Assessment of Risk Factors for Appropriate ICD (Implantable Cardioverter-defibrillator) Intervention in Patients With Ischemic Cardiomyopathy
Condition: ICD; Cardiomyopathy Ischemic; Primary Prevention
MeSH terms: Cardiomyopathies; Ischemia
Study type: Interventional

Summary: 
      Design: PARCADIA is a prospective non-randomized non-interventional multi-center clinical
      investigation in Europe. Patients with depressed LV (left ventricular) function assessed on
      local standards, of ischemic origin and on chronic optimal medical therapy will be selected
      according to inclusion and exclusion criteria, implanted with an ICD after executing baseline
      investigations and prospectively followed up for minimal 24 months and until the termination
      of the clinical investigation.

      General objective: analysis of baseline risk factors to identify predictors for appropriate
      ICD intervention in patients with ischemic cardiomyopathy receiving an ICD for primary
      prevention (MADIT II population).

      Hypothesis: The primary alternative hypothesis states that the mean relative infarct
      transmurality (RIT) is different in patients with (RITshock or ATP (Anti Tachy Pacing)) and
      without (RITno shock or ATP )appropriate ICD intervention, i.e. shock or ATP.

        -  Null hypothesis (H0): RITshock or ATP = RITno shock or ATP

        -  Alternative hypothesis (Ha): RITshock or ATP ≠ RITno shock or ATP

      Sample size: 200 patients.

      Follow-up: Enrolment visit, pre implant screening, ICD implantation, pre-hospital discharge
      visit, and follow-up (FUP) visits at 2, 6, 12, 18, 24 months including home monitoring.
      Additional routine FUP every 6 months until study termination after last enrolled patient has
      completed 2 years FUP.
    

Detailed description: 
      Rationale: Implantation of an ICD as primary prevention therapy is indicated according to the
      current guidelines based on the low LVEF (Left Ventricular Ejection Fraction) as it was shown
      to significantly reduce mortality. Although of proven efficacy, ICD therapy is associated
      with survival benefit in only a small fraction of patients. It is estimated that 18 patients
      would have to receive an ICD to save one life, resulting in a huge burden on national health
      systems. Moreover, only about one quarter of all guideline eligible primary prevention ICD
      patients receive appropriate shocks. The above considerations support the need for an
      effective risk-stratification method to identify patients that benefit most (or least) from
      this therapy. Evaluation of ventricular anatomy and function by imaging techniques has become
      more important since this provides information on the substrate (myocardial scar) and trigger
      of life-threatening ventricular arrhythmias. Besides accurate estimation of left and right
      ventricular volumes and functions, Late Gadolinium Enhanced Cardiac Magnetic Resonance
      (LGE-CMR) imaging has a very high sensitivity to detect myocardial scar. Quantification of
      scar characteristics by cardiac MRI might be useful for the prediction of future arrhythmic
      events in patients with ischemic cardiomyopathy. However evidence is conflicting and
      published papers are hampered by limited patient numbers and can only be regarded in the
      light of generating hypothesis. The PARCADIA clinical investigation will explore the
      potential of cardiac MRI as a predictor for appropriate ICD intervention in a multicenter
      setting.

      PARCADIA is a prospective non-randomized non-interventional multi-center clinical
      investigation in Europe. Patients with depressed LV (Left Ventricular) function assessed on
      local standards, of ischemic (at least 40 days post-MI (myocardial infarction) or 3 months
      post revascularization) origin and on chronic optimal medical therapy will be selected
      according to inclusion and exclusion criteria, implanted with an ICD after executing baseline
      investigations and prospectively followed up for minimal 24 months and until the termination
      of the clinical investigation

      General objective: analysis of baseline risk factors to identify predictors for appropriate
      ICD intervention in patients with ischemic cardiomyopathy receiving an ICD for primary
      prevention (MADIT II population).

      The primary objective of the clinical investigation is to determine whether there is a
      relationship between appropriate ICD intervention (shock or ATP) and the Relative Infarct
      Transmurality (RIT) obtained from Late Gadolinium Enhanced Cardiac Magnetic Resonance
      (LGE-CMR) imaging in patients with ischemic cardiomyopathy, receiving an ICD for primary
      prevention.

      Methodology: Screening: (within 6 months before enrolment) patients with LV depressed
      function due to Ischemic Cardiomyopathy with an indication for primary prevention ICD
      implantation according to ESC (European Society of Cardiology) guidelines or local standards
      will be screened within 6 months before enrolment.

      pre implant diagnostics: within 3 months after enrolment LGE-CMR imaging, 24h holter, 12-lead
      ECG, will be performed and biochemical markers will be obtained.

      ICD implantation: Implantation of a Lumax 540 single/dual chamber ICD or successor withiin 3
      months after enrolment. The ICD will be programmed according to protocol.

      Pre-hospital discharge an ICD interrogation wil be performed. Follow-up (FUP) visits at: 2,
      6, 12, 18, 24 months with inclusion of standard 12-lead ECG, ICD check-up and cardiologist
      visit in the outpatient clinic. Additional routine FUP every 6 months until study termination
      after last enrolled patient has completed 2 years FUP.
    

Intervention name(s): ICD implantation
Intervention type(s): Device
Intervention description(s): implantation of the Lumax 540 single/dual chamber ICD or successor
Other intervention name(s): Lumax 540 single/dual chamber ICD or successor
Intervention model: Single Group Assignment
Intervention model description: The study model is single group. At the analysis the patients will be divided in two groups bij outcome of ICD therapy/no ICD therapy.
The endpoints related to the primary hypothesis are appropriate ICD intervention (shock or ATP) and Relative Infarct Transmurality (RIT = transmural infarct mass / total infarct mass) obtained from LGE-CMR. ICD interventions will be labeled appropriate or non-appropriate by an independent endpoint committee.
RITshock or ATP: RIT expectation value in patients with ≥1 appropriate shock or ATP therapy until the 24mo follow-up
RIT no shock or ATP: RIT expectation value in patients without any appropriate shock or ATP therapy until the 24mo follow-up
Masking: None (Open Label)
Primary purpose: Prevention