Clinical trial NCT03389386: Serum Catestatin Expression and Cardiometabolic Parameters in Patients With Congestive Heart Failure
Official title: Serum Catestatin Expression and Cardiometabolic Parameters in Patients With Congestive Heart Failure
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Failure，Congestive
Keywords: Congestive Heart Failure
Catestatin
Chromogranin A
Echocardiography
Biomarkers
Ventricular Dysfunction, Left
Comorbidity
Lead sponsor: University Hospital of Split
Sponsor class: OTHER
Collaborators: name: University of Split, School of Medicine
First posted: 2018-01-03
Enrollment: 120
Sex: ALL
Minimum age (years): 35
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients in the Congestive Heart Failure group will be consecutively enrolled from the pool of patients that will present with signs and symptoms of heart failure at Internal Medicine Emergency Department (ED) of the University Hospital of Split and will be subsequently admitted and hospitalized with working diagnosis of decompensated heart failure (I50.0). Patients that meet eligibility criteria and do not fulfill any of the excluding criteria will be further included in the study.

Participants in the Healthy Control group will be enrolled from the sample of healthy residents of Split or nearby communities that meet the eligibility criteria for the study inclusion.

Brief summary: The congestive heart failure (HF) is a condition associated with substantial morbidity, mortality, and high healthcare expenditures. From the pathophysiological standpoint, several mechanisms contribute to the progression and dysfunction of the failing heart such as an increased hemodynamic overload, impaired myocyte calcium cycling, upregulated apoptotic activity, deficient or increased production of extracellular matrix, genetic predilections and, finally, excessive neurohumoral stimulation. The vasoactive neurohumoral systems such as sympathetic nervous system, renin-angiotensin-aldosterone system (RAAS) and arginine vasopressin (AVP) system all play a role in maintaining volume and circulatory homeostasis in the situation of impaired cardiac output.

Catestatin (CST), on another hand, is a novel endogenous peptide cleaved from chromogranin A (CgA) that is involved in the regulation of cardiac function and arterial blood pressure. The role of this peptide is to elicit potent catecholamine release-inhibitory activity by acting at the level of the nicotinic acetylcholine receptors. Therefore, the main hypothesis of this study is that the observed serum CST levels will reflect the degree of neurohormonal activation in HF, showing a significant relationship with the degree of disease severity as measured by relevant functional classifications (such as NYHA class and/or similar). Secondly, investigators expect to detect correlation of catestatin serum levels with the established risk stratification scores in HF and with the echocardiographic parameters of the ventricular function, both in terms of systolic and diastolic cardiac function. Parameters of inflammation, NT-proBNP, hs-cTnI, renal function parameters, and basic hematologic/biochemistry indices from peripheral blood will also be obtained and analyzed for all study participants.

Furthermore, according to the latest European Society of Cardiology (ESC) guidelines for the diagnosis and treatment of acute and chronic HF, participants with established congestive HF and the whole spectrum of left ventricular ejection fractions ranging from \<40% to ≥50% will be included in the study.

Finally, all echocardiographic and laboratory parameters obtained from peripheral blood will be recorded and compared with respective healthy and matched control participants while participants diagnosed with HF will additionally be analyzed for potential differences between subgroups of interest.


Eligibility criteria: Inclusion Criteria:

* Healthy adult men and women, 35-90 years of age
* Patients with clinically documented diagnosis of congestive heart failure (CHF) according to New York Heart Association (NYHA) functional classification (II-IV)

Exclusion Criteria:

* Age criteria:

  * Persons below legal age (\<18 years)
  * Adults younger than 35 years of age
  * Adults older than 90 years of age
* Participants with following conditions:

  * Diabetes mellitus type I
  * Documented or newly-established severe valvular or pericardial disease
  * Infiltrative or hypertrophic cardiomyopathy
  * Primary pulmonary disease or cor pulmonale
  * Active malignant disease and/or active infectious disease
  * Significant systemic autoimmune disease
  * A positive history of excessive alcohol, drug, narcotics, and sedative consumption
  * Significant psychiatric or neurologic condition
  * Immunocompromised patients or patients that are under immunosuppressive treatment
  * Significant liver or renal insufficiency (primary renal or hepatic disease)
  * Hemorrhagic diathesis or significant coagulopathy
  * Positive recent history of cancer chemotherapeutic drug use
  * A positive history of acute coronary syndrome or stroke within 3 months prior to study enrollment

Primary outcomes:
measure: Catestatin levels in blood serum
timeFrame: 3 months
Secondary outcomes:
measure: Relationship of serum catestatin levels with the echocardiographic parameters of cardiac function
timeFrame: 3 months
measure: Relationship of serum catestatin levels with the selected laboratory indices
timeFrame: 3 months
Other outcomes:
Locations:
city: Split
country: Croatia
facility: University Hospital of Split
state: Split-Dalmatia County
Study officials:
affiliation: Department of Pathophysiology, University of Split School of Medicine
name: Josko Bozic, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Borovac JA, Glavas D, Susilovic Grabovac Z, Supe Domic D, Stanisic L, D'Amario D, Kwok CS, Bozic J. Circulating sST2 and catestatin levels in patients with acute worsening of heart failure: a report from the CATSTAT-HF study. ESC Heart Fail. 2020 Oct;7(5):2818-2828. doi: 10.1002/ehf2.12882. Epub 2020 Jul 18.
citation: Borovac JA, Glavas D, Susilovic Grabovac Z, Supe Domic D, Stanisic L, D'Amario D, Duplancic D, Bozic J. Right Ventricular Free Wall Strain and Congestive Hepatopathy in Patients with Acute Worsening of Chronic Heart Failure: A CATSTAT-HF Echo Substudy. J Clin Med. 2020 May 2;9(5):1317. doi: 10.3390/jcm9051317.
citation: Borovac JA, Glavas D, Susilovic Grabovac Z, Supe Domic D, D'Amario D, Bozic J. Catestatin in Acutely Decompensated Heart Failure Patients: Insights from the CATSTAT-HF Study. J Clin Med. 2019 Jul 30;8(8):1132. doi: 10.3390/jcm8081132.