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Abstract 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. Graphical abstract

Medical checkups play a role in the identification of individuals at increased cardiovascular risk. However, the impact of each medical examination parameter on the incidence of major adverse cardiovascular events (MACE) has not been intensively studied. Here we assessed the predictors of MACE among parameters examined during medical checkups in the general Japanese population. A total of 13,522 individuals (mean age, 52.8 ± 12.3 years) who participated in our medical checkup program from 2008 to 2015 were followed up for a median of 1,827 days with the endpoint of MACE. MACE included cardiovascular death, non-fatal myocardial infarction, angina, decompensated heart failure, stroke, and other cardiovascular events requiring hospitalization. Possible associations between MACE and baseline clinical test parameters were investigated. During follow-up, MACE occurred in 196 participants. Participants with hypertension, diabetes mellitus, dyslipidemia, or metabolic syndrome were at increased risk of MACE on the univariate analysis. Multivariate Cox hazard analysis demonstrated that male sex, age, systolic blood pressure, and baseline B-type natriuretic peptide level were independently correlated with future MACE after the adjustment for confounders; the impact of B-type natriuretic peptide was most prominent among the investigated variables. These results suggest that B-type natriuretic peptide level obtained during a medical checkup examination is an independent and strong predictor of MACE. The inclusion of BNP as part of medical checkup parameters may improve the ability to identify individuals at increased cardiovascular risk and prevent cardiovascular disease among them.

Background The management of mixed aortic valve disease (MAVD), defined as the concomitant presence of aortic stenosis (AS) and aortic regurgitation, remains a clinical challenging. The present study assessed the impact of transcatheter aortic valve replacement (TAVR) on cardiac geometry and prognosis in patients with MAVD. Methods and Results A retrospective multicenter TAVR registry was conducted, including patients who underwent TAVR for severe symptomatic AS between January 2015 and March 2019. Patients were subdivided into 2 groups according to concomitant presence of moderate or more severe aortic regurgitation as the MAVD group, and with mild or less severe aortic regurgitation as the isolated AS group. The primary outcome was a composite of cardiovascular death and rehospitalization due to cardiovascular causes. A total of 1742 patients (isolated AS, 1522 patients; MAVD, 220 patients) were included (84.0±5.2 years). Although MAVD exhibited significantly larger left ventricular volumes and higher left ventricular mass index at the TAVR procedure than isolated AS (respectively, P

Aortic and valvular calcification are well-known risk factors for cardio-cerebrovascular events in patients undergoing hemodialysis. We investigated the clinical impact of an angulated aorto-septal angle as a result of aortic elongation due to aortic calcification on cardio-cerebrovascular outcomes in patients undergoing hemodialysis. We investigated 306 patients (mean age 65.4 years, 68% male) who underwent pre-scheduled routine echocardiography between April and September 2018. The angle between the anterior wall of the aorta and the ventricular septal surface (ASA) was quantified. We determined aortic and mitral valve calcification scores based on calcified cardiac changes; the aortic and mitral valve scores ranged between 0-9 and 0-6, respectively. The primary endpoint was a composite including cardio-cerebrovascular events and cardio-cerebrovascular death. The mean duration of dialysis among the patients in this analysis was 9.6 years. The primary endpoint was observed in 54 patients during the observational period (median 1095 days). Multivariable Cox proportional hazards analyses identified left ventricular ejection fraction (per 10% increase: hazard ratio [HR] 0.67; 95% confidential interval [CI] 0.53-0.84, P = 0.001), left ventricular mass index (per 10 g/m2 increase: HR 1.14; 95% CI 1.05-1.24, P = 0.001), ASA (per 10 degree increase: HR 0.69; 95% CI 0.54-0.88; P = 0.003), and aortic valve calcification score (HR 1.15; 95% CI 1.04-1.26, P = 0.005) as independent determinants of the primary endpoint. Kaplan-Meier analysis showed a higher incidence of the primary endpoint in patients with ASA

