Treatment of Predominant Central Sleep Apnoea by Adaptive Servo Ventilation in Patients With Heart Failure
- Conditions
- Heart FailureSleep Disordered Breathing
- Registration Number
- NCT00733343
- Lead Sponsor
- ResMed
- Brief Summary
The purpose of this trial is to evaluate the long-term effects and cost-effectiveness of adaptive servo-ventilation (ASV) on the mortality and morbidity of patients with stable heart failure due to left ventricular systolic dysfunction, already receiving optimal medical therapy, who have sleep disordered breathing (SDB) that is predominantly central sleep apnea. Assumptions: the intervention reduces the hazard rate by 20%. The event rate in the control group is 35% in the first year. It is assumed that the hazard rate is constant over time.
- Detailed Description
Objective: The purpose of this trial is to evaluate the long-term effects and cost-effectiveness of adaptive servo-ventilation (ASV) on the mortality and morbidity of patients with stable heart failure due to left ventricular systolic dysfunction, already receiving optimal medical therapy, who have sleep disordered breathing (SDB) that is predominantly central sleep apnea.
Study Design: Randomized, multicentre, international trial with parallel group design, with patients randomized to either control (optimal medical management) or active treatment (optimal medical treatment plus use of adaptive servoventilation) in a 1:1 ratio. There will be no sham-positive airway pressure treatment in the control arm. Assumptions: the intervention reduces the hazard rate by 20%. The event rate in the control group is 35% in the first year. It is assumed that the hazard rate is constant over time. The trial is an event driven design: the final analysis is to be performed latest when 651 events have been observed. The primary analysis is in the intention-to-treat population that consists of all patients randomized.
Number of Patients: 1116 patients will be randomly assigned to one of the two treatment groups. A 20% drop out rate is estimated.
Selection criteria: Patients at the age of or over 22 years with severe chronic heart failure (chronic HF), New York Heart Association (NYHA) class III-IV or NYHA class II with at least one hospitalization for HF within the last 24 months, with Left Ventricular Ejection Fraction (LVEF) less or equal 45% by means of echocardiography, radionuclide ventriculography or cardiac MRI and Sleep Disordered Breathing (SDB) (apnoea-hypopnoea-index (AHI \> 15/h) with 50% central events and a central AHI ≥ 10/h, no change of medication and no hospitalization for more than 1 month before randomization and medical therapy according to the applicable guidelines (European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) respectively).
Primary Endpoints: Time to first event of:
1. all cause mortality or unplanned hospitalisation/prolongation of hospitalisation for worsening heart failure
2. cardiovascular mortality or unplanned hospitalisation/prolongation of hospitalisation for worsening heart failure.
3. all cause mortality or all cause unplanned hospitalisation/prolongation of hospitalisation Heart transplantation, appropriate shock from implantable cardioverter-defibrillator (ICD), long term assist device (LTAD) insertion and survived resuscitation of sudden cardiac arrest are counted as cardiovascular death, survived resuscitation for other reasons is counted as all cause death.
The three combinations are not tested in parallel but in this hierarchical order.
Secondary Endpoints : Time until death, non cardiovascular death, cardiovascular death, hospitalization due to deterioration of heart failure or cardiovascular death, hospitalization for other reasons or death, hospitalization for cardiovascular cause or cardiovascular death, percent of follow-up (FU) days which patient survives and is not hospitalized for cardiovascular cause, percent of follow up days which patient survives and is not hospitalized for other reason, time to first adequate shock (in patients with ICD, evaluation of appropriateness will also be made by the ERC) or cardiovascular death, changes in NYHA class as compared to baseline, changes in difference in health costs between the two treatment groups, changes in QoL (Minnesota, Euroqol 5D (EQ5D)) as compared to baseline, changes in renal function (based on serum creatinine) as compared to baseline, changes in result of Six Minute Walking Test (6MWT) (50) as compared to baseline,changes of AHI and oxygen desaturation index compared to baseline, AHI below 10 per hour at twelve months and Oxygen desaturation index (ODI) below 5 per hour at twelve months, atrial fibrillation at follow-up visits.
Number and cost of hospitalizations (with tariff/diagnostic-related Group (DRG), diagnoses and procedures for calculating DRG or length of stay and level of care provided), cost of care (technology and service, nursing, physicians visit) related to ventilation, difference in utilities / QoL (Minnesota and EQ5D) compared to control arm, difference in cost of resources consumed, cost-efficacy, cost-utility. Secondary target parameters will be measured at the last follow up or at the last available observation within FU.
