. Conversely, the patient may not have any underlying CAD, in which case troponin I usually remains <0.5–1 ng/ml.2,3 Acute antithrombotic therapy is not warranted.

Cardiac causes of secondary unstable angina/NSTEMI include: severe hypertension, acute HF, aortic stenosis/hypertrophic cardiomyopathy, tachyarrhythmias. Non‐cardiac causes of secondary unstable angina/NSTEMI include: gastrointestinal bleed, severe anemia, hypoxia, sepsis.

While acute HF often leads to troponin elevation, ACS with severe diffuse ischemia may lead to acute HF, and in fact 30% of acute HF presentations are triggered by ACS.9 HF presentation associated with crescendo angina, ischemic ST changes, or severe troponin rise (>0.5–1 ng/ml) should be considered ACS until CAD is addressed with a coronary angiogram.

C. Coronary vasospasmIt was initially hypothesized by Prinzmetal and then demonstrated in a large series that vasospasm and vasospastic angina (Prinzmetal) often occur in patients with significant CAD at the site of a significant atherosclerotic obstruction.10,11 In one series, 90% of patients with vasospastic angina had significant, single‐ or multivessel CAD. Most frequently, CAD was not only significant but unstable.12 In fact, a ruptured plaque is frequently accompanied by vasospasm, as the activated platelets and leukocytes release vasoconstrictors. About 20% of these patients with underlying CAD go on to develop a large MI, while >25% develop severe ventricular arrhythmias or paroxysmal AV block with syncope.

Unstable angina and NSTEMI are grouped together as non‐ST‐segment elevation ACS (NSTE‐ACS). However, it must be noted that unstable angina has a much better prognosis than NSTEMI, and particularly that many patients labeled as unstable angina do not actually have ACS.6 In fact, in the current era of highly sensitive troponin assays, a true ACS is often accompanied by a troponin rise. Unstable angina is, thus, a “vanishing” entity.7

In the absence of clinical or ECG features of MI, the troponin rise is not even called MI.

Acute bleed, severe anemia, or tachyarrhythmia destabilizes a stable angina. Treating the anemia or the arrhythmia is a first priority in these patients, taking precedence over treating CAD.

While acute, malignant hypertension may lead to secondary ACS and troponin rise, ACS with severe angina may lead to hypertension (catecholamine surge). In ACS, hypertension drastically improves with angina relief and nitroglycerin, whereas in malignant hypertension, hypertension is persistent and difficult to control despite multiple antihypertensive therapies, nitroglycerin only having a minor effect. Nitroglycerin has a mild and transient antihypertensive effect, and thus a sustained drop in BP with nitroglycerin often implies that hypertension was secondary to ACS.

Chapter 1. Non-St-Segment elevation Acute Coronary Syndrome 3

Vasospasm may also occur chronically without plaque rupture, and, sometimes, without any significant atherosclerotic stenosis, and may lead to chronic vasospastic angina. Vasospasm is frequently the underlying disease process in patients with a typical angina or ACS yet no significant CAD (isolated vasospasm).13,14 The diagnosis is definitely made when: (i) vasospasm is angiographically reproduced with provocative testing, along with (ii) symptoms and (iii) ST changes during testing. Vasospasm may also occur at the microvascular level (endothelial dysfunction with diffuse microvascular constriction).

III. ECG, cardiac biomarkers, and echocardiography in ACSA. eCGThe following ECG findings are diagnostic of non‐ST elevation ischemia:

• ST depression ≥0.5 mm, especially if transient, dynamic, not secondary to LVH, and occurring during the episode of chest pain.• Deep T‐wave inversion ≥3 mm (T inversion <3 mm is non‐specific).• Transient ST elevation (lasting <20 minutes). This corresponds to a thrombus that occludes the lumen off and on, an unstable plaque with

vasospasm, or, less commonly, a stable plaque with vasospasm.

Only 50% of patients with non‐ST elevation ACS have an ischemic ECG.15 In particular, in the cases of NSTEMI and unstable angina, 20% and 37%, respectively, have an absolutely normal ECG.16 Also, many patients have LVH or bundle branch blocks that make the ECG less interpretable and non‐specific for ischemia. Of patients with a normal ECG, 2% end up having MI, mostly NSTEMI, and 2–4% end up having unstable angina.17

ECG performed during active chest pain has a higher sensitivity and specificity for detection of ischemia. However, even when performed during active ischemia, the ECG may not be diagnostic, particularly in left circumflex ischemia. In fact, up to 40% of acute LCx total occlusions and 10% of LAD or RCA occlusions are not associated with significant ST‐T abnormalities, for various reasons: (i) the vessel may occlude progressively, allowing the development of robust collaterals that prevent ST elevation or even ST depression upon coronary occlusion; (ii) the ischemic area may not be well seen on the standard leads (especially posterior or lateral area); (iii) underlying LVH or bundle branch blocks may obscure new findings; a comparison with old ECGs is valuable. In general, ~15–20% of NSTEMIs are due to acute coronary occlusion, frequently LCx occlusion, and are, pathophysiologically, STEMI‐equivalents missed by the ECG and potentially evolving into Q waves.18 NSTEMI patients with acute coronary occlusion have a higher 30‐day mortality than patients without an occluded culprit artery, probably related to delayed revascularization of a STEMI‐equivalent.19

