Clinical significance of aortic spontaneous echo contrast in patients with nonvalvular atrial fibrillation.

BACKGROUND: Little is known about spontaneous echo contrast (SEC) in the descending aorta (DASEC), occurring with or without SEC in the left atrium (LASEC), in the presence of atrial fibrillation (AF). We examined the clinical significance of DASEC, including its relationship with LASEC, in patients with nonvalvular AF. METHODS: Among 176 patients, 41 (23%) had DASEC and 51 (29%) had LASEC. The patients were divided into four groups based on the presence/absence of LASEC and DASEC, as Group A: no SEC (n = 107); Group B: only LASEC (n = 28); Group C: only DASEC (n = 18); and Group D: both types of SEC (n = 23). Clinical and echocardiographic parameters were compared between groups, and the possible determinants of DASEC were evaluated. RESULTS: Age, sex, and CHA2 DS2 -VASc score were similar in the four groups. Group D was more likely to have an increased LA diameter, decreased left ventricular ejection fraction (LVEF), and low LA appendage velocity compared to Group A. Group C had a smaller LA diameter and a higher appendage velocity than Group B. Multivariate logistic regression analysis, with age ≥75 years, female sex, LASEC, LVEF < 50%, and presence of DA plaques included as covariates, showed that LASEC (OR 4.22, 95% CI 1.92-9.26, p < .001) and LVEF < 50% (OR 2.70, 95% CI 1.12-6.52, p = .027) were significant determinants of DASEC. The prevalence of DASEC increased with increasing LASEC severity in order of none (13%), mild (28%), and dense (50%) (p < .001). CONCLUSIONS: In nonvalvular AF patients, DASEC is common, and it partly originates from LASEC, particularly in the presence of LV systolic dysfunction.

Echocardiographic manifestations in end-stage renal disease.

End-stage renal disease (ESRD) is a common but profound clinical condition, and it is associated with extremely increased morbidity and mortality. ESRD can represent four major echocardiographic findings-myocardial hypertrophy, heart failure, valvular calcification, and pericardial effusion. Multiple factors interplay leading to these abnormalities, including pressure/volume overload, oxidative stress, and neurohormonal imbalances. Uremic cardiomyopathy is characterized by left ventricular (LV) hypertrophy and marked diastolic dysfunction. In ESRD patients on hemodialysis, LV geometry is changeable bidirectionally between concentric and eccentric hypertrophy, depending upon changes in corporal fluid volume and arterial pressure, which eventually results in a characteristic of LV systolic dysfunction. Speckle tracking echocardiography enabling to detect subclinical disease might help prevent future advancement to heart failure. Heart valve calcification also is common in ESRD, keeping in mind which progresses faster than expected. In a modern era, pericardial effusion observed in ESRD patients tends to result from volume overload, rather than pericarditis. In this review, we introduce and discuss those four echocardiography-assessed findings of ESRD, with which known and conceivable pathophysiologies for each are incorporated.

An inhaled ACE2 decoy confers protection against SARS-CoV-2 infection in preclinical models.

The Omicron variant continuously evolves under the humoral immune pressure exerted by vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the resulting Omicron subvariants display further immune evasion and antibody escape. An engineered angiotensin-converting enzyme 2 (ACE2) decoy composed of high-affinity ACE2 and an IgG1 Fc domain could offer an alternative modality to neutralize SARS-CoV-2. We previously reported its broad spectrum and therapeutic potential in rodent models. Here, we demonstrate that the engineered ACE2 decoy retains neutralization activity against Omicron subvariants, including the currently emerging XBB and BQ.1 strains, which completely evade antibodies currently in clinical use. SARS-CoV-2, under the suboptimal concentration of neutralizing drugs, generated SARS-CoV-2 mutants escaping wild-type ACE2 decoy and monoclonal antibodies, whereas no escape mutant emerged against the engineered ACE2 decoy. Furthermore, inhalation of aerosolized decoys improved the outcomes of rodents infected with SARS-CoV-2 at a 20-fold lower dose than that of intravenous administration. Last, the engineered ACE2 decoy exhibited therapeutic efficacy for cynomolgus macaques infected with SARS-CoV-2. These results indicate that this engineered ACE2 decoy represents a promising therapeutic strategy to overcome immune-evading SARS-CoV-2 variants and that liquid aerosol inhalation could be considered as a noninvasive approach to enhance the efficacy of COVID-19 treatments.

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.

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.

Relationship of warfarin versus DOACs with thrombogenic milieu in the left atrium among patients with nonvalvular atrial fibrillation.

