Longitudinal Multimarker Risk Models for Very Elderly Patients With Heart Failure and Preserved Ejection Fraction

Heart Failure With Preserved Ejection Fraction Clinical Trial

Official title:

Development of Longitudinal Multimarker Risk Models for Decision Support Across the Clinical Follow-up of Very Elderly Patients With Heart Failure and Preserved Ejection Fraction

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05992558
• Other study ID #: PI21/00541
• Status: Recruiting
• Start date: March 21, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: August 2023
• Source: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
• Contact: Luis Manzano Espinosa, MD PhD
• Phone: 0034913369204
• Email: luis.manzano[@]uah.es
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The goal of this observational study is to develop longitudinal multimarker risk models for decision support during the clinical follow-up of very elderly patients with heart failure and preserved ejection fraction (HFpEF).

The main questions it aims to answer are:

• Can advanced risk prediction models accurately estimate the prognosis of very elderly patients with HFpEF over a 1-year follow-up after a hospitalization for acute heart failure?

• Do novel biomarkers, in addition to routine clinical variables and elderly-specific predictors, contribute to improved risk prediction for these patients?

To this end, very elderly patients (aged 80 or older) who have HFpEF and were admitted for acute heart failure will be included. Clinical and biological data will be collected during their hospitalization and also during follow-up visits 30 and 90 days after discharge.

There is no comparison group in this observational study.

Description:

Background: Very elderly patients with heart failure and preserved ejection fraction (HFpEF) are under-represented in risk prediction models, and the role of prognostic biomarkers in this population is unclear due to the presence of cumulative comorbidity burden. Risk prediction is a useful tool to support decision making across the clinical follow-up of very elderly HFpEF patients.

Aim: To develop longitudinal prognostic models based on readily available clinical and biological variables, novel biomarkers and elderly-specific predictors to estimate prognosis over 1-year follow-up after a HF hospitalization in very elderly patients with HFpEF.

Design: Observational, single-centre, prospective cohort study of very elderly patients (≥80 years old) with HFpEF consecutively admitted for acute HF.

Main outcome: Composite of 1-year all-cause mortality and/or HF-hospitalization. Sample size:

184 patients.

Follow-up time: 1 year. Predictors: Routine clinical variables (sociodemographic, medical history, physical examination, vital signs, laboratory tests, imaging, concomitant medication, quality of life and elderly-specific factors) and novel biomarkers will be longitudinally collected during index hospitalization, 30-day and 90-day post-discharge visits.

Statistical analysis: Kaplan-meier survival analysis. Logistic and Cox proportional-hazards regression models, time-to-event models for repeated events, linear-mixed effects, joint models, LASSO and machine learning techniques will be used for model development.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 184
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 80 Years and older

Eligibility

Inclusion Criteria:

1. age =80 years;

2. diagnosis of HFpEF, requiring the 4 following conditions: b1) typical symptoms and/or signs of HF; b2) left ventricular ejection fraction (LVEF) =50%; b3) elevated levels of natriuretic peptides (NTproBNP =300 pg/mL or BNP =100 pg/mL in sinus rhythm; NT-proBNP =900 pg/mL or BNP =300 pg/mL in atrial fibrillation); and b4) at least one additional criterion: b4.1) relevant structural heart disease (left ventricular hypertrophy and/or left atrial enlargement), or 4.2) diastolic dysfunction;

3. hospitalization with a primary diagnosis of acute HF; and

4. giving informed consent.

Exclusion Criteria:

1. any clinical condition, such as HF secondary to congenital heart disease and severe valve disease, severe renal (requiring dialysis) and liver disease, active malignant diseases, autoimmune diseases, other diseases resulting in <1-year life expectancy or any other condition that, according to investigators' criteria, could significantly interfere with the study objectives;

2. any clinical or social condition that prevents clinical follow-up.

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Preserved Ejection Fraction

Locations

Country	Name	City	State
Spain	Hospital Universitario Ramón y Cajal	Madrid

Sponsors (3)

Lead Sponsor	Collaborator
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal	European Union, Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

References & Publications (8)

Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022 May 3;79(17):1757-1780. doi: 10.1016/j.jacc.2021.12.011. Epub 2022 Apr 1. — View Citation

Kuster N, Huet F, Dupuy AM, Akodad M, Battistella P, Agullo A, Leclercq F, Kalmanovich E, Meilhac A, Aguilhon S, Cristol JP, Roubille F. Multimarker approach including CRP, sST2 and GDF-15 for prognostic stratification in stable heart failure. ESC Heart Fail. 2020 Oct;7(5):2230-2239. doi: 10.1002/ehf2.12680. Epub 2020 Jul 10. — View Citation

