Arthur Jay Moss MD PhD: The cardiology world has again lost one of its most respected and worldwide-honoured scholars and experienced clinician. Born 21 June 1931, Professor of Medicine and Cardiology at Rochester University Medical Center, Rochester, NY, Arthur passed away on 14 February 2018 at the age of 86

Arthur Jay Moss MD PhD: The cardiology world has again lost one of its most respected and... Knowing him, always being actively involved in many of the currently discussed electrophysiology topics even up to the last moments of his active scientific life, it is hard to comprehend that he is no any longer with us, to advise and stimulate his colleagues and friends to promote modern medicine. The scientific career of Arthur J. Moss is amazing. He received a bachelor’s degree at Yale University in 1953; thereafter, he attended Harvard Medical School and achieved his medical degree in 1957. He started a residency programme at Massachusetts General Hospital, which was interrupted after 1 year when he was drafted into military service with the US Navy, where he participated at the US astronaut program. After his military term in 1960, he returned to finish residency at Rochester University Medical Center (URMC) in Rochester, NY, USA and completed Internal Medicine and Cardiology training also at URMC in Rochester, NY, USA in 1965. He joined the medical faculty of URMC in 1966, and a few years later became Professor of Medicine at URMC and stayed there until the end of his clinical career, taking care of patients in private practice in Rochester while remaining a full member of the Medical Faculty with teaching and training commitments for medical students and trainees. But most importantly, he continued with multiple research projects at the Heart Research Follow-up Program at URMC founded by himself in 1970. The areas of clinical science and their impact on medical progress in the field of cardiology Arthur Moss has contributed to are astonishing. Among the multiple projects, he has initiated, worked on, and published, two need to be especially emphasized. In 1973, he strongly opposed Dr Bernard Lown, Editor-in-Chief of Circulation, by defending Dr Michel Mirowski’s first published idea of an implantable defibrillator to prevent sudden arrhythmic death.1 Lown had built the external defibrillator device a few years before and condemned the idea of an implantable defibrillator, calling it ‘a bomb in the body’. Fortunately, he was wrong, but this discussion brought about the first meeting of Arthur with Dr Mirowski and Dr Morton Mower in Baltimore shortly thereafter. This was the beginning of a long friendship between the three innovators of modern cardiology and the birth of implantable defibrillator therapy, although it took another 7 years until its first implantation in humans. In 1990, the history of the legendary Multicenter Automatic Defibrillator Implantation Trial (MADIT) started; all are linked to Arthur Moss, were all published in the New England Journal of Medicine, and each trial’s outcomes advanced the therapy with the ICD. Results of the MADIT-I trial were published in 1996,2 showing that patients after myocardial infarction with reduced left ventricular ejection fraction (LVEF ≤35%) who had shown non-sustained ventricular tachycardia, were inducible but not suppressible with an i.v.-administered antiarrhythmic drug, have significantly lower overall mortality with ICD therapy, thereby forecasting the end of widely used programmable ventricular stimulation (PVS) to guide antiarrhythmic therapy for ventricular tachyarrhythmias. MADIT-II, published in 2002, conclusively established the value of ICD implantation for primary prevention of sudden cardiac death in patients with severely reduced left ventricular function (LVEF ≤ 30%) after myocardial infarction. MADIT-CRT, published in 2009, demonstrated the benefit of cardiac resynchronization therapy (CRT) when applied to patients with mild heart failure in subjects with both ischaemic- and non-ischaemic cardiomyopathy. Long-term results of this landmark trial were confirmed in 2014. The advantage of sophisticated ICD programming, suspected to favour inappropriate therapy delivery, was challenged with the MADIT-RIT trial, published in 2012, and revealed that less aggressive and more delayed ICD intervention is superior to immediate delivery of anti-tachycardia pacing (ATP) or shock delivery and will reduce the incidence of inappropriate or unnecessary ICD intervention. All MADIT trials were followed—and will continue to be followed—by multiple sub-studies supporting the messages from the main trials. It seems legitimate to say that all MADIT studies and their sub-studies bear the signature and spirit of Arthur Moss. They had significant impact on guidelines for the treatment of life-threatening ventricular arrhythmias and prevention of sudden cardiac death. It is sad to realize that