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Heart failure is a syndrome with various aetiologies and a poor prognosis. New pathophysiological findings have led to treatment strategies with improved prognosis. For want of a causal treatment option the focus lies on drug strategies. In addition, surgical or other procedures come into consideration. All these treatment strategies are presented in detail, analysed and evaluated with reference to the pathophysiology and study data. An assessment is also made regarding the European (ESC) and US guidelines (ACC/AHA) on completion of each chapter topic. This emphasises the level of evidence for…mehr
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Heart failure is a syndrome with various aetiologies and a poor prognosis. New pathophysiological findings have led to treatment strategies with improved prognosis. For want of a causal treatment option the focus lies on drug strategies. In addition, surgical or other procedures come into consideration. All these treatment strategies are presented in detail, analysed and evaluated with reference to the pathophysiology and study data. An assessment is also made regarding the European (ESC) and US guidelines (ACC/AHA) on completion of each chapter topic. This emphasises the level of evidence for each recommended therapy. Such recommendations are important because a guideline-oriented treatment strategy improves the prognosis in heart failure! The authors have approached this sophisticated subject in a structured, vivid and richly illustrated form, where even the latest study data are taken into account. Thus, this book is a highly topical and practical treatment guideline for doctors practicing Cardiology.
Produktdetails
- Produktdetails
- Verlag: UNI-MED Verlag AG
- Seitenzahl: 321
- Erscheinungstermin: 12. Mai 2017
- Englisch
- ISBN-13: 9783837455205
- Artikelnr.: 62234866
- Verlag: UNI-MED Verlag AG
- Seitenzahl: 321
- Erscheinungstermin: 12. Mai 2017
- Englisch
- ISBN-13: 9783837455205
- Artikelnr.: 62234866
1.Definition of heart failure23 1.1.Fundamentals23 1.2.Clinical definition23 1.2.1.Present definition23 1.2.2.The NYHA stages24 1.3.Current guidelines of the ESC and ACCF/AHA24 1.3.1.The 2012 ESC guidelines25 1.3.2.The 2013 ACCF/AHA guidelines25 1.4.Haemodynamic differences in systolic/diastolic HF25 1.5.Summary26 1.6.References26 2.Prognosis of heart failure27 2.1.Fundamentals27 2.2.Prognosis in the era before ACE inhibitors27 2.3.Prognosis in controlled treatment studies28 2.4.Prognosis depending on atrial fibrillation28 2.4.1.The prognosis in atrial fibrillation28 2.4.2.Prevalence of AF in the heart failure studies29 2.5.Prognosis and heart rate30 2.5.1.The BEAUTIfUL study30 2.5.2.The CIBIS II study30 2.6.Prognosis in ischaemic vs non-ischaemic heart failure30 2.7.Prognosis in cardiomyopathies31 2.8.Prognosis depending on EF and LVH31 2.9.Prognosis in systolic vs diastolic HF31 2.10.Prognosis depending on GFR32 2.11.Prognosis depending on the BNP level33 2.12.Copeptin and prognosis34 2.13.Prognosis depending on CRP34 2.14.Prognosis in anaemia34 2.15.Prognosis depending intensity of management34 2.16.Prognosis depending on age35 2.17.Prognosis depending on sex35 2.18.Prognosis depending on diabetes mellitus35 2.19.Prognosis and guidelines-based therapy36 2.20.Improvement in the prognosis of heart failure 1950 to 199936 2.21.Quality of life in heart failure36 2.22.The obesity paradox37 2.23.Treatment successes as a result of evidence-based therapy37 2.24.Causes of death in heart failure37 2.25.Low cardiac index and risk of the development of dementia38 2.26.Prognosis in HF – The MAGGIC risk score38 2.27.Summary40 2.28.References40 3.Epidemiology43 3.1.Prevalence and incidence of heart failure43 3.2.Prevalence of ventricular dysfunction on the echocardiogram (since 1990)43 3.3.Systolic vs diastolic heart failure44 3.4.Obesity and heart failure44 3.5.Summary45 3.6.References45 4.Classification of heart failure46 4.1.Options for classification46 4.1.1.According to the affected ventricle46 4.1.2.According to time course46 4.1.3.According to the degree of compensation46 4.1.4.According to the cardiac output46 4.1.5.According to symptoms46 4.1.6.According to the disordered ventricular function46 4.1.7.According to exercise tolerance46 4.1.8.According to clinical features46 4.1.9.According to NYHA class (NYHA – New York Heart Association)47 4.1.10.According to the ACCF/AHA classification47 4.1.11.Stage D heart failure48 4.2.Summary48 4.3.References48 5.Aetiology of heart failure49 5.1.Heart failure – A syndrome of various aetiology49 5.2.The cardiomyopathies50 5.3.Antidiabetic agents and HF51 5.4.Summary51 5.5.References51 6.Pathophysiology of heart failure53 6.1.Pathophysiological basis 53 6.2.Importance of pre- and afterload for the healthy and diseased heart53 6.2.1.Effects of isolated preload reduction53 6.2.2.Effects of isolated reduction of afterload54 6.3.Importance of the heart rate increase for the healthy and failing heart54 6.3.1.The force-rate relationship54 6.3.2.Further effects of an increased heart rate54 6.3.3.Heart rate in CHD and HF55 6.4.Compensatory mechanisms in heart failure55 6.5.Vicious circle in heart failure56 6.6.Determinants of myocardial oxygen consumption57 6.7.Causes of heart failure57 6.8.Importance of apoptosis57 6.9.Heart failure concepts today58 6.10.Origin of the oedema in heart failure59 6.11.Haemodynamics in systolic vs diastolic heart failure59 6.12.The kidney in heart failure59 6.13.The lung in heart failure60 6.14.The importance of natriuretic peptides61 6.15.Summary61 6.16.References61 7.Main aspects of diagnostic investigation63 7.1.Aims of investigation63 7.2.Symptoms63 7.3.Investigations 63 7.4.Symptoms and severity of heart failure65 7.5.Laboratory investigation of heart failure65 7.5.1.BNP vs NT-proBNP65 7.5.1.1.The half-life of BNP65 7.5.1.2.The half-life of NT-proBNP66 7.5.1.3.Limit values of BNP66 7.5.1.4.Limit values of NT-proBNP66 7.5.1.5.Relationship with renal function, age and sex67 7.5.2.BNP and NT-proBNP levels in systolic heart failure67 7.5.3.BNP and NT-proBNP levels in diastolic heart failure68 7.5.4.Other causes of BNP level increases68 7.5.5.Obesity reduces BNP levels68 7.6.BNP levels for treatment monitoring69 7.7.BNP determination in the emergency clinic – The BASEL study69 7.8.BNP in chronic heart failure70 7.9.BNP as a prognostic indicator at the time of discharge from hospital70 7.10.BNP as a predictor of risk71 7.11.Diagnostic algorithms if heart failure is suspected71 7.12.The guidelines on heart failure71 7.12.1.2012 ESC71 7.12.2.2013 ACCF/AHA71 7.13.Summary72 7.14.References72 8.Treatment goals and treatment strategies in heart failure74 8.1.Treatment goals74 8.2.Treatment strategies74 8.2.1.General measures74 8.2.2.Drug therapy75 8.2.3.Surgical measures including