AVP-eGFP was significantly upregulated by hypovolemia in the parvocellular division of the paraventricular nucleus in the transgenic rats.

Arginine vasopressin (AVP) is produced in the paraventricular (PVN) and supraoptic nuclei (SON). Peripheral AVP, which is secreted from the posterior pituitary, is produced in the magnocellular division of the PVN (mPVN) and SON. In addition, AVP is produced in the parvocellular division of the PVN (pPVN), where corticotrophin-releasing factor (CRF) is synthesized. These peptides synergistically modulate the hypothalamic-pituitary-adrenal (HPA) axis. Previous studies have revealed that the HPA axis was activated by hypovolemia. However, the detailed dynamics of AVP in the pPVN under hypovolemic state has not been elucidated. Here, we evaluated the effects of hypovolemia and hyperosmolality on the hypothalamus, using AVP-enhanced green fluorescent protein (eGFP) transgenic rats. Polyethylene glycol (PEG) or 3% hypertonic saline (HTN) was intraperitoneally administered to develop hypovolemia or hyperosmolality. AVP-eGFP intensity was robustly upregulated at 3 and 6 h after intraperitoneal administration of PEG or HTN in the mPVN. While in the pPVN, eGFP intensity was significantly increased at 6 h after intraperitoneal administration of PEG with significant induction of Fos-immunoreactive (-ir) neurons. Consistently, eGFP mRNA, AVP hnRNA, and CRF mRNA in the pPVN and plasma AVP and corticosterone were significantly increased at 6 h after intraperitoneal administration of PEG. The results suggest that AVP and CRF syntheses in the pPVN were activated by hypovolemia, resulting in the activation of the HPA axis.

Discrepancy of Aortic Valve Area Measurements by Doppler vs. Biplane Stroke Volume Measurements and Utility of Combining the Different Areas in Aortic Valve Stenosis　- The Asian Valve Registry.

BACKGROUND: The aortic valve area index (AVAI) in aortic stenosis (AS) is measured by echocardiography with a continuity equation using the stroke volume index by Doppler (SVIDoppler) or biplane Simpson (SVIBiplane) method. AVAIDopplerand AVAIBiplaneoften show discrepancy due to differences between SVIDopplerand SVIBiplane. The degree of discrepancy and utility of combined AVAIs have not been investigated in a large population of AS patients, and the characteristics of subjects with larger discrepancies are unknown.Methods and Results:We studied 820 patients with significant AS (AVADoppler<1.5 cm2) enrolled in the Asian Valve Registry, a prospective multicenter registry at 12 Asian centers. All-cause death and aortic valve replacement were defined as events. SVIDopplerwas significantly larger than SVIBiplane(49±11 vs. 39±11 mL/m2, P<0.01) and AVAIDopplerwas larger than AVAIBiplane(0.51±0.15 vs. 0.41±0.14 cm2/m2, P<0.01). An increase in (AVAIDoppler- AVAIBiplane) correlated with shorter height, lower weight, older age, smaller left ventricular (LV) diameter and increased velocity of ejection flow at the LV outflow tract. Severe AS by AVAIDoppleror AVAIBiplaneenabled prediction of events, and combining these AVAIs improved the predictive value of each. CONCLUSIONS: Discrepancy in AVAI by Doppler vs. biplane method was significantly more pronounced with increased LV outflow tract flow velocity, shorter height, lower weight, older age and smaller LV cavity dimensions. Combining the AVAIs enabled mutual and incremental value in predicting events.

Novel noninvasive estimation of mixed venous oxygen saturation by echocardiography and expired gas analysis.