Arthur will not have the opportunity to await the outcome of the recently launched MADIT-S-ICD trial, also encouraged and designed by him together with many of his long-time colleagues and friends, to prove the benefit of the subcutaneous-ICD (S-ICD) in elderly patients with diabetes, coronary artery disease, and moderately reduced ventricular function. The second area of cardiac electrophysiology Arthur Moss is irrevocably attached to is the genetic Long QT-Syndrome (LQT) arrhythmia. In 1971, he was the first to use unilateral cervical-thoracic sympathetic ganglionectomy for a 40-year-old female patient—now 88 years old—with a typical LQT-Syndrome.3 This intervention had already been used 50 years earlier to reduce angina pectoris in coronary patients. Two years later, Dr Peter Schwartz from Milan, Italy, successfully performed left sided cardiac sympathetic denervation in a 9-year-old girl with LQT-Syndrome. Since 1972, Dr Schwartz had already started to assemble patient data with LQT-Syndrome from clinicians all over the world. Fortunately, Schwartz and Moss met first in 1975, and in 1977 they decided to establish together a prospective international registry on patients with LQT-Syndrome. This registry was founded in 1979 by means of a National Institute of Health Grant and was set up in the University of Rochester where Arthur Moss had already established the Heart Research Follow-up Program, a Center for national and international studies, closely connected to URMC. The first report of data from this important International LQT-Syndrome Registry appeared in 1985; in 1991 clinical- and genotyped data of 1016 patients from 328 LQT-Syndrome affected families were published by Arthur and Peter. A 25-year anniversary report of this Registry was published in 2005.4 The registry continued to collect data, particularly gathering results from genetic analyses, under the supervision of Dr Moss and Dr Wojciech Zareba until the present-day and will hopefully continue to be funded in the future. Without Arthur Moss’ and Peter Schwartz’ joint effort to gather data from genotyped subjects with mutations in the ion channel genes, research on genotype–phenotype relationship, epidemiologic data, risk factors, and treatment results during the last 25 years, our understanding of this inherited arrhythmia syndrome would be scarce. In the meantime, more than 30 publications on results from the registry originating from younger as well as advanced scientists were published, all mentored by Dr Moss. It is important to mention that there is continued cooperation with the research institute of Dr Schwartz, revealing an important characteristic of Arthur Moss, the willingness, friendship, and openness for international collaboration with numerous clinicians and scientists. However, it would be incomplete not to mention so many other fields of clinical electrophysiology Dr Arthur Moss was involved in or added significant knowledge to. In 1968, he reported on left atrial pacing via the coronary sinus and the vein of Marshall.5 Ten years later he reported on the 5-year long-term results of left atrial pacing with 76% effective pacing for sinus bradycardia and sick sinus syndrome.6 In the early 1980s, he became interested in post-infarction risk stratification for ventricular tachyarrhythmias and sudden cardiac death and co-operated later with Dr Tom J. Bigger, the investigator of the CABG-Patch Trial, who very sadly also passed away recently.7 Arthur Moss formed the Multicenter Diltiazem Post Infarction Research Group and investigated the effect of Diltiazem, a new Ca-Antagonist at this time, on post-infarction mortality.8 Later in 1994, the same group of well-known researchers formed the Multicenter Myocardial ischaemia Research Group which was involved in numerous studies on post-infarction arrhythmias and defibrillator therapy. He studied many aspects of electro cardiology, effects of antiarrhythmic drugs on cardiac repolarization; he already suspected the negative effect of digitalis after myocardial infarction, participated in studies that investigated the effect of dangerous QT prolongation of non-antiarrhythmic drugs, and became involved in studies of the arrhythmogenic right ventricular cardiomyopathy (ARVD). In the early 2000s, Arthur Moss and his Heart Research Follow-up Group started to evaluate the value of the Wearable Cardioverter-Defibrillator (WCD) for risk stratification in patients assumed to carry a high risk of sudden arrhythmic death prior to potential ICD implantation. The WCD was designed and built by Dr Steve Heilman, the engineer who helped Dr Michel Mirowski to develop the implantable defibrillator. Dr Moss was co-investigator of the WEARIT/BIROAD study that led to FDA approval of the WCD.9 Later, his group organized the prospective WEARIT-II Registry in the USA, the data of which were published 2 years ago by Dr Kutyifa, who joined the Heart