Implantable Cardiac Monitors in High-Risk Post-Infarction Patients With Cardiac Autonomic Dysfunction

Myocardial Infarction Clinical Trial

— SMART-MI  

Official title:

Implantable Cardiac Monitors in High-risk Post-infarction Patients With Cardiac Autonomic Dysfunction and Moderately Reduced Left Ventricular Ejection Fraction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02594488
• Other study ID #: 118-15
• Status: Completed
• Phase: N/A
• Start date: May 6, 2016
• Est. completion date: February 2021

Study information

• Verified date: June 2021
• Source: LMU Klinikum
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The majority of deaths after myocardial infarction occurs in patients with preserved left ventricular ejection fraction (>35%) for whom no prophylactic strategies exist. Periodic Repolarization Dynamics (PRD) and Deceleration Capacity (DC) of heart rate are autonomic risk markers that identify a new high risk group of patients with LVEF 35-50% who have the same poor prognosis as patients with LVEF ≤35%. In SMART-MI, post-infarction patients with LVEF 35-50% and abnormal PRD and/or DC will be randomly assigned to biomonitoring-guided therapy or conventional follow-up.

Description:

Sudden cardiac death (SCD) is the most common single cause of death in the industrialized world. Patients after myocardial infarction (MI) are at increased risk of SCD. Current guidelines recommend prophylactic ICD-implantation in post-MI patients with reduced left ventricular ejection fraction (LVEF ≤35%). However, the majority of arrhythmic deaths after MI occurs in patients with LVEF >35% in whom no specific prophylactic strategies exist, indicating an important unmet medical need. There is a large body of evidence that presence of cardiac autonomic dysfunction after MI is associated with an increased susceptibility to malignant brady- and tachyarrhythmias eventually culminating in SCD. Periodic repolarization dynamics (PRD) and heart rate deceleration capacity (DC) are clinically validated autonomic risk markers that provide strong and independent prognostic information in post-MI patients with LVEF >35%. PRD and DC reflect different facets of autonomic function and can therefore be used in combination to predict risk. Previous studies demonstrated that combined assessment of PRD and DC identifies a new high-risk group among post-MI patients with moderately reduced LVEF (36-50%). This new high-risk group has similar characteristics with respect to prognosis and patient numbers as the established high-risk group identified by LVEF ≤35%. However, the exact mechanisms leading to death in this new high-risk group need to be investigated in order to develop specific preventive strategies. As known from studies with implantable cardiac monitors (ICM) in post-MI patients with LVEF ≤40% eventual death is often preceded by primarily asymptomatic serious arrhythmic events. These data suggest a potential time frame for pre-emptive interventions in case of arrhythmic events, which could improve outcome. Therefore, SMART-MI will assess the occurrence and prognostic implications of serious arrhythmic events in this newly identified high-risk group by remote monitoring with ICM. Survivors of acute MI (<40 days) and LVEF 36-50% undergo autonomic testing for presence of abnormal PRD and/or DC. Those with autonomic dysfunction will be randomly assigned to ICM-implantation or conventional follow-up. Superiority of ICMs in detection of predefined serious arrhythmic events will be tested based on a time-to-event analysis. A central ICM core lab will be implemented allowing for a response to arrhythmias within 48h. The effect of remote monitoring on clinical outcomes will be tested as secondary endpoints. The study will provide the rationale for a future guideline-relevant study testing prophylactic therapies in this newly identified high-risk group.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. completion date: February 2021
• Est. primary completion date: February 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Acute myocardial infarction <40 days
• Left ventricular ejection fraction 36-50%
• Presence of cardiac autonomic dysfunction by means of abnormal periodic repolarization dynamics and/or abnormal deceleration capacity
• Age 18-80 years
• Sinus rhythm
• Optimal medical therapy

Exclusion Criteria:

• ICD or pacemaker indication
• Known paroxysmal or persistent atrial fibrillation
• Life expectancy < 12 months
• Inability to comply with follow-up
• Pregnancy
• Participation in another trial that may interfere

Related Conditions & MeSH terms

• Autonomic Nervous System Diseases
• Infarction
• Myocardial Infarction
• Nervous System Diseases
• Primary Dysautonomias

Intervention

Device:
• Medtronic Reveal LINQ implantable cardiac monitor
The implantable cardiac monitor is implanted under the skin in the region of the thorax. It continuously monitors the heart's electrical activity for up to three years. Predefined arrhythmias are daily transmitted to a central core lab. In case of arrhythmias, specific guideline-based treatment is initiated within 48h.

