Left Atrial Remodeling Related to Disproportionately Low B-Type Natriuretic Peptide in Acute Heart Failure Patients with Atrial Fibrillation.

The diagnostic performance of B-type natriuretic peptide (BNP) for acute heart failure (HF) is impaired in patients with atrial fibrillation (AF). Increased AF burden in HF is associated with left atrial (LA) remodeling. Recent studies have revealed that LA remodeling may affect LV filling. We hypothesized that LA remodeling affects BNP secretion in acute HF conditions. The study investigated the clinical impact of LA remodeling on admission BNP levels in acute HF patients with and without AF. Consecutive acute HF hospitalized patients (n = 899) were divided into groups with (n = 382) or without AF (n = 507) and subdivided into disproportionately low BNP (LB) (≤200 pg/ml), medium BNP (200 to 600 pg/ml) and high BNP (≥600 pg/ml) subgroups. The AF group had a higher proportion of patients with LB than the non-AF group (23.6% vs 16.6%, p = 0.009). BNP levels in both groups were positively correlated with LV end-diastolic volume and negatively correlated with LV ejection fraction in both groups. In contrast, BNP was positively correlated with LA volume index in the non-AF group, but negatively correlated in the AF group. The survival rates were significantly higher in the LB group than in the other groups in non-AF. Conversely, there were no significant differences across all groups in AF patients. In conclusion, in patients with acute HF and AF, disproportionately low BNP levels are associated with LA structural remodeling and poor prognosis.

Prognostic impact of a reduction in the fibrosis-4 index among patients hospitalized with acute heart failure.

Although the fibrosis-4 index (FIB-4) is associated with right atrial pressure or prognosis in acute heart failure (AHF), the prognostic impact of its reduction during hospitalization remains uncertain. We included 877 patients (age, 74.9 ± 12.0 years; 58% male) hospitalized with AHF. The reduction in FIB-4 was defined as: (FIB-4 on admission-FIB-4 at discharge)/FIB-4 on admission × 100. Patients were divided into low (< 1.0%, n = 293), middle (1.0-27.4%, n = 292), and high (> 27.4%, n = 292) FIB-4 reduction groups. The primary outcome was a composite of all-cause death or heart failure rehospitalization within 180 days. The median FIB-4 reduction was 14.7% (interquartile range - 7.8-34.9%). The primary outcome was observed in 79 (27.0%), 63 (21.6%), and 41 (14.0%) patients in the low, middle, and high FIB-4 reduction groups, respectively (P = 0.001). Adjusted Cox proportional-hazards analysis revealed that the middle and low FIB-4 reduction groups were associated with the primary outcome, independent of the pre-existing risk model including baseline FIB-4 ([high vs. middle] hazard ratio [HR]: 1.70, 95% confidence interval [CI]: 1.10-2,63, P = 0.017; [high vs. low] HR: 2.16, 95% CI 1.41-3.32, P < 0.001). FIB-4 reduction provided additional prognostic value to the baseline model, including well-known prognostic factors ([continuous net reclassification improvement] 0.304; 95% CI 0.139-0.464; P < 0.001; [integrated discrimination improvement] 0.011; 95% CI 0.004-0.017; P = 0.001). Additionally, the combination of the reduction in FIB-4 and brain natriuretic peptide was useful for risk stratification. In conclusion, among patients hospitalized with AHF, a greater FIB-4 reduction during hospitalization was associated with better prognoses.

Prognostic Impact of Multiple Drug Use at Discharge in Patients Hospitalized with Heart Failure.

The association between polypharmacy/multiple drug use (MDU) and prognosis in patients hospitalized with heart failure (HF) is unclear. It is also unknown whether the prognostic values of MDU vary depending on the presence/absence of a previous history of HF and preserved/reduced left ventricular ejection fraction (LVEF). We analyzed consecutive 1,034 patients hospitalized with HF (age, 74.9 ± 11.5 years; 58.7% male). MDU was defined as ≥5 drugs at discharge. The primary endpoint was a composite of all-cause death and HF readmission. MDU was observed in 695 patients (67.2%). Patients with MDU use had higher prevalences of a previous history of HF, reduced LVEF, and comorbidities than those without MDU. Cox proportional hazard analysis showed that MDU was significantly associated with the primary endpoint after adjustment for possible confounders (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.03-1.79; P = 0.030). There was significant interaction between the presence/absence of a history of HF and the prognostic impact of MDU (HF history [-]: HR, 0.86; 95% CI, 0.54-1.40; P = 0.553; HF history [+]: HR, 1.72; 95% CI, 1.16-2.55; P = 0.007; P for interaction = 0.005). However, there was no significant interaction between preserved/reduced LVEF and the prognostic impact of MDU (P for interaction = 0.274). In conclusion, MDU at discharge is an independent risk factor for the composite of death or HF readmission in patients hospitalized with HF. We observed a significant interaction between the presence of de novo versus recurrent HF and the prognostic value of MDU.