Scheduled follow up : Minimum follow up time will be 24 months, maximum about 70 months. There will be a final assessment for each patient at the end of the study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1325
- Patients must be at least 22 years old
- Chronic heart failure (at least 12 weeks since diagnosis) according to the current applicable guidelines (ESC, ACC/AHA)
- Left ventricular systolic dysfunction (LVEF ≤45% by imaging method such as echocardiography, radionuclide angiography, left ventriculography, or cardiac magnetic resonance imaging) documented less than 12 weeks before randomisation
- NYHA class III or IV at the time of inclusion or NYHA class II with at least one hospitalisation for HF in the last 24 months
- No hospitalisation for heart failure for at least 4 weeks prior to inclusion
- Optimised medical treatment according to applicable guidelines with no new class of disease modifying drug for more than 4 weeks prior to randomisation. In case of no beta blockers or ACE (angiotensin converting Enzyme) inhibitors/ ARB (angiotensin receptor blocker) antagonists the reasons must be documented
- SDB (AHI > 15/h with ≥ 50% central events and a central AHI ≥ 10/h, derived from polygraphy or polysomnography (based on total recording time (TRT)), documented less than 4 weeks before randomisation. Flow measurement has to be performed with nasal cannula
- Patients for whom the use of AutoSet CS2 (TM)/VPAP Adapt may be contra-indicated because of symptomatic hypotension or significant intravascular volume depletion or pneumothorax or pneumomediastinum
- Patient is able to fully understand study information and signed informed consent
- Significant COPD (chronic obstructive pulmonary disease) with Forced Expiratory Volume within one second (FEV1) <50% (European Respiratory Society criteria) in the last four weeks before randomisation
- Oxygen saturation at rest during the day ≤ 90% at inclusion
- Current use of Positive Airway Pressure (PAP) - therapy
- Life expectancy < 1 year for diseases unrelated to chronic HF
- Cardiac surgery, Percutaneous coronary intervention (PCI), Myocardial Infarction (MI) or unstable angina within 6 months prior to randomisation
- CRT (cardiac resynchronisation therapy)-implantation or ICD-implantation scheduled or within 6 months prior to randomisation
- Transient ischemic attack (TIA) or Stroke within 3 months prior to randomisation
- Primary hemodynamically significant uncorrected valvular heart disease, obstructive or regurgitant, or any valvular disease expected to lead to surgery during the trial
- Acute myocarditis/pericarditis within 6 months prior to randomisation
- Untreated or therapy refractory Restless legs-Syndrome (RLS) according to criteria listed in Appendix IX at the time of study entry
- Pregnancy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method All Cause Mortality or Unplanned Hospitalisation/Prolongation of Hospitalisation for Worsening Heart Failure time to first event, assessed for up to 70 weeks Cardiovascular Mortality or Unplanned Hospitalisation/Prolongation of Hospitalisation for Worsening Heart Failure time to first event, assessed for up to 70 weeks All Cause Mortality or All Cause Unplanned Hospitalisation/Prolongation of Hospitalisation time to first event, assessed for up to 70 weeks
- Secondary Outcome Measures
Name Time Method Death From Any Cause the last follow up or at the last available observation within Follow Up (FU), assessed for up to 70 weeks First Survived Resuscitation of Sudden Cardiac Arrest (Evaluation Will Also be Made by the ERC) the last follow up or at the last available observation within FU, assessed for up to 70 weeks Age Baseline 1 x at Baseline Creatinine Baseline 1 x at baseline 6-Min Walk Distance 1 x at baseline Epworth Sleepiness Scale (ESS) 1 x at baseline Measure Description: ESS is a self-administered questionnaire. It contains 8 questions. Questions are rated on a 4-point Likert scale (0-3); 0= would never doze, 3=high Chance of dozing. Range of scores 0-24. Global score= sum of all item scores. Copyright (c)MW Johns
Unplanned Hospitalisation/Prolongation of Hospitalisation Due to Worsening of Heart Failure the last follow up or at the last available observation within FU, assessed for up to 70 weeks Cardiovascular Death the last follow up or at the last available observation within FU, assessed for up to 70 weeks First Survived Resuscitation for Any Reason (Evaluation Will Also be Made by the ERC) the last follow up or at the last available observation within FU, assessed for up to 70 weeks Blood Pressure Diastolic Baseline 1 x at baseline Hemoglobine Baseline 1 x at baseline Glomerular Filtration Rate Baseline 1 x at baseline Adequate Shock in Patients With ICD (Evaluation of Appropriateness Will Also be Made by the Endpoint Review Committee, ERC), Long-Term Atrial Defibrillator Insertion or Cardiovascular Death the last follow up or at the last available observation within FU, assessed for up to 70 weeks Body Mass Index (BMI) Baseline 1 x baseline Apnoea-Hypopnea-Index (AHI) at Baseline 1 x at baseline Measure Description: The AHI is an index to describe the severity of Sleep Apnea. Apnea is cessation of breathing during sleep. Hypopnea is diminished breathing during sleep. The number of Apneas and Hypopneas are added up and divided by hours of sleep (Apneas + Hypopneas per hour). An AHI ranging from 5-15 describes mild Sleep Apnea. AHI 15-30 describes moderate Sleep Apnea. AHI \>30 describes severe Sleep Apnea.