Abstract Increasing blood pressure variability (BPV) has been reported to be a strong predictor of cardiovascular events in patients with hypertension. However, the effects of BPV in the general population have not been intensively studied. The present study was designed to investigate a possible relationship between year‐to‐year BPV and hypertensive target organ damage (TOD) in a relatively low‐risk general population. A total of 5489 consecutive patients (mean age 58.6 ± 10.7 years) who visited our hospital for an annual physical checkup for five consecutive years during 2008–2013 were enrolled in this study. The average systolic and diastolic blood pressures and pulse pressure were calculated, as well as standard deviation, coefficient of variation, and average real variability in blood pressures. Cross‐sectional analysis was conducted and subjects without TOD at baseline (n = 3115) were followed up (median 1827 days) with the endpoint of TOD, defined as left ventricular hypertrophy on electrocardiogram or declining glomerular filtration rate. At baseline, BPV was closely associated with TOD. During follow‐up, left ventricular hypertrophy and declining glomerular filtration rate developed in 189 and 400 subjects, respectively. Although the standard deviation for systolic blood pressure and pulse pressure predicted future development of TOD in a univariate analysis, BPV was not a significant determinant of incident TOD in adjusted Cox hazard models. These results suggest that year‐to‐year BPV is a marker of the presence of TOD in the general population but does not independently predict future TOD.

Background Prognostic implications of transcatheter aortic valve implantation (TAVI) in low‐gradient (LG) aortic stenosis (AS) remain controversial. The authors hypothesized that differences in cardiac functional recovery may solve this ongoing controversy. The aim was to evaluate clinical outcomes and the response of left ventricular (LV) function following TAVI in patients with LG AS. Methods and Results This multicenter retrospective study included 1742 patients with severe AS undergoing TAVI between January 2015 and March 2019. Patients were subdivided into low‐flow (LF) LG, normal‐flow (NF) LG, LF high‐gradient, and NF high‐gradient AS groups according to the mean gradient of the aortic valve (LG

Heart failure (HF) with preserved left ventricular ejection fraction (LVEF) is a heterogeneous syndrome. An LVEF of 50% is widely used to categorize patients with HF; however, this is controversial. Previously, we have reported that patients with an LVEF of ≥ 58% have good prognoses. Further, cardiac sympathetic nervous system (SNS) activation is a feature of HF. In this retrospective, observational study, the cardiac SNS activity of HF patients (n = 63, age: 78.4 ± 9.6 years; male 49.2%) with LVEF ≥ 58% (n = 15) and LVEF < 58% (n = 48) were compared using 123I-metaiodobenzylguanidine scintigraphy. During the follow-up period (median, 3.0 years), 18 all-cause deaths occurred. The delayed heart/mediastinum (H/M) ratio was significantly higher in the LVEF ≥ 58% group than in the LVEF < 58% group (2.1 ± 0.3 vs. 1.7 ± 0.4, p = 0.004), and all-cause mortality was significantly lower in patients in the former than those in the latter group (log-rank, p = 0.04). However, when these patients were divided into LVEF ≥ 50% (n = 22) and LVEF < 50% (n = 41) groups, no significant differences were found in the delayed H/M ratio, and the all-cause mortality did not differ between the groups (log-rank, p = 0.09). In conclusion, an LVEF of 58% is suitable for reclassifying patients with HF according to cardiac SNS activity.

