Comparison Between Heart Failure Without Left Ventricular Systolic Dysfunction and Progression to End-Stage in Hypertrophic Cardiomyopathy.

BACKGROUND: The incidence and prognostic predictors of heart failure (HF) without left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM), particularly their differences in terms of developing LVSD (progression to end-stage) or sudden cardiac death (SCD), are not fully elucidated.Methods and Results: This study included 330 consecutive HCM patients with left ventricular ejection fraction (LVEF) ≥50%. HF hospitalization without LVSD and development of LVSD were evaluated as main outcomes. During a median follow-up of 7.3 years, the incidence of HF hospitalization without LVSD was 18.8%, which was higher than the incidence of developing LVSD (10.9%) or SCD (8.8%). Among patients who developed LVSD, only 19.4% experienced HF hospitalization without LVSD before developing LVSD. Multivariable analysis showed that predictors for HF hospitalization without LVSD (higher age, atrial fibrillation, history of HF hospitalization, and higher B-type natriuretic peptide concentrations) were different from those of developing LVSD (male sex, lower LVEF, lower left ventricular outflow tract gradient, and higher tricuspid regurgitation pressure gradient). Known risk factors for SCD did not predict either HF without LVSD or developing LVSD. CONCLUSIONS: In HCM with LVEF ≥50%, HF hospitalization without LVSD was more frequently observed than development of LVSD or SCD during mid-term follow-up. The overlap between HF without LVSD and developing LVSD was small (19.4%), and these 2 HF events had different predictors.

Clinical application of artificial intelligence algorithm for prediction of one-year mortality in heart failure patients.

Risk prediction for heart failure (HF) using machine learning methods (MLM) has not yet been established at practical application levels in clinical settings. This study aimed to create a new risk prediction model for HF with a minimum number of predictor variables using MLM. We used two datasets of hospitalized HF patients: retrospective data for creating the model and prospectively registered data for model validation. Critical clinical events (CCEs) were defined as death or LV assist device implantation within 1 year from the discharge date. We randomly divided the retrospective data into training and testing datasets and created a risk prediction model based on the training dataset (MLM-risk model). The prediction model was validated using both the testing dataset and the prospectively registered data. Finally, we compared predictive power with published conventional risk models. In the patients with HF (n = 987), CCEs occurred in 142 patients. In the testing dataset, the substantial predictive power of the MLM-risk model was obtained (AUC = 0.87). We generated the model using 15 variables. Our MLM-risk model showed superior predictive power in the prospective study compared to conventional risk models such as the Seattle Heart Failure Model (c-statistics: 0.86 vs. 0.68, p < 0.05). Notably, the model with an input variable number (n = 5) has comparable predictive power for CCE with the model (variable number = 15). This study developed and validated a model with minimized variables to predict mortality more accurately in patients with HF, using a MLM, than the existing risk scores.

Transaortic Transcatheter Aortic Valve Replacement in Patients From a Single Institution　- Feasibility, Safety, and Midterm Outcomes.

BACKGROUND: Transaortic transcatheter aortic valve replacement (TAo-TAVR) is an alternative to peripheral or transapical TAVR. The procedural feasibility, safety, and midterm outcomes of TAo-TAVR were investigated in this study.Methods and Results:Eighty-four consecutive patients underwent TAo-TAVR from 2011 to 2021. Their median age was 83 years (interquartile range, 80-87 years). The Edwards SAPIEN and Medtronic CoreValve devices were used in 45 (53.6%) and 38 (45.2%) patients, respectively. The surgical approach was a right mini-thoracotomy in 43 patients (51.2%) and partial sternotomy in 4 patients (4.8%). The remaining 37 patients (44.0%) underwent full sternotomy because of concomitant off-pump coronary artery bypass grafting. VARC-3 device success was achieved in 77 patients (91.7%). Valve migration occurred in 3 patients (3.6%) using a first-generation CoreValve device, necessitating implantation of a second valve. No aortic annulus rupture, aortic dissection, or coronary orifice occlusion occurred. Conversion to surgery was required for 1 patient because of uncontrollable bleeding. Only 1 in-hospital death occurred. New pacemaker implantation was required in 6 patients (7.1%). Echocardiography at discharge showed no or trivial paravalvular leak (PVL) in 58 patients (69.0%), mild PVL in 23 (27.4%), and mild to moderate PVL in 2 (2.4%) patients. The 1- and 3-year incidence of cardiovascular death was 1.6% and 4.8%, respectively, with no structural valve deterioration. CONCLUSIONS: TAo-TAVR is feasible and safe with satisfactory midterm outcomes using both currently available devices.