Central Apnoea Index/Total AHI 1 x at baseline Measure Description: Central apneas are partial or complete cessations of airflow caused by reduced or stopped neural Stimulation of the breathing muscles. For comparison: In obstructive apneas are caused by blocked airways that shut off the air although the breathing Stimulus is working.
Changes in NYHA Classification as Compared to Baseline the last follow up or at the last available observation within FU, assessed for up to 70 weeks Non-cardiovascular Death the last follow up or at the last available observation within FU, assessed for up to 70 weeks Unplanned Hospitalisation/Prolongation of Hospitalisation for Other Reasons or Death the last follow up or at the last available observation within FU, assessed for up to 70 weeks Left Ventricular Ejection Fraction at Baseline 1x at baseline Oxygen Desaturation Index (ODI) at Baseline 1 x at baseline Number of oxygen desaturations per hour at baseline
Time Until Unplanned Hospitalisation/Prolongation of Hospitalisation for Cardiovascular Cause or Cardiovascular Death/ Time Frame the last follow up or at the last available observation within FU, assessed for up to 70 weeks Percent of Follow up Days Which Patient Survives and is Not Hospitalized/Hospital Stay is Not Prolonged for Cardiovascular Cause the last follow up or at the last available observation within FU, assessed for up to 70 weeks Changes in QoL (Minnesota) as Compared to Baseline the last follow up or at the last available observation within FU, assessed for up to 70 weeks Atrial Fibrillation at Follow-up Visits the last follow up or at the last available observation within FU, assessed for up to 70 weeks Body Weight Baseline 1 x at baseline Blood Pressure Systolic Baseline 1 x at baseline Central AHI/Total AHI at Baseline 1 x at baseline Changes of AHI and Oxygen Desaturation Index Compared to Baseline the last follow up or at the last available observation within FU, assessed for up to 70 weeks Oxygen Saturation Baseline 1 x at baseline Time With Oxygen Saturation Below 90% 1 x at baseline Changes in Six Minute Walking Distance (6MWD) as Compared to Baseline the last follow up or at the last available observation within FU, assessed for up to 70 weeks AHI Below 10 Per Hour at Twelve Months and ODI Below 5 Per Hour at Twelve Months the last follow up or at the last available observation within FU, assessed for up to 70 weeks Number and Cost of Hospitalisations (With Tariff/DRG, Diagnoses and Procedures for Calculating DRG or Length of Stay and Level of Care Provided) the last follow up or at the last available observation within FU, assessed for up to 70 weeks Difference in Utilities / QoL (Minnesota and EQ5D) Compared to Control Arm the last follow up or at