Heart failure (HF), a clinical syndrome in which the heart is unable to provide sufficient blood flow to meet metabolic requirements, is a major public health concern because of its high prevalence, poor prognosis, and significant healthcare costs [1]. In Taiwan, cardiovascular-related deaths have increased significantly from 4.3 to 6.5 persons per million population between 1981 and 2009 [2]. Despite major efforts to improve treatment of acute HF in the hospital setting, the 3 month readmission rates remain as high as 25–50 % and the 5 year survival is less than 50 % [1]. Consequently, more effective therapeutic targets and improved management approaches are urgently needed.

Although a beating heart utilizes fatty acids as a primary source of energy [3], an increased level of myocardial triglyceride (TG) content results in lipotoxicity and may contribute to the development of cardiac dysfunction [4–6]. Consequently, the in vivo measurement of myocardial TG content and metabolic activity has been proposed for guiding appropriate treatment in hospitalized HF patients [7].

Proton magnetic resonance spectroscopy (¹H-MRS) is increasingly being used as a non-invasive, non-radiation exposure technique for the clinical assessment of myocardial lipid content [8]. In recent years, the use of high-field scanners (3.0 T) has improved the chemical shift resolution and signal-to-noise ratio of cardiac ¹H-MRS, ultimately allowing the discrimination between fatty acids (FA) and unsaturated fatty acids (UFA) deposition in the myocardium. However, studies focusing on the clinical usefulness of ¹H-MRS imaging for the metabolic evaluation of HF patients are particularly lacking. We therefore designed the current cross-sectional investigation to analyze the associations between myocardial TG content measured on ¹H-MRS and left ventricular (LV) function assessed on cardiovascular magnetic resonance (CMR) in patients who were hospitalized with HF. We demonstrate that patients who were discharged after hospitalization for acute HF had increased myocardial UFA content, which was inversely related with LV ejection fraction (LVEF), LV mass and, to a lesser extent, LV end-diastolic volume (LVEDV).

¹H-MRS performed on 1.5 T MR scanner has been shown to be a reliable and reproducible imaging modality for the assessment of human myocardial TG content [11–13], while the high-field 3 T MR scanner, as used in this study, has significantly greater signal-to-noise ratio coupled with increased spectral resolution and has shown to be more accurate for in vivo quantification of myocardial fat fraction as compared to 1.5-Tesla [20]. ¹H-MRS research study on formalin-fixed specimens of human hearts at various locations demonstrated that septal fat content is largely representative of myocardial TG deposition [21]. Herein, we applied ¹H-MRS in the interventricular septum to assess the heart of a subgroup of HF patients 6 ~ 12 months after hospitalization on 3-T MR scanner. To the best of our knowledge, this is the first in vivo study specifically investigating the relation of different myocardial TG components and functional cardiac parameters on post-hospitalized HF patients with 3-T CMR plus ¹H-MRS. Our main results indicated an association between the accumulation of myocardial TG components and the damaged heart. First, myocardial UFA content was significantly higher in our patients than in controls, even those showed good recovery from HF with their LVEF restoring to the normal range. Second, the myocardial UFA/TG ratio was positively correlated with LV mass and LVEDV. The reproducibility of our results was confirmed by Bland-Altman plots [19]. Taken together, the current study support the clinical utility of 3 T ¹H-MRS for measuring myocardial TG components in patients who were hospitalized with acute HF.

In this study, our patients had significantly increased myocardial UFA content as compared with controls. Intriguingly, there was a stepwise decrease of myocardial UFA concentrations when comparing patients with low LVEF, normal LVEF, and controls (p = 0.02). The standard deviation of UFA/W was significantly larger in patients with low EF compared with values observed in patients with normal EF and controls (Table 3). This observation can be explained by the wider range of EF observed in patients with low EF, ultimately resulting in a higher standard deviation (12.3) than those observed in both subjects with normal EF (8.3) and controls (7.6, Table 2). The differences in the standard deviations are unlikely to be caused by a suboptimal UFA quantification. Accordingly, our phantom study clearly demonstrated the reproducibility of measuring and fitting UFA (Additional file: 1 Figure S1). The relationship of accumulation of myocardial TG in patients with cardiomyopathy has been previously reported, but with different results [14, 15, 22, 23]. Graner et al. [22] reported that myocardial TG content decreased in non-diabetic subjects with dilated cardiomyopathy, however, showed the opposite results in those with diabetic heart disease [14, 23]. Nakae et al. [15] found that myocardial TG may be related to the specific cause of disease rather than the severity of cardiac dysfunction. Nevertheless, notable finding from the current study is that myocardial UFA, instead of FA and TG, was increased in post-hospitalized HF patients and was related to the severity of LV systolic function.

