https://orcid.org/0000-0001-5788-575X
1. Progress in cardiovascular research
Every year, based on basic and clinical research findings, new scientific statements or updates to clinical practice guidelines are published. Wide dissemination and implementation of them lead to improvements in our understanding of diseases and disorders and in clinical care. Progress is also observed in cardiovascular research concerning rare cardiovascular diseases and disorders (RCDD). However, due to the infrequency of these diseases and disorders and the relative paucity of reliable basic research and clinical evidence, collaboration between clinicians and scientists from many centres and various scientific backgrounds is crucial. Such co-operation should also aim to gather evidence for better recognition of the pathogenesis of RCDD. Getting to know the molecular mechanisms of RCDD may result in introduction of novel disease modifying therapies in the field of RCDD.
Clinical classification of RCDD aids in the visualization and enhancing insight in common pathways implicated in the spectrum of RCDD and enables a systematic approach, including differential diagnosis, to these diseases and disorders. Such a classification was first published in the Journal of Rare Cardiovascular Diseases (JRCD) in 2013 and is available for free at www.jrcd.eu.1–3 However, since this publication, progress has been made in both the understanding of pathogenesis and management of RCDD.4–9 Furthermore, we have received many valuable comments from scientists and clinical practitioners, necessitating an updated version of RCDD classification.
2. New classification of RCDD
We have performed a search of the Orphanet rare diseases inventory, PubMed, and Scopus databases, as announced previously.10,11 Additionally, we have analysed the references of found papers. As a general guide for selection of rare diseases and disorders, we used a prevalence of 5 per 10 000 in the general population or less. Similar to the first version of the document, we included classes and groups of diseases and disorders in the updated RCDD classification (this article is also available for free at JRCD website).12 However, we decided that wider dissemination and a more detailed peer review of our approach would be achieved by publication of consecutive updated classes as separate documents. Thus, new RCDD subgroups and major diseases and disorders along with RCDD codes, the International Classification of Diseases and Related Health Problems 10th Revision (ICD-10) codes,13 and ORPHA numbers will be presented in updated classes of RCDD classification (Table 1). We have previously discussed the major changes introduced in the updated RCDD classification.12 However, upon re-evaluation, we have decided to change the ‘cardiac arrhythmogenic disorders and arrhythmias’ class into the ‘rare arrhythmogenic and conduction disorders, and rare arrhythmias’ (RACDRA) class.14
New clinical classification of RCDD
| Class | Group | Subgroup | Diseases and disorders | RCDD sample coding | ICD-10 code | ORPHA number |
|---|---|---|---|---|---|---|
| I—Rare diseases of systemic circulation | 1–7 | A … other | 1 … other | I-(1A)-(1) | Seea | Seeb |
| II—Rare diseases of pulmonary circulation | 1–3 | A … other | 1 … other | II-(1A)-(1) | Seea | Seeb |
| III—Rare diseases of the heart (cardiomyopathies) | 1–5 | A … other | 1 … other | III-(1A)-(1) | Seea | Seeb |
| IV—Rare congenital cardiovascular diseases | 1–6 | A … other | 1 … other | IV-(1A)-(1) | Seea | Seeb |
| V—Cardiac tumours and cardiovascular diseases in malignancy | 1–4 | A … other | 1 … other | V-(1A)-(1) | Seea | Seeb |
| VI—Rare arrhythmogenic and conduction disorders, and rare arrhythmias | 1–2 | A–C and other | 1–9 and other | VI-(1A)-(1) | Seea | Seeb |
| VII—RCDD in pregnancy | VII-(class)-(1A)-(1) | Seea | Seeb | |||
| VIII—Unclassified RCDD | VIII | Seea | Seeb |
| Class | Group | Subgroup | Diseases and disorders | RCDD sample coding | ICD-10 code | ORPHA number |
|---|---|---|---|---|---|---|
| I—Rare diseases of systemic circulation | 1–7 | A … other | 1 … other | I-(1A)-(1) | Seea | Seeb |
| II—Rare diseases of pulmonary circulation | 1–3 | A … other | 1 … other | II-(1A)-(1) | Seea | Seeb |
| III—Rare diseases of the heart (cardiomyopathies) | 1–5 | A … other | 1 … other | III-(1A)-(1) | Seea | Seeb |
| IV—Rare congenital cardiovascular diseases | 1–6 | A … other | 1 … other | IV-(1A)-(1) | Seea | Seeb |
| V—Cardiac tumours and cardiovascular diseases in malignancy | 1–4 | A … other | 1 … other | V-(1A)-(1) | Seea | Seeb |
| VI—Rare arrhythmogenic and conduction disorders, and rare arrhythmias | 1–2 | A–C and other | 1–9 and other | VI-(1A)-(1) | Seea | Seeb |
| VII—RCDD in pregnancy | VII-(class)-(1A)-(1) | Seea | Seeb | |||
| VIII—Unclassified RCDD | VIII | Seea | Seeb |
A sample code from ICD-10, bORPHA numbers from Orphanet rare diseases inventory. Some RCDD are not referenced in ICD-10 and/or in Orphanet rare diseases inventory.