To improve the diagnostic yield of the ECG:

• In a patient with persistent typical angina and non‐diagnostic ECG, record the ECG in leads V7–V9. ST elevation is seen in those leads in >80% of LCx occlusions, many of which are missed on the 12‐lead ECG.

• Repeat the ECG at 10–30‐minute intervals in a patient with persistent typical angina.• Perform urgent coronary angiography in a patient with persistent distress and a high suspicion of ACS, even if ECG is non‐diagnostic and

troponin has not risen yet.• ECG should be repeated during each recurrence of pain, when the diagnostic yield is highest. ECG should also be repeated a few hours

after pain resolution (e.g., 3–9 hours) and next day, looking for post‐ischemic T‐wave abnormalities and Q waves, even if the initial ECG is non‐diagnostic. The post‐ischemic T waves may appear a few hours after chest pain resolution.

B. Cardiac biomarkers: troponin I or t, CK‐MBThese markers start to rise 3–12 hours after an episode of ischemia lasting >30–60 minutes (they may take up to 12 hours to rise).

Troponin is highly specific for a myocardial injury. However, this myocardial injury may be secondary not to a coronary event but to other insults (e.g., critical illness, HF, hypoxia, hypotension), without additional clinical, ECG, or echocardiographic features of MI.

Kidney disease may be associated, per se, with a chronic mild elevation of troponin I. This is not related to reduced renal clearance of troponin, a marginal effect at best. It is rather due to the underlying myocardial hypertrophy, chronic CAD, and BP swings. This leads to a chronic ischemic imbalance, and, as a result, a chronic myocardial damage.

Any degree of troponin rise, even if very mild (e.g., 0.04 ng/ml), in a patient with angina and without a context of secondary ischemia indicates a high‐risk ACS. The higher the troponin rises (meaning >1 ng/ml or, worse, >5 ng/ml), the worse the prognosis.20 Also, an elevated troponin associated with elevated CK‐MB signifies a larger MI and a worse short‐term prognosis than an isolated rise in troponin.

CK‐MB and troponin peak at ~12–24 hours and 24 hours, respectively. CK and CK‐MB elevations last 2–3 days. Troponin elevation lasts 7–10 days; minor troponin elevation, however, usually resolves within 2–3 days. In acutely reperfused infarcts (STEMI or NSTEMI), those markers peak earlier (e.g., 12–18 hours) and sometimes peak to higher values than if not reperfused, but decline faster. Hence, the total amount of biomarkers released, meaning the area under the curve, is much smaller, and the troponin elevation resolves more quickly (e.g., 4–5 days). The area under the curve, rather than the actual biomarker peak, correlates with the infarct size.

Troponin I or T is much more sensitive and specific than CK‐MB. Frequently, NSTEMI is characterized by an elevated troponin and a normal CK‐MB, and typically CK‐MB only rises when troponin exceeds 0.5 ng/ml. To be considered cardiac‐specific, an elevated CK‐MB must be accompanied by an elevated troponin; the ratio CK‐MB/CK is typically >2.5% in MI, but even this ratio is not specific for MI. When increased, CK‐MB usually rises earlier than troponin, and thus an elevated CK‐MB with a normal troponin and normal CK may imply an early MI (as long as troponin eventually rises). Overall, CK‐MB testing is not recommended on a routine basis but has two potential values: (i) in patients with marked troponin elevation and subacute symptom onset, CK‐MB helps diagnose the age of the infarct (a normal CK‐MB implies that MI is several days old); (ii) CK‐MB elevation implies a larger MI.

Cardiac biomarkers, if negative, are repeated at least once 3–6 hours after admission or pain onset. If positive, they may be repeated every 8 hours until they trend down, to assess the area under the curve/infarct size.*

* A new generation of high‐sensitivity troponin assays (hs‐troponin) has a much lower detection cutoff (detection cutoff = 0.003 ng/ml vs. 0.01 ng/ml for the older generation; MI cutoff = 0.03 ng/ml for both generations). If hs‐troponin is lower than the detection cutoff on presentation or lower than the MI cutoff 3 hours later, MI can be ruled out with a very high negative predictive value >99.4%.4 The positive predictive value of these low values, however, is 75% at best, and is improved by seeking a significant rise or fall pattern.

