Impairment of Cognitive Function Increases Mortality Risk in Relation to Cardiac Sympathetic Denervation and Renal Dysfunction in Patients With Systolic Heart Failure.

BACKGROUND: In contrast to the well-known prognostic values of the cardiorenal linkage, it remains unclear whether impaired cognitive function affects cardiac prognosis in relation to cardiac sympathetic innervation and renal function in patients with heart failure (HF). METHODS AND RESULTS: A total of 433 consecutive HF patients with left ventricular ejection fraction (LVEF) <50% underwent the Mini-Mental State Examination (MMSE) and a neuropsychological test for screening of cognition impairment or subclinical dementia. Following metaiodobenzylguanidine (MIBG) scintigraphy, patient outcomes with a primary endpoint of lethal cardiac events (CEs) were evaluated for a mean period of 14.8 months. CEs were documented in 84 HF patients during follow-up. MMSE score, estimated glomerular filtration rate (eGFR) and standardized heart-to-mediastinum ratio of MIBG activity (sHMR) were significantly reduced in patients with CEs compared with patients without CEs. Furthermore, overall multivariate analysis revealed that these parameters were significant independent determinants of CEs. The cutoff values of MMSE score (<26), sHMR (<1.80) and eGFR (<47.0 mL/min/1.73 m2) determined by receiver operating characteristic (ROC) analysis successfully differentiated HF patients at more increased risk for CEs from other HF patients. CONCLUSIONS: Impairment of cognitive function is not only independently related to but also synergistically increases cardiac mortality risk in association with cardiac sympathetic function and renal function in patients with HF.

Head-to-Head Comparison of Hepatic Vein and Superior Vena Cava Flow Velocity Waveform Analyses for Predicting Elevated Right Atrial Pressure.

OBJECTIVE: Blood flow in the hepatic veins and superior vena cava (SVC) reflects right heart filling; however, their Doppler profiles are often not identical, and no studies have compared their diagnostic efficacies. We aimed to determine which venous Doppler profile is reliable for detecting elevated right atrial pressure (RAP). METHODS: In 193 patients with cardiovascular diseases who underwent cardiac catheterization within 2 d of echocardiography, the hepatic vein systolic filling fraction (HV-SFF) and the ratio of the peak systolic to diastolic forward velocities of the SVC (SVC-S/D) were measured. HV-SFF < 55% and SVC-S/D < 1.9 were regarded as elevated RAP. We also calculated the fibrosis 4 index (FIB-4) as a serum liver fibrosis marker. RESULTS: HV-SFF and SVC-S/D were feasible in 177 (92%) and 173 (90%) patients, respectively. In the 161 patients in whom both venous Doppler waveforms could be measured, HV-SFF and SVC-S/D were inversely correlated with RAP (r = -0.350, p < 0.001; r = -0.430, p < 0.001, respectively). SVC-S/D > 1.9 showed a significantly higher diagnostic accuracy of RAP elevation compared with HV-SFF < 55% (area under the curve, 0.842 vs. 0.614, p < 0.001). Multivariate analyses showed that both FIB-4 (ß = -0.211, p = 0.013) and mean RAP (ß = -0.319, p < 0.001) were independent determinants of HV-SFF. In contrast, not FIB-4 but mean RAP (ß = -0.471, p < 0.001) was an independent determinant of SVC-S/D. The diagnostic accuracy remained unchanged when HV-SFF < 55% was considered in conjunction with the estimated RAP based on the inferior vena cava morphology. Conversely, SVC-S/D showed an incremental diagnostic value over the estimated RAP. CONCLUSIONS: SVC-S/D enabled a more accurate diagnosis of RAP elevation than HV-SFF.

Monodisperse nanosheet mesophases.