Mixed venous oxygen (O2) saturation ([Formula: see text]) is an important measure for evaluating the sufficiency of cardiac output (CO) relative to whole body O2 consumption (V̇o2), while clinical use is limited to the required invasive catheterization. According to Fick's equation, V̇o2 (mL/min) = CO (L/min) × Hb (g/dL) × 1.36 (mL/g) × ([Formula: see text] - [Formula: see text])/10 (Hb = hemoglobin concentration, [Formula: see text] = arterial blood O2 saturation). Because V̇o2, CO, Hb, and [Formula: see text] can be measured noninvasively with expired gas analysis, echocardiography, a simple blood test, and percutaneous O2 saturation, respectively, [Formula: see text] can be calculated noninvasively. We hypothesized that noninvasively calculated [Formula: see text] shows a significant correlation and agrees well with invasively measured [Formula: see text]. In 47 patients (29 men; mean age, 70 ± 12 yr) who underwent right heart catheterization, [Formula: see text] was directly measured by sampling pulmonary artery blood. Noninvasively calculated [Formula: see text] was also obtained by the method described above. The calculated [Formula: see text] was significantly correlated with the measured [Formula: see text] (r = 0.79, P < 0.001) and was significantly smaller than the measured [Formula: see text] (70 ± 5.1 vs. 72.1 ± 4.9%, P < 0.001). Bias at [Formula: see text] was -2.2% (95% confidence interval, -3.2 to -1.1%) with limits of agreement from -9.5 to 5.2%, demonstrating acceptable agreement. The optimal cutoff value of calculated [Formula: see text] was 69% for reduced measured [Formula: see text] < 70% with an area under the curve of 0.94. Reduced calculated [Formula: see text] < 69% indicated a sensitivity of 92.9% and a specificity of 90.9% for reduced measured [Formula: see text] < 70%. Noninvasive [Formula: see text] calculated from echocardiography, expired gas analysis, percutaneous arterial blood O2 saturation, and hemoglobin level significantly correlated and agreed well with direct [Formula: see text] measured by catheterization. This novel method allows for practical evaluation of [Formula: see text] to assess the sufficiency of CO according to whole body metabolism.NEW & NOTEWORTHY Clinical use of mixed venous oxygen saturation ([Formula: see text]) is limited to the required invasive procedure. With Fick's equation, expired gas analysis, echocardiography, simple blood tests, and percutaneous oxygen saturation, [Formula: see text] can be calculated noninvasively. We hypothesized that noninvasively calculated [Formula: see text] shows a significant correlation and agrees well with invasively measured [Formula: see text]. The present study examined the relationship between measured [Formula: see text] and calculated [Formula: see text] in patients who underwent right heart catheterization and demonstrated acceptable agreement. This novel method can expand the indication of evaluating [Formula: see text].

Potential mechanism of left ventricular spherical remodeling: association of mitral valve complex-myocardium longitudinal tissue remodeling mismatch.

Since mitral valve (MV) complex (MVC) longitudinally bridges left ventricular (LV) base end and its middle, insufficient MVC longitudinal tissue length (TL) elongation relative to whole LV myocardial longitudinal TL elongation could limit LV-base-longitudinal-TL elongation, leading to predominant LV-base-transverse-TL elongation, constituting LV spherical remodeling. In 30 patients with dilated cardiomyopathy (DCM), 30 with aortic regurgitation (AR), and 30 controls, LV sphericity, LV-apex- or base-transverse- and longitudinal-TL, MVC-longitudinal-TL, and whole-LV-longitudinal-TL were measured by three-dimensional (3D) echocardiography. Ratio of each measure versus mean normal value (i.e., LV-apex-transverse-TL ratio) was considered to express the directional and regional tissue elongation. [LV-base-longitudinal-TL ratio/global-LV-TL ratio] and [MVC-longitudinal-TL ratio/whole-LV-longitudinal-TL ratio] were obtained as the degree of LV-base-longitudinal-TL or MVC-longitudinal-TL elongation relative to the whole LV elongation. LV-apex-transverse-, LV-apex-longitudinal-, and LV-base-transverse-TL ratios were significantly increased (1.27 to 1.42, P < 0.01) in both DCM and AR, while the LV-base-longitudinal-TL ratio was not increased in DCM [1.04 ± 0.19, not significant (ns)] and only modestly increased in AR (1.12 ± 0.21, P < 0.01). Whole-LV-longitudinal-TL ratio was significantly increased in both DCM and AR (1.22 ± 0.18 and 1.20 ± 0.16, P < 0.01), while MVC-longitudinal-TL ratio was not or only modestly increased in both groups (1.07 ± 0.15, ns, and 1.12 ± 0.17, P = 0.02, respectively). Multivariable analysis revealed that LV sphericity was independently related to a reduced [LV-base-longitudinal-TL ratio/global-LV-TL ratio] (standard ß = -0.42, P < 0.01), which was further related to a reduced [MVC-longitudinal-TL ratio/whole-LV-longitudinal-TL ratio] (standard ß = 0.72, P < 0.01). These are consistent with the hypothesis that relatively less MVC-longitudinal-TL elongation in the process of primary LV myocardial tissue elongation may limit LV-base-longitudinal-TL elongation, contributing to LV spherical remodeling.NEW & NOTEWORTHY Left ventricular (LV) spherical remodeling is associated with poor prognosis and less-effective cardiac performance, which commonly develops in dilated cardiomyopathy. However, its mechanism remains unclear. We hypothesized and subsequently clarified that less mitral valve complex (MVC) tissue longitudinal elongation relative to whole LV myocardial tissue longitudinal elongation is related to disproportionately less LV base longitudinal versus transverse myocardial tissue elongation, constituting spherical remodeling. This study suggests modification of MVC tissue elongation could be potential therapeutic targets.