Research follow-up group a few years ago.10 From the very beginning of the Heart Research Follow-up Program of URMC until the present-day, Dr Moss and his research group has successfully performed 37 large multicentre trials and studies, has set up an excellent clinical research organization for all study administration issues and installed large electronic data banks with an excellent statistician back-up team. Dr Moss’ publication record goes beyond 750 peer reviewed manuscripts, and few scientists have published more manuscripts in the New England Journal of Medicine than he has. He founded and was the Editor-in-Chief for ‘Annals of Noninvasive Electrocardiology’, was a member of the Editorial Board for many highly ranked medical journals and participated in many guideline committees. He received multiple distinguished awards, including the Distinguished Scientist (2011) and Pioneer in Cardiac Pacing and Electrophysiology (2017) Awards from the Heart Rhythm Society (HRS); 4 months prior to his death he received the James. B. Herrick Award of the American Heart Association. Arthur Moss was an excellent, well respected clinician, much beloved by his patients. Dr Eric Topol, at the Scripps Clinic in La Jolla, CA, USA said in a 2013 video tribute to Dr Moss, ‘He has probably done more to advance our understanding of heart rhythm disorders than any cardiologist or researcher in the world’. He is a worldwide respected and honoured scientist, a visionary, a wonderful teacher and mentor to his students, and is highly regarded by all his colleagues. To many of us he is a dear friend, humble, full of humour, wisdom, and compassion. The era of Dr Arthur J. Moss came to an end, but his spirit and accomplishments will remain and will direct the current and future generation of clinicians and scientists. He is survived by his wonderful wife Joy and his three children; two are Professors in Psychiatry and Paediatrics, Katherine in Tel Aviv and Deborah in Pittsburgh, and David is Professor at the Harvard Business School. Personal tributes to Arthur Jay Moss Arthur Moss had a wonderful sense of humour, combined with honesty. To his numerous friends, he often told us how he became a ‘space pioneer’ after being drafted into the military in 1959, when just an Intern in Hematology at MGH in Boston. With almost no knowledge about ECG or cardiovascular medicine, he had to teach ECG reading to Navy officers; then being considered a specialist in cardiology he was assigned to the Navy astronaut space program and had to work on a mission sending squirrel monkeys into space 300 miles high with a Jupiter rocket. The first two little monkeys were supposed to be a monkey couple, a male monkey named ‘Baker’ and female monkey called ‘Able’. After the first successful space mission, medical examination of the two ‘astronauts’ revealed that Mr Baker was not a male monkey but a young female. Smiling, Arthur told us that the lay press never learned about the ‘gender mismatch’ of the first monkey space flight. Arthur was a superb diplomatic role model. When he had a new, revolutionary idea for new trials or foresaw scientific questions that needed to be answered, he gathered well-known scientists and clinicians for a 2-day meeting over the weekend. Everyone came to the meeting with totally different ideas and opinions. The first day every member of the group had the opportunity to present proposals, ideas, or solutions to the problem. At the end of the day, we always felt that it would be impossible to come to an agreement. Overnight, Arthur digested the various concepts and proposals, and the next morning he presented a joint study concept everybody was happy with and felt well accepted and represented. This was the way all MADIT trials were born. Arthur’s greatest disappointment during his last years came about when we started to design the MADIT-RIT trial to find better ways for ICD programming to reduce inappropriate ICD interventions. His idea was to bring all ICD manufacturers together to participate and support the trial that would potentially bring great benefit to all ICD patients, but would not discriminate individual ICD manufacturers. However, after we had a long meeting with all ICD manufacturers together, chaired by Arthur Moss, they refused to co-operate with threadbare arguments. For the first time, we felt the great disappointment of Arthur at not being able to bring the medical device industry together. Fortunately, we were able to receive grant support from one ICD company Arthur had always successfully worked with. Conflict of interest: none declared. References References are available as supplementary material at European Heart Journal online. Published by Oxford University Press on behalf of the European Society of Cardiology 2018. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Heart Journal Oxford University Press

