Myocardial Infarction With Nonobstructive Coronary ArteriesPRISMANCT04681612
The Prognostic Role of Indices of Sympathetic Nervous System Overdrive in MINOCA
An observational study of Myocardial Infarction With Nonobstructive Coronary Arteries, run by Hippocration General Hospital at 1 site in Greece.
Trial summary
Myocardial infarction with non-obstructive coronary arteries (MINOCA) occurs in 1-13% of all patients with acute myocardial infarction (AMI). According to most studies MINOCA patients seem to have a more favorable prognosis compared to the obstructive AMI ones, but face a significant risk for recurrent events of… Read more about this study
- Who is it for?
- Ages 35 to 85 years
- Conditions the study is for
- Myocardial Infarction With Nonobstructive Coronary Arteries
- What is being tested?
- MSNA, Heart Rate Variability and Blood Pressure Variability
- How many people
- 150 participants
- Where
- 1 siteGreece
- Study dates
- 8 Oct 2019to 30 Oct 2023
- How long will I take part?
- 18 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients hospitalized with MINOCA according to working group position paper and after CMR confirmation of ischemic pattern LGE (excluding myocarditis and Takotsubo)
Who may be able to join
- Patients 35-85 years old.
- Signed ICF.
- Cases fulfilling the MINOCA criteria according to working group position paper and after CMR confirmation of ischemic pattern LGE (excluding myocarditis and Takotsubo)
Who cannot join
- Age <35 and >85 years old
- Myocarditis or Takotsubo (CMR confirmation)
- No CMR available (CKD stage IV-V, pacemaker)
- Inability to assess SNS (polyneuropathy, peripheral neuropathy, dysautonomy, permanent AF)
- Severe valvular disease
- LVEF<35%
Show all 9Show fewer
- Life expenctancy less than the follow up period on recruitement
- Active cancer on treatment
- Psychiatric illness compromising follow up
Trial locations and contacts
1 site in 1 country.
Greece1 site, 1 recruiting
- Recruiting
Hippokration Hospital
Athens, 11527
Emmanouil K. Mantzouranis, MD, 00306973023813, mantzoup@gmail.com
About this study
Official title: The Prognostic Role of Indices of Sympathetic Nervous System Overdrive in Patients With Myocardial Infarction With Non-obstructive Coronary Arteries
Myocardial infarction with non-obstructive coronary arteries (MINOCA) occurs in 1-13% of all patients with acute myocardial infarction (AMI). According to most studies MINOCA patients seem to have a more favorable prognosis compared to the obstructive AMI ones, but face a significant risk for recurrent events of angina. It has been demonstrated that sympathetic nervous system (SNS) overdrive during the acute phase of an acute coronary syndrome (ACS) has a deleterious impact on cardiovascular morbidity and mortality and this is the reason why contemporary treatment strategy of ACS aims towards the inhibition of SNS mechanisms. In the setting of MINOCA, however, data are scarce regarding the prognostic role of SNS activation and the concomitant utility of a similar therapeutical approach.
The aim of this study is to investigate the potential role of SNS in cardiovascular prognosis of MINOCA patients. In the same context, this study is the first, to the investigators' knowledge, registry where the working diagnosis of MINOCA will be confirmed with cardiac magnetic resonance (CMR) imaging.
Read more
This is an observational cohort study with a prospective follow-up of 18 months enrolling all patients aged 38-85 years old who fulfill the diagnostic criteria of MINOCA. Patients will receive treatment according to the latest guidelines and consensus documents. Assessment of SNS will include calculation of indices of heart rate and blood pressure variability, as well as the measurement of muscle sympathetic nerve activity (MSNA) during the first 14 days following the event. Follow-up will include a phone contact at 3, 6 and 12 months to record potential primary endpoints and a clinic visit at 18 months to reassess clinical and lab parameters and record primary and secondary endpoints. Definition of primary endpoints includes hospitalization for new onset of ACS, heart failure, stroke or transient ischemic attack, cardiovascular death or death from any cause. Secondary endpoints include the burden of arrythmias estimated from 24hr ECG recording, recurrent angina assessed via Seattle Angina Questionnaire (SAQ) and the general health condition and quality of life (QoL) assessed using SF-12 questionnaire.
The results of this study are expected to reveal the prognostic role of SNS assessment in patients with MINOCA with a potential clinical implication in a treatment approach towards the inhibition of SNS mechanisms.