Fibrosis-4 index identifies worsening renal function associated with adverse outcomes in acute heart failure.

AIMS: Worsening renal function (WRF) often develops during heart failure (HF) treatment. However, prognostic implications of WRF in acute HF remain controversial, and risk stratification of WRF is challenging. Although the fibrosis-4 index (FIB-4) was initially established as a liver fibrosis marker, recent studies show that high FIB-4 is associated with venous congestion and poor prognosis in acute HF. This study aimed to evaluate whether FIB-4 could identify prognostically relevant and non-relevant WRF in patients with acute HF. METHODS AND RESULTS: We retrospectively analysed data from a single-centre registry on acute HF at our university hospital between January 2015 and June 2021. This study included patients with acute HF aged ≥20 years who were immediately hospitalized and had brain natriuretic peptide levels ≥100 pg/mL at admission. WRF was defined as increases of ≥0.3 mg/dL and >25% in serum creatinine level from admission to discharge. FIB-4 scores were calculated before discharge. The primary endpoint was all-cause mortality within 1 year of discharge. Based on the presence of WRF and whether FIB-4 scores were above the median, patients were stratified into four groups: no WRF and lower FIB-4 scores, no WRF and higher FIB-4 scores, WRF and lower FIB-4 scores, and WRF and higher FIB-4 scores. The patients were followed up via clinical visits or telephone interviews. Clinical outcomes were collected from the electronic medical records. RESULTS: Of the 969 patients hospitalized for acute HF (76 ± 11 years, 59% men), 118 patients (12%) had WRF at discharge. The median (interquartile range) FIB-4 score at discharge was 2.36 (1.55-3.25). The primary endpoint occurred in 136 patients (14.0%). The 1 year mortality rates were 10.5% in the no WRF and lower FIB-4 scores (≤2.36) group (n = 428), 16.1% in the no WRF and higher FIB-4 scores (>2.36) group (n = 423), 12.5% in the WRF and lower FIB-4 scores group (n = 56), and 25.8% in the WRF and higher FIB-4 scores group (n = 62) (P = 0.005). Kaplan-Meier analysis demonstrated higher all-cause mortality in the WRF and higher FIB-4 group (log-rank P = 0.003). In the Cox regression analysis, only the WRF and higher FIB-4 scores group was associated with an increased risk of mortality compared with the no WRF and lower FIB-4 scores group (hazard ratio = 2.11, 95% confidence interval: 1.07-4.18, P = 0.032), despite adjusting for other confounding factors. CONCLUSIONS: FIB-4 is a valuable risk stratification marker for WRF in patients with acute HF. The underlying mechanism and potential clinical importance of these observations require further investigation.

Effect of ipragliflozin on carotid intima-media thickness in patients with type 2 diabetes: a multicenter, randomized, controlled trial.

AIMS: To examine the effects of a 24-month treatment with ipragliflozin on carotid intima-media thickness (IMT) in type 2 diabetes patients. METHODS AND RESULTS: In this multicenter, prospective, randomized, open-label, and blinded-endpoint investigator-initiated clinical trial, adults with type 2 diabetes and haemoglobin A1C (HbA1c) of 6.0-10.0% (42-86 mmol/mol) were randomized equally to ipragliflozin (50 mg daily) and non-sodium-glucose cotransporter-2 (SGLT2) inhibitor use of standard-care (control group) for type 2 diabetes and were followed-up to 24 months. The primary endpoint was the change in mean common carotid artery IMT (CCA-IMT) from baseline to 24 months. A total of 482 patients were equally allocated to the ipragliflozin (N = 241) and control (N = 241) groups, and 464 patients (median age 68 years, female 31.7%, median type 2 diabetes duration 8 years, median HbA1c 7.3%) were included in the analyses. For the primary endpoint, the changes in the mean CCA-IMT from baseline to 24 months were 0.0013 [95% confidence interval (CI), -0.0155-0.0182] mm and 0.0015 (95% CI, -0.0155-0.0184) mm in the ipragliflozin and control groups, respectively, with an estimated group difference (ipragliflozin-control) of -0.0001 mm (95% CI, -0.0191-0.0189; P = 0.989). A group difference in HbA1c change at 24 months was also non-significant between the treatment groups [-0.1% (95% CI, -0.2-0.1); P = 0.359]. CONCLUSION: Twenty-four months of ipragliflozin treatment did not affect carotid IMT status in patients with type 2 diabetes recruited in the PROTECT study, relative to the non-SGLT2 inhibitor-use standard care for type 2 diabetes.

