Evaluation of Myocardial Function by Global Longitudinal Strain (GLS) Measurement in 2D Echocardiography of Patients With Fibromyalgia

NCT ID: NCT07150455

Last Updated: 2025-12-01

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Total Enrollment: 118 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-08-01
• Study Completion Date: 2026-03-01

Brief Summary

Fibromyalgia (FM) is a chronic pain syndrome that affects multiple body systems and is often associated with fatigue, sleep disturbances, anxiety, and other comorbidities. Increasing evidence suggests that FM is also linked to cardiovascular dysfunction due to autonomic imbalance, sympathetic overactivity, and endothelial dysfunction. Patients with FM may therefore be at higher risk of developing subclinical ventricular dysfunction even before overt cardiovascular disease becomes apparent.

Traditional echocardiographic evaluation of left ventricular function is based on ejection fraction (LVEF). However, LVEF has important limitations. It may remain normal despite underlying myocardial impairment, is strongly influenced by loading conditions, and often fails to detect early myocardial dysfunction. Recent advances in echocardiography allow for the assessment of Global Longitudinal Strain (GLS), a sensitive and reproducible measure of myocardial deformation. GLS abnormalities can be detected earlier than changes in LVEF and are predictive of future declines in ejection fraction.

This study aims to evaluate myocardial function in fibromyalgia patients using GLS obtained by two-dimensional speckle-tracking echocardiography (2D-STE). By comparing FM patients with age- and sex-matched healthy controls, the study seeks to determine whether FM patients show a higher prevalence of subclinical ventricular dysfunction.

The study is designed as a prospective, observational, case-control study. A total of 118 participants will be enrolled: 59 patients diagnosed with fibromyalgia according to the 2010 American College of Rheumatology (ACR) criteria, and 59 control subjects without fibromyalgia. The control group will consist of volunteers presenting with mechanical low back pain but without systemic rheumatic disease.

All participants will undergo echocardiographic examination using a standardized protocol with Vivid E95 Dimension ultrasound equipment (GE Healthcare). Global Longitudinal Strain will be measured offline using EchoPAC software, and results will be analyzed according to recommendations of the American Society of Echocardiography. In addition, fibromyalgia patients will complete the Fibromyalgia Impact Questionnaire (FIQ) to evaluate disease severity, and results will be compared with echocardiographic findings.

Primary Outcome: Prevalence of subclinical left ventricular dysfunction, defined as impaired GLS, in fibromyalgia patients compared to controls.

Secondary Outcome: Correlation between GLS values and fibromyalgia disease severity scores.

This study is expected to provide new insights into the cardiovascular involvement of fibromyalgia. Detecting early myocardial impairment with GLS may help identify patients at risk of future cardiovascular complications and may support closer monitoring and preventive strategies in this population.

Detailed Description

Fibromyalgia (FM) is a chronic, multisystem disorder affecting approximately 2-4% of the general population, predominantly women. It is characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, anxiety, cognitive impairment, and autonomic symptoms such as gastrointestinal irregularities, Raynaud-like phenomena, and sicca complaints. The pathophysiology remains incompletely understood but is thought to involve central pain sensitization and dysautonomia.

Emerging evidence indicates that FM is associated with increased cardiovascular risk. Observational studies have demonstrated a higher prevalence of endothelial dysfunction, arterial stiffness, arrhythmias, and coronary artery disease in FM patients. Mechanistically, chronic sympathetic overactivity and persistent catecholamine release may increase myocardial oxygen demand, impair microvascular perfusion, and lead to subtle myocardial dysfunction. Autonomic imbalance has also been documented by heart rate variability studies, supporting impaired sympathetic-parasympathetic regulation. Importantly, the overlap between FM symptoms (fatigue, poor sleep, reduced functional capacity) and those of heart failure suggests a potential underrecognized cardiac component in FM.

Conventional echocardiography relies on left ventricular ejection fraction (LVEF) to evaluate systolic function. However, LVEF may remain normal despite underlying myocardial impairment and is strongly affected by loading conditions and observer variability. Many patients with heart failure present with preserved ejection fraction (HFpEF), underscoring the limitations of LVEF as an early marker of myocardial dysfunction.

Global Longitudinal Strain (GLS), assessed using two-dimensional speckle-tracking echocardiography (2D-STE), has emerged as a more sensitive and reproducible tool for detecting early myocardial dysfunction. GLS abnormalities can precede measurable reductions in LVEF and have prognostic value across diverse conditions including ischemic heart disease, hypertension, valvular disease, chemotherapy-related cardiotoxicity, and heart failure.

Preliminary studies in FM populations suggest possible subclinical myocardial involvement. Some reports describe increased risk of diastolic dysfunction and impaired GLS in FM patients, possibly reflecting the impact of chronic stress and autonomic dysregulation on cardiac mechanics. Nevertheless, systematic and adequately powered investigations remain scarce.