Self-assemblies of anisotropic colloidal particles into colloidal liquid crystals and well-defined superlattices are of great interest for hierarchical nanofabrications that are applicable for various functional materials. Inorganic nanosheets obtained by exfoliation of layered crystals have been highlighted as the intriguing colloidal units; however, the size polydispersity of the nanosheets has been preventing precise design of the assembled structures and their functions. Here, we demonstrate that the anionic titanate nanosheets with monodisperse size reversibly form very unusual superstructured mesophases through finely tunable weak attractive interactions between the nanosheets. Transmission electron microscopy, polarizing optical microscopy, small-angle x-ray scattering, and confocal laser scanning microscopy clarified the reversible formation of the mesophases (columnar nanofibers, columnar nematic liquid crystals, and columnar nanofiber bundles) as controlled by counter cations, nanosheet concentration, solvent, and temperature.

Guidance for performance, utilization, and education of cardiac and lung point-of-care ultrasonography from the Japanese Society of Echocardiography.

In recent years, bedside ultrasound examinations have been used in many clinical departments and are called point-of-care ultrasound (POCUS). Regarding POCUS in the cardiac field, a protocol called focus (focused) cardiac ultrasound (FoCUS) has been developed in Europe and the United States, is being used clinically, and an educational syllabus has been created. According to them, FoCUS is defined as a point-of-care cardiac ultrasound examination using standardized limited sections and protocols. FoCUS is primarily intended to be performed by non-cardiologists, and in order to avoid making mistakes in judgment, it is important to be familiar with its limitations and it is necessary to understand pathological conditions that can only be diagnosed using conventional comprehensive echocardiography. The Japanese Society of Echocardiography has edited this clinical guideline because we believe that FoCUS should be used effectively and appropriately in Japan, and that appropriate education is essential to popularize FoCUS in Japan. Furthermore, lung POCUS has recently come into clinical use. Lung POCUS is useful for the diagnosis and follow-up of heart failure when used in conjunction with FoCUS, and is especially useful in primary care where chest X-rays are not available. The working group that created this manual agreed that it is desirable to educate patients about lung POCUS in conjunction with FoCUS, so we decided to include the basic techniques of lung POCUS and how to use them in this manuscript.

Mural infective endocarditis with a mass on the fossa ovalis in the right atrium.

Infective endocarditis (IE) is a life-threatening disease that affects the endocardial surface of the heart. Although heart valves are commonly involved in IE, in rare cases, vegetation is attached to the cardiac walls without valvular endocardial involvement, which is referred to as mural IE. In this case, a 60-year-old female presented with a seven-day history of fever associated with worsening pain in the right shoulder and left hip. Streptococcus dysgalactiae subsp. Equisimilis was detected in both blood and joint fluid cultures. Although transthoracic echocardiography revealed no mass, transesophageal echocardiography revealed a mobile mass in the fossa ovalis of the right atrium. She was subsequently diagnosed with mural IE and successfully treated with antibiotics without cardiac surgery. To our knowledge, only a few reports have described mural IE with vegetation in or around the fossa ovalis of the right atrium. This case highlights the importance of transesophageal echocardiography in diagnosing mural IE. The treatment strategy for mural IE should be discussed individually and in a multidisciplinary manner because current IE guidelines may not be applicable to mural IE cases due to differences in disease characteristics and clinical course between mural and valvular IE.

Non-invasive assessment of left ventricular filling pressure in aortic stenosis.

BACKGROUND: The assessment of left ventricular (LV) filling pressure (FP) is important for the management of aortic stenosis (AS) patients. Although, it is often restricted for predict LV FP in AS because of mitral annular calcification and a certain left ventricular hypertrophy. Thus, we tested the predictive ability of the algorithm for elevated LV FP in AS patients and also applied a recently-proposed echocardiographic scoring system of LV FP, visually assessed time difference between the mitral valve and tricuspid valve opening (VMT) score. METHODS: We enrolled consecutive 116 patients with at least moderate AS in sinus rhythm who underwent right heart catheterization and echocardiography within 7 days. Mean pulmonary artery wedge pressure (PAWP) was measured as invasive parameter of LV FP. LV diastolic dysfunction (DD) was graded according to the ASE/EACVI guidelines. The VMT score was defined as follows: time sequence of opening of mitral and tricuspid valves was scored to 0-2 (0: tricuspid valve first, 1: simultaneous, 2: mitral valve first). When the inferior vena cava was dilated, one point was added and VMT score was finally calculated as 0-3. RESULTS: Of the 116 patients, 29 patients showed elevated PAWP. Ninety patients (93%) and 67 patients (63%) showed increased values for left atrium volume index (LAVI) and E/e', respectively when the cut-off values recommended by the guidelines were applied and thus the algorism predicted elevated PAWP with a low specificity and positive predictive value (PPV). VMT ≥ 2 predicted elevated PAWP with a sensitivity of 59%, specificity of 90%, PPV of 59%, and negative predictive value of 89%. An alternative algorithm that applied tricuspid regurgitation velocity and VMT scores was tested, and its predictive ability was markedly improved. CONCLUSION: VMT score was applicable for AS patients. Alternative use of VMT score improved diagnostic accuracy of guideline-recommended algorism.