BACKGROUND: Thrombogenic milieu (TM) within the left atrium plays a pivotal role in the pathogenesis of thromboembolic events, for which anticoagulation treatment is indicated typically on the mandatory basis. Little is known, however, about which regimen of anticoagulation, warfarin or direct oral anticoagulants (DOACs), is more likely associated with TM. We evaluated relative relationship of the two treatment options with concurrently-observed TM in patients with nonvalvular atrial fibrillation (AF) who underwent transesophageal echocardiography. METHODS: TM was defined as the presence of either left atrial spontaneous echo contrast (SEC) or thrombus, or both. To determine which regimen was more likely related to TM, we firstly compared the prevalence of TM in 208 patients taking warfarin (Warfarin group) versus 486 patients taking DOACs (DOAC group); and secondly, did the same analysis after propensity score matching. RESULTS: Warfarin group was more likely associated with TM compared with DOAC group (46% vs 29%, p < 0.001). Similar findings were observed for dense SEC (18% vs 7%, p < 0.001) and thrombus (4% vs 1%, p = 0.057). The propensity score matching (198 patients for each group), where several baseline parameters were matched including age, gender, chronicity of AF, estimated glomerular filtration rate and B-type natriuretic peptide as well as the left ventricular ejection fraction, resulted in similar findings to the original groups (TM, 47% vs 32%, p = 0.002; dense SEC, 18% vs 7%, p = 0.001; thrombus, 4% vs 1%, p = 0.047). CONCLUSIONS: This study may strengthen the data on randomized trials that DOACs are superior to warfarin in preventing thromboembolic events in nonvalvular AF patients. Further studies are required to elucidate the details behind this difference.

SRC kinase activator CDCP1 promotes hepatocyte growth factor-induced cell migration/invasion of a subset of breast cancer cells.

Cancer invasion and metastasis are the major causes of cancer patient mortality. Various growth factors, including hepatocyte growth factor (HGF), are known to promote cancer invasion and metastasis, but the regulatory mechanisms involved are not fully understood. Here, we show that HGF-promoted migration and invasion of breast cancer cells are regulated by CUB domain-containing protein 1 (CDCP1), a transmembrane activator of SRC kinase. In metastatic human breast cancer cell line MDA-MB-231, which highly expresses the HGF receptor MET and CDCP1, we show that CDCP1 knockdown attenuated HGF-induced MET activation, followed by suppression of lamellipodia formation and cell migration/invasion. In contrast, in the low invasive/nonmetastatic breast cancer cell line T47D, which had no detectable MET and CDCP1 expression, ectopic MET expression stimulated the HGF-dependent activation of invasive activity, and concomitant CDCP1 expression activated SRC and further promoted invasive activity. In these cells, CDCP1 expression dramatically activated HGF-induced membrane remodeling, which was accompanied by activation of the small GTPase Rac1. Analysis of guanine nucleotide exchange factors revealed that ARHGEF7 was specifically required for CDCP1-dependent induction of HGF-induced invasive ability. Furthermore, immunofluorescence staining demonstrated that CDCP1 coaccumulated with ARHGEF7. Finally, we confirmed that the CDCP1-SRC axis was also crucial for HGF and ARHGEF7-RAC1 signaling in MDA-MB-231 cells. Altogether, these results demonstrate that the CDCP1-SRC-ARHGEF7-RAC1 pathway plays an important role in the HGF-induced invasion of a subset of breast cancer cells.

Hypoplastic Left Atrial Appendage: A Case Report and Literature Review.

BACKGROUND The left atrial appendage (LAA) has considerable variations in its size, shape, and spatial relationship with other cardiac structures. Absence of the LAA is a congenital cardiac condition usually identified by an imaging modality intended for other purposes. Absence of the LAA has been described in a total of 19 case reports so far; however, no cases of "hypoplastic" LAA in a real sense have ever been reported. CASE REPORT We herein report a case of hypoplastic, but not truly absent, LAA in a 76-year-old man scheduled for catheter ablation against atrial flutter. Preprocedural transesophageal echocardiography (TEE) performed in this patient to exclude intracardiac thrombosis failed to detect the LAA, although Doppler color-flow mapping revealed a jet signal spewed out into the main LA around where the LAA would be located. The LAA was also not detectable by routinely developed tomographic images from computed tomography (CT) angiography. Eventually, however, the multiplanar reconstruction into 3-dimensional volume rendering via the CT angiography identified a very small LAA. Those findings by TEE and CT led to a diagnosis of hypoplastic LAA. CONCLUSIONS Hypoplastic LAA should be kept in mind when considering LAA interventions as well as anticoagulation treatment. Multiple imaging modalities are necessary to recognize morphological aberration of the LAA.