This prospective, observational, case-control study is designed to fill this knowledge gap. The study will enroll 59 FM patients diagnosed according to the 2010 American College of Rheumatology (ACR) criteria and 59 age- and sex-matched controls without systemic rheumatic disease. Echocardiographic examinations will be performed using a standardized protocol (Vivid E95, GE Healthcare), and GLS will be measured offline with EchoPAC software, following the American Society of Echocardiography guidelines. Disease severity in FM will be assessed using the Fibromyalgia Impact Questionnaire (FIQ).

The primary hypothesis is that FM patients will demonstrate a higher prevalence of impaired GLS, consistent with subclinical ventricular dysfunction, compared with controls. The secondary hypothesis is that higher FIQ scores will correlate with greater impairment in GLS, suggesting a relationship between disease burden and cardiac involvement.

The anticipated significance of this research lies in clarifying the cardiovascular component of fibromyalgia. Early identification of myocardial dysfunction using GLS may allow for improved risk stratification, closer clinical monitoring, and preventive strategies aimed at reducing long-term cardiovascular morbidity. Beyond its clinical relevance, this study also extends the application of GLS into a non-traditional, rheumatology-related context, reinforcing the systemic nature of FM and the need for interdisciplinary management approaches.

Conditions

Fibromyalgia (FM); Subclinical Ventricular Dysfunction; Myocardial Function

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Fibromyalgia Patients

Participants aged 18-50 years diagnosed with fibromyalgia according to the 2010 American College of Rheumatology (ACR) criteria. All participants in this group will undergo 2D speckle-tracking echocardiography, including Global Longitudinal Strain (GLS) measurement, for evaluation of myocardial function. No drug or device intervention is administered.

Echocardiographic Assessment (2D Speckle Tracking)

Intervention Type: OTHER

All participants will undergo standardized 2D echocardiographic examination including Global Longitudinal Strain (GLS) measurement. No drug or device intervention is applied.

Healthy Controls

Age- and sex-matched volunteers without fibromyalgia, presenting with mechanical low back pain, otherwise healthy.

Echocardiographic Assessment (2D Speckle Tracking)

Intervention Type: OTHER

All participants will undergo standardized 2D echocardiographic examination including Global Longitudinal Strain (GLS) measurement. No drug or device intervention is applied.

Interventions

Echocardiographic Assessment (2D Speckle Tracking)

All participants will undergo standardized 2D echocardiographic examination including Global Longitudinal Strain (GLS) measurement. No drug or device intervention is applied.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age between 18 and 50 years.
• No diagnosis of fibromyalgia.
• Volunteers presenting with mechanical low back pain but otherwise healthy.

Exclusion Criteria

• Hypertension.
• Coronary artery disease.
• Diabetes mellitus.
• Significant valvular heart disease.
• Documented arrhythmias.
• Congestive heart failure.
• Systemic rheumatic diseases (e.g., SLE, RA).
• Hyperthyroidism or hypothyroidism.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ankara Training and Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Nadide Koca

Physical Medicine & Rehabilitation Specialist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Physical Therapy and Rehabilitation, University of Health Sciences, Ankara Training and Research Hospital

Ankara, Altindag, Turkey (Türkiye)

Countries

Turkey (Türkiye)

References

Rong LQ, Neuburger PJ, Kim J, Devereux RB. Left ventricular global longitudinal strain and cardiac surgical outcomes. Minerva Cardioangiol. 2020 Oct;68(5):489-496. doi: 10.23736/S0026-4725.20.05251-2. Epub 2020 May 29.

Reference Type: BACKGROUND

PMID: 32472988 (View on PubMed)

Tschope C, Senni M. Usefulness and clinical relevance of left ventricular global longitudinal systolic strain in patients with heart failure with preserved ejection fraction. Heart Fail Rev. 2020 Jan;25(1):67-73. doi: 10.1007/s10741-019-09853-7.

Reference Type: BACKGROUND

PMID: 31489515 (View on PubMed)

Chang KV, Hung CH, Sun WZ, Wu WT, Lai CL, Han DS, Chen CC. Evaluating soreness symptoms of fibromyalgia: Establishment and validation of the Revised Fibromyalgia Impact Questionnaire with Integration of Soreness Assessment. J Formos Med Assoc. 2020 Jul;119(7):1211-1218. doi: 10.1016/j.jfma.2019.10.018. Epub 2019 Nov 9.

Reference Type: BACKGROUND

PMID: 31711726 (View on PubMed)

Galvez-Sanchez CM, Reyes Del Paso GA. Diagnostic Criteria for Fibromyalgia: Critical Review and Future Perspectives. J Clin Med. 2020 Apr 23;9(4):1219. doi: 10.3390/jcm9041219.

Reference Type: BACKGROUND

PMID: 32340369 (View on PubMed)

Ueyama H, Kuno T, Takagi H, Krishnamoorthy P, Prandi FR, Palazzuoli A, Sharma SK, Kini A, Lerakis S. Prognostic value of left ventricular global longitudinal strain in mitral regurgitation: a systematic review. Heart Fail Rev. 2023 Mar;28(2):465-483. doi: 10.1007/s10741-022-10265-3. Epub 2022 Jul 28.