Prognostic Value of the FAN Score, a Combination of the Fibrosis-4 Index, Albumin-Bilirubin Score and Neutrophil-Lymphocyte Ratio, in Patients Hospitalized with Heart Failure.

The fibrosis-4 index, albumin-bilirubin score and neutrophil-lymphocyte ratio are all prognostic markers in patients with heart failure. Recently, the FAN score, which includes all 3 of these markers, was developed as a useful risk stratification tool in patients with cancer. However, its cut-off values have not been validated for heart failure. We aimed to investigate the optimal cut-off and prognostic values of the FAN score in patients with heart failure. We analyzed 669 consecutive patients hospitalized with heart failure (age, 75.8 ± 11.3 years). Their median values of the fibrosis-4 index, albumin-bilirubin score, and neutrophil-lymphocyte ratio at discharge were 2.12, -2.25, and 2.41, respectively. The FAN score for heart failure (HF-FAN score) was calculated using these median values. The primary outcome was a composite of all-cause death and heart failure rehospitalization. Patients were divided into 4 groups according to HF-FAN scores of 0 (n = 112), 1 (n = 231), 2 (n = 242) and 3 (n = 84). Patients with HF-FAN scores of 3 were older, had higher brain natriuretic peptide levels, and larger inferior vena cava diameters. Kaplan-Meier analysis showed a direct correlation between higher HF-FAN scores and occurrence of the primary endpoint (log-rank P < 0.001). Cox proportional hazard analysis revealed a higher HF-FAN score was significantly associated with a worse prognosis even after adjustment for possible prognostic factors. Changing from the FAN score to HF-FAN score provided significant continuous net reclassification improvement. In conclusion, the HF-FAN score at discharge was useful for risk stratification in patients hospitalized with heart failure. The HF-FAN score might be more suitable for patients with heart failure than the FAN score.

Prognostic value of the liver fibrosis marker fibrosis-5 index in patients with acute heart failure.

AIMS: Recently, liver fibrosis markers, such as the fibrosis-4 index (FIB-4), have been shown to be associated with prognosis in patients with heart failure. The fibrosis-5 (FIB-5) index, which assesses albumin, alkaline phosphatase, aspartate transaminase, alanine aminotransferase and platelet count, is a simple liver fibrosis marker that was reported to be superior to FIB-4 for differentiation of liver fibrosis. This study aimed to compare the prognostic value of FIB-4 and FIB-5 in patients with heart failure. METHODS AND RESULTS: The FIB-4 and FIB-5 scores were calculated at discharge in 906 patients hospitalized with heart failure. The patients were stratified into three groups based on their FIB-5 scores: low (n = 303), middle (n = 301), and high (n = 302) FIB-5 groups. The primary endpoint was a composite of cardiac death or rehospitalization for heart failure. The low FIB-5 group was older and had larger inferior vena cava diameters and higher brain natriuretic peptide levels than the other two groups. The primary endpoint occurred in 156 (51.5%), 110 (36.5%), and 54 patients (17.9%) in the low, middle, and high FIB-5 groups, respectively (P < 0.001). On Cox proportional hazard analysis, the low FIB-5 was independently associated with the primary endpoint after adjustment for confounding factors. The association was consistent in both patients with preserved and reduced left ventricular ejection fraction (LVEF), and there was no significant interaction between LVEF phenotypes in terms of the prognostic impact of FIB-5 (P for interaction = 0.311). FIB-5 was superior to FIB-4 as a prognostic indicator of the primary endpoint (continuous net reclassification improvement, 0.530; 95% confidence interval [CI], 0.399-0.662; P < 0.001; integrated discrimination improvement, 0.072; 95% CI, 0.057-0.088; P < 0.001). CONCLUSIONS: The FIB-5 is a useful risk stratification marker with better prognostic value than FIB-4 in patients hospitalized with heart failure.