Accuracy of Shunt Volume Measured by Three-Dimensional Echocardiography and Cardiac Magnetic Resonance in Patients With an Atrial Septal Defect and a Dilated Right Ventricle.

BACKGROUND: The accuracy of right ventricular (RV) quantification by three-dimensional echocardiography (3DE) has been reported mainly in patients with a normal right ventricle (RV). However, there are no data regarding the accuracy of 3DE in patients with a dilated RV, as in shunt diseases. In this study, we evaluated the accuracy of 3DE and that of volumetric (Vol) cardiac magnetic resonance (CMR) for assessment of RV and left ventricular (LV) stroke volume (SV) and the pulmonary (Qp)/systemic (Qs) blood flow ratio in patients with an atrial septal defect (ASD) using the two-dimensional phase contrast (2DPC) method as the gold standard. METHODS: We retrospectively investigated 83 patients with ASD who underwent transcatheter closure and clinically indicated CMR and 3DE examinations. The ratio Qp/Qs was calculated using RV and LV SV measured by full-volume volumetric 3DE (Vol-3DE) and CMR (Vol-CMR) and by two-dimensional pulsed Doppler quantification (2D-Dop); the parameters were compared using 2DPC-CMR as the gold standard. RESULTS: There was no significant difference in the Qp/Qs value between 2DPC-CMR and Vol-3DE (2.29 ± 0.70 vs 2.21 ± 0.63, P = .79) and 2D-Dop (vs 2.21 ± 0.65, P = 1.00); however, a significant difference was found between 2DPC-CMR and Vol-CMR (P < .001). The Qp/Qs value obtained using Vol-3DE showed the best correlation with 2DPC-CMR (r = 0.93, P < .001). The RV and LV SV values obtained by Vol-3DE showed the best correlation with 2DPC-CMR (RV SV, r = 0.82, P < .001; LV SV, r = 0.73, P < .001), although the absolute values were underestimated. CONCLUSION: Qp/Qs was more accurately evaluated by Vol-3DE than by Vol-CMR or 2D-Dop. Three-dimensional echocardiography assessment was feasible and reproducible even in a dilated RV.

Determinants of reduced child stunting in Cambodia: analysis of pooled data from three demographic and health surveys.

OBJECTIVE: To assess how changes in socioeconomic and public health determinants may have contributed to the reduction in stunting prevalence seen among Cambodian children from 2000 to 2010. METHODS: A nationally representative sample of 10 366 children younger than 5 years was obtained from pooled data of cross-sectional surveys conducted in Cambodia in 2000, 2005, and 2010. The authors used a multivariate hierarchical logistic model to examine the association between the prevalence of childhood stunting over time and certain determinants. They estimated those changes in the prevalence of stunting in 2010 that could have been achieved through further improvements in public health indicators. FINDINGS: Child stunting was associated with the child's sex and age, type of birth, maternal height, maternal body mass index, previous birth intervals, number of household members, household wealth index score, access to improved sanitation facilities, presence of diarrhoea, parents' education, maternal tobacco use and mother's birth during the Khmer Rouge famine. The reduction in stunting prevalence during the past decade was attributable to improvements in household wealth, sanitation, parental education, birth spacing and maternal tobacco use. The prevalence of stunting would have been further reduced by scaling up the coverage of improved sanitation facilities, extending birth intervals, and eradicating maternal tobacco use. CONCLUSION: Child stunting in Cambodia has decreased owing to socioeconomic development and public health improvements. Effective policy interventions for sanitation, birth spacing and maternal tobacco use, as well as equitable economic growth and education, are the keys to further improvement in child nutrition.

Involvement of the phosphatidylinositol kinase pathway in augmentation of ATP-sensitive K(+) channel currents by hypo-osmotic stress in rat ventricular myocytes.

