Early Detection and Prediction of Anthracycline-Induced Cardiotoxicity　- A Prospective Cohort Study.

BACKGROUND: In the present study, we aimed to investigate whether early cardiac biomarker alterations and echocardiographic parameters, including left atrial (LA) strain, can predict anthracycline-induced cardiotoxicity (AIC) and thus develop a predictive risk score.Methods and Results: The AIC registry is a prospective, observational cohort study designed to gather serial echocardiographic and biomarker data before and after anthracycline chemotherapy. Cardiotoxicity was defined as a reduction in left ventricular ejection fraction (LVEF) ≥10 percentage points from baseline and <55%. In total, 383 patients (93% women; median age, 57 [46-66] years) completed the 2-year follow-up; 42 (11.0%) patients developed cardiotoxicity (median time to onset, 292 [175-440] days). Increases in cardiac troponin T (TnT) and B-type natriuretic peptide (BNP) and relative reductions in the left ventricular global longitudinal strain (LV GLS) and LA reservoir strain [LASr] at 3 months after anthracycline administration were independently associated with subsequent cardiotoxicity. A risk score containing 2 clinical variables (smoking and prior cardiovascular disease), 2 cardiac biomarkers at 3 months (TnT ≥0.019 ng/mL and BNP ≥31.1 pg/mL), 2 echocardiographic variables at 3 months (relative declines in LV GLS [≥6.5%], and LASr [≥7.5%]) was generated. CONCLUSIONS: Early decline in LASr was independently associated with subsequent cardiotoxicity. The AIC risk score may provide useful prognostication in patients receiving anthracyclines.

Association between intrarenal venous flow from Doppler ultrasonography and acute kidney injury in patients with sepsis in critical care: a prospective, exploratory observational study.

BACKGROUND: Intrarenal venous flow (IRVF) patterns assessed using Doppler renal ultrasonography are real-time bedside visualizations of renal vein hemodynamics. Although this technique has the potential to detect renal congestion during sepsis resuscitation, there have been few studies on this method. We aimed to examine the relationship between IRVF patterns, clinical parameters, and outcomes in critically ill adult patients with sepsis. We hypothesized that discontinuous IRVF was associated with elevated central venous pressure (CVP) and subsequent acute kidney injury (AKI) or death. METHODS: We conducted a prospective observational study in two tertiary-care hospitals, enrolling adult patients with sepsis who stayed in the intensive care unit for at least 24 h, had central venous catheters placed, and received invasive mechanical ventilation. Renal ultrasonography was performed at a single time point at the bedside after sepsis resuscitation, and IRVF patterns (discontinuous vs. continuous) were confirmed by a blinded assessor. The primary outcome was CVP obtained at the time of renal ultrasonography. We also repeatedly assessed a composite of Kidney Disease Improving Global Outcomes of Stage 3 AKI or death over the course of a week as a secondary outcome. The association of IRVF patterns with CVP was examined using Student's t-test (primary analysis) and that with composite outcomes was assessed using a generalized estimating equation analysis, to account for intra-individual correlations. A sample size of 32 was set in order to detect a 5-mmHg difference in CVP between IRVF patterns. RESULTS: Of the 38 patients who met the eligibility criteria, 22 (57.9%) showed discontinuous IRVF patterns that suggested blunted renal venous flow. IRVF patterns were not associated with CVP (discontinuous flow group: mean 9.24 cm H2O [standard deviation: 3.19], continuous flow group: 10.65 cm H2O [standard deviation: 2.53], p = 0.154). By contrast, the composite outcome incidence was significantly higher in the discontinuous IRVF pattern group (odds ratio: 9.67; 95% confidence interval: 2.13-44.03, p = 0.003). CONCLUSIONS: IRVF patterns were not associated with CVP but were associated with subsequent AKI in critically ill adult patients with sepsis. IRVF may be useful for capturing renal congestion at the bedside that is related to clinical patient outcomes.

Using computed tomography fusion imaging as learning data for sonographer training in identification of left ventricular endocardial boundaries.