the last available observation within FU, assessed for up to 70 weeks Difference in Cost of Resources Consumed the last follow up or at the last available observation within FU, assessed for up to 70 weeks Changes in Renal Function (Based on Serum Creatinine) as Compared to Baseline the last follow up or at the last available observation within FU, assessed for up to 70 weeks Incremental Cost-utility Ratio the last follow up or at the last available observation within FU, assessed for up to 70 weeks Incremental Cost-efficacy Ratio the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Trial Locations
- Locations (264)
Praxis Westend
🇩🇪Berlin, Germany
Helsinki University Hospital
🇫🇮Helsinki, Finland
CHU de Caen
🇫🇷Caen Cedex, France
Praxis Cardiologique Dr. Wickers
🇫🇷Bordeaux, France
CH de Forbach, Hospitalor, Hopital Marie Madeleine-Pneumology
🇫🇷Forbach, France
CHU Grenoble, Hopital Michallon
🇫🇷Grenoble, France
Hospices Civils de Lyon, Hopital de la Croix-Rousse
🇫🇷Lyon, France
CH de Mulhouse, Hopital Emile Muller
🇫🇷Mulhouse, France
CH Rene Dubos
🇫🇷Pontoise, France
CHU de Nancy, Hopital Brabois
🇫🇷Vandoeuvre les Nancy, France
Herzzentrum Bad Krozingen
🇩🇪Bad Krozingen, Germany
Kardiopraxis Rheinberg
🇩🇪Bergisch Gladbach, Germany
POLIKUM Friedenau
🇩🇪Berlin, Germany
Praxis für Lunge, Herz und Schlaf
🇩🇪Bielefeld, Germany
Universitätsklinikum Bergmannsheil
🇩🇪Bochum, Germany
Augusta Krankenanstalten Bochum
🇩🇪Bochum, Germany
St.-Josephs-Hospital
🇩🇪Bochum, Germany
Kardiologische Praxis Dr. Staubach
🇩🇪Bochum, Germany
Kardiologische Praxis Marschner
🇩🇪Bonn, Germany
Klinikum Bremen Ost
🇩🇪Bremen, Germany
Gemeinschaftspraxis Kardiologie
🇩🇪Bottrop, Germany
Internistenpraxis Alstertal Hamburg
🇩🇪Hamburg, Germany
Praxis Dr. Anselm Bäumer
🇩🇪Köln, Germany
Gemeinschaftspraxis Dr. Jocham
🇩🇪Memmingen, Germany
Kardiologische Praxis Dr. Muradi
🇩🇪Münster, Germany
Kardiologische Praxis Nienburg
🇩🇪Nienburg, Germany
Kreiskrankenhaus Stollberg GmbH
🇩🇪Stollberg, Germany
Missionsärztliche Klinik Würzburg
🇩🇪Würzburg, Germany
Cardiocentro Ticino
🇨🇭Lugano, Switzerland
Dansk Center For Søvnmedicin
🇩🇰Glostrup, Denmark
Krankenhaus Bethanien
🇩🇪Moers, Germany
CH Belfort
🇫🇷Belfort, France
CH de Besancon
🇫🇷Besancon, France
CHU Bordeaux, Hopital Pellegrin
🇫🇷Bordeaux, France
Clinique Mutualiste des Eaux Claires
🇫🇷Grenoble, France
Unesta Research Centre
🇫🇮Tampere, Finland
CHU Angers
🇫🇷Angers, France
Hopital Prive d'Antony
🇫🇷Antony, France
Clinique du Tondu
🇫🇷Bordeaux, France
CH de Forbach-Cardiology
🇫🇷Forbach, France
CHU Lille-Sleep medicine
🇫🇷Lille, France
Polyclinique La Louviere
🇫🇷Lille, France
Kardiologische Praxis Dr. Isbruch
🇩🇪Castrop-Rauxel, Germany
MECS Cottbus GmbH
🇩🇪Cottbus, Germany
Hôpital Bichat
🇫🇷Paris, France
Charité Campus Mitte CCM- Schlafmedizinisches Zentrum