Read the detailed description
BACKGROUND
Myocardial infarction with non-obstructive coronary arteries (MINOCA) occurs in 1-13% of all patients with acute myocardial infarction (AMI). According to most studies MINOCA patients seem to have a more favorable prognosis compared to the obstructive AMI ones, but face a significant risk for recurrent events of angina. MINOCA consists a clinical entity characterized by a heterogeneous and poorly understood pathophysiological substrate (plaque disruption, coronary epicardial and microvascular spasm, thromboembolism, thrombophilia, spontaneous dissection, myocardial bridges, microvascular dysfunction), whereas current data leave significant knowledge gaps regarding the risk stratification and the proper therapeutical approach of these patients. Sympathetic nervous system (SNS) overdrive during the acute phase of an acute coronary syndrome (ACS) is an expected reflex mechanism aiming to maintain homeostasis. On the other hand, it has been demonstrated that it has a deleterious impact on cardiovascular morbidity and mortality and this is the reason why contemporary treatment strategy of ACS aims towards the inhibition of SNS mechanisms. In the setting of MINOCA, however, data are scarce regarding the prognostic role of SNS activation and the concomitant utility of a similar therapeutical approach.
AIM OF THE STUDY
The primary aim of this study is to investigate the potential role of SNS in cardiovascular prognosis of MINOCA patients. Furthermore, investigators will assess relations between various SNS parameters and clinical characteristics of these patients, as well as other indices of cardiovascular function (biomarkers, imaging). In the same context, this study is the first, to the investigators' knowledge, registry where the working diagnosis of MINOCA will be confirmed with cardiac magnetic resonance (CMR) imaging.
METHODS
This is an observational cohort study with a prospective follow-up of 18 months enrolling all patients aged 35-85 years old who fulfill the diagnostic criteria of MINOCA, on the condition that CMR does not reveal findings compatible with a diagnosis of myocarditis or Takotsubo. Patients will receive treatment according to the latest guidelines and consensus documents. During hospitalization, a complete medical history will be recorded and all basic clinical and lab parameters will be collected. Assessment of SNS will include calculation of indices of heart rate and blood pressure variability derived from 24hr monitoring using validated devices, as well as the measurement of muscle sympathetic nerve activity (MSNA) during the first 14 days following the event. Follow-up will include a phone contact at 3, 6 and 12 months to record potential primary endpoints and a clinic visit at 18 months to reassess clinical and lab parameters and record primary and secondary endpoints. Definition of primary endpoints includes hospitalization for new onset of ACS, heart failure, stroke or transient ischemic attack, cardiovascular death or death from any cause. Secondary endpoints include the burden of arrythmias estimated from 24hr ECG recording, recurrent angina assessed via Seattle Angina Questionnaire (SAQ) and the general health condition and quality of life (QoL) assessed using SF-12 questionnaire and Hospital Anxiety and Depression Scale (HADS).
- Sympathetic tone estimation:
Α. MSNA. After patient's stabilization the test will be performed and the derived data will be the number of bursts per min and the average bursts per 100 beats.
- Ambulatory heart rate and blood pressure monitoring. Heart rate variability will be analyzed via Kubios software for short-term and long-term heart rate variability. Blood pressure short-term variability will be expressed as SD, wSD, ARV, CV, time rate of BP variation.
For data analysis, SPSS 24.0 software will be used. Continuous parametric data will be expressed as mean and SD. For categoric parametric data results will be presented in means of frequency and percentage. Comparisons between categoric parameters will be done with test x2. Comparisons between the mean values for continuous parameters with normal distribution will be done via unpaired student's test. Comparisons between categoric parameters will be done with Mann Whitney U test. Normal distribution will be checked with Kolmogorov-Smirnov test. Correlation analysis will be done via Pearson Phi coefficient or Spearman Rho. Statistically significant will be differences with p value < 0.05. Evaluation of correlations between selected variables and cardiovascular events and mortality will be via Kaplan Maier curves.
STUDY LIMITATIONS
- Study will include MINOCA patients irrespective of the underlying pathophysiological mechanism. This is the result of the inablity of most centers to perform intravascular imaging (IVUS, OCT) on a routine basis and the tendency to avoid spasm provoking procedures during coronary angiography.
- Although most data will be recorded during the acute/hospitalization phase, the time frame of MSNA and CMR is expected to vary according to the clinical state of the participants and the technical capabilities of the centers. However, an effort will be made not to overlap the 14 days time limit proposed by the majority of investigators.
- CMR will be take place in different centers thus some extent of interobserver variability is expected. However results will be reassessed by a single investigator.
ESTIMATED RESEARCH OUTCOMES
- It will be the first registry, to the investigators' knowledge, that will record data of SNS activation in patients will CMR-confirmed MINOCA.
- The results of the present study are expected to reveal the prognostic role of SNS assessment in patients with MINOCA with a potential clinical implication in a treatment approach towards the inhibition of SNS mechanisms.
- Furthermore, assessment of correlations between parameters of cardiac function and CMR imaging with the level of SNS activation will provide a valuable insight towards the elucidation of the potential role of SNS overdrive during the acute phase of MINOCA.
