European Heart Journal (1992) 13, 1445-1446
Editorial Unexplained cardiac arrest. The need for a prospective registry S. G. PRIORI, M. BORGGREFE, A. J. CAMM, R. N. W. HAUER, H. KLEIN, K.-H.
KUCK, P. J. SCHWARTZ,
P. TOUBOUL AND H . J. J. WELLENS
Centro di Fisiologia Clinica e Ipertensione, Clinica Medica II, Policlinico di Milano, Via F. Sforza, 35,20122 Milano, Italy
The problem The most widely recognized cause of sudden cardiac death is ventricular fibrillation in the setting of ischaemic heart disease. A wide range of other less common causes are also associated with ventricular fibrillation, and include cardiomyopathies, valvular defects, myocarditis, amyloidosis, and the long QT syndrome. In spite of such a wide variety of identified causes for sudden cardiac death, in a number of patients no cardiac abnormality can be found. Among those patients who are resuscitated, extensive clinical evaluation often does not disclose any cardiac abnormality. These patients are often diagnosed as having had an episode of'idiopathic ventricular fibrillation'. This enigmatic diagnosis is a heavy burden for the patient who, although perceiving the severity of a cardiac arrest, is nonetheless left with the unsettling feeling that his physician has not understood what has happened, and does not have a prognosis or a therapy for him. For the physician, to handle a case of idiopathic ventricular fibrillation (VF) is not an easy task either. The unexplained death of a healthy young individual is an occurrence rare enough to prevent the opportunity of developing an expertise among physicians, yet it is frequent enough to have left many of us in the circumstance, rather unusual in modern medicine, of taking decisions without any support from an established 'consensus'. The situation At this time, the incidence of idiopathic VF is unknown and can only be inferred. It has been reported that no cause is found in 1% of survivors of out-of-hospital cardiac arrest1'1 and in 8% of patients dying suddenly12*31. If this estimate has to be taken as the most likelyfigurefor the incidence of idiopathic VF, one might conclude that several thousand individuals with a 'normal' heart experience cardiac arrest every year. Such an impressive number makes it impossible for the medical community to continue to almost ignore this clinical entity, and serious efforts should be made to spread awareness of this poorly recognized cause of death. Only recently have some Submitted and accepted Tor publication on 12 June 1992. Correspondence. Silvia G. Priori, MD, Centro di Fisiologia Clinica e Ipertensione, Clinica Medica II, Polidinico di Milano, Via F. Sforza, 35, 20122 Milano, Italy. 0I95-668X/92/111445 + 02 $08.00/0
groups'4"91 begun to collect data on reasonably large series. By reviewing the reports published during the last 35 years we have found 125 such cases; however, information is not always complete. According to our analysis, 68% of reported idiopathic VF occurred in men, the age range was 9 to 79 years, and the follow-up had a wide range (2 months to 14 years). Electrophysiological studies were performed in 95 patients: non-sustained ventricular tachycardia (VT) was induced in 9% of patients, sustained VT in 26%, and VF in 12%. Unfortunately, the distinction between monomorphic and polymorphic VT is usually not available. The therapies used so far in this group of patients are extremely varied, as they include class I antiarrhythmic drugs, amiodarone, beta-blockers, combinations of the above, and the implantable cardioverter defibrillator (ICD). The value of any therapy obviously depends on the risk of a recurrence, a critical point on which there is no firm figure yet. Recently, Viskin and Belhassen'41 reported a recurrence rate of 11 % in 45 patients. In our own review of 100 analysable patients, 12 died or had successful defibrillation by ICDs. As another nine patients experienced recurrent non-sustained VT or syncopal episodes, the overall number of patients with recurrences of major arrhythmic events was 21%. These data are in agreement with the observations of Siebels et a/.|8) and Wever el al.[9] who recently suggested that ICD implantation is warranted in idiopathic VF patients. This seems to contrast with the report from one centre161, in which 25 ICDs were implanted in idiopathic VF patients; during the follow-up there were 13 discharges, only two of which were appropriate; the remainder occurred during physical exercise. In our analysis, 42 patients received an ICD and six appropriate shocks were delivered. The questions We do not know whether these patients are at an early stage with underlying cardiac disease, which is clinically undetectable but capable of decreasing cardiac electrical stability; if so, such an alteration might become manifest after a relatively long period. We do not know the recurrence rate in this condition. The data available are inconsistent, but some show significant recurrence. We do not know whether any therapy is necessary or helpful in modifying prognosis. The reports on medical © 1992 The European Society of Cardiology
