UNIVERSITY OF GENOA School of Medical and Pharmaceutical Sciences Master’s degree course in Medicine and Surgery DEGREE THESIS SURGICAL VENTRICULAR REMODELING IN ISCHEMIC HEART FAILURE: THE IMPACT OF OPTIMAL VOLUME REDUCTION ON LONG-TERM OUTCOME SUPERVISOR CANDIDATE Francesco Santini, M.D. Francesca Zanin CO-SUPERVISORS Antonio Salsano, M.D. Serenella Castelvecchio, M.D. Lorenzo Menicanti, M.D. Academic Year 2019-2020 Ai miei genitori, i miei punti cardinali 2 INDEX 1. Introduction ..................................................................................................... 6 2. Heart Failure .................................................................................................. 10 2.1. Definition and classification ................................................................................ 10 2.2. Epidemiology and Impact on the population ..................................................... 15 2.3. Etiology .................................................................................................................. 17 2.3.1. Ischemic etiology .................................................................................................. 19 2.4. Pathophysiology ................................................................................................... 22 2.4.1. Left Ventricular Remodeling ................................................................................. 25 2.5. Diagnosis ............................................................................................................... 29 2.5.1. Clinical presentation ............................................................................................. 30 2.5.2. Physical examination ........................................................................................... 31 2.5.3. Investigations ....................................................................................................... 33 2.5.3.1. Noninvasive single or combined Imaging techniques ....................................... 36 2.5.3.2. Invasive Imaging techniques ............................................................................. 38 2.5.4. Algorithm for diagnosis of HF ............................................................................... 39 2.6. Prognosis ............................................................................................................... 40 3. Current therapeutic strategies for chronic ischemic-Based HFrEF ......... 43 3.1. Medical therapies .................................................................................................. 43 3.1.1. Management of fluid retention .............................................................................. 45 3.1.2. Prevention of disease progression ....................................................................... 47 3.2. Device therapy ....................................................................................................... 49 3.2.1. Cardiac resynchronization therapy (CRT) ............................................................ 50 3.2.2. Implantable cardioverter defibrillator (ICD) .......................................................... 51 3.2.3. Left ventricular assist device (LVAD) ................................................................... 52 3.3. Surgical strategies ................................................................................................ 53 3.3.1. Cardiac transplantation ........................................................................................ 53 3.3.2. Coronary artery bypass grafting (CABG) ............................................................. 54 3.3.3. Mitral valve repair or replacement (MVR) ............................................................ 55 3.3.4. Surgical Ventricular Reconstruction (SVR) .......................................................... 56 4. Surgical Ventricular Reconstruction (SVR) ................................................ 57 4.1. Rationale to perform SVR ..................................................................................... 57 4.2. Indications ............................................................................................................. 58 4.3. History .................................................................................................................... 61 4.4. Technique .............................................................................................................. 61 4.5. Particular conditions ............................................................................................ 64 4.5.1. Mitral valve (MV) .................................................................................................. 64 4.5.2. Anterior versus Postero-inferior Remodeling ....................................................... 67 4.6. Drawbacks ............................................................................................................. 69 3 5. Previous studies ........................................................................................... 71 5.1. Dor and co-authors ............................................................................................... 71 5.2. The Restore Group ................................................................................................ 71 5.3. Menicanti, Castelvecchio et al. ............................................................................ 72 5.4. The role of LVESVI: White et al., the GUSTO-I trial and BaX et al. .................... 73 5.5. The STICH trial ...................................................................................................... 74 5.6. Di Donato, Castelvecchio and Menicanti ............................................................ 75 5.7. Witkowski et al. ..................................................................................................... 76 5.8. Criticisms of the STICH trial ................................................................................. 77 5.9. Michler et al. .......................................................................................................... 79 5.10. ESC/EACTS Guidelines on Myocardial Revascularization ............................... 80 6. Retrospective analysis at IRCCS Policlinico San Donato ......................... 82 6.1. Introduction ........................................................................................................... 82 6.2. Aim of the study .................................................................................................... 83 6.3. Materials and Methods ......................................................................................... 83 6.3.1. Study design ........................................................................................................ 83 6.3.2. Selection of Patients ............................................................................................ 84 6.3.3. End points ............................................................................................................ 85 6.3.4. Methods ............................................................................................................... 85 6.3.5. Statistical analysis ................................................................................................ 86 7. Results and discussion ................................................................................ 87 7.1. Results ................................................................................................................... 87 7.2. Discussion ............................................................................................................. 94 8. Conclusions .................................................................................................. 97 Bibliography ........................................................................................................ 98 Acknowledgements ........................................................................................... 123 4 5 1. Introduction Heart failure (HF), to use a term widely popular at present, can be defined as a global pandemic, i.e. “an epidemic occurring worldwide, or over a very wide area, crossing international boundaries and usually affecting a large number of people”1, since it is estimated to involve at least 26 million persons globally, with a 2% overall prevalence in the adult population, and >10% among individuals aged >70 years. Despite medical advances in therapies and implementation of prevention campaigns, its prevalence shows no sign of abating; indeed, it is increasing dramatically as the population ages, weighing heavily on global health expenditures. Moreover, mortality and morbidity of the disease remain high, and the quality of life remains poor. Projections for the coming years in terms of prevalence, hospitalization rates, and healthcare costs are even more alarming, making HF one of the major public health challenges worldwide. Although it is very difficult to provide a single definition of the complexity of this disease, according to the European Society of Cardiology, HF can be defined as a clinical syndrome, characterized by typical symptoms and signs, caused by a structural and/or functional cardiac abnormality, which results in reduced cardiac output and/or elevated intracardiac pressures at rest or during stress. In short, it is a progressive condition that inevitably leads to frequent hospitalization and decreased life expectancy. HF may result from