BACKGROUND: We hypothesized that if computed tomography (CT) images were used as learning data, we could overcome volume underestimation by echocardiography, improving the accuracy of left ventricular (LV) volume measurements. METHODS: We utilized a fusion imaging modality consisting of echocardiography with superimposed CT images for 37 consecutive patients to identify the endocardial boundary. We compared LV volumes obtained with and without CT learning trace-lines (TLs). Furthermore, 3D echocardiography was used to compare LV volumes obtained with and without CT learning for endocardial identification. The mean difference between the echocardiography and CT-derived LV volumes and the coefficient of variation were compared pre- and post-learning. Bland-Altman analysis was used to assess the differences in LV volume (mL) obtained from the 2D pre-learning TL and 3D post-learning TL. RESULTS: The post-learning TL was located closer to the epicardium than the pre-learning TL. This trend was particularly pronounced in the lateral and the anterior wall. The post-learning TL was along the inner side of the high echoic layer in the basal-lateral wall in the four-chamber view. CT fusion imaging determined that the difference in LV volume between 2D echocardiography and CT was small (-25.6 ±â€¯14.4 mL before learning, -6.9 ±â€¯11.5 mL after learning) and that CT learning improved the coefficient of variation (10.9 % before learning, 7.8 % after learning). Significant improvements were observed during 3D echocardiography; the difference in LV volume between 3D echocardiography and CT was slight (-20.5 ±â€¯15.1 mL before learning, 3.8 ±â€¯15.7 mL after learning), and the coefficient of variation improved (11.5 % before learning, 9.3 % after learning). CONCLUSIONS: Differences between the LV volumes obtained using CT and echocardiography either disappeared or were reduced after CT fusion imaging. Fusion imaging is useful in training regimens for accurate LV volume quantification using echocardiography and may contribute to quality control.

Association between right ventricular longitudinal strain and cardiovascular events in patients with cardiac sarcoidosis.

BACKGROUND: While right ventricular (RV) involvement is commonly observed in patients with cardiac sarcoidosis (CS), the utility of strain imaging to detect RV involvement is unclear. We aimed to investigate the association between RV free wall longitudinal strain (RVFWLS) and cardiovascular events in patients with CS. METHODS: We studied 51 patients with CS who were diagnosed between 2012 and 2020. All patients underwent comprehensive echocardiographic evaluation, and RVFWLS was assessed using 2-dimensional speckle tracking echocardiography. The primary outcome was major adverse cardiovascular events (MACEs). RESULTS: During a median follow-up duration of 548 days, 11 patients exhibited MACEs. In the univariable Cox proportional hazards model, the baseline RVFWLS was associated with MACEs (hazard ratio: 1.29, p = 0.008). The addition of RVFWLS to the conventional echocardiographic parameters exhibited a significant incremental value associated with MACEs. Patients with reduced RVFWLS showed a higher prevalence of late gadolinium enhancement on cardiac magnetic resonance imaging in RV wall (p = 0.02) and trends toward higher prevalence of fluorodeoxyglucose uptake in RV (p = 0.06). A serial echocardiographic evaluation revealed that patients with events showed a worsening in RVFWLS, while others showed a trend toward improvement. CONCLUSIONS: Impaired RVFWLS at baseline was associated with MACEs in patients with CS. RVFWLS could be an important surrogate of disease activity and prognosis by detecting active RV involvement in CS.

Echocardiography image quality of global longitudinal strain in cardio-oncology: a prospective real-world investigation.

