The Prognostic Role of Indices of Sympathetic Nervous System Overdrive in MINOCA

NCT04681612 | Unknown

• 1 other identifier: PRISMA-GR
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Myocardial Infarction With Nonobstructive Coronary Arteries

Keywords

Myocardial infarction; MINOCA; Sympathetic overdrive; SNS; MSNA; Muscle Microneurography; CMR; Heart rate variability

Outcome Measures

Primary Outcomes (3)

• Incidence (%) of Death during follow up

  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

  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

  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 Outcomes (4)

• Frequency (%) of increased long term arrythmia burden

  Assessed at 18 months after the acute event

• Frequency of long term Sustained/ Reccurent Angina

  Assessed at 18 months after the acute event

• Assessment of Quality of Life and General Health Status

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

• Assessment of Sentimental status

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

Study Arms (1)

MINOCA

Patients hospitalised with MINOCA according to the recently published consensus document of ESC after cardiac MRI confirmation.

Diagnostic Test: MSNA; Diagnostic Test: Heart Rate Variability; Diagnostic Test: Blood Pressure Variability; Diagnostic Test: CMR; Diagnostic Test: History, Lab, clinical and hemodynamic parameters

Interventions

MSNA DIAGNOSTIC_TEST

Assessed via Muscle Microneurography during the first 14 days of the acute phase. Indices: busts/min, busts/100bpm

MINOCA

Heart Rate Variability DIAGNOSTIC_TEST

Assessed via 24hr ECG monitoring during the first 14 days of the acute phase. Indices: Time-domain, Frequency-domain, Non-linear

MINOCA

Blood Pressure Variability DIAGNOSTIC_TEST

Assessed via Ambulatory BPM during the first 14 days of the acute phase. Indices: SD, wSD, ARV, CV

MINOCA

CMR DIAGNOSTIC_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

MINOCA

History, Lab, clinical and hemodynamic parameters DIAGNOSTIC_TEST

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

MINOCA

Eligibility Criteria

• Age: 35 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Hippocration General Hospital: lead
• 401 General Military Hospital of Athens: collaborator
• 251 Hellenic Air Force & VA General Hospital: collaborator
• Athens Naval Hospital: collaborator
• Evangelismos General Hospital: collaborator
• Aleksandra General Hospital: collaborator
• Sismanoglio General Hospital: collaborator
• G.Gennimatas General Hospital: collaborator
• Tzaneio General Hospital of Pireus: collaborator
• Elpis General Hospital: collaborator
• Thriasio General Hospital of Elefsina: collaborator
• Laiko General Hospital: collaborator
• Attikon Hospital: collaborator
• KAT General Hospital: collaborator

Study Sites (1)

Hippokration Hospital

Athens, 11527, Greece

RECRUITING

Related Publications (17)

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  PMID: 26597354 BACKGROUND

• Tamis-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.

  PMID: 30913893 BACKGROUND

• Agewall 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.

  PMID: 28158518 BACKGROUND

• Thygesen 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.

  PMID: 30153967 BACKGROUND

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  PMID: 28179398 BACKGROUND

• Dreyer 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.

  PMID: 31222249 BACKGROUND

• Grodzinsky 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.

  PMID: 28239487 BACKGROUND

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  PMID: 28462724 BACKGROUND

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  PMID: 27844333 BACKGROUND

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  PMID: 23399972 BACKGROUND

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  PMID: 24781510 BACKGROUND

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  PMID: 8598068 BACKGROUND

• Arsenos 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.

  PMID: 23912922 BACKGROUND

• Liao 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.

  PMID: 12453910 BACKGROUND

• Vallbo AB, Hagbarth KE, Wallin BG. Microneurography: how the technique developed and its role in the investigation of the sympathetic nervous system. J Appl Physiol (1985). 2004 Apr;96(4):1262-9. doi: 10.1152/japplphysiol.00470.2003.

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  PMID: 29412776 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum biomarkers Plasma biomarkers

MeSH Terms

Conditions

MINOCA; Myocardial Infarction

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Study Officials

• Emmanouil K. Mantzouranis, MD

  Hippokration Hospital

  STUDY DIRECTOR

• Ioannis E. Leontsinis, MD

  Hippokration Hospital

  STUDY DIRECTOR

Central Study Contacts

Costas P. Tsioufis, Prof

CONTACT

002132088000; ktsioufis@hippokratio.gr

Emmanouil K. Mantzouranis, MD

CONTACT

00306973023813; mantzoup@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 18 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Konstantinos Tsioufis, Prof. of Cardiology

Study Record Dates

• First Submitted: December 13, 2020
• First Posted: December 23, 2020
• Study Start: October 8, 2019
• Primary Completion: April 30, 2023
• Study Completion: October 30, 2023
• Last Updated: December 29, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)