Resting echocardiographic parameters to detect patients with less symptomatic primary mitral regurgitation who require exercise stress echocardiography.

Objectives: We aimed to identify which resting echocardiographic parameters can detect asymptomatic or mildly symptomatic patients with primary mitral regurgitation (MR) who require exercise stress echocardiography (ESE) to determine their suitability for surgery. Methods: We examined 56 consecutive patients with primary moderate/severe MR who underwent ergometer-based ESE. Patients who met the surgical indications at rest were excluded. Eligible patients were divided into Group I (pulmonary artery systolic pressure [PASP] during exercise >60 mmHg; n=11) and Group II (PASP during exercise ≤60 mmHg; n=30). Results: Forty-one patients were included. Group I was significantly older (65±12 vs. 54±14 years, P=0.042) and had significantly higher serum N-terminal pro-B-type natriuretic peptide concentrations than Group II (351±278 vs. 125±163 pg/mL, P=0.002). The univariate analysis demonstrated that peak E wave velocity (Group I vs. Group II: 125±45 vs. 101±24 cm/sec, P=0.050), left ventricular (LV) end-diastolic diameter index (32±4 vs. 30±3 mm/m2, P=0.035), and left atrial volume index (LAVI; 45±14 vs. 30±11 mL/m2, P=0.008) were predictors of increased PASP during exercise. In the multivariate analysis, resting LAVI best predicted exercise-induced pulmonary hypertension (hazard ratio 1.081 [95% confidence interval 1.009-1.158], P=0.028), with a cutoff value of 37 mL/m2. Conclusions: In asymptomatic or mildly symptomatic patients with primary moderate/severe MR, increased resting LAVI indicates the requirement for ESE, even without LV dilatation.

Association of resting left ventricular global longitudinal strain with myocardial perfusion abnormalities evaluated by 13 N-ammonia positron emission tomography in patients with stable angina pectoris and normal left ventricular ejection fraction.

AIMS: Little is known about whether resting left ventricular global longitudinal strain (GLS) impairment is associated with myocardial perfusion abnormalities evaluated using 13 N-ammonia positron emission tomography (13 N-NH3 -PET)-myocardial perfusion imaging (MPI). This study aimed to investigate the correlation between resting GLS and myocardial perfusion parameters in patients with a normal left ventricular ejection fraction (LVEF). We evaluated whether resting GLS can predict myocardial perfusion abnormalities in these patients. METHODS AND RESULTS: We selected 157 patients with suspected stable angina pectoris who underwent both ATP-stress NH3 -PET-MPI and 2-dimentional speckle tracing echocardiography. All subjects had a preserved LVEF and no known history of myocardial infarction. Patients were stratified into Group N (normal perfusion; summed stress score [SSS], 0-3; n = 101), Group M (mildly to moderately abnormal perfusion; SSS, 4-11; n = 41), or Group S (severely abnormal perfusion; SSS, 12+; n = 15). GLS was more impaired as myocardial perfusion abnormality severity increased (-17.9 ± 2.9% for Group N, -16.8 ± 3.1% for Group M, and -14.2 ± 3.5% for Group S; p < .001). GLS was weakly but significantly correlated with SSS (R = .32, p < .001), summed difference score (R = .32, p < .001), and myocardial blood flow during stress (R = -0.27, p < .001). Multivariate logistic regression analysis showed that male sex, diabetes mellitus, systolic blood pressure, and GLS were independent predictors of myocardial perfusion abnormality defined as Groups M and S. Additionally, the area under the curve for GLS for detecting myocardial perfusion abnormality was .65, and the optimal cutoff value for GLS was -16.5%, with sensitivity and specificity of 59% and 66%, respectively. CONCLUSION: In patients with suspected angina pectoris, resting GLS impairment despite a normal LVEF might aid the detection of hemodynamically significant coronary artery disease.

A simple proteinuria-based risk score predicts contrast-associated acute kidney injury after percutaneous coronary intervention.

