Outcomes and Safety of Very-Low-Dose Edoxaban in Frail Patients With Atrial Fibrillation in the ELDERCARE-AF Randomized Clinical Trial.

Importance: The prevalence of atrial fibrillation (AF) increases with age and is more common in frail patients. However, data are lacking on outcomes of oral anticoagulants (OACs) in very elderly patients with AF with frailty, who are ineligible for standard anticoagulant treatment. Objective: To compare very-low-dose edoxaban (15 mg daily) vs placebo across frailty status, including each of 5 frailty assessment parameters, among patients with AF involved in the ELDERCARE-AF (Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients) trial. Design, Setting, and Participants: This is a cohort study using data from ELDERCARE-AF, a multicenter, randomized, double-blind, placebo-controlled phase 3 study of Japanese patients with AF aged 80 years or older who were ineligible for OACs at doses approved for stroke prevention because of their high bleeding risks. Eligible patients were randomly assigned (1:1) to receive edoxaban or placebo. The study duration was from August 5, 2016, to November 5, 2019, with the last patient followed up on December 27, 2019. Data analysis was performed from February 2021 to February 2022. Exposure: Edoxaban (15 mg) once daily or placebo. Main Outcomes and Measures: The primary efficacy end point was the composite of stroke or systemic embolism, and the primary safety end point was major bleeding. Results: A total of 984 patients were randomly assigned to treatment (492 each to the edoxaban and placebo groups); 944 patients (402 frail patients [42.6%]; 542 nonfrail patients [57.4%]; mean [SD] age, 86.6 [4.3] years; 541 women [57.3%]) were included in this analysis. In the placebo group, the estimated event rates (SE) for stroke or systemic embolism were 7.1% (1.6%) per patient-year in the frail group and 6.1% (1.3%) per patient-year in the nonfrail group. Edoxaban was associated with lower event rates for stroke or systemic embolism with no interaction with frailty status or frailty assessment parameters. Major bleeding and major or clinically relevant nonmajor bleeding events were both numerically higher in the edoxaban group than in the placebo group, and no heterogeneity was observed with frailty status. Although both all-cause death and net clinical composite outcome occurred more frequently in the frail group than in the nonfrail group, there was no association with frailty status between the edoxaban and placebo groups. Conclusions and Relevance: Regardless of frailty status, among Japanese patients with AF aged 80 years or older who were ineligible for standard OACs, once-daily 15-mg edoxaban was associated with reduced incidence of stroke or systemic embolism and may be a suitable treatment option for these patients.

A case of right coronary artery chronic total occlusion with difficulty in retrograde system establishment.

Advances in microcatheters (MCs) enables the establishment of retrograde systems for the treatment of chronic total occlusion (CTO). However, there are still cases in which establishing a retrograde system is difficult because the guidewire or MC cannot pass through due to calcification, stenosis, or tortuosity. We present a case of a 56-year-old man with angina. Coronary angiography revealed a CTO of the right coronary artery (RCA). Although we started an antegrade approach at first, the guidewire went to subintimal lumen. We switched to a retrograde approach. Although the guidewire passed through posterolateral (PL) channel, the MC could not pass due to a stenosis at the junction of the main RCA trunk. Therefore, we negotiated the septal channel; however, it could only be guided in the peripheral direction. When the guidewire was more advanced in the peripheral direction, it crossed the guidewire that had previously passed through the PL channel. Then, when a balloon was delivered via the septal channel and trapped the guidewire from the PL channel, the MC was successfully delivered via the PL channel. After establishing the retrograde system, revascularization succeeded smoothly. In conclusion, this technique can be one option for the treatment of CTO patients. .

Preprocedural Planning Using a Three-Dimensional Printed Model for Percutaneous Coronary Intervention in an Anomalous Coronary Artery.

