林 睦晴

The study aimed to identify factors related to bone mineral density (BMD) among older patients with heart failure (HF). A total of 70 consecutive patients with HF aged 65 years or older who were admitted to an acute hospital due to worsening condition were enrolled before discharge. BMD of the femoral neck was evaluated using the DEXA method. Physical function, as well as echocardiographic and laboratory findings including biomarker of HF severity were collected. Bivariate and multiple regression analyses were employed to determine the association between BMD and the clinical variables. Bivariate analysis determined that age, grip strength, walking speed, serum albumin, and N-terminal pro B-type natriuretic peptide (NT-proBNP) were significantly correlated with BMD (P < 0.01), whereas other clinical parameters were not. The multiple regression analysis identified NT-proBNP as an independent related factor for BMD after adjusting with confounding clinical variables. NT-proBNP was independently related to BMD among older patients with HF. Our results suggest the inclusion of bone fracture prevention strategies in disease management programs, especially for older patients with HF.

The prognostic role of D-dimer in different types of heart failure (HF) is poorly understood. We investigated the prognostic value of D-dimer on admission, both independently and in combination with the Get With The Guidelines—Heart Failure (GWTG-HF) risk score and N-terminal pro-B-type natriuretic peptide (NT-proBNP), in patients with preserved left ventricular ejection fraction (LVEF) and acute decompensated HF (HFpEF) or reduced LVEF (HFrEF). Baseline D-dimer levels were measured on admission in 1670 patients (mean age: 75 years) who were hospitalized for worsening HF. Of those patients, 586 (35%) were categorized as HFpEF (LVEF ≥ 50%) and 1084 as HFrEF (LVEF &lt; 50%). During the 12-month follow-up period after admission, 360 patients died. Elevated levels (at least the highest tertile value) of D-dimer, GWTG-HF risk score, and NT-proBNP were all independently associated with mortality in all HFpEF and HFrEF patients (all p &lt; 0.05). Adding D-dimer to a baseline model with a GWTG-HF risk score and NT-proBNP improved the net reclassification and integrated discrimination improvement for mortality greater than the baseline model alone in all populations (all p &lt; 0.001). The number of elevations in D-dimer, GWTG-HF risk score, and NT-proBNP were independently associated with a higher risk of mortality in all study populations (HFpEF and HFrEF patients; all p &lt; 0.001). The combination of D-dimer, which is independently predictive of mortality, with the GWTG-HF risk score and NT-proBNP could improve early prediction of 12-month mortality in patients with acute decompensated HF, regardless of the HF phenotype.

OBJECTIVES: MicroRNAs (miRNA) are functional RNAs that have emerged as pivotal gene expression regulators in cardiac disease. Although several cardiomyocyte miRNAs have been reported to play roles in heart failure progression among patients with idiopathic dilated cardiomyopathy (DCM), the role of circulating miRNAs has not yet been well-examined. METHODS: After total RNA extraction from the peripheral blood samples of three control participants and six patients with DCM, miRNA profiling was performed using miRNA arrays. Based on the results of this initial screening, real-time polymerase chain reaction (RT-PCR) was used to perform a quantitative analysis of blood samples from a larger number of matched patients (DCM, n=20; controls, n=5). Finally, the correlations between specific miRNA expression levels and hemodynamic parameters were analyzed. RESULTS: A primary screening of 2,565 miRNAs resulted in the identification of nine miRNA candidates. Quantitative RT-PCR results revealed significantly increased miR-489 expression levels in the DCM group. Moreover, there was a significant positive correlation between miR-489 expression level and left ventricular ejection fraction. CONCLUSIONS: Our results suggest that circulating miR-489 could be a potential noninvasive diagnostic biomarker for DCM. Additionally, the quantification of circulating miR-489 may have value as a potential prognostic marker for patients with DCM.

OBJECTIVES: There are benefits of exercise-based cardiac rehabilitation (CR) in patients with heart failure (HF), but their underlying molecular mechanisms remain elusive. The effect of CR on the expression profile of circulating microRNAs (miRNAs), which are short noncoding RNAs that regulate posttranscriptional expression of target genes, is unknown. If miRNAs respond to changes following CR for HF, then serum profiling of miRNAs may reveal cardioprotective mechanisms of CR. METHODS: This study enrolled three hospitalized patients with progressed systolic HF and three normal volunteer controls. In patients, CR was initiated after improvement of HF, which included 2 weeks of bicycle ergometer and resistance exercises. Genome-wide expression profiling of circulating miRNAs was performed using microarrays for the patients (mean±SD age, 60.0±12.2 years) and controls (58.7±0.58 years). Circulating miRNA expression profiles were compared between patients with HF before and after CR and the controls. RESULTS: Expression levels of two miRNAs were significantly different in patients before CR compared with controls and patients after CR. The expression of hsa-miR-125b-1-3p was significantly downregulated and that of hsa-miR-1290 was significantly upregulated in patients before CR. CONCLUSIONS: When performing CR, expression of certain circulating miRNAs in patients with HF is restored to nonpathological levels. The benefits of CR for HF may result from regulation of miRNAs through multiple effects of gene expression.

Background: Anaerobic threshold (AT) during cardiopulmonary exercise testing (CPET) is not always determinable in patients with heart failure (HF). However, little is known about the clinical features of patients with HF who have indeterminable AT. Therefore, the present study aimed to clarify the clinical features of such patients. Methods: A total of 70 patients with HF (58 males; age: 68±12 years) who underwent CPET during hospitalization were divided into two groups: determinable AT (n=50) and indeterminable AT (n=20). Physical function, echocardiographic results, and laboratory findings were subsequently determined. Results: Univariate analyses showed that the indeterminable AT group had significantly higher age and left ventricular ejection fraction, and significantly lower body mass index, calf circumference, handgrip strength, walking speed, serum hemoglobin, and serum albumin than the determinable AT group. Multiple logistic regression analysis identified handgrip strength and walking speed as independent predictive factors for indeterminable AT. Receiver-operating characteristic analyses revealed that handgrip strength of 21.2 kg and walking speed of 0.97 m/s were optimal cutoff values for differentiating patients who were likely to experience indeterminable AT. Conclusions: The present study identified handgrip strength and walking speed as powerful predictors for indeterminable AT with HF.