Stakeholder Opinions: Heart Failure - When drugs do not work

Introduction
Advanced heart failure is a growing issue. Existing pharmacological strategies increase the survival rates of acute heart failure patients, providing a growing source of patients with advanced disease. In view of long waiting lists for heart transplantation and the growing lack of donors, cardiac resynchronization and mechanical circulatory support devices have demonstrated promising results.

Report Highlights
Highlights
With no new drug therapies addressing advanced heart failure and existing pharmacological strategies failing to compensate a weakening heart, alternative, non-pharmacological solutions have to be found. In view of long waiting lists for heart transplantation and the growing shortage of donor hearts, the focus of treatment must shift onto devices.

Ventricular dyssynchrony is a well recognized problem in advanced stages of heart failure. Clinical trials investigating ventricular dyssynchrony cardiac resynchronization have demonstrated promising results. However, this technology provides only temporary, symptomatic relief and neither cures nor fully stops the progression of the disease.

In light of the growing shortage of donor hearts and failing pharmacological strategies, an artificial mechanical heart has been a long sought-after technology. Although the developments started decades ago, a fully implantable total artificial heart is still at the concept stage, with many years of research and development yet to come.
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TABLE OF CONTENTS
ABOUT DATAMONITOR HEALTHCARE 2
About the cardiovascular analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Datamonitor insight into available therapies in advanced heart failure 4
Contributing experts 5
CHAPTER 2 HEART FAILURE DEFINITIONS AND PATHOPHYSIOLOGY 7
Definition of heart failure 7
Acute heart failure 7
Chronic heart failure 8
Etiology of heart failure 9
Segmentation of heart failure 10
Disease severity 10
Low versus high output failure 15
Systolic versus diastolic heart failure 15
Age group 17
Co-morbidities, complications and risk factors 17
CHAPTER 3 EPIDEMIOLOGY 22
Epidemiology of heart failure 22
Future incidence of acute heart failure 22
Future prevalence of chronic heart failure 23
Future trends in the incidence and prevalence of heart failure 23
CHAPTER 4 DIAGNOSIS AND INVESTIGATION 25
Diagnosis 25
Symptoms 25
Neurohormonal activation markers 28
Novel biomarkers 29
Role of medical imaging in heart failure 29
Chest x-ray 30
Echocardiography 30
Nuclear perfusion tests 31
Role of MRI in coronary heart disease diagnosis 33
CHAPTER 5 BASIC PHARMACOLOGICAL THERAPY 34
Drug classes in heart failure 34
ACE inhibitors 34
Angiotensin II receptor blockers 35
Diuretics 36
Betablockers 36
Digoxin 37
Antithrombotics 38
Calcium channel blockers 38
CHAPTER 6 DEVICE THERAPIES IN HEART FAILURE 40
Treatment options in advanced heart failure 40
Heart transplantation 40
Fundamental differences between drugs and devices 43
Arrhythmia Devices in Heart Failure 44
Ventricular dyssynchrony 44
Role of ICD therapy 45
Historical development of ICD device therapy 46
Indications and guidelines for ICD therapy 52
Cardiac resynchronization therapy 53
CRT-P vs. CRT-D vs. ICD 59
Limitations of cardiac resynchronization therapy 59
Guidelines and indications 60
Novel technologies 61
Prevention with advanced biosensors 61
Less invasion with leadless technology 62
Cardiac contractility modulation therapy 62
Mechanical circulatory support devices 63
Ventricular Assist Devices 64
Historical developments and design transformation 66
Pulsatile design 67
Rotary design and continuous flow 79
Guidelines and indications for mechanical assistance 96
Total artificial heart devices 101
Counterpulsation devices without blood contact 105
Short-term mechanical assistance 107
Extracorporeal membrane oxygenation (ECMO) 107
Intra-aortic Balloon Pumps 108
Percutaneous transseptal circulatory assist devices 109
Passive containment devices 113
Future technology with artificial heart muscle 117
Problems associated with mechanical circulatory assist devices 118
Biocompatibility, coagulation control and device surfaces 119
Infection and external components 120
Power sources, size and patient mobility 122
Mechanical durability 123
Future directions and industry challenges 125
Summary of design trends 126
Telemedicine for heart failure management 127
Device availability 127
FDA approved devices 129
APPENDIX A 132
Methodology 132
Epidemiology 132
Incidence of acute heart failure 132
Prevalence of chronic heart failure 134
APPENDIX B 137
Report methodology 137
Bibliography 137
APPENDIX C 140
About Datamonitor 140
About Datamonitor Healthcare 140
About the cardiovascular analysis team 141
Disclaimer 142
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Table 1: Causes of heart failure in the seven major markets (%), 2004 10
Table 2: Prevalence of chronic heart failure by age group in the seven major markets (000s), 2005 17
Table 3: Estimated proportion of chronic heart failure patients with co-morbid conditions and risk factors in the seven major markets (%), 2004 18
Table 4: Estimated incidence of acute heart failure in the seven major markets (000s), 2008-2016 22
Table 5: Future estimated incidence of chronic heart failure in the seven major markets (000s), 2008-2016 23
Table 6: Symptoms used in the diagnosis of chronic heart failure in the seven major markets, 2004 25
Table 7: Symptoms observed in chronic heart failure patients in the seven major markets, 2004 26
Table 8: Tests used in the diagnosis of chronic heart failure in the seven major markets, 2004 27
Table 9: Proportion of patients with chronic heart failure receiving each diagnostic test, 2004 28
Table 10: Historical development of ICD device therapy 47
Table 11: Major clinical trials for CRT 54
Table 12: Indications for CRT-D vs. ICD 59

Figure 1: Segmentation of diagnosed chronic heart failure patients by disease severity, 2004 11
Figure 2: ACC/AHA practice guidelines for the evaluation and management of chronic heart failure, 2005 13
Figure 3: Relationship between cardiac dysfunction, heart failure and heart failure rendered asymptomatic, as defined by the European Society of Cardiology 14
Figure 4: Breakdown of heart failure patients according to whether failure is systolic, diastolic or both in 7MM, 2004 16
Figure 5: Staging of heart failure and associated interventions 42
Figure 6: Prevalence of atrial fibrillation (AF) in heart failure patients 45
Figure 7: Current CRT devices 52
Figure 8: Ventricular assist devices and components 65
Figure 9: Types of ventricular assist devices 66
Figure 10: Modern pulatile ventricular assist pump 68
Figure 11: Centrifugal flow ventricular assist system 83
Figure 12: Jarvik Heart 90
Figure 13: HeartMate II 91
Figure 14: INCOR BerlinHeart 93
Figure 15: CardioWest Total Artificial Heart 102
Figure 16: Examples of counterpulsation devices 107
Figure 17: TandemHeart pVAD 110
Figure 18: Acorn CorCap 115
Figure 19: Type and rates of device-related complications 118
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