Rate-dependent pacing failure after pacemaker implantation: Novel insights into the mechanism of using adenosine.

An 82-year-old woman received pacemaker implantation for sick sinus syndrome. Two days after the implantation, electrocardiography showed 2:1 atrial pacing failure, followed by a bradycardia-dependent increase in the atrial pacing threshold during a pacemaker examination. However, transient 1:1 atrial pacing capture recovered by adenosine triphosphate (ATP) administration, which was performed to evaluate the bradycardia-dependent pacing failure mechanism. We considered this phenomenon to be caused by Phase 4 depolarization and avoided replacing this atrial lead. Three weeks later, the atrial pacing threshold had improved. We report the potential role of Phase 4 depolarization in a bradycardia-dependent increase in pacing threshold by using ATP.

Changes of echocardiographic parameters in primary mitral regurgitation and determinants of symptom: an assessment from the Asian Valve Registry data.

Clinicians often have a difficulty in determining the presence of mitral regurgitation (MR)-related symptoms because of subjectivity. However, there are few actual measurement data for echocardiographic left ventricular (LV) and left atrial (LA) size related to the severity of MR and the relationship between MR-related symptoms and these echocardiographic parameters. Among patients enrolled in the Asian Valve Registry, we investigated 778 consecutive patients with primary MR showing sinus rhythm. Symptoms were determined by New York Heart Association grade (≤ II or ≥ III). MR severity was mild in 106, moderate in 285, and severe in 387 patients. LA volume index, LV end-diastolic diameter, and LV mass index increased with increasing MR grade [LA volume index: 47.9 (mild), 56.2 (moderate), and 64.9 ml/m2 (severe) (p < 0.001), LV end-diastolic diameter: 51.2, 54.5, 58.1 mm (p < 0.001), and LV mass index: 101, 109, 123 g/m2 (p < 0.001)]. Regarding moderate and severe MR, 70 patients (10.4%) were symptomatic. In multivariable analysis, for being symptomatic in moderate and severe MR patients, LV mass index (odds ratio [OR] per 10 g/m2 increment; 1.09; 95% confidence interval [CI]: 1.005-1.18, p = 0.040), ejection fraction (OR per 1% increment; 0.96, 95%CI: 0.93-0.98, p < 0.001), female gender (OR 2.28; 95% CI: 1.31-3.98, p = 0.004), and heart rate (OR per 1 bpm increment; 1.03; 95%CI: 1.01-1.05, p = 0.007) were independent factors. LV and LA parameters on echocardiography worsened as MR severity progressed. Larger LV mass index and lower ejection fraction were independent determinant factors for MR-related symptoms. We should also pay attention to LV hypertrophy in patients with primary MR.

Relations of Augmented Systolic Annular Expansion and Leaflet/Papillary Muscle Dynamics in Late-Systolic Mitral Valve Prolapse Evaluated by Echocardiography with a Speckle Tracking Analysis.

The mechanism of systolic annular expansion in mitral valve prolapse (MVP) is not clarified. Since annular expansion is systolic outward shift of MV leaflet/chorda tissue complex at superior and outer ends, annular expansion could be related to inward (superior) shift of the complex at another inferior and inner end of the papillary muscle (PM) tip and/or systolic lengthening of the tissue complex, especially MV leaflets.MV annulus systolic expansion, PMs' systolic superior shift, and MV leaflets' systolic lengthening were evaluated by echocardiography with a speckle tracking analysis in 25 normal subjects, 25 subjects with holo-systolic MVP and 20 subjects with late-systolic MVP.PMs' superior shift, MV leaflets' lengthening, MV annular area at the onset of systole and subsequent MV annulus expansion were significantly greater in late-systolic MVP than in holo-systolic MVP (4.6 ± 1.6 versus 1.5 ± 0.7 mm/m2, 2.5 ± 1.4 versus 0.6 ± 2.0 mm/m2, 6.8 ± 2.5 versus 5.7 ± 1.0 cm2/m2 and 1.6 ± 0.8 versus 0.1 ± 0.5 cm2/m2, P < 0.001, respectively). Multivariate analysis identified MV leaflets' lengthening and PMs' superior shift as independent factors associated with MV annular expansion.Conclusions: These results suggest that systolic MV annular expansion in MVP is related to abnormal MV leaflets' lengthening and PMs' superior shift.