Prevalence and Risk Factors of Silent Cerebral Microbleeds in Patients with Coronary Artery Disease.

OBJECTIVES: Cerebral microbleeds (CMBs), which can be detected by gradient-echo T2*-weighted magnetic resonance imaging (MRI), represent small chronic brain hemorrhages caused by structural abnormalities in cerebral small vessels. CMBs are known to be a potential predictor of future stroke, and are associated with age, various cardiovascular risk factors, cognitive impairment, and the use of antithrombotic drugs. Patients with coronary artery disease (CAD) are at potentially high risk of CMBs due to the presence of coexistent conditions. However, little is known about CMBs in patients with CAD. We aimed to identify the factors associated with the presence of CMBs among patients with CAD. METHODS: We evaluated 356 consecutive patients [mean age, 72 ± 10 years; men = 276 (78%)] with angiographically proven CAD who underwent T2*-weighted brain MRI. The brain MRI was assessed by researchers blinded to the patients' clinical details. RESULTS: CMBs were found in 128 (36%) patients. Among 356 patients, 119 (33%) had previously undergone percutaneous coronary intervention (PCI), and 26 (7%) coronary artery bypass grafting (CABG). There was no significant relationship between CMBs and sex, hypertension, dyslipidemia, diabetes mellitus, anticoagulation therapy, antiplatelet therapy, or prior PCI. CMBs were significantly associated with advanced age, previous CABG, eGFR, non-HDL cholesterol, carotid artery disease, long-term antiplatelet therapy, and long-term dual antiplatelet therapy (DAPT) using univariate logistic regression analysis. The multivariate logistic regression analysis showed that long-term antiplatelet therapy (odds ratio, 1.73; 95% CI, 1.06 - 2.84; P = 0.03) or long-term DAPT (odds ratio, 2.92; 95% CI, 1.39 - 6.17; P = 0.004) was significantly associated with CMBs after adjustment for confounding variables. CONCLUSIONS: CMBs were frequently observed in patients with CAD and were significantly associated with long-term antiplatelet therapy, especially long-term DAPT.

Motivational interviewing as a new approach to improve outcome through self-care behavioural changes in advanced heart failure patient: a case report.

BACKGROUND: A lack of adherence and inadequate self-care behaviours are common reasons for recurrent hospitalizations among patients with heart failure (HF). Although patients recognize the importance of HF self-care, it is sometimes difficult to correct their behavioural patterns. Motivational interviewing is a communication technique to resolve ambivalence towards changing behaviour, and it has been widely used to promote behavioural changes and improve outcomes in various chronic diseases. We described a case of advanced HF with reduced ejection fraction in which motivational interviewing lead to stabilize the patient's condition. CASE SUMMARY: A 33-year-old man was diagnosed with dilated cardiomyopathy who experienced repeated episodes of HF requiring hospitalization despite optimal guideline-based HF treatment. Transthoracic echocardiography disclosed a severely reduced left ventricular (LV) contraction (LV ejection fraction 18%) and cardiopulmonary exercise testing disclosed markedly reduced functional capacity and increased ventilatory response (peak VO2 of 10.7 mL/min/kg, predicted peak VO2 of 34.7% and VE/VCO2 slope of 35.2). In this case, poor adherence to self-care such as excessive fluid intake and excessive daily activities after hospital discharge was the main cause of recurrent hospitalization for HF. Despite repeated patient education to correct his diet and lifestyle, he could not change his lifestyle behaviour. However, motivational interviewing dramatically helped stabilize the patient's condition and prevent HF re-hospitalization. DISCUSSION: In general, patients with advanced HF and reduced ejection fraction despite optimal medical therapy should be evaluated to assess their eligibility of cardiac transplantation or palliative care. Motivational interviewing might represent a new therapeutic approach for stabilizing and preventing HF through self-care behavioural changes, even in patients with advanced HF and severely reduced ejection fraction.