Arthur Jay Moss MD PhD: The cardiology world has again lost one of its most respected and worldwide-honoured scholars and experienced clinician. Born 21 June 1931, Professor of Medicine and Cardiology at Rochester University Medical Center, Rochester, NY, Arthur passed away on 14 February 2018 at the age of 86

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Abstract

Knowing him, always being actively involved in many of the currently discussed electrophysiology topics even up to the last moments of his active scientific life, it is hard to comprehend that he is no any longer with us, to advise and stimulate his colleagues and friends to promote modern medicine. The scientific career of Arthur J. Moss is amazing. He received a bachelor’s degree at Yale University in 1953; thereafter, he attended Harvard Medical School and achieved his medical degree in 1957. He started a residency programme at Massachusetts General Hospital, which was interrupted after 1 year when he was drafted into military service with the US Navy, where he participated at the US astronaut program. After his military term in 1960, he returned to finish residency at Rochester University Medical Center (URMC) in Rochester, NY, USA and completed Internal Medicine and Cardiology training also at URMC in Rochester, NY, USA in 1965. He joined the medical faculty of URMC in 1966, and a few years later became Professor of Medicine at URMC and stayed there until the end of his clinical career, taking care of patients in private practice in Rochester while remaining a full member of the Medical Faculty with teaching and training commitments for medical students and trainees. But most importantly, he continued with multiple research projects at the Heart Research Follow-up Program at URMC founded by himself in 1970. The areas of clinical science and their impact on medical progress in the field of cardiology Arthur Moss has contributed to are astonishing. Among the multiple projects, he has initiated, worked on, and published, two need to be especially emphasized. In 1973, he strongly opposed Dr Bernard Lown, Editor-in-Chief of Circulation, by defending Dr Michel Mirowski’s first published idea of an implantable defibrillator to prevent sudden arrhythmic death.1 Lown had built the external defibrillator device a few years before and condemned the idea of an implantable defibrillator, calling it ‘a bomb in the body’. Fortunately, he was wrong, but this discussion brought about the first meeting of Arthur with Dr Mirowski and Dr Morton Mower in Baltimore shortly thereafter. This was the beginning of a long friendship between the three innovators of modern cardiology and the birth of implantable defibrillator therapy, although it took another 7 years until its first implantation in humans. In 1990, the history of the legendary Multicenter Automatic Defibrillator Implantation Trial (MADIT) started; all are linked to Arthur Moss, were all published in the New England Journal of Medicine, and each trial’s outcomes advanced the therapy with the ICD. Results of the MADIT-I trial were published in 1996,2 showing that patients after myocardial infarction with reduced left ventricular ejection fraction (LVEF ≤35%) who had shown non-sustained ventricular tachycardia, were inducible but not suppressible with an i.v.-administered antiarrhythmic drug, have significantly lower overall mortality with ICD therapy, thereby forecasting the end of widely used programmable ventricular stimulation (PVS) to guide antiarrhythmic therapy for ventricular tachyarrhythmias. MADIT-II, published in 2002, conclusively established the value of ICD implantation for primary prevention of sudden cardiac death in patients with severely reduced left ventricular function (LVEF ≤ 30%) after myocardial infarction. MADIT-CRT, published in 2009, demonstrated the benefit of cardiac resynchronization therapy (CRT) when applied to patients with mild heart failure in subjects with both ischaemic- and non-ischaemic cardiomyopathy. Long-term results of this landmark trial were confirmed in 2014. The advantage of sophisticated ICD programming, suspected to favour inappropriate therapy delivery, was challenged with the MADIT-RIT trial, published in 2012, and revealed that less aggressive and more delayed ICD intervention is superior to immediate delivery of anti-tachycardia pacing (ATP) or shock delivery and will reduce the incidence of inappropriate or unnecessary ICD intervention. All MADIT trials were followed—and will continue to be followed—by multiple sub-studies supporting the messages from the main trials. It seems legitimate to say that all MADIT studies and their sub-studies bear the signature and spirit of Arthur Moss. They had significant impact on guidelines for the treatment of life-threatening ventricular arrhythmias and prevention of sudden cardiac death. It is sad to realize that Arthur will not have the opportunity to await the outcome of