4 Part 1. Coronary Artery Disease

C. echocardiography: acute resting nuclear scanThe absence of wall motion abnormalities during active chest pain argues strongly against ischemia. For optimal sensitivity, the patient must have active ischemia while the test is performed. Wall motion abnormalities may persist after pain resolution in case of stunning or suben-docardial necrosis involving >20% of the inner myocardial thickness (<20% subendocardial necrosis or mild troponin rise may not lead to any discernible contractile abnormality).24

On the other hand, wall motion abnormalities, when present, are not very specific for ongoing ischemia and may reflect an old infarct. However, the patient is already in a high‐risk category.

Acute resting nuclear scan, with the nuclear injection performed during active chest pain or within ~3 hours of the last chest pain episode, has an even higher sensitivity than echo in detecting ischemia. An abnormal resting scan, however, is not specific, as the defect may be an old infarct or an artifact.

IV. Approach to chest pain, likelihood of ACS, risk stratification of ACSOnly 25% of patients presenting with chest pain are eventually diagnosed with ACS. On the other hand, ~5% of patients discharged home with a presumed non‐cardiac chest pain are eventually diagnosed with ACS, and the ECG is normal in 20–37% of patients with ACS.17

Consider the following approach in patients presenting with acute or recent chest pain.A. Assess the likelihood of ACS (table 1.1)

B. Assess for other serious causes of chest pain at least clinically, by chest X‐ray and by ECG (always think of pulmonary embolism, aortic dissection, and pericarditis).

C. the patient with a probable ACS should be risk stratified into a high‐ or low‐risk category1. High‐risk ACS. Any of the following features implies a high risk of major adverse coronary events (mortality, MI, or need for urgent

revascularization within 30 days), and justifies early coronary angiography and a more aggressive antithrombotic strategy. These high‐risk features should only be sought after establishing that ACS is highly probable:25

In patients with a recent infarction (a few days earlier), the diagnosis of reinfarction relies on:

• CK or CK‐MB elevation, as they normalize faster than troponin, or• Change in the downward trend of troponin (reincrease >20% beyond the nadir)1

In the post‐PCI context, MI is diagnosed by a troponin elevation >5× normal, along with prolonged chest pain >20 min, ischemic ST changes or Q waves, new wall motion abnormality, or angiographic evidence of procedural complications.1 In patients with elevated baseline cardiac markers that are stable or falling, post‐PCI MI is diagnosed by ≥50% reincrease of the downward trending troponin (rather than 20% for spontaneous reinfarction). Note that spontaneous NSTEMI carries a much stronger prognostic value than post‐PCI NSTEMI, despite the often mild biomarker elevation in the former (threefold higher mortality). In fact, in spontaneous NSTEMI, the adverse outcome is related not just to the minor myocardial injury but to the ruptured plaques that carry a high future risk of large infarctions. This is not the case in the controlled post‐PCI MI.21,22 Along with data suggesting that only marked CK‐MB elevation carries a prognostic value after PCI, an expert document has proposed the use of CK‐MB ≥10× normal to define post‐PCI MI, rather than the mild troponin rise.22

In the post‐CABG context, MI is diagnosed by a troponin or CK‐MB elevation >10× normal, associated with new Q wave or LBBB, or new wall motion abnormality.1

In randomized trials recruiting patients with high‐risk non‐ST‐segment elevation ACS, only ~60–70% of patients had a positive troponin; the remaining patients had unstable angina. However, with the current generation of high‐sensitivity troponin, unstable angina is becoming a rare entity. In fact, in patients with a serially negative troponin, ACS is unlikely.7 This is particularly true in cases of serially undetectable troponin (<0.003–0.01 ng/ml), where ACS is very unlikely and the 30‐day risk of coronary events is <0.5%.4,23

When ischemic imbalance occurs without underlying CAD, troponin I usually remains <0.5–1 ng/ml.2,3 However, when ischemic imbalance occurs on top of underlying stable CAD, troponin I may rise to levels >0.5–1 ng/ml. Therefore, a troponin I level >0.5–1 ng/ml suggests obstructive CAD, whether the primary insult is coronary (thrombotic, type 1 MI) or non‐coronary (type 2 MI); the positive predictive value for CAD is very high and approaches 90%, less so if renal dysfunction is present.2

Conversely, any degree of troponin rise, even if very mild (e.g., 0.04 ng/ml), in a patient with angina and without a context of secondary ischemia indicates a high‐risk ACS.

• The relief of chest pain with sublingual nitroglycerin does not reliably predict ACS. Similarly, the relief of chest pain with a “GI cocktail” does not predict the absence of ACS.25

• Chest pain lasting over 30–60 minutes with consistently negative markers usually implies a low ACS likelihood. A prolonged pain is usually one of two extremes, an infarct or a non‐cardiac pain.

practical cardiovascular · 2017-01-26 · to my mother marie, my sister eliana, and my beautiful...

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