Effect of canagliflozin on N-terminal pro-brain natriuretic peptide in patients with type 2 diabetes and chronic heart failure according to baseline use of glucose-lowering agents.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of a deterioration in heart failure (HF) and mortality in patients with a broad range of cardiovascular risks. Recent guidelines recommend considering the use of SGLT2 inhibitors in patients with type 2 diabetes (T2D) and HF, irrespective of their glycemic control status and background use of other glucose-lowering agents including metformin. However, only a small number of studies have investigated whether the effects of SGLT2 inhibitor in these patients differ by the concomitant use of other glucose-lowering agents. METHODS: This was a post-hoc analysis of the CANDLE trial (UMIN000017669), an investigator-initiated, multicenter, open-label, randomized, controlled trial. The primary aim of the analysis was to assess the effect of 24 weeks of treatment with canagliflozin, relative to glimepiride, on N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration in patients with T2D and clinically stable chronic HF. In the present analysis, the effect of canagliflozin on NT-proBNP concentration was assessed in the patients according to their baseline use of other glucose-lowering agents. RESULTS: Almost all patients in the CANDLE trial presented as clinically stable (New York Heart Association class I to II), with about 70% of participants having HF with a preserved ejection fraction phenotype (defined as a left ventricular ejection fraction ≥ 50%) at baseline. Of the 233 patients randomized to either canagliflozin (100 mg daily) or glimepiride (starting dose 0.5 mg daily), 85 (36.5%) had not been taking any glucose-lowering agents at baseline (naïve). Of the 148 patients who had been taking at least one glucose-lowering agent at baseline (non-naïve), 44 (29.7%) and 127 (85.8%) had received metformin or a dipeptidyl dipeptidase-4 (DPP-4) inhibitor, respectively. The group ratio (canagliflozin vs. glimepiride) of proportional changes in the geometric means of NT-proBNP concentration was 0.95 (95% confidence interval [CI] 0.76 to 1.18, p = 0.618) for the naïve subgroup, 0.92 (95% CI 0.79 to1.07, p = 0.288) for the non-naïve subgroup, 0.90 (95% CI 0.68 to 1.20, p = 0.473) for the metformin-user subgroup, and 0.91 (95% CI 0.77 to 1.08, p = 0.271) for the DPP-4 inhibitor-user subgroup. No heterogeneity in the effect of canagliflozin, relative to glimepiride, on NT-proBNP concentration was observed in the non-naïve subgroups compared to that in the naïve subgroup. CONCLUSION: The impact of canagliflozin treatment on NT-proBNP concentration appears to be independent of the background use of diabetes therapy in the patient population examined. Trial registration University Medical Information Network Clinical Trial Registry, number 000017669. Registered on May 25, 2015.

Splenic Volume Index Determined Using Computed Tomography upon Admission Is Associated with Readmission for Heart Failure Among Patients with Acute Decompensated Heart Failure.

The spleen is associated with inflammation, and the size of the spleen is affected by hemodynamic congestion and sympathetic stimulation. However, the association between splenic size and prognosis in patients with heart failure remains unknown. Between January 2015 and March 2017, we analyzed 125 patients with acute decompensated heart failure who were assessed by computed tomography (CT) on the day of admission. The spleen was measured by 3-dimensional CT and then the patients were assigned to groups according to their median splenic volume indexes (SpVi; splenic volume/body surface area). We then compared their baseline characteristics and rates of readmission for heart failure after one year. The median SpVi was 63.7 (interquartile range: 44.7-95.3) cm3/m2. Age did not significantly differ between the groups. Patients with a high SpVi had more significantly enlarged left atria and left ventricles. Multiple regression analysis identified significant positive correlations between SpVi and posterior wall thickness as well as left ventricular mass index. Kaplan-Meier analysis revealed lower event-free rates in the patients with a high, than a low SpVi (P = 0.041, log-rank test). After adjustment for potential cofounding factors, SpVi was independently associated with readmission for heart failure (Hazard ratio, 2.25; 95% confidence interval, 1.01-5.02; P = 0.047). In conclusion, increased splenic volume is independently associated with readmission for heart failure among patients with acute decompensated heart failure.

Relation of Aspartate Aminotransferase to Alanine Aminotransferase Ratio to Nutritional Status and Prognosis in Patients With Acute Heart Failure.

Elevated liver fibrosis markers are associated with worse prognosis in acute heart failure (AHF). The aspartate aminotransferase to alanine aminotransferase ratio (AAR) is one such fibrosis marker, and low ALT is a surrogate marker of malnutrition. Here, we evaluated the association between AAR and nutritional status and prognosis in patients with AHF. Consecutive 774 patients who were admitted due to AHF were divided into 3 groups according to AAR at discharge: first tertile, AAR<1.16 (n = 262); second tertile, 1.16≤AAR<1.70 (n = 257); and third tertile, AAR≥1.70 (n = 255). Nutritional indices and a composite of all-cause death or HF rehospitalization were compared in the 3 tertiles. Patients in the third AAR tertile were older and had lower body mass index than patients in other AAR tertiles. A higher AAR was associated with worse nutritional indices (i.e., controlling nutritional status score, geriatric nutritional risk index, and prognostic nutritional index). Clinical outcome rates significantly increased along AAR tertiles (first tertile, 28%; second tertile, 43%; third tertile, 58%, p < 0.001). Cox proportional hazards models including potential prognostic factors revealed high AAR was an independent prognostic factor of AHF. In conclusion, AAR at discharge may be associated with nutritional status and worse clinical outcomes in patients with AHF.

