Andrea Nava MD (1938–2018), Associate Professor of Cardiology, University of Padova, Italy died in March 2018 after a long career dedicated to clinical cardiology Andrea Nava, a humble but brilliant pioneer of clinical cardiac arrhythmology (CA) whose achievements have scarcely been recognized, passed away at the age of 79 on 20 March 2018 after a courageous battle with valvular heart disease, diabetes, and cancer. Dr Nava was born at Borgo Valsugana, a small town located in a valley near Trento (Northern Italy) on 15 November 1938. His father was the town Pharmacist, born in another secluded valley, the Valtellina, who later moved his family again, to Murano, the glass isle of Venice, to open a new Pharmacy. In this astonishingly small island, Dr Nava spent his happy youth rowing the ‘Venetian gondola’, fishing in the lagoon, playing basketball, and enjoying life with his friends all belonging to ancient glass factory families. He was always proud of his different origins and organized until so recently a yearly meeting with his relatives and friends from the three valleys, where he was indeed the recognized leader both for his scientific and humanitarian profile. He graduated and specialized in Cardiology at the University of Padova, and initiated his professional career, as assistant to Prof. Sergio Dalla Volta. The prestigious Cardiology school in Padova, with Sergio Dalla Volta, Eligio Piccolo, Francesco Furlanello was a cultural extension of the Institute of Cardiology of Mexico City, where all the above doctors had acquired their relevant experiences. Most of the time in Padova was devoted to electrocardiogram (ECG) and vectorcardiogram (VCG) analysis and interpretation. From the ECG alone, our masters ‘deduced’ the underlying pathology, and for us junior doctors who had the opportunity to see the tail end of this period, it was a honour to learn that their level of knowledge was so high that they determined the aortic gradient in a valvular stenosis, or the right ventricular pressure in congenital heart diseases, by only relying on the ECG recording. At the beginning, Nava made serial original VCG observations regarding the origin of ectopic atrial beats and particularly the hemiblocks and their differentiation from the unusual patterns of incomplete right bundle branch block with a posterior loop. This pattern reflected a delay of the terminal forces that could be consistent with an isolated and zonal right conduction defect in the superior and posterior region of the right ventricle,1 that has been currently classified by Andres Perez-Riera as right end conduction delay. Another early original VCG demonstration was the presence of a re-entry circuit underlying atrial flutter with a significant slowing of conduction velocity localized in the right atrium inferiorly (lately called by Cosio ‘Cavo tricuspid isthmus’). Andrea’s only updating period abroad was in France, with Philippe Coumel, where he learned how to perform invasive electrophysiology studies. Back in Padova, he became interested in A-V conduction and confirmed the presence of the dual A-V pathway and described a novel pattern of nodal conduction, providing evidence in some patients of an intra-nodal final common pathway, distal to the fast and slow A-V nodal pathways.2 He did not have any technical knowledge in electronics, but he enjoyed discussing his knowledge of the cardiac conduction system with engineers. He planned and assembled together with engineer Desidera a cardiac stimulator that was used in all Italy during the following 20 years and participated in the construction of the first ventricular pacing following atrial sensing pacemaker first patented in Italy by engineer Antonio Morra in 1986 (Figure 1). Figure 1 View largeDownload slide The patented catheter allowing VDD pacing, called Phymos (MEDICO SpA, Rubano, Italy). Figure 1 View largeDownload slide The patented catheter allowing VDD pacing, called Phymos (MEDICO SpA, Rubano, Italy). Uptake of the atrial signal with a system of electrodes floating in the right atrium that are not in contact with the cardiac wall, had already been attempted in the late 1970s, but with unsatisfactory results. The signal was detected using an ‘orthogonal’ electrode approach that was designed for the best rejection of the undesirable signal coming from the ventricle (ventricular far field), but this same feature excessively penalized the detection of atrial activation. Nava’s credit after some experiments with a unipolar floating sensory system, was to convince the engineers that a bipolar system was indeed necessary. The group planned a catheter with differential electrodes arranged longitudinally and spaced out optimally to obtain both a good detection of the atrial activation signal and sufficient rejection of ventricular activation and artefacts. Early in the 1980s, after some studies on the conduction system in congenital heart diseases, Nava’s mind was captured by a series of young people who died suddenly, and in whom the electrocardiogram showed ‘ante mortem’ some ventricular arrhythmias and minor waves, previously named ‘idiopathic’. Most of these arrhythmias had a left bundle block morphology, indicating a right ventricular origin, so he turned his attention to this neglected cardiac structure. The cardiac pathologist Gaetano Thiene, transferred these observation into a major project for world Cardiology: the pathological study of the causes of sudden death in the young, that first documented a high prevalence of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), underlying this event.3–6 This entity, previously described by Fontaine and Marcus, remained rare before the Nava observations. He documented that the entity was not so rare and was characterized by generalized or localized forms with different clinical, electrocardiographic, and arrhythmic patterns. This achieved an improved and better definition than the original for the clinical, electrocardiographic, and familial condition. Nava did not speak English, read few