New and Future Developments in Microbial Biotechnology and Bioengineering: Sustainable Agriculture: Microorganisms as Biostimulants Harikesh Bahadur Singh
Royal Brompton & Harefield Hospitals GSST and Imperial College
National Heart & Lung Institute London, UK
1
Great Clarendon Street, Oxford, OX2 6DP, United Kingdom
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Dear Colleagues,
Cardiovascular medicine has experienced an unforeseen and impressive development over the last 50 years, particularly recently, as we developed new diagnostics and innovative medications, as well as interventional and surgical procedures to treat patients with cardiac disease. Thus, the number of cardiovascular diagnoses and the number of diagnostic modalities, as well as the number of treatment options has expanded enormously and made cardiovascular medicine one of the biggest specialties in medicine at large. Cardiac patients are among the most important patient groups, both for general practitioners and for physicians working in hospital centres, and therefore it is of utmost importance to have information about the management of such patients readily at hand. This cardiovascular manual focusing on diagnostic algorithms and therapeutic recommendations according to European Guidelines, provides such a tool. Indeed, it encompasses all aspects of cardiovascular medicine from hypertension to transplantation, from imaging to intervention, and from pharmacotherapy to surgical procedures. With therefore hope to provide an important guide based on the current levels of evidence for surgery and for clinical rounds whilst managing patients with cardiovascular problems. We sincerely hope that you enjoy using this manual.
Yours sincerely
Thomas F. Lüscher
Juan-Carlos Kaski, Jack Barton, and Hussein Al-Rubaye
Oliver
Oliver
Christian
Christoph
Christoph
Ardan M. Saguner and Hugh Calkins
Gerhard-Paul Diller and Michael A. Gatzoulis
Faisal Khan and Stephan Windecker 347
Francesco Maisano and Maurizio Tarramasso
Bernard Prendergast and Thomas F. Lüscher
Christian Schmied, Thomas F. Lüscher, and Steen Dalby Kristensen 377
Allan Davies and Christian Schmied
Contributors
Hatem Alkadhi, Institute of Diagnostic and Interventional Radiology, University of Zurich, Switzerland
Hussein Al-Rubaye, Ashford & St. Peter’s NHS Foundation Trust, UK
Beatrice Amann-Vesti, Angiology, Klinik im Park, Zurich, Switzerland
Jack Barton, St George’s, University of London, UK
Andreas Baumbach, Cardiology, Queen Mary University of London/Barts Heart Centre, UK
Felix Beuschlein, Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, University Hospital Zurich, Switzerland
Ronald Binder, Cardiology, Klinikum WelsGrieskirchen, Austria
Hugh Calkins, Cardiology, Johns Hopkins University, Baltimore, Maryland, USA
A. John Camm, Cardiac Clinical Academic Group, St. George’s University of London, London, UK
Nick Cheshire, Vascular Surgery, Royal Brompton & Harefield Hospitals, London, UK
John G.F. Cleland, Robinson Center for Biostatistics, University of Glasgow, UK
Allan Davies, Heart Division, Royal Brompton & Harefield Hospitals, London, UK
John E. Deanfield, Consultant Cardiologist, University College Hospital, London, UK
Gerhard-Paul Diller, Cardiology III, Congenital and Valvular Heart Disease, University Hospital, Münster, Germany
Sabine Ernst, Consultant Cardiologist & Electrophysiologist, The Royal Brompton Hospital, London, UK
David Faeh, Institut for Epidemiology, Biostatistics and Prevention, University of Zurich, Switzerland
Oliver Gämperli, Herzklinik Hirslanden Zürich, Switzerland
Michael A. Gatzoulis, Consultant Cardiologist, The Royal Brompton Hospital, London, UK
Silvia Guarguagli, Heart Division, The Royal Brompton Hospital, UK
Oliver P. Guttmann, Inherited and Inflammatory Cardiovascular Diseases & Interventional Cardiology, St Bartholomew’s Hospital, UK/UCL Centre for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, UK
Shouvik Haldar, Consultant Cardiologist & Electrophysiologist, Royal Brompton & Harefield NHS Foundation Trust, London, UK
