Acute Coronary Syndrome with Comorbidities: A Therapeutic Challenge Gurunath Parale
INDEX
A
Abciximab administration, safety of 19
Activated clotting time 52
Activated partial thromboplastin time 20
Acute antiplatelet treatment 53
Acute coronary syndrome 2, 3, 9, 11, 29, 49, 52, 58, 60, 68, 72, 8183, 85, 90, 91, 105, 116, 127
treatment of 111
Acute myocardial infarction 1, 7, 16, 36, 59, 76, 82, 84, 86
diagnosis of 60
management of 60
Adenosine diphosphate 18
Advanced cardiac life support guidelines 126
AIDS 2
Alberta Kidney Disease Network 32, 33
Alteplase 12
American Association for Study of Liver Diseases 77
American College of Cardiology 30, 92, 124
American Heart Association 10, 30, 92
American Stroke Association 10
Anemia 123, 124
autoimmune hemolytic 84, 85
Anesthesia 123
Angina, treatment of 111
Angiography 125
coronary 18, 36, 82, 125
Angioplasty
coronary 61
primary 16
stroke after primary 16
Angiotensin-converting enzyme 61
inhibitor 4, 34, 63
therapy 40
Antibody reaction 82
Anticoagulation 20
agents 18
periprocedural 52
therapy 18
Antiphospholipid
antibodies 83
syndrome, primary 112
Antiplatelet 64
therapy 18, 35
timing of resumption of 21
treatment 20, 75
Antiretroviral therapy 117
management of 117
Antirheumatic drugs, disease-modifying 109
Antithrombotic therapy 40
Anxiety 97
Aorta, ascending 22
Aortic valve
replacement 101
stenosis 101
symptomatic 101
Arrhythmias, cardiac 9
Arterial blood gas 126
Arterial disease, peripheral 30, 72
Aspirin 4, 20, 62
low-dose 108, 109
prophylactic use of 107
Atelectasis 97
Atherogenic lipid profile 116
Atherosclerosis 22, 30
accelerated 108
premature 108
B
Bare-metal stent 55
Beta-blockers 62, 76
Bivalirudin 52
Bleeding 123
risk 53
Blood pressure 107, 118
control of 34, 109
Body mass index 70
Bone mineral metabolism, disorders of 33
Brain 43
tissue 14
Breast cancer 99
British National Lymphoma Investigation Database 86
C
Calcium channel antagonists 34
Cancer 90, 94, 95
Cardiac disease 90, 95, 108
Cardiocerebral infarction 8, 9
hyperacute simultaneous 10
synchronous 8
Cardiopulmonary bypass 75
Cardiovascular disease 1, 30, 101, 105, 116
risk 117
Cardiovascular morbidity 106
Carotid artery
stenosis 22
stenting 23
Carotid endarterectomy 23
Carotid intima-media thickness 71
Carotid stenosis 22
symptomatic 22
Carotid stenting 23
Cerebral artery
anterior 14
middle 11, 14
Cerebrovascular disease 1, 4
Charlson comorbidity index 1
Chemotherapy 98
drugs 91
Child-Turcotte-Pugh classification 74
Cholesterol plaque formation 91
Chronic obstructive pulmonary disease 1, 58, 59, 61, 63, 64
Cigarette smoking, cessation of 118
Cirrhosis 71, 76
Clopidogrel 19, 5355, 95
plus aspirin 54, 55
Colon carcinoma 96
Combined combination antiretroviral therapy 116
Complete blood count 126
Connective tissue disease 1, 105
Conventional therapy 119
Coronary artery
bypass grafting 42, 51, 61, 93, 96, 119
surgery 18, 22, 23, 74
calcification score 31
disease 9, 30, 53, 59, 64, 69, 71, 72, 76, 82, 105, 108, 116, 123
management of 119
mechanisms of 91
risk of 118
stenosis, distribution of 70
thrombosis 85
Coronary computed tomography angiography 69, 70
Coronary flow velocity reserve 31
Coronary heart disease 32
atherosclerotic 85
treatment of 35
Coronary perfusion pressure 126
Coronary reperfusion strategies 38
Coronary revascularization 61
Corticosteroids 113
Creatine kinase, isoenzymes of 43
Cyclooxygenase-2 selective inhibitors 108
D
Dabigatran 54, 55
Danazol 82
Deep vein thrombosis 12, 20
Dementia 1
Dermatomyositis 113
Diabetes 30, 33, 116
mellitus 2, 71
Digestive tract tumors 95
Digital subtraction angiogram 15
Direct oral anticoagulant 53, 55
Disseminated intravascular coagulation 74