1446
Editorial
therapy and ICDs in this group of patients remain conflicting. The answer
An extensive international database of idiopathic VF is mandatory as it is the only way of achieving a large patient population. This will provide not only epidemiological data on the gross incidence and on the outcome, but also an evaluation of the effectiveness of therapy in a homogeneous population. An additional advantage of the establishment of an international database is the possibility of spreading awareness of this under-recognized condition among cardiologists. U-CARE (Unexplained Cardiac Arrest Registry of Europe) is the European project that will provide information on the incidence of idiopathic VF and will outline the profile of its victims. As a registry, U-CARE is open to anyone willing to participate by enrolling patients. U-CARE imposes no study protocol and the physician is free to make his or her own judgement, only being asked to report the decisions. One of the aims of the registry is to evaluate current therapeutic options selected by physicians to treat idiopathic VF. The major factor that has limited the understanding of idiopathic VF is the long follow-up of a large group of patients which is required to answer the most critical questions. Patients entering U-CARE will have a yearly follow-up for at least 10-15 years. Such a long-term project may seem difficult to realize; however, we are confident that a registry of a large number of individuals with a long follow-up is an achievable goal. Our confidence stems from the experience with a successful registry for another uncommon clinical cause of unexplained sudden cardiac death: the idiopathic long QT syndrome1101. When in 1979 a worldwide prospective registry was initiated by A. J. Moss, R. S. Crampton and P. J. Schwartz, understanding about the long QT syndrome was not much greater than current knowledge about idiopathic VF. In 1992, thanks to the collaboration of physicians around the world, after 12 years of enrollment, over 3000 individuals have been entered in the database, resulting in considerable progress in medical knowledge1"'. It was for these reasons that the Working Group on Arrhythmias of the European Society of Cardiology has decided to endorse U-CARE. With this editorial we are inviting European cardiologists to contribute to U-CARE. Contacts can be made with any member of the Steering Committee (see below for addresses). We will provide a detailed description of the entry criteria as well as enrollment forms for each patient, and every year we will send a short follow-up form. The Registry does not interfere with any management decisions concerning the enrolled patients, which continue to be the responsibility of their attending physicians. We believe that this approach will provide the information needed to understand the natural history as well as to identify the best management of patients with idiopathic VF, and will contribute to a spirit of cooperation among European cardiologists.
References [1] Myerburg RJ, Conde CA, Sung RJ el al. Clinical, electrophysiologic and hemodynamic profile of patients resuscitated from pre-hospital cardiac arrest Am J Med 1980; 68: 568-76. [2] Friedman M, Manwaring JH, Rosenmann RH, Danlon G, Ortega P, Grube SM. Instantaneous and sudden deaths. JAMA 1973; 225: 1319-28. [3] Raymand JR, van der Berg EK Jr, Knapp MJ. Non traumatic pre-hospital sudden death in young adults. Arch Int Med 1988; 148:303-8. [4] Viskin S, Belhassen B. Idiopathic ventricular fibrillation. Am Heart J 1990; 120:661-71. [5] Martini B, Nava A, Thiene G, Buja GF, Canciani B eI al. Ventricular fibrillation without apparent heart disease: description of six cases. Am Heart J 1989; 118: 1203-9. [6] Meissner RD, Mosteller RT, Steinman M, Akhtar D et al. Cardiac arrest in patients without significant structural heart disease: a multicenter experience with implantable cardioverter defibrillator therapy. J Am Coll Cardiol 1991; 17:92A. [7] Wellens HJJ, Lemery R, Smith JL, Brugada P el al. Sudden arrhythmic death without overt heart disease. Circulation 1992; 85(Suppl 1): 192-7. [8] Siebels J, Schneider MAE, Geiger M, Kuck H. Unexpected recurrences in survivors of cardiac arrest without organic heart disease. Eur Heart J 1991; 12(AbstrSuppl): 535. [9] Wever E, Hauer R, Oomen P, Bakker P, Robles de Medina E. Unfavorable outcome in patients with primary electrical disease who survived unexpected cardiac arrest. Eur Heart J 1991; 12 (Abstr Suppl): 534. [10] Moss AJ, Schwartz PJ, Crampton RS et al. The long QT syndrome: a prospective international study. Circulation 1985; 71: 17-21. [11] Moss AJ, Schwartz PJ, Crampton RS et al. The long QT syndrome. Prospective longitudinal study of 328 families. Circulation 1991; 84: 1136-44.