RCDD, rare cardiovascular diseases and disorders; ICD-10, International Classification of Diseases and Related Health Problems 10th Revision.
New clinical classification of RCDD
| Class | Group | Subgroup | Diseases and disorders | RCDD sample coding | ICD-10 code | ORPHA number |
|---|---|---|---|---|---|---|
| I—Rare diseases of systemic circulation | 1–7 | A … other | 1 … other | I-(1A)-(1) | Seea | Seeb |
| II—Rare diseases of pulmonary circulation | 1–3 | A … other | 1 … other | II-(1A)-(1) | Seea | Seeb |
| III—Rare diseases of the heart (cardiomyopathies) | 1–5 | A … other | 1 … other | III-(1A)-(1) | Seea | Seeb |
| IV—Rare congenital cardiovascular diseases | 1–6 | A … other | 1 … other | IV-(1A)-(1) | Seea | Seeb |
| V—Cardiac tumours and cardiovascular diseases in malignancy | 1–4 | A … other | 1 … other | V-(1A)-(1) | Seea | Seeb |
| VI—Rare arrhythmogenic and conduction disorders, and rare arrhythmias | 1–2 | A–C and other | 1–9 and other | VI-(1A)-(1) | Seea | Seeb |
| VII—RCDD in pregnancy | VII-(class)-(1A)-(1) | Seea | Seeb | |||
| VIII—Unclassified RCDD | VIII | Seea | Seeb |
| Class | Group | Subgroup | Diseases and disorders | RCDD sample coding | ICD-10 code | ORPHA number |
|---|---|---|---|---|---|---|
| I—Rare diseases of systemic circulation | 1–7 | A … other | 1 … other | I-(1A)-(1) | Seea | Seeb |
| II—Rare diseases of pulmonary circulation | 1–3 | A … other | 1 … other | II-(1A)-(1) | Seea | Seeb |
| III—Rare diseases of the heart (cardiomyopathies) | 1–5 | A … other | 1 … other | III-(1A)-(1) | Seea | Seeb |
| IV—Rare congenital cardiovascular diseases | 1–6 | A … other | 1 … other | IV-(1A)-(1) | Seea | Seeb |
| V—Cardiac tumours and cardiovascular diseases in malignancy | 1–4 | A … other | 1 … other | V-(1A)-(1) | Seea | Seeb |
| VI—Rare arrhythmogenic and conduction disorders, and rare arrhythmias | 1–2 | A–C and other | 1–9 and other | VI-(1A)-(1) | Seea | Seeb |
| VII—RCDD in pregnancy | VII-(class)-(1A)-(1) | Seea | Seeb | |||
| VIII—Unclassified RCDD | VIII | Seea | Seeb |
A sample code from ICD-10, bORPHA numbers from Orphanet rare diseases inventory. Some RCDD are not referenced in ICD-10 and/or in Orphanet rare diseases inventory.
RCDD, rare cardiovascular diseases and disorders; ICD-10, International Classification of Diseases and Related Health Problems 10th Revision.
Classes in the new clinical classification of RCDD include (Table 1):
Class I—Rare diseases of systemic circulation
Class II—Rare diseases of pulmonary circulation
Class III—Rare diseases of the heart (cardiomyopathies)
Class IV—Rare congenital cardiovascular diseases
Class V—Cardiac tumours and cardiovascular diseases in malignancy
Class VI—Rare arrhythmogenic and conduction disorders, and rare arrhythmias
Class VII—RCDD in pregnancy
Class VIII—Unclassified RCDD
3. Further perspectives
We hope that clinical classification of RCDD will be of interest for Cardiovascular Research readers. It may inspire some of them to validate their research findings in the field of RCDD.
There are several basic and translational research issues (among others) which seem to be of great importance for RCDD and where in-depth studies and potential collaboration between basic scientists and clinicians may be of major value:
Further assessment of common RCDD mechanisms.
Search for potential novel circulating blood-based biomarkers for cardiovascular risk stratification and/or looking for rational for validation of existing biomarkers in new clinical scenarios, including RCDD.15
Discovery of novel therapies targeting RCDD pathophysiological pathways (taking into account also genotype and/or molecular mechanism-specific therapies) and testing them in a translational way, including ex vivo and animal models.