Dobutamine stress echocardiography 77
Drug-eluting stent 55, 93, 119
Dual antiplatelet therapy 22, 54, 73
Dyslipidemia 30, 33, 116, 118
E
Echocardiography, transesophageal 125
Emboli, chemical composition of 14
Endothelial dysfunction 30
Endothelial surface 83
Enzymes, cardiac 9
Epicardial adipose tissue 31
Esophageal varices 74
Estimated glomerular filtration rate 29
Exercise 109
Extracorporeal membrane oxygenation 127
Extubation 123
F
Fatty liver disease, nonalcoholic 70, 72
Fibrinolysis therapy 14
Fibrinolytic agents 12
Forced expiratory volume 63
G
Gammaglobulin, intravenous infusion of 87
Gastrointestinal tract 73, 110
Global Registry of Acute Coronary Events 12, 51
Glomerular filtration rate 107
Glucocorticoids 109
dose, minimizing 107
supraphysiologic dose of 111
Glucose intolerance 106
Glycoprotein 35, 52
H
Heart disease 95, 98
risk equivalence for 32
stable 3
Heart failure 99
congestive 1, 16, 22, 82
Heart valves 55
Helicobacter pylori 73
Hematological disorders 81
Hematoma expansion 20
Hemiplegia 2
Hemodialysis 31
Hemolysis, intravascular 85
Hemophilia 83
Hemorrhage 73
intracerebral 12, 20
intracranial 19, 20
retroperitoneal 15, 94
Henoch-Schonlein purpura 112
Heparin 19, 52
unfractionated 40
Hepatitis
C virus 71
infection 71
viral replication 74
Hodgkin's disease 99
Hodgkin's lymphoma 86, 99
Human immunodeficiency virus 118
infection 116, 118
Hydroxychloroquine 107
Hydroxyurea 86
Hyperleukocytosis 85
Hypertension 30, 33, 106, 107
arterial 123
control of 107
Hypertrophy, myocardial 85
Hypotension 35, 123, 124
intraoperative 124
Hypothermia 123
Hypovolemia 123
I
Immune thrombocytopenic purpura 82
Inflammation, chronic 108
Inspired oxygen, fraction of 126
Insulin resistance 118
Intensive care unit 15, 97
Intravascular thrombi, formation of 85
Intravenous thrombolytic therapy 10
Intubation 123
Ischemia, myocardial 122, 125
Ivabradine 64
K
Kawasaki disease 112
Kidney
disease 35
chronic 1, 29, 38
injury, acute 36
L
Leflunomide 109
Left bundle branch block 125
Left ventricular
ejection fraction 22, 96
mural thrombus 17
Leukemia 2
acute 85
chronic lymphocytic 98
Lipid-lowering therapy 118
Lipoproteins
high-density 118
low-density 106
Liver
cirrhosis 1, 4, 69, 72, 74, 76
disease 2, 75
chronic 68
end-stage 72, 74
disorders, common 72
function 74
Low-cholesterol paradox 41
Low-molecular weight heparin 20, 40
Low-platelet count 82
Lung disease, obstructive 59
Lymphoma, malignant 2
M
Major adverse cardiovascular event 3, 13
Malnutrition, inflammation, atherosclerosis, calcification syndrome 31
Metabolic syndrome 72, 118
Metastatic solid tumor 2
Mitral regurgitation, acute 127
Monckeberg's sclerosis 31
Monoclonal gammopathy 86
Multiple myeloma 86
Muscle 43
Myocardial infarction 1, 9, 16, 22, 29, 59, 62, 106
coexistence of 76
perioperative 122, 125
stroke after 17
Myocardial injury 122
Myocardial Ischemia National Audit Project 60
Myocardial ischemia, intraoperative 124
Myocarditis, inflammatory 113
Myocytolysis 9
Myositis, adult inflammatory 113
N
N-acetylcysteine 44
National Health Insurance Research Database 76
National Kidney Foundation 30
Nephropathy, contrast-induced 43
Nifedipine 107
Non-Hodgkin's lymphoma 86, 99
Non-nucleoside reverse transcriptase inhibitors 117
Non-ST elevation
acute coronary syndromes 10
myocardial infarction 11, 83
Non-ST segment elevation myocardial infarction 60, 61, 122
Nonsteroidal anti-inflammatory drugs 44, 73, 108, 110, 111
Nucleoside reverse transcriptase inhibitors 117
O
Obesity, central 106
Obstructive coronary artery disease 70
Optical coherence tomography 94
Oral anticoagulant 54, 55
Orthotopic liver transplantation 76
Oxygen saturation 124
P