Bettina Heidecker, Cardiology, Benjamin Franklin Hospital, Charité, Berlin, Germany
Matthias Hermann, Cardiovascular Center, Cardiology University Hospital Zurich, Switzerland
Gerhard Hindricks, Department of Electrophysiology, Leipzig Heart Center at University of Leipzig, Germany
Dagmar I. Keller, Director, Emergency Unit, University Hospital Zürich, Switzerland
Juan-Carlos Kaski, Consultant Cardiologist, Molecular and Clinical Sciences Research Institute, St George’s, University of London, London, UK
Faisal Khan, St George’s Hospital, London, UK
Paulus Kirchhof, University Heart and Vascular Center Universitätsklinikum Eppendorf, Hamburg, Germany
Stavros V. Konstantinides, Centre for Thrombosis and Haemostasis, University Medical Centre Mainz, Germany
Steen Dalby Kristensen, Cardiology, Aarhus University Hospital, Aarhus, Denmark
Mario Lachat, Vascular Surgery, Clinic Hirslanden, Zurich, Switzerland
Roger Lehmann, Vice Director of the Department of Endocrinology, Diabetology and Clinical Nutrition and Director of Islet transplantation, University Hospital Zurich, Switzerland
Andreas Luft, Neurology, University Hospital Zurich, Switzerland
Thomas F. Lüscher, Director of Research, Education & Development, Royal Brompton & Harefield Hospitals, and Imperial and Kings College, London, UK and Chairman, Center for Molecular Cardiology, University of, Zurich, Zurich, Switzerland
François Mach, Director of Cardiology, University Hospital and University of Geneva, Switzerland
Francesco Maisano, Cardiovascular Surgery, San Raffaele Hospital, Milan, Italy
Marco Metra, Institute of Cardiology, SST Spedali Civili; Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Italy
Christoph A. Nienaber, Consultant in Cardiology, The Royal Brompton Hospital, London, UK
Antonis Pantazis, Consultant in Cardiology Royal Brompton and Harefield NHS Trust, London, UK
Sanjay K. Prasad, Faculty of Medicine, National Heart & Lung Institute, Imperial College London, UK
Bernard Prendergast, Consultant in Cardiology, St Thomas’ Hospital, London, UK
Bruno Reissmann, Department of Cardiology, Asklepios Klinik St Georg, Hamburg, Germany
Marco Roffi, Cardiology, Hospitaux Universitaire, Geneva, Switzerland
Ardan M. Saguner, University Heart Center, Cardiology, University Hospital Zürich, Switzerland
Christian Schmied, University Heart Center, University Hospital Zurich, Switzerland
Peter J. Schwartz, Center for Cardiac Arrhythmias of Genetic Origin, Istituto Auxologico Italiano IRCCS, Milan, Italy
Allireza Sepehri Shamloo, Department of Electrophysiology, Leipzig Heart Center at University of Leipzig, Germany
Sanjay Sharma, Consultant in Cardiology, St George’s University of London, London, UK
Isabella Sudano, University Heart Center Cardiology, University Hospital Zurich, Switzerland
Maurizio Tarramasso, Heart Center Hirslanden, Zurich, Switzerland
Christian Templin, University Heart Center, Cardiology, University Hospital Zurich, Switzerland
Jelena R. Templin-Ghadri, University Heart Center, Cardiology, University Hospital Zurich, Switzerland
Silvia Ulrich, Pulmonology, University Hospital Zurich, Switzerland
Stephan Windecker, Chairman of Cardiology, Inselspital, Bern, Switzerland
DLCO Diffusing capacity of the lung for carbon monoxide
DM Diabetes mellitus
DOPA-PET 18F-DOPA positron emission tomography
DPP Dipeptidyl peptidase-4
Echo Echocardiography
EF Ejection fraction
eGFR estimated glomerular filtration rate
ESCFH Familial hypercholesterolemia
FFR Fractional flow reserve
GLP-1 Glucagon-like peptide 1
HDL-C High-density lipoprotein cholesterol
HIV Human immunodeficiency virus
ICD Implantable cardioverter defibrillator
INR International normalized ratio
LDL-C Low-density lipoprotein cholesterol
LEAD Lower extremity arterial disease
LV Left ventricle
LVEF Left ventricular ejection fraction
MACE Major cardiovascular events
MAP Mean arterial pressure
MIBG Iodine-131metaiodobenzylguanidine
mPAP Mean pulmonary artery pressure
MRI Magnetic resonance imaging
NICE National Institute for Health and Care Excellence