Abstract Background The prevalence of multimorbidity and polypharmacy and its association with all‐cause mortality in older patients with pacemakers are largely unknown. We aimed to clarify the prevalence of multimorbidity and polypharmacy, and its association with all‐cause mortality in patients ≥75 years of age with pacemakers. Methods We retrospectively investigated 256 patients aged ≥75 years (mean age 84.0 ± 5.3 years; 45.7% male) with newly implanted pacemakers. The study endpoint was all‐cause mortality (“with events”). Multimorbidity was defined as a Charlson Comorbidity Index ≥3. Polypharmacy was defined as the use of ≥5 medications. Results During the follow‐up period (median, 3.1 years), 60 all‐cause deaths were reported. The Charlson Comorbidity Index (2.9 ± 1.9 vs. 1.7 ± 1.7, p

Purpose: Treatment of hypertension has recently shown remarkable advances. It is quite important to survey the current general status of blood pressure (BP) and recent changes to verify whether people are benefitting from these advances. The present study aimed to investigate the current status of, and recent changes in, BP, the prevalence and treatment rate of hypertension, the achievement rate of target BP, and salt intake in Japanese individuals. Methods: Recent changes in salt intake as well as BP, the prevalence and treatment rate of hypertension, and the rate of achievement of target BP were investigated in participants in our yearly physical checkup program from 2009 to 2018 (n = 79,789). Individual salt intake was assessed by estimating 24-hour urinary sodium excretion using a spot urine sample. Results: The prevalence of hypertension did not change, but the treatment rate of hypertension (from 64% to 75%) and the achievement rate of the target BP improved during the period (from 35% to 57%). BP decreased, prominently in hypertensive participants under antihypertensive treatment (from 133 ± 14/84 ± 9 to 128 ± 13/76 ± 10 mmHg). Salt intake did not decline noticeably during the 10 years of observation. Conclusions: The prevalence of hypertension did not change, but the treatment rate of hypertension and the achievement rate of the target BP improved during a recent 10-year period. These findings suggest that improved pharmacological management of hypertension resulted in a gradual reduction in BP levels, but lifestyle modification has not yet really taken root in the Japanese general population.

Abstract. The effect of renal dysfunction on clinical outcomes following fractional flow reserve (FFR)-guided deferral of revascularization remains unelucidated. We retrospectively analyzed 224 patients with atherosclerotic coronary lesions who underwent deferred revascularization based on an FFR of >0.80. The median follow-up interval was 28.1 months. Patients were divided into 2 groups: the hemodialysis (HD) and the non-HD group. The non-HD group was further classified into 2 subgroups according to their estimated glomerular filtration rate (eGFR) level: eGFR

Purpose Self-measured blood pressure at home (HBP) is quite important for the management of hypertension. We hypothesized that winter HBP measured according to the recommendation of the guidelines, but not HBP measured inside bed before getting up, is elevated in response to cold ambient temperatures in winter. This study aimed to investigate differences in HBP measured before and after getting up in winter and summer.Methods: Hypertensive subjects whose blood pressure was stably controlled were enrolled (n = 46, 73 years). They were instructed to measure HBP while in bed just after waking (HBP-bed), in addition to the ordinary HBP measurement in the morning (HBP-morning) according to the guidelines. The mean value of HBP for 7 consecutive days before the day of a regular hospital visit was considered as the HBP of each subject, and characteristics of the winter and summer BPs were investigated.Results: HBP-morning was significantly higher (P

Abstract We investigated the incidence of cardiotoxicity, its risk factors, and the clinical course of cardiac function in patients with malignant lymphoma (ML) who received a cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) regimen. Among all ML patients who received a CHOP regimen with or without rituximab from January 2008 to December 2017 in Nagoya City University hospital, 229 patients who underwent both baseline and follow‐up echocardiography and had baseline left ventricular ejection fraction (LVEF) ≥50% were analyzed, retrospectively. Cardiotoxicity was defined as a ≥10% decline in LVEF and LVEF

Abstract Three-dimensional (3D) left ventricular (LV) myocardial strain measurements using transthoracic 3D echocardiography speckle tracking analysis have several advantages over two-dimensional (2D) LV strain measurements, because 3D strain values are derived from the entire LV myocardium, yielding more accurate estimates of global and regional LV function. In this review article, we summarize the current status of 3D LV myocardial strain. Specifically, we describe how 3D LV strain analysis is performed. Next, we compare characteristics of 2D and 3D strain, and we explain validation of 3D strain measurements, feasibility and measurement differences between 2D and 3D strain, reference values of 3D strain, and its applications in several clinical scenarios. In some parts of this review, we used a meta-analysis to draw reliable conclusions. We also describe the added value of 3D over 2D strain in several specific pathologies and prognoses. Finally, we discuss novel techniques using 3D strain and suggest its future directions.

