Risk classification of pulmonary arterial hypertension by echocardiographic combined assessment of pulmonary vascular resistance and right ventricular function.

Which combination of clinical parameters improves the prediction of prognosis in patients with pulmonary arterial hypertension (PAH) remains unclear. We examined whether combined assessment of pulmonary vascular resistance and right ventricular function by echocardiography is useful for classifying risks in PAH. In 41 consecutive patients with PAH (mean age of 48.9 ± 17.3 years, 31 females), a 6-min walk test, pulmonary function test, and echocardiography were performed at baseline and during PAH-specific therapies. The study endpoint was defined as a composite of cardiovascular death and hospitalization for PAH and/or right ventricular failure. During a follow-up period of 9.2 ± 8.7 months, 18 patients reached the endpoint. Multivariate regression analysis showed that the ratio of tricuspid regurgitation pressure gradient to the time-velocity integral of the right ventricular outflow tract (TRPG/TVI) and tricuspid annular plane systolic excursion (TAPSE) during PAH-specific treatment were independent prognostic predictors of the endpoint. Using cutoff values indicated by receiver operating characteristic analysis, the patients were divided into four subsets. Multivariate analyses by Cox's proportional hazards model adjusted for age, sex and body mass index indicated that subset 4 (TRPG/TVI ≥ 3.89 and TAPSE ≤ 18.9 mm) had a significantly higher event risk than did subset 1 (TRPG/TVI < 3.89 and TAPSE > 18.9 mm): HR = 25.49, 95% CI 4.70-476.97, p < 0.0001. Combined assessment of TRPG/TVI and TAPSE during adequate PAH-specific therapies enables classification of risks for death and/or progressive right heart failure in PAH.

Circulating Fatty Acid-Binding Protein 4 Concentration Predicts the Progression of Carotid Atherosclerosis in a General Population Without Medication.

BACKGROUND: Fatty acid-binding protein 4 (FABP4), which is expressed in both adipocytes and macrophages, is secreted from the cells and acts as an adipokine. An elevated circulating FABP4 level is associated with insulin resistance and atherosclerosis.Methods and Results:We investigated the causative association between FABP4 level and progression of atherosclerosis in subjects of the Tanno-Sobetsu Study, a population-based cohort. In 281 subjects without medication (male/female: 109/172) in the year 2010 or 2013, the carotid intima-media thickness (CIMT) assessed using carotid ultrasonography was significantly correlated with age, adiposity, blood pressure, renal dysfunction and levels of cholesterol, triglycerides, fasting glucose, HbA1c and FABP4 (r=0.331, P<0.001). Multiple regression analysis demonstrated that age, sex and FABP4 concentration were independent predictors of CIMT. A total of 78 (male/female: 29/49) of the 156 subjects in 2010 underwent carotid ultrasonography again in 2013. The change in CIMT each year during that 3-year period (mean±SD: 3.8±22.3 µm/year) was positively correlated with basal levels of high-sensitivity C-reactive protein (hsCRP) (r=0.231, P=0.046) and FABP4 (r=0.267, P=0.018) in 2010. After adjustment for age, sex and hsCRP level, the basal FABP4 level was independently associated with the change in CIMT per year. CONCLUSIONS: FABP4 concentration is an independent predictor of the progression of carotid atherosclerosis.

"Ballooning" patterns in takotsubo cardiomyopathy reflect different clinical backgrounds and outcomes: a BOREAS-TCM study.

Whether different patterns of ventricular ballooning in takotsubo cardiomyopathy (TCM) reflect differences in trigger mechanisms or clinical outcomes is unclear. Here we examined differences in the clinical characteristics of typical and atypical forms of TCM. TCM patients (n = 251) in the BOREAS Registry were enrolled for comparison of TCM with apical ballooning (type A, n = 217) and TCM with non-apical ballooning (type non-A, n = 34). The percentage of females was significantly lower in the type non-A group (58.8 vs. 75.6 %), while other demographic parameters and triggers of TCM were similar in the two groups. Rate of mid-ventricular obstruction (MVO) was lower (2.9 vs. 14.3 %) in the type non-A group than in the type A group, though left ventricular ejection fractions in the two groups were comparable. During a follow-up period of 2.6 ± 2.8 years, TCM recurred in 2.9 % of the patients and cardiac death occurred in 4.0 %. Cox proportional hazard analysis indicated that body mass index (hazard ratio [HR]: 0.75, 95 % confidence interval [CI] 0.54-0.99) and MVO (HR: 14.71, CI 1.87-304.66) were determinants of TCM recurrence and that advanced age (HR: 1.09, CI 1.02-1.17) and cardiogenic shock (HR: 4.27, CI 1.07-18.93) were significantly associated with cardiac death. In conclusion, approximately 20 % of TCM patients show non-apical left ventricular ballooning, and female sex and MVO are less frequent in this type than in apical ballooning type TCM. Low body mass index and MVO are risk factors of recurrence, and advanced age and cardiogenic shock are risk factors of cardiac death in TCM.

