Screening for Advanced Heart Failure IN Stable ouTpatientS - The SAINTS Study (SAINTS-A)

Screening for Advanced Heart Failure IN Stable ouTpatientS (The SAINTS Study) - Early Identification of Advanced Heart Failure

The purpose of the Screening for Advanced heart failure IN stable ouTpatientS (SAINTS) study is to determine the prevalence of advanced heart failure (HF) in symptomatic patients with HF and reduced left ventricular ejection fraction (HFrEF), corresponding to the New York Heart Association functional class II-III.

Recognition of advanced HF is a challenge for physicians and under referral for advanced management is a considerable problem. There are excellent treatment options for patients with advanced HF, i.e. heart transplantation or left ventricular assist device (LVAD) implantation, and outcomes with these therapies are considerably better if patients are treated before irreversible end-organ damage occurs. International consensus highlights the importance of timely recognition and referral of these patients to advanced HF centers.

The investigators aim to screen patients with symptomatic HFrEF who are followed in Danish HF clinics in the Copenhagen region with echocardiography, cardiopulmonary exercise test, 6 minute walk test, and NT-proBNP. The investigators hypothesize that 20% of patients with symptomatic heart failure followed in HF clinics in the Copenhagen Region will fulfill the modified criteria for advanced HF from the HFA-ESC (primary end-point in the study)(Reference 1). Patients who are identified with advanced HF will be offered right heart catheterization, guided by ultrasound and inserted through the internal jugular vein, determining pulmonary capillary wedge pressure, cardiac index, central venous pressure, mean pulmonary artery pressure, and central venous oxygen saturation. Patients not fulfilling criteria for advanced HF will be offered right heart catheterization consecutively until 50 patients have been examined (this group will be a comparator group to the patients with advanced HF).

Patients identified with advanced HF will be offered listing for HTx or LVAD if an indication without a contraindication is present. Patients who fulfill the primary endpoint of modified HFA-ESC criteria for advanced HF, and are ineligible for, or unwilling to undergo HTx or LVAD implantation will be invited to participate in the SAINTS B study.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure With Reduced Ejection Fraction
• Intervention / Treatment: Diagnostic test: Cardiopulmonary exercise test, NT-proBNP, Echocardiography, 6 minute walk test, Right heart catheterization

Detailed Description

Number of patients and sample size More than 3000 patients are followed in the HF clinics on Zealand including the greater Copenhagen region. The investigators plan to include 400 patients in the primary outcome analysis (SAINTS A) and hypothesize that 20% will fulfill the modified criteria for advanced HF.

Statistical analysis Descriptive statistics will be reported as mean +/- standard deviation (SD) or median (interquartile range (IQR)) depending on distribution. Comparisons between groups at baseline will be performed by unpaired t-tests for normally distributed continuous variables, by the Mann-Whitney U test (Wilcoxon rank-sum) for non-normally distributed continuous variables and χ2 or Fisher's exact test for categorical variables.

The primary outcome will be analyzed as the proportion n (%) of included patients who fulfill the modified HFA-ESC criteria for advanced HF. As for secondary outcomes, the investigators will analyze the proportion n (%) of patients who within the first 3 months are; 1) offered heart transplant listing, 2) offered LVAD implantation, 3) listed for HTx and 4) undergoing LVAD implantation. Further, comparisons of invasive hemodynamics, CPET measures, 6MWT, QoL and NTproBNP levels between patients with and without advanced HF will be made using an unpaired t-test or the Mann-Whitney U test for non-normally distributed continuous variables.

• Study Type: Observational
• Enrollment (Anticipated): 400

Contacts and Locations

• Study Contact: Name: Finn Gustafsson, MD, PhD, DMSci; Phone Number: +45 35459743; Email: finng@dadlnet.dk
• Study Contact Backup: Name: Johan Larsson, MD; Phone Number: +45 50298907; Email: johanlarsson923@gmail.com

Study Locations

• Denmark
  • Copenhagen, Denmark, 2400
    • Not yet recruiting
    • Bispebjerg-Frederiksberg Hospital
    • Contact: Olav Wendelbo Nielsen, MD, ph.d, dr.med.
  • Copenhagen, Denmark, 2650
    • Not yet recruiting
    • Amager/Hvidovre Hospital
    • Contact: Morten Petersen, MD, ph.d
  • Copenhagen, Denmark, 2730
    • Not yet recruiting
    • Herlev and Gentofte Hospital
    • Contact: Morten Schou, MD, ph.d
  • Glostrup, Denmark, 2600
    • Recruiting
    • Glostrup Hospital
    • Contact: Anders Barasa, MD, ph.d
  • Hillerød, Denmark, 3400
    • Not yet recruiting
    • Nordsjællands Hospital Hillerød
    • Contact: Nis Stride, MD, ph.d
  • Roskilde, Denmark, 4000
    • Not yet recruiting
    • Zeeland University Hospital Roskilde
    • Contact: Nadia Dridi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients followed in Danish HF clinics in the Copenhagen region.