heart transplantation75 8.2.4.Haemofiltration75 8.3.Prevention of heart failure75 8.4.Behaviour of ejection fraction during treatment76 8.5.The 2103 ACCF/AHA guidelines76 8.6.Summary77 8.7.References77 9.Diuretics79 9.1.Pathophysiology and mechanism of action79 9.2.Classification and differentiation of diuretics80 9.3.Dose-effect relationship of diuretics80 9.4.Value of diuretics in heart failure81 9.5.Study evidence81 9.6.Thiazide or loop diuretic?82 9.7.Furosemide vs torasemide82 9.8.Practical approach with diuretic therapy83 9.9.Pharmacological data on some diuretics83 9.10.Sequential nephron blockade84 9.11.Interactions with non-steroidal anti-inflammatory drugs84 9.12.Potassium-sparing diuretics84 9.13.Heart failure guidelines85 9.13.1.The 2012 ESC HF guidelines85 9.13.2.The 2013 ACCF/AHA HF guidelines85 9.14.Summary86 9.15.References86 10.Positive inotropic drugs87 10.1.Mechanism of action of positive inotropic drugs87 10.2.Digitalis88 10.2.1.Mechanism of action88 10.2.2.Pharmacological data on cardiac glycosides88 10.2.3.Clinical use of digitalis89 10.2.4.First clinical studies90 10.2.5.The DIG study90 10.2.6.Post-hoc analyses of the DIG study91 10.2.7.Digitalis after infarction in symptomatic heart failure91 10.2.8.Does digoxin increase mortality in atrial fibrillation?91 10.2.8.1.Analyses of the AFFIRM study91 10.2.8.2.Subgroup analysis of the DIG study92 10.2.8.3.Post-hoc analysis of the ROCKET AF study92 10.2.8.4.Results of a recent meta-analysis92 10.2.9.The guidelines93 10.2.9.1.The 2012 ESC guidelines on heart failure93 10.2.9.2.The 2013 ACCF/AHA guidelines93 10.2.10.Summary (digitalis)93 10.3.Dobutamine93 10.4.Phosphodiesterase inhibitors94 10.5.Xamoterol95 10.6.Vesnarinone95 10.7.Ibopamine95 10.8.Pimobendan96 10.9.Levosimendan96 10.10.The guidelines on the drugs in sections 10.3 to 10.9.96 10.10.1.The 2012 ESC HF guidelines96 10.10.2.The ACCF/AHA HF guidelines97 10.11.Summary of section 10.3 to 10.1097 10.12.References97 11.ACE inhibitors99 11.1.Comparison of vasodilators 99 11.2.Pathophysiological background to ACE inhibitor therapy100 11.3.Mechanism of action100 11.4.Contraindications101 11.5.Pharmacological data on ACE inhibitors102 11.6.Clinical use of ACE inhibitors102 11.6.1.Gradual dosing102 11.6.2.Correct dosage102 11.6.3.Doses in the intervention studies103 11.6.4.Dosage recommendations103 11.6.5.The ATLAS study103 11.6.6.Consideration of renal function104 11.6.7.Treatment risks/adverse reactions104 11.6.8.ACE inhibitors and NSAIDs104 11.6.9.ACE inhibitors and acetylsalicylic acid105 11.7.Heart failure clinical trials with ACE inhibitors106 11.7.1.The CONSENSUS I study106 11.7.2.The V-HeFT II study106 11.7.3.The SOLVD-Treatment arm in symptomatic heart failure107 11.7.4.The SOLVD-Prevention study in asymptomatic heart failure107 11.7.5.X-SOLVD108 11.7.6.Cause of death: acute cardiac death vs pump failure108 11.8.Post-infarct studies with ACE inhibitors108 11.8.1.The SAVE study (Survival And Ventricular Enlargement)109 11.8.2.The AIRE study109 11.8.3.The TRACE study109 11.8.4.Meta-analysis of ACE inhibitor studies with LV dysfunction or heart failure110 11.8.5.ACE inhibitors and risk of atrial fibrillation110 11.8.6.Cause of death on ACE inhibitors: acute cardiac death vs pump failure111 11.9.ACE inhibitor studies in acute infarction111 11.10.ACE inhibitors in potential heart failure candidates111 11.10.1.The HOPE study112 11.10.2.The EUROPA study112 11.11.The guidelines113 11.11.1.The 2012 ESC heart failure guidelines113 11.11.2.The 2013 ACCF/AHA HF guidelines114 11.12.Summary114 11.13.References114 12.AT1 receptor antagonists117 12.1.Mechanism of action117 12.2.AT1 receptor antagonists compared118 12.3.Comparison of AT1 receptor antagonists vs ACE inhibitors118 12.4.Neuroendocrine parameters on ARBs119 12.4.1.Angiotensin II escape119 12.4.2.Angiotensin II level and prognosis119 12.5.Clinical trials119 12.5.1.The ELITE I study120 12.5.2.The RESOLVD study120 12.5.3.The ELITE II study120 12.5.4.Other results for AT1 receptor antagonists121 12.6.AT1 receptor antagonists vs/plus ACE inhibitors in HF121 12.6.1.The Val-HeFT study121 12.6.1.1.Neuroendocrine parameters123 12.6.1.2.Echocardiographic parameters of the left ventricle123 12.6.1.3.BNP levels are prognostic indicators in Val-HeFT124 12.6.2.The CHARM study124 12.6.2.1.The CHARM-Overall Programme124 12.6.2.2.The CHARM-Alternative study125 12.6.2.3.The CHARM-Added study125 12.6.2.4.The CHARM-Preserved study126 12.6.2.5.The CHARM-Alternative plus Added study127 12.7.AT1 receptor antagonists vs/plus ACE inhibitors in post-infarct patients127 12.7.1.The OPTIMAAL study127 12.7.2.The VALIANT study128 12.7.3.ACE inhibitors vs ARBs in heart failure and acute myocardial infarction129 12.8.Combination of ACE inhibitor and AT1 receptor antagonist? Why not first-line?130 12.9.Is triple therapy possible?130 12.10.LVH regression and heart failure131 12.11.Occurrence of atrial fibrillation on AT1 receptor antagonists131 12.12.The dose of the ARB – the HEAAL study131 12.13.The guidelines132 12.13.1.The 2012 ESC HF guidelines132 12.13.2.The 2013 ACCF/AHAHF guidelines132 12.13.3.The dosage of AT1 receptor antagonists132 12.14.Summary132 12.15.References133 13.Angiotensin-receptor neprilysin inhibitor (ARNI)136 13.1.The mechanism of action136 13.2.Why an AT1 antagonist and not an ACE inhibitor?136 13.3.Antihypertensive effects of LCZ696137 13.4.The PARAMOUNT study137 13.5.The PARADIGM-HF study137 13.5.1.The clinical results137 13.5.2.Post-hoc analyses of the PARADIGM study139 13.5.3.BNP and NT-proBNP in the PARADIGM post-hoc analysis139 13.5.4.Death due to sudden death vs death due to pump failure140 13.5.5.Comparison of number needed to treat (NNT) in heart failure studies140 13.5.6.A putative placebo analysis of the effects of LCZ696140 13.5.7.Life-years gained with sacubitril/valsartan140 13.5.8.Why was the comparison made with enalapril?141 13.6.A paradigm shift in the treatment of chronic systolic HF?141 13.7.Soluble neprilysin is predictive of cardiovascular death and HF hospitalisation141 13.8.Current indications for LCZ696141 13.9.The guidelines142 13.10.Summary142 13.11.References142 14.Other vasodilators144 14.1.Hydralazine/ISDN144 14.1.1.Hydralazine/ISDN in the V-HeFT I study144 14.1.2.The V-HeFT II study144 14.1.3.The A-HeFT study144 14.2.Alpha-1 blockers145 14.3.Nitrates145 14.4.Epoprostenol145 14.5.Flosequinan145 14.6.The guidelines145 14.6.1.The 2012 ESC HF guidelines145 14.6.2.The 2013 ACCF/AHA HF guidelines146 14.7.Summary146 14.8.References146 15.Calcium antagonists148 15.1.Classification of calcium antagonists148 15.2.Mechanism of action148 15.3.Clinical studies in heart failure148 15.3.1.The VHeFT III study148 15.3.2.The PRAISE I study149 15.3.3.The PRAISE II study149 15.4.The guidelines149 15.4.1.The 2012 ESC HF guidelines149 15.4.2.The 2013 ACCF/AHA