Long noncoding RNAs (lncRNAs) have potential as novel therapeutic targets in cardiac disease, but their function in heart failure (HF) is not yet fully understood. Using a gene trapping approach in mouse embryonic stem cells, we identified a novel cytoplasmic lncRNA, dubbed Caren (cardiomyocyte-enriched noncoding transcript), which was predominantly expressed in cardiomyocytes. Caren was markedly downregulated in the mouse failing heart that was subjected to transverse aortic constriction (TAC). The ablation of Caren in the mouse heart accelerated HF-related phenotypes by TAC, whereas mice overexpressing Caren (CAG-Caren Tg mice) resisted TAC-induced HF. Proteomic analysis identified histidine triad nucleotide-binding protein 1 (Hint1) as a Caren target protein, while bioinformatic analysis of proteome revealed that Caren regulates the proteins involved in mitochondrial energetics in the heart. Furthermore, we found that Caren suppressed Hint1 expression at the translational level and that Hint1 overexpression reduced mitochondrial respiration capacity. Similar to CAG-Caren Tg mice, the reduced Hint1 expression in mice exerted cardioprotective effects on TAC-induced HF, which was associated with the decreased level of ATM serine/threonine kinase phosphorylation, known to activate DNA damage responses. Overall, we identify a novel cytoplasmic lncRNA that protects against the development of HF through suppressing the Hint1-ATM signaling, which presumably maintains mitochondrial energetics and prevents the DNA damage under pathological stress.