🇩🇪Berlin, Germany
Centre Hospitalier d'Antibes Juan-les-Pins
🇫🇷Antibes, France
Hopital Henri Mondor
🇫🇷Creteil, France
CHU de Montpellier
🇫🇷Montpellier, France
CHU de Bordeaux, Hopital Haut Leveque
🇫🇷Pessac, France
Cardiopraxis Ingelheim
🇩🇪Mainz, Germany
Klinik Lazariterhof
🇩🇪Bad Krozingen, Germany
Tampere University Hospital, Pirkanmaa sairaanhoitopiiri
🇫🇮Tampere, Finland
Hôpital Sud
🇫🇷Echirolles, France
Clinique de L'Union
🇫🇷L'Union, France
CHU Lille- Hopital Cardiologique
🇫🇷Lille, France
CHR Metz, Hôpital de Bon-Secours
🇫🇷Metz, France
Kardiologie Kemnade
🇩🇪Bochum, Germany
Helios Klinikum Borna
🇩🇪Borna, Germany
Gemeinschaftspraxis Kardiologie Dr. Becker
🇩🇪Castrop-Rauxel, Germany
Mediclin Rehazentrum Spreewald
🇩🇪Burg, Germany
Charité Campus Mitte - Kardiologie
🇩🇪Berlin, Germany
Hôpital St. André
🇫🇷Bordeaux, France
Praxis Cardiologique Dr. Puel
🇫🇷Bordeaux, France
CH Haguenau
🇫🇷Haguenau, France
Clinique des Trois Frontières
🇫🇷Saint Louis, France
Zentralklinikum Bad Berka
🇩🇪Bad Berka, Germany
Schlaflabor Breisgau
🇩🇪Bad Krozingen, Germany
Universitätsklinikum Bonn
🇩🇪Bonn, Germany
Kardiologische Praxis Dr. Dröse
🇩🇪Dortmund, Germany
Gemeinschaftspraxis Dres. Schmidt/Gronke
🇩🇪Dresden, Germany
Kardiologische Praxis Dr. Kruse
🇩🇪Forst, Germany
Kardiologische Praxis Dr. Schlichting
🇩🇪Herne, Germany
Augusta-Kranken-Anstalt gGmbH Thoraxzentrum Ruhrgebiet
🇩🇪Herne, Germany
Lungenfachklinik Immenhausen
🇩🇪Immenhausen, Germany
Gemeinschaftspraxis Dres. Dobler/Turin
🇩🇪Karlstadt, Germany
Helios Klinikum Krefeld
🇩🇪Krefeld, Germany
Helios Krankenhaus Leisnig
🇩🇪Leisnig, Germany
Kardiologische Praxis Dr. Faber
🇩🇪Lindlar, Germany
Cabinet de cardiologie
🇫🇷Pont-à-mousson, France
Praxis Dr. Frieske
🇩🇪Aachen, Germany
Universitätsklinikum Aachen
🇩🇪Aachen, Germany
Praxis Dr. Rau
🇩🇪Essen, Germany
Universitaetsklinikum Freiburg
🇩🇪Freiburg im Breisgau, Germany
Gemeinschaftspraxis Dres Leischik/Littwitz
🇩🇪Hagen, Germany
Kardiologische Praxis Dr. Cierpka
🇩🇪Hannover, Germany
Ärztezentrum Holthausen-Biene
🇩🇪Lingen, Germany
Universitätsklinikum Mannheim-Schlafmedizin
🇩🇪Mannheim, Germany
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Jüdisches Krankenhaus Berlin
🇩🇪Berlin, Germany
Asklepios Klinik Barmbek
🇩🇪Hamburg, Germany
Praxis Dr. Hecker
🇩🇪Dortmund, Germany
Helios Klinikum Erfurt-Kardiologie
🇩🇪Erfurt, Germany
Kardiologie Praxis Dr. Bonnekamp
🇩🇪Essen, Germany
Kardiologische Praxis Dr. Hartung
🇩🇪Hannover, Germany
Thoraxklinik Heidelberg gGmbH
🇩🇪Heidelberg, Germany
Lungenklinik Hemer
🇩🇪Hemer, Germany
St.-Vinzenz Hospital
🇩🇪Köln, Germany
Universitätsklinikum Leipzig-Herzzentrum
🇩🇪Leipzig, Germany
Klinikum der Johannes Gutenberg-Universität Mainz
🇩🇪Mainz, Germany
Universitätsklinikum Münster
🇩🇪Münster, Germany
Universitätsklinikum Würzburg