HF guidelines149 15.5.Summary149 15.6.References149 16.Beta-blockers151 16.1.Clinical background151 16.2.Pathophysiological background151 16.3.Beta-blocker – from contraindication to indication152 16.4.Beta-blockers153 16.4.1.Classification of beta-blockers153 16.4.2.Haemodynamic effects153 16.5.Possible mechanisms of beta-blockers in heart failure153 16.6.Type of beta-blocker and negative inotropy154 16.7.Clinical studies with beta-blockers in heart failure155 16.7.1.USCarvedilol study155 16.7.2.The CIBIS II study156 16.7.3.The MERIT-HF study156 16.7.4.Comparison of the results of the three large beta-blocker studies157 16.8.Beta-blockers in NYHA class IV?157 16.8.1.Data prior to the COPERNICUS study157 16.8.2.The COPERNICUS study157 16.9.The BEST study158 16.10.Beta-blockersin asymptomatic LV dysfunction?158 16.10.1.The data before CAPRICORN158 16.10.2.The CAPRICORN study158 16.11.Clinical use of beta-blockers159 16.11.1.Which dose of a beta-blocker should be achieved?159 16.11.2.What approach in patients with beta-blockers and cardiac decompensation?160 16.11.3.Risks of beta-blocker therapy160 16.11.4.Beta-blockers should already be started in hospital – the IMPACT-HF study161 16.12.Which beta-blocker in heart failure?161 16.12.1.Improvement in EF on metoprolol vs carvedilol161 16.12.2.Carvedilol vs metoprolol: results of a meta-analysis161 16.12.3.The COMET study161 16.13.Elderly patients in the HF studies162 16.14.The SENIORS study162 16.15.Beta-blockers vs ACE inhibitors in heart failure163 16.16.Beta-blockers in the VALIANT study163 16.17.Start with an ACE inhibitor or beta-blocker?164 16.17.1.The CARMEN study164 16.17.2.The CIBIS III study164 16.18.Dosage and titration steps for beta-blockers165 16.19.Is there a target heart rate?165 16.20.Is sudden cardiac death positively influencedon beta-blockers?166 16.21.Beta-blockers in heart failure and atrial fibrillation?166 16.21.1.Results of a meta-analysis166 16.21.2.Results of a further meta-analysis166 16.22.The guidelines167 16.22.1.The 2012 ESC guidelines on HF167 16.22.2.The 2013 ACCF/AHA HF guidelines167 16.23.Summary167 16.24.References168 17.Aldosterone antagonists in heart failure171 17.1.Rationale for the treatment of heart failure with aldosterone antagonists171 17.2.Heart failure as a salt problem172 17.3.Effects of aldosterone and aldosterone antagonists172 17.4.The RALES study173 17.4.1.The results173 17.4.2.Results of subgroup analyses of the RALES study174 17.4.2.1.Behaviour of neuroendocrine parameters174 17.4.2.2.Spironolactone in the elderly and diabetics175 17.4.2.3.Spironolactone and collagen turnover175 17.4.3.High incidence of hyperkalaemia after publication of RALES175 17.4.4.Aldosterone, a prognostic indicator in chronic HFrEF176 17.5.The EMPHASIS-HF study in HF NYHA class II176 17.6.Aldosterone antagonists in post-infarction failure177 17.6.1.Aldosterone, a prognostic indicator in acute myocardial infarction177 17.6.2.The rationale for aldosterone antagonists in AMI178 17.6.3.Eplerenone in the EPHESUS study179 17.6.3.1.Eplerenone, ACE inhibitor and beta-blocker180 17.6.3.2.Eplerenone and acute cardiac death180 17.6.3.3.The tolerability of eplerenone181 17.6.3.4.Eplerenone and impaired GFR181 17.6.3.5.Early start of treatment with aldosterone antagonists181 17.7.Hypokalaemia and hypomagnesaemia182 17.8.The dose of aldosterone antagonists182 17.9.The guidelines183 17.9.1.2011 and 2012 ESC guidelines183 17.9.2.The 2013 ESC/EASD guidelines183 17.9.3.The 2013 ACCF/AHA guidelines183 17.10..Summary184 17.11.References184 18.Ivabradine, the If channel blocker187 18.1.The prognostic significance of heart rate in heart failure187 18.1.1.The CIBIS studies187 18.1.2.The DIAMOND study (heart failure arm)188 18.1.3.The COMETand MERIT-HF study188 18.1.4.Heart rate and LVEF189 18.2.The BEAUTIfUL study189 18.3.The SHIfT study190 18.4.Indications for ivabradine (European Medicines Agency)191 18.5.The guidelines192 18.5.1.The 2012 ESC heart failure guidelines192 18.5.2.The 2013 ESC/EASD guidelines192 18.5.3.The2012 ACCF/AHA et al. guidelines on stable CHD192 18.6.Summary192 18.7.References193 19.Antiarrhythmic Drugs195 19.1.Pathophysiological background195 19.2.The pro-arrhythmogenic effect in relation to the ejection fraction195 19.3.Ventricular extrasystoles – the CAST study195 19.4.Amiodarone in heart failure196 19.4.1.The CHF-STAT study with amiodarone196 19.4.2.The GESICA study196 19.5.Amiodarone in post-infarct patients196 19.5.1.The EMIAT and CAMIAT study with amiodarone196 19.5.2.Combination of amiodarone and beta-blockers197 19.5.3.The meta-analysis of the amiodarone studies197 19.6.Antiarrhythmics in atrial fibrillation197 19.6.1.Atrial fibrillation and prognosis197 19.6.2.Atrial fibrillation in heart failure198 19.6.2.1.Atrial fibrillation as a prognostic indicator198 19.6.2.2.Prognosis in the presence of atrial fibrillation depending on the cause of the heart failure199 19.6.2.3.The AF-CHF study199 19.6.3.The DIAMOND study199 19.6.4.Dronedarone199 19.6.4.1.Dronedarone in heart failure200 19.6.4.2.The ATHENA study200 19.6.4.3.The PALLAS study201 19.6.5.Heart failure therapy and atrial fibrillation201 19.6.6.Rate control vs rhythm control in atrial fibrillation202 19.6.6.1.The AFFIRM study202 19.6.7.The RACE I-study202 19.6.8.The RACE II study202 19.7.Does digoxin increase mortality in atrial fibrillation?203 19.8.Vernakalant203 19.9.Short-term vs long-term antiarrhythmic therapy after cardioversion for atrial fibrillation204 19.10.Catheter ablation in atrial fibrillation204 19.11.Current guidelines204 19.11.1.2012 ESC guidelines in atrial fibrillation204 19.11.2.2012 ESC guidelines on HF205 19.11.3.2011 ACCF/AHA/HRS guidelines on atrial fibrillation205 19.11.4.The 2014 AHA/ACC/HRS AF guidelines205 19.12.Summary205 19.13.References206 20.Anticoagulant substances in heart failure209 20.1.Clinical background209 20.2.Anticoagulation in HF and sinus rhythm? – The WARCEF study209 20.3.Antithrombotic treatment in atrial fibrillation210 20.3.1.Meta-analysis210 20.3.2.Aspirin plus clopidogrel vs warfarin – the ACTIVE W study210 20.3.3.The ACTIVE A study211 20.4.The preventive value of aspirin in atrial fibrillation211 20.4.1.Aspirin vs control211 20.4.2.Aspirin vs coumarins211 20.5.A new era for anticoagulation in atrial fibrillation212 20.5.1.Dabigatran – the RE-LY study212 20.5.2.Rivaroxaban – The ROCKET-AF study213 20.5.3.Apixaban – The ARISTOTLE study214 20.5.4.Edoxaban – The ENGAGE AF-TIMI 48 study215 20.5.5.Comparison of the end-points in RE-LY, ROCKET-AF and ARTISTOLE215 20.5.6.Meta-analysis of RE-LY, ROCKET-AF and ARISTOTLE216 20.5.7.Meta-analysis of RE-LY, ROCKET-AF, ARISTOTLE and ENGAGE AF216 20.5.8.Pharmacodynamics of NOACs216 20.6.Apixaban vs aspirin in atrial fibrillation – The AVERROES study217 20.7.Dabigatran in mechanical heart valves – The RE-ALIGN