Clinical trial NCT05960968: Gender Specific Registry in Subjects Hospitalized With Heart Failure in Santiago
Official title: Gender Specific Registry in Subjects Hospitalized With Heart Failure in Santiago( GENESIS Registry): Pilot Heart Failure Registry Looking for Sex Analysis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Heart Failure
Keywords: Heart Failure,
Gender
Women
Epidemiology
Lead sponsor: Fundacion de la Sociedad Chilena de Cardiologia y Cirugia Cardiovascular
Sponsor class: OTHER
Collaborators: name: Hospital Dipreca
name: Pontificia Universidad Catolica de Chile
First posted: 2023-07-27
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population must comply with the definition of Heart Failure according to 2021 European Society of Cardiology (ESC) Guidelines. A practical definition of HF will be shortness of breath and/or fatigue and /or ankle swelling, and/or jugular venous distention and /or rales at the lung examination, with an ejection fraction by echocardiography \>= 40% ( HF with Reduced ejection fraction- HFrEF) and /or greater than 40% (41 to 49 % represents HF with midly reduced ejection fraction-HFmrEF and \>= 50% Preserved Eyection Fraction-HFpEF); this last one associated with pro BNP \> 125 pg/ml in sinusal rhythm.

Brief summary: This is an observational registry, which main purpose is to assess sex-related differences in heart failure (HF) presentation, management, and prognosis in patients admitted to a hospital with a certain diagnosis of HF. The diagnosis will be based on European Society of Cardiology (ESC) definition of HF ( clinical syndrome characterized by symptoms and/or signs caused by a cardiac abnormality, that results in elevated intracardiac pressure and/or inadequate output at rest or exercise ). The sample will be obtained prospectively by recruitment of patients of two hospitals of Santiago de Chile.

Detailed description: -Methods Study design and participants

Observational and prospective registry led by the Chilean Society of Cardiology and Cardiac Surgery Foundation (Fundación SOCHICAR), that will be held at hospitals of different communes in urban Santiago. This project will incorporate two hospitals in a period of one year.

The hospital selection will be based on the purpose of having the most clinical information of the patient regarding his/her cardiac condition. Both participating centers must have coronary units, cardiac surgery, and interventional cardiology. Also, both hospitals must have medical teams with expertise in cardiac imaging, and have access to a local laboratory that performs biomarkers (i.e. NT-terminal pro-brain natriuretic peptide (NTpro-BNP), usTroponin).

The registry consists of a descriptive cross-sectional survey. Thereby, this study is a one-time assessment, with no visit schedule.

Ethics consideration The registry must be approved by the Ethics committee of each clinical center, or in case of not having one, by the Metropolitan Region Ethics Committee respective of each area. Each patient must be informed about the study's rationale and his/ her potential willingness of participation. Written informed consent will be obtained from all participants before data collection.

Study population: approximately 500 patients hospitalized in the two recruiting centers during one year who comply with all the eligible criteria and without exclusion criteria.

-Data source Data will be obtained from the medical files, and will be collected prospectively by a center coordinator using a tablet electronic survey. The survey will be created using a Google form questionnaire, easy to fill in and register.

The confidentiality of the patient will be protect, using patients´ identification based on their initials (first name - first last name - second last name) plus an odd or even sequential number according to the belonging hospital (ie: Mary Jo Salas Gómez MSG1).

The registry will include: demographic, cardiovascular (CV) risk factors, medical history, comorbidities, blood biochemical parameters, diagnostic imaging determinants, treatment, and outcomes data.

The information about Patient Healthe Questionnaire (PHQ) 9 questionnaire will be answered confidentially by the patient in the tablet

* Study assessment The registry consists of a descriptive cross-sectional survey. Thereby, this study is a one-time assessment, with no visit schedule
* Study limitations The main study limitation will be the failure to recruit 500 patients in the one-year period.

With respect to data limitation, the investigators will be conditioned by the information available in the medical file, and the laboratory and imaging exams requested by the head and referral physicians.

STATISTICAL METHODS Sample size and statistical power; precision assessment The sample size was estimated considering the data reported in one of the largest trials that have addressed sex differences in heart failure (HF-Action Trial by Sex, Am Heart J. 2009 Oct; 158(40): S16-S23.) 20. This trial shows that the prevalence of Heart Failure of ischemic cause (one of the main objectives of our trial) was 59% in males and 32% in females.

The calculation of the sample size was carried out to find significant differences between the prevalence of heart failure from ischemic etiology in female patients consecutively hospitalized compared to male, based on Chi-square test for comparison of proportions, considering a significance of 95% and power of 90 %. Therefore,the investigators will included in our study approximately 500 patients knowing that to get a significance of 95 % and a power of 90% the investigators must recruit at least 156 patients (52 females and 104 males) considering 2:1 male-to-female proportion. In order to perform a stratified analysis, the investigators estimated that the lowest sample size for each center should be 78 patients.( with 2:1 male -to - female proportion)

-Statistical considerations

Data management:

The data completeness and accuracy will be addressed through out-of-range alerts and control of unreported data. The nurse coordinator will verify the completeness and accuracy of the information and send the respective queries on a daily basis.

