Practical Cardiology M Gabriel Khan
INDEX
Page numbers followed by f refer to figure fc refer to flowchart and t refer to table.
A
Acetyl-CoA-acyltransferase 217
Acid-base imbalance 256
Acidosis 170
Acinar shadows 117, 119
Acquired immunodeficiency syndrome 200
Acute infarction ramipril efficacy
study 158
trial 189
Adenopathy 109
Adenosine 257
intravenous 91
Adenovirus 201
African-American heart failure trial 173, 185
Air bronchogram 117
Airflow obstruction 4
Airspace disease 115, 116
Airways 124, 313
Alcohol 94
abuse 215
Aldosterone antagonists 183
Allopurinol 20
Alpha 1-antitrypsin deficiency 120f
Alpha-blockers 39
Alveolar disease 116
Alveolar pulmonary edema, diffuse 166f
American Association of Clinical Endocrinologists 265
American College of Cardiology 214, 229, 313
Foundation 137
American College of Endocrinology 265
American Heart Association 39, 182, 214, 229, 313
Guidelines 137
Amiloride 34, 167, 172, 173, 183, 190
Amiodarone 65, 98, 188
Amlodipine 19, 30, 37, 39
Amoxicillin 182
Ampicillin 178
Amprenavir 217
Amyloid 291
Amyloidosis 150, 170, 186
systemic 292f
Anemias 4, 12, 15
Aneurysmal dilation, mild 115f
Angina 20, 226
variant 23
Angioedema 31, 218
Angiotensin-converting enzyme inhibitor 9, 28, 31, 3739, 130, 133, 158, 159, 164, 168, 169, 173, 183, 187, 189, 190, 212, 229, 266, 269, 296, 306
Angiotensin-receptor blockers 28, 37, 38, 164, 168, 184, 186, 187, 190, 266, 269, 306
Anglo-scandinavian cardiac outcomes trial 26, 297
Anorexia 171
Anteroseptal myocardial infarction 148f
Antibiotic
drug 271, 283
intravenous 178
prophylaxis 182
Anticoagulants 197, 260, 283
Antidepressants 92
Antidromic preexcited tachycardia 246
Antifungal
agents 250
drugs 271
medicines 216
Antihistamines 92
Antihypertensive agent 33, 37
Antithrombotic regimes 226
Antituberculosis drug 271
Antiviral agents 250
Anxiety 5, 240
Aorta 178f, 221, 224, 225, 229, 230, 233, 234, 237, 238, 285, 286
ascending 105f
coarctation of 182
descending 285
proximal descending 205f
thoracic 104, 110
Aortic aneurysm 110
rupture 28
Aortic dissection 13, 39, 197, 204, 207, 228, 311
Aortic knuckle 111f
Aortic regurgitation 164, 226, 229f
severe 221, 229, 229f, 236f
Aortic root, dilation of 228
Aortic stenosis 73, 164, 165, 207, 221, 223f, 311
moderate 222
severe 221, 222
Aortic valve
disease 94
level of 225f
orifice 224f
Apical hypertrophic cardiomyopathy 284, 284f
Apical infarction 145
Apixaban 191
Arch of aorta, posterior aspect of 105f
Arizona observational study 312
Arrhythmias 12, 45, 79, 92, 194, 241, 255, 256, 298
classification of 79
diagnosis 244
life-threatening 245
treatment 244
Arrhythmogenic right ventricular dysplasia 291, 291f
Arterial hypertension, pulmonary 1
Artery, pulmonary 107f, 229f, 234
Arthralgia 218, 242
Arthritis 242
rheumatoid 150, 197
Aspergillosis 202
Aspirin 16, 149, 153, 159, 187, 311
Astemizole 65
Asteroid 127
Asthma 4, 244
Atelectasis 107, 115, 117
radiographic signs of 118
types of 117
Atenolol 17, 36, 158, 159, 185, 194, 298, 299
Atheroma 12, 127, 129
formation, pathophysiology of 129fc
obstructive plaque of 12
Atherothrombosis 127
Atorvastatin 188, 216
Atrial fibrillation 12, 28, 32fc, 81, 86, 86f, 9294, 95f, 96f, 132, 164, 169, 194, 194, 207, 232, 246, 247, 249, 249f, 250f, 259, 260, 283, 285
Atrial flutter 79, 81, 86, 91, 92, 92f95f, 246, 247, 248f, 251f, 258
Atrial hypertrophy, right 62f, 319f
Atrial myxoma 207, 242
Atrial premature
beats 81, 82f, 253
P wave, nonconduction of 81
Atrial septal defect 67, 164
Atrial tachycardia 79, 86, 87, 246
persistent 87, 88, 91
Atrioventricular block 88, 253
complete 102f
second-degree 100, 171, 251
third-degree 101, 171, 254, 256f
Atrioventricular dissociation 96
Atrioventricular nodal reentrant tachycardia 67, 86, 91, 246
Automatic external defibrillators 311
Autopsy 214
Azithromycin 188, 217
Azole antifungals 217
B
Bacteraemia 181
Bacterial origin, acute pneumonia of 117
Balloon valvuloplasty 235
Basal emphysema 119
Basic life support 313
Basilar reticulonodular disease 126f
Benazepril 190
Bendrofluazide 30
Benign solitary pulmonary nodule, signs of 121
Berry aneurysm 28
Beta-adrenergic blockade, effects of 131fc
Beta-blocker 7, 16, 22, 34, 65, 132fc, 158, 171, 174, 185, 187, 190, 191, 193, 251, 266, 288, 302fc
diuretics and statins 25
heart attack trial 17
lower plasma endothelin-1 16
therapy 25, 187
thiazide diuretics 25
Bicuspid aortic valve 182, 221f, 224f
Bilateral pulmonary disease 122
Biphasic wave 59
Bisoprolol 17, 18, 30, 36, 133, 159, 170, 185, 187, 188, 245, 267, 298, 312
Biventricular endomyocardial fibrosis 289f
Blood pressure 1, 28, 31f, 32fc, 40, 132, 204, 266, 302
control 267
diastolic 227
goal 194
systolic 28, 31fc, 186, 207
Blood sitosterol, reduction of 264
Bones 105, 106
Borrelia burgdorferi 202
Bounding pulse 228
Bradyarrhythmias 100, 150, 207, 250
Bradycardia 37
Breast cancer 8
Breath
shortness of 4, 226, 231
sounds, quality of 7
Bronchial wall thickening 119
Bronchiectasis 4, 115, 120, 120f, 125f
evaluation of 124
Bronchoalveolar carcinoma 117
Bronchogenic carcinoma
bilateral synchronous 124f
large cell 121f
Bruce protocol 13
Brugada syndrome 91, 91f, 92, 130, 311
B-type natriuretic peptide 166
Bundle branch block 65, 81, 174
Burning-like indigestion 135
Burns, severe 151
c
Calcific aortic valve disease 223
Calcinosis cutis 125f
Calcium
antagonists 7, 18, 22, 31, 28, 36, 190
supplements 308
Candesartan 168, 184, 190
Candida 202
Captopril 168, 184, 189191
Cardiac arrest 311, 313
major causes of 311
Cardiac arrhythmias 171
Cardiac insufficiency bisoprolol 171
Cardiac nuclear scans 14
Cardiac pain, locations of 33f, 13f, 133f
Cardiac resynchronization therapy 174, 285
Cardiac shadow 109
Cardiac shunts, right-to-left 4
Cardiac tamponade 6, 201, 207, 311
Cardiac troponins 21
Cardiac tumors, benign primary 242
Cardioactive drugs 251
Cardiomyopathy 67, 70, 73, 86, 94, 278
dilated 284, 285f, 286f
disease 69
hypertrophic 76, 83, 146, 207, 278, 279f, 311
peripartum 287
restrictive 286
Cardiopulmonary resuscitation technique 311, 313
Cardiotomy 197
Cardiovascular disease 29, 30, 127, 190, 264, 297, 311
Carditis 241
Carotid sinus
massage 91, 92, 256
syncope 207, 213
Carvedilol 17, 36, 158, 160, 171, 185, 299
postinfarct survival controlled evaluation 299
prospective randomized cumulative survival 300
Catecholamine
crisis 39
infusion 131
Catheter ablation 258
Catheter insertion 109
Cavitation 115
Cerebral
arteries 12, 23
blood flow 207
Cerebrovascular disease 65
Cervical
disc disease 1
osteoarthritis 1
Chagas disease 67, 292
Chagasic myocarditis 76
Chaotic atrial tachycardia 88
Chest compression 313
Chest computed tomography 124
Chest pain 1, 240
acute 21, 290f
causes of 1
common causes of 1
evaluation of 1
Chest pain, pleuritic 10
Chest radiograph
lateral 113
normal lateral 105
normal posteroanterior 104, 104f
posteroanterior 104, 106
Chest wall
abnormalities 116
pain 1, 2
Chest X-ray 165, 232
interpretation 104
Cheyne-Stokes respiration 6
Chlorthalidone 33, 34, 190
Cholecystitis 218
Cholelithiasis 218
Chordae tendineae, rupture 235, 241
Chorea 241
Cicatrization atelectasis 118
Circus movement tachycardia 91
Cirrhosis 8, 100, 250
biliary 215
Clarithromycin 188, 217, 271
Clopidogrel 188, 194
Clostridia 202
Coalescence 117
Cocaine 92
Cocoa 305
Coenzyme 306, 307
Colchicine 194
plus conventional therapy 200
Collagen disease 197
Combination pill chlorthalidone 190
Congenital heart disease, congenital 11, 67, 76, 94, 167, 174
Conn's syndrome 34
Constipation 37
Continuous chest compressions 312
Cor pulmonale 61, 67, 86, 94, 146, 165
Coronary angiography 130, 159, 231
Coronary arteriography 159
Coronary artery 130, 156, 189
bypass graft 12
disease 38, 67, 132, 217, 264, 280, 302
prevention of 128t
spasm 52, 130, 207
Coronary computed tomography angiography 14, 136
Coronary insufficiency, acute 39
Coronary peripheral artery 23
Coronary syndrome, acute 159, 167
Corrigan's pulse 228
Corticosteroid 39
therapy 200
Corynebacterium 202
Costochondritis 1
Cough 6, 9, 11, 200, 231
expectorants 11
suppressants 11
Coxsackie B virus 197, 201, 202
C-reactive protein 242
Crisis, hypertensive 39, 41
Cromolyn 197
Cryptococcus 202
Cyanide metabolism, abnormalities of 40
Cyanosis 11
Cyanotic heart disease, congenital 10
Cyclosporine 188, 217
Cystic fibrosis 121
Cytomegalovirus 201
D
Dabigatran 191
Danazol 188
Dantrolene 197
Daunorubicin 197
Degenerative regurgitation 236
Dense hilum 107
Dextrocardia 45, 59
Diabetes 25, 192, 214, 215, 264
diagnosis of 264
mellitus 25, 300
Diabetics new novel therapy 23
Diaphragm 112, 114
eventration of 112
flattening of 120
Diaphragmatic pleural calcification 113
Diarrhea 136, 171
Digitalis intoxication 65
Digitalis investigation group 185
Digitalis toxicity 256
Digoxin 65, 169, 170, 185, 186, 190, 194, 217, 251, 258, 259, 260
immune fab 171
randomized assessment of 169
toxicity 171
causes of 171
clinical evidence of 171
management of 171
Dihydropyridines 31
Diltiazem 37, 65, 188, 194, 216, 258, 260
Dipeptidyl peptidase-IV inhibitors 271
Discoid atelectasis 118
Disopyramide 65, 98, 164, 282, 283
Diuretics 28, 32, 34, 167, 183
Dizziness 136, 240
Dobutamine 131
Doxazosin 30, 39
Duchenne muscular dystrophy 67, 76, 83
Duroziez's sign 228
Dysfunction, diastolic 167, 307
Dyskinetic cilia syndrome 125f
Dyslipidemias, secondary 215
Dyspnea 5, 11, 200, 287
acute 4, 166
pathophysiology of 4
E
Echocardiogram 293
transthoracic 177, 204
Echocardiography 167, 204, 222, 232, 236, 240, 287, 291, 292
transesophageal 178, 204, 226, 227f
Echovirus 197
Eclampsia 39
Edema 8, 8t
airspace 119
alveolar 119
interstitial 119, 165
interstitial pulmonary 111f, 165f
pulmonary 6, 115, 118, 119f
Eisenmenger syndrome 319f
Ejection fraction 36, 167, 187, 285, 307
Electrocardiogram 1, 44, 197, 315
Electrocardiography 13, 20, 167, 222, 228, 232
Electrolyte 63
abnormalities 65