study217 20.8.Risk stratification in atrial fibrillation218 20.9.Bridging in AF with LMWH or not?218 20.10.Current guidelines219 20.10.1.The ESC heart failure guidelines219 20.10.2.2012 ESC guidelines on atrial fibrillation219 20.10.3.The 2013 ACCF/AHA guidelines219 20.10.4.The 2014 AHA/ACC/HRS guidelines on AF220 20.10.5.2014 AHA/ASA guidelines after stroke/TIA220 20.11.Summary220 20.12.References221 21.ICD, CRT, cardiac pacemakers, implantable AF recorders224 21.1.The implantable defibrillator (ICD)224 21.1.1.The AVID study in sustained ventricular tachycardia224 21.1.2.The CASH study224 21.1.3.The CIDS study225 21.1.4.The MADIT I study in non-sustained ventricular tachycardia225 21.1.5.The CABG-Patch study225 21.1.6.The meta-analysis of the ICD studies225 21.1.7.The MADIT II study225 21.1.8.The SCD-HeFT study226 21.1.9.In the case of ICD, VVIR or DDDR – The DAVID study227 21.1.10.ICD in dilated cardiomyopathy – The DEFINITE study227 21.1.11.When should ICD be used after myocardial infarction?228 21.1.11.1.The DINAMIT study228 21.1.11.2.The IRIS study228 21.1.12.ICD used too often229 21.1.13.Reduction in mortality through ICD programming229 21.1.14.Indication for prophylactic ICD – The guidelines229 21.1.14.1.ESC guidelines on the treatment of heart failure229 21.1.14.2.ACCF/AHA guidelines – An overview230 21.1.14.3.Guidelines on the treatment of heart failure230 21.1.14.4.2012 ACCF/AHA/HRS guidelines on device-based therapy230 21.1.14.5.2013 ACCF/AHA guidelines on the treatment in STEMI230 21.1.15.Heart rate in ICD patients230 21.1.16.Temporary wearable cardioverter defibrillator (WCD)231 21.2.Resynchronisation therapy (CRT)231 21.2.1.The MUSTIC study231 21.2.2.The MIRACLE study232 21.2.3.The meta-analysis of the resynchronisation studies to date232 21.2.4.The COMPANION study232 21.2.5.The RAFT study233 21.2.6.The CARE-HF study233 21.2.7.CRT in NYHA class I and II – The REVERSE study234 21.2.8.The MADIT-CRT study234 21.2.9.CRT in atrial fibrillation?235 21.2.10.Indication for CRT235 21.2.10.1.2012 ESC guidelines on CRT in heart failure235 21.2.10.2.The 2013 ACCF/AHA guidelines on the treatment of HF236 21.2.11.Prognosis in LBBB with QRS ³150 ms vs LBBB with QRS 120-149 ms236 21.2.12.CRT if a narrow QRS complex? – The EchoCRT study236 21.3.Programmed stimulation for risk identification237 21.4.Cardiac pacemaker therapy238 21.4.1.Pacing in the case of bradycardia238 21.4.2.Atrioventricular pacing (DDD) vs VVI238 21.4.3.The MOST study238 21.4.4.The UKPACE study238 21.4.5.The BLOCK HF study238 21.4.6.Intracardiac leadless pacemakers239 21.4.7.The 2013 ESC guidelines on pacing239 21.5.Implantable cardiac recorders to detect atrial fibrillation239 21.6.Summary239 21.7.References240 22.Treatment of diastolic heart failure245 22.1.Definition of diastolic heart failure245 22.2.Incidence of HFpEF246 22.3.Causes and pathophysiology of diastolic heart failure246 22.4.Diagnostic investigations247 22.4.1.Colour Doppler echocardiography248 22.4.2.Laboratory diagnosis with BNP248 22.4.3.HFpEF vs diastolic heart failure249 22.5.Prognosis in diastolic heart failure249 22.6.Treatment targets250 22.7.Significance of diastolic heart rate in summary250 22.8.Studies251 22.8.1.The CHARM Preserved trial251 22.8.2.The SENIORS subgroup with preserved LF function252 22.8.2.1.The importance of heart rate lowering252 22.8.2.2.The results of the SENIORS study in preserved LF function252 22.8.3.The DIG ancillary trial252 22.8.4.The PEP-CHF study253 22.8.5.The I-PRESERVE study253 22.8.6.The PARAMOUNT study253 22.8.7.The Swedish registry study254 22.8.8.The Aldo-DHF study254 22.8.9.The VALIDD study254 22.8.10.The TOPCAT study254 22.8.11.ISMN in HFpEF without benefits255 22.9.Prevention of HFpEF through antihypertensive agents255 22.10.Prognosis of impaired systolic function in HFpEF255 22.11.Treatment strategies255 22.12.The guidelines on HFpEF257 22.12.1.The 2012 ESC guidelines on HF257 22.12.2.The 2103 ACCF/AHA guidelines on HF257 22.13.Summary258 22.14.References258 23.Coronary revascularisation in heart failure, ventricular surgery, LVADs and heart transplantation262 23.1.Coronary revascularisation262 23.1.1.CABG in coronary artery disease and LVEF £35% – The STICH study262 23.2.The Batista and Dor procedure263 23.2.1.The STICH substudy with surgical ventricular reconstruction263 23.2.2.The DOR procedure263 23.3.Cardiomyoplasty263 23.3.1.Dynamic cardiomyoplasty263 23.3.2.Cellular cardiomyoplasty263 23.4.Mitral valve reconstruction264 23.5.Mechanical support systems (LV assist devices, LVADs)264 23.6.Heart transplantation266 23.6.1.Indications for heart transplantation266 23.6.2.Contraindications266 23.6.3.Complications266 23.6.4.Immunosuppressant therapy266 23.7.The guidelines267 23.7.1.The 2012 ESC guidelines on HF267 23.7.2.The 2013 ACCF/AHA guidelines on HF267 23.8.Summary268 23.9.References268 24.General measures271 24.1.Weight loss271 24.2.Salt restriction271 24.3.Alcohol271 24.4.Treatment of risk factors272 24.4.1.Hypertension272 24.4.2.The SPRINT study272 24.4.3.Diabetes and heart failure273 24.4.3.1.Antidiabetics and heart failure273 24.4.3.2.The EMPA-REG OUTCOME study274 24.4.4.Statins in heart failure?274 24.4.4.1.The CORONA study275 24.4.4.2.The GISSI-HF statin study275 24.5.Physical exercise276 24.5.1.Various studies on exercise276 24.5.2.The HF-ACTION study276 24.6.Contraception277 24.7.Explaining the point of treatment277 24.8.Anaemia278 24.8.1.The ANCHOR study279 24.8.2.The COMET study279 24.8.3.The CONFIRM-HF study279 24.8.4.The significance of haemodilution279 24.8.5.The importance of the treatment of true anaemia279 24.8.5.1.Treatment studies279 24.8.5.2.The RED-HF study280 24.9.Treatment of depression281 24.10.Healthy lifestyle as prevention of HF281 24.11.Adaptive servo-ventilation for central sleep apnoea?281 24.12.Summary281 24.13.References282 25.Current and experimental treatments285 25.1.Retrospective285 25.2.Nesiritide (BNP)285 25.2.1.The PRECEDENT study285 25.2.2.The VMAC study285 25.2.3.The Colucci study285 25.2.4.The ASCEND-HF study285 25.2.5.2013 ACCF/AHA HF guidelines286 25.3.Arginine-vasopressin (AVP) antagonists (= ADH antagonists)286 25.3.1.The ACTIV in CHF study286 25.3.2.The EVEREST Outcome study286 25.3.3.The 2013 ACCF/AHA heart failure guidelines287 25.3.4.Hyponatraemia guidelines of the European Society of Endocrinology287 25.4.The renin inhibitor aliskiren 287 25.4.1.The ASPIRE study287 25.4.2.The AQUARIUS study288 25.4.3.The ASTRONAUT study288 25.4.4.The ATMOSPHERE study288 25.4.5.The 2012 ESC heart failure guidelines288 25.5.The RELAX-AHF study289 25.6.Non-steroidal mineralocorticoid receptor antagonist289 25.7.Ularitide289 25.8.Gene therapy in heart failure?290 25.9.Summary290 25.10.References290 26.Acute left-sided heart failure292 26.1.Definition and prognosis292 26.2.Investigation and treatment292 26.3.Drug therapy292 26.4.Non-pharmacological strategies294 26.5.The guidelines295 26.5.1.The ESC HF guidelines295 26.5.2.The 2013 ACCF/AHA HF guidelines296 26.5.3.The 2015 ESC recommendations on the management of acute heart failure296 26.6.Summary296 26.7.References298 27.Treatment standards in chronic left ventricular systolic failure300 27.1.From pathophysiology to treatment300 27.2.Haemodynamic treatment goals301 27.3.Drug treatment of heart failure today301 27.3.1.ACE inhibitors301 27.3.2.What do ACE inhibitors actually bring in terms of prognosis?302 27.3.3.Beta-blockers303 27.3.4.AT1 receptor antagonists (ARBs)303 27.3.5.Combination of ACE inhibitor and AT1 receptor antagonist?303 27.3.6.Aldosterone antagonists (MRA)304 27.3.7.Thiazides and loop diuretics305 27.3.8.Ivabradine306 27.3.9.Digitalis glycosides306 27.3.10.The angiotensin receptor neprilysin inhibitor (ARNI)307 27.4.General measures309 27.5.Outlook309 27.6.Summary and treatment standards in NYHA class I-IV310 27.7.References310 28.Abbreviations313 Index315
