The Role of Sympathetic Tone Regarding the Anatomical and Functional Recovery of the Left Ventricle in TakoTsubo Syndrome

NCT04695587 | Unknown DMC

• 1 other identifier: 1920004531
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

TakoTsubo Syndrome (TTS) constitutes an increasingly recognised, heterogenous clinical entity which is associated with considerable short-term mortality. In addition, emerging evidence suggests that, in the long term, TTS can induce the expression of a phenotype similar to HFpEF . Apart from the typical (apical left ventricular) type, the current TTS definition has been expanded to also include the mid-ventricular, the basal and the focal type. Several previous studies on the typical form of the syndrome demonstrated that the principal underlying pathophysiology is sympathetic overactivation. Purpose The aim of this study is to investigate the potential association between the sympathetic tone and the acute phase clinical features of TTS. Furthermore, the investigators aim at exploring possible correlations between the sympathetic tone activity and the diastolic dysfunction, a reported complication occurring one year after the acute phase. This is a prospective observational study enrolling patients aged 18-85 years who fulfill the InterTaK diagnostic criteria and whose CMR within 14 days of the onset is not suggestive of an alternative diagnosis. All patients will be treated on individual basis according to the recent expert consensus statement for TTS. During the baseline evaluation the sympathetic tone will be assessed by means of Muscle Sympathetic Nerve Activity study (MSNA), heart rate and blood pressure variability parameters. Additionally, in a subgroup of participants sympathetic activity and cardiac sympathetic enervation will be evaluated with radioactive Iodine Metaiodobenzylguanidine scintigraphy (mIBG). Sequential echocardiography and CMR indices will be used for heart function and geometry assessment. The investigators will investigate the correlation between the sympathetic tone and the severity of cardiac dysfunction (systolic and diastolic) during the acute phase. Furthermore, the investigators will examine differences of the sympathetic tone effect in association with the localisation of the wall motion abnormality. Stress levels and quality of life will be assessed with respective validated questionnaires. The participants will be followed-up with quarterly clinic reviews for 12 months after the acute event. Baseline measurements will be repeated at the end of the follow-up period. Ethics approval has been obtained from the hospital ethical committee board. The study results are expected to determine the role of the sympathetic tone on the extend, the severity and the localisation of cardiac dysfunction during the acute phase. They are also expected to demonstrate the role of the sympathetic tone on the long-lasting disorder that persists for months following the acute event.

Conditions

Takotsubo Cardiomyopathy

Keywords

sympathetic tone; autonomic nervous system; takotsubo; stress cardiomyopathy; 123MIBG; MSNA; Heart Rate Variability; Blood Pressure Variability

Outcome Measures

Primary Outcomes (2)

• Degree of systolic dysfunction at baseline regarding the sympathetic tone activity

  Assesses the impact of sympathetic tone activity over the subacute phase of syndrome with regards to the degree of the systolic dysfunction during the acute event.

  14 days (subacute phase)

• Degree of systolic dysfunction at baseline with regards to the sympathetic tone activity 12 months after the event

  Assesses the impact of sympathetic tone activity over the subacute phase of syndrome as well as one year after the acute episode with regards to the degree of the systolic dysfunction during the acute event.

  12 months after the acute event

Secondary Outcomes (9)

• Degree of diastolic dysfunction at 12 months regarding the sympathetic tone activity at baseline

  12 months follow up

• Degree of diastolic dysfunction at 12 months regarding the sympathetic tone activity at baseline

  12 months follow up

• Degree of diastolic dysfunction at 12 months regarding the change of sympathetic tone activity during the follow up period

  12 months follow up

• Degree of diastolic dysfunction at 12 months regarding the change of sympathetic tone activity during the follow up period

  12 months follow up

• Degree of myocardial fibrosis at 12 months regarding the sympathetic tone activity at baseline

  12 months follow up

Study Arms (1)

TakoTsubo

Patients hospitalized with TakoTsubo syndrome according to the INTERTAK criteria

Diagnostic Test: 123 MIBG scintigraphy testing; Diagnostic Test: MSNA; Diagnostic Test: ABPM; Diagnostic Test: ECHO; Diagnostic Test: 24hour ECG; Diagnostic Test: CMR

Interventions

123 MIBG scintigraphy testing DIAGNOSTIC_TEST

123 MIBG scintigraphy testing in subacute phase and 12 months after the acute episode in a subgroup of patients according to individualized needs.

TakoTsubo

MSNA DIAGNOSTIC_TEST

MSNA in subacute phase and 12 months after the acute episode

TakoTsubo

ABPM DIAGNOSTIC_TEST

ABPM in subacute phase and 12 months after the acute episode

TakoTsubo

ECHO DIAGNOSTIC_TEST

ECHO in subacute phase and 12 months after the acute episode

TakoTsubo

24hour ECG DIAGNOSTIC_TEST

24hour ECG in subacute phase and 12 months after the acute episode

TakoTsubo

CMR DIAGNOSTIC_TEST

CMR in 12 months after the acute episode

TakoTsubo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This is a prospective, non-interventional observational study which will enroll patients 18-85-year-old, who fulfil the InterTAK diagnostic criteria. The diagnosis will be confirmed with CMR and ECHO which will show the LV systolic recovery. Signed consent form will be obtained and cases that the symptoms were attributed to myocarditis or subendocardial infarction will be excluded. Patients with severe chronic kidney disease (eGFR \< 30 ml/min), severe valvular disease, contraindication to perform any of the aforementioned measurements, chronic atrial fibrillation, permanent pacing, autonomic failure, pregnant or breastfeeding women, psychiatric disease which does not allow adequate co-operation or patients with life expectancy less than a year will not be enrolled. The enrolled cases will be followed up for one year. Data will be collected in a specific form (CRF). These include demographic and somatometric data, past medical history, hemodynamics and sympathetic tone measurements.

