Pulmonary arterial hypertension : diagnosis and evidence-based treatment

1 Introduction 1 Robyn J. Barst 2 Diagnosis and assessment of pulmonary arterial hypertension 7 Michael D. McGoon, Adam Torbicki and Ronald J. Oudiz 2.1 Hemodynamics of pulmonary hypertension 7 2.2 Venice classification 8 2.3 Overview of the diagnostic process (algorithm) 10 2.4 Screening (identifying a pre-existing risk) 11 2.5 Detection (discovering pulmonary hypertension) 13 2.6 Definition (diagnosing the clinical context) 14 2.7 Prediction (estimating prognosis) 14 2.8 Principles of follow-up (evaluating and responding to outcome) 16 2.9 Specific tests in the evaluation of pulmonary hypertension 20 3 Conventional therapy in pulmonary arterial hypertension 47 Richard N. Channick 3.1 Calcium channel antagonists 48 3.2 Diuretics 52 3.3 Warfarin 52 3.4 Supplemental oxygen 54 3.5 Inotropic therapy 55 3.6 General measures 56 3.7 Conclusions 57 4 Prostanoid treatment for pulmonary arterial hypertension 61 Olivier Sitbon and Gérald Simonneau 4.1 Epoprostenol 63 4.2 Treprostinil 77 4.3 Iloprost 80 4.4 Beraprost 81 4.5 Treatment selection 82 4.6 Conclusions 83 5 Endothelin receptor antagonists in pulmonary arterial hypertension 89 David B. Badesch and Marc Humbert 5.1 Bosentan 92 5.2 Sitaxsentan 96 5.3 Ambrisentan 99 5.4 Safety and tolerability with endothelin receptor antagonists 101 5.5 Conclusions 102 6 Phosphodiesterase-5 inhibitors in pulmonary arterial hypertension 105 Hossein A. Ghofrani, Werner Seeger and Friedrich Grimminger 6.1 The origins of phosphodiesterase-5 inhibitor development 105 6.2 Pulmonary hypertension as a new indication for phosphodiesterase-5 inhibitor treatment 108 6.3 Role of phosphodiesterase-5 in the pulmonary vasculature 109 6.4 Clinical experience with sildenafil for the treatment of chronic pulmonary hypertension 110 6.5 Pivotal trial and approval of sildenafil for the treatment of pulmonary arterial hypertension (SUPER-1 study) 111 6.6 Other phosphodiesterase-5 inhibitors 112 6.7 Combination therapy 114 vi CONTENTS 6.8 Potential new indications for phosphodiesterase-5 inhibitors outside pulmonary arterial hypertension 116 6.9 Conclusions 118 7 Combination therapy for pulmonary arterial hypertension 127 Anne Keogh and Marius Hoeper 7.1 Background 127 7.2 Combination therapy to date 130 7.3 Conclusions 142 8 Interventional and surgical modalities of treatment for pulmonary arterial hypertension 147 Julio Sandoval and Ramona Doyle 8.1 Introduction 147 8.2 Atrial septostomy 148 8.3 Pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension 157 8.4 Lung transplantation for pulmonary hypertension 161 8.5 Conclusions 172 9 End points and clinical trial design in pulmonary arterial hypertension: Clinical and regulatory perspectives 179 Andrew J. Peacock 9.1 Introduction 179 9.2 Trial design 180 9.3 End points in trials of therapy for pulmonary arterial hypertension 185 9.4 Conclusions 197 10 Comparative analysis of clinical trials and evidence-based treatment algorithm for pulmonary arterial hypertension 203 Nazzareno Galiè, Alessandra Manes, Naushad Hirani and Robert Naeije 10.1 Introduction 203 10.2 Randomized controlled studies 207 10.3 Long-term continuation studies 209 10.4 Combination studies 213 10.5 Evidence-based treatment algorithm 214 10.6 Conclusions 216 CONTENTS vii 11 Diagnosis and assessment of non-pulmonary arterial hypertension masquerading as idiopathic pulmonary arterial hypertension: Diastolic heart failure - evaluation and interactions 223 Mardi Gomberg-Maitland and Stuart Rich 11.1 Definition of heart failure 223 11.2 Epidemiology 224 11.3 Physiology 225 11.4 Evaluation of diastolic heart failure: Invasive and noninvasive techniques 226 11.5 Diagnosis and treatment of diastolic dysfunction 229 11.6 Pulmonary hypertension and diastolic dysfunction 230 11.7 Conclusions 232 12 Treatment of pulmonary arterial hypertension: A look to the future 237 Lewis J. Rubin 12.1 Therapy of pulmonary arterial hypertension 240 12.2 Measuring outcomes and monitoring the course of therapy 243 12.3 Conclusions 243