Intervendor Variabilities of Left and Right Ventricular Myocardial Velocities among Three Tissue Doppler Echocardiography Systems.

BACKGROUND: Whether an intervendor discordance of myocardial velocities determined by tissue Doppler echocardiography (TDE) can be generalized remains unclear. We compared intervendor variabilities of left ventricular (LV) and right ventricular (RV) myocardial velocities among three TDE systems. METHODS: Examinations with TDE were performed in 41 healthy subjects and 11 patients with cardiovascular risk factors (CVR) using α-7 (V1, Hitachi Aloka Medical), Artida (V2, Toshiba Medical Systems), and Vivid E9 (V3, GE Healthcare) on the same day. Peak systolic (s'), early diastolic (e'), and late diastolic (a') myocardial velocities at medial and lateral sites of the mitral annulus and lateral site of the tricuspid annulus were measured using both pulsed-wave TDE and color TDE. Intra-observer and inter-observer variabilities were determined in 10 subjects and test-retest variability in 14 subjects. RESULTS: As for test-retest variability, reproducibilities of LV and RV myocardial velocities determined by pulsed-wave TDE and color TDE were relatively low but comparable between V1, V2, and V3. Myocardial velocities in healthy subjects determined by both pulsed-wave TDE and color TDE were significantly different among the three TDE systems. Myocardial velocities by pulsed-wave TDE in V3 were 2-12% lower (P < 0.05) than those by V2 and 5-14% lower (P < 0.05) than those by V1. Similar differences in myocardial velocities determined by both pulsed-wave TDE and color TDE were found in patients with CVR. CONCLUSIONS: LV and RV myocardial velocities determined by both pulsed-wave TDE and color TDE are vendor dependent, and reproducibility of the myocardial velocities determined by both TDE systems is relatively low.

Elevation of circulating fatty acid-binding protein 4 is independently associated with left ventricular diastolic dysfunction in a general population.

BACKGROUND: Fatty acid-binding protein 4 (FABP4) is expressed in both adipocytes and macrophages. Recent studies have shown secretion of FABP4 from adipocytes and association of elevated serum FABP4 level with obesity, insulin resistance, hypertension, and atherosclerosis. However, little is known about role of FABP4 in cardiac function. METHODS: From the database of the Tanno-Sobetsu Study, data for 190 subjects (male/female: 82/108) who were not treated with any medication and underwent echocardiography in 2011 or 2012 were retrieved for analyses of relationships between serum FABP4 concentration, metabolic markers and parameters of echocardiography. RESULTS: Serum FABP4 level was positively correlated with age, body mass index (BMI), blood pressure (BP), LDL cholesterol, HOMA-R and mean left ventricular (LV) wall thickness (LVWT, males: r = 0.315, females: r = 0.401, p < 0.01) and was negatively correlated with HDL cholesterol, estimated glomerular filtration rate (eGFR) and peak myocardial velocity during early diastole (e'; males: r = -0.434, females: r = -0.353, p < 0.01), an index of LV diastolic function. However, no significant correlation was found between FABP4 level and LV end-diastolic dimension, LV ejection fraction or LV mass index. There were significant correlations of e' with age, BMI, BP, eGFR, brain natriuretic peptide (BNP), FABP4, metabolic markers and LVWT. Multivariate regression analysis adjusted by HOMA-R, BMI, eGFR, BNP or LVWT in addition to age, gender and BP revealed that serum FABP4 concentration was independently correlated with e'. CONCLUSIONS: Elevation of circulating FABP4 may contribute to LV diastolic dysfunction in a general population.

Inter-vendor variability of left ventricular volumes and strains determined by three-dimensional speckle tracking echocardiography.

BACKGROUND: Inter-vendor discordance in three-dimensional speckle-tracking echocardiography (3DS) remains uncharacterized. We aimed to examine inter-vendor discordance of left ventricular (LV) volumes, and functional parameters and their reproducibilities between two commercially available 3DS systems. METHODS: Echocardiographic examinations with 3DS were performed in 26 healthy subjects (age 34 ± 13 years, 85% men) using a Vivid E9 system (V1) with 4V probe (GE Health Care) and Artida (V2) with PST-25SX probe (Toshiba Medical Systems) on the same day. LV variables and global LV longitudinal, circumferential, radial, and area strains were measured by vendor-specific softwares, 4D strain EchoPAC BT11 (for V1) and 3D WMT (for V2), respectively. Reproducibility of data was assessed by an intra-class correlation coefficient (ICC). RESULTS: The mean time required for 3DS analysis was 5.4 ± 1.5 min for V1, being 21% less than that for V2 (6.8 ± 1.9 min, P < 0.01). Reproducibilities of all LV strains were comparable between V1 (ICC 0.50-0.82) and V2 (ICC 0.51-0.76), except for intra-observer and inter-observer reproducibilities of radial strain being lower in V2 (ICC for V1 0.82 and 0.82 and ICC for V2 0.44 and 0.40, respectively). LV strains in all directions and area were significantly different between V1 and V2, though LV volumes and ejection fraction were comparable. CONCLUSIONS: Global longitudinal, circumferential, and area LV strains are reproducible in both 3DS vendors. However, values of three-dimensional LV strains by 3DS are highly vendor-dependent.

