title: Survival prospects of treatment naïve patients with Eisenmenger: a systematic review of the literature and report of own experience.
abstract: OBJECTIVE
  To investigate survival in patients with Eisenmenger syndrome based on a systematic review of the literature and reanalysis of data. We specifically tested the hypothesis that previous publications have been subject to immortal time bias, confounding survival analyses.
  
  
  METHODS
  A systematic review of the literature was performed to evaluate survival in treatment naïve patients with Eisenmenger syndrome and standardised mortality ratios were calculated. Furthermore, we used a contemporary cohort of 219 treatment naïve patients with Eisenmenger syndrome from the own institution as a comparison group.
  
  
  RESULTS
  Overall, 12 studies (published 1971-2013) were identified, including a total of 1131 patients. Only one study seemed to deal appropriately with immortal time bias in this setting. All other studies did not account for this effect, thus overestimating survival prospects of patients with Eisenmenger syndrome by up to 20 years. After accounting for this effect we found high standardised mortality ratios, a 10-year mortality rate approaching 30-40% and no evidence of superior survival prospects of current era patients compared with those seen in the 1970s, 1980s and 1990s. Only, a historical Eisenmenger-cohort from the 1950s/1960s had worse survival.
  
  
  CONCLUSIONS
  The current analysis challenges the traditional view of benign survival prospects of patients with Eisenmenger syndrome. In addition, survival prospects do not seem to have considerably improved over the last decades in untreated patients. These results support a proactive treatment strategy including a more aggressive approach trying to avoid the development of the condition.
authors.affiliation: Division of Adult Congenital and Valvular Heart Disease, Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany NIHR Cardiovascular and Respiratory Biomedical Research Unit, Adult Congenital Heart Centre and Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Gerhard-Paul
authors.initials: GP
authors.lastname: Diller
authors.affiliation: NIHR Cardiovascular and Respiratory Biomedical Research Unit, Adult Congenital Heart Centre and Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kempny
authors.affiliation: NIHR Cardiovascular and Respiratory Biomedical Research Unit, Adult Congenital Heart Centre and Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK.
authors.forename: Ryo
authors.initials: R
authors.lastname: Inuzuka
authors.affiliation: Division of Adult Congenital and Valvular Heart Disease, Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Radke
authors.affiliation: NIHR Cardiovascular and Respiratory Biomedical Research Unit, Adult Congenital Heart Centre and Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Stephen John
authors.initials: SJ
authors.lastname: Wort
authors.affiliation: Division of Adult Congenital and Valvular Heart Disease, Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Baumgartner
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gatzoulis
authors.affiliation: NIHR Cardiovascular and Respiratory Biomedical Research Unit, Adult Congenital Heart Centre and Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Konstantinos
authors.identifier: http://orcid.org/0000-0003-1300-0504
authors.initials: K
authors.lastname: Dimopoulos
mesh_terms: D015982:Bias; D004541:Eisenmenger Complex / Q000175:diagnosis / Q000401:mortality* / Q000503:physiopathology; D006801:Humans; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors
keywords: CONGENITAL HEART DISEASE