Myocardial findings evaluated by echocardiography in cardiac sarcoidosis: A report of seven cases.

Sarcoidosis is a multisystem granulomatous disease of unknown cause. With cardiac sarcoidosis (CS), patients represent a wide range of cardiac manifestations from subtle to overt morphological and functional abnormalities. The advent of ultrasound technologies has enabled to identify not only typical findings to CS such as basal thinning of the ventricular septum, but also subclinical myocardial alterations. Based on our recent experiences, we currently introduce a variety of myocardial manifestations evaluated by echocardiography on seven CS patients being selected. Most of the patients exhibited typical cardiac involvement and the remaining fairly unusual.

An infectivity-enhancing site on the SARS-CoV-2 spike protein targeted by antibodies.

Antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein prevent SARS-CoV-2 infection. However, the effects of antibodies against other spike protein domains are largely unknown. Here, we screened a series of anti-spike monoclonal antibodies from coronavirus disease 2019 (COVID-19) patients and found that some of antibodies against the N-terminal domain (NTD) induced the open conformation of RBD and thus enhanced the binding capacity of the spike protein to ACE2 and infectivity of SARS-CoV-2. Mutational analysis revealed that all of the infectivity-enhancing antibodies recognized a specific site on the NTD. Structural analysis demonstrated that all infectivity-enhancing antibodies bound to NTD in a similar manner. The antibodies against this infectivity-enhancing site were detected at high levels in severe patients. Moreover, we identified antibodies against the infectivity-enhancing site in uninfected donors, albeit at a lower frequency. These findings demonstrate that not only neutralizing antibodies but also enhancing antibodies are produced during SARS-CoV-2 infection.

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.

Left Atrial Appendage Ostial Stenosis: A Case Report and Literature Review.

BACKGROUND Left atrial appendage (LAA) ostial stenosis is a rare cardiac condition usually identified by transesophageal echocardiography (TEE). LAA ostial stenosis can be classified into 2 types: one is idiopathic and the other is a complication after incomplete surgical LAA ligation. The former one is even rarer and only 12 cases have previously been reported. CASE REPORT An asymptomatic young woman was found at a medical checkup to have an abnormal jet signal in the left atrium on transthoracic echocardiography. TEE revealed that the abnormal signal originated from a narrowed orifice of the LAA. There were no other cardiac abnormalities in this woman. Unlike the previously reported cases, our case had LAA ostial stenosis detected by transthoracic echocardiography but not by TEE. CONCLUSIONS We describe a case of anatomic narrowing of the LAA orifice in a young woman. This was a first-ever case of idiopathic LAA ostial stenosis that was detected by transthoracic echocardiography. Because of the very small number of such cases reported, it remains unknown whether anticoagulation is required to prevent intra-atrial thrombus formation.

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.

Left atrial spontaneous echo contrast occurring in patients with low CHADS2 or CHA2DS2-VASc scores.

BACKGROUND: Left atrial spontaneous echo contrast (LASEC) is common in patients with atrial fibrillation (AF), although scarce information exists on LASEC occurring in nonvalvular AF patients who have low thromboembolic risk scores. We therefore examined prevalence and determinants of LASEC under low CHADS2 or CHA2DS2-VASc scores in these patients. METHODS: Among 713 patients who underwent transesophageal echocardiography, 349 with a CHADS2 score < 2 (CHADS2 group) (93 women, mean age 65 years) and 221 with a CHA2DS2-VASc score < 2 (CHA2DS2-VASc group) (39 women, mean age 62 years) were separately examined for clinical and echocardiographic findings. RESULTS: LASEC was found in 77 patients of CHADS2 group (22%) and in 41 of CHA2DS2-VASc group (19%). Multivariate logistic regression analysis, adjusted for several parameters including non-paroxysmal AF, LA enlargement (LA diameter ≥ 50 mm), left ventricular (LV) hypertrophy, and an elevated B-type natriuretic peptide (BNP) (BNP ≥200 pg/mL) revealed that for CHADS2 group, non-paroxysmal AF (Odds ratio 5.65, 95%CI 3.08-10.5, P < 0.001), BNP elevation (Odds ratio 3.42, 95%CI 1.29-9.06, P = 0.013), and LV hypertrophy (Odds ratio 2.26, 95%CI 1.19-4.28, P = 0.013) were significant independent determinants of LASEC, and that for CHA2DS2-VASc group, non-paroxysmal AF (Odds ratio 3.38, 95%CI 1.51-7.54, P = 0.003) and LV hypertrophy (Odds ratio 2.53, 95%CI 1.13-5.70, P = 0.025) were significant independent determinants of LASEC. CONCLUSIONS: LASEC was present in a considerable proportion of patients with nonvalvular AF under low thromboembolic risk scores. Information on AF chronicity, BNP, and LV hypertrophy might help identify patients at risk for thromboembolism, although large-scale studies are necessary to confirm our observations.