The objective of this study was to investigate the mechanisms of increase in the efficacy of ATP-sensitive K(+) channel (KATP) openings by hypo-osmotic stress. The whole-cell KATP currents (IK,ATP) stimulated by 100 µmol/L pinacidil, a K(+) channel opening drug, were significantly augmented during hypo-osmotic stress (189 mOsmol/L) compared with normal conditions (303 mOsmol/L). The EC50 and Emax value for pinacidil-activated IK,ATP (measured at 0 mV) was 154 µmol/L and 844 pA, respectively, in normal solution and 16.6 µmol/L and 1266 pA, respectively, in hypo-osmotic solution. Augmentation of IK,ATP during hypo-osmotic stress was attenuated by wortmannin (50 µmol/L), an inhibitor of phosphatidylinositol 3- and 4-kinases, but not by (i) phalloidin (30 µmol/L), an actin filament stabilizer, (ii) the absence of Ca(2+) from the internal and external solutions, and (iii) the presence of creatine phosphate (3 mmol/L), which affects creatine kinase regulation of the KATP channels. In the single-channel recordings, an inside-out patch was made after approximately 5 min exposure of the myocyte to hypo-osmotic solution. However, the IC50 value for ATP under such conditions was not different from that obtained in normal osmotic solution. In conclusion, hypo-osmotic stress could augment cardiac IK,ATP through intracellular mechanisms involving the phosphatidylinositol kinase pathway.

Clinical Outcomes of Radiologic Relapse in Patients With Cardiac Sarcoidosis Under Immunosuppressive Therapies.

Although nuclear imaging can detect cardiac involvement of cardiac sarcoidosis (CS), including subclinical states, little is known about the prevalence and outcomes of radiologic relapse under prednisolone (PSL) therapy. This study aimed to investigate the clinical characteristics and outcomes in patients with radiologic relapse. A total of 80 consecutive patients with CS whose disease activity on nuclear imaging decreased at least once after initiation of immunosuppressive therapy were identified through a retrospective chart review. Radiologic relapse of CS was diagnosed using 18F-fluoro-2-deoxyglucose positron emission tomography or gallium-67 scintigraphy. Composite adverse events were defined as at least 1 of the following: all-cause death, hospitalization for heart failure, or lethal arrhythmia. During the follow-up period (median 2.9 years), radiologic relapse was observed in 31 patients (38.8% of overall patients) at 30 months (median) after immunosuppressive therapy initiation. After radiologic relapse was detected, all patients were treated with intensified immunosuppressive therapies (increasing PSL, n = 26 [83.9%], adding other immunosuppressive therapies to PSL, n = 5 [16.1%]). There were no differences in occurrences of composite adverse events in patients with and patients without radiologic relapse. Radiologic relapse under immunosuppressive therapy was observed in many patients with CS, but it was not associated with clinical outcomes under intensified immunosuppressive therapy.

Prevalence and predictive factors for clinical outcomes of isolated functional tricuspid regurgitation.

BACKGROUND: A substantial number of patients have functional tricuspid regurgitation (TR). Isolated functional TR has been undertreated and may be a next target for transcatheter intervention. However, the prevalence, patient characteristics, and predictive factors for prognosis remain unclear. METHODS: From patients in our echocardiographic database (N = 64,242), we extracted those with severe TR and examined prognosis according to etiologies of TR. Thereafter, we focused on two types of isolated functional TR; progressive TR after left-sided valve surgery (postoperative TR) and TR associated with annular dilatation (atrial TR). Composite adverse events were defined as all-cause death or hospitalization for heart failure (HF). RESULTS: Of 1001 patients with severe TR (median age, 77 years; female, 58 %), 71 (7 %) patients were classified as postoperative TR, and 149 (15 %) as atrial TR. During the follow-up period (median, 1.6 years), 30 composite adverse events were observed (postoperative TR, n = 14; atrial TR, n = 16). Composite adverse events were less frequent in these two types of functional TR than TR of other etiologies. Multivariate analysis adjusted for age and sex showed that a history of hospitalization for HF, history of cardiac surgery >2 times, loop diuretics, estimated glomerular filtration rate, blood urea nitrogen, hemoglobin, platelet level, left ventricular ejection fraction, and right ventricular dimension were associated with clinical adverse events (p < 0.05), while B-type natriuretic peptide level was not. CONCLUSIONS: A considerable number of patients had isolated functional TR. Extracardiac factors such as renal function, hemoglobin and platelet are important in determining clinical outcomes.

