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Non-Surgical Septal Reduction Therapy in Hypertrophic Obstructive Cardiomyopathy

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Non-Surgical Septal Reduction Therapy in Hypertrophic Obstructive Cardiomyopathy Non-Surgical Septal Reduction Therapy in Hypertrophic Obstructive Cardiomyopathy: Current practice and future potential 1 Robert Michael Cooper CID 744810 National Heart and Lung Institute Imperial College London PhD 2 This body of work is my own and represents original work. All else is appropriately referenced. The copyright of this thesis rests with the author and is made available under a Creative Commons Attribution Non-Commercial No Derivatives licence. Researchers are free to copy, distribute or transmit the thesis on the condition that they attribute it, that they do not use it for commercial purposes and that they do not alter, transform or build upon it. For any reuse or redistribution, researchers must make clear to others the licence terms of this work 3 Abstract Obstruction in hypertrophic cardiomyopathy is associated with increased morbidity and mortality. Effective resolution of outflow tract obstruction can provide relief of symptoms and perhaps improve prognosis. Non-surgical septal reduction in the form of alcohol septal ablation (ASA) has been performed since 1994 with limited progress in the last decade. ASA using traditional methods has an unacceptably high rate of failure to resolve LVOT gradient. By creating and populating a relational database I was able to show that failure to treat LVOT gradient satisfactorily was seen in 41% after one procedure and 18% after multiple procedures. This can be partly explained by inaccurate location of the iatrogenic infarction, seen on CMR. Improving accuracy of infarction in ASA could be achieved by better peri- procedural imaging. Intracardiac echocardiography (ICE) provides excellent image quality of the contact point of the mitral valve on the septum in HOCM, but is no better than standard transthoracic echocardiography in describing detail of the septum or other cardiac structures relevant to ASA. ICE cannot see myocardial contrast well and therefore cannot be used to guide ASA alone. 4 Computed tomography (CT) angiography can visualise small septal arteries. The ability to merge angiographic images with structural detail allows description of the path of arteries to guide alcohol injection in ASA. The use of CT planning improved the success rate of ASA after one procedure from 59% to 85%. We observed less RBBB (13% vs 62%) due to improved targeting of the LV septum, confirmed by CMR. Patient selection in ASA is important. A standard operating procedure for assessment and treatment of HOCM patients is now part of routine clinical care. Some patients cannot receive trans-coronary alcohol due to arterial anatomical restrictions. Direct endocardial radiofrequency ablation of the interventricular septum with merged ICE/CARTO electrophysiology mapping system guidance was explored with encouraging results. 5 Acknowledgments: First and foremost I must acknowledge the input and guidance of my primary supervisor, Professor Rod Stables. He was responsible for setting up an ASA service in Liverpool and it was with his reputation and funding that a research project was allowed at Liverpool Heart and Chest Hospital. He was approachable and involved from day 1 to the end. He was enthusiastic and took his pastoral role very seriously. This project would not have been possible without him. I hope this working clinical and research relationship continues for many years. With regard to the expert assessors for specific chapters in this thesis I must thank the following people: Dr James Newton; Consultant Cardiologist Oxford John Radcliffe Hospital. Expert reviewer for ICE and TTE in chapter 4. Dr Niels Vejlstrup: Consultant cardiologist at Rigshospitalet, Copenhagen. Expert reviewer for ICE and TTE in chapter 4. Dr Jonathan Hasleton: Consultant Cardiologist at Royal Liverpool Hospital. Expert reviewer for assessment of myocardial infarction and CMR appearances post ASA Chapter 3. Dr Sukumaran Binukrishnan: Consultant Cardiac Radiologist Liverpool Heart and Chest Hospital. Expert reviewer for CT analysis in Chapters 5 and 6. Lastly I must thank my wife Menna and children, Sam and Ben or their ongoing support. Without them this project would have been completed much sooner. 6 Author’s contributions: As the author of this thesis I should clarify my role in the creation of the project, the collection of data and the writing of subsequent manuscripts. I interviewed for a research post that was already approved at Liverpool Heart and Chest Hospital and was appointed ahead of other candidates. The basic structure of a project of appraising outcomes so far and introducing ICE was in place. The use of CT angiography was simply at a conceptual stage, as was the use of RF ablation. I was therefore involved in the ethical approvals for each section of study and the methods and data collection protocols. I was present for and collected and collated the imaging data for each chapter. I did not personally score any data as I wanted to exclude this opportunity for bias. I also did not acquire the echocardiography images as part of chapter 4, this was to remove the possibility of acquisition bias. An independent qualified sonographer therefore acquired all images, I was present for all echoes commented on in this thesis. The CT scans were analysed by one expert radiologist – I am not formally trained in CT and therefore couldn’t perform this duty. All ASA procedures were performed by Professor Rod Stables. The second operator varied somewhat according to lab rotas etc. I was present for all procedures for peri-ASA imaging guidance and to ensure research protocols were adhered to. All RF procedures were performed by Dr Simon Modi with me as the second operator. I operated the ICE catheter for these procedures. I then descrubbed to delineate the borders of the cardiac structures on the echo console. 7 Abbreviations list HCM: Hypertrophic cardiomyopathy HOCM: Hypertrophic obstructive cardiomyopathy ASA: Alcohol septal ablation LV: Left ventricle RV: Right ventricle MV: Mitral valve SAM: Systolic anterior motion CT: Computed tomography ICE: Intracardiac echocardiography NYHA: New York Heart Association LAD: Left anterior descending RCA: Right coronary artery OTW: Over the wire (balloon) LA: Left atrium LHCH: Liverpool Heart and Chest Hospital RF(A): Radiofrequency (ablation) 8 Contents Acknowledgments: ................................................................................................................................. 6 Author’s contributions: ........................................................................................................................... 7 Abbreviations list .................................................................................................................................... 8 Chapter 1: Current status of Non-surgical Septal Reduction Therapy (NSRT) in Hypertrophic Obstructive Cardiomyopathy (HOCM) .................................................................................................. 31 1.1 Introduction .............................................................................................................................. 32 1.2 Pathophysiology of LVOT obstruction in HOCM ....................................................................... 34 1.3 Patient selection for NSRT ........................................................................................................ 36 1.4 Alcohol septal ablation: The procedure .................................................................................... 39 1.5 Results of ASA case series reports ............................................................................................ 42 1.5.1 Survival .............................................................................................................................. 42 1.5.2 Risk of ventricular arrhythmia........................................................................................... 42 1.5.3 Symptom and gradient resolution .................................................................................... 43 1.5.4 Comparison to surgical myectomy ................................................................................... 46 1.5.5 Predictors of outcome in ASA ........................................................................................... 49 1.5.6 Peri-procedural complications of ASA .............................................................................. 49 1.6 Alternative methods of NSRT .................................................................................................... 51 1.7 Summary ................................................................................................................................... 55 1.7.1 What questions must we seek to answer? ....................................................................... 55 1.7.1.1 What proportion of patients derives no benefit from ASA? ........................................ 55 9 1.7.1.2 Why do some ASA procedures fail to have the desired effect on LVOTO? ................. 56 1.7.1.3 If ASA procedures fail because of inaccurate infarct; how can we improve? .............. 56 1.7.1.4 What if patients cannot receive trans-coronary alcohol as part of ASA? .................... 57 Chapter 2: The Liverpool Experience: Describing outcomes in patients undergoing ASA during the period 2000-2011 .................................................................................................................................. 59 2.1 Introduction .............................................................................................................................
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