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Background Interruption in Doppler intrarenal venous flow (IRVF) has been used in assessing renal congestion and in the prediction of prognosis of cardiovascular diseases. However, there is a paucity of pathophysiological knowledge, so we aimed to clarify the determinants of IRVF interruption.Methods and Results:Intrarenal Doppler studies were performed within 24 h before right-side catheterization studies. The interruption in IRVF in 73 patients was divided into a continuous pattern, and 4 discontinuous types based on the timing of interruption. Type 1, with an interruption in early systole, was associated with a-wave elevation of right atrial pressure (RAP). Type 2, with an interruption in early diastole, was associated with v-wave elevation, tricuspid regurgitation (TR), and right ventricular dysfunction. Both Type 1 and 2 were observed even in the normal range of mean RAP. Type 3, with an interruption throughout systole, was observed in advanced right heart failure patients with markedly elevated RAP, particularly elevated x-descend and atrial fibrillation. Finally, Type 4, with limited flow at systole, was observed in 2 of the patients with pulmonary arterial hypertension. Conclusions IRVF interruption was closely related to RAP elevation at each specific point of the cardiac cycle rather than to mean RAP levels, suggesting that the characteristics of IRVF mirror right-sided heart hemodynamics, not mean RAP.

Background: Circulating triglyceride (TG) levels are a current focus as a residual risk for cardiovascular (CV) events. We evaluated the relationship between circulating TG levels and future CV events in patients with coronary artery disease (CAD) who were treated with conventional therapy. Methods and Results: We analyzed data for 652 patients who were enrolled in the FMD-J Study A. We investigated the associations between serum TG levels and first major CV events (death from CV cause, nonfatal acute coronary syndrome (ACS), nonfatal stroke, and CAD) for a 3-year follow-up period. Patients were divided into 4 groups based on serum TG level: low-normal (

Background Although experimental animal studies report many pleiotropic effects of dipeptidyl peptidase-4 inhibitors (DPP-4i), their prognostic value has not been demonstrated in clinical trials.Methods and Results:Among 838 prospectively enrolled heart failure (HF) patients hospitalized for acute decompensated HF, 79 treated with DPP-4i were compared with 79 propensity score-matched non-DPP-4i diabetes mellitus (DM) patients. The primary endpoint was all-cause mortality; the secondary endpoint was a composite of cardiovascular death and hospitalization. During follow-up (423±260 days), 8 patients (10.1%) in the DPP-4i group and 13 (16.5%) in the non-DPP-4i group died (log-rank, P=0.283). The DPP-4i group did not have a significantly higher rate of all-cause mortality (log-rank, P=0.283), or cardiovascular death or hospitalization (log-rank, P=0.425). In a subgroup analysis of HF with preserved ejection fraction (HFpEF; n=75), the DPP-4i group had a significantly better prognosis than the non-DPP-4i group regarding the primary endpoint (log-rank, P=0.021) and a tendency to have better prognosis regarding the secondary endpoint (log-rank, P=0.119). In patients with HF with reduced EF (n=83), DPP-4i did not result in better prognosis. Conclusions DPP-4i did not increase the risk of adverse clinical outcomes in patients with DM and HF. DPP-4i may be beneficial in HFpEF.

BACKGROUND Left atrial remodeling caused by persistent atrial fibrillation (AF) causes atrial functional mitral regurgitation (MR), even though left ventricular (LV) remodeling and organic changes of the mitral leaflets are lacking. The detailed mechanism of atrial functional MR has not been fully investigated. METHODS AND RESULTS Of 1,167 patients with AF who underwent 3D transesophageal echocardiography, 75 patients were retrospectively selected who developed no, mild, or moderate-to-severe atrial functional MR (n=25 in each group) despite an LV ejection fraction ≥50% and LV volumes within the normal range. Mitral valve morphology and dynamics were analyzed. Patients with moderate-to-severe MR had a larger mitral annulus (MA) area, smaller MA area fraction, and greater nonplanarity angle and tethering angle of the posterior mitral leaflet (PML) compared with other groups (all P

BACKGROUND It remains uncertain whether diabetes itself causes specific echocardiographic features of myocardial morphology and function in the absence of hypertension or ischemic heart disease. The purpose of the present study was to determine the characteristics of pure diabetic cardiomyopathy-related echocardiographic morphology and function using layer-by-layer evaluation with myocardial strain echocardiography. METHODS AND RESULTS We enrolled 104 patients with poorly controlled type 2 diabetes mellitus (mean HbA1c level, 10%) with (n=74) or without (n=40) hypertension and 24 age- and sex-matched healthy volunteers. Patients with coronary artery stenosis or structural heart disease were excluded. Myocardial layer-specific strain was analyzed by speckle tracking echocardiography. Compared with the healthy control group, the normotensive diabetes group showed no significant difference in ejection fraction, left ventricular mass index, diastolic properties, left atrial volume index, or B-type natriuretic protein (BNP) level, but global longitudinal strain and subendocardial radial strain were significantly deteriorated. The deterioration of longitudinal strain correlated with body mass index (R=0.49, P