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.

Etiology of Atrial Functional Mitral Regurgitation: Insights from Transthoracic Echocardiography in 159 Consecutive Patients with Atrial Fibrillation and Preserved Left Ventricular Ejection Fraction.

BACKGROUND: Left atrial (LA) dilatation in patients with atrial fibrillation (AF) can induce functional mitral regurgitation (MR) despite a preserved left ventricular ejection fraction (LVEF). The purpose of this study was to investigate the etiology of this functional MR. METHODS: We retrospectively examined clinical and echocardiographic data from 5,202 consecutive cases that underwent transthoracic echocardiography. AF appeared in 544 patients, and we selected 159 with AF and LVEF ≥50% after excluding patients with other underlying heart diseases. RESULTS: Significant (moderate or greater) degrees of functional MR were seen in 13 (8.2%) patients and were more frequently seen in patients with an AF duration of >10 years than in others (27 vs. 4%, p = 0.0057). Multiple regression analysis revealed that both the LA dimension index and the left ventricular (LV) systolic dimension index were independent determinants of the MR grading. Among the mitral morphologic parameters, the mitral annular (MA) dimension index and the hamstringing phenomenon of the posterior mitral leaflet were independent determinants of MR grading. Significant MR was not seen in patients without LA dilatations, but it occurred in 14% of patients with LA dilatation alone and in 55% with both LA and LV dilatations; the MA dimension index increased in this order. CONCLUSIONS: The grading of functional MR occurring in patients with AF and preserved LVEF depends on both the LA dimension and the LV systolic dimension. The MR grading also depends on both the MA dilatation and the hamstringing phenomenon of the posterior mitral leaflet.

Transient depression of myocardial function after influenza virus infection: A study of echocardiographic tissue imaging.

BACKGROUND: Influenza virus infection (IVI) was reported to be associated with minor cardiac changes, mostly those detected on electrocardiogram with and without elevated blood markers of myocardial injury; however, the characteristics of myocardial involvement in association with IVI are poorly understood. This study used echocardiographic tissue imaging (tissue Doppler, strain, and strain rate) to evaluate changes in left atrial (LA) and left ventricular (LV) myocardial function after IVI. METHODS AND RESULTS: We examined 20 adult individuals (mean age, 43 years) at 2 and 4 weeks after diagnosis of IVI. For myocardial functional variables, we obtained LV global longitudinal strain (GLS), LV early diastolic strain rate (e'sr), LA strain, and LA stiffness (E/e'/LA strain), in addition to data on tissue Doppler (s', e', and a') and myocardial performance index. Blood markers of myocardial injury were also examined. During follow-up, there were no significant changes in global chamber function such as LV ejection fraction, E/e', and LA volume. However, significant changes in myocardial function were observed, namely, in s' (8.0 ± 1.6 cm/s to 9.3 ± 1.5 cm/s; p = 0.01), e' (10.2 ± 2.8 cm/s to 11.4 ± 3.0 cm/s; p < 0.001), e'sr (1.43 ± 0.44 1/s to 1.59 ± 0.43 1/s; p = 0.005), and LA strain (35 ± 8% to 40 ± 12%; p = 0.025), and the myocardial performance index (0.52 ± 0.20 to 0.38 ± 0.09; p = 0.009), but not in a', LA stiffness, or GLS. Cardiac troponin T and creatinine kinase isoenzyme MB were not elevated significantly at any examination. CONCLUSIONS: Myocardial dysfunction during IVI recovery appeared to be transient particularly in the absence of myocardial injury. Echocardiographic tissue imaging may be useful to detect subclinical cardiac changes in association with IVI.

Left Atrial Ball-Shaped Thrombus with Concomitant Biatrial Appendage Thrombi in a Patient with Prior Mitral Valve Replacement.

We reported a 67-year-old woman in whom large atrial thrombi were found by chance during discontinuation of therapeutic anticoagulation. The patient, with a history of mitral valve replacement surgery, had stopped anticoagulation for months because of intractable gastrointestinal bleeding, during which she was found to have 3 large thrombi in the atria on transesophageal echocardiography: left atrial free-floating ball-shaped thrombus, left atrial appendage thrombus, and right atrial appendage thrombus. One month following diagnosis, she still had the free-floating thrombus despite adequate anticoagulation. Free-floating ball-shaped thrombus is a rare finding observed on echocardiography in patients with mitral valve disease and an even rarer finding in case of appendage thrombi coexisting.