BACKGROUND: Left-ventricular (LV) global longitudinal strain (GLS) has been reported to be a robust and sensitive marker of chemotherapy-induced cardiac damage. Image quality is paramount for accurate GLS measurements. In real-world cardio-oncology settings, the incidence of suboptimal echocardiography quality and its significance in clinical decision-making have not been well investigated. This prospective study examined the incidence and impact of suboptimal echocardiographic image quality on detecting subtle myocardial damage by chemotherapy. METHODS: Seventy-seven consecutive patients with breast cancer (age, 52 ± 12 years, 76 women, 33 with left-sided breast cancer) were included in this study. Echocardiography was performed at 3-month intervals 1 year before and after chemotherapy initiation. We classified the image quality of each echocardiographic acquisition into three groups: optimal, suboptimal, or inadequate for speckle tracking. RESULTS: Among the 376 examinations obtained during the cardiac monitoring, the image quality in 194 (52%) was optimal, suboptimal in 159 (42%), and inadequate in 23 (6%). The interobserver reproducibility was 0.91 in the optimal and 0.21 in the suboptimal group. In contrast, the optimal group showed progressive impairment in both GLS (p = 0.001) and LV ejection fraction (LVEF) (p < 0.001) during follow-up, and the suboptimal group showed a progressive decrease in LVEF (p = 0.006), but not in GLS (p = 0.13). Left-sided mammotomy and/or reconstruction surgery and high body mass index were significant determinants of suboptimal image quality. CONCLUSIONS: Even in cases of minor image quality impairment, the physician should assess GLS carefully to avoid errors in crucial clinical decision-making.

BDK knockout skeletal muscle satellite cells exhibit enhanced protein translation initiation signal in response to BCAA in vitro.

We examined the effects of branched-chain amino acids (BCAAs) and electrical pulse stimulation (EPS) on the mTORC1 pathway in muscle satellite cells (MSCs) isolated from branched-chain α-keto acid dehydrogenase kinase (BDK) knockout (KO) mice in vitro. MSCs were isolated from BDK KO and wild-type (WT) mice, proliferated, and differentiated into myotubes. BCAA stimulation increased the phosphorylation of p70 S6 kinase (p70S6K), a marker of protein translation initiation, in MSCs from WT and BDK KO mice, but the rate of the increase was higher in MSCs isolated from BDK KO mice. Contrarily, there was no difference in the increase in p70S6K phosphorylation by EPS. Acute BDK knockdown in MSCs from WT mice using shRNA decreased p70S6K phosphorylation in response to BCAA stimulation. Collectively, the susceptibility of mTORC1 to BCAA stimulation was elevated by chronic, but not acute, enhancement of BCAA catabolism.

Rationale, Design, and Feasibility of a Prospective Multicenter Registry Study of Anthracycline-Induced Cardiotoxicity (AIC Registry).

As the number of cancer survivors increases, cardiac management in anthracycline-treated patients has become more important. We planned to conduct a prospective multicenter registry study for comprehensive echocardiographic and biomarker data collection and an evaluation of the current practice in terms of diagnosis and management of anthracycline-induced cardiotoxicity (AIC registry). To examine the feasibility of this registry study, we analyzed the 1-year follow-up data of 97 patients registered during the first year of this registry. The AIC registry was launched in July 2016. Data on echocardiographic parameters (e.g., two-and three-dimensional [(2- and 3-D) left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS)) and biomarkers (e.g., troponin T and brain natriuretic peptide) were collected before anthracycline treatment, every 3 months during the first year after starting anthracycline, and every 6 months during the second year. Eighty-three patients (86%) completed a 1-year follow-up. The measurable rates of 2D LVEF, 3D LVEF, and GLS on each visit were nearly optimal (100%, 86-93%, and 84-94%, respectively). During the 1-year follow-up, 5 patients (6.0%) developed cardiotoxicity (a reduction in LVEF ≥ 10 percentage points from baseline and <55%). The AIC registry study is feasible and will be the first study to collect sizable echocardiographic and biomarker data on cardiotoxicity in Japanese patients treated with anthracycline in a real-world setting.

Prognostic Impact of Changes in Intrarenal Venous Flow Pattern in Patients With Heart Failure.

