Dietrich Strödter & Frans Santosa 
State-of-the-art Treatment of Heart Failure 

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.

Tabla de materias

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 BEAUTIf UL 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-pro BNP65
7.5.1.1.The half-life of BNP65
7.5.1.2.The half-life of NT-pro BNP66
7.5.1.3.Limit values of BNP66
7.5.1.4.Limit values of NT-pro BNP66
7.5.1.5.Relationship with renal function, age and sex67
7.5.2.BNP and NT-pro BNP levels in systolic heart failure67
7.5.3.BNP and NT-pro BNP 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-He FT 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-He FT 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-He FT124
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-pro BNP 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-He FT I study144
14.1.2.The V-He FT II study144
14.1.3.The A-He FT 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 VHe FT 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 HFr EF176
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 BEAUTIf UL study189
18.3.The SHIf T 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-He FT 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 Echo CRT 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 HFp EF246
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.HFp EF 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 HFp EF without benefits255
22.9.Prevention of HFp EF through antihypertensive agents255
22.10.Prognosis of impaired systolic function in HFp EF255
22.11.Treatment strategies255
22.12.The guidelines on HFp EF257
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