Delayed visceral bleeding from liver injury after cardiopulmonary resuscitation.

BACKGROUND: Visceral injury is a life-threatening complication of cardiopulmonary resuscitation (CPR); however, the clinical significance has been masked by the lethal outcome of out-of-hospital cardiac arrest (OHCA). OBJECTIVE: The objective is to share our experience of successful treatment of OHCA patients with serious, CPR-related visceral complications. CASE REPORTS: We report two cases of cardiac-origin OHCA with liver injury exacerbated by heparinization during mechanical circulatory support. Although both patients presented with delayed massive liver bleeding (intrahepatic or peritoneal) that compromised hemodynamic status, one patient was successfully treated by selective transcatheter arterial embolization and the other by a surgical procedure. CONCLUSION: Preventive measures such as careful CPR, as well as interventional or surgical repair after the early diagnosis of visceral injury, are required to improve the outcome in some cases of OHCA.

Left atrial strain assessed by three-dimensional speckle tracking echocardiography predicts atrial fibrillation recurrence after catheter ablation in patients with paroxysmal atrial fibrillation.

BACKGROUND: Several studies have shown the utility of left atrial (LA) function determined by two-dimensional or three-dimensional speckle tracking echocardiography (2D- or 3D-STE) for identifying patients with paroxysmal atrial fibrillation (AF). However, whether 3D-STE is applicable for prediction of the recurrence of AF after catheter ablation (CA) remains unknown. We examined whether any 3D-STE parameters are better than 2D-STE parameters for the prediction of AF recurrence. METHODS: Forty-two patients with paroxysmal AF (58 ± 10 years old, 69% male) underwent 2D- and 3D-STE within 3 days before first-time CA. The global peak LA longitudinal, circumferential, and area strains during systole (3D-GLSs, -GCSs, and -GASs, respectively) and those just before atrial contraction (3D-GLSa, -GCSa, and -GASa, respectively) were determined by 3D-STE and standard deviations of times to peaks of regional LA strains were calculated as indices of LA dyssynchrony. In 2D-STE, global LA longitudinal strains during systole and just before atrial contraction (2D-GLSs and -GLSa) were determined. RESULTS: During follow-up of 441 ± 221 days, 12 patients (29%) had AF recurrence. In the univariate Cox proportional hazard analysis, age [hazard ratio (HR): 1.08, p = 0.04], 3D-GCSs (HR: 0.91, p = 0.03), and 3D-GASs (HR: 0.95, p = 0.01) were predictors of AF recurrence, though associations of recurrence with 2D-STE parameters, indices of LA synchrony, and LA volume were not significant. Multivariable analysis showed that 3D-GASs was an independent predictor of AF recurrence (HR: 0.96, p = 0.048). CONCLUSIONS: LA strain determined by 3D-STE is a novel and better predictor of AF recurrence after CA than that determined by 2D-STE or other known predictors.

Serum FABP5 concentration is a potential biomarker for residual risk of atherosclerosis in relation to cholesterol efflux from macrophages.

Cholesterol efflux capacity (CEC) from macrophages, the first step in the reverse cholesterol transport pathway, is inversely associated with residual risk for atherosclerotic cardiovascular disease. Fatty acid-binding protein 4 (FABP4) and FABP5 are expressed in both adipocytes and macrophages and play significant roles in the development of insulin resistance and atherosclerosis. Both FABP4 and FABP5 are secreted from cells, and their circulating levels are associated with insulin resistance and atherosclerosis. We investigated the association between CEC and levels of FABP4 and FABP5 in 250 subjects without any medications. CEC was positively correlated with HDL cholesterol level and negatively correlated with concentrations of high-sensitivity C-reactive protein (hsCRP) and FABP5, but not FABP4. Multiple regression analysis demonstrated that FABP5 concentration was an independent predictor of CEC after adjustment of age, gender and levels of HDL cholesterol and hsCRP. In 129 of the 250 subjects who underwent carotid ultrasonography, mean intima-media thickness was negatively correlated with CEC and was positively correlated with concentrations of FABP4 and FABP5. In conclusion, in contrast to FABP4, circulating FABP5 is associated with decreased CEC and carotid atherosclerosis, suggesting that FABP5 level is a regulatory factor of CEC and a potential biomarker for residual risk of atherosclerosis.