Background:The aim of the present study was to assess the impact of pulmonary regurgitation (PR) and right ventricle (RV) volume on left ventricle (LV) longitudinal strain (LS) in patients with surgically repaired tetralogy of Fallot (r-TOF).Methods and Results:The study subjects were 32 adolescent asymptomatic r-TOF subjects and 30 adolescent healthy controls. Two-dimensional (2-D) and 3-dimensional (3-D) echocardiography were performed in all subjects using Vivid E9 (GE Healthcare). On 3-D analysis, LV and RV volumes were measured using 4D auto LVEF and TomTec RV analysis. PR fraction (PRF) was calculated by the volumetric method (PRF=[RV stroke volume–LV stroke volume]/RV stroke volume). LV-LS was assessed on 2-D speckle tracking echocardiography, and “free wall LS” represented the average of 3 lateral segments. Although RVEF and LVEF were not different between the 2 groups, free wall LS (–17.1±3.2%) was reduced significantly in the r-TOF group compared to the control (–20.5±4.9%, P=0.008), and correlated with the RV variables RVEDVI, RV/LV EDVI ratio and PRF. On multivariate stepwise linear regression analysis, RVEDVI was the only risk factor for the reduction of free wall LS (P=0.004).Conclusions:Free wall LS was significantly reduced despite preserved LVEF. The severity of LS reduction was correlated with RV dilation even in asymptomatic r-TOF patients. (Circ J 2014; 78: 1960–1966)

Speckle tracking echocardiography (STE) was popularized in the first decade of this century. Analysis of cardiac mechanics has been the focus of ultrasonics, and the breakthrough came with STE. Beyond analysis solely of left ventricular ejection fraction, STE allows the assessment of various pathophysiologies, including myocardial layer-specific myocardial function, twist and rotation, and dyssynchrony. Recent developments in the technology have resulted in commercially available 3-dimensional (D)-STE systems. Through experimental studies and clinical investigations, the reliability and feasibility of 3D-STE-derived data have been validated, and the advantages of 3D-STE over 2D-STE have been revealed. In addition, because of the 3D nature of the technology, 3D-STE provides novel deformation parameters (ie, 3D-strain and area change ratio) that have the potential for more accurate assessment of overall and regional myocardial function. Recently, various preliminary studies using 3D-STE have reported on myocardial characteristics, novel mechanics in the left ventricle, prediction of therapeutic effects, observations of cardiac function through interventions, and challenges for left atrial and right ventricular functions. In this review, we focus on the features of the methodology, validation, and clinical application of 3D-ST.

Background: Activation imaging with 3-dimensional speckle-tracking echocardiography (3D-STE) aims to visualize the time required for the onset of regional contraction from QRS onset. We hypothesized that the optimal setting of activation imaging was associated with electrical activation. This study was designed to determine an optimal setting of activation imaging with 3D-STE in comparison with that of a voltage mapping system and to assess the feasibility of this imaging method. Methods and Results: We enrolled 7 patients who underwent electrical voltage mapping. Regional deformation was measured by area change ratio (ACR) with 3D-STE. Activation imaging data were obtained at 10%, 25%, 50%, and 100% of maximal ACR values as the threshold for onset of regional contraction. Duration of LV electrical intraventricular activation time (IVATelectrical) by voltage mapping and mechanical IVAT (IVATmechanical) by activation imaging was defined as the time difference between the first and latest endocardial activation sites. We obtained 21 data sets under various conduction patterns and pacing configurations. The strongest correlation between IVATmechanical and IVATelectrical was observed at 25% of maximal ACR values (IVATelectrical=0.47 * IVATmechanical+20, R=0.80, P

