Clinical trial NCT02594488: Implantable Cardiac Monitors in High-Risk Post-Infarction Patients With Cardiac Autonomic Dysfunction
Official title: Implantable Cardiac Monitors in High-risk Post-infarction Patients With Cardiac Autonomic Dysfunction and Moderately Reduced Left Ventricular Ejection Fraction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Myocardial Infarction
Autonomic Nervous System Diseases
Keywords: Myocardial infarction
Autonomic nervous system
Risk stratification
Implantable cardiac monitor
Sudden cardiac death
ECG
Lead sponsor: LMU Klinikum
Sponsor class: OTHER
Collaborators: name: Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
name: Medtronic Cardiac Rhythm and Heart Failure
First posted: 2015-11-03
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Detection of serious arrhythmic events
timeFrame: 18 months
Secondary outcomes:
measure: Composite of all-cause mortality, stroke, systemic arterial thromboembolism and unplanned hospitalizations for decompensated heart failure
timeFrame: 18 months
measure: All cause mortality
timeFrame: 18 months
measure: Cardiovascular mortality
timeFrame: 18 months
measure: Unplanned hospitalizations for decompensated heart failure
timeFrame: 18 months
measure: Sinus arrest >6sec
timeFrame: 18 months
measure: Atrial fibrillation ≥6 min
timeFrame: 18 months
measure: Higher degree AV-block ≥ IIb
timeFrame: 18 months
measure: Non-sustained ventricular tachycardia
timeFrame: 18 months
measure: Sustained ventricular tachycardia / ventricular fibrillation
timeFrame: 18 months
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck, Universitätsklinik für Innere Medizin III
city: Karlsruhe
country: Germany
facility: Städtisches Klinikum Karlsruhe, Medizinische Klinik IV
state: Baden-Württemberg
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen, Medizinische Klinik III
state: Baden-Württemberg
city: Munich
country: Germany
facility: Klinikum der Universität München
state: Bayern
city: München
country: Germany
facility: Technische Universität München, Medizinische Klinik und Poliklinik I
state: Bayern
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin II
state: Bayern
city: Wuppertal
country: Germany
facility: HELIOS Herzzentrum Wuppertal, Klinik für Kardiologie
state: NRW
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes, Medizinische Klinik III
state: Saarland
city: Aachen
country: Germany
facility: Universtitätsklinikum der RWTH Aachen, Medizinische Klinik I
city: Berlin
country: Germany
facility: Universitätsmedizin Berlin, Klinik für Kardiologie, Charite, Campus Benjamin Franklin
city: Berlin
country: Germany
facility: Universitätsmedizin Berlin, Klinik für Kardiologie, Charite, Campus Virchow Kinikum
city: Bernried
country: Germany
facility: Klinik Höhenried, Rehabilitationszentrum am Starnberger See
city: Dresden
country: Germany
facility: Herzzentrum Dresden, Univeristätsklinik an der TU Dresden
city: Essen
country: Germany
facility: Universitätklinikum Essen, Klinik für Kardiologie und Angiologie
city: Füssen
country: Germany
facility: Kliniken Ostallgäu-Kaufbeuren, Klinik Füssen
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald, Klinik für Innere Medizin B
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen, Klinikum für Kardiologie und Pneumologie
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg, Abteilung für Kardiologie
city: Hamburg
country: Germany
facility: Universitäres Herzzentrum Hamburg GmbH
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Innere Medizin III
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Leipzig
country: Germany
facility: Leipzig Heart Institute GmbH
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Medizinische Klinik II
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim
city: München
country: Germany
facility: Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen
city: München
country: Germany
facility: Klinikum Neuperlach, Städtisches Klinikum München GmbH
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Nürnberg
country: Germany
facility: Universitätsklinik der Paracelsus Medizinischen Privatuniversität, Klinikum Nürnberg
city: Weiden
country: Germany
facility: Kliniken Nordoberpfalz AG, Klinikum Weiden
city: Wiesbaden
country: Germany
facility: St. Josefs-Hospital Wiesbaden
Study officials:
affiliation: LMU Klinikum
name: Axel Bauer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: LMU Klinikum
name: Stefan Kaeaeb, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: LMU Klinikum
name: Steffen Massberg, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.