Echocardiographic estimation of right ventricular diastolic stiffness based on pulmonary regurgitant velocity waveform analysis in precapillary pulmonary hypertension.

Right ventricular (RV) diastolic stiffness is an independent predictor of survival and is strongly associated with disease severity in patients with precapillary pulmonary hypertension (PH). Therefore, a fully validated echocardiographic method for assessing RV diastolic stiffness needs to be established. This study aimed to compare echocardiography-derived RV diastolic stiffness and invasively measured pressure-volume loop-derived RV diastolic stiffness in patients with precapillary PH. We studied 50 consecutive patients with suspected or confirmed precapillary PH who underwent cardiac catheterization, magnetic resonance imaging, and echocardiography within a 1-week interval. Single-beat RV pressure-volume analysis was performed to determine the gold standard for RV diastolic stiffness. Elevated RV end-diastolic pressure (RVEDP) was defined as RVEDP ≥ 8 mmHg. Using continuous-wave Doppler and M-mode echocardiography, an echocardiographic index of RV diastolic stiffness was calculated as the ratio of the atrial-systolic descent of the pulmonary artery-RV pressure gradient derived from pulmonary regurgitant velocity (PRPGDAC) to the tricuspid annular plane movement during atrial contraction (TAPMAC). PRPGDAC/TAPMAC showed significant correlation with ß (r = 0.54, p < 0.001) and RVEDP (r = 0.61, p < 0.001). A cut-off value of 0.74 mmHg/mm for PRPGDAC/TAPMAC showed 83% sensitivity and 93% specificity for identifying elevated RVEDP. Multivariate analyses indicated that PRPGDAC/TAPMAC was independently associated with disease severity in patients with precapillary PH, including substantial PH symptoms, stroke volume index, right atrial size, and pressure. PRPGDAC/TAPMAC, based on pulmonary regurgitation velocity waveform analysis, is useful for the noninvasive assessment of RV diastolic stiffness and is associated with prognostic risk factors in precapillary PH.

Impact of Hemoglobin Level, White Blood Cell Count, Renal Dysfunction, and Staphylococcus as the Causative Organism on Prediction of In-Hospital Mortality from Infective Endocarditis.

Infective endocarditis (IE) is a highly fatal disease in cases of delayed diagnosis and treatment, although its incidence is low. However, there have been few single-center studies in which the risk of in-hospital death from IE was stratified according to laboratory findings on admission and the organism responsible for IE. In this study, a total of 162 patients who were admitted to our hospital during the period from 2009 to 2021, who were suspected of having IE according to the modified Duke classification, and for whom IE was confirmed by transesophageal echocardiography were retrospectively analyzed. Patients were observed for a mean-period of 43.7 days with the primary endpoint being in-hospital death. The in-hospital death group had a lower level of hemoglobin (Hb), higher white blood cell (WBC) count, lower level of estimated glomerular filtration rate (eGFR), and higher frequency of Staphylococcus being the causative agent than those in the non-in-hospital death group. In overall multivariate analysis, Hb, WBC count, eGFR, and Staphylococcus as the causative agent were identified to be significant prognostic determinants. IE patients with Hb < 10.6 g/dL, WBC count > 1.4 × 104/µL, eGFR < 28.1 mL/minute/1.7 m2, and Staphylococcus as the causative agent had significantly and synergistically increased in-hospital death rates compared to those in other IE patients. Low level of Hb, high WBC count, low eGFR, and Staphylococcus as the causative agent of IE were independent predictors of in-hospital mortality, suggesting that these 4 parameters may be combined to additively stratify the risk of in-hospital mortality.