[A Case of Change from Normal-flow High-pressure Gradient Severe Aortic Stenosis to Paradoxical Low-flow Low-pressure Gradient Severe Aortic Stenosis].

We report a case of a 77-year-old male who had been diagnosed with normal-flow high-pressure gradient severe aortic stenosis (AS) two years previously. In accordance with his wishes, it was decided not to perform surgery. He visited our hospital with anorexia and weight loss and was diagnosed with gastric cancer. Echocardiography showed a change to paradoxical low-flow low-pressure gradient severe AS (PLFLPG AS). A decrease in stroke volume is typically associated with a smaller LV size, but the reason for a smaller LV size in PLFLPG AS remains unclear. In this case, the change to PLFLPG AS was thought to be due to a decrease in whole body oxygen consumption, and this may help to understand the pathology.

Estimation of B-type Natriuretic Peptide Values from N-Terminal proBNP Levels.

Both brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are established biomarkers that are necessary in the diagnosis and management of heart failure (HF). However, it is difficult to infer BNP concentration from NT-proBNP concentration for a clinician who is familiar with BNP. We investigated whether estimated BNP concentration from NT-proBNP has an equivalent prognostic strength compared with the actual BNP concentration in the prediction of future outcomes. We created a formula for estimating BNP concentration using multivariate analysis in a derivation cohort with known or suspected HF (n = 374). We determined whether the estimated BNP level had a similar prognostic power compared with the actual BNP and NT-proBNP levels in a validation cohort (n = 375). There was a strong correlation between log-transformed BNP and log-transformed NT-proBNP (r = 0.90) in the derivation cohort. We created two types of equation from the derivation cohort. During a median of 1 year of follow up, 49 major adverse cardiac events developed in the validation cohort. Cox proportional analysis revealed that the actual and estimated BNP levels represented equivalent and significant predictors of the future cardiovascular outcome. The estimated BNP levels calculated by our new formula showed a prognostic power similar to the actual BNP levels. This equation will be useful, especially for a physician who is not familiar with NT-proBNP testing.

High-Dose Versus Low-Dose Pitavastatin in Japanese Patients With Stable Coronary Artery Disease (REAL-CAD): A Randomized Superiority Trial.

BACKGROUND: Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous "more versus less statins" trials. However, no clear evidence for more versus less statins has been established in an Asian population. METHODS: In this prospective, multicenter, randomized, open-label, blinded end point study, 13 054 Japanese patients with stable coronary artery disease who achieved low-density lipoprotein cholesterol (LDL-C) <120 mg/dL during a run-in period (pitavastatin 1 mg/d) were randomized in a 1-to-1 fashion to high-dose (pitavastatin 4 mg/d; n=6526) or low-dose (pitavastatin 1 mg/d; n=6528) statin therapy. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. The secondary composite end point was a composite of the primary end point and clinically indicated coronary revascularization excluding target-lesion revascularization at sites of prior percutaneous coronary intervention. RESULTS: The mean age of the study population was 68 years, and 83% were male. The mean LDL-C level before enrollment was 93 mg/dL with 91% of patients taking statins. The baseline LDL-C level after the run-in period on pitavastatin 1 mg/d was 87.7 and 88.1 mg/dL in the high-dose and low-dose groups, respectively. During the entire course of follow-up, LDL-C in the high-dose group was lower by 14.7 mg/dL than in the low-dose group (P<0.001). With a median follow-up of 3.9 years, high-dose as compared with low-dose pitavastatin significantly reduced the risk of the primary end point (266 patients [4.3%] and 334 patients [5.4%]; hazard ratio, 0.81; 95% confidence interval, 0.69-0.95; P=0.01) and the risk of the secondary composite end point (489 patients [7.9%] and 600 patients [9.7%]; hazard ratio, 0.83; 95% confidence interval, 0.73-0.93; P=0.002). High-dose pitavastatin also significantly reduced the risks of several other secondary end points such as all-cause death, myocardial infarction, and clinically indicated coronary revascularization. The results for the primary and the secondary composite end points were consistent across several prespecified subgroups, including the low (<95 mg/dL) baseline LDL-C subgroup. Serious adverse event rates were low in both groups. CONCLUSIONS: High-dose (4 mg/d) compared with low-dose (1 mg/d) pitavastatin therapy significantly reduced cardiovascular events in Japanese patients with stable coronary artery disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01042730.

