Effect of implanted device-based impedance monitoring with - PowerPoint PPT Presentation

Effect of implanted device-based impedance monitoring with telemedicine alerts on mortality and morbidity in heart failure (OptiLink HF) Michael Böhm, Helmut Drexler†, Hanno Oswald, Karin Rybak, Ralph Bosch, Christian Butter, Gunnar Klein, Bart Gerritse, Johannes Brachmann for the OptiLink HF Study Investigators † In memoriam

In Memoriam Helmut Drexler

Participating German Investigators (65 active Centres) H. Oswald (Medizinische Hochschule Hannover); J. Brachmann (Klinikum Coburg); K. Rybak (Kardiologische Praxis Dessau); C. Israel (Evangelisches Krankenhaus Bielefeld); S. Käab (Klinikum München-Grosshadern); Chr. Butter (Herzzentrum Bernau); D. Bimmel (St. Marien Hospital Bonn); B. Huegl (Marienhaus Neuwied); Th. Heitzer (Klinikum Dortmund); Y. Seivani (Klinikum Bad Segeberg); R. Bosch (Cardio Centrum Ludwigsburg); D. Puplat (Asklepios Klinik Schwalmstadt); M. Ringwald (Kardiologische Praxis Bruchsal); D. Bänsch (Universitätsklinikum Rostock); M. Böhm (Universitätsklinikum Homburg-Saar); K. Gutleben (Herz- und Diabetes Zentrum Bad Oeynhausen); K. Seidl (Klinikum Ingolstadt); U. Tebbe (Klinikum Lippe-Detmold); K. Mischke (Universitätsklinikum Aachen); Chr. Perings (St. Marien Hospital Lünen); M. Haude (Lukaskrankenhaus Neuss); A. Knapp (Kardiologische Praxis Parchim); B. Zrenner (Krankenhaus Landshut-Achdorf); V. Schächinger (Klinikum Fulda); J. Schmitt (Universitätsklinikum Giessen); S. Willems (Universitätsklinikum Hamburg-Eppendorf); Chr. Stellbrink (Städtisches Klinikum Bielefeld); M. Hinterseer (Klinik Füssen); R. Erbel (Universitätsklinikum Essen); E. Hoffmann (Städtisches Klinikum München- Bogenhausen); C. Felder (Kardiologische Praxis Köln); U. Sechtem (Robert-Bosch Krankenhaus Stuttgart); H. Killat (Kardiologische Praxis Hassloch); M. Sotiriou (Kardiologische Praxis Wiesbaden); J. Schwab (Universitätsklinikum Bonn); S. Kuster (DRK- Krankenhaus Ratzeburg); F. Nagel (Kardiologische Praxis Augsburg); U. Fossmeyer (Kardiologische Praxis Traben-Trabach); S. Ruppert (Kardiologische Praxis Nürtingen); W. Raut (Krankenhaus Buchholz); D. Jäger (Klinikum Friedrichshafen); G. Mentz (Kardiologische Praxis Mainz); J. Schlichting (Kardiologische Praxis Herne); H. Keller (Kardiologische Praxis Coburg); T. Markert (Kardiologische Praxis Gaggenau); R. Jochheim (Kardiologische Praxis Hattingen); K. Jocham (Kardiologische Praxis Memmingen); Th. Muenzel (Universitätsklinikum Mainz); K. Goehl (Klinikum Nürnberg-Süd); H.P. Schultheiss (Charite Berlin); B. Lemke (Märkische Kliniken Lüdenscheid); P. Mahr (Kardiologische Praxis Wiesbaden); Chr. Weiss (Städtisches Klinikum Lüneburg); Th. Wetzel (Kardiologische Praxis Dortmund); J. Stachowitz (St. Vincenz Krankenhaus Paderborn); M. Gawaz (Universitätsklinikum Tübingen); R. Gradaus (Klinikum Kassel); H. Fahlenbrach (Kardiologische Praxis Krefeld); S. Sack (Städtisches Klinikum München- Schwabing); B. Hammer (Kreiskrankenhaus St. Ingbert); J. Rieber (Kardiologische Praxis Leinfelden); G. Metzger (Kardiologische Praxis Bochum); Th. Lawo (Kliniken Bergmannsheil Bochum); S. Brune (Kardiologische Praxis Stade); A. Hummel (Universitätsklinikum Greifswald); R. Cierpka (Kardiologische Praxis Hannover); W. Hartung (Kardiologische Praxis Hannover); U. Gremmler (Kardiologische Praxis Peine); G. Bauer (Kardiologische Praxis Bad Mergentheim); S. Zieger (Kardiologische Praxis Esslingen); W. Haerer (Kardiologische Praxis Ulm); A. Hostert (Kardiologische Praxis Bad Neuenahr); M. Boitz (Kardiologische Praxis Berlin); G. Gola (Kardiologische Praxis Bernau); M. Henrichs (Kardiologische Praxis Rangsdorf); E. Liomin (Kardiologische Praxis Friedrichshafen); N. Schoen (Kardiologische Praxis Mühldorf); S. Helbig (Kardiologische Praxis Nürnberg); K. Droese (Kardiologische Praxis Dortmund); B. Lodde (Kardiologische Praxis Dortmund); W. Landgraf (Kardiologische Praxis Dortmund); Th. Fadgyas (Kardiologische Praxis Dortmund); Chr. Kirsch (St. Josef Krankenhaus Salzkotten)