The clinical impact of ABO blood type on cardio-cerebrovascular outcomes in patients undergoing dialysis has not been clarified. A total of 365 hemodialysis patients participated in the current study. The primary endpoint was defined as a composite including cardio-cerebrovascular events and cardio-cerebrovascular death. The primary endpoint was observed in 73 patients during a median follow-up period of 1182 days, including 16/149 (11%) with blood type A, 22/81 (27%) with blood type B, 26/99 (26%) with blood type O, and 9/36 (25%) with blood type AB. At baseline, no difference was found in the echocardiographic parameters. Multivariable Cox regression analyses revealed that blood type (type A vs. non-A type; hazard ratio (HR): 0.46, 95% confidence interval (95% CI): 0.26–0.81, p = 0.007), age (per 10-year increase; HR: 1.47, 95% CI: 1.18–1.84), antiplatelet or anticoagulation therapy (HR: 1.91, 95% CI: 1.07–3.41), LVEF (per 10% increase; HR: 0.78, 95% CI: 0.63–0.96), and LV mass index (per 10 g/m2 increase; HR: 1.07, 95% CI: 1.01–1.13) were the independent determinants of the primary endpoint. Kaplan–Meier curves also showed a higher incidence of the primary endpoint in the non-A type than type A (Log-rank p = 0.001). Dialysis patients with blood type A developed cardio-cerebrovascular events more frequently than non-A type patients.

Using 3-dimensional speckle-tracking echocardiography-derived activation imaging system, we visualized interventricular dyssynchrony in a repaired tetralogy of Fallot case with pacing-induced left ventricular dysfunction. The activation imaging system visualized interventricular dyssynchrony and resynchronization after cardiac resynchronization therapy and may be useful to assess electromechanical disturbance in complicated congenital heart diseases. (Level of Difficulty: Intermediate.)

Background: A few studies to evaluate an incidence of bradyarrhythmia in patients with hypertrophic cardiomyopathy (HCM) have been reported. Methods: We enrolled 161 patients with HCM to evaluate their bradyarrhythmia risk, especially the risk of patients who were at risk for sudden cardiac death (SCD) and eligible for implantation of an implantable cardiac defibrillator (ICD). We defined symptomatic bradyarrhythmia requiring a pacing therapy as a bradyarrhythmia event and collected the data on an occurrence of the event after the time of diagnosis of HCM. The incidence of bradyarrhythmia events was compared between patients with ICD indications (ICD-candidate group) and those without (non-ICD-candidate group). Furthermore, we investigated the associated factors with bradyarrhythmia events using a Cox proportional-hazards model. Results: During 5.5 ± 4.4 years follow-up, bradyarrhythmia events occurred in 8% (13 patients) of whole patients, and in 15% of the ICD-candidate group (n = 74). In contrast, only 2 events (2%) occurred in the non-ICD-candidate group. The incidence of bradyarrhythmia in the ICD-candidate group was significantly higher than that in the non-ICD-candidate group (log-rank p = 0.015). In the ICD-candidate group, a Cox proportional-hazards model demonstrated that lower heart rate at the time of diagnosis (HR: 1.072, 95%CI: 1.012 to 1.135, p = 0.018), and an eligibility of ICD implantation for secondary prevention of SCD (HR: 9.092, 95%CI: 2.644 to 31.258, p