Pain, postoperative 97
Paroxysmal nocturnal hemoglobinuria 85
Peptic ulcer disease 2
Percutaneous coronary intervention 10, 13, 19, 22, 30, 54, 72, 73, 82, 93, 119
stroke after 13
Pericarditis 92
Peritoneal dialysis 31
Pexelizumab, assessment of 16
Platelets
excessive production of 84
microparticles, release of 82
Polycythemia vera 84
Polymyositis 113
Prasugrel 95
Proatherogenic lipid profile 112
Protease inhibitors 117
Pulmonary embolism 12
prophylaxis 20
R
Radiotherapy 99
Recombinant tissue plasminogen activator 10
Renal disease
end-stage 30
reduce progression of 34
Renal dysfunction, chronic 107
Renal failure, acute 36
Renal transplant 42
Reperfusion therapy 4
Respiratory system 86
Resuscitation, cardiopulmonary 126
Reteplase 12
Rheumatoid arthritis 105, 108, 111
S
Sickle cell
anemia 85
disease 85
Sickness, dominant cause of 1
Single antiplatelet therapy 54, 55
Sjögren's syndrome 112
Solid tumor 2
Splenectomy 82
Spontaneous bacterial peritonitis prophylaxis 74
Stable angina, pharmacological treatment of 42
Standard medical therapy 39
Statins 41, 63, 106
therapy 34
Steatohepatitis, nonalcoholic 72
ST-elevation myocardial infarction 8, 12, 37, 42, 83
Stenosis
bilateral asymptomatic 22
unilateral asymptomatic 22
Steroids 82
Streptokinase 12
Stress 97
Stroke 13, 19, 22, 53
acute 15
ischemic 7, 12
hemorrhagic 15
ischemic 9, 10
symptoms of 14
volume variation 127
ST-segment elevation myocardial infarction 4, 30, 60, 61, 122
Systemic lupus erythematosus 105, 107
Systemic vasculitis, primary 112
T
Tachycardia 123
Takayasu's arteritis 112
Takotsubo cardiomyopathy 92
Tenecteplase 12
Thrombocythemia, essential 84
Thrombocytopenia 82, 94
Thrombotic thrombocytopenic purpura 82
Ticagrelor 19
Tissue plasminogen activator 14
Transient ischemic attacks 9
Transjugular intrahepatic portosystemic shunts 74
Triglycerides 119
Tumor necrosis factor 30, 123
U
Unstable angina, pharmacological treatment of 42
V
Vascular disease, peripheral 1
Vasculitis, systemic 105
Vitamin K antagonist 55
von Willebrand disease 83
von Willebrand factor 40, 83
W
WOEST trial 53
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Chapter Notes

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IntroductionCHAPTER 1

Cardiovascular disease (CVD) is a dominant cause of sickness and death all over the world. It accounts for almost 30% of all-cause mortality in the world.1 Since the burden of CVD increases with age, it is not surprising that a major portion of the patients with CVD tend to be older and frailer with multiple comorbidities. Presence of a comorbid condition not only affects the disease progression in CVD but also profoundly influences clinical outcome and decision-making. It is a known that cardiovascular comorbidities such as hypertension, diabetes, atrial fibrillation, heart failure and stroke are independent predictors of risk and mortality in patients presenting to the emergency department of a hospital with acute myocardial infarction (AMI). However, the fact that many of the patients with CVD harbor a broad spectrum of noncardiovascular comorbidities receives less attention. The cardiovascular and noncardiovascular morbidities such as chronic obstructive pulmonary disease (COPD), liver cirrhosis, chronic kidney disease (CKD) and connective tissue disorders have a significant bearing on presentation, management and prognosis of CVD (Figs. 1 and 2).2
The Charlson comorbidity index (CCI) is a well-recognized measure of comorbid conditions.3 It quantifies prognostic impact of twenty-two comorbid conditions by means of a score—making it a useful tool for objective assessment of prognosis in multiple coexisting illnesses.