Board Members Executive Committee Prof. Dr. med. Michael Böhm (Co-Chair) Homburg / Saar Prof. Dr. med. Johannes Brachmann (Co -Chair) Coburg Prof. Dr. med. Gunnar Klein Hannover Dr. med. Hanno Oswald Hannover Dr. med. Karin Rybak Dessau PD Dr. med. Ralph Bosch Ludwigsburg PD Dr. med. Christian Butter Bernau Event Adjudication Committee Prof. Dr. med. Markus Haass Mannheim Prof. Dr. med. Wilhelm Haverkamp Berlin PD Dr. med. Stefan Stoerk Wuerzburg Data Safety Monitoring Board Prof. Dr. med. Stefan Anker (Chairman) Berlin Prof. Karl Swedberg Gothenburg, Sweden Prof. Hein Wellens Maastricht, Netherlands Prof. Luigi Tavazzi Cotignola (RA), Italy Prof. Stuart Pocock London, United Kingdom 4

Disclosures Authors received grant support from the study sponsor. Authors are responsible for the design and conduct of this study, the drafting and editing of the presentation and its final contents. Statistical support for the presentation and for the study design was provided by Bart Gerritse, Medtronic Bakken Research Center (BRC) Maastricht, Netherlands, and Joao Monteiro, Medtronic plc., United States. Sponsored and funded by Medtronic (Minneapolis, MN, USA).

Opti mization of H eart F ailure Management using OptiVol TM Fluid Status Monitoring and Care Link TM (OptiLink HF Study) Primary objective Does Intrathoracic Impedance Monitoring with an Automatic Wireless Telemedicine Notification Compared to Standard Clinical Assessment Reduces All-cause Death or Cardiovascular Hospitalizations? Rationale and design of OPTILINK HF : Eur J. Heart Fail 2011;13:796-804 Trial Registration ClinicalTrials.gov ID: NCT00769457

Inclusion criteria ICD Indication according to SCD-HeFT Chronic Heart Failure (HF), NYHA II – III, LVEF <= 35%, Optimized Medical Therapy (OMT) CRT-ICD Indication according to the ESC Guidelines (2008) Chronic Heart Failure (HF), only NYHA III, LVEF <= 35%, QRS >= 120msec , LVEDD >= 55mm Optimized Medical Therapy (OMT)

Additional Inclusion criteria Patients with potentially higher risk of cardiac decompensation / detoriation At least 1 out of 4 criteria HF-related Hospitalization within the last 12 months • or IV-/Oral Diuretic Treatment within last 30 days • or Increased BNP within last 30 days • > 400pg/ml or Increased NT-pro-BNP within last 30 days • > 400 pg/ml (< 50 years) > 900 pg/ml (50-75 years) > 1.800 pg/ml (> 75 years)

Exclusion criteria Chronic renal failure needing renal dialysis Increased serum creatinine value (> 2,5 mg/dl) within 14 days prior to enrollment Chronic Obstructive Pulmonary Disease (COPD) GOLD standard class III (severe) and IV (very severe)

OptiLink HF Study Design Access arm: telemedicine guided, Implant no audible alert for fluid retention day 3 – 21 Enrollment Control arm: after implant standard clinical assessment, Randomization no alert for fluid retention 1:1 Risk stratified: Access arm Control arm NYHA II vs. III, Ischemic vs. Non-Ischemic, Atrial Fibrillation, Follow up Follow up 6 Months 6 Months Primary vs. Secondary Prevention every 6 Months every 6 Months (VT/VF before Implant)

OptiLink HF Study Design Follow-Up - 18 months/Patient - Extended Follow-Up, if re-consent achievable Primary endpoint - composite of all-cause mortality and CV hospitalizations Analysis - time to first event

Secondary endpoints - all-cause mortality - CV hospitalizations - composite of all-cause death and HF hospitalizations - HF hospitalizations - CV mortality - all-cause hospitalizations during follow-up

Statistical methods - Study was designed to include 1000 patients - 80% power to detect 8.4% event free rate difference at 18 months (72% control vs. 80.4% intervention, 30% relative risk reduction) - Two interims analyses at 33% and 67% of 238 expected primary endpoints (using p<0.0001 and p<0.001 respectively) - Stratified log-rank test to compare between randomized arms (Stratification variables: NYHA, Ischemic status, VT/VF history, AF history, device type) - Hazard ratios (HR) and 95% confidence intervals (CI) reported from Stratified Cox proportional hazards regression models

Telemedicine guided Intervention Brachmann J, et al. Eur J HF . 2011;13(7):796-804.

Patient flow Patients enrolled (n = 1002) Excluded (n = 0) Randomised Patients 1:1 (n = 1002) Allocated to transmit fluid index alerts (n = 505) Allocated to no alert transmission (n = 497) Received alert enabled system (n = 505) Received alert disabled system (n = 497) Did not receive alert enabled system (n = 0) Did not receive alert disabled system (n = 0) Follow-up (mean 23.6 ± 14.0 months) Follow-up (mean 22.3 ± 13.7 months) Died (n = 59) Died (n = 63) Withdraw consent / Not completed (n = 61) Withdraw consent / Not cpmpleted (n = 65) Device replaced with incompatible (n = 2) system Analysed intention-to-treat Analysed intention-to-treat (n = 505) (n = 497) Mean follow-up was 22.9 ± 18.2 months 15