BACKGROUND: It remains unclear whether intrarenal venous flow (IRVF) patterns in patients with heart failure (HF) could change over the clinical course, and whether the changes could have a clinical impact. Thus, this study aimed to clarify these characteristics as well as to identify the relation between changes in the IRVF pattern and renal impairment progression. METHODS AND RESULTS: Patients with HF with repetitive IRVF evaluations were enrolled. Doppler waveforms of IRVF were classified into the following 3 flow patterns: continuous, biphasic discontinuous, and monophasic discontinuous. Primary end points included death from cardiovascular diseases and unplanned hospitalization for HF. Finally, 108 patients with adequate images were enrolled. The IRVF in 35 patients (32.4%) shifted to another pattern at the follow-up examinations. The median brain natriuretic peptide level in the continuous flow pattern at follow-up was significantly decreased (183 to 60 pg/mL, P < .001), whereas that of the discontinuous flow pattern at follow-up was increased (from 339 to 366 pg/mL, P = .042) and the estimated glomerular filtration rate was decreased (from 55 to 50 mL/min/1.73 m2, P = .013). A multivariable Cox proportional hazard model analysis revealed that the discontinuous pattern at follow-up (P < .001) and brain natriuretic peptide (P = .021) were significantly associated with the end points, independent of age, estimated glomerular filtration rate, and serum sodium level. CONCLUSIONS: The IRVF pattern could be changed depending on the status of congestion. Persistent or worsened renal congestion, represented by discontinuous flow patterns, during the clinical courses indicated a poor prognosis accompanied by renal impairment in patients with HF.

Features of Lead-Induced Tricuspid Regurgitation in Patients With Heart Failure Events After Cardiac Implantation of Electronic Devices　- A Three-Dimensional Echocardiographic Study.

BACKGROUND: Lead-induced tricuspid regurgitation (TR) after cardiac implantable electronic device (CIED) implantation is not fully understood. This study aimed to reveal the features of lead-induced TR by 3-dimensional echocardiography (3DE) in patients with heart failure (HF) events after CIED implantation.Methods and Results:In 143 patients, 3DE assessments for the tricuspid valve (TV) and right ventricular morphologies were sequentially performed within 3 days after CIED implantations, during TR exacerbations, and at ≥6 months after TR exacerbations. TR exacerbations were observed in 29 patients (median 10 months after CIED implantation, range 1-28 months), 15 of whom had lead-induced TR. In the 29 patients, the tenting height of the TV, tricuspid annular (TA) height, and TA area at baseline were independent predictors for worsening TR. In patients with lead-induced TR, tenting height of the TV and TA area were identified as the risk factors. In addition, all patients with a lead positioned on a leaflet immediately after CIED implantations developed lead-induced TR. At follow up, TR exacerbation of lead-induced TR persisted with TA remodeling, but it was improved in the lead non-related-TR group. CONCLUSIONS: TA remodeling at baseline and a lead location on a leaflet immediately after CIED implantation were associated with lead-induced TR in patients with HF events after CIED implantation. Persistent TA remodeling may make lead-induced TR refractory against HF treatments.

Autophagy under glucose starvation enhances protein translation initiation in response to re-addition of glucose in C2C12 myotubes.

Proteolysis is known to play a crucial role in maintaining skeletal muscle mass and function. Autophagy is a conserved intracellular process for the bulk degradation of proteins in lysosomes. Although nutrient starvation is known to induce autophagy, the effect of nutrient repletion following starvation on the mTOR pathway-mediated protein translation remains unclear. In the present study, we examined the effect of glucose starvation on the initiation of protein translation in response to glucose re-addition in C2C12 myotubes. Glucose starvation decreased the phosphorylation of p70 S6 kinase (p70S6K), a bonafide marker for protein translation initiation. Following re-addition of glucose, phosphorylation of p70S6K markedly increased only in glucose-starved cells. Inhibiting autophagy using pharmacological inhibitors diminished the effect of glucose re-addition on the phosphorylation of p70S6K, whereas inhibition of the ubiquitin-proteasome system did not exert any effect. In conclusion, autophagy under glucose starvation partially accounts for the activation of translation initiation by re-addition of glucose.

Cardiology consultation in oncology practice: a 5-year survey.