LV mass and LVEDV of our patients were positively correlated with myocardial UFA/TG ratio but were negatively correlated with myocardial FA/TG ratio. Their correlations with TG/W were not significant. In a series of 15 healthy humans evaluated with 1.5 T 1H- MRS, Szczepaniak et al. [24] found that increased myocardial triglyceride content was accompanied by elevated LV mass. In another series with ten male endurance athletes and 15 healthy male controls evaluated with 1.5 T ¹H- MRS, Sai et al. [25] showed that the myocardial TG content was significantly lower in the athlete group than in the control group, and was negatively correlated with LV mass and volume. We believe that the study participants selection and MRI scanner field strength may, at least, partly account to the discrepancies of our results from those previously reported. Of note, the averaged TG/W ratio found in our control group was 15.3 which fell between those of our stable HF (11.8) and unstable HF group (17.2). Accordingly, our control subjects had a mean body mass index of 26.3 kg/m², being overweight according to the WHO definition. In addition, the TG/W ratio is characterized by a diurnal course, with higher levels in the morning than in the evening [9]. The impact of these potential confounders on the TG/W needs further scrutiny.

It has been reported that myocardial TG accumulation promotes the development of cardiac hypertrophy, ventricular dysfunction, and interstitial fibrosis [5]. Although an increased TG deposition in the pancreatic islets has been linked to non-insulin-dependent diabetes mellitus [26], the potential relationship between myocardial TG accumulation and diabetic heart disease remains unclear. An animal study has demonstrated that increased TG content within the myocardium contributes to the development of cardiac dysfunction through lipotoxic effects [27]. In patients with HF, accumulation of myocardial UFA may reflect a switch of the myocardial energy metabolism to the fetal transcriptional program with a reduced rate of β-oxidation, which is partially compensated by an increased of glucose utilization [28]. Moreover, Lahey et al. have shown that UFA are more potent activators of TG turnover than saturated FA in animal models. In decompensated HF, UFA may serve as a beneficial energy substrate versus FA by upregulating TG dynamics and nuclear receptor signaling [29]. Notwithstanding the scarce evidence, it has been alternatively suggested that myocardial TG accumulation may be protective against fatty acid-induced lipotoxicity by limiting the deposition of ceramides and diacylglycerols [30, 31]. Although our study did not provide the mechanisms how TG content mediates cardiac dysfunction, the in vivo identification of the associations of TG components, particularly UFA, with cardiac function using 3-T CMR in the post-treated failed heart is an important step forward.

The mean BMI of the entire study population (comprising both patients and controls) was 26.1 kg/m², suggesting the presence of overweight according to the World Health Organization criteria [32]. Previous studies have linked the presence of cardiac steatosis with obesity and related metabolic diseases [10, 16, 17]. Notably, ectopic TG accumulation within and around the myocardium in moderately obese individuals has been associated with free fatty acid exposure, generalized ectopic fat excess, and peripheral vascular resistance [33]. However, we failed to identify significant associations between myocardial TG content and serum lipid levels. These results suggest that ¹H-MRS measurements of myocardial TG content may provide complementary clinical information beyond serum lipid profile.

Patients who were discharged after hospitalization for acute HF had increased myocardial UFA content as compared with controls. Furthermore, UFA was inversely related with LVEF, LV mass and, to a lesser extent, LVEDV. Our current report may stimulate further research aimed at measuring myocardial UFA content by ¹H-MRS for predicting clinical outcomes.