The Clinical Utility of Noninvasive Forrester Classification in Acute Heart Failure from PREDICT Study.

The Forrester classification plays a crucial role in comprehending the underlying pathophysiology of heart failure (HF) and is employed to categorize the severity and predict the outcomes of patients with acute HF. Our objective was to assess the predictive value of the Forrester classification, based on noninvasive hemodynamic measurements obtained through Doppler echocardiography at admission, in forecasting the short-term prognosis posthospitalization of patients with acute HF. Patients were recruited for the Prospect trial to elucidate the utility of EchocarDIography-based Cardiac ouTput in acute heart failure (PREDICT) study, a multicenter, prospective study conducted in Japan. Participants were stratified into 4 profiles using cardiac index (CI) and early mitral filling velocity (E)/early-diastolic mitral annular velocity (e') ratio obtained from Doppler echocardiography upon admission (profile I: CI >2.2, E/e' ≤15, profile II: CI >2.2, E/e' >15, profile III: CI ≤2.2, E/e' ≤15, profile IV: CI ≤2.2, E/e' >15). The primary composite outcome of the study was all-cause mortality or worsening HF during the 14 days of hospitalization. Cox proportional hazards model analysis was employed to identify prognostic factors during the observation period. A total of 270 subjects, with a mean age of 74 ± 14 years and a male proportion of 60%, were enrolled in the study. During the 14-day period of hospitalization, 58 participants (22%) had a composite outcome. Patients with low CI (i.e., profiles III and IV) demonstrated an elevated risk of composite outcome after adjusting for confounding variables, as evidenced by the adjusted hazard ratios of 5.85 (95% confidence interval 1.17 to 29.09, p <0.01, vs profile III) and 6.50 (95% confidence interval 1.53 to 27.68, p <0.01, vs profile IV) in comparison with profile I, respectively. In conclusion, the Forrester classification, derived from noninvasive Doppler echocardiography at admission, may predict early deterioration in patients hospitalized with acute HF.

Cardiac Reversibility and Survival After Transcatheter Aortic Valve Implantation in Patients With Low-Gradient Aortic Stenosis.

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 <40 mm Hg) and LV stroke volume index (LF <35 mL/m2). Outcomes and changes in echocardiographic parameters after TAVI were compared between the groups. A total of 227 patients (13%) had reduced ejection fraction, and 486 patients (28%) had LG AS (LF-LG 143 [8%]; NF-LG 343 [20%]). During a median follow-up period of 747 days, 301 patients experienced a composite end point of cardiovascular death and rehospitalization for cardiovascular events, which was higher in the LF-LG and NF-LG groups than in the high-gradient groups. LG AS was independently associated with the primary outcome (hazard ratio, 1.69; P<0.001). Among 1239 patients with follow-up echocardiography, LG AS showed less improvement in the LV mass index and LV end-diastolic volume compared with high-gradient AS after 1 year, while LV recovery was similar between the LF AS and NF AS groups. Conclusions LG AS was associated with poorer outcomes and LV recovery, regardless of flow status after TAVI. Careful evaluation of AS severity may be required in LG AS to provide TAVI within the appropriate time and advanced care afterward.

Paradoxical increase in global longitudinal strain by handgrip exercise despite left ventricular diastolic dysfunction.