OBJECTIVE: Onco-cardiology services are expanding rapidly in Japan. To provide a better service, it is important to consider the needs of oncologists. However, little is known regarding specific needs for which oncologists should consult cardiologists to manage cardiovascular problems of their patients. We analysed cardiology consultations sought by oncologists to evaluate the role of cardiologists in cancer treatment. METHOD: We retrospectively investigated consecutive 2064 cardiology consultations of cancer patients in the University of Tsukuba Hospital, Tsukuba, Japan, between January 2014 and December 2018. RESULTS: The most common timing of cardiology consultation was before the commencement of cancer treatment (n = 1355; 65.7%), followed by after the commencement of cancer treatment (n = 686; 33.2%). Among the 361 consultations before the administration of anticancer drugs, 235 (65.1%) were for anthracycline-based regimens. There were 506 (24.5%) consultations for the management of cardiovascular emergencies developing after the commencement of cancer treatment; venous thromboembolism was the most frequent (n = 125; 24.7%), followed by atrial fibrillation (n = 110; 21.7%) and heart failure (n = 74; 14.6%). There were marked differences in the types of cardiovascular emergencies depending on the type of cancer. CONCLUSIONS: This survey revealed the various cardiovascular problems for which oncologists sought interventions by cardiologists. A multidisciplinary approach in an onco-cardiology service is essential to achieve optimal long-term outcomes.

Doppler-Derived Intrarenal Venous Flow Mirrors Right-Sided Heart Hemodynamics in Patients With Cardiovascular Disease.

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.

Comparison of Outcomes in Patients With Heart Failure With Versus Without Lead-Induced Tricuspid Regurgitation After Cardiac Implantable Electronic Devices Implantations.

Cardiac implantable electronic devices (CIED) implantations may cause lead-induced tricuspid regurgitation (LITR). Although patients with CIED have the risk of functional non-lead induced TR (Non-LITR). This study aimed to compare of clinical outcome between LITR and Non-LITR. The mechanism of TR was determined by 3-dimensional echocardiography. The primary end point was heart failure (HF) hospitalizations after CIED implantation. In patients with HF events, subsequent clinical outcomes after HF hospitalization were compared between no TR, LITR, and Non-LITR groups. In eligible 373 patients, 67 patients had HF hospitalization, of whom worsened TR was observed in 49 patients. In the remaining 307 patients, worsened TR was observed in only 10 patients (3.3%). Of the 49 patients with worsened TR, 18 patients (37%) had LITR. In 67 patients with HF hospitalization, 25 patients (37%) met rehospitalization. All severe LITR persisted after HF events. Meanwhile, severe Non-LITR improved to moderate or mild level. Cox proportional hazard model analyses revealed LITR was the independent risk factor of rehospitalization. Both LITR and Non-LITR were common at HF events after CIED implantations. However, LITR persisted and might contribute to a worse prognosis. In patients with TR after CIED implantations, 3-dimensional echocardiography should be performed to diagnose the LITR accurately, which may contribute to improving the clinical outcome.

Induction of Autophagy and Changes in Cellular Metabolism in Glucose Starved C2C12 Myotubes.

Mouse myoblast C2C12 cells are commonly used as a model system for investigating the metabolic regulation of skeletal muscle. As it is therefore important to understand the metabolic features of C2C12 cells, we examined the effect of glucose starvation on autophagy in C2C12 myotubes. After culture of C2C12 myotubes with high (HG, 25.0 mM) or low (LG, 5.6 mM) glucose concentrations, the concentration of glucose in the LG group had decreased to 0 mM after 24 h of culture and was around 17 mM after 48 h of culture in the HG group. The concentration of lactate increased from 0 to approximately 9 mM at 24 h and then dropped slightly in the LG group, while it increased linearly to 21 mM in the HG group at 48 h. The phosphorylation of p70 S6 kinase, marker for the protein translation initiation was significantly lower and the ratio of LC3-II/LC3-I, marker for the induction of autophagy was significantly higher in the LG group. GLUT1 and hexokinase II expression were significantly higher in the LG group. Together, these changes in glucose and lactate concentrations in the culture media suggest that C2C12 myotubes depend on anaerobic glycolysis. Our findings also suggest that glucose depletion stimulates the expression of key molecules involved in glycolysis and that cellular autophagy is also activated in C2C12 myotubes.