Electromechanical dissociation 311
Elevated low-density lipoprotein cholesterol, management of 215
Embolic protection devices 226
Embolization, systemic 241
Empagliflozin 272
Emphysema 76
mediastinal 1
pulmonary 115, 120
Emphysematous bullae, Large 120f
Enalapril 184, 189191
Encephalopathy, hypertensive 39
Endocardial thickening 288f
Endocarditis 177, 179, 197, 235, 236, 241
bacterial 177
infective 177, 182, 228
nosocomial 177
subacute 235
Endomyocardial fibrosis 67, 287, 288f, 289f
tropical 287
Enterococci infections 177
Enterovirus 201
Epinephrine 313
Episode, acute 259
Eplerenone 158, 167, 172, 173, 183
Epstein-Barr virus 197, 201, 202
Erosion 129fc
Erythema marginatum 241
Erythrocyte sedimentation rate 242
Erythromycin 188, 217
Esmolol 194, 206, 257
Esophageal dysfunction 125f
Esophagitis 4
Esophagus, ruptured 94, 256
Estimated glomerular filtration rate 33, 169, 186
European Society of Cardiology 28, 137
European Society of Hypertension 28
Exercise stress test 13
Ezetimibe 159, 215, 217, 275
F
Fabry's disease 65
Familial homozygous disease 214
Familial restrictive cardiomyopathy 288f
Fascicular block, left anterior 70, 72f
Fast rate tachycardias 246
Fasting blood glucose 192, 270
Fasting plasma glucose 264
Fatigue 240
Fenofibrate 216
Fenofibric acid 216
Fever 200, 241, 242
rheumatic 65, 150, 197, 241
Fibrates 217
Fibrillation, ventricular 17, 18, 128, 132, 132fc, 298, 302, 302fc, 311
Fibrosis 107
pulmonary 4, 118
subvalvular 235
Fine needle aspiration biopsy 121f
Finger pulsations 228
First-degree atrioventricular block 100, 251
Flail posterior mitral valve leaflet 238f
Flavanols 305
Flecainide 259
Fleischner sign 123
Fluconazole 216, 271
Fludrocortisone 212
Fluid, aspiration of 117
Fucloxacillin 178, 179
Fungal origin, acute pneumonia of 117
Furosemide 183
G
Gastroesophageal reflux 9
Gastrointestinal
disturbances 218
origin, pain of 2
procedures 182
Gemfibrozil 188, 216
Gentamicin 178, 179
Ginkgo biloba 306
Gliclazide 193, 271
Glomerulonephritis 215
Glycated hemoglobin concentration 25
Glycemia reduction 271
Glycogen storage disease 65
Gonococcus 200
Granulomatous infection 118
Great vessels 1
Greater septal hypertrophy 281f
Gruppo Italiano Per Lo Studio Della Sopravvivenza Nell'infarto Miocardico Trial 156, 189
H
Haemophilus influenzae 177
Hamartomas, typical of 121
Headache 218
Head-up tilt testing 212
Heart
attack 289
block 150
complete 103f, 255f
disease 32fc, 65, 95f, 244
acquired 67
coronary 13, 30, 69, 164, 270, 297
ischemic 2, 12, 62, 65, 70, 73, 94, 164, 236, 251
rheumatic 65, 67, 239
signs of 1
symptoms of 1
valvular 73, 86, 94, 174
failure 12, 28, 164, 167, 169, 171, 173, 177, 183, 232, 256, 305, 308
causes of 164
congestive 4, 6, 8, 69, 94, 164, 183, 256, 307
diagnosis 166
refractory 173
signs 110
studies 267t, 298t
hypertrophy of 278, 284
muscle disease 86, 94
outcomes prevention evaluation 37
rate 64
Heartbeats, rapid 244
Heat edema 8
Hemiblock, Left anterior 73f
Hemidiaphragm, elevation of 118
Hemochromatosis 150
Hemoptysis 10, 231
evaluation of 124
Hemorrhage 109
intracranial 146, 157
mediastinal 123
pulmonary 117
splinter 177
subarachnoid 39, 100, 130, 146, 250
Heparin 157
Hepatitis 218
Hering-Breuer reflexes 4
Herpes zoster 1
Hiatus hernia 1
fixed 115f
High-density lipoprotein-cholesterol 215
Hila 106, 124
Human herpesvirus 201
Human immunodeficiency virus 177, 188, 197, 216
Hydralazine 41, 173, 185, 197, 287
Hydrochlorothiazide 33, 190
Hydrophilic beta-blocker 36
Hypercalcemia 65, 170
Hypercholesterolemia 135, 215
Hyperglycemia 273
Hyperkalemia 65, 78, 130, 170, 172, 183, 186
mild 78
severe 78
Hyperlipidemia
diagnosis 214
management 214
Hyperlucent lung 116
Hyperparathyroidism 65
Hypersensitivity reactions 218
Hypertension 28, 35, 38, 67, 73, 94, 135, 150, 164, 190, 214, 296
effects of 28
perioperative 39
primary pulmonary 109
pulmonary 1, 61, 207
venous 10, 118
refractory 40
resistant 39
secondary pulmonary 109
severe pulmonary venous 6
systemic 29f
systolic 34
treatment of 33, 34
Hypertrophic anterior costal cartilages 106
Hypertrophy 167, 278, 279
asymmetric 278
Hyperventilation states 5
Hypoglycemia 193
Hypokalemia 78, 98, 170, 186, 250, 256
Hypomagnesemia 98, 170, 186, 250, 256
Hypotension 150, 169, 204
orthostatic 212
persistent 39
Hypothermia 130, 145
Hypothesis 160
Hypothyroidism 65, 170, 186, 215, 251
Hypoxemia 4, 94, 170, 256
I
Ibutilide 260
Idarucizumab 191
Idiopathic restrictive cardiomyopathy 287f
Implantable cardioverter defibrillator 174
Indinavir 217
Infective endocarditis, diagnosis of 182
Influenza 197, 201, 202
Infracardiac translucency 120
Insecticide poisoning 250
Insomnia 171
Intensive care unit 155
Interlobar fissures, thickening of 119
Interlobular septa, thickening of 119
Intermediate bronchus 104f, 109f
Interstitial lung disease, diffuse 115, 122
Interventional therapy 20
Intracellular cyclic guanosine monophosphate 305
Intravenous propranolol dose 149
Intraventricular conduction
defect 81
delay 65, 174, 247
Irbesartan 184, 190, 191
Irregular narrow QRS tachycardias, causes of 86
Irregular rhythm 244, 251f
Ischemia 76, 256
anterior 22f
anterolateral 64f
chronic 164
recurrent 21
Ischemic attack, transient 296
Isoniazid 197
Isosorbide
dinitrate 18, 185
mononitrate 18
Itraconazole 188, 216, 217
Ivabradine 20
J
Jaundice, obstructive 215
Jones criteria 241
Jugular venous pressure 3, 6, 8, 165, 199, 284
K
Kawasaki disease 151
Ketoconazole 188, 216, 217, 315f
Kidney disease 215
Kussmaul breathing 6
Kyphosis, thoracic 120
L
Labetalol 40, 206
Laryngismus 5
Left atrial hypertrophy 80f, 223f
Left atrium 178f, 202, 221, 224, 225, 229, 230, 233, 234, 237, 238
Left bundle branch block 44, 52f, 57f, 67, 70f, 130, 144, 145, 151f, 174
genesis of 69f
Left hilum 108f
Left paravertebral
opacity 112f
soft-tissue 111f
Left posterior fascicular block 70
Left pulmonary artery 105f
Left upper lobe cavity 125f
Left ventricle 178f, 202, 224, 225, 229, 230, 233, 234, 237, 238
Left ventricular
aneurysm 130, 164
chamber dimensions 228
dysfunction 17
ejection fraction 174
failure 4, 39, 226
hypertrophy 28, 71, 130, 143, 222, 223f
causes of 73
diagnosis of 72
typical of 75f
outflow tract 228, 279, 282
pressure gradient 281f
Legionella pneumonia 117f
Lidocaine 171, 195
Lignocaine 195
Limb, descending 223f
Lines of Kerley 119
Lipids, abnormal 214
Liquid protein diets 65
Lisinopril 30, 184, 189-191
Liver disease 215
Lobar fissures, displacement of 118
Long QT syndrome 207, 213
Losartan 168, 173, 184, 187, 190
heart failure survival study 168
intervention for endpoint reduction 38
Low molecular weight heparin 167
Low-density lipoprotein 214
cholesterol 12, 127, 128, 128t, 214, 215, 223, 265, 266, 297
elevation, causes of 215
Lower thoracic aorta 115f
Lung 124
abnormalities 116
biopsy, assessment for 124
cancer, staging of 124
disease, chronic restrictive 124
fields 106
overinflation of 120
parenchyma 106, 115
tumor 1
unilateral hyperlucency of 115, 116
volume, normal 117
Lupus erythematosus 200
Lyme disease 202
Lymphatic obstruction 8
Lymphoma 117
M
MacLeod's syndrome 116
Macrolide antibiotics 217
Magnesium sulfate 262, 314
Magnetic resonance imaging 203, 204
Maiden hair tree leaf extracts 306
Main pulmonary artery 105f
Major blood vessel, acute disruption of 311
Malaria 202
Malignant hypertension, accelerated 39
Manubriosternal junction 105f
Masses, pulmonary 115, 121
Massive right pleural effusion 112f
Mechanical obstruction, acute 311
Mediastinal primary tumors, anterior 114f
Mediastinum 124
anterior 113
divisions of 106f
posterior 105, 114
superior 105, 115
Meningococci 202
Meningococcus 200
Mental confusion 171
Metastatic infection 177
Metformin 192, 270
Methadone 92
Methicillin-resistant Staphylococcus aureus 179
Methicillin-sensitive strains 179
Methysergide 197
Metolazone 183
Metoprolol 18, 36, 133, 149, 153, 159, 170, 185, 187, 188, 194, 206, 244, 258, 260, 267, 298, 299, 312
succinate 172, 190
Miconazole 271
Microalbuminuria 192
Midodrine 212
Minoxidil 197
Mitral and aortic annular calcification 225f
Mitral leaflet, anterior 233f
Mitral regurgitation 164, 235, 236, 238, 240, 278
acute 235
chronic 236
severe 221, 229f, 240
Mitral stenosis 6, 67, 76, 119, 165, 207, 231, 233f
mild 231
moderately severe 231
rheumatic 235f
severe 221, 231
Mitral value 178f, 234, 240, 279
apparatus 235
disease, rheumatic 94
prolapse 65, 207, 235, 239
severe 182
syndrome 2
systolic anterior motion of 280, 281f, 282f
Mobile coronary care ambulances 155
Mobitz type atrioventricular block 100, 254
Monotherapy 179
Multifocal atrial tachycardia 81, 8688, 94, 246, 261
Multifocal ventricular premature beats 84f, 85f
Multiple masses 121
Mumps 197, 202
Murmurs, presence of 7
Muscle pump, loss of 8
Muscular pain 1
Myalgia 218
Myasthenia gravis 124
Mycobacteria 202
Mycoplasma 197
Myectomy, septal 283
Myocardial
contraction 17
disease 167
fibrosis 293f
infarction 1, 3, 19, 28, 39, 44, 127, 129f, 130, 132, 194, 204, 217, 264, 302, 315
acute 13, 86, 135, 153, 164, 186, 189, 197, 214, 235, 281f, 311
acute anterior 54f, 55f, 140f, 142
acute inferior 53f, 55f, 137f, 138f, 253
fatal 12, 127, 132fc, 160, 302fc
inferior 60f, 89f, 142, 207
inferolateral 280f
long-term evaluation, survival of 158, 189
nonfatal 12
ischemia 12, 13
anterior 21f
chronic phase of 86
ECG hallmarks of 76
perfusion imaging 14
revascularization 159
rupture 311
stunning, transient 290f, 303f
Myocarditis 63, 65, 67, 170, 201
acute 76, 130, 202, 253
Myocardium 1, 292f
hypertrophied 226
Myopathy 218
Myopericarditis 150
Myxedema 197
Myxomatous mitral valve prolapse 94, 236
N
Nadolol 194
Nafcillin, combination of 178
Narrow complex tachycardia 89
Narrow QRS irregular tachycardia 246
management of 259
Narrow QRS regular tachycardia 246
management of 256
Narrow QRS tachycardia 79, 86
National Institute of Health 33, 299
National Osteoporosis Foundation 309
Native valve endocarditis 178
