Severity of myocardial fatty acid dysmetabolism induced by coronary spasm does not differ with Thrombolysis in Myocardial Infarction (TIMI) grade during intracoronary acetylcholine provocation tests.

Whether additional intracoronary acetylcholine (ACH) injections are required for severe coronary spasm without limited coronary flow in the ACH provocation test remains unclear. We used (123)I-ß-methyl-iodophenyl pentadecanoic acid ((123)I-BMIPP) to identify myocardial ischemic memory to compare the severity of myocardial fatty acid dysmetabolism among Thrombolysis in Myocardial Infarction (TIMI) grade flow.Thirteen hypertensive volunteers (mean age, 69.5 years) and 37 patients with VSA (mean age, 62.8 years) were enrolled. The patients with VSA were stratified according to TIMI flow grades of 3 (90% luminal narrowing; n = 12) or TIMI 0-2 (≥ 99% or total occlusion; n = 25) during ACH provocation tests. Two weeks after cardiac catheterization, (123)I-BMIPP myocardial scintigraphic images were obtained at 15 minutes (early) and at 4 hours (delayed) after tracer injection. The heart-to-mediastinum (H/M) ratio and washout rates (WR) were calculated from planar images.The TIMI 3 and TIMI 0-2 groups had significantly lower early and delayed H/M ratios than controls but the difference did not reach significance between the two groups (Early: 2.7 ± 0.5 versus 2.3 ± 0.4 and 2.2 ± 0.3, P = 0.024; Delayed: 2.4 ± 0.4 versus 1.8 ± 0.3 and 1.8 ± 0.3, P = 0.001). The washout rate was greater for TIMI 0-2 than the controls.The severity of myocardial fatty acid dysmetabolism did not differ between TIMI 3 and TIMI 0-2 coronary spasms. Additional ACH might not be required considering safety and the severity of coronary spams with TIMI 3 grade flow.

D-dimer levels in patients with nonvalvular atrial fibrillation and acute heart failure treated with edoxaban.

BACKGROUND: D-dimer levels can predict ischemic stroke in patients with acute heart failure (AHF). However, the effects of direct oral anticoagulants on D-dimer levels have not been investigated during admission for AHF in patients with atrial fibrillation (AF). This study examined D-dimer levels immediately after admission and following edoxaban initiation as a sub-analysis of a multi-center study that investigated the pharmacokinetics and pharmacodynamics of edoxaban in patients with nonvalvular AF (NVAF) and AHF. METHODS: Hospitalized patients with NVAF and AHF received edoxaban according to the label. The primary measure was the change in D-dimer levels on 7 consecutive days after admission for AHF. We also investigated differences according to prior edoxaban use (de novo at the time of admission or continuation). RESULTS: In 10/13 (76.9%) de novo patients, D-dimer levels exceeded the reference value (1.0 µg/mL) at admission (mean, 2.12 µg/mL) and subsequently decreased in 9 patients (at final blood sampling: mean, 1.12 µg/mL); 1 patient did not fall below the reference value due to stasis dermatitis. In the continuation group, most patients had D-dimer levels below the reference value from Day 1 (mean, 0.93 µg/mL), and levels remained stable or decreased (at final blood sampling: mean, 0.49 µg/mL). No events of stroke were observed. CONCLUSIONS: D-dimer levels may be elevated in patients with NVAF and AHF, particularly in those without prior anticoagulant treatment. Edoxaban may be effective for lowering and keeping D-dimer levels, a biomarker for predicting ischemic stroke, below the reference value in patients with NVAF and AHF.

Plasma Concentration and Pharmacodynamics of Edoxaban in Patients with Nonvalvular Atrial Fibrillation and Acute Heart Failure.