Different variables in Charlson comorbidity index with respective score are as follows:
  • Cerebrovascular disease: 1
  • Congestive heart failure: 1
  • Peripheral vascular disease: 1
  • Myocardial infarction: 1
  • Connective tissue disease: 1
  • Dementia: 1
  • Chronic obstructive pulmonary disease: 12
  • Peptic ulcer disease: 1
  • Moderate-to-severe CKD: 2
  • Leukemia: 2
  • Hemiplegia: 2
  • Malignant lymphoma: 2
  • AIDS: 6
  • Diabetes mellitus: 1 (if uncomplicated) and 2 (if end organ is damaged)
  • Liver disease: 1 (if mild) and 2 (if moderate-to-severe)
  • Solid tumor (any): 2
  • Metastatic solid tumor: 6.
Many randomized controlled studies from a wide spectrum of populations have shown that majority of the patients with CVD have at least one comorbidity. Over the years, the prevalence of comorbidity has shown an upward trend. Conversely, the number of CVD patients without comorbidity has steadily fallen during the past couple of decades.
A meta-analysis by Rashid et al. looked at the impact of CCI on the outcomes in following cardiovascular conditions:
  • Acute coronary syndrome (ACS)
  • Stable coronary heart disease (CHD)
  • Patients undergoing percutaneous intervention (PCI).
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FIG. 1: Showing prognostic influence of cardiac and noncardiac comorbidities on cardiovascular events.Source: Canivell S, Muller O, Gencer B, et al. Prognosis of cardiovascular and non-cardiovascular multimorbidity after acute coronary syndrome. PLoS One. 2018;13(4):e0195174.
3
zoom view
FIG. 2: Showing impact of cardiac and noncardiac comorbidities on coronary events.Source: Canivell S, Muller O, Gencer B, et al. Prognosis of cardiovascular and non-cardiovascular multimorbidity after acute coronary syndrome. PLoS One. 2018;13(4):e0195174.
 
ACUTE CORONARY SYNDROME WITH COMORBIDITIES
The risk of death in patients of ACS with a comorbidity increases proportionately with incremental increase in CCI score. Similarly, the risk of death was almost two times more in patients with any comorbidity (CCI >0) when compared to patients with no comorbidity (CCI = 0).
Jeger et al. reported in an ACS registry that the incidence of major adverse cardiovascular events (MACEs) increased with a CCI score—equal to or more than 2 during a 1-year follow-up period after ACS.4
In yet another study, Nunez et al. revealed that a higher CCI score is an independent predictor of mortality or AMI at 30 days and 1 year.5
 
RELATIONSHIP OF COMORBIDITY AND STABLE HEART DISEASE
It was revealed in the meta-analysis by Rashid et al. that an incremental increase in CCI score is associated with increased mortality even in stable heart disease.14
 
PATIENTS UNDERGOING PERCUTANEOUS INTERVENTION
Majority of the studies looking into the long-term survival after PCI for CAD have reported increased mortality with each point increase in CCI score.1
The conclusion of the study by Rashid et al. reveals that association of comorbidity has an inverse relationship to the survival outcomes in patients with heart disease. This finding has important implications in management of heart disease. Since the noncardiovascular comorbidities are usually not factored into while calculating mortality and survival outcomes in CHD unlike the traditional comorbid conditions such as diabetes, hyperlipidemia, hypertension, the findings of the study by Rashid et al. carry important long-term implications.
