Rationale and design of the PACIFIC-PRESERVED (PhenomApping, ClassIFication and Innovation for Cardiac dysfunction in patients with heart failure and PRESERVED left ventricular ejection fraction) study

Jean-Sébastien Hulot; Philip Janiak; Philippe Boutinaud; Pierre Boutouyrie; Frédérique Chézalviel-Guilbert; Jean-Joseph Christophe; Ariel Cohen; Thibaud Damy; Juliette Djadi-Prat; Hüseyin Firat; Pierre-Yves Hervé; Richard Isnard; Guillaume Jondeau; Elie Mousseaux; Mathieu Pernot; Pierre Prot; Benoit Tyl; Gilles Soulat; Damien Logeart; PACIFIC consortium

doi:10.1016/j.acvd.2024.02.011

Rationale and design of the PACIFIC-PRESERVED (PhenomApping, ClassIFication and Innovation for Cardiac dysfunction in patients with heart failure and PRESERVED left ventricular ejection fraction) study

Arch Cardiovasc Dis. 2024 Apr 12:S1875-2136(24)00057-3. doi: 10.1016/j.acvd.2024.02.011. Online ahead of print.

Authors

Jean-Sébastien Hulot¹, Philip Janiak², Philippe Boutinaud³, Pierre Boutouyrie⁴, Frédérique Chézalviel-Guilbert², Jean-Joseph Christophe⁵, Ariel Cohen⁶, Thibaud Damy⁷, Juliette Djadi-Prat⁸, Hüseyin Firat⁹, Pierre-Yves Hervé³, Richard Isnard¹⁰, Guillaume Jondeau¹¹, Elie Mousseaux¹², Mathieu Pernot¹³, Pierre Prot¹⁴, Benoit Tyl¹⁵, Gilles Soulat¹², Damien Logeart¹⁶; PACIFIC consortium

Affiliations

¹ Université Paris Cité, INSERM, PARCC, 75015 Paris, France; CIC1418 and DMU CARTE, Hôpital Européen Georges-Pompidou, AP-HP, 75015 Paris, France. Electronic address: jean-sebastien.hulot@APHP.fr.
² Sanofi R&D, 91380 Chilly-Mazarin, France.
³ FEALINX, 92400 Courbevoie, France.
⁴ Université Paris Cité, INSERM, PARCC, 75015 Paris, France; Pharmacology and DMU CARTE, Hôpital Européen Georges-Pompidou, AP-HP, 75015 Paris, France.
⁵ CASIS, 21000 Dijon, France.
⁶ Cardiology, Hôpital Saint-Antoine, AP-HP, ICAN 1166, Sorbonne Université, 75012 Paris, France.
⁷ Cardiology, Hôpital Henri-Mondor, AP-HP, 94000 Créteil, France.
⁸ Clinical Research Unit, Hôpital Européen Georges-Pompidou, AP-HP, 75015 Paris, France.
⁹ Firalis, 68330 Huningue, France.
¹⁰ Cardiology, Hôpital Pitié-Salpêtrière, AP-HP, 75013 Paris, France.
¹¹ Cardiology, Hôpital Bichat, AP-HP, 75018 Paris, France.
¹² Université Paris Cité, INSERM, PARCC, 75015 Paris, France; Cardiac Imaging Radiology, Hôpital Européen Georges-Pompidou, AP-HP, 75015 Paris, France.
¹³ Physics for Medicine Paris, INSERM U1273, ESPCI Paris, PSL University, CNRS FRE 2031, 75015 Paris, France.
¹⁴ BioSerenity, ICM iPeps, 75013 Paris, France.
¹⁵ Servier R&D, 92150 Suresnes, France.
¹⁶ Cardiology, Hôpital Lariboisière, AP-HP, 75018 Paris, France.

PMID: 38644067
DOI: 10.1016/j.acvd.2024.02.011

Abstract

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome that is poorly defined, reflecting an incomplete understanding of its pathophysiology.

Aim: To redefine the phenotypic spectrum of HFpEF.

Methods: The PACIFIC-PRESERVED study is a prospective multicentre cohort study designed to perform multidimensional deep phenotyping of patients diagnosed with HFpEF (left ventricular ejection fraction≥50%), patients with heart failure with reduced ejection fraction (left ventricular ejection fraction≤40%) and subjects without overt heart failure (3:2:1 ratio). The study proposes prospective investigations in patients during a 1-day hospital stay: physical examination; electrocardiogram; performance-based tests; blood samples; cardiac magnetic resonance imaging; transthoracic echocardiography (rest and low-level exercise); myocardial shear wave elastography; chest computed tomography; and non-invasive measurement of arterial stiffness. Dyspnoea, depression, general health and quality of life will be assessed by dedicated questionnaires. A biobank will be established. After the hospital stay, patients are asked to wear a connected garment (with digital sensors) to collect electrocardiography, pulmonary and activity variables in real-life conditions (for up to 14 days). Data will be centralized for machine-learning-based analyses, with the aim of reclassifying HFpEF into more distinct subgroups, improving understanding of the disease mechanisms and identifying new biological pathways and molecular targets. The study will also serve as a platform to enable the development of innovative technologies and strategies for the diagnosis and stratification of patients with HFpEF.

Conclusions: PACIFIC-PRESERVED is a prospective multicentre phenomapping study, using novel analytical techniques, which will provide a unique data resource to better define HFpEF and identify new clinically meaningful subgroups of patients.

Keywords: Diagnosis; Heart failure; Heart failure with preserved ejection fraction; Machine learning; Phenomapping.