1.Definition of heart failure23 1.1.Fundamentals23 1.2.Clinical definition23 1.2.1.Present definition23 1.2.2.The NYHA stages24 1.3.Current guidelines of the ESC and ACCF/AHA24 1.3.1.The 2012 ESC guidelines25 1.3.2.The 2013 ACCF/AHA guidelines25 1.4.Haemodynamic differences in systolic/diastolic HF25 1.5.Summary26 1.6.References26 2.Prognosis of heart failure27 2.1.Fundamentals27 2.2.Prognosis in the era before ACE inhibitors27 2.3.Prognosis in controlled treatment studies28 2.4.Prognosis depending on atrial fibrillation28 2.4.1.The prognosis in atrial fibrillation28 2.4.2.Prevalence of AF in the heart failure studies29 2.5.Prognosis and heart rate30 2.5.1.The BEAUTIfUL study30 2.5.2.The CIBIS II study30 2.6.Prognosis in ischaemic vs non-ischaemic heart failure30 2.7.Prognosis in cardiomyopathies31 2.8.Prognosis depending on EF and LVH31 2.9.Prognosis in systolic vs diastolic HF31 2.10.Prognosis depending on GFR32 2.11.Prognosis depending on the BNP level33 2.12.Copeptin and prognosis34 2.13.Prognosis depending on CRP34 2.14.Prognosis in anaemia34 2.15.Prognosis depending intensity of management34 2.16.Prognosis depending on age35 2.17.Prognosis depending on sex35 2.18.Prognosis depending on diabetes mellitus35 2.19.Prognosis and guidelines-based therapy36 2.20.Improvement in the prognosis of heart failure 1950 to 199936 2.21.Quality of life in heart failure36 2.22.The obesity paradox37 2.23.Treatment successes as a result of evidence-based therapy37 2.24.Causes of death in heart failure37 2.25.Low cardiac index and risk of the development of dementia38 2.26.Prognosis in HF – The MAGGIC risk score38 2.27.Summary40 2.28.References40 3.Epidemiology43 3.1.Prevalence and incidence of heart failure43 3.2.Prevalence of ventricular dysfunction on the echocardiogram (since 1990)43 3.3.Systolic vs diastolic heart failure44 3.4.Obesity and heart failure44 3.5.Summary45 3.6.References45 4.Classification of heart failure46 4.1.Options for classification46 4.1.1.According to the affected ventricle46 4.1.2.According to time course46 4.1.3.According to the degree of compensation46 4.1.4.According to the cardiac output46 4.1.5.According to symptoms46 4.1.6.According to the disordered ventricular function46 4.1.7.According to exercise tolerance46 4.1.8.According to clinical features46 4.1.9.According to NYHA class (NYHA – New York Heart Association)47 4.1.10.According to the ACCF/AHA classification47 4.1.11.Stage D heart failure48 4.2.Summary48 4.3.References48 5.Aetiology of heart failure49 5.1.Heart failure – A syndrome of various aetiology49 5.2.The cardiomyopathies50 5.3.Antidiabetic agents and HF51 5.4.Summary51 5.5.References51 6.Pathophysiology of heart failure53 6.1.Pathophysiological basis 53 6.2.Importance of pre- and afterload for the healthy and diseased heart53 6.2.1.Effects of isolated preload reduction53 6.2.2.Effects of isolated reduction of afterload54 6.3.Importance of the heart rate increase for the healthy and failing heart54 6.3.1.The force-rate relationship54 6.3.2.Further effects of an increased heart rate54 6.3.3.Heart rate in CHD and HF55 6.4.Compensatory mechanisms in heart failure55 6.5.Vicious circle in heart failure56 6.6.Determinants of myocardial oxygen consumption57 6.7.Causes of heart failure57 6.8.Importance of apoptosis57 6.9.Heart failure concepts today58 6.10.Origin of the oedema in heart failure59 6.11.Haemodynamics in systolic vs diastolic heart failure59 6.12.The kidney in heart failure59 6.13.The lung in heart failure60 6.14.The importance of natriuretic peptides61 6.15.Summary61 6.16.References61 7.Main aspects of diagnostic investigation63 7.1.Aims of investigation63 7.2.Symptoms63 7.3.Investigations 63 7.4.Symptoms and severity of heart failure65 7.5.Laboratory investigation of heart failure65 7.5.1.BNP vs NT-proBNP65 7.5.1.1.The half-life of BNP65 7.5.1.2.The half-life of NT-proBNP66 7.5.1.3.Limit values of BNP66 7.5.1.4.Limit values of NT-proBNP66 7.5.1.5.Relationship with renal function, age and sex67 7.5.2.BNP and NT-proBNP levels in systolic heart failure67 7.5.3.BNP and NT-proBNP levels in diastolic heart failure68 7.5.4.Other causes of BNP level increases68 7.5.5.Obesity reduces BNP levels68 7.6.BNP levels for treatment monitoring69 7.7.BNP determination in the emergency clinic – The BASEL study69 7.8.BNP in chronic heart failure70 7.9.BNP as a prognostic indicator at the time of discharge from hospital70 7.10.BNP as a predictor of risk71 7.11.Diagnostic algorithms if heart failure is suspected71 7.12.The guidelines on heart failure71 7.12.1.2012 ESC71 7.12.2.2013 ACCF/AHA71 7.13.Summary72 7.14.References72 8.Treatment goals and treatment strategies in heart failure74 8.1.Treatment goals74 8.2.Treatment strategies74 8.2.1.General measures74 8.2.2.Drug therapy75 8.2.3.Surgical measures including heart transplantation75 8.2.4.Haemofiltration75 8.3.Prevention of heart failure75 8.4.Behaviour of ejection fraction during treatment76 8.5.The 2103 ACCF/AHA guidelines76 8.6.Summary77 8.7.References77 9.Diuretics79 9.1.Pathophysiology and mechanism of action79 9.2.Classification and differentiation of diuretics80 9.3.Dose-effect relationship of diuretics80 9.4.Value of diuretics in heart failure81 9.5.Study evidence81 9.6.Thiazide or loop diuretic?82 9.7.Furosemide vs torasemide82 9.8.Practical approach with diuretic therapy83 9.9.Pharmacological data on some diuretics83 9.10.Sequential nephron blockade84 9.11.Interactions with non-steroidal anti-inflammatory drugs84 9.12.Potassium-sparing diuretics84 9.13.Heart failure guidelines85 9.13.1.The 2012 ESC HF guidelines85 9.13.2.The 2013 ACCF/AHA HF guidelines85 9.14.Summary86 9.15.References86 10.Positive inotropic drugs87 10.1.Mechanism of action of positive inotropic drugs87 10.2.Digitalis88 10.2.1.Mechanism of action88 10.2.2.Pharmacological data on cardiac