Finding rational for potential drug repositioning, which at a very low cost provides incremental innovation.6
We understand that our efforts have potential limitations. Thus, we encourage clinicians and scientists, including those in basic and translational research, to co-operate with us and to provide comments and suggestions in order to refine the RCDD classification system. Working together, we would add to the body of knowledge in cardiovascular research and improve clinical practice in the field of RCDD.
Conflict of interest: none declared.
References
List of Rare Diseases and Synonyms: Listed in Alphabetical Order. Orphanet Report Series, Rare Diseases collection,
International Statistical Classification of Diseases and Related Health Problems 10th Revision. http://apps.who.int/classifications/icd10/browse/2016/en (8 October 2017, date last accessed).
Authors
Biography: Piotr Podolec, MD, PhD, is Director of the Institute of Cardiology, Jagiellonian University Medical College, Head of the Department of Cardiac and Vascular Diseases, Institute of Cardiology, Jagiellonian University Medical College, and Editor-in-Chief of the Journal of Rare Cardiovascular Diseases. His initial research interests focused on assessment of the usefulness of homogeneic heart valves in the treatment of heart defects, introduction and assessment of new diagnostic methods such as echocardiography, ultrasound, spiroergometry, and scintigraphy in cardiology. In the following years, he initiated various research projects and became a principle researcher in numerous fields including haemodynamics, pathophysiology of congenital heart defects, pulmonary hypertension, atherosclerosis, prevention of cardiovascular disease, sports cardiology, and rare cardiovascular diseases. Prof Piotr Podolec was the creator and chairman of the working group of the Polish Forum for the Prevention of Cardiovascular Diseases. Since 2012, he has been director of the Coordination Team for Rare Cardiological Diseases at the John Paul II Hospital in Kraków. Moreover, he was editor and co-author of pioneering textbook relating to rare cardiovascular diseases, entitled ‘Rare cardiovascular diseases: from classification to clinical examples’. He was a member of the General Board of the Polish Cardiac Society (2004–11—three consecutive terms) and founding member of the following Polish Cardiac Society Sections: Heart Valve Defects, Congenital Heart Defects in Juvenile and Adult Patients, Prevention and Epidemiology, Pulmonary Circulation, Nursing and Medical Technology, Sports Cardiology, and Nuclear Cardiology. He was also a member of the Board of the European Association of Echocardiography (2005–07). He has received numerous awards and distinctions, such as from the Ministry of Science and Higher Education and the Polish Cardiac Society. He is an honorary member of the Polish Cardiac Society. In addition, he has received the following medals and distinctions: Plus Ratio Quam Vis, Honoris Gratia from the Mayor of Kraków, 30th anniversary of the Institute of Cardiology, Medal of the 50th anniversary of the Polish Cardiac Society, Honorary Medal of the Polish Society of Internal Medicine, Golden Cross of Merit, and the Knight’s Cross of the Order of the Rebirth of Poland.
Biography: Paweł T. Matusik, MD, PhD, FEHRA, works at the Institute of Cardiology, Jagiellonian University Medical College and at the Department of Electrocardiology, the John Paul II Hospital in Kraków. Additionally, he is an editor of the Journal of Rare Cardiovascular Diseases. His research interests primarily include electrocardiology, mechanisms and biomarkers of cardiovascular diseases (especially cardiac arrhythmias), translational medicine with applications in cardiovascular medicine, geriatric cardiology and rare cardiovascular diseases and disorders. Recently, he received a Polish Cardiac Society 2018 Scientific Grant in co-operation with Berlin-Chemie/Menarini for a project entitled: ‘Head-to-head comparison of biomarkers for risk stratification of adverse cardiovascular events in heart failure with reduced ejection fraction’. He received his MD (2011) and PhD (2015) from the Faculty of Medicine, Jagiellonian University Medical College in Kraków. He gained valuable clinical and research experience during his visits and trainings at the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK, at the Cardiovascular Division in the Department of Medicine at Washington University School of Medicine in Saint Louis, Missouri, USA, and at Barnes-Jewish Hospital, Saint Louis, Missouri, USA. He has received various awards and distinctions, including 1st place in the best student of the Republic of Poland contest (the Student Nobel Prize 2011), a distinction of honour and medal from the Polish Academy of Sciences, Faculty of Medical Sciences (the Doctor Wacław Mayzl Medical Laurel), and the Ministry of Science and Higher Education scholarship for outstanding achievements. Moreover, he has obtained scholarships from the Foundation for Polish Science.