Nausea 136, 171
Nebivolol 172, 185
Nefazodone 188
Nelfinavir 217
Nephrotic syndrome 8, 215
Nerve route pain 1
Neuritis, intercostal 1
Neurologic disorders 8
New York Heart Association 168, 169, 283, 307
Niacin 217, 219
Nicorandil 19
Nicotinamide adenine dinucleotide 306
Nicotine 15
Nifedipine 19
Night sweats 11, 200
Nipple shadow 106
Nitric oxide 305
Nitroglycerin 18, 77, 267
sublingual 18
Nitroprusside 205
Nodal premature beats 81
Nodules 121
pulmonary 106
subcutaneous 241
Nonatelectatic lung 118
Noncardiac disease 174
Non-Hodgkin's lymphoma 114f
Non-ST-elevation
acute coronary syndrome 19
myocardial infarction 21, 76, 76f, 130, 290
Nonsteroidal anti-inflammatory drugs 7, 8, 39, 164, 200, 271
Non-ST-segment elevation myocardial infarction 159
O
Obesity 8
abdominal 214
Obstructive cardiomyopathy, hypertrophic 182
Obstructive coronary artery disease 12
Obstructive pulmonary disease, chronic 4, 5, 15, 31, 109, 190, 256, 300
Optimal medical therapy 15
Oral antihypertensive 40
Oral nitrates 18
Orthopnea 5, 10, 200
Osler's nodes 177
Oxacillin 178
P
P wave abnormalities 59
Pain
abdominal 171
cardiac 1
location of 136
pattern 135
pleuritic 11
Pancarditis 242
Pancreatitis 218
Panic disorders 240
Papillary muscle
dysfunction 235
rupture of 235
Parasites 202
Parenchymal consolidation, causes of 117
Paroxysmal atrial
fibrillation 194
tachycardia 87, 88, 253
ECG hallmarks of 88
Paroxysmal nocturnal dyspnea 6, 234f
Paroxysmal supraventricular tachycardia 195, 258
Patent ductus arteriosus 164
Pediatric cardiomyopathies 278
Penicillin 182
Peptic ulcer 1
Percutaneous coronary intervention 2, 15, 44, 136, 151, 152, 188
Percutaneous transluminal coronary angioplasty 23
Pericardial disease 167
Pericardial fat 109f
Pericardial fluid, anterior 202f
Pericardiocentesis 200
Pericarditis 1, 3, 63, 67, 77, 197
acute 130, 143, 147f, 198f
consider causes of 197
constrictive 8, 94, 174
diagnosis of 77
neoplastic 200
tuberculous 200
Perindopril protection against recurrent stroke study 28
Perioperative ischemic evaluation trial 194
Perivalvular abscesses 228
Petechiae 177
Pharyngitis, acute 242
Phenothiazines 65, 98
Phenylephrine 258
Phenytoin 197
Pheochromocytoma 65, 151
Pindolol 194
Pioglitazone 272
Pironolactone 167
Plasma glucose 264
Platelet hyperaggregability 132
Pleurisy 1
Pleurodynia 1
Pneumococcus 200
Pneumonia 1, 2, 4
Pneumothorax 1-3, 118
Polyarthritis 241
Popcorn calcifications 121
Postmediastinoscopy 109
Postmyocardial infarction 133t, 267t
maintenance management of 187t
Postpericardiotomy syndrome 195
prevention of 194
Post-thoracotomy 94
Potassium efflux 44f
Premature beats 244
Pressure, pulmonary venous 6
Presyncope 240
Prinzmetal angina 23, 77, 130
Procainamide 65, 92, 98, 164, 195, 197, 262
Prominent thrombi 286f
Propafenone 259
Propofol 92
Propranolol 16, 18, 36, 132fc, 133, 153, 158160, 170, 187, 188, 258, 267, 282, 298, 300, 302fc, 312, 314
Prosthetic valve 179
dysfunction 207
Protease inhibitors 217
Proteinosis, alveolar 117
Pseudomonas aeruginosa 177
Pulmonary edema
acute 39
alveolar 117
cardiogenic 118
Pulmonary embolism 1, 2, 4, 10, 67, 78, 122, 167, 207, 256
diagnosis 122
without infarction 123
Pulmonary emphysema, evaluation of 124
Pulmonary hila
displacement of 118
haziness of 119
Pulmonary hypertension, causes of 76
Pulmonary neoplasms, search for 124
Pulmonary vessels, loss of sharp definition of 119
Pulseless ventricular tachycardia 311
Pyrexia 2
Q
Q waves, causes of 53
QRS complex, genesis of 44
QRS tachycardia 88f
Quincke's sign 228
Quinidine 65, 98
R
Rabbit ear 83
Radiation fibrosis 118
Radiographic technique 116
Ramipril 159, 184, 187, 189, 190, 269
Randomized clinical trials 16, 28, 215, 222, 296
Randomized controlled trial 25, 168, 184, 306, 313
Ranolazine 19
Rash 218
Rate pressure product 16
Raynaud's phenomenon 125f
Reciprocal depression 130
Recurrent laryngeal nerve, compression of 10
Recurrent pulmonary embolism 76
Reflux
esophagitis 1, 2
syndrome 4
Regular narrow QRS tachycardias, causes of 86
Regurgitant fraction 236, 238
Regurgitation
mild 229
moderate 229
Rehabilitation 160
Renal artery stenosis 39
Renal dysfunction 39
acute 39
postoperative 133
Renal failure 28, 197
chronic 215
Renin angiotensin system 300
Respiratory distress syndrome, acute 4, 5
Respiratory system 3
Reteplase 157
Reticular pattern 122
Reticulonodular pattern 122
Retrosternal airspace, increased size of 120
Retrotracheal triangle 105f
Rhabdomyolysis 150, 218
Rheumatic fever 253
Rib fracture 1
Right atrium 104f, 109f, 202, 221, 234, 237, 238
Right bundle branch block 44, 51f, 65, 67, 72f, 73f, 77f, 83, 151f
Right heart border, blurring of 110f
Right hilum 108f
Right innominate vein 104f, 109f
Right lower lobe collapse 119f
Right main bronchus 104f, 109f
Right upper lobe
artery 104f, 109f
collapse 119f
vein 104f, 109f
Right ventricle 178f, 202, 221, 230, 234, 237, 238
Right ventricular hypertrophy 61, 62f, 67, 73, 83, 319f
causes of 76
diagnosis of 73
Right ventricular infarction 144
Ritonavir 217
Rivaroxaban 191
Rosiglitazone 272
medication 269
Rosuvastatin 188, 216
Rubella 197
S
Saquinavir 217
Sarcoidosis 150, 292, 293f
pulmonary 107f
Schistosomes 202
Scleroderma 150, 197
Sclerotic foci 106
Scorpion sting 146
Second Chinese Cardiac Study 194
Septal ablation, alcohol-induced 283
Septal defect, ventricular 164
Septal hypertrophy, asymmetric 279f
Septicemia 197
Septum, severe thickening of 282f
Serratia marcescens 177
Shock 150
cardiogenic 131, 132
Short QT interval, causes of 65
Shortness of breath, causes of 5t
Sick sinus syndrome 37, 94, 207, 212, 251, 256
Sildenafil 217
Silhouette sign 109
Simvastatin 188, 217
Sinus
arrhythmia 79, 79f
bradycardia 80f, 100, 250
causes of 251
node dysfunction 207
of Valsalva 237f, 311
rhythm 51f, 54f, 61f, 62f, 69f, 89
tachycardia 82f, 86, 87f, 147f, 198f, 241, 285
Sitosterol 159, 194, 265, 273
blood levels, reduce 275
Sitosterolemia 218
Skeletal mass, low 170
Small peripheral bronchial carcinoma 108f
Snake venom 151
Sodium
glucose cotransporter 2 272
influx 44f
nitroprusside 40
Soft tissues 105, 106
Sotalol 36, 65, 98, 194, 259, 260
Spironolactone 33, 34, 172, 173, 174, 183, 190
Stable angina 1, 12, 13
Staphylococcus aureus 177
endocarditis 179
Staphylococcus infections 177
Starry-sky speckled appearance 292f
Statins 16, 22, 188, 266, 307
adverse effects 216
Status asthmaticus 289
Stenosis, pulmonary 61, 76, 164, 207
Sternoclavicular joint pulsation 204
Stokes-Adams attacks 212
Strenuous exertion 132
Streptococcus
gallolyticus 178, 179
mitis 177
viridans 177
Streptokinase 157, 189
global utilization of 156
Stress 14
cardiomyopathy 130, 131, 146, 289
echocardiography 14
Stroke 12, 29, 177, 274, 289
fatal 28
nonfatal 28
volume 207
ST-segment depression 57
ST-segment elevation 51
causes of 130
myocardial infarction 128, 142, 197
Sudden cardiac death 17, 129fc, 160, 170t, 188t, 282, 300, 312t
Sulfa drugs 271
Sulfonamides 271
Superior vena cava 104f, 109f
obstruction 6
Surgery, thoracic 197
Surgical open commissurotomy 235
Swyer-James syndrome 116
Syncope 204, 207, 213, 240
cardiac causes of 207t
consider causes of 207
Systolic anterior motion 278
Systolic blood pressure intervention trial 29
Systolic function, normal 167
Systolic hypertension
mild to moderate 31f, 32fc
severe 39
T
Tachyarrhythmia 98f, 150, 207, 246
Tachycardia 81, 88f, 89
supraventricular 81, 100, 207, 246
ventricular 81, 96, 97, 97f, 98f, 156, 171, 195, 246, 262
Takotsubo stress cardiomyopathy 150, 289, 290f
Telaprevir 216
Telithromycin 188
Telmisartan 168, 184
randomized assessment study 168
Tenecteplase 157, 189
Tension pneumothorax 2
Terfenadine 98, 250
Tetralogy of Fallot 76
Thiazide 34, 183
Thiazolidinediones 272
Thromboembolism, venous 167
Thrombolytic agents 155, 156
Thrombolytic therapy 76, 153, 156
Thromboprophylaxis 167
Thromboxane 16
Thrombus 207
formation 288f
Thymoma 114f
Thyrotoxicosis 94, 256
Timolol 17, 18, 36, 131, 132fc, 133, 153, 158160, 170, 187, 188, 267, 302fc
study 300
Tissue plasminogen activator 156, 189
Torsades de pointes 65, 98, 207, 250, 262, 314
Torsemide 173
Toxoplasma 202, 173
Trachea 104f, 105f, 107, 109f
Tracheobronchial tree 104, 107
compression of 10
Trandolapril 159, 189, 190
Transcatheter aortic valve replacement 226, 227f
Transthoracic echocardiography, two-dimensional 286f, 291f, 293f
Traube's sign 228
Trauma, severe 146
Treadmill exercise test 13
Tricuspid
stenosis 61
valve 221, 230, 239
Tricyclic antidepressants 65, 98
Trifascicular block 71
Triglycerides 218, 267
Trilipix 216
Trimetazidine 20
Troponins 21
True posterior infarction 76, 83
Trypanocidal therapy 293
Tuberculosis 197, 200
Tuberculous pneumonia, acute 118f
Tumor, large esophageal 115f
U
Unstable angina 1, 3, 12, 20
Uremic pericarditis 200
Urinary tract infection 272
Urine testing 192, 193
Valsalva maneuver 256
Valsartan 169, 184
Valve
area index 233
disease 221, 228
leaflets 235
replacement 235
V
Valvular disease 164
absence of 167
Valvulitis 241
Vancomycin 178
Varicella 197
Vascular disease, peripheral 265, 274
Vasculitis 197
systemic 150
Vasopressin 314
Venous waves, abnormal 3
Ventricular premature beats 81, 81f, 83, 84f, 85f, 86f, 194, 244, 244f, 245f
causes of 86
Ventricular tachycardia
nonsustained 85f, 207, 253f
sustained 207
Verapamil 37, 65, 188, 251, 257, 283
Viral infections 197
Viral origin, acute pneumonia of 117
Viridans streptococci 178
Vision, blurring of 171
Vitamin K1 260
Vomiting 136, 171
Voriconazole 216
W
Warfarin 191, 216, 217
Weight loss 11, 171, 200
Wenckebach phenomenon 99f
Westermark's sign 123
Wheeze 231
Wide QRS irregular tachycardia 246, 249
management of 262
Wide QRS regular tachycardia 246, 247
management of 262
Wide QRS tachycardia 81, 95
Wolff-Parkinson-White syndrome 65, 67, 73, 79, 83, 86, 89, 89f, 90f, 98f, 100, 143, 207, 246, 249f, 256, 311
Z
Zofenopril 159, 189, 190
×
Chapter Notes