Prognostic Predictors of Tricuspid Regurgitation Worsening after Mitral Regurgitation Surgery with Mild Tricuspid Regurgitation.

We aimed to investigate the prevalence and predictors of postoperative tricuspid regurgitation (TR) worsening in patients with mitral regurgitation (MR) and concomitant ≤mild TR. A total of 620 patients underwent surgery for MR from 2013 to 2017. Of these, 260 had ≤mild preoperative TR and no concomitant tricuspid valve surgery and were enrolled in this single-center retrospective study. The primary endpoint was postoperative worsening of ≥moderate TR. The primary endpoint occurred in 28 of 260 patients (11%) during the follow-up period [median: 4.1 years (interquartile range: 2.9-6.1 years)]. In the multivariable analysis, age, female sex, and left atrial volume index (LAVI) were significant predictors of the primary outcome during intermediate-term follow-up (age: hazard ratio [HR] 1.05 per 1-year increment, 95% confidence interval [CI] 1.02-1.10, P = 0.003; female sex: HR 3.53, 95% CI 1.61-7.72, P = 0.002; LAVI: HR 1.17 per 10-mL/m2 increment, 95% CI 1.07-1.26, P < 0.001). The optimal LAVI cut-off value for predicting postoperative TR worsening was 79 mL/m2 (area under the curve: 0.69). A high LAVI (>79 mL/m²) was significantly associated with a low rate of freedom from postoperative TR worsening compared with a low LAVI (≤79 mL/m²) (82.6% vs 93.9% at 5 years, respectively; log-rank P = 0.008). In patients with ≤mild preoperative TR and no concomitant tricuspid surgery, the rate of postoperative TR worsening was 11% during intermediate-term follow-up. LA enlargement in patients with MR and ≤mild preoperative TR was significantly associated with postoperative TR worsening.

Association of adherence to a 3 month cardiac rehabilitation with long-term clinical outcomes in heart failure patients.

AIMS: Although comprehensive cardiac rehabilitation (CCR) is recommended for patients with heart failure (HF), participants often show low adherence. The aim of this study was to evaluate the association of CCR completion and response with long-term clinical outcomes. METHODS AND RESULTS: We screened 824 HF patients who participated in a 3 month CCR programme and underwent baseline assessment, including cardiopulmonary exercise testing (CPX). After excluding 52 participants who experienced all-cause death or HF hospitalization within 180 days, long-term outcomes were compared between those who attended 3 month follow-up assessment including CPX (completers) and those who did not (non-completers). We also compared the prognostic value of the changes in peak oxygen uptake (VO2 ) vs. quadriceps muscle strength (QMS) during the 3 month CCR programme. Among the 772 study patients, there were no significant differences in baseline characteristics, including left ventricular ejection fraction, B-type natriuretic peptide levels, and peak VO2 , between the completers (n = 561) and non-completers (n = 211), except for a higher age (63.2 ± 14.2 vs. 59.4 ± 16.2 years; P = 0.0015) and proportion of females (27% vs. 17%; P = 0.0030) among the completers. During a median follow-up of 55.4 months, the completers had lower rates of the composite of all-cause death or HF hospitalization (34.4% vs. 44.6%; P = 0.0015) and all-cause death (16.9% vs. 24.6%; P = 0.0037) than the non-completers. After adjustment for prognostic baseline characteristics, including age and sex, CCR completion was associated with 34% and 44% reductions in the composite outcome and all-cause death, respectively. Among the completers, peak VO2 and QMS increased significantly (8.9 ± 15.8% and 10.5 ± 17.9%, respectively) over 3 months. Patients who had an increase in peak VO2  ≥ 6.3% (median value) during the CCR programme had significantly lower rates of the composite outcome (27.0% vs. 33.8%; P = 0.048) and all-cause mortality (10.0% vs. 17.4%; P = 0.0069) than those who did not. No statistically significant difference was observed in the composite outcome (30.5% vs. 30.4%; P = 0.76) or all-cause mortality (13.0% vs. 14.4%; P = 0.39) between those with and without an increase in QMS ≥8.3% (median value). CONCLUSIONS: In HF patients who participated in a 3 month CCR programme, its completion was associated with lower risks of subsequent HF hospitalization and death. Within the group of patients who completed the programme, the improvement in exercise capacity, but not in skeletal muscle strength, over the 3-month period was associated with better outcomes. These findings highlight the importance of the post-CCR follow-up assessment, including CPX, to identify a patient's adherence and response to the CCR programme.