the recently launched MADIT-S-ICD trial, also encouraged and designed by him together with many of his long-time colleagues and friends, to prove the benefit of the subcutaneous-ICD (S-ICD) in elderly patients with diabetes, coronary artery disease, and moderately reduced ventricular function. The second area of cardiac electrophysiology Arthur Moss is irrevocably attached to is the genetic Long QT-Syndrome (LQT) arrhythmia. In 1971, he was the first to use unilateral cervical-thoracic sympathetic ganglionectomy for a 40-year-old female patient—now 88 years old—with a typical LQT-Syndrome.3 This intervention had already been used 50 years earlier to reduce angina pectoris in coronary patients. Two years later, Dr Peter Schwartz from Milan, Italy, successfully performed left sided cardiac sympathetic denervation in a 9-year-old girl with LQT-Syndrome. Since 1972, Dr Schwartz had already started to assemble patient data with LQT-Syndrome from clinicians all over the world. Fortunately, Schwartz and Moss met first in 1975, and in 1977 they decided to establish together a prospective international registry on patients with LQT-Syndrome. This registry was founded in 1979 by means of a National Institute of Health Grant and was set up in the University of Rochester where Arthur Moss had already established the Heart Research Follow-up Program, a Center for national and international studies, closely connected to URMC. The first report of data from this important International LQT-Syndrome Registry appeared in 1985; in 1991 clinical- and genotyped data of 1016 patients from 328 LQT-Syndrome affected families were published by Arthur and Peter. A 25-year anniversary report of this Registry was published in 2005.4 The registry continued to collect data, particularly gathering results from genetic analyses, under the supervision of Dr Moss and Dr Wojciech Zareba until the present-day and will hopefully continue to be funded in the future. Without Arthur Moss’ and Peter Schwartz’ joint effort to gather data from genotyped subjects with mutations in the ion channel genes, research on genotype–phenotype relationship, epidemiologic data, risk factors, and treatment results during the last 25 years, our understanding of this inherited arrhythmia syndrome would be scarce. In the meantime, more than 30 publications on results from the registry originating from younger as well as advanced scientists were published, all mentored by Dr Moss. It is important to mention that there is continued cooperation with the research institute of Dr Schwartz, revealing an important characteristic of Arthur Moss, the willingness, friendship, and openness for international collaboration with numerous clinicians and scientists. However, it would be incomplete not to mention so many other fields of clinical electrophysiology Dr Arthur Moss was involved in or added significant knowledge to. In 1968, he reported on left atrial pacing via the coronary sinus and the vein of Marshall.5 Ten years later he reported on the 5-year long-term results of left atrial pacing with 76% effective pacing for sinus bradycardia and sick sinus syndrome.6 In the early 1980s, he became interested in post-infarction risk stratification for ventricular tachyarrhythmias and sudden cardiac death and co-operated later with Dr Tom J. Bigger, the investigator of the CABG-Patch Trial, who very sadly also passed away recently.7 Arthur Moss formed the Multicenter Diltiazem Post Infarction Research Group and investigated the effect of Diltiazem, a new Ca-Antagonist at this time, on post-infarction mortality.8 Later in 1994, the same group of well-known researchers formed the Multicenter Myocardial ischaemia Research Group which was involved in numerous studies on post-infarction arrhythmias and defibrillator therapy. He studied many aspects of electro cardiology, effects of antiarrhythmic drugs on cardiac repolarization; he already suspected the negative effect of digitalis after myocardial infarction, participated in studies that investigated the effect of dangerous QT prolongation of non-antiarrhythmic drugs, and became involved in studies of the arrhythmogenic right ventricular cardiomyopathy (ARVD). In the early 2000s, Arthur Moss and his Heart Research Follow-up Group started to evaluate the value of the Wearable Cardioverter-Defibrillator (WCD) for risk stratification in patients assumed to carry a high risk of sudden arrhythmic death prior to potential ICD implantation. The WCD was designed and built by Dr Steve Heilman, the engineer who helped Dr Michel Mirowski to develop the implantable defibrillator. Dr Moss was co-investigator of the WEARIT/BIROAD study that led to FDA approval of the WCD.9 Later, his group organized the prospective WEARIT-II Registry in the USA, the data of which were published 2 years ago by Dr Kutyifa, who joined the Heart Research follow-up group a few years ago.10 From the very