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Original research
Sex differences in implantable cardiac defibrillator therapy according to arrhythmia detection times
  1. Maurizio Gasparini1,
  2. Axel Kloppe2,
  3. Maurizio Lunati3,
  4. Niraj Varma4,
  5. Jose B Martinez-Ferrer5,
  6. Ahmed Hersi6,
  7. Marcin Gulaj7,
  8. Maurits C E F Wijffels8,
  9. Angel Arenal9,
  10. Lorenza Mangoni di Santo Stefano10,
  11. Alessandro Proclemer11
  1. 1 Electrophysiology and Pacing Unit, Humanitas Clinical and Research Hospital, IRCCS, Rozzano, Italy
  2. 2 Cardiology and Angiology, Bergmannsheil, Ruhr University, Bochum, Germany
  3. 3 Cardiology Department, Niguarda Ca' Granda Hospital, Milano, Italy
  4. 4 Cardiology Department, University of Pennsylvania, Cleveland, Ohio, USA
  5. 5 Department of Cardiology, Hospital Universitario de Araba, Vitoria, Alava, Spain
  6. 6 College of Medicine, King Saud University, Riyadh, Riyadh Province, Saudi Arabia
  7. 7 Department of Cardiology, MSWiA Hospital, Bialystok, Poland
  8. 8 Cardiology, St Antonius Hospital, Nieuwegein, Netherlands
  9. 9 Cardiology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
  10. 10 Study and Scientific Solutions, Medtronic Core Clinical Solutions, Rome, Italy
  11. 11 Department of Cardiology, Azienda Ospedaliera Universitaria S Maria della Misericordia, Udine, Friuli-Venezia Giulia, Italy
  1. Correspondence to Dr Maurizio Gasparini, Electrophysiology and Pacing Unit, Humanitas Clinical and Research Hospital, 20089 Rozzano, Italy; maurizio.gasparini{at}


Objective In implantable cardiac defibrillators (ICDs), long-detection times safely reduce unnecessary and inappropriate therapies. We aimed to evaluate ICD treatment of ventricular arrhythmias in women, compared with men, also taking into account ICD detection.

Methods The Advance III trial randomised patients implanted with an ICD for primary or secondary prevention in two arms—long and nominal ventricular arrhythmias detection times before therapy delivering (number of intervals needed to detect (NID) 30/40 and 18/24, respectively). The main endpoint of this post hoc analysis was the incidence of ICD therapies evaluated through Kaplan-Meier method and univariate Cox regression models.

Results Overall, 1902 patients (304 women, 65±11 years) were randomised. Women showed a lower risk of ICD therapy (HR 0.63, 95% CI 0.43 to 0.93, p=0.022); this difference was observed only in the long-detection arm (HR 0.37, p=0.013) and not in the short detection arm (HR 0.82, p=0.414). No significant sex differences were observed concerning inappropriate therapies and mortality rate. Long-detection settings significantly reduced overall ICD therapies and appropriate ICD therapies, both in women (overall HR 0.31, p=0.007; appropriate HR 0.33, p=0.033) and in men (overall HR 0.69, p=0.006; appropriate HR 0.73, p=0.048).

Conclusions In patients with ICDs, the strategy of setting a long-detection time to treat ventricular arrhythmias (NID 30/40) reduces overall delivered therapies, both in women and men, when compared with nominal setting (NID 18/24). The reduction was significantly higher in women. Overall, women were less likely to experience ICD therapies than men; this result was only observed in the long-detection arm.

Clinical trial registration NCT00617175.

  • implanted cardiac defibrillators
  • ventricular fibrillation
  • ventricular tachycardia
  • heart failure with reduced ejection fraction

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  • Contributors Eleven authors have made substantial contributions to this research either for the conception and design of the analysis or acquisition of data, or analysis and interpretation of data or drafting the article or revising it critically for important intellectual content.

  • Funding The study was sponsored by Medtronic plc. The principal investigator of the trial had the ability to directly access the clinical trial derived datasets and to query any aspect of the data either directly or through an independent analysis.

  • Competing interests AA reported research grants from Medtronic, Biosense Webster and St. Jude Medical. AK reported consulting fees from Medtronic and St. Jude Medical, as well as lecture fees from Medtronic, Boston Scientific and St. Jude Medical. ML reported consulting fees from Medtronic. JBM-F reported consulting fees from Medtronic and St. Jude Medical. LMdSS is an employee of Medtronic. AP reported consulting fees from Medtronic. NV reported consulting fees from Medtronic, Boston Scientific, Biotronik and Sorin Group. All other authors report no disclosures.

  • Patient consent for publication Obtained.

  • Ethics approval The study was approved by the ethics committee of all centres and was conducted in compliance with the Declaration of Helsinki.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request.