BACKGROUND: Although global longitudinal strain (GLS) is recognized as a sensitive marker of intrinsic left ventricular (LV) dysfunction, its afterload dependency has also been pointed. We hypothesized that decrease in GLS during handgrip exercise could be more sensitive marker of intrinsic myocardial dysfunction. METHODS: Handgrip exercise-stress echocardiography was performed in 90 cardiovascular disease patients with preserved LV ejection fraction. LV diastolic function was graded according to the guidelines. Diastolic wall stress (DWS) and ratio of left atrial (LA) volume index to late-diastolic mitral annular velocity (LAVI/a') were measured at rest as LV stiffness. As well, LA strains were measured to assess LA function. GLS was expressed as absolute value and significant changes in GLS by handgrip exercise was defined as changes over prespecified mean absolute test-retest variability (2.65%). RESULTS: While mean value of GLS did not change by the exercise, substantial patients showed significant changes in GLS: decreased (group I, n = 28), unchanged (group II, n = 34), and increased (group III, n = 28). Unexpectedly, patients in group I did not show any clinical and echocardiographic characteristics, while those in group III were characterized by elevated natriuretic peptide levels, blunted heart rate response to handgrip exercise, and advanced LV diastolic dysfunction. Multivariable analyses revealed that DWS, left atrial booster strain, and grade II or more diastolic dysfunction determined the increase in GLS even after adjustment for elevated natriuretic peptides and the changes in heart rate by the exercise. CONCLUSION: In contrast to our hypothesis, paradoxical increase in GLS by handgrip exercise could be associated with advanced LV diastolic dysfunction in cardiovascular patients with preserved LV ejection fraction. Our findings suggest that HG exercise for heart failure patients does not enhance the afterload straightforward, resulting in variable changes of GLS according to the individual conditions.

Multimodal Imaging of Constrictive Pericarditis Induced by Long-term Pergolide Treatment for Parkinson's Disease.

We herein report the first case of constrictive pericarditis (CP) induced by long-term pergolide treatment for Parkinson's disease that was assessed using multimodal imaging in a 72-year-old patient with leg edema and dyspnea. The patient was correctly diagnosed with CP using multimodal imaging and successfully treated with pericardiectomy. The treatment history of Parkinson's disease and pathological findings of the removed pericardium suggested that long-term pergolide was the cause of CP. Properly recognizing pergolide as the cause of CP and accurately diagnosing CP using multimodal imaging may contribute to the early detection and treatment of pergolide-induced CP.

Application of an echocardiographic scoring system of left ventricular filling pressure to diagnose acute heart failure in patients complaining dyspnea.

BACKGROUND: Dyspnea is a common symptom in acute heart failure (AHF) patients. Although an accurate and rapid diagnosis of AHF is essential to improve prognosis, estimation of left ventricular (LV) filling pressure (FP) remains challenging, especially for noncardiologists. We evaluated the usefulness of a recently-proposed parameter of LV FP, visually assessed time difference between the mitral valve and tricuspid valve opening (VMT) score, to detect AHF in patients complaining of dyspnea. METHODS: Echocardiography and lung ultrasonography (LUS) were performed in 121 consecutive patients (68 ±â€¯14 years old, 75 males) presenting with dyspnea. The VMT score was determined from the atrioventricular valve opening phase (tricuspid valve first: 0, simultaneous: 1, mitral valve first: 2) and inferior vena cava dilatation (absent: 0, present: 1), and VMT ≥2 was judged as positive. LUS was performed with the 8 zones method and judged as positive if 3 or more B-lines were observed in bilateral regions. The AHF diagnosis was performed by certified cardiologists according to recent guidelines. RESULTS: Of the 121 patients, 33 were diagnosed with AHF. The sensitivity and specificity for diagnosing AHF were 64 % and 84 % for LUS and 94 % and 88 % for VMT score. In logistic regression analysis, VMT score showed a significantly higher c-index than LUS (0.91 vs 0.74, p = 0.002). In multivariable analyses, VMT score was associated with AHF independently of clinically relevant covariates and LUS. In addition, serial assessment of VMT score followed by LUS provided a diagnostic flow chart to diagnose AHF (VMT 3: AHF definitive, VMT 2 and LUS positive: AHF highly suspicious; VMT 2 and LUS negative: further investigation is needed; VMT ≤ 1: AHF rejected). CONCLUSIONS: VMT score showed high diagnostic accuracy in diagnosing AHF. Combined assessment of the VMT score and LUS could become a reliable strategy for diagnosis of AHF by non-cardiologists.

Impact of right ventricular stiffness on discordance between hemodynamic parameter and regurgitant volume in patients with pulmonary regurgitation.

