CATSTAT-HF: Serum Catestatin Expression and Cardiometabolic Parameters in Patients With Congestive Heart Failure

Sponsor

Josko Bozic (Other)

Overall Status

Completed

CT.gov ID

NCT03389386

Collaborator

University of Split, School of Medicine (Other)

120

Enrollment

Location

14.7

Actual Duration (Months)

8.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure，Congestive	Diagnostic Test: Blood withdrawal for laboratory analysis Other: Standard-of-care treatment Diagnostic Test: Transthoracic echocardiography (TTE)

Study Design

Study Type:

Observational

Actual Enrollment :

120 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Serum Catestatin Expression and Cardiometabolic Parameters in Patients With Congestive Heart Failure

Actual Study Start Date :

Jan 25, 2018

Actual Primary Completion Date :

Apr 16, 2019

Actual Study Completion Date :

Apr 16, 2019

Arms and Interventions

Arm	Intervention/Treatment
Congestive Heart Failure (NYHA II-IV) N=90 Patients with a clinically documented diagnosis of congestive heart failure (CHF), as assessed per New York Heart Association (NYHA) functional classification will be prospectively and consecutively enrolled in this group. Patients will be of both sexes, enrolled in 1:1 ratio. All subjects in this group will undergo blood withdrawal for laboratory analysis, transthoracic echocardiography (TTE) examination and will be treated with the Standard-of-care treatment according to their current clinical condition at admission.	Diagnostic Test: Blood withdrawal for laboratory analysis Participants in this study will have their peripheral blood sampled from the cubital vein and the total volume withdrawn for the purposes of this study will be no more than 22 mL per person. Parameters of interest in the laboratory analysis will include serum catestatin levels, NT-proBNP levels, hs-cTnI, parameters of inflammation and renal function as well as standard biochemistry and complete blood count (CBC) panels. Other: Standard-of-care treatment Patients diagnosed with chronic heart failure will receive optimal standards of care in terms of pharmacologic management, according to their current clinical condition. Diagnostic Test: Transthoracic echocardiography (TTE) Participants from both groups will undergo transthoracic echocardiography examination that will measure established hemodynamic parameters of systolic and diastolic cardiac function as well as parameters of LV and RV strain in the selected subset of patients.
Healthy Control Group N=30 Healthy volunteers (both sexes, enrolled in 1:1 ratio) with a negative history of cardiovascular diseases will be enrolled in this group that will serve as a study control. All subjects in this group will undergo blood withdrawal for laboratory analysis and transthoracic echocardiography (TTE) examination.	Diagnostic Test: Blood withdrawal for laboratory analysis Participants in this study will have their peripheral blood sampled from the cubital vein and the total volume withdrawn for the purposes of this study will be no more than 22 mL per person. Parameters of interest in the laboratory analysis will include serum catestatin levels, NT-proBNP levels, hs-cTnI, parameters of inflammation and renal function as well as standard biochemistry and complete blood count (CBC) panels. Diagnostic Test: Transthoracic echocardiography (TTE) Participants from both groups will undergo transthoracic echocardiography examination that will measure established hemodynamic parameters of systolic and diastolic cardiac function as well as parameters of LV and RV strain in the selected subset of patients.

Arm

Intervention/Treatment

Congestive Heart Failure (NYHA II-IV)

N=90 Patients with a clinically documented diagnosis of congestive heart failure (CHF), as assessed per New York Heart Association (NYHA) functional classification will be prospectively and consecutively enrolled in this group. Patients will be of both sexes, enrolled in 1:1 ratio. All subjects in this group will undergo blood withdrawal for laboratory analysis, transthoracic echocardiography (TTE) examination and will be treated with the Standard-of-care treatment according to their current clinical condition at admission.

Diagnostic Test: Blood withdrawal for laboratory analysis

Participants in this study will have their peripheral blood sampled from the cubital vein and the total volume withdrawn for the purposes of this study will be no more than 22 mL per person. Parameters of interest in the laboratory analysis will include serum catestatin levels, NT-proBNP levels, hs-cTnI, parameters of inflammation and renal function as well as standard biochemistry and complete blood count (CBC) panels.

Other: Standard-of-care treatment

Patients diagnosed with chronic heart failure will receive optimal standards of care in terms of pharmacologic management, according to their current clinical condition.

Diagnostic Test: Transthoracic echocardiography (TTE)

Participants from both groups will undergo transthoracic echocardiography examination that will measure established hemodynamic parameters of systolic and diastolic cardiac function as well as parameters of LV and RV strain in the selected subset of patients.

Healthy Control Group

N=30 Healthy volunteers (both sexes, enrolled in 1:1 ratio) with a negative history of cardiovascular diseases will be enrolled in this group that will serve as a study control. All subjects in this group will undergo blood withdrawal for laboratory analysis and transthoracic echocardiography (TTE) examination.

Diagnostic Test: Blood withdrawal for laboratory analysis

Diagnostic Test: Transthoracic echocardiography (TTE)

Outcome Measures

Primary Outcome Measures

Catestatin levels in blood serum [3 months]
The goal is to determine and compare serum catestatin levels in patients with congestive heart failure, stratified by the left ventricular ejection fraction (LVEF) in three groups: reduced, mid-range, and preserved ejection fraction (HFrEF, HFmrEF, HFpEF). Furthermore, catestatin plasma levels will be compared between patients with congestive heart failure and healthy volunteers.

Secondary Outcome Measures

Relationship of serum catestatin levels with the echocardiographic parameters of cardiac function [3 months]
The potential relationship of catestatin serum levels with established parameters of systolic and diastolic cardiac function, as assessed by transthoracic echocardiography among patients with congestive heart failure will be examined.
Relationship of serum catestatin levels with the selected laboratory indices [3 months]
The potential relationship of catestatin serum levels with the NT-proBNP, inflammatory biomarkers and standard hematologic/biochemical indices will be examined.

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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