glycosides88 10.2.3.Clinical use of digitalis89 10.2.4.First clinical studies90 10.2.5.The DIG study90 10.2.6.Post-hoc analyses of the DIG study91 10.2.7.Digitalis after infarction in symptomatic heart failure91 10.2.8.Does digoxin increase mortality in atrial fibrillation?91 10.2.8.1.Analyses of the AFFIRM study91 10.2.8.2.Subgroup analysis of the DIG study92 10.2.8.3.Post-hoc analysis of the ROCKET AF study92 10.2.8.4.Results of a recent meta-analysis92 10.2.9.The guidelines93 10.2.9.1.The 2012 ESC guidelines on heart failure93 10.2.9.2.The 2013 ACCF/AHA guidelines93 10.2.10.Summary (digitalis)93 10.3.Dobutamine93 10.4.Phosphodiesterase inhibitors94 10.5.Xamoterol95 10.6.Vesnarinone95 10.7.Ibopamine95 10.8.Pimobendan96 10.9.Levosimendan96 10.10.The guidelines on the drugs in sections 10.3 to 10.9.96 10.10.1.The 2012 ESC HF guidelines96 10.10.2.The ACCF/AHA HF guidelines97 10.11.Summary of section 10.3 to 10.1097 10.12.References97 11.ACE inhibitors99 11.1.Comparison of vasodilators 99 11.2.Pathophysiological background to ACE inhibitor therapy100 11.3.Mechanism of action100 11.4.Contraindications101 11.5.Pharmacological data on ACE inhibitors102 11.6.Clinical use of ACE inhibitors102 11.6.1.Gradual dosing102 11.6.2.Correct dosage102 11.6.3.Doses in the intervention studies103 11.6.4.Dosage recommendations103 11.6.5.The ATLAS study103 11.6.6.Consideration of renal function104 11.6.7.Treatment risks/adverse reactions104 11.6.8.ACE inhibitors and NSAIDs104 11.6.9.ACE inhibitors and acetylsalicylic acid105 11.7.Heart failure clinical trials with ACE inhibitors106 11.7.1.The CONSENSUS I study106 11.7.2.The V-HeFT II study106 11.7.3.The SOLVD-Treatment arm in symptomatic heart failure107 11.7.4.The SOLVD-Prevention study in asymptomatic heart failure107 11.7.5.X-SOLVD108 11.7.6.Cause of death: acute cardiac death vs pump failure108 11.8.Post-infarct studies with ACE inhibitors108 11.8.1.The SAVE study (Survival And Ventricular Enlargement)109 11.8.2.The AIRE study109 11.8.3.The TRACE study109 11.8.4.Meta-analysis of ACE inhibitor studies with LV dysfunction or heart failure110 11.8.5.ACE inhibitors and risk of atrial fibrillation110 11.8.6.Cause of death on ACE inhibitors: acute cardiac death vs pump failure111 11.9.ACE inhibitor studies in acute infarction111 11.10.ACE inhibitors in potential heart failure candidates111 11.10.1.The HOPE study112 11.10.2.The EUROPA study112 11.11.The guidelines113 11.11.1.The 2012 ESC heart failure guidelines113 11.11.2.The 2013 ACCF/AHA HF guidelines114 11.12.Summary114 11.13.References114 12.AT1 receptor antagonists117 12.1.Mechanism of action117 12.2.AT1 receptor antagonists compared118 12.3.Comparison of AT1 receptor antagonists vs ACE inhibitors118 12.4.Neuroendocrine parameters on ARBs119 12.4.1.Angiotensin II escape119 12.4.2.Angiotensin II level and prognosis119 12.5.Clinical trials119 12.5.1.The ELITE I study120 12.5.2.The RESOLVD study120 12.5.3.The ELITE II study120 12.5.4.Other results for AT1 receptor antagonists121 12.6.AT1 receptor antagonists vs/plus ACE inhibitors in HF121 12.6.1.The Val-HeFT study121 12.6.1.1.Neuroendocrine parameters123 12.6.1.2.Echocardiographic parameters of the left ventricle123 12.6.1.3.BNP levels are prognostic indicators in Val-HeFT124 12.6.2.The CHARM study124 12.6.2.1.The CHARM-Overall Programme124 12.6.2.2.The CHARM-Alternative study125 12.6.2.3.The CHARM-Added study125 12.6.2.4.The CHARM-Preserved study126 12.6.2.5.The CHARM-Alternative plus Added study127 12.7.AT1 receptor antagonists vs/plus ACE inhibitors in post-infarct patients127 12.7.1.The OPTIMAAL study127 12.7.2.The VALIANT study128 12.7.3.ACE inhibitors vs ARBs in heart failure and acute myocardial infarction129 12.8.Combination of ACE inhibitor and AT1 receptor antagonist? Why not first-line?130 12.9.Is triple therapy possible?130 12.10.LVH regression and heart failure131 12.11.Occurrence of atrial fibrillation on AT1 receptor antagonists131 12.12.The dose of the ARB – the HEAAL study131 12.13.The guidelines132 12.13.1.The 2012 ESC HF guidelines132 12.13.2.The 2013 ACCF/AHAHF guidelines132 12.13.3.The dosage of AT1 receptor antagonists132 12.14.Summary132 12.15.References133 13.Angiotensin-receptor neprilysin inhibitor (ARNI)136 13.1.The mechanism of action136 13.2.Why an AT1 antagonist and not an ACE inhibitor?136 13.3.Antihypertensive effects of LCZ696137 13.4.The PARAMOUNT study137 13.5.The PARADIGM-HF study137 13.5.1.The clinical results137 13.5.2.Post-hoc analyses of the PARADIGM study139 13.5.3.BNP and NT-proBNP in the PARADIGM post-hoc analysis139 13.5.4.Death due to sudden death vs death due to pump failure140 13.5.5.Comparison of number needed to treat (NNT) in heart failure studies140 13.5.6.A putative placebo analysis of the effects of LCZ696140 13.5.7.Life-years gained with sacubitril/valsartan140 13.5.8.Why was the comparison made with enalapril?141 13.6.A paradigm shift in the treatment of chronic systolic HF?141 13.7.Soluble neprilysin is predictive of cardiovascular death and HF hospitalisation141 13.8.Current indications for LCZ696141 13.9.The guidelines142 13.10.Summary142 13.11.References142 14.Other vasodilators144 14.1.Hydralazine/ISDN144 14.1.1.Hydralazine/ISDN in the V-HeFT I study144 14.1.2.The V-HeFT II study144 14.1.3.The A-HeFT study144 14.2.Alpha-1 blockers145 14.3.Nitrates145 14.4.Epoprostenol145 14.5.Flosequinan145 14.6.The guidelines145 14.6.1.The 2012 ESC HF guidelines145 14.6.2.The 2013 ACCF/AHA HF guidelines146 14.7.Summary146 14.8.References146 15.Calcium antagonists148 15.1.Classification of calcium antagonists148 15.2.Mechanism of action148 15.3.Clinical studies in heart failure148 15.3.1.The VHeFT III study148 15.3.2.The PRAISE I study149 15.3.3.The PRAISE II study149 15.4.The guidelines149 15.4.1.The 2012 ESC HF guidelines149 15.4.2.The 2013 ACCF/AHA HF guidelines149 15.5.Summary149 15.6.References149 16.Beta-blockers151 16.1.Clinical background151 16.2.Pathophysiological background151 16.3.Beta-blocker – from contraindication to indication152 16.4.Beta-blockers153 16.4.1.Classification of beta-blockers153 16.4.2.Haemodynamic effects153 16.5.Possible mechanisms of beta-blockers in heart failure153 16.6.Type of beta-blocker and negative inotropy154 16.7.Clinical studies with beta-blockers in heart failure155 16.7.1.USCarvedilol study155 16.7.2.The CIBIS II study156 16.7.3.The MERIT-HF study156 16.7.4.Comparison of the results of the three large beta-blocker studies157 16.8.Beta-blockers in NYHA class IV?157 16.8.1.Data prior to the COPERNICUS study157 16.8.2.The COPERNICUS study157 16.9.The BEST study158 16.10.Beta-blockersin asymptomatic LV dysfunction?158 16.10.1.The data before CAPRICORN158 16.10.2.The CAPRICORN study158 16.11.Clinical use of beta-blockers159 16.11.1.Which dose of a beta-blocker should be achieved?159 16.11.2.What approach in patients