Left Ventricular Hypertrophic Change Indicating Poor Prognosis in Patients With Normal-Flow, Low-Gradient Severe Aortic Stenosis With Preserved Left Ventricular Ejection Fraction.

Background: Risk stratification of normal-flow, low-gradient (NFLG) severe aortic stenosis (SAS) with preserved left ventricular (LV) ejection fraction (EF) remains unclear. Methods and Results: Of 289 consecutive patients diagnosed with SAS by aortic valve area <1.0 cm2, 66 with NFLG-SAS (stroke volume index >35 mL/m2, mean pressure gradient <40 mmHg, LVEF ≥50%) were enrolled in this study; patients with bicuspid aortic valve, acute coronary syndrome, hemodialysis, or a history of aortic valve replacement (AVR) were excluded. Adverse events (AEs) were defined as cardiovascular death, hospitalization for heart failure, and deteriorating condition requiring AVR. Factors associated with AEs were investigated using a Cox proportional hazards model. Over a median of 675 days of follow-up, 25 AEs were recorded: 4 cardiovascular deaths, 12 hospitalizations for heart failure, and 9 patients requiring AVR. In addition, there were 14 events of progression to high-gradient SAS. Multivariable analysis showed significant associations between AEs and the presence of symptoms (hazard ratio [HR] 10.276; 95% confidence interval [CI] 3.724-28.357; P<0.001), LV hypertrophy (LV mass index >115 and >95 mg/m2 for males and females, respectively; HR 3.257; 95% CI 1.172-9.050; P=0.024), and tricuspid regurgitation (TR) velocity (HR 2.761; 95% CI 1.246-6.118; P=0.012). Conclusions: The presence of symptoms, LV hypertrophy, and high TR velocity could be reliable prognostic indicators and may require watchful waiting for timely AVR in patients with NFLG-SAS.

Future bradyarrhythmia in patients with hypertrophic cardiomyopathy.

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 < 0.001) were significantly associated with future bradyarrhythmia. CONCLUSIONS: HCM patients with eligibility for ICD implantation, especially for secondary prevention of SCD, more frequently suffered from bradyarrhythmia events.

Left Ventricular End-Systolic Volume Is a Reliable Predictor of New-Onset Heart Failure with Preserved Left Ventricular Ejection Fraction.

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 < 0.001), +dP/dt (r = -0.324, p < 0.001), -dP/dt (r = 0.391, p < 0.001), and tau (r = 0.337, p < 0.001). Multivariable analysis with a stepwise procedure using the variables with statistical significance in the univariable analysis revealed that aging, an increase in BNP level, and enlargement of LVESVI were significant prognostic indicators (age: HR: 1.071, 95% CI: 1.009-1.137, p=0.024; log BNP : HR : 1.533, 95% CI: 1.090-2.156, p=0.014; LVESVI : HR : 1.051, 95% CI: 1.011-1.093, p=0.013, respectively). According to the receiver-operating characteristic curve analysis for adverse events, log BNP level of 3.23 pg/ml (BNP level: 25.3 pg/ml) and an LVESVI of 24.1 ml/m2 were optimal cutoff values (BNP : AUC : 0.753, p < 0.001, LVESVI : AUC : 0.729, p < 0.001, respectively). CONCLUSION: In patients with LVEF ≥ 50%, an increased LVESVI is related to the adverse events. LV contractile performance even in the range of preserved LVEF should be considered as a role of a prognostic indicator.

Left ventricular contractile performance and heart failure in patients with left ventricular ejection fraction more than 40.

Heart failure (HF) with mid-range left ventricular ejection fraction (LVEF) (HFmrEF) is considered a new category of HF and LVEF < 50%, which is the upper threshold of LVEF for HFmrEF, is thought to represent a mild decrease in LV contractile performance. We aimed to consider an LVEF threshold value to be taken as a surrogate for impairment of LV contractile performance, resulting in new-onset HF. We enrolled 398 patients with LVEF ≥ 40% that underwent cardiac catheterization. Using the LV pressure recording with a catheter-tipped micromanometer, we calculated the inertia force of late systolic aortic flow (IFLSAF), which was sensitive to the slight impairment in LV contractile performance. We evaluated the utility of the IFLSAF for predicting future cardiovascular death or hospitalization for HF. We performed a receiver operating characteristic (ROC) curve analysis to determine the best LVEF threshold value for distinguishing whether the LV maintained the IFLSAF. A multivariate Cox proportional-hazards model revealed that the loss of IFLSAF was significantly associated with the future adverse events (HR: 7.798, 95%CI 2.174-27.969, p = 0.002). According to the ROC curve analysis, an LVEF ≥ 58% indicated that the LV could maintain the IFLSAF. We concluded that the loss of IFLSAF, which could reflect even slight impairment in LV contractile performance, was a reliable indicator for new-onset HF in patients with LVEF ≥ 40%. LVEF ≥ 58% could be taken as a surrogate for the IFLSAF maintenance; this threshold could be useful for risk stratification of new-onset HF in patients with preserved LVEF.

Physical activity and mortality in older patients with a pacemaker.

