The Prognostic Role of Indices of Sympathetic Nervous System Overdrive in MINOCA (PRISMA)

December 27, 2020 updated by: Konstantinos Tsioufis, Hippocration General Hospital

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.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

B. 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 Type

Observational

Enrollment (Anticipated)

150

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Emmanouil K. Mantzouranis, MD
  • Phone Number: 00306973023813
  • Email: mantzoup@gmail.com

Study Locations

  • Greece
      • Athens, Greece, 11527
        • Recruiting
        • Hippokration Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients hospitalized with MINOCA according to working group position paper and after CMR confirmation of ischemic pattern LGE (excluding myocarditis and Takotsubo)

Description

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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%
  • Life expenctancy less than the follow up period on recruitement
  • Active cancer on treatment
  • Psychiatric illness compromising follow up

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
MINOCA
Patients hospitalised with MINOCA according to the recently published consensus document of ESC after cardiac MRI confirmation.
Diagnostic test: MSNA

Assessed via Muscle Microneurography during the first 14 days of the acute phase.

Indices: busts/min, busts/100bpm

Diagnostic test: Heart Rate Variability
Assessed via 24hr ECG monitoring during the first 14 days of the acute phase. Indices: Time-domain, Frequency-domain, Non-linear
Diagnostic test: Blood Pressure Variability
Assessed via Ambulatory BPM during the first 14 days of the acute phase. Indices: SD, wSD, ARV, CV
Diagnostic test: CMR
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
Diagnostic test: History, Lab, clinical and hemodynamic parameters
1. 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
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
Assessed at 4 time points after the acute event: 3 months, 6 months, 12 months, 18 months
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
Assessed at 4 time points after the acute event: 3 months, 6 months, 12 months, 18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency (%) of increased long term arrythmia burden
Time Frame: Assessed at 18 months after the acute event

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
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

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.
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
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.
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

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).
Assessed at 1-14 days and 18 months after the acute event

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hippocration General Hospital

Collaborators

KAT General Hospital
Sismanoglio General Hospital
Thriasio General Hospital
Elpis General Hospital
401 General Military Hospital of Athens
251 General Airforce Hospital
Athens Naval Hospital
Evangelismos General Hospital
Aleksandra General Hospital
Genimatas General Hospital of Athens
Tzaneio General Hospital of Pireus
Laiko General Hospital
Attikon General Hospital

Investigators

  • Study Director: Emmanouil K. Mantzouranis, MD, Hippokration Hospital
  • Study Director: Ioannis E. Leontsinis, MD, Hippokration Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 8, 2019

Primary Completion (Anticipated)

April 30, 2023

Study Completion (Anticipated)

October 30, 2023

Study Registration Dates

First Submitted

December 13, 2020

First Submitted That Met QC Criteria

December 19, 2020

First Posted (Actual)

December 23, 2020

Study Record Updates

Last Update Posted (Actual)

December 29, 2020

Last Update Submitted That Met QC Criteria

December 27, 2020

Last Verified

December 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRISMA-GR

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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