BACKGROUND: Accurate detection of significant pulmonary regurgitation (PR) is critical in management of patients after right ventricular (RV) outflow reconstruction in Tetralogy of Fallot (TOF) patients, because of its influence on adverse outcomes. Although pressure half time (PHT) of PR velocity is one of the widely used echocardiographic markers of the severity, shortened PHT is suggested to be seen in conditions with increased RV stiffness with mild PR. However, little has been reported about the exact characteristics of patients showing discrepancy between PHT and PR volume in this population. METHODS: Echocardiography and cardiac magnetic resonance imaging (MRI) were performed in 74 TOF patients after right ventricular outflow tract (RVOT) reconstruction [32 ± 10 years old]. PHT was measured from the continuous Doppler PR flow velocity profile and PHT < 100 ms was used as a sign of significant PR. Presence of end-diastolic RVOT forward flow was defined as RV restrictive physiology. By using phase-contrast MRI, forward and regurgitant volumes through the RVOT were measured and regurgitation fraction was calculated. Significant PR was defined as regurgitant fraction ≥ 25%. RESULTS: Significant PR was observed in 54 of 74 patients. While PHT < 100 ms well predicted significant PR with sensitivity of 96%, specificity of 52%, and c-index of 0.72, 10 patients showed shortened PHT despite regurgitant fraction < 25% (discordant group). Tricuspid annular plane systolic excursion and left ventricular (LV) ejection fraction were comparable between discordant group and patients showing PHT < 100 ms and regurgitant fraction ≥ 25% (concordant group). However, discordant group showed significantly smaller mid RV diameter (30.7 ± 4.5 vs. 39.2 ± 7.3 mm, P < 0.001) and higher prevalence of restrictive physiology (100% vs. 42%, P < 0.01) than concordant group. When mid RV diameter ≥ 32 mm and presence of restrictive physiology were added to PHT, the predictive value was significantly improved (sensitivity: 81%, specificity: 90%, and c-index: 0.89, P < 0.001 vs. PHT alone by multivariable logistic regression model). CONCLUSION: Patients with increased RV stiffness and non-enlarged right ventricle showed short PHT despite mild PR. Although it has been expected, this was the first study to demonstrate the exact characteristics of patients showing discrepancy between PHT and PR volume in TOF patients after RVOT reconstruction.

Usefulness of the pulmonary venous flow waveform for assessing left atrial stiffness.

PURPOSE: This study investigated the novel non-invasive left atrial (LA) stiffness parameter using pulmonary venous (PV) flow measurements and the clinical usefulness of the novel LA stiffness parameter. METHODS: We retrospectively analyzed 237 patients who underwent right heart catheterization and echocardiography less than one week apart. From the pulmonary artery wedge pressure waveform, the difference between x-descent and v-wave (ΔP) was measured. Using the echocardiographic biplane method of disks, the difference between LA maximum volume and that just before atrial contraction (ΔVMOD) was calculated, and the ΔP/ΔVMOD was calculated as a standard LA stiffness index. From the PV flow waveform, the peak systolic velocity (S), peak diastolic velocity (D), and minimum velocity between them (R) were measured, and S/D, S/R, and D/R were calculated. From the speckle tracking echocardiography-derived time-LA volume curve, the difference between LA maximum volume and that just before atrial contraction (ΔVSTE) was measured. Each patient's prognosis was investigated until three years after echocardiography. RESULTS: Among the PV flow parameters, D/R was significantly correlated with ΔP (r = 0.62), and the correlation coefficient exceeded that between S/D and ΔP (r = - 0.39) or S/R and ΔP (r = 0.14). The [D/R]/ΔVSTE was significantly correlated with ΔP/ΔVMOD (r = 0.61). During the follow-up, 37 (17%) composite endpoints occurred. Kaplan-Meier analysis showed that patients with [D/R]/ΔVSTE greater than 0.13 /mL were at higher risk of cardiac events. CONCLUSION: The [D/R]/ΔVSTE was useful for assessing LA stiffness non-invasively and might be valuable in the prognostic evaluation of patients with cardiac diseases.