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Symptoms and Signs of Heart DiseasesCHAPTER 1

 
INTRODUCTION
Symptoms and signs of heart diseases and pulmonary disturbances overlap and present diagnostic problems. These two vital organs are in the chest “married to each other”. Thus, the text also gives salient symptoms of pulmonary disorders.
 
EVALUATION OF CHEST PAIN
Chest pain is one of the most important and common symptoms of heart disease and must be assigned a cause quickly. The resolution of this symptom is sometimes easy, but often it presents considerable difficulty for the physician. A systematic approach is necessary; taking an accurate and relevant history is crucial to the diagnosis.
  • What are the vital signs?
  • Is the patient stable or unstable?
  • Is the pain in the central, the left, or the right lateral chest?
  • Is there associated shortness of breath and is it mild, moderate, or severe?
  • If the patient is unstable, order an electrocardiogram (ECG) immediately.
  • Give nitroglycerin, 0.3 mg sublingually or sublingual puffer, twice as needed (PRN); this only relieves mild angina and cannot prevent or limit size of myocardial infarction (MI). A dose of 0.4 mg is used only if the blood pressure (BP) is higher than 130 mm Hg.
  • Give soft chew aspirin 75–81 mg × 3 tablets. This can prevent MI or reduce infarct size; reduces risk of death.
 