with beta-blockers and cardiac decompensation?160 16.11.3.Risks of beta-blocker therapy160 16.11.4.Beta-blockers should already be started in hospital – the IMPACT-HF study161 16.12.Which beta-blocker in heart failure?161 16.12.1.Improvement in EF on metoprolol vs carvedilol161 16.12.2.Carvedilol vs metoprolol: results of a meta-analysis161 16.12.3.The COMET study161 16.13.Elderly patients in the HF studies162 16.14.The SENIORS study162 16.15.Beta-blockers vs ACE inhibitors in heart failure163 16.16.Beta-blockers in the VALIANT study163 16.17.Start with an ACE inhibitor or beta-blocker?164 16.17.1.The CARMEN study164 16.17.2.The CIBIS III study164 16.18.Dosage and titration steps for beta-blockers165 16.19.Is there a target heart rate?165 16.20.Is sudden cardiac death positively influencedon beta-blockers?166 16.21.Beta-blockers in heart failure and atrial fibrillation?166 16.21.1.Results of a meta-analysis166 16.21.2.Results of a further meta-analysis166 16.22.The guidelines167 16.22.1.The 2012 ESC guidelines on HF167 16.22.2.The 2013 ACCF/AHA HF guidelines167 16.23.Summary167 16.24.References168 17.Aldosterone antagonists in heart failure171 17.1.Rationale for the treatment of heart failure with aldosterone antagonists171 17.2.Heart failure as a salt problem172 17.3.Effects of aldosterone and aldosterone antagonists172 17.4.The RALES study173 17.4.1.The results173 17.4.2.Results of subgroup analyses of the RALES study174 17.4.2.1.Behaviour of neuroendocrine parameters174 17.4.2.2.Spironolactone in the elderly and diabetics175 17.4.2.3.Spironolactone and collagen turnover175 17.4.3.High incidence of hyperkalaemia after publication of RALES175 17.4.4.Aldosterone, a prognostic indicator in chronic HFrEF176 17.5.The EMPHASIS-HF study in HF NYHA class II176 17.6.Aldosterone antagonists in post-infarction failure177 17.6.1.Aldosterone, a prognostic indicator in acute myocardial infarction177 17.6.2.The rationale for aldosterone antagonists in AMI178 17.6.3.Eplerenone in the EPHESUS study179 17.6.3.1.Eplerenone, ACE inhibitor and beta-blocker180 17.6.3.2.Eplerenone and acute cardiac death180 17.6.3.3.The tolerability of eplerenone181 17.6.3.4.Eplerenone and impaired GFR181 17.6.3.5.Early start of treatment with aldosterone antagonists181 17.7.Hypokalaemia and hypomagnesaemia182 17.8.The dose of aldosterone antagonists182 17.9.The guidelines183 17.9.1.2011 and 2012 ESC guidelines183 17.9.2.The 2013 ESC/EASD guidelines183 17.9.3.The 2013 ACCF/AHA guidelines183 17.10..Summary184 17.11.References184 18.Ivabradine, the If channel blocker187 18.1.The prognostic significance of heart rate in heart failure187 18.1.1.The CIBIS studies187 18.1.2.The DIAMOND study (heart failure arm)188 18.1.3.The COMETand MERIT-HF study188 18.1.4.Heart rate and LVEF189 18.2.The BEAUTIfUL study189 18.3.The SHIfT study190 18.4.Indications for ivabradine (European Medicines Agency)191 18.5.The guidelines192 18.5.1.The 2012 ESC heart failure guidelines192 18.5.2.The 2013 ESC/EASD guidelines192 18.5.3.The2012 ACCF/AHA et al. guidelines on stable CHD192 18.6.Summary192 18.7.References193 19.Antiarrhythmic Drugs195 19.1.Pathophysiological background195 19.2.The pro-arrhythmogenic effect in relation to the ejection fraction195 19.3.Ventricular extrasystoles – the CAST study195 19.4.Amiodarone in heart failure196 19.4.1.The CHF-STAT study with amiodarone196 19.4.2.The GESICA study196 19.5.Amiodarone in post-infarct patients196 19.5.1.The EMIAT and CAMIAT study with amiodarone196 19.5.2.Combination of amiodarone and beta-blockers197 19.5.3.The meta-analysis of the amiodarone studies197 19.6.Antiarrhythmics in atrial fibrillation197 19.6.1.Atrial fibrillation and prognosis197 19.6.2.Atrial fibrillation in heart failure198 19.6.2.1.Atrial fibrillation as a prognostic indicator198 19.6.2.2.Prognosis in the presence of atrial fibrillation depending on the cause of the heart failure199 19.6.2.3.The AF-CHF study199 19.6.3.The DIAMOND study199 19.6.4.Dronedarone199 19.6.4.1.Dronedarone in heart failure200 19.6.4.2.The ATHENA study200 19.6.4.3.The PALLAS study201 19.6.5.Heart failure therapy and atrial fibrillation201 19.6.6.Rate control vs rhythm control in atrial fibrillation202 19.6.6.1.The AFFIRM study202 19.6.7.The RACE I-study202 19.6.8.The RACE II study202 19.7.Does digoxin increase mortality in atrial fibrillation?203 19.8.Vernakalant203 19.9.Short-term vs long-term antiarrhythmic therapy after cardioversion for atrial fibrillation204 19.10.Catheter ablation in atrial fibrillation204 19.11.Current guidelines204 19.11.1.2012 ESC guidelines in atrial fibrillation204 19.11.2.2012 ESC guidelines on HF205 19.11.3.2011 ACCF/AHA/HRS guidelines on atrial fibrillation205 19.11.4.The 2014 AHA/ACC/HRS AF guidelines205 19.12.Summary205 19.13.References206 20.Anticoagulant substances in heart failure209 20.1.Clinical background209 20.2.Anticoagulation in HF and sinus rhythm? – The WARCEF study209 20.3.Antithrombotic treatment in atrial fibrillation210 20.3.1.Meta-analysis210 20.3.2.Aspirin plus clopidogrel vs warfarin – the ACTIVE W study210 20.3.3.The ACTIVE A study211 20.4.The preventive value of aspirin in atrial fibrillation211 20.4.1.Aspirin vs control211 20.4.2.Aspirin vs coumarins211 20.5.A new era for anticoagulation in atrial fibrillation212 20.5.1.Dabigatran – the RE-LY study212 20.5.2.Rivaroxaban – The ROCKET-AF study213 20.5.3.Apixaban – The ARISTOTLE study214 20.5.4.Edoxaban – The ENGAGE AF-TIMI 48 study215 20.5.5.Comparison of the end-points in RE-LY, ROCKET-AF and ARTISTOLE215 20.5.6.Meta-analysis of RE-LY, ROCKET-AF and ARISTOTLE216 20.5.7.Meta-analysis of RE-LY, ROCKET-AF, ARISTOTLE and ENGAGE AF216 20.5.8.Pharmacodynamics of NOACs216 20.6.Apixaban vs aspirin in atrial fibrillation – The AVERROES study217 20.7.Dabigatran in mechanical heart valves – The RE-ALIGN study217 20.8.Risk stratification in atrial fibrillation218 20.9.Bridging in AF with LMWH or not?218 20.10.Current guidelines219 20.10.1.The ESC heart failure guidelines219 20.10.2.2012 ESC guidelines on atrial fibrillation219 20.10.3.The 2013 ACCF/AHA guidelines219 20.10.4.The 2014 AHA/ACC/HRS guidelines on AF220 20.10.5.2014 AHA/ASA guidelines after stroke/TIA220 20.11.Summary220 20.12.References221 21.ICD, CRT, cardiac pacemakers, implantable AF recorders224 21.1.The implantable defibrillator (ICD)224 21.1.1.The AVID study in sustained ventricular tachycardia224 21.1.2.The CASH study224 21.1.3.The CIDS study225 21.1.4.The MADIT I study in non-sustained ventricular tachycardia225 21.1.5.The CABG-Patch study225 21.1.6.The meta-analysis of the ICD studies225 21.1.7.The MADIT II study225 21.1.8.The SCD-HeFT study226 21.1.9.In the case of ICD, VVIR or DDDR – The DAVID study227 21.1.10.ICD in dilated cardiomyopathy – The DEFINITE study227 21.1.11.When should ICD be used after myocardial infarction?228 21.1.11.1.The