medical articles, did not know anything about computers, protocols, or statistical analysis. He was however a profound inquirer, observer, and investigator, who had an obsessive attention for minor ECG waves, minor findings at echocardiography and angiography, and for clinical and family history. After this preliminary phase, he used to discuss with us junior doctors, the possible pathophysiology, and he always had the most brilliant interpretation and theory. The complete database of all patients was in his mind, and when he decided to write an article he told some of us: ‘this is the list of the patients that I have seen with this unusual pattern. This pattern indicates that the pathophysiology of this illness is linked to some right ventricular abnormality. Now you go in search of the medical reports, describe extensively the findings, look at previous references, and draw the conclusions that we have reached’. This way of conducting research was something different from Galilei’s rules and the positive results did not depend on a scientific method but only on the intuition of a superior intellectual skill. As mentioned before, the major limitation of Nava was language and his first scientific paper did not go abroad. He was so fortunate that one of the reviewers3 was Frank Marcus, who appreciated the paper so much, went on to give it an English style. Marcus was indeed one the most respected friends of Nava, even though any conversation during Marcus visits to Padova resulted in heated discussions (Figure 2). Figure 2 View largeDownload slide Frank Marcus, Andrea Nava, and Gaetano Thiene (front L to R) and Gianfranco Buja behind, discussing arrhythmogenic right ventricular dysplasia (ARVD) in Padova 1989. Figure 2 View largeDownload slide Frank Marcus, Andrea Nava, and Gaetano Thiene (front L to R) and Gianfranco Buja behind, discussing arrhythmogenic right ventricular dysplasia (ARVD) in Padova 1989. Nava and his group first described a series of chromosomal localization of the disease gene for ARVC/D,7 and the genes involved,8 but his most relevant scientific interest was the study of polymorphic exercise induced ventricular tachycardia, to which study he dedicated most of his last decade in Padova. He fully described the clinical picture, and first published the chromosome and the genes involved.9–11 He distinguished his observation from other authors because he attributed the occurrence of the arrhythmias not only to the ryanodine receptors but also to some structural abnormalities of the right ventricle. Nava was also interested in the ventricular arrhythmias originating from the right outflow tract (RVOT), and in 1990 in opposition to the global consensus, demonstrated in some patients the structural abnormalities underlying these worldwide defined idiopathic arrhythmias.12 His most important discovery happened, 30 years ago when he first described a new syndrome (as always by analysing a single case). He published an ECG tracing with ‘an early repolarization pattern in the precordial leads associated with aborted sudden death’, from a 42-year-old male cook who was successfully resuscitated and is still alive in 2018 (Figure 3). He first had an intuition that this ECG pattern could be linked to cases of sudden death and documented with VCG and endocavity recordings, that the ST elevation was induced by some delayed conduction at the RVOT level, and all was related to some structural abnormalities of the right ventricle. The paper was initially presented at a French conference,13 and a year later, more extensively with two additional cases including a necropsy study.14 The observation did not receive much attention, but after the description of similar cases by the Brugada brothers, this syndrome became the second most discussed cause of sudden death in the young, after LQTS. Andrea Nava had never been invited to a conference on the syndrome, that is nowadays cited in more than 4000 papers. The paternity and the pathophysiology of this discovery has been fiercely disputed during the decades that followed and only history will give its verdict.15 Figure 3 View largeDownload slide Bortolo Martini (L) Andrea Nava (R) in 1984 with the first patient affected by the syndrome of sudden death and ‘repolarization precoce dans le precordiales droits’. Figure 3 View largeDownload slide Bortolo Martini (L) Andrea Nava (R) in 1984 with the first patient affected by the syndrome of sudden death and ‘repolarization precoce dans le precordiales droits’. None of us have heard him mention even a minor complaint, as he never looked back to the past, but only searched for new ideas in the future. He did not have a peaceful life, and the premature death of his beloved wife and daughter probably forced him to seek refuge in science. He was a great scientist but mostly a good honest man. He most liked to join the GECA (group of families of young patients affected by sudden death) meetings, at their voluntary outpatient clinics, spend peaceful times in Murano with his pupils and friends, and walking around medieval Padova with his students, discussing new theories and the beauty of life (Figure 4). Figure 4 View largeDownload slide Front row (L) to (R): Gianfranco Buja MD, Bruno Canciani MD, Bortolo Martini MD, Professor Sergio Dalla Volta, Professor Andrea Nava, and Professor Mariano Ferrari, discussing new theories and the beauty of life. Figure 4 View largeDownload slide Front row (L) to (R): Gianfranco Buja MD, Bruno Canciani MD, Bortolo Martini MD, Professor Sergio Dalla Volta, Professor Andrea Nava, and Professor Mariano Ferrari, discussing new theories and the beauty of life. Conflict of interest: none declared. References References are available as supplementary material at European Heart Journal online. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: firstname.lastname@example.org. 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)
European Heart Journal – Oxford University Press
Published: Jun 7, 2018
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