BACKGROUND Three-dimensional (3D) printed models have been recently introduced for diagnosis and preprocedural planning for percutaneous interventions or surgery in cardiovascular disease. CASE REPORT We treated a 71-year-old woman with angina. Although we performed coronary angiography, we could not engage the catheters for the left coronary artery (LCA). Then, we withdrew the catheter and examined her anatomy using coronary computed tomographic angiography (CCTA). The CCTA revealed that the LCA originated from the noncoronary cusp (NCC). Because anomalous LCA originating from the NCC is a rare congenital anomaly, percutaneous coronary intervention was considered difficult. We decided to use a 3D-printed model, which enabled us to clearly see the anatomy and simulation before the actual procedure, which went smoothly according to the preprocedural planning using the 3D printed model. 3D printed modeling is feasible for use in reproducing coronary artery anatomy and enhancing understanding of coronary abnormalities. CONCLUSIONS Use of 3D-printed models is a useful new option that can help visualize the anatomy and perform preprocedural planning for complex cases.

Prognostic Importance of Hippocampal Atrophy in Patients With Chronic Heart Failure.

Mild cognitive impairment (MCI) impedes a patient's decision-making ability to support self-care and is associated with increased mortality in patients with chronic heart failure (CHF). Thus, screening for MCI is very important. The assessment of hippocampal atrophy using magnetic resonance imaging can effectively diagnose early MCI. The purpose of this study was to assess the prevalence and prognostic significance of hippocampal atrophy using magnetic resonance imaging in patient with CHF. Of the 491 patients with CHF included in the study, 170 demonstrated hippocampal atrophy. Patients with hippocampal atrophy were older, and showed a higher rate of renal dysfunction and cardiac events than patients without hippocampal atrophy. A total of 180 cardiac events occurred during the follow-up period. A Cox proportional hazards regression model and Kaplan-Meier analysis showed that hippocampal atrophy was significantly associated with cardiac events. In conclusion, hippocampal atrophy is a significant and independent predictor of poor prognosis in patients with CHF and can aid risk stratification of these patients.

Difficult Wiring of a Recanalized Thrombotic Lesion in the Right Coronary Artery Analyzed with Optical Coherence Tomography.

BACKGROUND Recanalized thrombi are usually unrecognized in conventional coronary angiography. However, multiple channels have been observed in recanalized thrombotic lesions. Therefore, the wire apparently crosses the lesion in some difficult cases. We analyzed the cause of difficult wiring of a recanalized thrombotic lesion using optical coherence tomography (OCT). CASE REPORT An 87-year-old man with chest pain was admitted to our hospital. Coronary angiography showed significant stenosis of the proximal right coronary artery with irregular linear filling and haziness. Crossing of the wire for the lesion was very difficult but was achieved using a parallel wire technique. OCT clearly demonstrated multiple small channels which had ambiguous findings on angiography and intravascular ultrasound. These structures showed a honeycomb-like appearance suggests the recanalized thrombi. A drug-eluting stent was subsequently deployed to fully cover the entire lesion. CONCLUSIONS OCT is useful to evaluate the accurate tissue characteristics of a recanalized thrombotic lesion. Because recanalized thrombi have multiple small channels and since there are some cases in which a part of the channel only flows into a side branch, it is necessary to carefully monitor wiring at the time of percutaneous coronary intervention.

A randomized controlled trial of eicosapentaenoic acid in patients with coronary heart disease on statins.

BACKGROUND: There is a residual risk of coronary heart disease (CHD) despite intensive statin therapy for secondary prevention. The aim of this study was to investigate whether coronary plaque regression and stabilization are reinforced by the addition of eicosapentaenoic acid (EPA) to high-dose pitavastatin (PTV). METHODS: We enrolled 193 CHD patients who underwent percutaneous coronary intervention (PCI) in six hospitals. Patients were randomly allocated to the PTV group (PTV 4mg/day, n=96) or PTV/EPA group (PTV 4mg/day and EPA 1800mg/day, n=97), and prospectively followed for 6-8 months. Coronary plaque volume and composition in nonstenting lesions were analyzed by integrated backscatter intravascular ultrasound (IB-IVUS). RESULTS: The PTV/EPA group showed a greater reduction in total atheroma volume compared to PTV group. IB-IVUS analyses revealed that lipid volume was significantly decreased during follow-up period in only PTV/EPA group. The efficacy of additional EPA therapy on lipid volume reduction was significantly higher in stable angina pectoris (SAP) patients compared to acute coronary syndrome patients. EPA/AA ratio was significantly improved in PTV/EPA group compared to PTV group. There was no significant difference in the incidence of major adverse cardiovascular events and side effects. CONCLUSIONS: Combination EPA/PTV therapy significantly reduced coronary plaque volume compared to PTV therapy alone. Plaque stabilization was also reinforced by EPA/PTV therapy in particular SAP patients. The addition of EPA is a promising option to reduce residual CHD risk under intensive statin therapy.