NOACs novel oral anticoagulants
nonHDL-C Non high-density lipoprotein cholesterol
NSAIDS Nonsteroidal anti-inflammatory drugs
NSTEMI Non ST-segment elevation myocardial infarction
PA Pulmonary artery
PAD Peripheral arterial disease
PAH Pulmonary arterial hypertension
PAWP pulmonary artery wedge pressure
PCI Percutaneous coronary intervention
PCSK9 Proprotein convertase subtilisin/Kexin Type 9
PEA Pulmonary endarterectomy
PFT Pulmonary function testing
PH Pulmonary hypertension
PVR Pulmonary vascular resistance
RAAS Renin-angiotensinaldosterone system
RHC Right heart catheterisation
RV Right ventricle
SGLT2 Sodium-glucose co-transporter-2
STEMI ST-segment elevation myocardial infarction
TAVI Transcatheter aortic valve implantation
TC Total cholesterol
TIA Transient ischaemic attack
TOE transoesophageal echocardiography
TTE Transthoracic echocardiography
UFH Unfractionated heparin
V/Q Ventilations perfusion quotient
VKA Vitamin K antagonist
Global Cardiovascular Risk
Thomas F. Lüscher and John E. Deanfield
Risk Assessment 2
Commonly Used Risk Scores 2
Population-Dependence of CV Risk Scores 3
Short-Term versus Lifetime Risk 4
Risk Assessment
The assessment of the probability that an individual will experience major cardiovascular (CV) events (MACe) in the future is of utmost importance as a basis for recommendations on lifestyle and, if necessary, pharmacotherapy.
Currently risk assessment is based on the classical CV risk factors such as:
• Age (one of the strongest CV risk factors)
• Sex (with male sex in general being at higher risk)
• Smoking (see Chapter 7: Smoking Cessation; this volume)
• Dyslipidaemias (see Chapter 4: Lipid Disorders; this volume)
• Arterial hypertension (see Chapter 2: Arterial hypertension; this volume)
• Diabetes mellitus (see Chapter 6: Diabetes Mellitus; this volume).
The Global CV Risk attempts to integrate all these commonly used variables. Of primary clinical importance are those CV risk factors that are amenable to change, either by improving life style (e.g. smoking cessation, exercise, and weight loss to lower blood pressure, certain lipids, and glucose levels) and/or pharmacotherapy.
There are numerous other variables that predict future MACe (e.g. genetics, inflammation, platelet reactivity, coagulation factors, lipids such as triglycerides and lipoprotein(a), and periodontitis among others), but they are not commonly integrated into currently used risk scores. however, in addition to the risk obtained from a given risk score, they should be considered, if available, when assessing an individual patient.
Commonly Used Risk Scores
A number of risk scores have been developed and are commonly used in primary prevention (i.e. in individuals without evidence of CV disease):
• SCORe Risk Charts of the european Society of Cardiology (eSC) (www.heartscore.org)
• ASCVD Risk estimator Plus of the American College of Cardiology (ACC) (https://www.acc.org/tools-and-practice-support/mobileresources/features/2013-prevention-guidelines-ascvd-risk-estimator)
• heart Risk Calculator ACC/American heart Association (www. cvriskcalculator.com)
• Risk score of the International Society of Atherosclerosis.
Population-Dependence of CV Risk Scores
Risk scores have usually been developed based on a specific population. however, the CV risk as a result of classical CV risk factors (see section ‘Risk Assessment’) differs in different populations, i.e. higher risks in northern european countries compared to those from the south of europe, as well as higher risks in the United States compared to europe. The SCORe Risk Chart of the eSC is based on 12 european cohort studies with 250,000 patientdata sets averaging 3 million person-years of observation and 7,000 fatal CV events (www.heartscore.org). This has allowed derivation of a SCORe Risk chart for high, medium, and low risk countries. Figure 1.1 shows a chart for medium risk countries (see also https://academic.oup.com/eurheartj/ advance-article-abstract/doi/10.1093/eurheartj/ehz455/5556353).
