The Role of CD34+ Stem Cells in the Pathogenesis of Takotsubo Syndrome

NCT07604467 | Recruiting

• 1 other identifier: 0120-118/2021/3
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The underlying mechanisms of microvascular dysfunction in Takotsubo cardiomyopathy remain incompletely understood. As CD34+ cells are essential to coronary microvascular homeostasis we will investigate the potential association between CD34+ cell count and changes in left ventricular function in patients with Takotsubo cardiomyopathy at baseline and 6-month follow-up.

Conditions

Tako Tsubo Cardiomyopathy; Microvascular Dysfunction; CD34+ Stem Cells; Heart Failure; Cardiac Contractility Recovery

Keywords

Takotsubo syndrome; CD34+ stem cells; heart failure; microvascular dysfunction; cardiac contractility recovery

Outcome Measures

Primary Outcomes (1)

• Recovery of left ventricular systolic function assessed by change in left ventricular ejection fraction (LVEF)

  Change in LVEF (%), measured by transthoracic echocardiography using Biplane Simpson's method.

  From enrollment to the end of observational period at 6-month follow-up.

Secondary Outcomes (11)

• Improvement in myocardial contractility and deformation assesed by change in left ventricular global longitudinal strain (LV GLS)

  From enrollment to the end of observational period at 6-month follow-up.

• Reduction in left ventricular filling pressure assessed by change in early mitral inflow velocity (E-wave) and the average of the septal and lateral early diastolic mitral annular velocities ratio (E/e' average)

  From enrollment to the end of observational period at 6-month follow-up.

• Recovery of impaired myocardial relaxation assessed by change in peak early mitral inflow velocity and peak atrial contraction wave velocity ratio (E/A ratio)

  From enrollment to the end of observational period at 6-month follow-up.

• Reduction in pulmonary artery systolic pressure assessed by change in tricuspid regurgitation maximum gradient (TR max gradient)

  From enrollment to the end of observational period at 6-month follow-up.

• Reduction in left ventricular size assessed by left ventricular end-diastolic volume index (LVEDVi)

  From enrollment to the end of observational period at 6-month follow-up.

Study Arms (1)

Takotsubo patients with preserved OR mildly reduced/reduced LVEF at acute event.

Takotsubo patients divided in subgroups based on preserved or mildly reduced/reduced LVEF at acute event.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adult patients, predominantly females, with cardiovascular risk factors.

You may qualify if:

• Minimum age 18 years
• Established TTS per InterTak registry criteria
• Signed consent form

You may not qualify if:

• Patients under the age of 18 years
• Ischemic heart disease with at least one complete total occlusion
• Other concurrent cardiomyopathies
• Active infectious myocarditis
• obstructive coronary artery disease
• Previous hospital stay due to acute coronary syndrome (myocardial infarction) in the last 6 months before TTS acute event
• Previous interventional coronary artery procedure in the last 6 months before TTS acute event
• Significant valvular heart disease
• Significant peripheral artery occlusive disease
• Active or remitted hematologic malignancy
• Patients receiving immunosuppressive therapy
• Significant comorbiditeis affecting patients survival (malignancy)
• Failure to obtain freely given, informed consent form.

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead

Study Sites (1)

Advanced Heart Failure and Transplantation Program, Department of Cardiology, UMC Ljubljana, Slovenia

Ljubljana, Ljubljana, 1000, Slovenia

RECRUITING

Related Publications (5)

• Rai B, Shukla J, Henry TD, Quesada O. Angiogenic CD34 Stem Cell Therapy in Coronary Microvascular Repair-A Systematic Review. Cells. 2021 May 8;10(5):1137. doi: 10.3390/cells10051137.

  PMID: 34066713 BACKGROUND

• Eerdekens R, El Farissi M, De Maria GL, Shetrit A, Sykes R, Ekenback C, Persson J, Spaak J, Couch LS, Alfonso F, Rivero F, Gonzalo N, Escaned J, Nunez Gil IJ, Cruz OV, Shamir RA, Freund O, Vanderheyden M, Belmonte M, Barbato E, Tonino PAL, Banning A, Solberg OG, Berry C, Fearon WF, Zimmermann FM. Prognostic Value of Microvascular Function in Takotsubo Syndrome: A Pooled Analysis of Individual Patient Data. JACC Cardiovasc Interv. 2025 Jul 14;18(13):1646-1656. doi: 10.1016/j.jcin.2025.05.028. Epub 2025 May 22.

  PMID: 40415182 BACKGROUND

• Almendro-Delia M, Lopez-Flores L, Uribarri A, Vedia O, Blanco-Ponce E, Lopez-Flores MDC, Rivas-Garcia AP, Fernandez-Cordon C, Sionis A, Martin-Garcia AC, Vazirani R, Corbi-Pascual M, Salamanca J, Perez-Castellanos A, Martinez-Selles M, Becerra VM, Aritza-Conty D, Lopez-Pais J, Guillen-Marzo M, Lluch-Requerey C, Garcia-Rubira JC, Nunez-Gil IJ; RETAKO Investigators. Recovery of Left Ventricular Function and Long-Term Outcomes in Patients With Takotsubo Syndrome. J Am Coll Cardiol. 2024 Sep 24;84(13):1163-1174. doi: 10.1016/j.jacc.2024.05.075.

  PMID: 39293882 BACKGROUND

• Shaikh N, Sardar M, Jacob A, Alagusundaramoorthy SS, Eng M, Checton J, Shah A. Possible predictive factors for recovery of left ventricular systolic function in Takotsubo cardiomyopathy. Intractable Rare Dis Res. 2018 May;7(2):100-105. doi: 10.5582/irdr.2018.01042.

  PMID: 29862151 BACKGROUND

• 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.

  PMID: 26332547 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples

MeSH Terms

Conditions

Takotsubo Cardiomyopathy; Heart Failure

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Mark Jovanović, MD

CONTACT

+38640977307; mark.jovanovic@kclj.si

Principal Investigator

CONTACT

gregor.poglajen@kclj.si

Study Design

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

Study Record Dates

• First Submitted: May 17, 2026
• First Posted: May 22, 2026
• Study Start: September 6, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 22, 2026

Record last verified: 2026-05

Locations

SL (1)