COMMON CAUSES OF CHEST PAIN
 
Cardiac Causes
Cardiac pain can be life-threatening and should be assessed rapidly. The following are the three sources of cardiac pain (Box 1.1):
Box 1.1   Causes of chest pain.
  • Cardiac
    • Myocardial infarction
    • Stable angina
    • Unstable angina
    • Pericarditis
    • Aortic dissection
    • Pulmonary hypertension
  • Pulmonary
    • Pulmonary embolism
    • Pleurisy
    • Pneumothorax
    • Pneumonia
    • Mediastinal emphysema
    • Lung tumor
    • Pleurodynia
  • Gastrointestinal
    • Reflux esophagitis
    • Esophageal spasm
    • Hiatus hernia
    • Peptic ulcer
  • Chest wall pain
    • Costochondritis
    • Muscular pain
    • Rib fracture
  • Nerve route pain
    • Cervical disc disease
    • Cervical osteoarthritis
    • Intercostal neuritis
    • Herpes zoster (shingles)
  • Psychogenic
  1. The myocardium: Acute MI and unstable angina (see Chapters 2 and 7)
  2. The pericardium: Pericarditis
  3. The great vessels: Aortic dissection, pulmonary embolism and pulmonary arterial hypertension.
 
Pulmonary Causes
  • Pleurisy: The pain becomes worse on deep breathing and coughing and is unrelated to change in posture. 2There may be associated cough and pyrexia owing to underlying chest infection.
  • Pulmonary embolism: The pain may be severe, central, or pleuritic and is often associated with acute shortness of breath; the patient is often apprehensive and may be sweaty. Pulmonary embolism should be suspected when chest pain occurs in a setting that predisposes to thromboembolism (e.g. after surgery or with sudden immobilization for >2 days). Request arterial blood gas study and ventilation-perfusion lung scan.
  • Pneumothorax: Chest pain is usually associated with acute shortness of breath. Chest pain is often located in the lateral chest. Underlying causes include asthma, pneumocystis pneumonia, emphysema, tuberculosis, cystic fibrosis, interstitial pulmonary fibrosis, sarcoidosis, eosinophilic granuloma, blunt or penetrating trauma, and positive-pressure ventilation.
  • Pneumonia: Shortness of breath, fever and chills are associated with pleuritic or nonpleuritic pain and cough, with or without sputum production.
 
Chest Wall Pain
A common cause of chest wall pain is costochondritis. Pain is usually mild to moderate; it is usually localized to a fingertip area and is often present over the second or third costochondral junction. Chest wall pain from other causes may last seconds to several hours. Pain is unrelated to exertion or activities and may seem to respond to nitroglycerin in some patients. Chest wall pain accompanies most types of heart disease, particularly ischemic heart disease and mitral valve prolapse syndrome.
 
Pain of Gastrointestinal Origin
  • Reflux esophagitis may mimic cardiac pain and may radiate from the upper epigastrium to the substernal area, the upper chest, the throat and the arms. Pain does not radiate to the lower jaw, a feature of anginal pain. Pain lasting minutes to several hours may be mild to moderate but can be severe. Pain usually is not associated with profuse sweating or shortness of breath. The discomfort is worse on lying flat or on stooping but may start in the upright position. Pain is unrelated to exertional activities.
 
CHEST PAIN CAUSING A MAJOR THREAT TO LIFE
  • Acute MI
  • Aortic dissection
  • Pulmonary embolism
  • Tension pneumothorax
A patient in cardiogenic shock is usually sweaty, pale and apprehensive; there may be associated clouding of consciousness.
 
PATIENT EXAMINATION
Does the patient look well (comfortable), sick (uncomfortable or distressed), or critical (about to die)?
If the patient is critically ill or is unstable (i.e. systolic BP is <100 mm Hg, pulse rate is <45 beats/min or >140 beats/min, or with a cardiac arrhythmia, or there is clouding of consciousness), send by ambulance to an emergency room (ER); put up IV line with dextrose to keep vein open.
Bradycardia may be caused by treatment with beta-blockers, diltiazem, or a combination of these two agents. Also, inferior MI commonly causes sinus bradycardia. Bradycardia usually requires no treatment, unless it is symptomatic
 
Selective History
It is necessary to become familiar with the description of cardiac pain so that the diagnosis of stable angina, unstable angina, or MI can be made clinically within a few minutes. Because urgent administration of thrombolytic therapy or percutaneous coronary intervention [PCI] is crucial to reducing morbidity and mortality, it is vital to make the diagnosis of acute MI within a few minutes of assessment in the home, the physician's office, or in the ER.
Salient features of cardiac pain are as follows:
  • Pain of acute MI is usually described as crushing, viselike, or a tightness or a heaviness
  • The location of pain in acute MI is usually substernal across the chest, often accompanied by diaphoresis and sometimes shortness of breath.
Figure 1.1 gives the location and the radiation of cardiac pain.
The pain is unlikely to be due to MI if it can be located with one fingertip or if it is made worse by deep breathing or coughing.
If the patient is stable and the diagnosis is not yet clarified, obtain relevant information from all sources (i.e. the patient, the spouse, a relative, a chart review).
  • The pain of MI usually lasts minutes to several hours
  • The pain of angina is typically a retrosternal discomfort, precipitated by a particular activity, especially walking quickly up an incline or against a wind.
  • Pain or discomfort disappears within seconds to minutes of stopping the precipitating activity, in keeping with the concept of oxygen supply insufficient to meet myocardial demand.3
    zoom view
    Fig. 1.1: Common locations of cardiac pain.Source: Adapted from Khan M Gabriel. Heart Trouble Encyclopedia. Toronto: Stoddart; 1996.
    The discomfort is usually located in the lower, middle, or upper substernal area, the arm, or the lower jaw. The discomfort is usually described as tightness, squeezing, heaviness, pressure, constriction, strangulation, burning, nausea, or an indigestion-like feeling of gradual onset that disappears at rest, except with unstable anginal syndromes.
  • The area of pain in MI is usually at least the size of a clenched fist and often occupies most of the central chest area. The patient uses more than two fingers, the fist, or the entire palm of the hand to indicate the site. Patients with unstable angina have pain that has changed in pattern and frequency.
  • Pericardial pain is usually sharp or stabbing. It is relieved by sitting and leaning forward or standing, is made worse on lying down or on deep inspiration and does not usually radiate to the neck or arms.
  • Pain of dissecting aneurysm is sudden like a gunshot; the pain is excruciating and persists with the same intensity for hours; pain may radiate to the back.
  • Myocardial ischemia or infarction may cause only minimal chest discomfort for a few minutes; pain may range from causing minor distress to being severe and unbearable.
 
What Does the ECG Show?
Is the ECG in keeping with acute MI? Acute MI poses a threat to life; the diagnosis must be made rapidly. Thrombolytic therapy has proved effective in saving life if given within 4 hours of the onset of chest pain. It is important, however, that triage through the ER be efficient; patients presenting with chest pain caused by acute MI should receive thrombolytic therapy within 20 minutes of presentation to the ER or ambulance, if no facilities for coronary stenting is available.
 
Selective Physical Examination
  • Assess the BP and heart rate
  • Assess the cardiovascular system
    • Is the patient orthopneic? Is the patient apprehensive or sweaty? Assess for elevated jugular venous pressure (JVP) or abnormal venous waves. With the bell of the stethoscope placed gently on the chest wall, listen for gallop sounds. Listen with the diaphragm of the stethoscope for murmurs and, with the patient leaning forward with the breath held in deep expiration, for an aortic diastolic murmur and pericardial friction rubs (see Chapters 11 and 15).
  • Assess the respiratory system
    • Assess for crackles over the lower lung fields that may indicate left ventricular failure; unilaterally decreased air entry and hyperresonance suggest a pneumothorax.
 