Left Ventricular Dysfunction Caused by IgG4-related Small Intramural Coronary Periarteritis.

IgG4-related disease (IgG4-RD) is a systemic autoimmune disorder known to affect multiple organs. However, IgG4-RD rarely affects the myocardium. We herein report a case of left ventricular dysfunction due to cardiac involvement of IgG4-RD.

Left coronary ostial stenosis developing 15 months after transcatheter aortic valve replacement with balloon-expandable valve.

We present the case of an 82-year-old man whose left coronary ostium became obstructed 15 months after transcatheter aortic valve replacement (TAVR) with a balloon-expandable valve. The patient underwent TAVR for symptomatic severe aortic stenosis with no complications. Fifteen months after the initial TAVR, the patient complained of chest pain while exercising, and the exercise stress myocardial perfusion scintigraphy demonstrated the development of regional myocardial ischemia in the region of the left coronary artery. Coronary angiography implied severe stenosis in the ostium of the left coronary artery. Computed tomography angiography and intravascular ultrasonography indicated a soft tissue component along with stent struts, which was considered to cause delayed coronary obstruction. Our report emphasizes the importance of having a low threshold for clinically suspecting delayed coronary obstruction in patients who have undergone TAVR, even after several years of the procedure. .

Substitute parameters of exercise-induced pulmonary hypertension and usefulness of low workload exercise stress echocardiography in mitral regurgitation.

In asymptomatic patients with mitral regurgitation (MR), data of exercise-induced pulmonary hypertension (EIPH) are limited, and feasibility of evaluating EIPH is not high. We aimed to investigate prognostic impact of EIPH and its substitute parameters. Exercise stress echocardiography (ESE) were performed in 123 consecutive patients with moderate to severe degenerative MR. The endpoint was a composite of death, hospitalization for heart failure, and worsening of symptoms. EIPH [tricuspid regurgitation peak gradient (TRPG) at peak workload ≥ 50 mmHg] was shown in 57 patients (46%). TRPG at low workload was independently associated with TRPG at peak workload (ß = 0.67, p < 0.001). Early surgical intervention (within 6 months after ESE) was performed in 65 patients. Of the remaining 58 patients with the watchful waiting strategy, the event free survival was lower in patients with EIPH than in patients without EIPH (48.1 vs. 97.0% at 1-year, p < 0.001). TRPG at low workload ≥ 35.0 mmHg as well as EIPH were associated with poor prognosis in patients with the watchful waiting strategy. In conclusion, the importance of ESE and evaluating EIPH in patients with MR was re-acknowledged. TRPG at peak workload can be predicted by TRPG at low workload, and TRPG at low workload may be useful in real-world clinical settings.

Comparison of Clinical Characteristics, Natural History and Predictors of Disease Progression in Patients With Degenerative Mitral Stenosis Versus Rheumatic Mitral Stenosis.

Mitral annular calcification (MAC) is a common echocardiographic finding and an increasingly recognized cause of degenerative mitral stenosis (DMS). However, little is known about the clinical characteristics and disease progression in DMS, particularly in comparison with rheumatic mitral stenosis (RMS). We retrospectively reviewed 203 consecutive patients with mitral stenosis (113 with DMS and 90 with RMS) who underwent echocardiography at our institution between January 2014 and December 2017. We compared the clinical characteristics and disease progression between the 2 groups. In addition, we analyzed the predictors of disease progression (defined as annual progression rate of a mean gradient >0 mm Hg/year) among patients with DMS. Patients with DMS were significantly older and had higher prevalence of atherosclerotic comorbidities than those with RMS. During the median follow-up period of 2.2 years, the annual progression rates were comparable (0.8 ± 0.8 mm Hg/year in DMS vs 1.0 ± 1.2 mm Hg/year in RMS; p = 0.32) and were highly variable (0.0 to 3.5 mm Hg/year in DMS and 0.0 to 5.5 mm Hg/year in RMS) within both groups among disease progression. In DMS patients, atherosclerotic comorbidities and lower initial mean gradient were significantly associated with disease progression even after adjustment by age and sex. There was no significant difference in the disease progression according to the circumferential MAC severity determined by echocardiography among DMS. In conclusion, DMS disease progression was slow but highly variable, similar to that of RMS. In patients with DMS, the baseline MAC severity did not correlate with disease progression, suggesting the importance of follow-up echocardiography regardless of the MAC severity.