U-CARE steering committee members
Martin Borggrefe, MD, Medizinische Klinik und Poliklinik, Innere Medizin C, Westfalische WilhelmsUniversitat Munster, Albert Schweitzer Strasse 33, D-4400 Munster, Germany; John A. Camm, MD, Department of Cardiological Sciences, St George's Hospital, Medical School, Cranmer Terrace, London SW17 ORE, U.K; Richard N. W. Hauer, MD, Heart Lung Institute, University Hospital and State University of Utrecht, Utrecht, The Netherlands; Helmut Klein, MD, Medizinische Hochschule, Abteilung Kardiologie, Konstanty Gutschow Strasse 8, D-3000 Hannover, Germany; Karl-Heinz Kuck, MD, Universitatsspital Eppendorf, Kardiologische Abt., 2 Med. Klinik, Martinistrasse, 52, D-2000 Hamburg 20, Germany; Silvia G. Priori, MD, Centro di Fisiologia Clinica e Ipertensione, Clinica Medica II, Policlinico di Milano, Via F. Sforza, 35,20122 Milano, Italy; Peter J. Schwartz, MD, Centro di Fisiologia Clinica e Ipertensione, Clinica Medica II, Policlinico di Milano, Via F. Sforza, 35, 20122 Milano, Italy; Paul Touboul, MD, Hopital Cardiovasculaire et Pneumologique Louis Pradel, B.P. Lyon Montchat, F-69394 Lyon Cedex 03, France; Hein J. J. Wellens, MD, Department of Cardiology, Academisch Ziekenhuis Maastricht, Rijksuniversiteit Limburg, Postbus 5800, 6202 AZ Maastricht, The Netherlands. U-CARE is supported by a Research Grant of the European Society of Cardiology.
Editorial Unexplained cardiac arrest. The need for a prospective registry S. G. PRIORI, M. BORGGREFE, A. J. CAMM, R. N. W. HAUER, H. KLEIN, K.-H.
KUCK, P. J. SCHWARTZ,
P. TOUBOUL AND H . J. J. WELLENS
Centro di Fisiologia Clinica e Ipertensione, Clinica Medica II, Policlinico di Milano, Via F. Sforza, 35,20122 Milano, Italy
The problem The most widely recognized cause of sudden cardiac death is ventricular fibrillation in the setting of ischaemic heart disease. A wide range of other less common causes are also associated with ventricular fibrillation, and include cardiomyopathies, valvular defects, myocarditis, amyloidosis, and the long QT syndrome. In spite of such a wide variety of identified causes for sudden cardiac death, in a number of patients no cardiac abnormality can be found. Among those patients who are resuscitated, extensive clinical evaluation often does not disclose any cardiac abnormality. These patients are often diagnosed as having had an episode of'idiopathic ventricular fibrillation'. This enigmatic diagnosis is a heavy burden for the patient who, although perceiving the severity of a cardiac arrest, is nonetheless left with the unsettling feeling that his physician has not understood what has happened, and does not have a prognosis or a therapy for him. For the physician, to handle a case of idiopathic ventricular fibrillation (VF) is not an easy task either. The unexplained death of a healthy young individual is an occurrence rare enough to prevent the opportunity of developing an expertise among physicians, yet it is frequent enough to have left many of us in the circumstance, rather unusual in modern medicine, of taking decisions without any support from an established 'consensus'. The situation At this time, the incidence of idiopathic VF is unknown and can only be inferred. It has been reported that no cause is found in 1% of survivors of out-of-hospital cardiac arrest1'1 and in 8% of patients dying suddenly12*31. If this estimate has to be taken as the most likelyfigurefor the incidence of idiopathic VF, one might conclude that several thousand individuals with a 'normal' heart experience cardiac arrest every year. Such an impressive number makes it impossible for the medical community to continue to almost ignore this clinical entity, and serious efforts should be made to spread awareness of this poorly recognized cause of death. Only recently have some Submitted and accepted Tor publication on 12 June 1992. Correspondence. Silvia G. Priori, MD, Centro di Fisiologia Clinica e Ipertensione, Clinica Medica II, Polidinico di Milano, Via F. Sforza, 35, 20122 Milano, Italy. 0I95-668X/92/111445 + 02 $08.00/0