- Last but not least, follow up assessment will provide information regarding the long-term incidence of persistent or recurrent angina as well as the impact of MINOCA in future quality of life, sentimental state and general health status.
- Being tested
- MSNA, Heart Rate Variability, Blood Pressure Variability, CMR, History, Lab, clinical and hemodynamic parameters
- Keywords
- Myocardial infarction, MINOCA, Sympathetic overdrive, SNS, MSNA, Muscle Microneurography, CMR, Heart rate variability
- Medical subject headings
- MINOCA, Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MSNADiagnostic test
Assessed via Muscle Microneurography during the first 14 days of the acute phase.
Indices: busts/min, busts/100bpm
Heart Rate VariabilityDiagnostic test
Assessed via 24hr ECG monitoring during the first 14 days of the acute phase. Indices: Time-domain, Frequency-domain, Non-linear
Blood Pressure VariabilityDiagnostic test
Assessed via Ambulatory BPM during the first 14 days of the acute phase. Indices: SD, wSD, ARV, CV
CMRDiagnostic test
Cardiac Magnetic Resonance during the first 14 days of the acute phase. Assessment of oedema, Late Gadolinium Enhancement ischaemic pattern. Assessment of cardiac function parameters
History, Lab, clinical and hemodynamic parametersDiagnostic test
- Description of event, 2. Risk factors, 3. Medical history, 4. ECG parameters, 5. ECHO parameters, 6. Hemodynamic parameters of acute phase and hospitalization, 7. Coronary angiogram paraemeters, 7. Complete lab parameter assessment, 8. Thrombofilia assessment, 9. SF-12 QoL and Anxiety and Depression Scale (HADS) questionnaires
| Study group | Role | What they receive |
|---|---|---|
| MINOCA | Patients hospitalised with MINOCA according to the recently published consensus document of ESC after cardiac MRI confirmation. Receives: Diagnostic Test: MSNA; Diagnostic Test: Heart Rate Variability; Diagnostic Test: Blood Pressure Variability; Diagnostic Test: CMR; Diagnostic Test: History, Lab, clinical and hemodynamic parameters |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence (%) of Death during follow up
Number of participants dead due to cardiovascular or any other cause
Measured: Assessed at 4 time points after the acute event: 3 months, 6 months, 12 months, 18 months
Incidence (%) of Hospitalization for Major Cardiovascular Events (MACEs) during follow up
Number of participants hospitalized due to: ACS (STEMI,NSTEMI,Unstable Angina), Decompensated heart failure, Stroke
Measured: Assessed at 4 time points after the acute event: 3 months, 6 months, 12 months, 18 months
Incidence (%) of the Composite endpoint
Incidence (%) of the composite endpoint that includes: Number of participants either hospitalized for MaCEs (ACS, Decompensated heart failure, Stroke) or dead due to a cardiovascular or any other cause
Measured: Assessed at 4 time points after the acute event: 3 months, 6 months, 12 months, 18 months
Secondary outcomes (4)
Frequency (%) of increased long term arrythmia burden
Number of participants fulfilling 1 or more criteria for increased arrythmia burden assessed via 24hr ECG monitor at follow up visit.
Criteria assessed: PVCs>10%, AF>30sec, NSVT, complete heart block
Measured: Assessed at 18 months after the acute event
Frequency of long term Sustained/ Reccurent Angina
Seattle angina questionnaire (SAQ) will be filled by participants at follow up visit.
SAQ provides a quantification of sentimental and physical impact of angina on participants. It is a 19-question self-administered questionnaire assessing physical limitation, angina persistence and frequency, satisfaction of treatment and the overall impact of the disease on the participant. Scores range from 0 to 100. Lower scores depict a greater overall impact of angina on the participant.
Measured: Assessed at 18 months after the acute event
Assessment of Quality of Life and General Health Status
Medical Outcomes Study 12-Item Short Form (SF-12) will be filled by participants during the acute phase and follow up visit in order to assess the long term impact of MINOCA on the participants' quality of life. SF-12 consists of 12 questions and its score ranges from 0 to 100. Lower scores depict a worse quality of life for the participant.
Measured: Assessed at 1-14 days and 18 months after the acute event
Assessment of Sentimental status
Hospital Anxiety and Depresion Scale (HADS) questionnaire will be filled by participants during the acute phase and follow up visit in order to assess the long term impact of MINOCA on the participants' emotional status (anxiety, depression). HADS consists of 14 questions and its score ranges from 0 to 21 separetely for anxiety and depression quantification.
Scores: 0-7 = Normal, 8-10 = Borderline abnormal (borderline case), 11-21 = Abnormal (case).