Embolization of the Deep Vein Thrombus During Ultrasound Examination.

Thrombus embolization is a rare consequence of ultrasonographic examination of the vessels of the lower limbs. We present a case of a 77-year-old woman with lung cancer who developed pulmonary embolism originating from the right femoral deep vein thrombus during the compression maneuver of the ultrasonographic examination of the lower limbs. (Level of Difficulty: Beginner.).

Low-carbohydrate high-protein diet diminishes the insulin response to glucose load via suppression of SGLT-1 in mice.

The purpose of this study was to examine the effects of a low-carbohydrate high-protein (LCHP) diet on the expression of glucose transporters and their relationships to glucose metabolism. Male C57BL/6 mice were fed a normal control or LCHP diet for 2 weeks. An oral glucose tolerance test and insulin tolerance test (ITT) were performed, and the expression of glucose transporters was determined in the gastrocnemius muscle, jejunum and pancreas. The increase in plasma insulin concentrations after glucose administration was reduced in the LCHP group. However, LCHP diet had no effects on peripheral insulin sensitivity or glucose transporters expression in the gastrocnemius and pancreas. Soluble glucose transporter (SGLT)-1 protein content in jejunum was lower in the LCHP group. Taken together, these results suggest that the blunted insulin response after glucose administration in LCHP diet-fed mice might be due to decreased SGLT-1 expression, but not to an increase in peripheral insulin sensitivity. Abbreviations: LCHP: low-carbohydrate high-protein; ITT: insulin tolerance test; GLUT: glucose transporter; SGLT: soluble glucose transporter; OGTT: oral glucose tolerance test; AUC: area under the curve.

Endothelial Dysfunction of Conduit Arteries in Patients with Repaired Coarctation of the Aorta.

Adult patients with repaired coarctation of the aorta (r-CoA) show high prevalence of late hypertension, but the exact mechanisms of this phenomenon are unknown. Endothelial dysfunction has been implicated in this paradoxical hypertension. We evaluated the endothelial function of both conduit and resistance arteries by using flow-mediated dilation (FMD) and digital peripheral artery tonometry (PAT).Seventeen patients with r-CoA and one patient with repaired interrupted aortic arch (r-CoA group) aged 22.0 ± 6.9 years (5 females) underwent FMD of the right brachial artery, PAT of the right finger, blood marker tests, ambulatory blood pressure monitoring, echocardiography, carotid ultrasonography, and brachio-ankle pulse wave velocity measurement. The median age at aortic arch reconstruction was 2.0 months (interquartile range: 15 days to 7.0 years). Results were compared with 17 age-matched healthy subjects (control group).Eight (44%) patients of the r-CoA group were hypertensive (5 received antihypertensive drugs). Patients in the r-CoA group showed significantly lower FMD (3.8 ± 1.5 versus 6.6 ± 2.5%, P < 0.001), larger intima-media thickness (0.63 ± 0.17 versus 0.47 ± 0.09 mm, P = 0.001), and higher left ventricular mass index (91.4 ± 24.6 versus 73.4 ± 17.3 g/m2, P = 0.017) than those in the control group. There were no significant differences in PAT (refractory hyperemia index, 1.86 ± 0.43 versus 1.99 ± 0.59, P = 0.48) and brachio-ankle pulse wave velocity between the two groups.Vascular dysfunction in r-CoA patients, particularly endothelial dysfunction, tends to occur more significantly in conduit arteries than in resistance arteries.

Clinical implications of organ congestion in heart failure patients as assessed by ultrasonography.

In the management of heart failure (HF), decongestion is critical for improving clinical outcomes in addition to patients' symptoms. Although physicians accept this theory, there are no established markers for the achievement of optimal decongestion status. Organ congestion, in particular liver and kidney congestion, has recently attracted substantial attention. Ultrasound methods have been introduced for assessing organ congestion, although this is merely a preliminary step. Here, we review the clinical implications of the assessment of organ congestion by ultrasound.