Contrast-associated acute kidney injury (CA-AKI) is a complication of percutaneous coronary intervention (PCI). Because proteinuria is a sentinel marker of renal dysfunction, we assessed its role in predicting CA-AKI in patients undergoing PCI. A total of 1,254 patients undergoing PCI were randomly assigned to a derivation (n = 840) and validation (n = 414) dataset. We identified the independent predictors of CA-AKI where CA-AKI was defined by the new criteria issued in 2020, by a multivariate logistic regression in the derivation dataset. We created a risk score from the remaining predictors. The discrimination and calibration of the risk score in the validation dataset were assessed by the area under the receiver-operating characteristic curves (AUC) and Hosmer-Lemeshow test, respectively. A total of 64 (5.1%) patients developed CA-AKI. The 3 variables of the risk score were emergency procedures, serum creatinine, and proteinuria, which were assigned 1 point each based on the correlation coefficient. The risk score demonstrated a good discriminative power (AUC 0.789, 95% CI 0.766-0.912) and significant calibration. It was strongly associated with the onset of CA-AKI (Cochran-Armitage test, p < 0.0001). Our risk score that included proteinuria was simple to obtain and calculate, and may be useful in assessing the CA-AKI risk before PCI.

Circulating miR-489 as a potential new biomarker for idiopathic dilated cardiomyopathy.

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.

Impact of physical function on indeterminable anaerobic threshold in patients with heart failure.

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.

Effect of cardiac rehabilitation on circulating microRNA expression in heart failure: a preliminary study.

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.

The difference in determinant factor of six-minute walking distance between sarcopenic and non-sarcopenic elderly patients with heart failure.

BACKGROUND: The purpose of this study was to identify the factors determining exercise capacity in elderly patients with heart failure (HF) with and without sarcopenia. METHODS: We studied 186 consecutive patients with HF who met the criteria of being >60 years, with no physical disability. During hospitalization, we measured the 6-min walking distance (6MWD) and other physical functional parameters and evaluated echocardiographic and laboratory measurements indicating the severity of HF. First, we divided patients into two groups (the sarcopenia group and the nonsarcopenia group) according to the presence of sarcopenia defined as fulfilling more than or equal to two criteria-body mass index <18.5, walking speed <0.8m/s, and grip strength <26kg in males, or <18kg in females. Then the association between the 6MWD and the clinical variables mentioned above was analyzed by univariate and multiple logistic regression analyses. RESULTS: The sarcopenia group comprised 77 patients (41.2%). In univariate analysis, age, grip strength, walking speed, and knee extensor muscle strength were significantly correlated with the 6MWD (p<0.05), whereas other clinical parameters were not. In multivariate analysis, walking speed was selected as an independent factor determining the 6MWD in both groups; however, knee extensor muscle strength was selected as an independent factor determining the 6MWD only in the sarcopenia group. CONCLUSION: We demonstrated that knee extensor muscle strength was an independent factor determining exercise capacity-especially in elderly patients with HF with sarcopenia, and provided useful information in terms of exercise prescription.

Serum microRNA-126 and -223 as new-generation biomarkers for sarcoidosis in patients with heart failure.

BACKGROUND: Although cardiac sarcoidosis is associated with poor prognosis, diagnosis of the disease is challenging and the sensitivity and specificity of diagnostic modalities are limited. This study was performed to evaluate the potential of serum microRNAs (miRNAs) as diagnostic biomarkers for cardiac sarcoidosis. METHODS: We performed genome-wide expression profiling for 2565 miRNAs (Human-miRNA ver.21) using peripheral blood samples from 5 patients with cardiac sarcoidosis (61±9 years) and 3 healthy controls (54±7 years). From this screening study, we selected 12 miRNAs that were significantly related to cardiac sarcoidosis. Next, we performed real-time polymerase chain reaction (PCR) on blood samples from 15 new patients with cardiac sarcoidosis and 4 healthy controls to quantify the expression of these 12 miRNAs. RESULTS: In the screening study, 12 miRNAs were differentially expressed (p<0.01) in all 5 patients with cardiac sarcoidosis, showing greater fold-change values (>4 or <0.25) compared with the expression in the 3 healthy controls. Analysis of the real-time PCR for blood samples from the other 15 patients and 4 controls using Mann-Whitney U tests revealed that the expression of miR-126 and miR-223 was significantly higher in the patients than in the healthy individuals. However, there were no differences in the expressions of miRNA-126 and miR-223 between patients with only cardiac lesions and those with extra-cardiac lesions. CONCLUSIONS: Our results demonstrate the potential of serum miR-126 and miR-223 as new-generation biomarkers for the differential diagnosis of cardiac sarcoidosis in patients with heart failure.