Abstract
BackgroundLeft ventricular reverse remodeling (LVRR) has been detected in non-ischemic dilated cardiomyopathy (NIDCM) patients following optimal treatment. However, its prediction with only conventional modalities is often difficult. This study sought to examine whether RNA sequencing (RNA-seq) of myocardium tissue samples could predict LVRR in NIDCM.MethodsA total of 17 advanced NIDCM patients with left ventricular ejection fraction (LVEF) below 30% who underwent cardiac biopsy from Left ventricle (LV) were prospectively recruited. They received optimal treatment and followed with echocardiogram every 6 months. Based on LVRR status after 12 months of treatment, patients were divided into the reverse remodeling (RR) or non-RR group. Tissue samples were analyzed by RNA-seq, and a functional analysis of differentially expressed genes was carried out.ResultsThere were eight and nine patients in the RR and non-RR groups, respectively. No difference was found in age, sex, disease duration, LV end-diastolic diameter, and LVEF between the two groups. There were 155 genes that were differentially expressed between the two groups. Nicotinamide adenine dinucleotide ubiquinone oxidoreductase subunit (NDUF)S5 and Growth arrest and DNA-damage-inducible protein (GADD)45G, along with several genes related to the mitochondrial respiratory chain and ribosome, were significantly downregulated in the RR as compared to the non-RR group.ConclusionGADD45G and NDUFS5 are potential biomarkers for LVRR in patients with advanced NIDCM.
Highlights
Left ventricular reverse remodeling (LVRR) has been detected in non-ischemic dilated cardiomyopathy (NIDCM) patients following optimal treatment
Non-ischemic dilated cardiomyopathy (NIDCM)—which is characterized by left ventricular (LV) dilation and a severely reduced LV ejection fraction (LVEF) without coronary artery disease—is often refractory to established drugs such as β-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers and to cardiac resynchronization therapy (CRT)
Patients were followed for 6 to 12 months, with echocardiogram performed at each follow up; they were divided into the reverse remodeling (RR) and non-RR groups according to positive or negative LVRR status, respectively
Summary
Left ventricular reverse remodeling (LVRR) has been detected in non-ischemic dilated cardiomyopathy (NIDCM) patients following optimal treatment. NIDCM often requires heart transplantation or ventricular assist device (VAD) implantation The former is available only to a limited number of patients, whereas the latter is associated with complications like stroke, bleeding, and infection that can be fatal during the long waiting period for transplantation [1]. Many NIDCM patients show recovery of cardiac function after optimal pharmacological or device therapy [2, 3]. This phenomenon, known as LV reverse remodeling (LVRR), is associated with improved clinical outcomes. Conventional modalities cannot accurately predict the occurrence of LVRR
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