MANAGEMENT
Management of the following problems is given in their respective chapters:
 
Pneumothorax
Intervention is necessary for symptomatic primary pneumothoraces or if the pneumothorax is more than 40%. Tension pneumothorax causes severe respiratory distress and is a medical emergency that requires urgent relief of the pressure by using a 16-gauge IV catheter. After rapid radiologic confirmation, insert a 16-gauge IV catheter as follows:
  • Put on sterile gloves; clean the area of the second intercostal space in the midclavicular line on the affected side of the chest4
  • Infiltrate the area with lidocaine and insert a 16-gauge IV catheter above the rib into the site until air is aspirated. Remove the inner needle and attach the catheter to a three-way stopcock and a 60-mL syringe to allow repeated aspirations. Aspiration is discontinued when no more air can be withdrawn, or when about 2.5 L has been removed. Occlude the catheter for about 6 hours and if the chest radiograph shows no recurrence, remove the catheter.
The insertion of a chest tube (tube thoracostomy) is required in patients with underlying lung disease, with respiratory compromise, or for failure of simple aspiration. A small, asymptomatic pneumothorax usually resolves spontaneously over a few days.
 
Esophagitis and Reflux Syndrome
The following steps need to be followed:
  • Elevate the head of the patient's bed
  • Give Maalox or a similar antacid, 30 mL at 1 hour and 3 hours after meals plus at bedtime
  • Give lansoprazole 30 mg, omeprazole 20 mg, or similar agent 30 minutes before breakfast for 1 week and reassess.
 
Shortness of Breath
Shortness of breath, or dyspnea, is a common problem. Dyspnea by definition is difficult breathing. The term “dyspnea” is used synonymously with shortness of breath or breathlessness and may be expressed by individuals as follows: “I can't get enough air”; “I'm breathless or short of breath”; “I feel like I'm being smothered”; or “I'm out of breath, running after my breath”.
Because shortness of breath on exertion may be a normal phenomenon, it is necessary to make a careful assessment of the normal or altered lifestyle of the patient in relation to the degree of shortness of breath. A change from a very active lifestyle, to a few years of sedentary life, then resumption of exercise or strenuous work may be the cause of shortness of breath. Increasing body weight and advancing or intercurrent illness may be important causal factors:
  • Is the shortness of breath mild, moderate, or severe?
  • Did it occur suddenly and become severe within minutes?
This suggests pulmonary embolism, pneumothorax, or acute pulmonary edema.
  • How long has the patient been short of breath?
  • What are the vital signs?
Heart failure and pulmonary embolism are the most likely causes of acute dyspnea.
The causes of dyspnea are listed in Table 1.1. Pathophysiology of Dyspnea
Given here is a brief review of pathophysiology of dyspnea:
  • An increase in the work of breathing secondary to changes in lung compliance or resistance, as occurs with interstitial pulmonary edema owing to congestive heart failure (CHF) or pulmonary fibrosis.
The respiratory center receives indirect stimuli via lung stretch (Hering-Breuer reflexes). Stretch receptors in the lung parenchyma relay information to the respiratory center, resulting directly or indirectly in dyspnea. Stretch receptors in respiratory muscles, irritant receptors and juxtacapillary (J) receptors are sensitive to congestion, vascular engorgement and mechanical stimulation.
  • Shunting and other hypoxic stimulation to breathing (e.g. caused by acute respiratory distress syndrome, pneumonia, pulmonary embolism and right-to-left cardiac shunts).
  • Airflow obstruction: Chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis.
  • Mechanical limitation to ventilation: Thoracic and neurologic abnormalities.
  • Decrease in cardiac output.
  • Decrease in hemoglobin (anemias).
  • High altitude.
 
Major Threat to Life
Given below are major threats to life related to dyspnea:
  • Hypoxemia
  • Left ventricular failure
  • Pulmonary embolism.
Does the patient look sick (uncomfortable or distressed) or critical (about to die)?
  • Ensure that the upper airway is clear:
    • Determine the respiratory rate; if more than 20 breaths/min, consider hypoxemia, or anxiety and apprehension caused by pain and distress. Paradoxical abdominal and diaphragmatic movement during respiration indicates diaphragmatic fatigue or weakness; the presence of this sign is ominous, and some patients may require ventilator assistance.5
      Table 1.1   Causes of shortness of breath.
      Cause
      Meaning or association
      Normal: To be expected because of relative age and lack of exercise, overweight
      Excessive strenuous effort precipitates symptoms
      Elevation of the diaphragm, e.g. pregnancy, ascites
      Mechanical problem
      Heart failure
      Increased pulmonary venous pressure; interstitial pulmnary edema; frank pulmonary alveolar edema
      Pericardial effusion
      Restriction to ventricular filling
      Angina equivalent of chest discomfort
      Left ventricular dysfunction or discomfort appreciated as breathing with difficulty or suffocation
      Pulmonary embolism
      Apprehension, presyncope, pain
      Pulmonary diseases
      Pneumonia, asthma, pneumothorax, ARDS, pleural effusion, COPD, restrictive lung disease, lymphangitis carcinomatosa
      Laryngeal stridor
      Laryngotracheal obstruction
      Thoracic defects
      Neuromuscular or bony mechanical conditions
      Decreased hemoglobin or available oxygen
      Anemia, high altitude
      (ARDS: Acute respiratory distress syndrome; COPD: Chronic obstructive pulmonary disease).
      A respiratory rate of less than 12 breaths/min indicates a central depression of ventilation caused by drugs or overdose, narcotics, or cerebrovascular accident.
  • Assess the heart rate and the BP. Hypotension suggests CHF caused by underlying cardiac disease or pulmonary embolism (check for pulsus paradoxus and cardiac tamponade; see Chapter 11).
 
Dyspnea
The most common symptom of cardiac and respiratory disorders. It is often a difficult symptom to resolve, unless a clear description is obtained.
It is necessary to exclude the following conditions, which are not truly dyspnea:
  • Hyperventilation states caused by anxiety: The patient refers to “feeling hungry for air”
  • Sighing respirations: The patient sighs, “I feel like I need to take a deep breath”
  • Splinting caused by pleuritic pain or rib or chest wall problems
  • Laryngismus caused by hypocalcemia, which may occur because of hypoparathyroidism (occasionally surgically induced).
When it is determined that the patient is complaining of genuine shortness of breath, consider the following:
  • Define what level of activity precipitated the shortness of breath (e.g. the number of stairs climbed, the number of steps taken, the number of blocks walked, the extent of the incline, the relation to various types of effort or exertion). Shortness of breath is abnormal when it occurs at rest or at a level of activity not expected to cause this situation.
  • Duration: Seconds, minutes, hours? If the sensation lasts less than 10 seconds, it is not true dyspnea.
  • Is it occurring at rest? If so, determine the duration and what makes it better or worse.
  • If it occurred suddenly and with the patient at rest, is it improving or getting worse?
  • Is it accompanied by cough, wheeze, chest pain, palpitations, or edema?
  • Is it worse on inspiration and accompanied by tracheal or laryngeal stridor? This indicates upper respiratory tract obstruction, which can be life-threatening.
  • Is it mainly with expiration? The patient has difficulty getting air out of the lungs because airflow is obstructed (a prolonged expiratory phase); this is usually due to an exacerbation of asthma or COPD.
  • Is it worse only when lying down or when the trunk is immersed in water? This suggests diaphragmatic paresis or paralysis.
 
Orthopnea
Shortness of breath that occurs within minutes of lying down and is relieved within a few minutes (not a few seconds) of sitting upright or dangling the legs over the bedside. This symptom is not usually accompanied by wheezing or flatulence.
Orthopnea is usually caused by severe left ventricular dysfunction, subtle left ventricular failure, or increased 6pulmonary venous pressure (e.g. owing to mitral stenosis). In patients with poor left ventricular function, blood returning to the heart from the lower limbs when the person is reclining is not ejected efficiently from the left ventricle. This situation results in an increase in left atrial and pulmonary venous pressures, causing increases in lung water and lung stiffness, which incite reflexes that trigger the sensation of shortness of breath. The upright position decreases venous return and improves the abnormal sensation within minutes. Orthopnea lasts 1–5 minutes and does not usually exceed 10 minutes.
Warning: Shortness of breath of more than 10 minutes’ duration while at rest is a life-threatening situation.
 
Paroxysmal Nocturnal Dyspnea
Shortness of breath (a suffocating feeling) that occurs after the patient has been lying in bed for more than 1 hour. The patient usually awakens several hours after retiring, typically between 1 am and 3 am, with severe shortness of breath.
  • Relief is obtained only by getting out of bed, sitting in a chair, dangling the legs, or standing. In contrast to orthopnea, sitting up in bed does not cause relief in 1 or 2 minutes.
  • Shortness of breath usually lasts 10–30 minutes. Paroxysmal nocturnal dyspnea is more common in patients with poor left ventricular function who have peripheral edema.
  • After the patient lies down for the night, it takes 1–3 hours for edema fluid from the lower limbs to return to the heart. An extra volume of sodium and water precipitates left ventricular failure, this causes an increase in left atrial pressure (i.e. severe pulmonary venous hypertension that results in pulmonary edema).
  • Cough is often associated with the feeling of suffocation and with the production of frothy, blood-tinged sputum.
 
Cheyne-Stokes Respiration
In this condition, the patient takes deep inspirations, the depth of inspiration increases with each consecutive breath for 1–2 minutes, and then there is cessation of breathing for 10–30 seconds, after which the patient resumes deep breathing.
  • Cheyne-Stokes respiration is usually observed in patients with cerebrovascular accidents, in patients with head injury, and in patients with severe left ventricular failure with coexisting cerebral disease.
 