Locations

Country	Name	City	State
Austria	Medizinische Universität Innsbruck, Universitätsklinik für Innere Medizin III	Innsbruck
Germany	Universtitätsklinikum der RWTH Aachen, Medizinische Klinik I	Aachen
Germany	Universitätsmedizin Berlin, Klinik für Kardiologie, Charite, Campus Benjamin Franklin	Berlin
Germany	Universitätsmedizin Berlin, Klinik für Kardiologie, Charite, Campus Virchow Kinikum	Berlin
Germany	Klinik Höhenried, Rehabilitationszentrum am Starnberger See	Bernried
Germany	Herzzentrum Dresden, Univeristätsklinik an der TU Dresden	Dresden
Germany	Universitätklinikum Essen, Klinik für Kardiologie und Angiologie	Essen
Germany	Kliniken Ostallgäu-Kaufbeuren, Klinik Füssen	Füssen
Germany	Universitätsmedizin Göttingen, Klinikum für Kardiologie und Pneumologie	Göttingen
Germany	Universitätsmedizin Greifswald, Klinik für Innere Medizin B	Greifswald
Germany	Asklepios Klinik St. Georg, Abteilung für Kardiologie	Hamburg
Germany	Universitäres Herzzentrum Hamburg GmbH	Hamburg
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum des Saarlandes, Medizinische Klinik III	Homburg	Saarland
Germany	Städtisches Klinikum Karlsruhe, Medizinische Klinik IV	Karlsruhe	Baden-Württemberg
Germany	Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Innere Medizin III	Kiel
Germany	Leipzig Heart Institute GmbH	Leipzig
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Medizinische Klinik II	Lübeck
Germany	Universitätsmedizin Mainz	Mainz
Germany	Universitätsklinikum Mannheim	Mannheim
Germany	Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen	München
Germany	Klinikum Neuperlach, Städtisches Klinikum München GmbH	München
Germany	Technische Universität München, Medizinische Klinik und Poliklinik I	München	Bayern
Germany	Klinikum der Universität München	Munich	Bayern
Germany	Universitätsklinikum Münster	Münster
Germany	Universitätsklinik der Paracelsus Medizinischen Privatuniversität, Klinikum Nürnberg	Nürnberg
Germany	Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin II	Regensburg	Bayern
Germany	Universitätsklinikum Tübingen, Medizinische Klinik III	Tübingen	Baden-Württemberg
Germany	Kliniken Nordoberpfalz AG, Klinikum Weiden	Weiden
Germany	St. Josefs-Hospital Wiesbaden	Wiesbaden
Germany	HELIOS Herzzentrum Wuppertal, Klinik für Kardiologie	Wuppertal	NRW

Sponsors (3)

Lead Sponsor	Collaborator
LMU Klinikum	Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), Medtronic Bakken Research Center

Countries where clinical trial is conducted

Austria,  Germany, 

References & Publications (2)

Bauer A, Kantelhardt JW, Barthel P, Schneider R, Mäkikallio T, Ulm K, Hnatkova K, Schömig A, Huikuri H, Bunde A, Malik M, Schmidt G. Deceleration capacity of heart rate as a predictor of mortality after myocardial infarction: cohort study. Lancet. 2006 May 20;367(9523):1674-81. — View Citation

Rizas KD, Nieminen T, Barthel P, Zürn CS, Kähönen M, Viik J, Lehtimäki T, Nikus K, Eick C, Greiner TO, Wendel HP, Seizer P, Schreieck J, Gawaz M, Schmidt G, Bauer A. Sympathetic activity-associated periodic repolarization dynamics predict mortality following myocardial infarction. J Clin Invest. 2014 Apr;124(4):1770-80. doi: 10.1172/JCI70085. Epub 2014 Mar 18. Erratum in: J Clin Invest. 2014 Jun 2;124(6):2808. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Detection of serious arrhythmic events	Time to detection of one of the following serious arrhythmic events: atrial fibrillation =6 min, higher degree AV-block = IIb, ventricular tachycardia with a cycle length =320ms lasting for =12 sec (corresponding to 40 beats), sustained ventricular tachycardia and ventricular fibrillation	18 months
Secondary	Composite of all-cause mortality, stroke, systemic arterial thromboembolism and unplanned hospitalizations for decompensated heart failure	Time to one of following clinical events: death, stroke, systemic arterial thromboembolism and unplanned hospitalization for decompensated heart failure	18 months
Secondary	All cause mortality	Time to death	18 months
Secondary	Cardiovascular mortality	Time to cardiovascular death	18 months
Secondary	Unplanned hospitalizations for decompensated heart failure	Time to unplanned hospitalizations for decompensated heart failure	18 months
Secondary	Sinus arrest >6sec	Time to detection of sinus arrest >6sec	18 months
Secondary	Atrial fibrillation =6 min	Time to detection of atrial fibrillation =6 min	18 months
Secondary	Higher degree AV-block = IIb	Time to detection of higher degree AV-block = IIb	18 months
Secondary	Non-sustained ventricular tachycardia	Time to detection of ventricular tachycardia with a cycle length =320ms lasting for =12 sec	18 months
Secondary	Sustained ventricular tachycardia / ventricular fibrillation	Time to detection of sustained ventricular tachycardia / ventricular fibrillation	18 months

External Links

•   Deutsches Zentrum für Herzkreislaufforschung
•   Related Info