Most risk scores in current use, provide estimates of the probability of future MACe over a 5–10-year period. however, with the growing emphasis on CVD prevention, attention is shifting to evaluation of life time risk, particularly in primary care (Figure 1.2). This is based on evidence that the impact of risk factors not only depends on their magnitude but also on duration of exposure. early intervention can provide ‘leveraged gains’. The Joint British Societies 3 (JBS3) guidelines provide a calculator for communicating both short-term and lifetime risk (http://www.jbs3risk.com/pages/ risk_calculator.htm). This approach will increasingly be incorporated in new guidelines to communicate both risk and opportunities for intervention from behavioural change and, where appropriate, drug therapy.
Figure 1.2 Lifetime risk of individuals without evidence of CV disease at study entry over 35 years depending on the number of elevated CV risk factors in the Framingham Study.
Thomas F. Lüscher, Felix Beuschlein, and Isabella Sudano
Definition 8
History 9
Diagnostic Aspects 12
Comorbidities 17
Therapy 18
Definition
Blood pressure is essential for proper perfusion of the organs of the body. However, if elevated above certain levels, blood pressure is also an important cardiovascular risk factor for myocardial infarction, stroke, renal and heart failure, and death (Figure 2.1 and Table 2.1).
Primary Hypertension (95% of All Forms of Hypertension)
• No diagnostic findings of a known reversible cause
• Hyperactivity of the sympathetic nervous system, of baroreceptor function and neurohumoral systems
• Familial clustering (genetic factors)
• Modifiable risk factors: Obesity, sedentary life style, high salt and/or alcohol consumption, drugs (non-steroidal anti-inflammatory drugs; NSAIDs), catecholamines, hormones (mineralocorticoids, steroids, oestrogens), liquorice.
Secondary Hypertension
• renovascular, renal parenchymatous, or endocrine disease, coarctation of the aorta, obstructive sleep apnoea.
Measuring Blood Pressure
• Sitting (after ≥3 minutes of rest), three measurements on at least 2 days, reading with a 2 mmHg precision, average of second and third measurement
• ‘Unattended recording’ with automatic device in a separate room (mainly to exclude ‘White Coat Hypertension’)
• Standing to exclude or confirm orthostatic hypotension (i.e. >20 mmHg fall in systolic Bp), particularly important in elderly patients and those with heart failure (n=1233)
• Width of the cuff has to be adapted to upper arm circumference (i.e. >33 cm = large cuff)
• Decompression 2 mmHg/sec
• Calibrate device regularly
• Systolic blood pressure
• Appearance of Korotkoff sounds
• Diastolic blood pressure
• phase V (disappearance of Korotkoff sounds)
• phase IV (‘muffling’ of Korotkoff sounds). Only useful in special cases (pregnancy, arterial calcification [Mönckeberg syndrome], etc.).
Table 2.1 Definitions and classification of blood pressure values (mmHg)
Category Systolic BP Diastolic BP
Ideal <120 <80
Normal 120–129 80–84
High normal2 130–139 85–89
Stage 1 hypertension 140–159 90–99
Stage 2 hypertension 160–179 100–109
Stage 3 hypertension 180 110
Isolated systolic hypertension >140 <90
1 Average of 3 measurement on different days; White coat hypertension: elevated office blood pressure; masked hypertension: elevated blood pressure only outside medical institution.
2 The 2017 US Hypertension Guidelines (J Amer. Coll Cardiol. 2017; doi: 10.1016/j. jacc. 2017. 11.006) have defined a systolic blood pressure of <120/80 mmHg as normal, 120–129 mmHg as elevated, and 130–139/80–89 mmHg as grade 1 hypertension and > 140/90 mmHg as grade 2 hypertension. The 2018 eSC Guidelines on Arterial Hypertension (Eur Heart J. 2018;39:3021–104) are more cautious.