AIM: With increasing lifespans, patients requiring a pacemaker are older than they were in the past. Data regarding all-cause mortality in older patients implanted with a pacemaker are scarce. As physical activity is associated with a decrease in all-cause mortality, we investigated whether daily physical activity time, expressed as the activity rate determined by pacemakers, can predict all-cause mortality in older patients (aged ≥75 years) with a pacemaker. METHODS: We retrospectively investigated the baseline characteristics, echocardiographic indices, laboratory data and pacemaker parameters of 107 consecutive older patients with a newly implanted pacemaker at our hospital (age 83.8 ± 5.0 years; 54.2% men). The study end-point was all-cause mortality. RESULTS: During the follow-up period (mean 3.0 years), 21 cases of all-cause death were reported. The area under the receiver operating characteristic curve for activity rate to predict all-cause mortality was 0.82 (95% confidence interval 0.72-0.92, P < 0.001). An activity rate of 3.4% (50 min/day) had a sensitivity of 86.0% and a specificity of 66.7% for predicting all-cause mortality. The survival rate was significantly higher among patients with an activity rate ≥3.4% than among those with an activity rate <3.4% (log-rank, P < 0.001). A multivariate Cox regression analysis identified low activity rates as a predictor of all-cause mortality (hazard ratio 15.0, 95% confidence interval 4.29-52.6; P < 0.001). CONCLUSIONS: Low activity rates appear to be a strong predictor of all-cause mortality in older patients with a pacemaker. Geriatr Gerontol Int 2020; 20: 106-111.

Intramolecular Electron Transfers in a Series of [Co2Fe2] Tetranuclear Complexes.

Discrete cyanide-bridged Co-Fe multinuclear complexes can be considered as functional units of bulk Co-Fe Prussian blue analogues, and they have been recognized as a new class of switching molecules in the last decade. The switching property of the cyanide-bridged Co-Fe complexes is based on intramolecular electron transfers between Co and Fe ions, and we herein refer to this phenomenon as an electron transfer-coupled spin transition (ETCST). Although there have been numerous reports on the complexes exhibiting ETCST behavior, the systematic study of the substituent effects on the thermal ETCST equilibrium in solution has not been reported yet, and the rational control of the equilibrium temperature remains challenging. We report here the syntheses and thermal ETCST behavior both in the solid state and solution for a series of tetranuclear [Co2Fe2] complexes, [Co2Fe2(CN)6(L1)2(L2)4]X2 (L1 and L2: tri- and bidentate capping ligands for Fe and Co ions, X: counteranions). All complexes showed thermal ETCST equilibrium between high-spin ([(hs-CoII)2(ls-FeIII)2]) and low-spin ([(ls-CoIII)2(ls-FeII)2]) states in butyronitrile, and the equilibrium temperatures (T1/2) showed systematic shifts by chemical modifications and chemical stimuli. The T1/2 values were correlated with the redox potential differences (ΔE) of the Fe and Co ions in the constituent units, and the larger ΔE values led to the lower T1/2. The present result suggests that the thermal ETCST behavior in solution can be rationally designed by considering the redox potentials of the constituent molecules.

Solid-State Hydrogen-Bond Alterations in a [Co2 Fe2 ] Complex with Bifunctional Hydrogen-Bonding Donors.

A hydrogen-bonding donor-acceptor system, [Co2 Fe2 (bpy*)4 (CN)6 (tp*)2 ](PF6 )2 ⋅2ABA⋅4BN⋅2PE (1 solv ), was prepared by co-crystallization of an external stimuli-responsive cyanide-bridged tetranuclear [Co2 Fe2 ] complex and bifunctional hydrogen-bonding donors, p-aminobenzoic acid. Compound 1 solv exhibited a gradual electron-transfer-coupled spin transition (ETCST), and the removal of solvent molecules led to an abrupt thermal ETCST behavior with increased transition temperature. X-ray structural analysis revealed that the modification of ETCST was caused by a significant alteration of a hydrogen-bonding mode between the tetranuclear [Co2 Fe2 ]2+ cations and ABA molecules. Variable temperature IR measurements indicated that the desolvated form, 1 desolv , showed dynamic alteration of hydrogen-bonding interactions coupled with thermal ETCST behavior. These results suggested that the tetranuclear [Co2 Fe2 ] complex shows solid-state modulations of hydrogen-bond strengths by external stimuli.

Total Synthesis of (+)-Pyrenolide D.

An efficient approach to stereoselective construction of a spiro-γ-lactone core structure via BF3-promoted formal [3 + 2] annulation of aldehydo-aldose derivatives with γ-methylene-γ-butyrolactone has been developed. The spiro-γ-lactone derivative was then used in an efficient total synthesis of (+)-pyrenolide D. The developed chemistry paves the way for total synthesis of structurally diverse natural products containing spiro-lactone cores.

[Usefulness of hybrid small group learning and age-mixing method in early exposure learning in 2006 and 2007].

In 2006 the Faculty of Pharmacy, Meijo University has introduced an early exposure learning into the first-year curriculum of the 6-year pharmacy education system, with the aim of "understanding of patients," "enhancing motivation to learn pharmacy," and "understanding of the roles of pharmacists in the clinical setting". This program has three approaches: "active learning", "hybrid small group learning (SGL)" and "age-mixing". The 2006 questionnaire survey on this program revealed some disadvantages, including the inability of student facilitators to get the program in perspective, due to their lack of numbers and time assigned to each group. In response to the survey results, steps were taken to rectify these defects. Accordingly, in the 2007 questionnaire survey, the first-year undergraduates, student facilitators and faculty facilitators responded that the program was achieving its aims. In particular, they acknowledged the usefulness of "age-mixing" and "hybrid SGL" as educational approaches fundamental to the 6-year education system. Thus, in 2007 the program became more useful through our efforts to remedy the issues pointed out in 2006, including the low degree of understanding of "age-mixing" among the first-year undergraduates, and poor assignment of student facilitators to each group. The challenges for 2008 include further enhancing motivation of first-year undergraduates regarding SGL and establishment of a method for student facilitator intervention in SGL. Focusing on these challenges, we will continue our efforts to enhance the quality of pharmaceutical education through such approaches as early exposure learning.