Kussmaul Breathing
  • The patient takes deep breaths, with long inspiratory and expiratory phases, without wheezing and without the use of accessory muscles.
  • The patient has no difficulty getting air into or out of the lungs and does not describe the sensation as a feeling of shortness of breath or breathlessness.
  • This pattern of breathing is observed in patients with diabetic ketoacidosis, uremia and salicylate overdose.
  • Metabolic acidosis stimulates the respiratory center to produce this breathing pattern, which blows carbon dioxide out of the lungs and into the atmosphere. The loss of carbon dioxide causes a compensatory adjustment in blood pH. The degree of acidosis is usually too intense to be corrected completely by ridding the lungs of carbon dioxide.
 
Assessment
  • Is the patient in distress, requiring being propped upright to ease difficult breathing?
  • Is the patient using accessory muscles of respiration?
  • Is cyanosis present?
Do not forget that severe hypoxia may be present with no cyanosis apparent on observation.
  • Is the patient wheezing, or is the patient a known asthmatic?
Do not forget, all that wheezes is not asthma; patients with pulmonary embolism, pulmonary edema and exacerbation of chronic bronchitis may exhibit audible wheezing.
  • Repeat vital signs and recheck patency of the airways. Sinus tachycardia is commonly caused by hypoxemia, pain and anxiety. If the systolic BP is less than 90 mmHg with signs of hypoperfusion, begin measures for managing cardiogenic shock.
 
Jugular Venous Pressure
This should be elevated to more than 3 cm above the sternal angle in patients with CHF.
Venous pressure may be markedly elevated, and the top of the blood column may be masked by the angle of the jaw. The earlobes may pulsate in patients with markedly elevated JVP and tricuspid incompetence. Look tangentially across the neck for prominent venous waves.
The JVP is elevated in the following conditions:
  • Congestive heart failure
  • Cardiac tamponade
  • Superior vena cava obstruction.7
A unilateral elevation of the JVP, which is nonpulsatile, is observed with superior vena cava obstruction. Watch for false elevation of the JVP in patients with an exacerbation of COPD. Venous pressure is elevated during the phase in which exhalation is difficult and it decreases during inspiration.
 
Listen for the Presence of Murmurs
A loud mitral systolic murmur with radiation to the left axilla or the spine may occur in patients with ruptured chordae or flail mitral valve leaflet. The murmur of aortic stenosis may be loud, but in the presence of a low cardiac output it may diminish in intensity and result in a misdiagnosis. The murmur of mitral regurgitation may be soft in patients with low cardiac output or a thick chest wall or concomitant COPD. Patients with severe aortic stenosis may die during an episode of pulmonary edema.
  • Listen carefully for S3, a gallop that is commonly present if CHF is the cause of severe shortness of breath (see Chapter 8)
  • Is the heart clinically enlarged?
    • Cardiomegaly may be mild and may be absent in patients with aortic stenosis or pure mitral stenosis.
  • Observe for abnormal pulsations, including visible gallops:
    • Abnormal dyskinetic myocardium may be visible just above the apex beat, in the region of the fourth interspace, caused by recurrent MI or left ventricular aneurysm, severe valvular defects, or cardiomyopathy.
  • Observe for bilateral ankle edema:
    • Assess the extent of edema up to the knee and the degree of pitting. If shortness of breath was present for several days and the patient was confined to bed, check for presacral edema.
  • If CHF is present, verify the underlying cause of heart disease: Valvular disease, coronary artery disease, congenital heart disease, hypertension, cardiomyopathy and cor pulmonale.
  • Define a precipitating cause: Recent MI or MI and mechanical defect, ruptured chordae tendineae, flail mitral valve, worsening of valvular defect, increased salt intake and medications that precipitate CHF (beta-blockers, calcium antagonists and nonsteroidal anti-inflammatory drugs).
 
Pulmonary Assessment
  • Is the patient cyanotic?
  • Is the trachea in the midline?
    • A shift away from the side of the lesion is observed with pneumothorax and pleural effusion; a shift to the side of the lesion indicates atelectasis.
  • Is there dullness to percussion?
    • Stony dullness is in keeping with pleural effusion. If there is mild impairment to percussion, consider consolidation.
  • Is there unilateral hyper-resonance?
    • Consider pneumothorax.
  • Auscultate for breath sounds:
  • Air entry: If air entry is decreased or absent over an area of dullness, with decreased bronchophony, consider pleural effusion; air entry absent over a hyperresonant area is diagnostic of pneumothorax.
    • Quality of breath sounds: If bronchial breathing is present, consider consolidation.
    • Added sounds: Crackles (crepitations) over both lower lung fields associated with an increased JVP is diagnostic of CHF, but crackles may be maximal on one side.
 
Diagnostic Tests
  • A chest X-ray confirms pulmonary edema or interstitial edema caused by heart failure (see Chapters 6 and 8):
    • For pulmonary causes, posteroanterior and left lateral X-rays are essential: Assess for pleural effusions, diaphragmatic paralysis, emphysema, tumors and lymphangitis carcinomatosa. If emphysema or restrictive lung disease is suspected, a computed tomography scan and gas transfer assessment are recommended.
  • Troponin testing in the ER helps differentiate cardiac from pulmonary causes of severe dyspnea.
  • An echocardiogram helps document the degree of valvular lesions, left ventricular systolic function, ejection fraction and pericardial effusion with tamponade.
  • Measures of arterial blood gases assess hypoxemia and response to therapy.
 
Management
  • Dangle the patient's legs over the bedside and prop the patient upright as much as possible.8
  • Give furosemide 80 mg intravenously immediately, then oral furosemide 40–80 mg daily after breakfast.
  • If needed, give oxygen by nasal prongs or mask 4–8 L/min until arterial blood gases show the absence of hypoxemia and the underlying cause improves or is corrected.
Causes of shortness of breath are given in Table 1.1.
 
Edema
Edema is an excessive accumulation of interstitial fluid in the subcutaneous tissue.
 
Assessment
  • Does the patient complain that shoes feel tighter or that sock tops leave indentations as the day progresses?
  • Is the swelling more prominent at the end of the day?
  • Is the swelling unilateral or bilateral?
  • Is the swelling of recent onset or is it recurrent?
  • Is the swelling associated with shortness of breath?
Table 1.2   Edema of lower limbs.
Causes
Comments
Congestive heart failure
Symmetric, occurs before ascites
Constrictive pericarditis
Symmetric, but occurs weeks after the occurrence of prominent ascites; high JVP
Cirrhosis
Ascites first, then leg edema; normal or slight increase of JVP
Venous obstruction
Commonly unilateral, one leg more than the other leg; toes are spared
Lymphatic obstruction
One side more than the other side; toes are involved
Obesity
Dependent and stasis edema
Neurologic disorders; loss of muscle pump
Edema mainly on the paralyzed side
Nephrotic syndrome
Edema may involve the face; JVP is normal with noncardiac causes
Pregnancy
Left leg more than right leg
Psychogenic factors
Young women during tension states: abnormal water tolerance
Heat edema
Caused by aldosterone-mediated Na+ and water retention
Drugs
Calcium antagonists, estrogens, NSAIDs, steroids
(JVP: Jugular venous pressure; NSAIDs: Nonsteroidal anti-inflammatory drugs).
 
Causes
Many patients are inappropriately treated with diuretics and digitalis for edema that is noncardiac in origin. A careful history and physical examination are necessary to determine the cause accurately localization is determined mainly by gravity (Table 1.2):
  • Edema of cardiac origin involves both of the feet and ankles
  • It may involve the lower limbs, the trunk, the face, and the arms and may be associated with ascites and pleural effusions; this generalized edema is referred to as anasarca.
  • Unilateral leg edema is typical of venous and lymphatic obstruction. Venous edema is soft, pits easily and spares the toes; lymphatic edema is firm, pits poorly and involves the toes. Patients with neurologic disease are commonly allowed to sit out of bed for prolonged periods; edema may worsen because the leg muscles are not being used.
  • Edema confined to the upper limbs and face occurs with superior vena cava obstruction
  • Edema of one arm may be due to venous occlusion or lymphatic obstruction (e.g. caused by breast cancer)
  • Bilateral edema of the lower limbs does not usually occur until more than 7 lbs of fluid has accumulated. Weight gain of 5–10 lbs over a few days is a more reliable sign of intense sodium and water retention than is the demonstration of edema.
  • Edema in patients with heart failure occurs mainly when right-sided heart failure is present for several days. Acute left ventricular failure rarely causes significant leg edema. However, the most common cause of right-sided heart failure is chronic left ventricular failure. Some degree of inappropriate shortness of breath is virtually always present when edema is caused by heart failure. Edema becomes more prominent if tricuspid regurgitation ensues.
    The mechanism of edema formation is threefold:
  • A decrease in cardiac output causes activation of the sympathetic and renin-angiotensin-aldosterone systems, which results in sodium and water retention, and a high venous pressure. The JVP is always elevated in patients with heart failure who manifest edema. High systemic venous pressure increases the hydrostatic pressure at the venous end of capillaries, and sodium and water leak out into the subcutaneous tissue. The 9patient is not waterlogged but has an excess of brine (salt and water) in these tissues.
  • In patients with nephrotic syndrome or cirrhosis, hypoalbuminemia causes a decrease in oncotic pressure and fluid that exudes into the interstitial tissue is not able to regain entry into the vascular compartment. Because salt and water leave the vascular compartment, the decrease in effective vascular volume causes stimulation of the renin-angiotensin-aldosterone system. This stimulation results in retention of sodium and water by the kidney, and edema worsens.
  • Edema of pregnancy is caused by activation of the renin-angiotensin system, which results in sodium and water retention; this increases blood volume. Approximately 8 L of water accumulates during normal pregnancy. Normally the common iliac artery partially compresses the left common iliac vein; this increases venous pressure in the left leg. In pregnancy, and in most individuals with edema, the left limb shows edema before or of greater severity than that observed in the right leg.
  • Lymphatic obstruction may be caused by inflammatory, parasitic, or neoplastic processes, resulting in unilateral or bilateral lower or upper limb edema.
 
