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European Journal of Heart Failure 2005 7(2):157-165; doi:10.1016/j.ejheart.2004.05.008
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© 2005 European Society of Cardiology

Distinct molecular portraits of human failing hearts identified by dedicated cDNA microarrays

Marja Steenman*, Guillaume Lamirault, Nolwenn Le Meur, Martine Le Cunff, Denis Escande and Jean J. Léger

Laboratoire de Physiopathologie et de Pharmacologie Cellulaires et Moléculaires INSERM U533, Faculté de Médecine, 1 Rue Gaston Veil, BP 53508, 44035 Nantes, Cedex 1, France

* Corresponding author. Tel.: +33-240412844; fax: +33-240412950. E-mail address: marja.steenman{at}nantes.inserm.fr


   Abstract

Aims: This study aimed to investigate whether a molecular profiling approach should be pursued for the classification of heart failure patients.

Methods and results: Applying a subtraction strategy we created a cDNA library consisting of cardiac- and heart failure-relevant clones that were used to construct dedicated cDNA microarrays. We measured relative expression levels of the corresponding genes in left ventricle tissue from 17 patients (15 failing hearts and 2 nonfailing hearts). Significance analysis of microarrays was used to select 159 genes that distinguished between all patients. Two-way hierarchical clustering of the 17 patients and the 159 selected genes led to the identification of three major subgroups of patients, each with a specific molecular portrait. The two nonfailing hearts clustered closely together. Interestingly, our classification of patients based on their molecular portraits did not correspond to an identified etiological classification. Remarkably, patients with the highest medical urgency status (United Network for Organ Sharing, Status 1A) clustered together.

Conclusion: With this pilot feasibility study we demonstrated a novel classification of end-stage heart failure patients, which encourages further development of this approach in prospective studies on heart failure patients at earlier stages of the disease.

Key Words: Classification • Idiopathic dilated cardiomyopathy • Coronary artery disease • Gene expression profiling • Cluster analysis

Received March 31, 2004; Revised April 19, 2004; Accepted May 17, 2004


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