OBJECTIVE: The objective of this study was to assess the pharmacokinetic and pharmacodynamic profiles and safety of edoxaban in patients with nonvalvular atrial fibrillation (NVAF) who were hospitalized with acute heart failure (AHF). METHODS: The trough plasma concentrations of edoxaban, and the coagulation biomarkers prothrombin fragments 1 and 2 (F1+2) and D-dimer, were determined. Twenty-six patients received edoxaban 60 mg (30 mg when dose adjustment was required) and blood samples were collected immediately before oral edoxaban administration for 7 consecutive days after hospitalization and on the day of discharge. RESULTS: The mean observation period was 13 (range 7-46) days. Trough plasma concentrations of edoxaban were constant from day 2 onwards. On day 1, the variation was greater owing to the differing intervals between the last edoxaban dose and day 1 blood collection. Trough plasma concentrations were higher in patients with reduced creatinine clearance (≤ 50 mL/min). Median values for F1+2 and D-dimer remained within normal ranges throughout the study. There were no drug discontinuations, and no serious adverse events were reported. CONCLUSIONS: This is the first study of edoxaban pharmacokinetics and pharmacodynamics in patients with NVAF and AHF, and shows that the pharmacokinetic and pharmacodynamic profiles of edoxaban were constant during hospitalization. Thus, even in patients with NVAF and AHF, edoxaban anticoagulation therapy with guided dose adjustment is considered to be a safe and appropriate intervention. In particular, patients with reduced creatinine clearance should adhere to dose adjustment criteria. CLINICAL TRIAL REGISTRATION: jRCTs031190006 (Japan Registry of Clinical Trials), 5 April, 2019 retrospectively registered.

Prognostic value of exercise stress echocardiography in patients with secondary mitral regurgitation: a long-term follow-up study.

BACKGROUND: Secondary mitral regurgitation (MR) remains a challenging problem in the diagnosis and treatment of patients with heart failure. Although it is well known that secondary MR is dynamic, the impact of the severity of MR during exercise on long-term outcome has not been fully evaluated. The aim of the present study was to investigate the prognostic value of exercise stress echocardiography (ESE) in patients with secondary MR. METHODS: This prospective study included 118 consecutive patients with secondary MR and left ventricular dysfunction (mean ejection fraction at rest: 38 ± 14%) who underwent semi-supine ESE. Their major cardiovascular events (MACE) including cardiac death were followed up for a median of 41.7 (range: 6-128) months. RESULTS: MR significantly increased from rest to exercise (effective regurgitant orifice: 0.18 ± 0.09 vs. 0.25 ± 0.12 cm2, P < 0.001). The prevalence of severe MR was higher during exercise than those at rest (37% vs. 56%, P < 0.001). During follow-up, MACE occurred in 49 patients (41.5%) including 12 cardiac deaths. Cox proportional-hazard multivariate analysis revealed that older age and MR severity during exercise were significantly associated with increased risk of MACE (hazard ratio: 1.04 and 8.4, respectively, both P < 0.05). CONCLUSIONS: ESE provides prognostic information in patients with secondary MR that is useful for predicting long-term outcome.

Prognostic value of exercise left ventricular end-systolic volume index in patients with asymptomatic aortic regurgitation: an exercise echocardiography study.

BACKGROUND: Surgical timing of chronic aortic regurgitation (AR) remains a matter of debate because of limited data. This study assessed the prognostic value of exercise echocardiography in asymptomatic AR. METHODS: This prospective study included 60 consecutive asymptomatic patients with isolated moderate or severe AR (mean regurgitant volume 56.7 ± 11.8 ml) and preserved ejection fraction who underwent exercise echocardiography. The clinical outcomes were defined by the presence of major adverse cardiovascular events (MACE) and the indication for aortic valve replacement (AVR) with class I or IIa classification in the current guidelines. RESULTS: During the average follow-up of 731 days, 12 patients suffered from the clinical events, including two patients developing MACE (3%) and ten patients indicating for AVR (17%). No difference in left ventricular (LV) ejection fraction at rest was found between the patients with and without the clinical events. The indexed LV diameters and LV volumes were significantly dilated in the patients with the clinical events. The Cox proportional hazards regression analysis resulted that the exercise LV end-systolic volume index (LVESVi) was significantly associated with the clinical outcomes [hazard ratio, 1.116; 95% CI (1.032-1.205); p = 0.006]. The Kaplan-Meier analysis showed that exercise LVESVi was clearly stratified the event-free survival. CONCLUSIONS: Exercise LVESVi might be an independent predictor of prognosis in patients with asymptomatic moderate or severe AR.