The mechanism by which the comorbid conditions such as CKD, liver cirrhosis, cerebrovascular disease influence outcomes in CVD is complex and multifactorial. Moreover, older and frailer patients with a relatively higher burden of comorbidity are likely to be treated with increased caution and often unwarranted conservative approach unlike the younger patients with no comorbid condition. For instance, it was found in a large, national ACS registry that there was an incremental reduction in the provision of evidence-based treatments such as aspirin, statins, angiotensin-converting enzyme (ACE) inhibitors and reperfusion therapy in older patients with multiple comorbid conditions.6 In another recent analysis involving 18,814 patients, Patel et al. reported that patients with comorbid burden, as defined by CCI score, were less likely to be offered coronary angiography and/or reperfusion therapy when presented with ST segment elevation myocardial infarction (STEMI).7 In addition, in the setting of acute ischemic stroke, thrombolysis is often denied to older patients with comorbidities due to fear of hemorrhage unlike the younger patients with no comorbidity.8 While managing chronic heart failure, deployment of ACE inhibitors and spironolactone is many a times withheld if there is a concurrent chronic kidney disease. Similarly, the treating physicians are often reluctant to use beta-blockers in elderly patients with chronic obstructive pulmonary disease.9
It is also true that aggressive treatment strategies in elderly patients with multiple comorbidities can result in adverse outcomes and heightened probability of complications. For instance, patients with leukemia are at an increased risk for in-stent thrombosis. Similarly, patients with liver cirrhosis have a greater likelihood of hemorrhage after PCI when antiplatelet agents are used. Consequently, the treating physicians face a daunting challenge to find a balance between the risks and benefits of a therapeutic intervention. The challenge is particularly stiff while managing patients with CHD and comorbidities in the present time because multiple treatment options such as medical therapies, PCI, surgical revascularization, device therapies and thrombolysis are now readily available to wider spectrum of patients.5
The author has faced many such challenges in his daily practice. Through this book, author intend to help his colleagues in cardiology to live up to the difficult task of managing patients of heart disease harboring various comorbid conditions. The author had to sift through a large amount of available literature on this subject before presenting this book so that the reader can make management decisions that are evidence-based. The author intend to drive home the message that there must be a thorough assessment of the comorbid status in patients of heart disease and that the impact of comorbidity on long-term survival must be integrated into the counseling of such patients. Any choice of treatment must be preceded by assessment of comorbid conditions apart from traditional risk assessment.
REFERENCES
  1. Rashid M, Kwok CS, Gale CP, et al. Impact of comorbid burden on mortality in patients with coronary heart disease, heart failure, and cerebrovascular accident: a systematic review and meta-analysis. Eur Heart J Qual Care Clin Outcomes. 2017;3:20–36.
  1. Canivell S, Muller O, Gencer B, et al. Prognosis of cardiovascular and non-cardiovascular multimorbidity after acute coronary syndrome. PLoS One. 2018;13(4):e0195174.
  1. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40: 373–83.
  1. Jeger R, Jaguszewski M, Nallamothu BN, et al. Acute multivessel revascularization improves 1-year outcome in ST-elevation myocardial infarction: a nationwide study cohort from the AMIS Plus registry. Int J Cardiol. 2014;172:76–81.
  1. Nunez JE, Nunez E, Facila L, et al. Prognostic value of Charlson comorbidity index at 30 days and 1 year after acute myocardial infarction. Rev Esp Cardiol. 2004;57:842–9.
  1. Zaman MJ, Stirling S, Shepstone L, et al. The association between older age and receipt of care and outcomes in patients with acute coronary syndromes: a cohort study of the Myocardial Ischaemia National Audit Project (MINAP). Eur Heart J. 2014;35:1551–8.
  1. Patel N, Patel NJ, Thakkar B, et al. Management strategies and outcomes of ST-segment elevation myocardial infarction patients transferred after receiving fibrinolytic therapy in the United States. Clin Cardiol. 2016;39:9–18.
  1. Bateman BT, Schumacher HC, Boden-Albala B, et al. Factors associated with In-hospital mortality after administration of thrombolysis in acute ischemic stroke patients: an analysis of the nationwide inpatient sample 1999 to 2002. Stroke. 2006;37:440–6.
  1. Muzzarelli S, Maeder MT, Toggweiler S, et al. Frequency and predictors of hyperkalemia in patients ≥60 years of age with heart failure undergoing intense medical therapy. Am J Cardiol. 2012;109:693–8.