🇩🇪Würzburg, Germany
Unfallkrankenhaus Berlin
🇩🇪Berlin, Germany
Evangelische Lungenfachklinik Buch
🇩🇪Berlin, Germany
Charité Campus Virchow Klinikum
🇩🇪Berlin, Germany
Klinikum Nürnberg Süd
🇩🇪Nürnberg, Germany
Kardiologische Praxis Dr. Golling
🇩🇪Dortmund, Germany
Kardiologische Praxis Dr. Horowitz
🇩🇪Düsseldorf, Germany
Ruhrlandklinik Essen
🇩🇪Essen, Germany
CardioVasculäres Centrum Frankfurt
🇩🇪Frankfurt, Germany
Kardiologische Praxis Dr. Arens
🇩🇪Hagen, Germany
Siloah Krankenhaus
🇩🇪Hannover, Germany
Ambulantes Herzzentrum Kassel
🇩🇪Kassel, Germany
Praxis Dr. Krater
🇩🇪Krefeld, Germany
Kardiologische Praxis Dr. Fritsch
🇩🇪Köln, Germany
Universitätsklinikum Schleswig-Holstein Campus Lübeck-Kardiologie
🇩🇪Lübeck, Germany
Evangelisches Krankenhaus Mülheim
🇩🇪Mülheim an der Ruhr, Germany
Clinical Trial Site Services
🇩🇪Dortmund, Germany
Kardiologische Praxis Gütersloh
🇩🇪Gütersloh, Germany
MH Hannover
🇩🇪Hannover, Germany
Kardiologische Praxis Dr. Furche
🇩🇪Herne, Germany
Klinikum Dahme-Spreewald GmbH
🇩🇪Königs Wusterhausen, Germany
Kardiologische Praxis Dr. Rudolf/ Dr. Bernhardt
🇩🇪Worms, Germany
Oslo University Hospital, Rikshospitalet
🇳🇴Oslo, Norway
Zentrum für Innere Medizin Uni Ulm
🇩🇪Ulm, Germany
Ullevål University Hospital
🇳🇴Oslo, Norway
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Rivercity Private Hospital
🇦🇺Auchenflower, Queensland, Australia
St Vincents and Mercy Private Hospital
🇦🇺Melbourne, Victoria, Australia
Melbourne Sleep Disorders Centre
🇦🇺East Melbourne, Victoria, Australia
Hollywood Private Hospital (CVS)
🇦🇺Nedlands, Western Australia, Australia
St. Anne's University Hospital BRNO
🇨🇿Brno, Czechia
Rigshospitalet
🇩🇰Copenhagen, Denmark
Bispebjerg Hospital
🇩🇰Copenhagen, Denmark
Cardiologist Dr. Papola
🇫🇷Amneville, France
Glostrup Hospital
🇩🇰Glostrup, Denmark
Århus Universitets Hospital
🇩🇰Århus C, Denmark
Århus Universitets Hospital Skejby
🇩🇰Århus N, Denmark
Centre Hospitalier de Béziers
🇫🇷Beziers, France
Centre Hospitalier de Cannes
🇫🇷Cannes, France
CH Montbeliard
🇫🇷Montbeliard, France
CH Intercommunal André Grégoire
🇫🇷Montreuil, France
Clinique les Fleurs
🇫🇷Ollioules, France
CHU Tenon
🇫🇷Paris, France
CHU de Poitiers
🇫🇷Poitiers, France
Polyclinique Saint-Laurent
🇫🇷Rennes, France
CH Lemire - St Avold
🇫🇷Saint Avold, France
CHU de Rouen, Hopital de Bois Guillaume
🇫🇷Rouen, France
CHU Toulouse, Hopital Larrey
🇫🇷Toulouse, France
CH de St Dié des Vosges
🇫🇷St Dié des Vosges, France
CHU de Saint-Etienne, Hopital Nord
🇫🇷Saint- Etienne, France
Ch St. Nicolas
🇫🇷Verdun, France
CHU Toulouse, Hopital de Rangueil
🇫🇷Toulouse, France
CH Trouville
🇫🇷Trouville, France
DRK Krankenhaus
🇩🇪Alzey, Germany
Gemeinschaftspraxis Weiß / Dr. Heesing
🇩🇪Arnsberg, Germany
Praxis Dr. Bauer
🇩🇪Bad Mergentheim, Germany
Herz- und Diabeteszentrum NRW