Insights into the mechanism of paradoxical low-flow, low-pressure gradient severe aortic stenosis: association with reduced O2 consumption by the whole body.

The mechanism of reduced stroke volume index (SVi) in paradoxical low-flow, low-pressure gradient (PLFLPG) aortic stenosis (AS) remains unclarified. Guyton et al. ( 21 ) demonstrated that SVi is determined by whole body O2 consumption (V̇o2) in many subjects, including patients with heart disease. We hypothesized that reduced SVi in PLFLPG AS is associated with reduced V̇o2 by the whole body. This study investigated the relationship between V̇o2, SVi, and AS severity in patients with AS to examine the association between reduced V̇o2 and PLFLPG AS. In 59 patients (24 men and 35 women, mean age: 78 ± 7 yr old) with severe AS, SVi, AS severity, and type were evaluated by echocardiography, and V̇o2 was measured by the fraction of O2 in expired gases. SVi and V̇o2 were significantly decreased in 20 patients with PLFLPG AS compared with 39 patients with non-PLFLPG AS (30 ± 4 vs. 41 ± 7 ml/m2 and 2.4 ± 0.5 vs. 3.0 ± 0.5 ml·min-1·kg-1, respectively, P < 0.01). The SVi-to-V̇o2 ratio was not different between the two groups (13.1 ± 2.6 vs. 13.6 ± 2.1, not significant). SVi was independently correlated with V̇o2 ( r = 0.74, P < 0.01) but not with the aortic valve area index. Categorized PLFLPG AS was also significantly associated with reduced V̇o2 ( P < 0.001). PLFLPG AS is associated with reduced V̇o2 by the whole body, which may offer insights into the mechanism of PLFLPG AS. NEW & NOTEWORTHY Paradoxical low-flow, low-pressure gradient severe aortic stenosis (PLFLPG AS) is an important and problematic subtype, and its central pathophysiology with reduced stroke volume is yet to be clarified. We hypothesized and subsequently clarified that reduced stroke volume in PLFLPG AS is associated with reduced O2 consumption by the whole body. This study suggests important insights into the mechanism of PLFLPG AS and may further promote studies to investigate further mechanisms and novel treatment.

Possible mechanism of late systolic mitral valve prolapse: systolic superior shift of leaflets secondary to annular dilatation that causes papillary muscle traction.

Progressive superior shift of the mitral valve (MV) during systole is associated with abnormal papillary muscle (PM) superior shift in late systolic MV prolapse (MVP). The causal relation of these superior shifts remains unclarified. We hypothesized that the MV superior shift is related to augmented MV superiorly pushing force by systolic left ventricular pressure due to MV annular dilatation, which can be corrected by surgical MV plasty, leading to postoperative disappearance of these superior shifts. In 35 controls, 28 patients with holosystolic MVP, and 28 patients with late systolic MVP, the MV coaptation depth from the MV annulus was measured at early and late systole by two-dimensional echocardiography. The PM tip superior shift was monitored by echocardiographic speckle tracking. MV superiorly pushing force was obtained as MV annular area × (systolic blood pressure - 10). Measurements were repeated after MV plasty in 14 patients with late systolic MVP. Compared with controls and patients with holosystolic MVP, MV and PM superior shifts and MV superiorly pushing force were greater in patients with late systolic MVP [1.3 (0.5) vs. 0.9 (0.6) vs. 3.9 (1.0) mm/m2, 1.3 (0.5) vs. 1.2 (1.0) vs. 3.3 (1.3) mm/m2, and 487 (90) vs. 606 (167) vs. 742 (177) mmHg·cm2·m-2, respectively, means (SD), P < 0.001]. MV superior shift was correlated with PM superior shift ( P < 0.001), which was further related to augmented MV superiorly pushing force ( P < 0.001). MV and PM superior shift disappeared after surgical MV plasty for late systolic MVP. These data suggest that MV annulus dilatation augmenting MV superiorly pushing force may promote secondary superior shift of the MV (equal to late systolic MVP) that causes subvalvular PM traction in patients with late systolic MVP. NEW & NOTEWORTHY Late systolic mitral valve prolapse (MVP) is associated with mitral valve (MV) and papillary muscle (PM) abnormal superior shifts during systole, but the causal relation remains unclarified. MV and PM superior shifts were correlated with augmented MV superiorly pushing force by annular dilatation and disappeared after surgical MV plasty with annulus size and MV superiorly pushing force reduction. This suggests that MV annulus dilatation may promote secondary superior shifts of the MV (late systolic MVP) that cause subvalvular PM traction.