Levy WC, Mozaffarian D, Linker DT, Sutradhar SC, Anker SD, Cropp AB, Anand I, Maggioni A, Burton P, Sullivan MD, Pitt B, Poole-Wilson PA, Mann DL, Packer M. The Seattle Heart Failure Model: prediction of survival in heart failure. Circulation. 2006 Mar 21;113(11):1424-33. doi: 10.1161/CIRCULATIONAHA.105.584102. Epub 2006 Mar 13. — View Citation

McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. No abstract available. Erratum In: Eur Heart J. 2021 Oct 14;: — View Citation

Nunez J, Bayes-Genis A, Revuelta-Lopez E, Ter Maaten JM, Minana G, Barallat J, Cserkoova A, Bodi V, Fernandez-Cisnal A, Nunez E, Sanchis J, Lang C, Ng LL, Metra M, Voors AA. Clinical Role of CA125 in Worsening Heart Failure: A BIOSTAT-CHF Study Subanalysis. JACC Heart Fail. 2020 May;8(5):386-397. doi: 10.1016/j.jchf.2019.12.005. Epub 2020 Mar 11. — View Citation

Pacho C, Domingo M, Nunez R, Lupon J, Nunez J, Barallat J, Moliner P, de Antonio M, Santesmases J, Cediel G, Roura S, Pastor MC, Tor J, Bayes-Genis A. Predictive biomarkers for death and rehospitalization in comorbid frail elderly heart failure patients. BMC Geriatr. 2018 May 9;18(1):109. doi: 10.1186/s12877-018-0807-2. — View Citation

Sicras-Mainar A, Sicras-Navarro A, Palacios B, Varela L, Delgado JF. Epidemiology and treatment of heart failure in Spain: the HF-PATHWAYS study. Rev Esp Cardiol (Engl Ed). 2022 Jan;75(1):31-38. doi: 10.1016/j.rec.2020.09.033. Epub 2020 Dec 27. English, Spanish. — View Citation

Taylor CJ, Moore J, O'Flynn N. Diagnosis and management of chronic heart failure: NICE guideline update 2018. Br J Gen Pract. 2019 May;69(682):265-266. doi: 10.3399/bjgp19X702665. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of 1-year all-cause mortality and/or HF-hospitalization	Combined outcome of all-cause mortality and/or readmission for acute heart failure during a 12-month follow-up period after index hospitalization	12 months
Secondary	1-year HF-hospitalization	Readmission for acute heart failure during a 12-month follow-up period after index hospitalization	12 months
Secondary	3-month HF-hospitalization	Readmission for acute heart failure during a 3-month follow-up period after index hospitalization	3 months
Secondary	1-month HF-hospitalization	Readmission for acute heart failure during a 1-month follow-up period after index hospitalization	1 month
Secondary	1-year all-cause hospitalization	All-cause readmission during a 12-month follow-up period after index hospitalization	12 months
Secondary	3-month all-cause hospitalization	All-cause readmission during a 3-month follow-up period after index hospitalization	3 months
Secondary	1-month all-cause hospitalization	All-cause readmission during a 1-month follow-up period after index hospitalization	1 month
Secondary	1-year all-cause mortality	All-cause mortality during a 12-month follow-up period after index hospitalization	12 months
Secondary	1-year cardiovascular mortality	Cardiovascular mortality during a 12-month follow-up period after index hospitalization	12 months
Secondary	1-year urgent HF visits	Urgent or unscheduled visit with new or worsening symptoms of acute heart failure requiring initiation of intravenous diuretic or vasoactive agent or mechanical or surgical intervention, with no hospital admission, during a 12-month follow-up period after index hospitalization	12 months
Secondary	3-month urgent HF visits	Urgent or unscheduled visit with new or worsening symptoms of acute heart failure requiring initiation of intravenous diuretic or vasoactive agent or mechanical or surgical intervention, with no hospital admission, during a 3-month follow-up period after index hospitalization	3 months
Secondary	1-month urgent HF visits	Urgent or unscheduled visit with new or worsening symptoms of acute heart failure requiring initiation of intravenous diuretic or vasoactive agent or mechanical or surgical intervention, with no hospital admission, during a 1-month follow-up period after index hospitalization	1 month
Secondary	1-year worsening in NYHA class	Worsening of New York Heart Association (NYHA) Functional Classification (Class I to IV) at 12 months from the index hospitalization.	12 months