Description

Inclusion Criteria:

1. History of Chronic heart failure > 3 months
2. Stable (no hospitalization last 3 months) NYHA functional class II-III
3. HFrEF patients (Left ventricular ejection fraction (LVEF) ≤ 30%)
4. On or attempted betablocker and Renin-Angiotensin System (RAS) inhibitor treatment
5. Informed consent

Exclusion Criteria:

1. Body Mass Index (BMI) > 40 kg/m2
2. Chronic renal replacement therapy or estimated Glomerular Filtration Rate (eGFR) < 15 ml/min/1.73m2
3. Cardiac Resynchronization Therapy (CRT) implantation < 3 months ago or planned CRT
4. Severe primary valvular disease
5. On waiting list for heart transplantation or referred for evaluation
6. Cancer or other severe non-cardiac disease with estimated life expectancy less than 1 year

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Symptomatic patients with HFrEF corresponding to NYHA II-III	Diagnostic test: Cardiopulmonary exercise test, NT-proBNP, Echocardiography, 6 minute walk test, Right heart catheterization; Screening for advanced HF with modified criteria from the Heart Failure Association of the European Society of Cardiology

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients screened who fulfill advanced HF criteria using a modified HFA-ESC definition	Modified HFA-ESC criteria for advanced HF defined as: • LVEF ≤ 30% as estimated by echocardiography AND • Peak oxygen uptake (VO2peak) < 12 ml/kg/min (14 if on betablocker) with a Respiratory Exchange Ratio (RER) > 1.05 OR < 50% expected for age and gender OR 6 minute walk test (6MWT) distance < 300 meters AND • N-terminal pro B-type natriuretic peptide (NTproBNP) > 2000 pg / ml	At time of screening

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients offered heart transplant listing < 3 months after primary outcome		3 months after meeting modified HFA-ESC criteria for advanced HF
Proportion of patients offered LVAD implantation < 3 months after primary outcome		3 months after meeting modified HFA-ESC criteria for advanced HF
Proportion of patients listed for heart transplantation < 3 months after primary outcome		3 months after meeting modified HFA-ESC criteria for advanced HF
Proportion of patients undergoing LVAD implantation < 3 months after primary outcome		3 months after meeting modified HFA-ESC criteria for advanced HF
Pulmonary capillary wedge pressure (PCWP) in mmHg compared between patients with, and without advanced HF	Measured during right heart catheterization	Within 30 days from screening
Cardiac index (CI) in l/min/m2 compared between patients with, and without advanced HF	Measured during right heart catheterization	Within 30 days from screening
Central venous pressure (CVP) in mmHg compared between patients with, and without advanced HF	Measured during right heart catheterization	Within 30 days from screening
Mean pulmonary artery pressure (mPAP) in mmHg compared between patients with, and without advanced HF	Measured during right heart catheterization	Within 30 days from screening
Central venous oxygen saturation in % compared between patients with, and without advanced HF	Measured during right heart catheterization	Within 30 days from screening
Peak oxygen uptake (VO2peak) in ml/kg/min compared between patients with, and without advanced HF	Measured during cardiopulmonary exercise test	At time of screening
Peak respiratory exhange ratio compared between patients with, and without advanced HF	The ratio between metabolic production of CO2 and the uptake of O2 measured during cardiopulmonary exercise test	At time of screening
Minute ventilation-to-carbon dioxide output slope (VE/VCO2) compared between patients with, and without advanced HF	The ratio between metabolic production of CO2 and the uptake of O2 measured during cardiopulmonary exercise test	At time of screening
Peak Borg scale score compared between patients with, and without advanced HF	The Borg scale score is a rating of perceived exertion on a scale from 6-20, with 6 representing at rest, and 20 the most strenuous exercise imaginable. Measured during cardiopulmonary exercise test	At time of screening
6 minute walk test compared between patients with, and without advanced HF		At screening
Quality of Life (Kansas City Cardiomyopathy Questionnaire (KCCQ)		At screening
NT-proBNP compared between patients with, and without advanced HF		At screening

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: Novo Nordisk A/S

Publications and helpful links

General Publications

• Crespo-Leiro MG, Metra M, Lund LH, Milicic D, Costanzo MR, Filippatos G, Gustafsson F, Tsui S, Barge-Caballero E, De Jonge N, Frigerio M, Hamdan R, Hasin T, Hülsmann M, Nalbantgil S, Potena L, Bauersachs J, Gkouziouta A, Ruhparwar A, Ristic AD, Straburzynska-Migaj E, McDonagh T, Seferovic P, Ruschitzka F. Advanced heart failure: a position statement of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2018 Nov;20(11):1505-1535. doi: 10.1002/ejhf.1236. Epub 2018 Jul 17. Review.

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2022
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: March 7, 2022
• First Submitted That Met QC Criteria: March 18, 2022
• First Posted (Actual): March 29, 2022

Study Record Updates

• Last Update Posted (Actual): November 1, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Screening; Advanced heart failure
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: RH-SAINTS-A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No