Prevention of serious air embolism during cryoballoon ablation; risk assessment of air intrusion into the sheath by catheter selection and change in intrathoracic pressure: An ex vivo study.

INTRODUCTION: One cause of cerebral infarction during cryoballoon ablation is the entry of air into a sheath due to the use of inappropriate catheters. It is known that the left atrial pressure of patients with obstructive sleep apnea syndrome can be negative. However, the effects of catheter selection and negative pressure changes in the sheath on air intrusion are not yet well understood. The aim of this study was to evaluate how catheter selection and negative pressure changes affect air intrusion and to perform countermeasures for air intrusion. METHODS AND RESULTS: This experiment used siphon principle to create negative pressure in the sheath. Noncryoablation catheters (not designed exclusively for cryoballoon ablation) and cryoballoon catheters were investigated. Catheters were inserted into the sheath and then removed. Thereafter, the amount of air in the sheath was measured. For catheters producing significantly larger amounts of air intrusion, the catheters were inserted via a long sheath in the sheath (sheath-in-sheath technique) and the same procedures were repeated. We found that the amount of air intrusion through most of the noncryoablation catheters was significantly larger than that through cryoablation catheters. An increase in the magnitude of negative pressure in the sheath resulted in a proportional increase in air intrusion, but the sheath-in-sheath technique significantly reduced air intrusion. CONCLUSION: The amount of air intrusion increased when using catheters with complicated tip shapes and thin outer diameters and when the magnitude of negative pressure in the sheath increased. The sheath-in-sheath technique may be an effective countermeasure.

Comparison between minimum lumen cross-sectional area and intraluminal ultrasonic intensity analysis using integrated backscatter intravascular ultrasound for prediction of functionally significant coronary artery stenosis.

Intravascular ultrasound (IVUS)-derived minimum lumen cross-sectional area (MLA) is useful to predict myocardial ischemia using fractional flow reserve (FFR). Recent studies reported an increase in the intraluminal ultrasonic integrated backscatter (IB) value using IVUS across the coronary artery stenosis (CAS) was significantly correlated with FFR. However, these details have not been fully understood. We evaluated the utility of intraluminal IB analysis for predicting myocardial ischemia based on FFR measurements by comparing that with conventional IVUS-derived MLA. A total of 65 patients with 75 intermediate lesions underwent both FFR and IB-IVUS simultaneously were analyzed. We measured IVUS-derived MLA and intraluminal IB value at the coronary ostial site, 5 mm distal site to the CAS, and far distal site, which is the same as the position of the pressure wire sensor. The increase in IB values was calculated as the distal IB value - the ostial IB value (focal ∆IB) and the far distal IB value - the ostial IB value (total ∆IB). MLA did not show a significant correlation with FFR (p = 0.13); however, focal ∆IB and total ∆IB showed significant correlations with FFR (p = 0.008 and p < 0.001, respectively). The receiver operating characteristic curve analysis shows that the best cut-off value of focal ∆IB and total ∆IB was 8 and 14, respectively. Although the diagnostic abilities to predict FFR ≤ 0.75 among IVUS-derived MLA ≤ 3.0 mm2, focal ∆IB ≥ 8, and total ∆IB ≥ 14 were similar, a multivariate analysis showed that total ∆IB was the most useful index (p < 0.001). In conclusion, total ∆IB, which is measured at the same as the position of FFR measurement, might be useful for functional assessment of intermediate CAS.

Relationship between abdominal adiposity and incident chronic kidney disease in young- to middle-aged working men: a retrospective cohort study.