Utility of three-dimensional transesophageal echocardiography for diagnosis of unroofed coronary sinus.

We report a case of unroofed coronary sinus (URCS) in a 42-year-old female. At an outpatient clinic, she was found to have an atrioventricular septal defect and mitral regurgitation with pulmonary hypertension, and she was transferred to our institute for surgical treatment. Both atrioventricular valves were located at the same level, and both the right atrium (RA) and right ventricle were enlarged on two-dimensional transthoracic echocardiography. Color Doppler imaging demonstrated severe mitral and tricuspid regurgitation and a left-to-right shunt from the left atrium (LA) to the RA. Although an ostium primum defect of the atrial septum was suspected, the exact position of the shunt flow was unclear. Two-dimensional transesophageal echocardiography (2D-TEE) could visualize a direct communication between the LA and coronary sinus. Three-dimensional transesophageal echocardiography (3D-TEE) clearly visualized the entire route from the coronary sinus into the LA and RA. The utility of 3D-TEE as a modality complementary to 2D-TEE in diagnosis of URCS was confirmed.

Does a Reduction in the Glomerular Filtration Rate Increase the Overall Severity of Coronary Artery Stenosis?

OBJECTIVE: Chronic kidney disease is a risk factor of coronary events, however, its impact on coronary artery stenosis has not yet been clarified with the use of a large database. We examined the association between a reduced glomerular filtration rate (GFR) and the overall severity of coronary stenosis. METHODS: We enrolled 1,150 patients [mean age, 68±12 (SD) years; 66.6% men] who consecutively underwent coronary angiography for suspected stable angina pectoris. The overall severity of stenosis in the coronary arteries was assessed by the Gensini score (GS), and its logarithmic values (log-GS) were used for statistical analyses since the GS does not follow a normal distribution. RESULTS: The log-GS was significantly larger in men than in women (2.5±1.5 vs. 1.9±1.7), while the estimated GFR (eGFR) and comorbidities were comparable between both sexes. A multivariate regression analysis indicated that age, smoking, eGFR, HDL-cholesterol and HbA1c were independent explanatory variables of the log-GS in men, although the eGFR explained only 1.2% of the log-GS variation. In women, the eGFR was not included in the significant explanatory variables shown by the multivariate analysis. However, the sex difference in the regression for the eGFR-log-GS relationship was not statistically significant. CONCLUSION: A reduced eGFR is a significant, but minor, determinant of the overall severity of coronary artery stenosis in men and potentially women.

Assessment of left atrial deformation and synchrony by three-dimensional speckle-tracking echocardiography: comparative studies in healthy subjects and patients with atrial fibrillation.

BACKGROUND: The aim of this study was to examine whether left atrial (LA) strain and synchrony can be assessed using three-dimensional (3D) speckle-tracking echocardiography (STE) and how 3D STE parameters are modified by atrial fibrillation (AF). METHODS: LA peak ventricular systolic longitudinal strain (LSs), circumferential strain (CSs), and area strain (ASs) and LA peak pre-atrial contraction longitudinal strain, circumferential strain (CSa), and area strain were determined using 3D STE, and SDs of times to peaks of regional LA strain were calculated as indices of LA dyssynchrony. Three-dimensional speckle-tracking was able to measure LA strain in 75 of the 77 healthy subjects and in all 47 patients with AF (31 with paroxysmal AF [PAF] and 16 with permanent AF). RESULTS: The mean time for analysis with 3D STE was 18% shorter than with two-dimensional (2D) STE (P < .05). On 3D STE, values of interobserver and intraobserver variability of LA strain were <10% and <12%, respectively. LSs, CSs, ASs, and 2D STE LSs were reduced in patients with PAF compared with controls, and further reductions of these parameters were observed in patients with permanent AF. SDs of LSs, CSs, and ASs were similarly larger in patients with PAF and in those with permanent AF compared with controls. Patients with PAF showed smaller LA peak pre-atrial contraction longitudinal strain, CSa, and LA peak pre-atrial contraction area strain and larger SDs of CSa and LA peak pre-atrial contraction area strain compared with controls. In multivariate analysis, 2D STE LSs (P = .044), LSs (P = .040), ASs (P = .007), and CSa (P = .020) were independent predictors of PAF. CONCLUSIONS: Three-dimensional speckle-tracking enables the measurement of both LA strain and synchrony with excellent reproducibility. Three-dimensional LA strain appears to be beneficial compared with 2D LA strain for identifying patients with PAF.