Measured: Assessed at 1-14 days and 18 months after the acute event
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2020
- Study start8 Oct 2019
- Primary completion30 Apr 2023 (estimated)
- Study completion30 Oct 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for Myocardial Infarction With Nonobstructive Coronary ArteriesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 150 participants (estimated)
- Target duration
- 18 Months
Sponsor and investigators
- Lead sponsor
- Hippocration General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- 401 General Military Hospital of Athens, 251 Hellenic Air Force & VA General Hospital, Athens Naval Hospital, Evangelismos Hospital, Aleksandra General Hospital, Sismanoglio General Hospital, G.Gennimatas General Hospital, Tzaneio General Hospital of Pireus, Elpis General Hospital, Thriasio General Hospital of Elefsina, Laiko General Hospital, Attikon Hospital, KAT General Hospital
- Responsible party
- Principal investigator, Konstantinos Tsioufis, Hippocration General Hospital
- Investigators
- Emmanouil K. Mantzouranis, MD, Study director, Hippokration HospitalIoannis E. Leontsinis, MD, Study director, Hippokration Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04681612
- Sponsor's protocol ID
- PRISMA-GR
- Acronym
- PRISMA
- Status last verified
- Dec 2020
- First submitted
- 13 Dec 2020
- Last updated
- 29 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pasupathy S, Tavella R, Beltrame JF. The What, When, Who, Why, How and Where of Myocardial Infarction With Non-Obstructive Coronary Arteries (MINOCA). Circ J. 2016;80(1):11-6. doi: 10.1253/circj.CJ-15-1096. Epub 2015 Nov 20.
PubMed 26597354Tamis-Holland JE, Jneid H, Reynolds HR, Agewall S, Brilakis ES, Brown TM, Lerman A, Cushman M, Kumbhani DJ, Arslanian-Engoren C, Bolger AF, Beltrame JF; American Heart Association Interventional Cardiovascular Care Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Epidemiology and Prevention; and Council on Quality of Care and Outcomes Research. Contemporary Diagnosis and Management of Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease: A Scientific Statement From the American Heart Association. Circulation. 2019 Apr 30;139(18):e891-e908. doi: 10.1161/CIR.0000000000000670.
PubMed 30913893Agewall S, Beltrame JF, Reynolds HR, Niessner A, Rosano G, Caforio AL, De Caterina R, Zimarino M, Roffi M, Kjeldsen K, Atar D, Kaski JC, Sechtem U, Tornvall P; WG on Cardiovascular Pharmacotherapy. ESC working group position paper on myocardial infarction with non-obstructive coronary arteries. Eur Heart J. 2017 Jan 14;38(3):143-153. doi: 10.1093/eurheartj/ehw149. No abstract available.
PubMed 28158518Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol. 2018 Oct 30;72(18):2231-2264. doi: 10.1016/j.jacc.2018.08.1038. Epub 2018 Aug 25. No abstract available.
PubMed 30153967Pasupathy S, Air T, Dreyer RP, Tavella R, Beltrame JF. Systematic review of patients presenting with suspected myocardial infarction and nonobstructive coronary arteries. Circulation. 2015 Mar 10;131(10):861-70. doi: 10.1161/CIRCULATIONAHA.114.011201. Epub 2015 Jan 13.
PubMed 25587100Lindahl B, Baron T, Erlinge D, Hadziosmanovic N, Nordenskjold A, Gard A, Jernberg T. Medical Therapy for Secondary Prevention and Long-Term Outcome in Patients With Myocardial Infarction With Nonobstructive Coronary Artery Disease. Circulation. 2017 Apr 18;135(16):1481-1489. doi: 10.1161/CIRCULATIONAHA.116.026336. Epub 2017 Feb 8.
PubMed 28179398Dreyer RP, Tavella R, Curtis JP, Wang Y, Pauspathy S, Messenger J, Rumsfeld JS, Maddox TM, Krumholz HM, Spertus JA, Beltrame JF. Myocardial infarction with non-obstructive coronary arteries as compared with myocardial infarction and obstructive coronary disease: outcomes in a Medicare population. Eur Heart J. 2020 Feb 14;41(7):870-878. doi: 10.1093/eurheartj/ehz403.
PubMed 31222249Grodzinsky A, Arnold SV, Gosch K, Spertus JA, Foody JM, Beltrame J, Maddox TM, Parashar S, Kosiborod M. Angina Frequency After Acute Myocardial Infarction In Patients Without Obstructive Coronary Artery Disease. Eur Heart J Qual Care Clin Outcomes. 2015;1(2):92-99. doi: 10.1093/ehjqcco/qcv014. Epub 2015 Jul 23.
PubMed 28239487Tsioufis C, Iliakis P, Kasiakogias A, Konstantinidis D, Lovic D, Petras D, Doumas M, Tsiamis E, Papademetriou V, Tousoulis D. Non-pharmacological Modulation of the Autonomic Nervous System for Heart Failure Treatment: Where do We Stand? Curr Vasc Pharmacol. 2017;16(1):30-43. doi: 10.2174/1570161115666170428124756.