DINAMIT study228 21.1.11.2.The IRIS study228 21.1.12.ICD used too often229 21.1.13.Reduction in mortality through ICD programming229 21.1.14.Indication for prophylactic ICD – The guidelines229 21.1.14.1.ESC guidelines on the treatment of heart failure229 21.1.14.2.ACCF/AHA guidelines – An overview230 21.1.14.3.Guidelines on the treatment of heart failure230 21.1.14.4.2012 ACCF/AHA/HRS guidelines on device-based therapy230 21.1.14.5.2013 ACCF/AHA guidelines on the treatment in STEMI230 21.1.15.Heart rate in ICD patients230 21.1.16.Temporary wearable cardioverter defibrillator (WCD)231 21.2.Resynchronisation therapy (CRT)231 21.2.1.The MUSTIC study231 21.2.2.The MIRACLE study232 21.2.3.The meta-analysis of the resynchronisation studies to date232 21.2.4.The COMPANION study232 21.2.5.The RAFT study233 21.2.6.The CARE-HF study233 21.2.7.CRT in NYHA class I and II – The REVERSE study234 21.2.8.The MADIT-CRT study234 21.2.9.CRT in atrial fibrillation?235 21.2.10.Indication for CRT235 21.2.10.1.2012 ESC guidelines on CRT in heart failure235 21.2.10.2.The 2013 ACCF/AHA guidelines on the treatment of HF236 21.2.11.Prognosis in LBBB with QRS ³150 ms vs LBBB with QRS 120-149 ms236 21.2.12.CRT if a narrow QRS complex? – The EchoCRT study236 21.3.Programmed stimulation for risk identification237 21.4.Cardiac pacemaker therapy238 21.4.1.Pacing in the case of bradycardia238 21.4.2.Atrioventricular pacing (DDD) vs VVI238 21.4.3.The MOST study238 21.4.4.The UKPACE study238 21.4.5.The BLOCK HF study238 21.4.6.Intracardiac leadless pacemakers239 21.4.7.The 2013 ESC guidelines on pacing239 21.5.Implantable cardiac recorders to detect atrial fibrillation239 21.6.Summary239 21.7.References240 22.Treatment of diastolic heart failure245 22.1.Definition of diastolic heart failure245 22.2.Incidence of HFpEF246 22.3.Causes and pathophysiology of diastolic heart failure246 22.4.Diagnostic investigations247 22.4.1.Colour Doppler echocardiography248 22.4.2.Laboratory diagnosis with BNP248 22.4.3.HFpEF vs diastolic heart failure249 22.5.Prognosis in diastolic heart failure249 22.6.Treatment targets250 22.7.Significance of diastolic heart rate in summary250 22.8.Studies251 22.8.1.The CHARM Preserved trial251 22.8.2.The SENIORS subgroup with preserved LF function252 22.8.2.1.The importance of heart rate lowering252 22.8.2.2.The results of the SENIORS study in preserved LF function252 22.8.3.The DIG ancillary trial252 22.8.4.The PEP-CHF study253 22.8.5.The I-PRESERVE study253 22.8.6.The PARAMOUNT study253 22.8.7.The Swedish registry study254 22.8.8.The Aldo-DHF study254 22.8.9.The VALIDD study254 22.8.10.The TOPCAT study254 22.8.11.ISMN in HFpEF without benefits255 22.9.Prevention of HFpEF through antihypertensive agents255 22.10.Prognosis of impaired systolic function in HFpEF255 22.11.Treatment strategies255 22.12.The guidelines on HFpEF257 22.12.1.The 2012 ESC guidelines on HF257 22.12.2.The 2103 ACCF/AHA guidelines on HF257 22.13.Summary258 22.14.References258 23.Coronary revascularisation in heart failure, ventricular surgery, LVADs and heart transplantation262 23.1.Coronary revascularisation262 23.1.1.CABG in coronary artery disease and LVEF £35% – The STICH study262 23.2.The Batista and Dor procedure263 23.2.1.The STICH substudy with surgical ventricular reconstruction263 23.2.2.The DOR procedure263 23.3.Cardiomyoplasty263 23.3.1.Dynamic cardiomyoplasty263 23.3.2.Cellular cardiomyoplasty263 23.4.Mitral valve reconstruction264 23.5.Mechanical support systems (LV assist devices, LVADs)264 23.6.Heart transplantation266 23.6.1.Indications for heart transplantation266 23.6.2.Contraindications266 23.6.3.Complications266 23.6.4.Immunosuppressant therapy266 23.7.The guidelines267 23.7.1.The 2012 ESC guidelines on HF267 23.7.2.The 2013 ACCF/AHA guidelines on HF267 23.8.Summary268 23.9.References268 24.General measures271 24.1.Weight loss271 24.2.Salt restriction271 24.3.Alcohol271 24.4.Treatment of risk factors272 24.4.1.Hypertension272 24.4.2.The SPRINT study272 24.4.3.Diabetes and heart failure273 24.4.3.1.Antidiabetics and heart failure273 24.4.3.2.The EMPA-REG OUTCOME study274 24.4.4.Statins in heart failure?274 24.4.4.1.The CORONA study275 24.4.4.2.The GISSI-HF statin study275 24.5.Physical exercise276 24.5.1.Various studies on exercise276 24.5.2.The HF-ACTION study276 24.6.Contraception277 24.7.Explaining the point of treatment277 24.8.Anaemia278 24.8.1.The ANCHOR study279 24.8.2.The COMET study279 24.8.3.The CONFIRM-HF study279 24.8.4.The significance of haemodilution279 24.8.5.The importance of the treatment of true anaemia279 24.8.5.1.Treatment studies279 24.8.5.2.The RED-HF study280 24.9.Treatment of depression281 24.10.Healthy lifestyle as prevention of HF281 24.11.Adaptive servo-ventilation for central sleep apnoea?281 24.12.Summary281 24.13.References282 25.Current and experimental treatments285 25.1.Retrospective285 25.2.Nesiritide (BNP)285 25.2.1.The PRECEDENT study285 25.2.2.The VMAC study285 25.2.3.The Colucci study285 25.2.4.The ASCEND-HF study285 25.2.5.2013 ACCF/AHA HF guidelines286 25.3.Arginine-vasopressin (AVP) antagonists (= ADH antagonists)286 25.3.1.The ACTIV in CHF study286 25.3.2.The EVEREST Outcome study286 25.3.3.The 2013 ACCF/AHA heart failure guidelines287 25.3.4.Hyponatraemia guidelines of the European Society of Endocrinology287 25.4.The renin inhibitor aliskiren 287 25.4.1.The ASPIRE study287 25.4.2.The AQUARIUS study288 25.4.3.The ASTRONAUT study288 25.4.4.The ATMOSPHERE study288 25.4.5.The 2012 ESC heart failure guidelines288 25.5.The RELAX-AHF study289 25.6.Non-steroidal mineralocorticoid receptor antagonist289 25.7.Ularitide289 25.8.Gene therapy in heart failure?290 25.9.Summary290 25.10.References290 26.Acute left-sided heart failure292 26.1.Definition and prognosis292 26.2.Investigation and treatment292 26.3.Drug therapy292 26.4.Non-pharmacological strategies294 26.5.The guidelines295 26.5.1.The ESC HF guidelines295 26.5.2.The 2013 ACCF/AHA HF guidelines296 26.5.3.The 2015 ESC recommendations on the management of acute heart failure296 26.6.Summary296 26.7.References298 27.Treatment standards in chronic left ventricular systolic failure300 27.1.From pathophysiology to treatment300 27.2.Haemodynamic treatment goals301 27.3.Drug treatment of heart failure today301 27.3.1.ACE inhibitors301 27.3.2.What do ACE inhibitors actually bring in terms of prognosis?302 27.3.3.Beta-blockers303 27.3.4.AT1 receptor antagonists (ARBs)303 27.3.5.Combination of ACE inhibitor and AT1 receptor antagonist?303 27.3.6.Aldosterone antagonists (MRA)304 27.3.7.Thiazides and loop diuretics305 27.3.8.Ivabradine306 27.3.9.Digitalis glycosides306 27.3.10.The angiotensin receptor neprilysin inhibitor (ARNI)307 27.4.General measures309 27.5.Outlook309 27.6.Summary and treatment standards in NYHA class I-IV310 27.7.References310 28.Abbreviations313 Index315