🇩🇪Bad Oeynhausen, Germany
Oberlausitz-Kliniken gGmbH
🇩🇪Bautzen, Germany
Kardiologie Brühl
🇩🇪Brühl, Germany
Gemeinschaftspraxis Groß-Ziethener Chaussee
🇩🇪Berlin, Germany
Herzzentrum Brandenburg
🇩🇪Bernau, Germany
Kardiologie Gemeinschaftspraxis Dres Tenholt&Metzger&Dexling
🇩🇪Bochum, Germany
Klinikum Coburg GmbH
🇩🇪Coburg, Germany
MVZ am Küchwald
🇩🇪Chemnitz, Germany
Fachkrankenhaus Coswig
🇩🇪Coswig, Germany
Carl-Thiem-Klinikum gGmbH
🇩🇪Cottbus, Germany
Ambulantes Zentrum für Lungenkrankheiten&Schlafmedizin
🇩🇪Cottbus, Germany
Kardiologische Praxis Dr. Lodde
🇩🇪Dortmund, Germany
Kardiologische Praxis Dr. Wetzel
🇩🇪Dortmund, Germany
Facharztzentrum Dresden-Neustadt GbR
🇩🇪Dresden, Germany
Herzzentrum Universität Dresden
🇩🇪Dresden, Germany
Praxis Dr. Hohensee
🇩🇪Dresden, Germany
goMedus Gesundheitszentrum
🇩🇪Düsseldorf, Germany
Evangelisches Krankenhaus
🇩🇪Düsseldorf, Germany
Kardiologische Praxis Dr. Raff
🇩🇪Düsseldorf, Germany
Florence-Nightingale Krankenhaus
🇩🇪Düsseldorf, Germany
Kardiologie Oberkassel
🇩🇪Düsseldorf, Germany
Gemeinschaftspraxis PD. Dr. Lankisch
🇩🇪Düsseldorf, Germany
Fachärzte für Innere Medizin Dres Ritter, Richter, Mehrer, Kahl
🇩🇪Emmendingen, Germany
Helios Klinikum Erfurt-Schlafmedizin
🇩🇪Erfurt, Germany
Universitätsklinikum Erlangen
🇩🇪Erlangen, Germany
Westdeutsches Herzzentrum, Universitätsklinikum Essen
🇩🇪Essen, Germany
Schwerpunktpraxis Kardiologie Drs. Ophoff/Fritzsch
🇩🇪Essen, Germany
Kardiologische Praxis Dr. Cord Müller
🇩🇪Essen, Germany
Kardiologische Praxis Prof. Winter
🇩🇪Essen, Germany
Elisabeth-Krankenhaus Essen
🇩🇪Essen, Germany
Kath. Kliniken Essen / Philippusstift
🇩🇪Essen, Germany
Praxis Dr. Tekiyeh
🇩🇪Essen, Germany
Gemeinschaftspraxis Dres. Guckenbiehl
🇩🇪Flonheim, Germany
Praxis Dr. Diedrichs
🇩🇪Frechen, Germany
Gemeinschaftspraxis Dres. Böhmeke/Schmidt
🇩🇪Gladbeck, Germany
Kardiologische Praxis Dr. Hug
🇩🇪Günzburg, Germany
Gemeinschaftspraxis Dres. Subin/Lutter
🇩🇪Hamburg, Germany
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Praxis Dr. Hötte
🇩🇪Hannover, Germany
Praxis Dr. Durak
🇩🇪Heidelberg, Germany
Klinikum Hannover Oststadt-Heidehaus
🇩🇪Hannover, Germany
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Gemeinschaftspraxis Dr. Bruch
🇩🇪Herne, Germany
St. Elisabeth-Hospital Herten gGmbH
🇩🇪Herten, Germany
Kardiologische Praxis Dr. Siegfried Frickel
🇩🇪Kempen, Germany
Gemeinschaftspraxis Dres. Heifer/Loster/Schernus
🇩🇪Mannheim, Germany
Malteser Krankenhaus St.Hildegardis
🇩🇪Köln, Germany
Prof. Franzen Institut
🇩🇪Köln, Germany
Gemeinschaftspraxis Dres. Gysan/Heinzler/May
🇩🇪Köln, Germany
Gemeinschaftspraxis Dr. Hilgedieck/Sava
🇩🇪Lengerich, Germany
Universitätsklinikum Schleswig-Holstein Campus Lübeck-Schlaflabor
🇩🇪Lübeck, Germany
Gemeinschaftspraxis für Herz & Gefäße
🇩🇪Mannheim, Germany
Universitätsklinik Mannheim-Kardiologie