A Case of Chronic Total Occlusion of the Left Anterior Descending Artery Successfully Treated with Side Branch Technique Using the Soutenir CV.

BACKGROUND Success rates for treatment of chronic total occlusion (CTO) have dramatically improved in recent years with the development of new CTO guidewires and development of new techniques such as the retrograde approach. In the antegrade approach, a guidewire is occasionally passed through a side branch despite successful wire crossing of the CTO lesion. In order to pass a wire through the main artery, there are a few side branch techniques such as a reverse wire technique. CASE REPORT A 54-year-old man with symptoms of heart failure was admitted to our hospital. Coronary angiography showed CTO of the proximal left anterior descending artery. Percutaneous coronary intervention with an antegrade approach was started. We succeeded in passing the wire through a side branch but not the main artery. Unfortunately, a reverse wire technique failed in this case. Next, the wire passed through a side branch was exchanged with the Soutenir CV, and a retrograde approach was started. The wire crossing from retrograde was entwined around the Soutenir CV. After that, the retrograde wire was snared and guided to the antegrade guiding catheter, which resulted in successful wiring into the main artery easily. CONCLUSIONS The side branch technique using the Soutenir CV may be an effective strategy in some cases.

A Case of Cystic Adventitial Degeneration of the Left Popliteal Artery Diagnosed by Intravascular Ultrasound.

An 87-year-old male was admitted with intermittent claudication of the left calf. We performed lower extremity angiography, which revealed stenosis of the left popliteal artery. Intravascular ultrasound (IVUS) image correctly identified the cystic appearance of visualized extravascular hypodensity, causing extrinsic compression of the lumen. We diagnosed the condition as cystic adventitial degeneration (CAD) of the popliteal artery. We operated a resection of a cyst with the artery and replaced the autovein graft (saphenous vein). After surgery, the patient was free of symptoms. CAD is a rare disease; thus, our IVUS findings may provide unique diagnostic clues in patients with CAD.

Endovascular therapy for fibromuscular dysplasia of the bilateral external iliac arteries visualized with optical coherence tomography.

BACKGROUND: Fibromuscular dysplasia (FMD) is a non-inflammatory, non-atherosclerotic, degenerative vascular disease that most frequently affects renal and carotid arteries in women aged 30-50 years, and rarely complicating arteries of the lower limbs. CASE REPORT: A 60-year-old woman was admitted with intermittent claudication of both legs. We performed pelvic and bilateral lower-extremities angiography, which revealed that the bilateral external iliac arteries (EIAs) had the 'string of beads' appearance with a diagnosis of FMD. Endovascular therapy (EVT) was performed for the bilateral EIAs. Optical coherence tomography (OCT) images showed thickening and thinning of the middle layer, while three-dimensional OCT images showed a 'haustra coli'-like appearance. After successful balloon angioplasty, claudication completely disappeared. CONCLUSIONS: We report a rare case of EVT successfully performed for FMD of the bilateral EIAs. Our findings suggest that OCT may provide unique diagnostic clues in FMD patients.

Combination therapy of eicosapentaenoic acid and pitavastatin for coronary plaque regression evaluated by integrated backscatter intravascular ultrasonography (CHERRY study)-rationale and design.