You may qualify if:

• age limits
• Subjects able to provide ICF
• Cases fullfilling the InterTAK criteria with CMR to exclude acute myocarditis or myocardial infarction

You may not qualify if:

• age limits
• eGFR \< 30ml/min
• Cases diagnosed with acute myocarditis or acute myocardial infarction
• Severe valvular disease not related to TakoTsubo syndrome
• Pacemaker dependent patients
• Contraindications for CMR performance
• Permanent atrial fibrillation
• Neurological conditions related with autonomic failure
• Pregnancy, lactation
• Iodine allergy
• Chronic heart failure with LVEF \< 35%
• Any condition related with reduced life expectancy at recruitement
• Cancer on active treatment

Sponsors & Collaborators

• Hippocration General Hospital: lead
• Naval Hospital, Athens: collaborator
• General Hospital of Athens Elpis: collaborator
• 401 General Military Hospital of Athens: collaborator
• 251 Hellenic Air Force & VA General Hospital: collaborator
• Evangelismos Hospital: collaborator
• Alexandra Hospital, Athens, Greece: collaborator
• Sismanoglio General Hospital: collaborator
• G.Gennimatas General Hospital: collaborator
• Laikο General Hospital, Athens: collaborator
• Tzaneio General Hospital: collaborator
• Thriasio General Hospital of Elefsina: collaborator
• National and Kapodistrian University of Athens: collaborator

Study Sites (1)

First Cardiology Clinic, Hippocration General Hospital, National and Kapodistrian University of Athens, Athens, Greece

Athens, 11527, Greece

RECRUITING

Related Publications (19)

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• Ghadri JR, Wittstein IS, Prasad A, Sharkey S, Dote K, Akashi YJ, Cammann VL, Crea F, Galiuto L, Desmet W, Yoshida T, Manfredini R, Eitel I, Kosuge M, Nef HM, Deshmukh A, Lerman A, Bossone E, Citro R, Ueyama T, Corrado D, Kurisu S, Ruschitzka F, Winchester D, Lyon AR, Omerovic E, Bax JJ, Meimoun P, Tarantini G, Rihal C, Y-Hassan S, Migliore F, Horowitz JD, Shimokawa H, Luscher TF, Templin C. International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology. Eur Heart J. 2018 Jun 7;39(22):2032-2046. doi: 10.1093/eurheartj/ehy076.

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• Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M, Cammann VL, Sarcon A, Geyer V, Neumann CA, Seifert B, Hellermann J, Schwyzer M, Eisenhardt K, Jenewein J, Franke J, Katus HA, Burgdorf C, Schunkert H, Moeller C, Thiele H, Bauersachs J, Tschope C, Schultheiss HP, Laney CA, Rajan L, Michels G, Pfister R, Ukena C, Bohm M, Erbel R, Cuneo A, Kuck KH, Jacobshagen C, Hasenfuss G, Karakas M, Koenig W, Rottbauer W, Said SM, Braun-Dullaeus RC, Cuculi F, Banning A, Fischer TA, Vasankari T, Airaksinen KE, Fijalkowski M, Rynkiewicz A, Pawlak M, Opolski G, Dworakowski R, MacCarthy P, Kaiser C, Osswald S, Galiuto L, Crea F, Dichtl W, Franz WM, Empen K, Felix SB, Delmas C, Lairez O, Erne P, Bax JJ, Ford I, Ruschitzka F, Prasad A, Luscher TF. Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy. N Engl J Med. 2015 Sep 3;373(10):929-38. doi: 10.1056/NEJMoa1406761.

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• Stiermaier T, Thiele H, Eitel I. Long-term excess mortality in Takotsubo syndrome: is it justified to charge Takotsubo for the excess long-term mortality?: Reply. Eur J Heart Fail. 2016 Jul;18(7):879. doi: 10.1002/ejhf.573. Epub 2016 May 30. No abstract available.

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• Nowak R, Fijalkowska M, Gilis-Malinowska N, Jaguszewski M, Galaska R, Rojek A, Narkiewicz K, Gruchala M, Fijalkowski M. Left ventricular function after takotsubo is not fully recovered in long-term follow-up: A speckle tracking echocardiography study. Cardiol J. 2017;24(1):57-64. doi: 10.5603/CJ.a2017.0001. Epub 2017 Jan 10.

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• Burgdorf C, von Hof K, Schunkert H, Kurowski V. Regional alterations in myocardial sympathetic innervation in patients with transient left-ventricular apical ballooning (Tako-Tsubo cardiomyopathy). J Nucl Cardiol. 2008 Jan-Feb;15(1):65-72. doi: 10.1016/j.nuclcard.2007.08.005. Epub 2007 Oct 29.

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Biospecimen

Retention: SAMPLES WITHOUT DNA

serum and plasma biomarkers

MeSH Terms

Conditions

Takotsubo Cardiomyopathy

Interventions

Electrocardiography

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction, Left; Ventricular Dysfunction

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis

Study Officials

• Konstantinos P Tsioufis, Professor

  1st Cardiolgogy Clinic, Hippocratio General Hospital of Athens, National and Kapodistrian University of Athens, Greece

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Konstantinos P Tsioufis, Professor

CONTACT

21320880000; ktsioufis@hippocratio.gr

Ioannis Leontsinis, MD

CONTACT

00306937171268; giannisleontsinis@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor in Cardiology

Study Record Dates

• First Submitted: December 23, 2020
• First Posted: January 5, 2021
• Study Start: October 8, 2019
• Primary Completion: October 7, 2022
• Study Completion: October 7, 2023
• Last Updated: January 5, 2021

Record last verified: 2021-01

Locations

GR (1)