🇩🇪Mannheim, Germany
Gemeinschaftspraxis Dres. Brandt / Jakobs
🇩🇪Mannheim, Germany
Universitätsklinikum Gießen/Marburg Standort Marburg-Kardiologie
🇩🇪Marburg, Germany
Universitätsklinikum Gießen / Marburg, Standort Marburg-Schlafmedizin
🇩🇪Marburg, Germany
Praxis Dr. Schnabel
🇩🇪Meissen, Germany
Praxis Für Kardiologie Dr. med. Menz
🇩🇪Menden, Germany
Kardiologische Praxis Dr. Schön
🇩🇪Mühldorf, Germany
Kardiologie am Rotkreuzplatz
🇩🇪München, Germany
Lungenärzte am Rotkreuzplatz
🇩🇪München, Germany
Klinik Augustinum München
🇩🇪München, Germany
Gemeinschaftspraxis Dres. Wauer / Windstetter
🇩🇪München, Germany
Kardiologische Praxis Dr. Herholz
🇩🇪München, Germany
Praxis Dres. Böhme/Linke
🇩🇪München, Germany
Praxis für Kardiologie Dr. med. Hewing
🇩🇪Münster, Germany
Lukaskrankenhaus GmbH
🇩🇪Neuss, Germany
Klinikum Nürnberg Nord
🇩🇪Nürnberg, Germany
Kardiologische Praxis Dr. Gumbrecht
🇩🇪Ochtrup, Germany
Kardiologische Praxis Dr. Wiethölter
🇩🇪Radebeul, Germany
Praxis für Kardiologie Ratingen
🇩🇪Ratingen, Germany
DRK Krankenhaus Mölln-Ratzeburg
🇩🇪Ratzeburg, Germany
Krankenhaus Reinbek St. Adolf-Stift
🇩🇪Reinbek, Germany
Praxis Dr. Fröhlich
🇩🇪Ratingen, Germany
Gemeinschaftspraxis Dr. Weber/Dr. Feja
🇩🇪Recklinghausen, Germany
Universitätsklinikum Regensburg
🇩🇪Regensburg, Germany
Ambulantes Cardiovaskuläres Centrum
🇩🇪Ravensburg, Germany
Knappschafts-Krankenhaus Recklinghausen
🇩🇪Recklinghausen, Germany
Praxis Dr. Kestermann
🇩🇪Rheine, Germany
Kardiologische Praxis Dr. Heinze
🇩🇪Schwerte, Germany
Praxis Dr. Nebel
🇩🇪Rheine, Germany
Praxis Dr. Hein
🇩🇪Reinbek, Germany
Praxis Dr. Ebeling
🇩🇪Schönefeld, Germany
Praxisgemeinschaft Cardio-Soest
🇩🇪Soest, Germany
Klinikum Uelzen GmbH
🇩🇪Uelzen, Germany
Herzklinik Ulm Dr. Haerer und Partner
🇩🇪Ulm, Germany
Facharztzentrum Sonneberg
🇩🇪Sonneberg, Germany
Katharinen Hospital Unna
🇩🇪Unna, Germany
Stiftungsklinik Weißenhorn
🇩🇪Weißenhorn, Germany
Praxis Dr. Gerritsen
🇩🇪Waldkraiburg, Germany
Kardiologische Praxis Dr. Burkhard-Meier
🇩🇪Viersen, Germany
Fachkliniken Wangen
🇩🇪Wangen, Germany
Kardiologische Praxis Dr. Vrettos
🇩🇪Witten, Germany
Evangel. Khs Zweibrücken
🇩🇪Zweibrücken, Germany
Stavanger AS
🇳🇴Stavanger, Norway
Specialistläkarmottagning Residenset AB
🇸🇪Jönköping, Sweden
Sahlgrenska University Hospital / Östra
🇸🇪Göteborg, Sweden
Linköping University Hospital
🇸🇪Linköping, Sweden
Skaraborgs Hospital
🇸🇪Lidköping, Sweden
Chesterfield Royal Hospital
🇬🇧Chesterfield, United Kingdom
Brompton Hospital
🇬🇧London, United Kingdom
Ospedale Regionale di Lugano
🇨🇭Lugano, Switzerland
Royal Wolverhampton Hospitals NHS Trust
🇬🇧Wolverhampton, United Kingdom
Freeman Hospital
🇬🇧Newcastle, United Kingdom
Musgrove Park Hospital
🇬🇧Taunton, United Kingdom
Castle Hill Hospital
🇬🇧Cottingham, East Yorkshire, United Kingdom