BACKGROUND: Obesity is a risk factor for the development of chronic kidney disease (CKD). However, it remains to be fully examined whether fatness is more useful in predicting incident CKD. We aimed this study to determine the association of body fat, body mass index and waist circumference (WC) with subsequent changes in estimated glomerular filtration rate (eGFR) and incident CKD in young- to middle-aged working men. METHODS: We analyzed data from annual health check-up in male workers aged from 20 to 60 years with basal eGFR of 60-90 mL/min/1.73 m2. Cut-off values of parameters and odds ratio (OR) for the incident CKD were calculated by receiver operator characteristics analysis andχ2 test, respectively. We also tested trends of changes in eGFR according to changes in WC in each age decade. RESULTS: There were 8,015 men participants. During the 5-year follow-up, 11.0% of the participants (N = 878) had developed to incident CKD. When basal WC was greater than 80.0 cm, which was decided by Youden's Index, there was a significantly higher risk of incident CKD [OR 1.57 (95% confident interval 1.35-1.84)]. Changes in WC over 5 years were significantly related to eGFR decline in young men (< 40 years old) with normal blood pressures and normoglycemia. CONCLUSIONS: These findings suggest that WC > 80.0 cm is a risk factor for incident CKD and strongly associated with a decline in eGFR in the young- to middle-aged working healthy men.

Impact of a training program incorporating cardiac magnetic resonance imaging on the accuracy and reproducibility of two-dimensional echocardiographic measurements of left ventricular volumes and ejection fraction.

BACKGROUND: Left ventricular (LV) ejection fraction (LVEF) assessed by two-dimensional echocardiography (2DE) is the most widely used parameter for clinical decision-making, but reproducibility and accuracy problems remain. We evaluated the usefulness of a novel training program based on cardiac magnetic resonance (CMR) imaging to obtain more reliable values of 2DE-derived LVEF and LV volumes. METHODS: Fifty-four sonographers from five hospitals independently measured LV volumes and LVEF using the same 2DE images from 15 patients who underwent CMR and 2DE. After receiving a lecture from an expert on how to properly trace the LV endocardium, each sonographer voluntary performed the measurements using the same datasets, and was invited to perform the same analysis for additional patients. The effect of the training intervention was evaluated using the coefficient of variation (CV) and coverage probability (CP). RESULTS: Before the intervention, the LV volumes were significantly underestimated and the LVEF was significantly overestimated compared to the CMR results; however, these differences were reduced after the intervention. In particular, the CP (0.52 vs. 0.76, p < 0.001) for the LVEF showed significant improvement. However, the degree of improvement differed among institutions, and the CV actually became worse in two hospitals after the intervention. Level of experience and self-practice was associated with the reproducibility after the intervention. CONCLUSIONS: A training program using CMR as a reference improved the accuracy of 2DE-determined LV measurements. Since the degree of improvements differed among hospitals, individualization of training programs and periodical objective evaluation may be required to reduce inter-institutional variability.

Impact of High-Sensitivity Cardiac Troponin Elevation in Relation to Diagnostic Invasive Intravascular Imaging for the Assessment of Coronary Artery Disease.

Recent studies reported that cardiac troponin elevation after percutaneous coronary intervention is related to adverse cardiac events. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are often used to assess lesion characteristics in the coronary arteries. However, little is known about the trend of cardiac troponin elevation after diagnostic invasive intracoronary examination and the prognostic influence. We assessed the relationship between myocardial injury manifested by the high-sensitivity cardiac troponin T (hs-cTnT) level after invasive intracoronary examination and future adverse cardiac outcomes. We evaluated 115 patients with stable coronary artery disease who underwent IVUS or OCT for detailed coronary assessment during coronary angiography (CAG). Baseline and post-procedural (within 24 hours after examination) hs-cTnT were measured. In consequence, post-procedural hs-cTnT level and percentage increase were higher in patients with IVUS or OCT during CAG than in those without. Periprocedural myocardial injury (PMI, defined as post-procedural hs-cTnT with upper reference limit greater than five-fold) occurred in 10 (8.6%) patients. There were no significant differences in baseline characteristics between patients with and without PMI, except for left-ventricular diastolic dimension. Only two major adverse cardiac events (MACE, defined as cardiovascular death, nonfatal myocardial infarction, and target lesion revascularization) occurred in non-PMI during a mean observation period of 32 ± 18 months. On Kaplan-Meier analysis, MACE-free survival rate was similar between PMI and non-PMI. In conclusion, a few imperceptible PMI derived by hs-cTnT assay occurred after diagnostic invasive intracoronary examination. However, it was not associated with subsequent poor cardiac outcome.

Usefulness of Cibenzoline Stress Echocardiography to Determine Severity of Aortic Stenosis in a Patient with Combined Left Ventricular Outflow Tract Obstruction and Aortic Stenosis.