Missing data will be addressed according to covariate. Given the observational data collection of the registry, few data could be missing. These data will be addressed according the kind of covariate. In general, a multiple imputation strategy will be performed.

All the data will be electronically registered in an Excel file. Privileges will be conferred according the role of the personnel on the study. The Principal Investigators will have access to all data.

-Statistical Analyses: All the important covariates will be recorded. Specifically, information on patients' characteristics, demographics, basal functional capacity, complete blood test analyses, EKG, echocardiography, and relevant clinical information will be registered at baseline according to the protocol of each center. For analyses purposes, the prevalence of HF phenotype (ie. with preserved, mildly and reduced ejection fraction), and etiology (ie. ischemic and non ischemic) will be considered as primary outcomes.

All the variables will be tested for normality using Shapiro-Wilk test. The investigatorswill compare the percentages of heart failure with preserved ejection fraction (HFpEF), with mildly reduced ejection fraction (HFmrEF) and reduced ejection fraction (HFrEF) phenotypes according to gender, using Chi-square test. Also, the investigators will compare the percentages of HF etiology (ie. Ischemic and non ischemic) according to gender, using Chi-square test. Moreover, T-test statistics will be used according the variable.

The demographic variables that will be incorporated are:

* Age
* Sex
* Educational Level: years of education \< 8, \> 8 and/or \< 12, \>12 years
* Married, single, divorced, widowed
* Race and Ethnic origin
* Insurance status
* Family income: ≤ $ 326.000 pesos (basic income) or less U$ 500 $ 326.000 -$ 652.000 $ 652.000 - $ 1.000.000 $ 1.000.000 -$2.000.000 $ ≥ 2.000.000- \<3.000.000 $ ≥ 3.000.000
* Employed, non employed, retired

The medical history that will be asked are:

* Anemia
* Smoking
* Diabetes
* Obesity
* Depression
* Hyperlipidemia
* Hypertension
* Atrial fibrillation /atrial flutter
* Ventricular arrhythmias
* Coronary disease
* Ischemic heart disease /Previous myocardial infarction (MI)
* Chronic obstructive pulmonary disease (COPD) / asthma
* Cerebrovascular disease: Ischemic Stroke /Haemorrhagic stroke / transient ischaemic attack (TIA)
* Peripheral vascular disease
* Renal insufficiency (MRDR: less 60 ml /min /m2)
* Dialysis (peritoneo/ Hemodialysis)
* Preeclampsia / Gestational Diabetes / Premature delivery
* Premature or late menarche
* Premature of late menopause
* Hyperkalemia
* Previous hospitalization
* Malignancies
* Autoimmune diseases ( i.e. Erythematosus Systemic Lupus, Rheumatoid Arthritis, Chron Disease, Vasculitis , etc)
* Genetic and Metabolic Disease (i.e. Fabry Disease, Muscular Dystrophies)

HF Characteristics.

* Preserved
* Mildly Reduced
* Reduced

HF cause: ischemic, non ischemic and hypertensive.

Decompensating HF clinical factors.

* Medication and diet non-adherence
* Atrial fibrillation /flutter
* Arrhythmias (other than AF) including bradyarrhythmias
* Infections
* Acute renal failure
* Acute coronary syndrome
* Anemia
* Pulmonary thromboembolism
* Others: specified

Precipitating clinical factors.

* Respiratory ( pneumonia and others)
* Arrhythmias
* Medication non-compliance
* Diet non-compliance
* Uncontrolled Hypertension
* Renal Failure
* Myocardial Ischemia (ACS)

Questionnaires:

* Quality of life Kansas City Cardiomyopathy Questionnaire.
* Depression: Patient Health Questionnaire 9 (PHQ-9(scale)
* HFpEF approach: The new H2FPEF (Heavy, 2 or more Hypertensive drugs, atrial Fibrillation, Pulmonary hypertension \[pulmonary artery systolic pressure \> 35 mmHg\], Elder age \> 60 years, and elevated Filling pressures \[E/e´\>9\] ) score in patients hospitalized with HFpEF
* Frailty Score: The Frail Score

Laboratory Determinations:

* Nt-pro BNP
* Hemoglobin levels
* White blood count
* Creatinine
* Blood urea nitrogen (BUN)
* Plasma Electrolytes
* Troponin US
* Albumin
* Lipid profile
* Thyroid stimulating hormone (TSH)
* Hemoglobin A 1 C (if appropriate)
* Ferritin and Iron levels

Imaging Determinations

1. Echocardiography:

   * Ejection Fraction
   * Left Atrial volume
   * Left ventricular dimensions ( Systolic, Diastolic) and /or volumes.
   * LV segmentary motility (septal, anterior, inferior, posterior, lateral): akinesia,hypokinesia, dyskinesia( Yes/No for each one),
   * Presence of left ventricule (LV) thrombus
   * Pulmonary systolic arterial pressure
   * Mitral E/e´ratio
   * Global Longitudinal Strain
   * Valvular Regurgitations
   * Valvular Stenosis
   * Tricuspide annular plane systolic excursion (TAPSE)
2. Thoracic Radiography (RX)

   * Pulmonary congestion
   * Left Ventricular enlargement
   * Right Ventricular enlargement
   * Pleural effusion
3. Magnetic cardiac resonance

   * Late Gadolinium enhancement
   * Left ventricular volumen and ejection fraction
   * Right ventricular volumen and ejection fraction
   * Infiltrative cardiomyopathy pattern
   * Constrictive pericarditis
   * Thrombus
   * Hypertropic cardiomyopathy
4. Coronary angiogram

   * Coronary stenosis ≥ 50 %: one vessel, two vessels or three vessels
   * Coronary stenosis ≥ 70 %:
   * Coronary Occlusion
   * Ventriculography (Yes or No): ejection fraction and motility description.