groups'4"91 begun to collect data on reasonably large series. By reviewing the reports published during the last 35 years we have found 125 such cases; however, information is not always complete. According to our analysis, 68% of reported idiopathic VF occurred in men, the age range was 9 to 79 years, and the follow-up had a wide range (2 months to 14 years). Electrophysiological studies were performed in 95 patients: non-sustained ventricular tachycardia (VT) was induced in 9% of patients, sustained VT in 26%, and VF in 12%. Unfortunately, the distinction between monomorphic and polymorphic VT is usually not available. The therapies used so far in this group of patients are extremely varied, as they include class I antiarrhythmic drugs, amiodarone, beta-blockers, combinations of the above, and the implantable cardioverter defibrillator (ICD). The value of any therapy obviously depends on the risk of a recurrence, a critical point on which there is no firm figure yet. Recently, Viskin and Belhassen'41 reported a recurrence rate of 11 % in 45 patients. In our own review of 100 analysable patients, 12 died or had successful defibrillation by ICDs. As another nine patients experienced recurrent non-sustained VT or syncopal episodes, the overall number of patients with recurrences of major arrhythmic events was 21%. These data are in agreement with the observations of Siebels et a/.|8) and Wever el al.[9] who recently suggested that ICD implantation is warranted in idiopathic VF patients. This seems to contrast with the report from one centre161, in which 25 ICDs were implanted in idiopathic VF patients; during the follow-up there were 13 discharges, only two of which were appropriate; the remainder occurred during physical exercise. In our analysis, 42 patients received an ICD and six appropriate shocks were delivered. The questions We do not know whether these patients are at an early stage with underlying cardiac disease, which is clinically undetectable but capable of decreasing cardiac electrical stability; if so, such an alteration might become manifest after a relatively long period. We do not know the recurrence rate in this condition. The data available are inconsistent, but some show significant recurrence. We do not know whether any therapy is necessary or helpful in modifying prognosis. The reports on medical © 1992 The European Society of Cardiology
1446
Editorial
therapy and ICDs in this group of patients remain conflicting. The answer
An extensive international database of idiopathic VF is mandatory as it is the only way of achieving a large patient population. This will provide not only epidemiological data on the gross incidence and on the outcome, but also an evaluation of the effectiveness of therapy in a homogeneous population. An additional advantage of the establishment of an international database is the possibility of spreading awareness of this under-recognized condition among cardiologists. U-CARE (Unexplained Cardiac Arrest Registry of Europe) is the European project that will provide information on the incidence of idiopathic VF and will outline the profile of its victims. As a registry, U-CARE is open to anyone willing to participate by enrolling patients. U-CARE imposes no study protocol and the physician is free to make his or her own judgement, only being asked to report the decisions. One of the aims of the registry is to evaluate current therapeutic options selected by physicians to treat idiopathic VF. The major factor that has limited the understanding of idiopathic VF is the long follow-up of a large group of patients which is required to answer the most critical questions. Patients entering U-CARE will have a yearly follow-up for at least 10-15 years. Such a long-term project may seem difficult to realize; however, we are confident that a registry of a large number of individuals with a long follow-up is an achievable goal. Our confidence stems from the experience with a successful registry for another uncommon clinical cause of unexplained sudden cardiac death: the idiopathic long QT syndrome1101. When in 1979 a worldwide prospective registry was initiated by A. J. Moss, R. S. Crampton and P. J. Schwartz, understanding about the long QT syndrome was not much greater than current knowledge about idiopathic VF. In 1992, thanks to the collaboration of physicians around the world, after 12 years of enrollment, over 3000 individuals have been entered in the database, resulting in considerable progress in medical knowledge1"'. It was for these reasons that the Working Group on Arrhythmias of the European Society of Cardiology has decided to endorse U-CARE. With this editorial we are inviting European cardiologists to contribute to U-CARE. Contacts can be made with any member of the Steering Committee (see below for addresses). We will provide a detailed description of the entry criteria as well as enrollment forms for each patient, and every year we will send a short follow-up form. The Registry does not interfere with any management decisions concerning the enrolled patients, which continue to be the responsibility of their attending physicians. We believe that this approach will provide the information needed to understand the natural history as well as to identify the best management of patients with idiopathic VF, and will contribute to a spirit of cooperation among European cardiologists.