Disproportionately low BNP levels in patients of acute heart failure with preserved vs. reduced ejection fraction.

BACKGROUND: B-type natriuretic peptide (BNP) has been widely used for the diagnosis of heart failure, its severity, and prognosis. However, little is known about factors related to disproportionately low BNP levels even during acute heart failure conditions. METHODS AND RESULTS: Among 424 patients hospitalized for acute heart failure, we categorized the patients into the HFpEF (LVEF > 50%) or HFrEF (LVEF ≤ 50%) group and subdivided them into disproportionately low BNP (LB) group and high BNP (HB) group using a cut-off BNP level of 200 pg/mL at admission. The proportion of patients with LB was higher in the HFpEF group (22.2%) than in the HFrEF group (10.9%, p = 0.002). Patients with LB had a high BMI, lower blood pressure, and history of previous cardiovascular surgery in the HFpEF group, while patients in the HFrEF group had a high BMI and smaller left ventricular end-diastolic volume index. Furthermore, presence of LB in the HFrEF group was related to good prognosis, but LB in the HFpEF group was an indicator of poor prognosis as HB group. CONCLUSIONS: The factors associated with LB were different between the HFpEF and HFrEF groups. LB was related to good prognosis in HFrEF, but not in HFpEF.

A Patient with Cardiac Sarcoidosis in Whom an Abnormal Myocardial Uptake of Fluorine-18 Fluorodeoxyglucose and Sustained Ventricular Tachycardia Recurred 3.5 Years after Discontinuing Oral Corticosteroid Therapy.

We herein report a woman diagnosed with cardiac sarcoidosis (CS) based on the presence of epithelioid granulomas in non-cardiac organs and clinical findings including sustained ventricular tachycardia (VT) and cardiac dysfunction. She stopped oral corticosteroid after 4 years of treatment, and an abnormal myocardial uptake of fluorine-18 fluorodeoxyglucose and sustained VT recurred 3.5 years later. There is no consensus concerning whether or not corticosteroid therapy should be discontinued in the treatment of CS. As a relapse of sarcoidosis-related inflammation may be associated with life-threatening arrhythmia, some patients should continue corticosteroid therapy, even at low doses.

Usefulness of tissue Doppler-derived atrial electromechanical delay for identifying patients with paroxysmal atrial fibrillation.

BACKGROUND: Tissue Doppler imaging (TDI)-derived atrial electromechanical delay (AEMD) has been reported to be useful for detecting paroxysmal atrial fibrillation (PAF). However, its usefulness remains unknown when analyzed along with patients seemingly at high-risk for AF as controls. From this standpoint, we investigated whether AEMD would be of use for identifying patients with PAF. METHODS: We retrospectively analyzed TDI recordings to obtain AEMD in 63 PAF patients. Thirty-three patients with multiple cardiovascular risk factors (MRFs) but without history of AF and 50 healthy individuals served as disease and healthy controls, respectively. AEMD was defined as the time-interval between the electrocardiogram P-wave and the beginning of the spectral TDI-derived A' for the septal (septal EMD) and lateral (lateral EMD) sides of the mitral annulus. RESULTS: There was no significant difference in the left atrial volume index between PAF patients and disease controls (28 ± 9 mL/m2 vs. 27 ± 5 mL/m2). PAF patients had longer AEMD, particularly for the lateral EMD (75 ± 23 ms), compared with disease (62 ± 22 ms, P = 0.009) and healthy (54 ± 24 ms, P < 0.001) controls. Multivariate logistic regression analysis revealed that the lateral EMD (OR 1.25, 95%CI 1.03-1.52, P = 0.023), along with the left atrial volume index (OR 2.25, 95%CI 1.44-3.51, P < 0.001), was one of the significant independent associates of identifying PAF patients. CONCLUSIONS: This cross-sectional study indicates that even analyzed together with MRFs patients, AEMD remains useful for identifying patients at risk for AF. Our results need to be confirmed by a large-scale prospective study.