Background: The aim of this study was to carry out 3-dimensional speckle tracking imaging (3DSTI) of the right ventricle (RV) and evaluate RV regional wall deformation. Methods and Results: 3DSTI of the RV was performed in 35 normal subjects, 8 patients with arrhythmogenic right ventricular cardiomyopathy, and 8 patients with pulmonary arterial hypertension. Peak systolic area change ratio and regional contraction timing relative to global systolic time (time to peak strain/time to end-systole×100) were measured in each segment. Good-quality images were acquired of the inflow segment in 87%, apex in 87%, outflow in 57%, and septum in 94% of the 35 normal subjects. In normal subjects, peak systolic area change ratio of the inflow anterior wall was –41±14%; inflow inferior wall, –35±9%; apical anterior wall, –41±10%; apical inferior wall, –31±11%; outflow, –31±9%; and septum wall, –36±11%. Contraction timing of the apical anterior wall and septum wall were earlier than those of other segments. In patients with RV dysfunction, 3DSTI indicated low peak systolic area change ratio in the damaged area. Conclusions: RV 3DSTI indicated segmental heterogeneity in magnitude and timing of RV contraction. 3DSTI may be a promising modality for providing precise quantitative information on complex RV wall motion. (Circ J 2013; 77: 1760–1768)

Background: The aim of this study was to propose modified tissue Doppler imaging (TDI) parameters derived from the first active wall motion and to assess them for the better prediction of cardiac resynchronization therapy (CRT) responders in comparison with to original TDI parameters. Methods and Results: In 61 patients with CRT, time from QRS onset to peak velocities by TDI (Ts), which were derived from active wall motion identified by longitudinal strain rate (LSR) value, were assessed. Time from QRS onset to the negative peak of LSR (TLSR) was also assessed. Modified standard deviation of Ts in 12 left ventricular (LV) segments (Ts-SD), that of TLSR (TLSR-SD), differences of Ts between septum and lateral wall (Ts-SL), and that of TLSR (TLSR-SL) were calculated. Original Ts-SD and Ts-SL were calculated by previously described methods. Responders were defined as patients with LV end-systolic volume reduction (>15%) at 6 months after CRT: 35 patients (57%) were identified as CRT responders. Area under the receiver-operating characteristics curve (AUC) of modified Ts-SD (0.87) was significantly higher than that of Ts-SD (0.65), Ts-SL (0.62), and TLSR-SL (0.69). AUC of modified Ts-SL was significantly higher than those of Ts-SD, and Ts-SL. AUC of TLSR-SD (0.82) also was significantly higher than that of Ts-SD. Conclusions: Modified TDI dyssynchrony parameters derived from the first active wall motion improve the ability to predict responders to CRT. (Circ J 2012; 76: 689-697)

Background: The early diagnosis of myocardial ischemia is still challenging. The aim of the present study was to determine whether subendocardial hypokinesis and post-systolic contraction could be early markers of myocardial ischemia. Methods and Results: Thirty-one consecutive patients with flow-limiting severe coronary stenosis but without visually abnormal left ventricular wall motion underwent quantitative echocardiography. Myocardial strain was measured using layer-by-layer analysis in severely hypoperfused segments. Radial strain (RS) was measured in the subendocardial, subepicardial, and total wall (innerRS, outerRS, and totalRS, respectively). Circumferential strain (CS) was also measured as 3 separate layers: subendocardial, mid-layer, and subepicardial layers (innerCS, midCS, and outerCS, respectively). Post-systolic shortening (PSS) was defined as the peak strain after end systole, and post-systolic strain index (PSI) was calculated as PSS divided by end-systolic strain. TotalRS was similar between ischemic and normally perfused segments, but innerRS and inner/outer RS ratio were significantly smaller in the ischemic segments than in corresponding segments in healthy subjects. Receiver operating characteristic analysis identified an optimum cut-off for PSI of 0.6. The combined criteria of inner/outer RS ratio 0.6 achieved 95% specificity for the presence of flow-limiting stenosis. Conclusions: Combined assessment of both subendocardial contractile impairment and PSS is very useful in identifying a severely hypoperfused left ventricular wall even without visual wall motion abnormality. (Circ J 2011; 75: 1934-1941)

Background: Cholesterol crystal embolism (CCE) is a serious complication of vascular procedures and based on the clinical features of patients with CCE, the aim of the present study was to establish screening criteria for aortic complex plaques (ACP) at high-risk of CCE. Methods and Results: For the first study, 10 patients diagnosed as having CCE were recruited. They had prior multiple atherosclerotic disease and a high proportion of complex plaques of the carotid artery and aorta. Elevated levels of high-sensitivity C-reactive protein (hs-CRP), eosinophilia, and renal insufficiency were already recognized before CCE diagnosis. The second study prospectively enrolled 102 patients. ACP is related to CCE and predictive criteria of ACP were established. Among 19 patients with ACP, 2 presented with CCE. Multivariate analysis revealed carotid complex plaque, eosinophilia and multiple atherosclerotic risk factors as independent predictors of ACP. The criteria including these factors (multiple atherosclerotic risk factors, carotid complex plaque, hs-CRP ≥0.2 mg/dl, eGFR ≤60 ml · min-1 · 1.73 m-2, eosinophil count ≥400 /μl) could detect patients with ACP with 95% sensitivity, 94% specificity, and 79% positive predictive value. Conclusions: Multiple atherosclerotic risk factors, elevated hs-CRP, renal insufficiency, eosinophilia before CCE diagnosis and carotid complex plaques were features of patients with CCE. Diagnostic criteria including these characteristics effectively predict ACP patients at high-risk of CCE. (Circ J 2010; 74: 51 - 58)