Improvements of predictive power of B-type natriuretic peptide on admission by mathematically estimating its discharge levels in hospitalised patients with acute heart failure.

BACKGROUNDS: Earlier studies showed that in patients with heart failure (HF), circulating levels of B-type natriuretic peptide (BNP) at hospital discharge (BNPdis) are more predictive of prognosis than BNP levels on admission (BNPad). However, the mechanism underlying that difference has not been fully elucidated. We examined the association between confounding factors during hospitalisation and BNPdis in patients with HF. METHODS: We identified patients admitted to our hospital for HF (BNPad ≥100 pg/mL). Estimated left ventricular end-diastolic pressure (eLVEDP) was calculated using echocardiographic data. To identify the factors associated with the relation between BNPad and BNPdis, we performed a stepwise regression analysis of retrospective data. To validate that analysis, we performed a prospective study. RESULTS: Through stepwise regression of the patient data (n=688, New York Heart Association 3-4, 88%), we found age, blood urea nitrogen and eLVEDP to be significantly (p<0.05) associated with BNPdis. Through multivariate analysis after accounting for these factors, we created a formula for predicting BNP levels at discharge (predicted-BNPdis) from BNPad and other parameters measured at admission (p<0.05). By statistically adjusting for these factors, the prognostic power of BNPad was significantly improved (p<0.001). The prospective study also confirmed the strong correlation between predicted-BNPdis and BNPdis (n=104, r=0.625, p<0.05). CONCLUSION: This study showed that statistically accounting for confounding factors affecting BNP levels improves the predictive power of BNP levels measured at the time of hospital admission, suggesting that these confounding factors are associated with lowering predictive power of BNP on admission. TRIAL REGISTRATION NUMBER: UMIN 000034409, 00035428.

Successful lymphatic embolization using N-butyl-2-cyanoacrylate for postoperative lymphorrhea in a patient with renal pelvic cancer.

We present a successful case of percutaneous lymphatic embolization using N-butyl-2-cyanoacrylate (NBCA) for postoperative lymphorrhea in a patient with urothelial carcinoma of renal pelvis. A 75-year-old man with urothelial carcinoma of left renal pelvis with para-aortic lymph nodes metastases. The patient presented severe lymphorrhea after neo-adjuvant chemotherapy followed by laparoscopic total left nephroureterectomy and lymph nodes dissection. Since conservative treatments were ineffective, percutaneous lymphatic embolization using NBCA resulted in healing of the lymphorrhea without recurrence. Percutaneous lymphatic embolization using NBCA followed by intranodal lymphography is a powerful treatment option for intractable postoperative lymphorrhea after lymph nodes dissection.

7-O-Methylated anthocyanidin glycosides from Catharanthus roseus.

Anthocyanins were isolated from orange-red flowers of Catharanthus roseus cv 'Equator Deep Apricot', and identified as rosinidin 3-O-[6-O-(alpha-rhamnopyranosyl)-beta-galactopyranoside] (1), and also 7-O-methylcyanidin 3-O-[6-O-(alpha-rhamnopyranosyl)-beta-galactopyranoside] (2) by chemical and spectroscopic methods. Pigment 1 was found to be a major anthocyanin in the flowers of this cultivar. By contrast, the distribution of rosinidin glycosides is very limited in plants, and reported only in the flowers of Primula. Pigment 2 was found in smaller concentrations, but its aglycone, 7-O-methylcyanidin, has been reported only once before, from the fruit of mango.