Reference Type: BACKGROUND

PMID: 35900680 (View on PubMed)

Smiseth OA, Rider O, Cvijic M, Valkovic L, Remme EW, Voigt JU. Myocardial Strain Imaging: Theory, Current Practice, and the Future. JACC Cardiovasc Imaging. 2025 Mar;18(3):340-381. doi: 10.1016/j.jcmg.2024.07.011. Epub 2024 Sep 11.

Reference Type: BACKGROUND

PMID: 39269417 (View on PubMed)

Velagapudi VM, Pidikiti R, Tighe DA. Is Left Ventricular Global Longitudinal Strain by Two-Dimensional Speckle Tracking Echocardiography in Sepsis Cardiomyopathy Ready for Prime Time Use in the ICU? Healthcare (Basel). 2019 Jan 3;7(1):5. doi: 10.3390/healthcare7010005.

Reference Type: BACKGROUND

PMID: 30609787 (View on PubMed)

Potter E, Marwick TH. Assessment of Left Ventricular Function by Echocardiography: The Case for Routinely Adding Global Longitudinal Strain to Ejection Fraction. JACC Cardiovasc Imaging. 2018 Feb;11(2 Pt 1):260-274. doi: 10.1016/j.jcmg.2017.11.017.

Reference Type: BACKGROUND

PMID: 29413646 (View on PubMed)

Cho KI, Lee JH, Lee HG, Kim SM, Kim TI. Assessment of myocardial function in patients with fibromyalgia and the relationship to chronic emotional and physical stress. Korean Circ J. 2010 Feb;40(2):74-80. doi: 10.4070/kcj.2010.40.2.74. Epub 2010 Feb 23.

Reference Type: BACKGROUND

PMID: 20182592 (View on PubMed)

Sayilir S, Ergun G, Ekiz T. Evaluation of Ventricular Diastolic Function in Patients With Fibromyalgia Syndrome. Arch Rheumatol. 2017 Aug 15;33(2):150-153. doi: 10.5606/ArchRheumatol.2018.6541. eCollection 2018 Jun.

Reference Type: BACKGROUND

PMID: 30207569 (View on PubMed)

Gist AC, Guymer EK, Ajani AE, Littlejohn GO. Fibromyalgia has a high prevalence and impact in cardiac failure patients. Eur J Rheumatol. 2017 Dec;4(4):245-249. doi: 10.5152/eurjrheum.2017.17026. Epub 2017 Nov 2.

Reference Type: BACKGROUND

PMID: 29308277 (View on PubMed)

Zetterman T, Markkula R, Miettinen T, Kalso E. Heart rate variability responses to cognitive stress in fibromyalgia are characterised by inadequate autonomous system stress responses: a clinical trial. Sci Rep. 2023 Jan 13;13(1):700. doi: 10.1038/s41598-023-27581-9.

Reference Type: BACKGROUND

PMID: 36639565 (View on PubMed)

Su CH, Chen JH, Lan JL, Wang YC, Tseng CH, Hsu CY, Huang L. Increased Risk of Coronary Heart Disease in Patients with Primary Fibromyalgia and Those with Concomitant Comorbidity-A Taiwanese Population-Based Cohort Study. PLoS One. 2015 Sep 14;10(9):e0137137. doi: 10.1371/journal.pone.0137137. eCollection 2015.

Reference Type: BACKGROUND

PMID: 26366998 (View on PubMed)

Tsai PS, Fan YC, Huang CJ. Fibromyalgia is associated with coronary heart disease: a population-based cohort study. Reg Anesth Pain Med. 2015 Jan-Feb;40(1):37-42. doi: 10.1097/AAP.0000000000000190.

Reference Type: BACKGROUND

PMID: 25436616 (View on PubMed)

Sethi P, Peiris CD. A Review of Catecholamine Associated Cardiomyopathies and Channelopathies. Cureus. 2020 Feb 11;12(2):e6957. doi: 10.7759/cureus.6957.

Reference Type: BACKGROUND

PMID: 32195067 (View on PubMed)

Kocyigit BF, Akyol A. Coexistence of fibromyalgia syndrome and inflammatory rheumatic diseases, and autonomic cardiovascular system involvement in fibromyalgia syndrome. Clin Rheumatol. 2023 Mar;42(3):645-652. doi: 10.1007/s10067-022-06385-8. Epub 2022 Sep 23.

Reference Type: BACKGROUND

PMID: 36151442 (View on PubMed)

Kulshreshtha P, Deepak KK, Yadav RK, Mukherjee D. Cardiac autonomic neuropathy in fibromyalgia: Revisited. J Back Musculoskelet Rehabil. 2022;35(1):111-117. doi: 10.3233/BMR-200209.

Reference Type: BACKGROUND

PMID: 34092594 (View on PubMed)

Other Identifiers

AnkaraTRH-FTR-NK-07

Identifier Type: -

Identifier Source: org_study_id