Estimation of Central Venous Pressure Using the Ratio of Short to Long Diameter from Cross-Sectional Images of the Inferior Vena Cava.

BACKGROUND: Long-axis images of the inferior vena cava (IVC) have limitations as surrogates for IVC morphology in grading central venous pressure (CVP) by two-dimensional echocardiography (2DE), because of the various cross-sectional morphologies and the translational motion of the IVC induced by sniffing. On the basis of the relationship between venous pressure and compliance, it was hypothesized that the cross-sectional morphology of the IVC, which was obtained using three-dimensional echocardiography, might estimate CVP more accurately compared with standard grading by 2DE. METHODS: Sixty consecutive patients who underwent right-heart catheterization studies were prospectively enrolled. Echocardiography was performed <24 hours before catheterization. From three-dimensional data sets, a cross-section of the IVC was determined that was perpendicular to the long-axis reference of the IVC. Short diameter (SD), long diameter (LD), the ratio of SD to LD (S/L) as the sphericity index, and area were measured on this cross-sectional IVC image. RESULTS: CVP correlated moderately with SD (r = 0.69, P < .001), strongly with S/L (r = 0.75, P < .001), and modestly with area (r = 0.47, P < .001) but not with LD (r = 0.24, P = .17). The largest areas under the curve by receiver operating characteristic analyses to detect CVP ≥ 10 mm Hg were 0.98 (95% CI, 0.97-1.0; P < .001) for S/L, 0.83 for SD (95% CI, 0.74-0.94; P < .001), and 0.70 for area (95% CI, 0.56-0.84; P = .02). If a cutoff value of 0.69 for S/L was used, the sensitivity, specificity, and accuracy to detect CVP ≥ 10 mm Hg were 0.94, 0.95, and 0.95 and for CVP grading by 2DE were 0.59, 0.98, and 0.85, respectively. Estimations of CVP were more accurately reclassified using S/L rather than grading by 2DE (net reclassification improvement, 0.38; 95% CI, 0.31-0.44; P < .001). CONCLUSIONS: S/L of an IVC cross-section measured using three-dimensional echocardiography may be a reliable parameter to estimate CVP compared with standard grading by 2DE.

Clinical Implications of Intrarenal Hemodynamic Evaluation by Doppler Ultrasonography in Heart Failure.

OBJECTIVES: This study clarified the characteristics of intrarenal Doppler ultrasonography (IRD) profiles and their prognostic implications in heart failure (HF). BACKGROUND: IRD can assess intrarenal hemodynamics. METHODS: Initially, 224 patients with HF were prospectively enrolled; 151 inpatients were enrolled during hospitalization for HF, and 73 were outpatients in our institution. In IRD profiles of interlobar vessels, the arterial resistance index (RI), venous impedance index (VII), and intrarenal venous flow (IRVF) pattern were assessed. Patients were followed to evaluate the associations with 1-year prognosis. Primary endpoints included death from cardiovascular disease and unplanned hospitalization for HF. RESULTS: Finally, 217 patients with adequate IRD images were enrolled. IRD profiles were associated with conventional risk factors for HF. In particular, IRVF was associated with mean right atrial pressure (RAP); 3 IRVF patterns were stratified by RAP (in a continuous pattern: 5.4 ± 2.5; in a biphasic pattern: 9.5 ± 3.5; and in a monophasic pattern: 14.9 ± 4.3 mm Hg; p < 0.001). In addition, the monophasic IRVF pattern had a poorer prognosis than the other patterns (log rank p < 0.001), and prognosis was poorer for the biphasic pattern than for the continuous flow pattern (log rank p = 0.01). Multivariate Cox proportional hazard model analysis revealed that IRVF patterns were associated with the endpoints, independent of other HF risk factors. CONCLUSIONS: IRVF patterns, rather than RI, depended on RAP, suggesting a correlation with renal congestion. In addition, IRVF patterns strongly correlated with clinical outcomes independent of RAP and other risk factors and might provide additional information to stratify vulnerable HF patients.