BACKGROUND AND PURPOSE: Many clinical trials have shown that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) can significantly reduce coronary artery disease in both primary and secondary prevention. A recent study showed that aggressive lipid-lowering therapy with strong statins could achieve coronary artery plaque regression, as evaluated with gray-scale intravascular ultrasound (IVUS). However, it is unknown whether coronary plaque regression and stabilization are reinforced when eicosapentaenoic acid (EPA) is used with a strong statin. METHODS AND SUBJECTS: We aim to assess patients with stable angina or acute coronary syndrome who had undergone successful percutaneous coronary intervention (PCI) with integrated backscatter IVUS (IB-IVUS) guidance. They will be randomly allocated to receive pitavastatin (4mg), or pitavastatin (4mg) plus EPA (1800mg), and prospectively followed for 6-8 months. RESULTS: The primary endpoint will be changes in tissue characteristics in coronary plaques, evaluated by IB-IVUS, and secondary endpoints will include absolute changes in coronary plaque volume, serum lipid levels, and inflammatory markers. The safety profile will also be evaluated. CONCLUSIONS: The combination therapy of EPA and pitavastatin for regression of coronary plaque evaluated by IB-IVUS (CHERRY) study will be the first multicenter study using IB-IVUS to investigate the effects of combination therapy with pitavastatin and EPA on coronary plaque volume and tissue characteristics.

Short cardiac iodine-123-metaiodobenzylguanidine imaging protocol in heart failure.

BACKGROUND: For assessment of cardiac sympathetic nervous activity, the conventional protocol for iodine-123-metaiodobenzylguanidine ((123)I-MIBG) imaging requires several hours. METHODS AND RESULTS: To establish whether it is possible to shorten the conventional (123)I-MIBG imaging protocol, anterior planar imaging was performed in 42 heart failure (HF) patients at 5, 15 and 180 min. The washout rate of (123)I-MIBG from 5 to 15 min (WR5-15 min) was calculated as a novel index. WR5-15 min closely correlated with the conventional washout rate and inversely correlated with the heart to mediastinum ratio. Univariate Cox analysis revealed that rapid WR5-15 min, augmented plasma B-type natriuretic peptide level, and decreased left ventricular ejection fraction (LVEF) were predictors for cardiac events. Multivariate analysis showed WR5-15 min and LVEF were independent predictors. The cardiac event rate was markedly higher (73%) in patients when both WR5-15 min and LVEF were abnormal. CONCLUSIONS: WR5-15 min obtained from anterior planar imaging is useful for evaluating the severity of HF and clinical outcome, and may shorten the cardiac (123)I-MIBG scintigraphy protocol.

Electroanatomical mapping in partial atrial standstill for visualization of atrial viability and a suitable pacing site.

Partial atrial standstill is characterized by the failure of atrial activity either spontaneously or in response to electrical stimulation in restricted site of atria. In this case with bradycardia, atrial standstill was restricted to the lateral and posterior right atrium. The markedly prolonged intraatrial conduction delay was observed in the superior to septal region of the right atrium. The electroanatomical mapping was successfully utilized to estimate atrial activity and to find a suitable site for atrial lead placement. The electroanatomical mapping may become an innovated strategy to estimate atrial electrical status in partial atrial standstill.

Lipomatous hypertrophy of the interatrial septum with cutaneous lipomatosis.

A mass was identified in the atrial septum by clinical imaging in a patient who had multiple large lipomas of the skin. Multislice computed tomography and magnetic resonance imaging indicated that the interatrial mass was a fatty infiltration. In order to discriminate the myocardial lesion from myxoma and other benign conditions and malignant tumors, percutaneous transvenous biopsy was performed. Microscopic examination demonstrated the cardiac mass to be lipomatous hypertrophy of the interatrial septum (LHIS), and the skin lesions, simple lipomas. The LHIS is itself a rare condition, and its development in patients having multiple ponderous lipomas, or lipomatosis, could not be found in a previous report. This may be the first published case of LHIS, which likely represents cardiac involvement of lipomatosis.