beginning of the Heart Research Follow-up Program of URMC until the present-day, Dr Moss and his research group has successfully performed 37 large multicentre trials and studies, has set up an excellent clinical research organization for all study administration issues and installed large electronic data banks with an excellent statistician back-up team. Dr Moss’ publication record goes beyond 750 peer reviewed manuscripts, and few scientists have published more manuscripts in the New England Journal of Medicine than he has. He founded and was the Editor-in-Chief for ‘Annals of Noninvasive Electrocardiology’, was a member of the Editorial Board for many highly ranked medical journals and participated in many guideline committees. He received multiple distinguished awards, including the Distinguished Scientist (2011) and Pioneer in Cardiac Pacing and Electrophysiology (2017) Awards from the Heart Rhythm Society (HRS); 4 months prior to his death he received the James. B. Herrick Award of the American Heart Association. Arthur Moss was an excellent, well respected clinician, much beloved by his patients. Dr Eric Topol, at the Scripps Clinic in La Jolla, CA, USA said in a 2013 video tribute to Dr Moss, ‘He has probably done more to advance our understanding of heart rhythm disorders than any cardiologist or researcher in the world’. He is a worldwide respected and honoured scientist, a visionary, a wonderful teacher and mentor to his students, and is highly regarded by all his colleagues. To many of us he is a dear friend, humble, full of humour, wisdom, and compassion. The era of Dr Arthur J. Moss came to an end, but his spirit and accomplishments will remain and will direct the current and future generation of clinicians and scientists. He is survived by his wonderful wife Joy and his three children; two are Professors in Psychiatry and Paediatrics, Katherine in Tel Aviv and Deborah in Pittsburgh, and David is Professor at the Harvard Business School. Personal tributes to Arthur Jay Moss Arthur Moss had a wonderful sense of humour, combined with honesty. To his numerous friends, he often told us how he became a ‘space pioneer’ after being drafted into the military in 1959, when just an Intern in Hematology at MGH in Boston. With almost no knowledge about ECG or cardiovascular medicine, he had to teach ECG reading to Navy officers; then being considered a specialist in cardiology he was assigned to the Navy astronaut space program and had to work on a mission sending squirrel monkeys into space 300 miles high with a Jupiter rocket. The first two little monkeys were supposed to be a monkey couple, a male monkey named ‘Baker’ and female monkey called ‘Able’. After the first successful space mission, medical examination of the two ‘astronauts’ revealed that Mr Baker was not a male monkey but a young female. Smiling, Arthur told us that the lay press never learned about the ‘gender mismatch’ of the first monkey space flight. Arthur was a superb diplomatic role model. When he had a new, revolutionary idea for new trials or foresaw scientific questions that needed to be answered, he gathered well-known scientists and clinicians for a 2-day meeting over the weekend. Everyone came to the meeting with totally different ideas and opinions. The first day every member of the group had the opportunity to present proposals, ideas, or solutions to the problem. At the end of the day, we always felt that it would be impossible to come to an agreement. Overnight, Arthur digested the various concepts and proposals, and the next morning he presented a joint study concept everybody was happy with and felt well accepted and represented. This was the way all MADIT trials were born. Arthur’s greatest disappointment during his last years came about when we started to design the MADIT-RIT trial to find better ways for ICD programming to reduce inappropriate ICD interventions. His idea was to bring all ICD manufacturers together to participate and support the trial that would potentially bring great benefit to all ICD patients, but would not discriminate individual ICD manufacturers. However, after we had a long meeting with all ICD manufacturers together, chaired by Arthur Moss, they refused to co-operate with threadbare arguments. For the first time, we felt the great disappointment of Arthur at not being able to bring the medical device industry together. Fortunately, we were able to receive grant support from one ICD company Arthur had always successfully worked with. Conflict of interest: none declared. References References are available as supplementary material at European Heart Journal online. Published by Oxford University Press on behalf of the European Society of Cardiology 2018. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

European Heart JournalOxford University Press

Published: May 31, 2018

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