QUAD-HF - Prospective Registry of Patients With Incident Heart Failure and Left Ventricular Ejection Fraction <50%

Heart failure (HF) is a widespread global health challenge, affecting approximately 1 million individuals in the United Kingdom and the prevalence is predicted to almost double in the next decades due to the ageing population. In the United Kingdom, hospitalizations for HF account for 5% of emergency medical admissions with a substantial economic burden.

The management of heart failure however is a true success story of modern medicine. Four decades of randomised clinical trials, provide the evidence base for an extensive catalogue of disease-modifying pharmacological and device treatments that have improved prognosis, particularly in patients with HF and a reduced LVEF \<50%.

However, controlled studies tend to evaluate treatments in selected patient cohorts defined by strict trial inclusion criteria and often exclude older patients, include less women and patient background is often non-diverse. Furthermore, while within clinical trials these treatments are readily available and delivered to patients in meticulous and tightly controlled settings, this does not usually reflect real-world clinical environments, where there may be resource deficiencies. Indeed, a recent cross-sectional survey of hospital-based HF services in the UK, demonstrates wide variation in access to treatment and services. It is therefore important to evaluate the utilization of these treatments and adherence to practice guidelines in a real-world setting.

In England \& Wales, a National Heart Failure Audit collects data in patients with HF who have unplanned hospitalisations for worsening symptoms. This does not extend outside of hospital settings, where the majority of patients time is spent managing their condition. The UK HFpEF study is an ongoing study which caters for patients who have heart failure with a preserved left ventricular ejection fraction (\>50%).

There is however no readily available database or registry outside of hospital, that provides contemporaneous information about the care, changes in management or long-term outcomes for patients with HF and a left ventricular ejection fraction of \<50%, as exists in other healthcare systems.

The QUAD-HF registry is designed as a UK multi-centre, prospective longitudinal registry and would enrol adult patients (\>18 years) who present with incident heart failure and a left ventricular ejection fraction \<50%. NHS secondary or primary care centres in the United Kingdom would be invited to enroll patients into the registry if they have an established HF clinic that routinely documents patient characteristics and pharmacological therapy at each visit. Site selection would be by the steering committee.

Consecutive ambulatory patients attending these clinics, would be approached by managing clinicians; usually specialist HF nurses or cardiologists; to participate. For those hospitalized at the time of their new diagnosis, this approach would be by treating clinician when they are clinically stable. All patients would be treated according to contemporary guidelines.

In the initial phase of the study (1st 12 months), investigators aim to recruit 10 sites, with each site expected to enroll 100 patients into the study over 18 months. Additional sites will be invited as the registry develops. Selection of sites will be determined by the Steering Committee. At that recruitment rate and with additional sites added, investigators expect to onboard approximately 4000 participants into the registry by month 60.

Participants will provide oral and written informed consent to enable future data linkage of data relevant to their past and future health from medical, health, social care and other health-related records, which are collected or held in local, regional and national systems. The study has received ethical approval from the Cambridgeshire South Research Ethics Committee (25/EE/0088) and local research and development departments of participating hospitals.

Broadly, the registry will evaluate the implementation of current HF guidelines and assess the quality of care in daily clinical practice in these patients. The primary clinical endpoint is a composite of cardiovascular mortality and hospitalization for heart failure, 1 year after diagnosis. Secondary endpoints include components of the primary endpoint, all-cause mortality, QUAD score at final therapy titration, days alive out of hospital, time to first HF-related hospitalization and patient-reported outcome measures.

The QUAD-HF registry would provide longitudinal analysis of profiles, management and outcomes for patients with incident HF and a left ventricular ejection fraction of \<50% and provide a platform to support improved knowledge, the development of personalized care and support future research for these patients.

• All-cause mortality [Time frame: From enrolment to 12 months after diagnosis]
• Cardiovascular Mortality [Time frame: From enrolment to 12 months after diagnosis]
• Hospitalization for Heart Failure [Time frame: From enrolment to 12 months after diagnosis]