PubMed 28462724Jamali HK, Waqar F, Gerson MC. Cardiac autonomic innervation. J Nucl Cardiol. 2017 Oct;24(5):1558-1570. doi: 10.1007/s12350-016-0725-7. Epub 2016 Nov 14.
PubMed 27844333Parati G, Ochoa JE, Lombardi C, Bilo G. Assessment and management of blood-pressure variability. Nat Rev Cardiol. 2013 Mar;10(3):143-55. doi: 10.1038/nrcardio.2013.1. Epub 2013 Feb 12.
PubMed 23399972Stergiou GS, Kollias A, Ntineri A. Assessment of drug effects on blood pressure variability: which method and which index? J Hypertens. 2014 Jun;32(6):1197-200. doi: 10.1097/HJH.0000000000000201. No abstract available.
PubMed 24781510Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996 Mar 1;93(5):1043-65. No abstract available.
PubMed 8598068Arsenos P, Gatzoulis K, Dilaveris P, Manis G, Tsiachris D, Archontakis S, Vouliotis AI, Sideris S, Stefanadis C. Arrhythmic sudden cardiac death: substrate, mechanisms and current risk stratification strategies for the post-myocardial infarction patient. Hellenic J Cardiol. 2013 Jul-Aug;54(4):301-15. No abstract available.
PubMed 23912922Liao D, Carnethon M, Evans GW, Cascio WE, Heiss G. Lower heart rate variability is associated with the development of coronary heart disease in individuals with diabetes: the atherosclerosis risk in communities (ARIC) study. Diabetes. 2002 Dec;51(12):3524-31. doi: 10.2337/diabetes.51.12.3524.
PubMed 12453910
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Prognostic Role of Indices of Sympathetic Nervous System Overdrive in Patients With Myocardial Infarction With Non-obstructive Coronary Arteries
- ClinicalTrials.gov ID
- NCT04681612
- Acronym / sponsor ID
- PRISMA / PRISMA-GR
- Keywords
- Myocardial infarction, MINOCA, Sympathetic overdrive, SNS, MSNA, Muscle Microneurography, CMR, Heart rate variability
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Hippocration General HospitalUniversity, hospital or other
- Collaborators
- 401 General Military Hospital of Athens, 251 Hellenic Air Force & VA General Hospital, Athens Naval Hospital, Evangelismos Hospital, Aleksandra General Hospital, Sismanoglio General Hospital, G.Gennimatas General Hospital, Tzaneio General Hospital of Pireus, Elpis General Hospital, Thriasio General Hospital of Elefsina, Laiko General Hospital, Attikon Hospital, KAT General Hospital
- Study start
- 8 Oct 2019 (actual)
- Primary completion
- 30 Apr 2023 (estimated)
- Study completion
- 30 Oct 2023 (estimated)
- First posted
- 23 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Myocardial infarction with non-obstructive coronary arteries (MINOCA) occurs in 1-13% of all patients with acute myocardial infarction (AMI). According to most studies MINOCA patients seem to have a more favorable prognosis compared to the obstructive AMI ones, but face a significant risk for recurrent events of angina. It has been demonstrated that sympathetic nervous system (SNS) overdrive during the acute phase of an acute coronary syndrome (ACS) has a deleterious impact on cardiovascular morbidity and mortality and this is the reason why contemporary treatment strategy of ACS aims towards the inhibition of SNS mechanisms. In the setting of MINOCA, however, data are scarce regarding the prognostic role of SNS activation and the concomitant utility of a similar therapeutical approach.
The aim of this study is to investigate the potential role of SNS in cardiovascular prognosis of MINOCA patients. In the same context, this study is the first, to the investigators' knowledge, registry where the working diagnosis of MINOCA will be confirmed with cardiac magnetic resonance (CMR) imaging.
This is an observational cohort study with a prospective follow-up of 18 months enrolling all patients aged 38-85 years old who fulfill the diagnostic criteria of MINOCA. Patients will receive treatment according to the latest guidelines and consensus documents. Assessment of SNS will include calculation of indices of heart rate and blood pressure variability, as well as the measurement of muscle sympathetic nerve activity (MSNA) during the first 14 days following the event. Follow-up will include a phone contact at 3, 6 and 12 months to record potential primary endpoints and a clinic visit at 18 months to reassess clinical and lab parameters and record primary and secondary endpoints. Definition of primary endpoints includes hospitalization for new onset of ACS, heart failure, stroke or transient ischemic attack, cardiovascular death or death from any cause. Secondary endpoints include the burden of arrythmias estimated from 24hr ECG recording, recurrent angina assessed via Seattle Angina Questionnaire (SAQ) and the general health condition and quality of life (QoL) assessed using SF-12 questionnaire.
