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

NCT ID: NCT02594488

Last Updated: 2021-06-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-06
• Study Completion Date: 2021-02-28

Brief 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.

Detailed 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.

Conditions

Myocardial Infarction; Autonomic Nervous System Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Remote monitoring

Remote cardiac monitoring by the Reveal® LINQ implantable cardiac monitor

Group Type: ACTIVE_COMPARATOR

Medtronic Reveal LINQ implantable cardiac monitor

Intervention Type: DEVICE

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.

Control arm

Follow-up at the same frequency, but with no implantable cardiac monitor

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DEVICE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)

OTHER

Sponsor Role: collaborator

Medtronic Cardiac Rhythm and Heart Failure

INDUSTRY

Sponsor Role: collaborator

LMU Klinikum

OTHER

Sponsor Role: lead

Responsible Party

Axel Bauer

Prof. Dr. med. Axel Bauer

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Axel Bauer, MD

Role: PRINCIPAL_INVESTIGATOR

LMU Klinikum

Stefan Kaeaeb, MD

Role: PRINCIPAL_INVESTIGATOR

LMU Klinikum

Steffen Massberg, MD

Role: STUDY_CHAIR

LMU Klinikum

Locations

Medizinische Universität Innsbruck, Universitätsklinik für Innere Medizin III

Innsbruck, , Austria

Städtisches Klinikum Karlsruhe, Medizinische Klinik IV

Karlsruhe, Baden-Wurttemberg, Germany

Universitätsklinikum Tübingen, Medizinische Klinik III

Tübingen, Baden-Wurttemberg, Germany

Klinikum der Universität München

Munich, Bavaria, Germany

Technische Universität München, Medizinische Klinik und Poliklinik I

München, Bavaria, Germany

Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin II

Regensburg, Bavaria, Germany

HELIOS Herzzentrum Wuppertal, Klinik für Kardiologie

Wuppertal, North Rhine-Westphalia, Germany

Universitätsklinikum des Saarlandes, Medizinische Klinik III

Homburg, Saarland, 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 Schleswig-Holstein, Campus Kiel, Klinik für Innere Medizin III

Kiel, , Germany

Universitätsklinikum Leipzig

Leipzig, , Germany

Leipzig Heart Institute GmbH

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

Universitätsklinikum Münster

Münster, , Germany

Universitätsklinik der Paracelsus Medizinischen Privatuniversität, Klinikum Nürnberg

Nuremberg, , Germany

Kliniken Nordoberpfalz AG, Klinikum Weiden

Weiden, , Germany

St. Josefs-Hospital Wiesbaden

Wiesbaden, , Germany

Countries

Austria; Germany

References

Rizas KD, Nieminen T, Barthel P, Zurn CS, Kahonen M, Viik J, Lehtimaki 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.

Reference Type: BACKGROUND

PMID: 24642467 (View on PubMed)

Bauer A, Kantelhardt JW, Barthel P, Schneider R, Makikallio T, Ulm K, Hnatkova K, Schomig 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. doi: 10.1016/S0140-6736(06)68735-7.

Reference Type: BACKGROUND

PMID: 16714188 (View on PubMed)

Bauer A, Sappler N, von Stulpnagel L, Klemm M, Schreinlechner M, Wenner F, Schier J, Al Tawil A, Dolejsi T, Krasniqi A, Eiffener E, Bongarth C, Stuhlinger M, Huemer M, Gori T, Wakili R, Sahin R, Schwinger R, Lutz M, Luik A, Gessler N, Clemmensen P, Linke A, Maier LS, Hinterseer M, Busch MC, Blaschke F, Sack S, Lennerz C, Licka M, Tilz RR, Ukena C, Ehrlich JR, Zabel M, Schmidt G, Mansmann U, Kaab S, Rizas KD, Massberg S; SMART-MI-DZHK9 investigators. Telemedical cardiac risk assessment by implantable cardiac monitors in patients after myocardial infarction with autonomic dysfunction (SMART-MI-DZHK9): a prospective investigator-initiated, randomised, multicentre, open-label, diagnostic trial. Lancet Digit Health. 2022 Feb;4(2):e105-e116. doi: 10.1016/S2589-7500(21)00253-3.

Reference Type: DERIVED

PMID: 35090674 (View on PubMed)

Hamm W, Rizas KD, Stulpnagel LV, Vdovin N, Massberg S, Kaab S, Bauer A. Implantable cardiac monitors in high-risk post-infarction patients with cardiac autonomic dysfunction and moderately reduced left ventricular ejection fraction: Design and rationale of the SMART-MI trial. Am Heart J. 2017 Aug;190:34-39. doi: 10.1016/j.ahj.2017.05.006. Epub 2017 May 19.

Reference Type: DERIVED

PMID: 28760211 (View on PubMed)

Rizas KD, Hamm W, Kaab S, Schmidt G, Bauer A. Periodic Repolarisation Dynamics: A Natural Probe of the Ventricular Response to Sympathetic Activation. Arrhythm Electrophysiol Rev. 2016 May;5(1):31-6. doi: 10.15420/aer.2015:30:2.

Reference Type: DERIVED

PMID: 27403291 (View on PubMed)

Related Links

http://dzhk.de/

Deutsches Zentrum für Herzkreislaufforschung

Other Identifiers

118-15

Identifier Type: -

Identifier Source: org_study_id