Treatment

1- Pharmacological: names and daily doses

* B -blockers (total daily dose): bisoprolol, metoprolol,carvedilol, nebivolol, others
* Angiotensin converting enzyme (ACE) inhibitors (total daily dose): enalapril, ramipril, captopril, perindopril, lisinopril, others/ Angiotensin 2 Receptors blockers (total daily dose): losartan, valsartan, telmisartan, candesartan, Olmesartan, others
* Angiotensin receptor/neprilysin inhibitor (ARNI) (total daily dose): Sacubitril / Valsartan
* Mineralocorticoid antagonist receptors (total daily dose): spironolactone /eplerenone/finerenone
* Sodium glucose cotransporter 2 (SGLT 2) Inhibitors (total daily dose): dapagliflozin, empagliflozin.
* Diuretics (total daily dose): furosemide (Intravenous /oral) metolazone, hydrochlorothiazide,chlortalidone, indapamide, others
* Vericiguat
* Ivabradine
* Digoxin
* Calcium Channel Blockers: amlodipine, others
* Nitrites: Intravenous nitroglycerine/ Isosorbide dinitrate / Isosorbide mononitrate
* Other vasodilators: hydralazine
* Statins: atorvastatin, rosuvastatin, simvastatin, others
* Ezetimibe
* Anti diabetic drugs: metformin, glibenclamide, glipizide, insulin, dipeptidyl peptidase 4 (DPP4) such as sitagliptin, saxagliptin, linagliptin, vildagliptin and glucagon like peptide 1 (GLP1) analogues such as semaglutide, liraglutide, dulaglutide.
* Anticoagulants: vitamin K antagonists (VKA), direct oral anticoagulants (OACs): apixaban, rivaroxaban, dabigatran.
* Platelet inhibitors: aspirin, clopidogrel, ticagrelor.
* Intravenous Iron Therapy
* Intravenous Inotropic therapy: dobutamine, milrinone, levosimendan.

  2. Non pharmacological
* Cardiovascular Rehabilitation (Yes /No)
* Devices: Pacemaker / Cardiac resynchronization therapy/ (ICD) implantable cardioverter-defibrillator.

Eligibility criteria: Inclusion criteria:

* Patient with ≥ 18 years old
* Signed informed consent
* Admitted to the hospital with a :
* 1) diagnosis of acute HF as the leading cause of admission, and in which a CV therapy is needed and prescribed (ie. diuretic, vasodilator, inotropic, device), or
* 2) diagnosis of chronic HF is established during the patient hospitalization based on clinical, biochemical and/or imaging studies, and in which cardiovascular therapy is needed and prescribed (ie. diuretic, vasodilator, inotropic, device ) during the hospitalization.

Exclusion criteria:

* The patient presents a Covid 19 acute infection and/ or severe acute respiratory syndrome (SARS) -CoV 2 pneumonia is confirmed
* The patient presents a psychiatric decompensated disorder and/or a cognitive impairment which preclude assessment of this survey.

Primary outcomes:
measure: The prevalence of HF phenotype( preserved, mildly reduced or reduced) by sex
timeFrame: 12 months
Secondary outcomes:
measure: Prevalence of HF etiologies (ischemic, non ischemic or hypertensive) by sex.
timeFrame: 12 months
measure: To evaluate socioeconomic level in the study population (patients hospitalized with HF) by sex specific analysis.
timeFrame: 12 months
measure: To evaluate educational level in the study population ( patients hospitalized with HF) by sex specific analysis.
timeFrame: 12 months
measure: To assess the prevalence of comorbidities associated with HF by sex-specific analysis
timeFrame: 12 months
measure: To determine the main decompensating risk factors in HF patients by sex-specific analysis
timeFrame: 12 months
Other outcomes:
measure: To determine the presence of depressive symptoms and depression in hospitalized HF patients by a pre-specified sex analysis.
timeFrame: 12 months
measure: To determine if frailty prevalence is different in hospitalized HF patients by sex pre-specified analysis.
timeFrame: 12 months
Locations:
city: Santiago
country: Chile
facility: Paola Varleta
state: Region Metropolitana
Study officials:
affiliation: Fundacion de la Sociedad Chilena de Cardiologia y Cirugia Cardiovascular
name: PAOLA VARLETA, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion de la Sociedad Chilena de Cardiologia y Cirugia Cardiovascular
name: MONICA ACEVEDO, MD
role: PRINCIPAL_INVESTIGATOR
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