Background Right ventricular (RV) dysfunction is a prognostic factor for cardiovascular disease. However, its mechanism and pathophysiology remain unknown. We investigated RV function using RV‐specific 3‐dimensional (3D)‐speckle‐tracking echocardiography (STE) in patients with chronic thromboembolic pulmonary hypertension. We also assessed regional wall motion abnormalities in the RV and chronological changes during balloon pulmonary angioplasty (BPA). Methods and Results Twenty‐nine patients with chronic thromboembolic pulmonary hypertension who underwent BPA were enrolled and underwent right heart catheterization and echocardiography before, immediately after, and 6 months after BPA. Echocardiographic assessment of RV function included both 2‐dimensional‐STE and RV‐specific 3D‐STE. Before BPA, global area change ratio measured by 3D‐STE was significantly associated with invasively measured mean pulmonary artery pressure and pulmonary vascular resistance (r=0.671 and r=0.700, respectively). Dividing the RV into the inlet, apex, and outlet, inlet area change ratio showed strong correlation with mean pulmonary artery pressure and pulmonary vascular resistance before BPA (r=0.573 and r=0.666, respectively). Only outlet area change ratio was significantly correlated with troponin T values at 6 months after BPA (r=0.470), and its improvement after BPA was delayed compared with the inlet and apex regions. Patients with poor outlet area change ratio were associated with a delay in RV reverse remodeling after treatment. Conclusions RV‐specific 3D‐STE analysis revealed that 3D RV parameters were novel useful indicators for assessing RV function and hemodynamics in pulmonary hypertension and that each regional RV portion presents a unique response to hemodynamic changes during treatment, implicating that evaluation of RV regional functions might lead to a new guide for treatment strategies.

Background. Left ventricular (LV) ejection fraction (EF) and LV volumes were reported to have prognostic efficacy in cardiac diseases. In particular, the end-systolic volume index (LVESVI) has been featured as the most reliable prognostic indicator. However, such efficacy in patients with LVEF ≥ 50% has not been elucidated. Methods. We screened the patients who received cardiac catheterization to evaluate coronary artery disease concomitantly with both left ventriculography and LV pressure recording using a catheter-tipped micromanometer and finally enrolled 355 patients with LVEF ≥ 50% and no history of heart failure (HF) after exclusion of the patients with severe coronary artery stenosis requiring early revascularization. Cardiovascular death or hospitalization for HF was defined as adverse events. The prognostic value of LVESVI was investigated using a Cox proportional hazards model. Results. A univariable analysis demonstrated that age, log BNP level, tau, peak − dP/dt, LVEF, LV end-diastolic volume index (LVEDVI), and LVESVI were associated with adverse events. A correlation analysis revealed that LVESVI was significantly associated with log BNP level (r = 0.356, p

BackgroundSpeckle tracking echocardiography (STE) is reported as a useful method to predict cardiac resynchronization therapy (CRT) responders. This study aimed to identify the incremental value of a STE parameter to predict CRT responders. Methods and ResultsWe enrolled 171 patients from the Speckle Tracking imaging for the Assessment of cardiac Resynchronization Therapy (START) study. CRT responders were defined as patients with ≥15% reduction of left ventricular (LV) end‐systolic volume at 6 months post‐CRT. Based on multivariable logistic regression analysis, incremental values of STE were assessed by c‐statistics, net reclassification improvement (NRI)/integrated discrimination improvement (IDI), and decision curve analysis. Six parameters (left bundle branch block or right ventricular pacing, use of beta‐blocker, blood urea nitrogen ≤3.0 mg/dL, LV end‐systolic diameter ≤50 mm, mitral regurgitation index ≤40%, and STE parameter standard deviation of time from QRS onset to first peak on the circumferential strain curves [TSD] ≥116 ms) were identified as the determinants. Compared to the multivariable logistic regression model without TSD (model 1), that with TSD (model 2) showed significant improvement to predict CRT responders: c‐statistic (0.86 vs 0.77; P