The results of this study are expected to reveal the prognostic role of SNS assessment in patients with MINOCA with a potential clinical implication in a treatment approach towards the inhibition of SNS mechanisms.
Detailed description
BACKGROUND
Myocardial infarction with non-obstructive coronary arteries (MINOCA) occurs in 1-13% of all patients with acute myocardial infarction (AMI). According to most studies MINOCA patients seem to have a more favorable prognosis compared to the obstructive AMI ones, but face a significant risk for recurrent events of angina. MINOCA consists a clinical entity characterized by a heterogeneous and poorly understood pathophysiological substrate (plaque disruption, coronary epicardial and microvascular spasm, thromboembolism, thrombophilia, spontaneous dissection, myocardial bridges, microvascular dysfunction), whereas current data leave significant knowledge gaps regarding the risk stratification and the proper therapeutical approach of these patients. Sympathetic nervous system (SNS) overdrive during the acute phase of an acute coronary syndrome (ACS) is an expected reflex mechanism aiming to maintain homeostasis. On the other hand, it has been demonstrated that it has a deleterious impact on cardiovascular morbidity and mortality and this is the reason why contemporary treatment strategy of ACS aims towards the inhibition of SNS mechanisms. In the setting of MINOCA, however, data are scarce regarding the prognostic role of SNS activation and the concomitant utility of a similar therapeutical approach.
AIM OF THE STUDY
The primary aim of this study is to investigate the potential role of SNS in cardiovascular prognosis of MINOCA patients. Furthermore, investigators will assess relations between various SNS parameters and clinical characteristics of these patients, as well as other indices of cardiovascular function (biomarkers, imaging). In the same context, this study is the first, to the investigators' knowledge, registry where the working diagnosis of MINOCA will be confirmed with cardiac magnetic resonance (CMR) imaging.
METHODS
This is an observational cohort study with a prospective follow-up of 18 months enrolling all patients aged 35-85 years old who fulfill the diagnostic criteria of MINOCA, on the condition that CMR does not reveal findings compatible with a diagnosis of myocarditis or Takotsubo. Patients will receive treatment according to the latest guidelines and consensus documents. During hospitalization, a complete medical history will be recorded and all basic clinical and lab parameters will be collected. Assessment of SNS will include calculation of indices of heart rate and blood pressure variability derived from 24hr monitoring using validated devices, as well as the measurement of muscle sympathetic nerve activity (MSNA) during the first 14 days following the event. Follow-up will include a phone contact at 3, 6 and 12 months to record potential primary endpoints and a clinic visit at 18 months to reassess clinical and lab parameters and record primary and secondary endpoints. Definition of primary endpoints includes hospitalization for new onset of ACS, heart failure, stroke or transient ischemic attack, cardiovascular death or death from any cause. Secondary endpoints include the burden of arrythmias estimated from 24hr ECG recording, recurrent angina assessed via Seattle Angina Questionnaire (SAQ) and the general health condition and quality of life (QoL) assessed using SF-12 questionnaire and Hospital Anxiety and Depression Scale (HADS).
- Sympathetic tone estimation:
Α. MSNA. After patient's stabilization the test will be performed and the derived data will be the number of bursts per min and the average bursts per 100 beats.
- Ambulatory heart rate and blood pressure monitoring. Heart rate variability will be analyzed via Kubios software for short-term and long-term heart rate variability. Blood pressure short-term variability will be expressed as SD, wSD, ARV, CV, time rate of BP variation.
For data analysis, SPSS 24.0 software will be used. Continuous parametric data will be expressed as mean and SD. For categoric parametric data results will be presented in means of frequency and percentage. Comparisons between categoric parameters will be done with test x2. Comparisons between the mean values for continuous parameters with normal distribution will be done via unpaired student's test. Comparisons between categoric parameters will be done with Mann Whitney U test. Normal distribution will be checked with Kolmogorov-Smirnov test. Correlation analysis will be done via Pearson Phi coefficient or Spearman Rho. Statistically significant will be differences with p value < 0.05. Evaluation of correlations between selected variables and cardiovascular events and mortality will be via Kaplan Maier curves.
STUDY LIMITATIONS
- Study will include MINOCA patients irrespective of the underlying pathophysiological mechanism. This is the result of the inablity of most centers to perform intravascular imaging (IVUS, OCT) on a routine basis and the tendency to avoid spasm provoking procedures during coronary angiography.
- Although most data will be recorded during the acute/hospitalization phase, the time frame of MSNA and CMR is expected to vary according to the clinical state of the participants and the technical capabilities of the centers. However, an effort will be made not to overlap the 14 days time limit proposed by the majority of investigators.
- CMR will be take place in different centers thus some extent of interobserver variability is expected. However results will be reassessed by a single investigator.
ESTIMATED RESEARCH OUTCOMES
- It will be the first registry, to the investigators' knowledge, that will record data of SNS activation in patients will CMR-confirmed MINOCA.