Background This study evaluated the usefulness of 3-dimensional echocardiography (3-DE) for identifying permanent pacemaker (PPM) or implantable cardioverter defibrillator (ICD) lead-related symptomatic tricuspid regurgitation (TR). Methods and Results Eighty-seven patients underwent 3-DE examination: 50 patients with PPM, 17 with ICD, and 20 with cardiac resynchronization therapy devices. TR severity was classified as trivial/mild, moderate, or severe according to the ratio of TR area to right atrium area. The 3-DE identified the lead route and position at the tricuspid valve in 82 patients (94.2%). In 5 patients, images without lead-induced artifacts could not be obtained. TR severity was trivial/mild in 50 patients, moderate in 20 patients, and severe in 12 patients. In all patients with trivial/mild TR and all but 1 patient with moderate TR, leads were positioned on the annulus side between leaflets. Lead-induced obstruction to tricuspid valve closing was identified in 1 patient with moderate TR and in 7 of 12 patients with severe TR: 4 patients had septal leaflet obstruction, and 4 had posterior leaflet obstruction. Conclusions The 3-DE can identify the lead route and position at the tricuspid valve and lead-related severe TR, so may be a useful technique of diagnosing the cause of severe TR in patients with PPM or ICD. (Circ J 2008; 72: 1465 - 1470)

Background Carotid arterial ultrasound examination may be helpful for screening populations at high risk for acute coronary syndrome (ACS), so the present study was designed to identify the carotid arterial characteristics of patients with ACS. Methods and Results Carotid ultrasound examinations were performed in 172 patients with ACS, 166 patients with stable coronary artery disease (CAD), and 96 control subjects. Common carotid arterial structures were assessed by the intima - media thickness (IMT), interadventitial diameter (IAD), lumen diameter (LD), the IMT to LD ratio (IMT/LD), and the plaque burden based on the plaque score. Plaque morphology was assessed by the echogenecity based on the gray-scale median (GSM). IMT, IAD, IMT/LD, and plaque score did not differ between the ACS and stable CAD groups. The GSM in the ACS group was lower (47.5±25.3, p

Wall motion abnormality in the apical legion of the left ventricle (LV) with stagnant flow alone is not sufficient to identify patients at high risk for LV thrombus formation among those with first anterior acute myocardial infarction (AMI). The aim of this study was to identify the determinants of LV thrombus formation using contrast echocardiography.In 75 patients with first anterior AMI, standard and contrast echocardiography was performed to detect LV thrombus. Although LV thrombus was found in 10 patients (13%) using standard echocardiography, it was found in 15 patients (20%) using contrast echocardiography. Apical stagnant flow was observed in 14 patients (93%) with LV thrombus. In addition, patients with LV thrombus had a higher peak C-reactive protein (CRP) concentration (18.2+/-4.3 vs 7.9+/-5.5 mg/dl, p0.0001). In multivariate analysis, only peak CRP concentration was identified as an independent predictor of LV thrombus (p=0.02, odds ratio: 1.400, confidence interval: 1.040-1.884). The receiver-operating characteristics (ROC) analysis revealed the best cutoff value of a peak CRP concentration10.7 mg/dl to identify patients with LV thrombus (sensivity 0.93, specificity 0.75, area under ROC curve 0.91).The peak CRP concentration is a useful marker of patients with first anterior AMI who are at high risk for LV thrombus.

Peripartum cardiomyopathy is a rare cardiac disorder characterized by the development of heart failure in the last month of pregnancy or up to 5 months postpartum in women without other determinable causes of cardiac failure. Intracardiac thrombi have been found at autopsy in some patients with this condition and have been demonstrated in the left or right ventricles on 2-dimensional echocardiography. A 23-year-old woman presented with peripartum cardiomyopathy and biventricular thrombi on echocardiography. The thrombi were spherical, pedunculate, shaggy and irregular in configuration, and freely mobile, suggesting that they were fresh. She was treated with conventional heart failure therapy and anticoagulants. Four days later, the apical thrombi within both ventricles had disappeared and there was no evidence of embolism on physical examination. The hypercoagulable state of the peripartum period and the severe biventricular dysfunction most likely led to the formation of biventricular thrombi.