Left ventricular outflow tract obstruction (LVOTO) is sometimes accompanied by aortic stenosis (AS). Reliable estimation of the true severity of AS is often difficult because it cannot be discriminated from dual stenosis. A 75-year-old woman was referred to our hospital due to traumatic hemopneumothorax with exertional dyspnea. Echocardiography revealed AS and LVOTO by chance. A continuous Doppler echocardiography revealed a late-systolic peaking dagger-shaped profile with a 6.0 m/s of peak jet velocity across the LVOT and aortic valve, but it was difficult to discriminate between the coexisting peak flows. For an accurate evaluation of AS, we performed landiolol (short acting beta-blocker) and cibenzoline (Na+ channel-blocking agent) stress echocardiography with simultaneous recordings of both left ventricular and aortic pressure by catheter examination. Cibenzoline successfully eliminated the LVOTO, but landiolol did not. Cibenzoline stress echocardiography enabled us to evaluate the AS severity as less than moderate, resulting in proper decision-making. The findings in this case clearly showed that cibenzoline stress echocardiography has a potential utility for determining AS severity in a patient with coexistent dynamic LVOTO.

Effects of Ezetimibe-Statin Combination Therapy on Coronary Atherosclerosis in Acute Coronary Syndrome.

BACKGROUND: The results of previous clinical trials on the effects of ezetimibe-statin combination therapy on atherosclerosis are inconsistent, and the anti-atherosclerotic effect of ezetimibe remains controversial.Methods and Results:We conducted a prospective, randomized open-label study at 10 centers. One hundred and twenty-eight statin-naïve patients with acute coronary syndrome (ACS) undergoing intravascular ultrasound (IVUS)-guided percutaneous coronary intervention were randomized to receive either 2 mg/day pitavastatin plus 10 mg/day ezetimibe, or 2 mg/day pitavastatin. One hundred and 3 patients had evaluable IVUS of non-culprit coronary lesions at baseline and at follow-up. The primary endpoint was the percentage change in non-culprit coronary plaque volume (PV) and lipid PV on integrated backscatter IVUS. Mean low-density lipoprotein cholesterol was reduced from 123 mg/dL to 64 mg/dL in the combination therapy group (n=50) and 126 mg/dL to 87 mg/dL in the statin alone group (n=53; between-group difference, 16.9%, P<0.0001). The percent change in PV was -5.1% in the combination therapy group and -6.2% in the statin alone group (P=0.66), although both groups had reduction of PV compared with baseline (both P<0.01). The percent change in lipid PV did not differ between the groups (4.3 vs. -3.0%, P=0.37). CONCLUSIONS: In statin-naïve patients with ACS, combined therapy with ezetimibe and statin did not result in a significant change in coronary plaque regression or tissue component compared with statin alone. [Clinical Trial Registration: www.clinicaltrials.gov (NCT00549926)].

Surgical as Opposed to Transcatheter Aortic Valve Replacement Improves Basal Interventricular Septal Hypertrophy.

BACKGROUND: Basal interventricular septum (IVS) hypertrophy (BSH) with reduced basal IVS contraction and IVS-aorta angle is frequently associated with aortic stenosis (AS). BSH shape suggests compression by the longitudinally elongated ascending aorta, causing basal IVS thickening and contractile dysfunction, further suggesting the possibility of aortic wall shortening to improve the BSH. Surgical aortic valve replacement (SAVR), as opposed to transcatheter AVR (TAVR), includes aortic wall shortening by incision and stitching on the wall and may potentially improve BSH. We hypothesized that BSH configuration and its contraction improves after SAVR in patients with AS. Methods and Results: In 32 patients with SAVR and 36 with TAVR for AS, regional wall thickness and systolic contraction (longitudinal strain) of 18 left ventricular (LV) segments, and IVS-aorta angle were measured on echocardiography. After SAVR, basal IVS/average LV wall thickness ratio, basal IVS strain, and IVS-aorta angle significantly improved (1.11±0.24 to 1.06±0.17; -6.2±5.7 to -9.1±5.2%; 115±22 to 123±14°, P<0.001, respectively). Contractile improvement in basal IVS was correlated with pre-SAVR BSH (basal IVS/average LV wall thickness ratio or IVS-aorta angle: r=0.47 and 0.49, P<0.01, respectively). In contrast, BSH indices did not improve after TAVR. CONCLUSIONS: In patients with AS, SAVR as opposed to TAVR improves associated BSH and its functional impairment.