- The results of the present study are expected to reveal the prognostic role of SNS assessment in patients with MINOCA with a potential clinical implication in a treatment approach towards the inhibition of SNS mechanisms.
- Furthermore, assessment of correlations between parameters of cardiac function and CMR imaging with the level of SNS activation will provide a valuable insight towards the elucidation of the potential role of SNS overdrive during the acute phase of MINOCA.
- Last but not least, follow up assessment will provide information regarding the long-term incidence of persistent or recurrent angina as well as the impact of MINOCA in future quality of life, sentimental state and general health status.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 18 Months
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MINOCA | – | Diagnostic Test: MSNA, Diagnostic Test: Heart Rate Variability, Diagnostic Test: Blood Pressure Variability, Diagnostic Test: CMR, Diagnostic Test: History, Lab, clinical and hemodynamic parametersPatients hospitalised with MINOCA according to the recently published consensus document of ESC after cardiac MRI confirmation. |
Who may qualify
- Ages
- 35 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients hospitalized with MINOCA according to working group position paper and after CMR confirmation of ischemic pattern LGE (excluding myocarditis and Takotsubo)
Key inclusion criteria (3 listed)
- Patients 35-85 years old.
- Signed ICF.
- Cases fulfilling the MINOCA criteria according to working group position paper and after CMR confirmation of ischemic pattern LGE (excluding myocarditis and Takotsubo)
Key exclusion criteria (9 listed)
- Age <35 and >85 years old
- Myocarditis or Takotsubo (CMR confirmation)
- No CMR available (CKD stage IV-V, pacemaker)
- Inability to assess SNS (polyneuropathy, peripheral neuropathy, dysautonomy, permanent AF)
- Severe valvular disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MSNAAssessed via Muscle Microneurography during the first 14 days of the acute phase. Indices: busts/min, busts/100bpm | Diagnostic test | MINOCA |
| Heart Rate VariabilityAssessed via 24hr ECG monitoring during the first 14 days of the acute phase. Indices: Time-domain, Frequency-domain, Non-linear | Diagnostic test | MINOCA |
| Blood Pressure VariabilityAssessed via Ambulatory BPM during the first 14 days of the acute phase. Indices: SD, wSD, ARV, CV | Diagnostic test | MINOCA |
| CMRCardiac Magnetic Resonance during the first 14 days of the acute phase. Assessment of oedema, Late Gadolinium Enhancement ischaemic pattern. Assessment of cardiac function parameters | Diagnostic test | MINOCA |
| History, Lab, clinical and hemodynamic parameters1. Description of event, 2. Risk factors, 3. Medical history, 4. ECG parameters, 5. ECHO parameters, 6. Hemodynamic parameters of acute phase and hospitalization, 7. Coronary angiogram paraemeters, 7. Complete lab parameter assessment, 8. Thrombofilia assessment, 9. SF-12 QoL and Anxiety and Depression Scale (HADS) questionnaires | Diagnostic test | MINOCA |
Primary outcome
Incidence (%) of Death during follow up
Time frame: Assessed at 4 time points after the acute event: 3 months, 6 months, 12 months, 18 months
Number of participants dead due to cardiovascular or any other cause
Incidence (%) of Hospitalization for Major Cardiovascular Events (MACEs) during follow up
Time frame: Assessed at 4 time points after the acute event: 3 months, 6 months, 12 months, 18 months
Number of participants hospitalized due to: ACS (STEMI,NSTEMI,Unstable Angina), Decompensated heart failure, Stroke
Incidence (%) of the Composite endpoint
Time frame: Assessed at 4 time points after the acute event: 3 months, 6 months, 12 months, 18 months
Incidence (%) of the composite endpoint that includes: Number of participants either hospitalized for MaCEs (ACS, Decompensated heart failure, Stroke) or dead due to a cardiovascular or any other cause
4 secondary outcomes
Frequency (%) of increased long term arrythmia burden
Time frame: Assessed at 18 months after the acute event
Frequency of long term Sustained/ Reccurent Angina
Time frame: Assessed at 18 months after the acute event
Assessment of Quality of Life and General Health Status
Time frame: Assessed at 1-14 days and 18 months after the acute event
Assessment of Sentimental status
Time frame: Assessed at 1-14 days and 18 months after the acute event
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2020.
- Background: PubMed 26597354Pasupathy S, Tavella R, Beltrame JF. The What, When, Who, Why, How and Where of Myocardial Infarction With Non-Obstructive Coronary Arteries (MINOCA). Circ J. 2016;80(1):11-6. doi: 10.1253/circj.CJ-15-1096. Epub 2015 Nov 20.