References [1] Myerburg RJ, Conde CA, Sung RJ el al. Clinical, electrophysiologic and hemodynamic profile of patients resuscitated from pre-hospital cardiac arrest Am J Med 1980; 68: 568-76. [2] Friedman M, Manwaring JH, Rosenmann RH, Danlon G, Ortega P, Grube SM. Instantaneous and sudden deaths. JAMA 1973; 225: 1319-28. [3] Raymand JR, van der Berg EK Jr, Knapp MJ. Non traumatic pre-hospital sudden death in young adults. Arch Int Med 1988; 148:303-8. [4] Viskin S, Belhassen B. Idiopathic ventricular fibrillation. Am Heart J 1990; 120:661-71. [5] Martini B, Nava A, Thiene G, Buja GF, Canciani B eI al. Ventricular fibrillation without apparent heart disease: description of six cases. Am Heart J 1989; 118: 1203-9. [6] Meissner RD, Mosteller RT, Steinman M, Akhtar D et al. Cardiac arrest in patients without significant structural heart disease: a multicenter experience with implantable cardioverter defibrillator therapy. J Am Coll Cardiol 1991; 17:92A. [7] Wellens HJJ, Lemery R, Smith JL, Brugada P el al. Sudden arrhythmic death without overt heart disease. Circulation 1992; 85(Suppl 1): 192-7. [8] Siebels J, Schneider MAE, Geiger M, Kuck H. Unexpected recurrences in survivors of cardiac arrest without organic heart disease. Eur Heart J 1991; 12(AbstrSuppl): 535. [9] Wever E, Hauer R, Oomen P, Bakker P, Robles de Medina E. Unfavorable outcome in patients with primary electrical disease who survived unexpected cardiac arrest. Eur Heart J 1991; 12 (Abstr Suppl): 534. [10] Moss AJ, Schwartz PJ, Crampton RS et al. The long QT syndrome: a prospective international study. Circulation 1985; 71: 17-21. [11] Moss AJ, Schwartz PJ, Crampton RS et al. The long QT syndrome. Prospective longitudinal study of 328 families. Circulation 1991; 84: 1136-44.
U-CARE steering committee members
Martin Borggrefe, MD, Medizinische Klinik und Poliklinik, Innere Medizin C, Westfalische WilhelmsUniversitat Munster, Albert Schweitzer Strasse 33, D-4400 Munster, Germany; John A. Camm, MD, Department of Cardiological Sciences, St George's Hospital, Medical School, Cranmer Terrace, London SW17 ORE, U.K; Richard N. W. Hauer, MD, Heart Lung Institute, University Hospital and State University of Utrecht, Utrecht, The Netherlands; Helmut Klein, MD, Medizinische Hochschule, Abteilung Kardiologie, Konstanty Gutschow Strasse 8, D-3000 Hannover, Germany; Karl-Heinz Kuck, MD, Universitatsspital Eppendorf, Kardiologische Abt., 2 Med. Klinik, Martinistrasse, 52, D-2000 Hamburg 20, Germany; Silvia G. Priori, MD, Centro di Fisiologia Clinica e Ipertensione, Clinica Medica II, Policlinico di Milano, Via F. Sforza, 35,20122 Milano, Italy; Peter J. Schwartz, MD, Centro di Fisiologia Clinica e Ipertensione, Clinica Medica II, Policlinico di Milano, Via F. Sforza, 35, 20122 Milano, Italy; Paul Touboul, MD, Hopital Cardiovasculaire et Pneumologique Louis Pradel, B.P. Lyon Montchat, F-69394 Lyon Cedex 03, France; Hein J. J. Wellens, MD, Department of Cardiology, Academisch Ziekenhuis Maastricht, Rijksuniversiteit Limburg, Postbus 5800, 6202 AZ Maastricht, The Netherlands. U-CARE is supported by a Research Grant of the European Society of Cardiology.