Patient Assessment
  • Confirm that edema is unilateral or bilateral.
  • Test for pitting:
    • Using two finger pads held about 1 cm apart, apply firm pressure to the lower tibial area. Press firmly for about 10 seconds. Edema leaves two pits, 0.5–2 cm deep, with a ridge in between. Observe the extent of edema—ankles only, to below the knee, or above the knee (presacral edema).
  • Is there associated swelling of the eyelids?
  • Assess the JVP; JVP elevated to more than 3 cm bilaterally indicates CHF.
  • Edema occurring weeks after the onset of ascites in a patient with an elevated JVP suggests constrictive pericarditis. If the JVP is not elevated, consider cirrhosis.
  • Is generalized edema (i.e. anasarca) present?
    • Anasarca often occurs in patients with nephrotic syndrome but can occur with severe chronic CHF.
 
Management
Management involves treatment of the underlying cause. Symptomatic relief is obtained as follows:
  • Use a diuretic: Furosemide 40–80 mg daily for a few days, then 40 mg daily for maintenance
  • If CHF is the cause, treat with furosemide, angiotensin-converting enzyme (ACE) inhibitor and digoxin
  • Treat the underlying cause of CHF
  • If edema is chronic, furosemide may not cause complete clearing of edema. The addition of an aldosterone antagonist (e.g. amiloride 5 mg, spironolactone 25 mg, or eplerenone 25–50 mg daily) is advisable if more than 40 mg furosemide is needed.
  • Furosemide, large doses, stimulates the renin-angiotensin-aldosterone system and is best used with eplerenone, amiloride, or an ACE inhibitor.
 
Bothersome Cough
Cough is a common symptom of patients with cardiopulmonary disease. Cough is a defense mechanism that helps to protect the airways from the effects of irritant substances and to clear the airways of unwanted secretions.
  • Is the cough productive or nonproductive?
  • If productive, is the sputum blood-tinged or mucopurulent?
  • Is there associated shortness of breath or wheezing?
  • Is the patient's temperature elevated?
If cough is associated with hemoptysis and shortness of breath, consider left ventricular failure and mitral stenosis. A “brassy” cough may indicate a thoracic aortic aneurysm:
  • Cough can be caused by reflux [gastroesophageal reflux (GER)], occurring mainly at nights. But unnoticeable reflux can cause sufficient irritation of the laryngotracheal area. The irritated nerve fibers in that small irritated spot triggers cough, which can be like a dog barking. This can occur day or night without a sensation of reflux and may last several weeks to months.
 
Salient Features of Cough
  • Acute:
    • Episodes lasting several minutes suggest an irritating phenomenon, mechanical or chemical (e.g. related to an allergic response or inhalation of smoke).
    • Episodes lasting several days with associated fever and evidence of upper respiratory tract infection suggest virus or laryngotracheobronchitis.
    • Association with chills, rigors, weakness, or confusion suggests pneumonia.10
  • Chronic:
    • Coughing related to smoking suggests chronic bronchitis.
    • A change in character or pattern suggests carcinoma of the lung.
    • Weight loss, fever and night sweats suggest tuberculosis.
    • Paroxysmal coughing, at night or with exercise, with or without wheezing, suggests asthma.
    • Coughing precipitated by exercise or sexual intercourse may suggest tight mitral stenosis.
    • Paroxysmal brassy cough, often with stridor, suggests tracheal obstruction produced by an aortic aneurysm.
  • Productive of sputum:
    • Purulent sputum associated with acute illness and fever suggests inflammatory conditions.
    • Purulent and chronic sputum, occurring especially in the early morning, suggests bronchiectasis.
    • Foul-smelling sputum suggests bronchoalveolar carcinoma.
    • Pink, foamy and voluminous sputum with shortness of breath is typical of pulmonary edema.
    • Rusty prune juice sputum with fever and chills is diagnostic of pneumonia.
  • Nonproductive:
    • This may result from a hyperactive cough reflex that responds to ordinary innocuous stimuli.
    • Several diseases may cause nonproductive cough, depending on the phase of the disease, notably cancer of the lung.
    • Sarcoidosis may cause cough with dyspnea and can be complicated by conduction disturbances, including complete heart block.
    • Medications, including ACE inhibitors, amiodarone and methotrexate, may be implicated.
  • Character:
    • Barking or croupy owing to laryngeal disease.
    • Paroxysmal with whoops typical of whooping cough.
    • Brassy from major airways.
  • Time relationships:
    • Nighttime, nonproductive, chronic, paroxysmal cough with wheeze suggests asthma.
    • Nighttime cough, with orthopnea or paroxysmal nocturnal dyspnea, with or without wheeze, is typical of CHF.
    • Cough occurring with meals and in bed may indicate GER or diverticulum; details on GER causing cough was mentioned earlier.
    • Cough on awakening or with change of posture is a hallmark of bronchiectasis; on awakening in a smoker, cough suggests chronic bronchitis or bronchogenic carcinoma.
  • Intractable, chronic, but nonproductive cough suggests medications (especially ACE inhibitors and amiodarone).
  • Associations:
    • Paroxysmal wheezing strongly suggests asthma.
    • Fever, chills, and rigors suggest pneumonia.
    • Stridor is a hallmark of involvement of the pharynx, larynx, extrathoracic trachea by foreign body, branchial cyst, acute epiglottitis, diphtheritic infection, or laryngeal edema caused by allergic reaction to drugs, such as ACE inhibitors, or other causes of angioneurotic edema.
    • Orthopnea suggests heart failure.
    • Weight loss, weakness and night sweats suggest tuberculosis or carcinoma.
    • With particular occupations, consider restrictive lung disease.
    • Pleuritic chest pain: Pneumonia, pulmonary embolism.
    • Central chest pain suggests pulmonary embolism.
 
Cardiac Causes
  • Conditions that cause an increase in left atrial pressure: Pulmonary venous hypertension that results in interstitial or pulmonary edema, left ventricular failure due to all causes, mitral stenosis, and left atrial myxoma.
  • Pulmonary embolism.
  • Compression of the tracheobronchial tree, as with aortic aneurysm.
  • Compression of the recurrent laryngeal nerve caused by an aortic aneurysm, a greatly enlarged left atrium, or pulmonary artery, which can cause cough and hoarseness.
  • Congenital cyanotic heart disease, in particular Eisenmenger's syndrome.
 
Hemoptysis
Determine if the sputum is:
  • Blood-streaked: This can originate in the upper respiratory tract or bronchi and, although common in patients with COPD, may be the only clue to bronchogenic carcinoma in a smoker.11
  • Pink, frothy, voluminous and associated with acute shortness of breath: These are hallmarks of pulmonary edema.
  • Rusty, “prune juice” with fever and chills: These are typical of pneumonia.
  • Rank blood, bright red or dark, suggests the following in the differential diagnosis: Bronchogenic carcinoma, pulmonary embolism, aortic aneurysm, arteriovenous fistula, mitral stenosis, Goodpasture's syndrome, blood dyscrasias and hereditary telangiectasia.
Determine whether the episodes of hemoptysis are associated with the following:
  • Early-morning cough or cough with change in posture: This suggests bronchiectasis, chronic bronchitis and bronchogenic carcinoma.
  • Dyspnea at rest, during effort, or during pregnancy: In this situation, small amounts of rusty sputum or small amounts of bright red blood suggest mitral stenosis. Sudden increase in left atrial pressure during effort or pregnancy may cause rupture of small bronchopulmonary anastomosing veins. Severe dyspnea and blood-tinged sputum are typical of pulmonary edema caused by mitral stenosis or left ventricular failure.
  • Weight loss and night sweats: These suggest tuberculosis.
  • Pleuritic pain: This suggests pulmonary embolism.
  • Congenital heart disease and cyanosis: These suggest Eisenmenger's syndrome.
 
Physical Examination
  • Assess vital signs.
  • Examine for the presence of left ventricular failure: Crackles over the lower lung fields, gallop rhythm and increased JVP; valvular lesions, in particular mitral stenosis (see Chapter 15). Assess for consolidation caused by pneumonia.
 
Testing
Chest X-ray:
  • Review posteroanterior and left lateral films; assess for lung lesions and subtle signs of left ventricular failure (see Chapters 6 and 8).
 
Management
Treat the underlying problem:
  • Cardiac
  • Pulmonary
  • Drugs-causing cough: Consider discontinuing drugs that cause cough, in particular ACE inhibitors, rarely angiotensin receptor blockers [ARBs] and amiodarone.
Cough suppressants: Cough suppressants are not recommended without considerable thought. Treatment of the underlying condition is recommended; if cough persists and is bothersome and is preventing sleep, give a trial of dextromethorphan 15 mg at bedtime: but this is not advisable if the cough is productive of sputum.
Cough expectorants: Cough expectorants are not recommended because they are ineffective. It is virtually impossible to liquefy thick, tenacious sputum. Ensure that the patient is well hydrated and improve the humidity of the inspired air.
SUGGESTED READING
  1. Farkouh ME, Douglas PS. The management of acute chest pain: what lies beyond the emergency department doors? J Am Coll Cardiol. 2016;67(1):27–8.
  1. Khan MG. Cardiac Drug Therapy, 8e. New York: Humana Press.  Springer Science+Business Media New York; 2015.