- Background: PubMed 30913893Tamis-Holland JE, Jneid H, Reynolds HR, Agewall S, Brilakis ES, Brown TM, Lerman A, Cushman M, Kumbhani DJ, Arslanian-Engoren C, Bolger AF, Beltrame JF; American Heart Association Interventional Cardiovascular Care Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Epidemiology and Prevention; and Council on Quality of Care and Outcomes Research. Contemporary Diagnosis and Management of Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease: A Scientific Statement From the American Heart Association. Circulation. 2019 Apr 30;139(18):e891-e908. doi: 10.1161/CIR.0000000000000670.
- Background: PubMed 28158518Agewall S, Beltrame JF, Reynolds HR, Niessner A, Rosano G, Caforio AL, De Caterina R, Zimarino M, Roffi M, Kjeldsen K, Atar D, Kaski JC, Sechtem U, Tornvall P; WG on Cardiovascular Pharmacotherapy. ESC working group position paper on myocardial infarction with non-obstructive coronary arteries. Eur Heart J. 2017 Jan 14;38(3):143-153. doi: 10.1093/eurheartj/ehw149. No abstract available.
- Background: PubMed 30153967Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol. 2018 Oct 30;72(18):2231-2264. doi: 10.1016/j.jacc.2018.08.1038. Epub 2018 Aug 25. No abstract available.
- Background: PubMed 25587100Pasupathy S, Air T, Dreyer RP, Tavella R, Beltrame JF. Systematic review of patients presenting with suspected myocardial infarction and nonobstructive coronary arteries. Circulation. 2015 Mar 10;131(10):861-70. doi: 10.1161/CIRCULATIONAHA.114.011201. Epub 2015 Jan 13.
- Background: PubMed 28179398Lindahl B, Baron T, Erlinge D, Hadziosmanovic N, Nordenskjold A, Gard A, Jernberg T. Medical Therapy for Secondary Prevention and Long-Term Outcome in Patients With Myocardial Infarction With Nonobstructive Coronary Artery Disease. Circulation. 2017 Apr 18;135(16):1481-1489. doi: 10.1161/CIRCULATIONAHA.116.026336. Epub 2017 Feb 8.
- Background: PubMed 31222249Dreyer RP, Tavella R, Curtis JP, Wang Y, Pauspathy S, Messenger J, Rumsfeld JS, Maddox TM, Krumholz HM, Spertus JA, Beltrame JF. Myocardial infarction with non-obstructive coronary arteries as compared with myocardial infarction and obstructive coronary disease: outcomes in a Medicare population. Eur Heart J. 2020 Feb 14;41(7):870-878. doi: 10.1093/eurheartj/ehz403.
- Background: PubMed 28239487Grodzinsky A, Arnold SV, Gosch K, Spertus JA, Foody JM, Beltrame J, Maddox TM, Parashar S, Kosiborod M. Angina Frequency After Acute Myocardial Infarction In Patients Without Obstructive Coronary Artery Disease. Eur Heart J Qual Care Clin Outcomes. 2015;1(2):92-99. doi: 10.1093/ehjqcco/qcv014. Epub 2015 Jul 23.
- Background: PubMed 28462724Tsioufis C, Iliakis P, Kasiakogias A, Konstantinidis D, Lovic D, Petras D, Doumas M, Tsiamis E, Papademetriou V, Tousoulis D. Non-pharmacological Modulation of the Autonomic Nervous System for Heart Failure Treatment: Where do We Stand? Curr Vasc Pharmacol. 2017;16(1):30-43. doi: 10.2174/1570161115666170428124756.
- Background: PubMed 27844333Jamali HK, Waqar F, Gerson MC. Cardiac autonomic innervation. J Nucl Cardiol. 2017 Oct;24(5):1558-1570. doi: 10.1007/s12350-016-0725-7. Epub 2016 Nov 14.
- Background: PubMed 23399972Parati G, Ochoa JE, Lombardi C, Bilo G. Assessment and management of blood-pressure variability. Nat Rev Cardiol. 2013 Mar;10(3):143-55. doi: 10.1038/nrcardio.2013.1. Epub 2013 Feb 12.
- Background: PubMed 24781510Stergiou GS, Kollias A, Ntineri A. Assessment of drug effects on blood pressure variability: which method and which index? J Hypertens. 2014 Jun;32(6):1197-200. doi: 10.1097/HJH.0000000000000201. No abstract available.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emmanouil K. Mantzouranis, MD study director
Hippokration Hospital
Ioannis E. Leontsinis, MD study director
Hippokration Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Myocardial Infarction With Nonobstructive Coronary Arteries, run by Hippocration General Hospital at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Costas P. Tsioufis, Prof (002132088000, ktsioufis@hippokratio.gr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence (%) of Death during follow up (time frame: Assessed at 4 time points after the acute event: 3 months, 6 months, 12 months, 18 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04681612, which also lists 17 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2020.