Adverse clinical events after percutaneous coronary intervention in very elderly patients with acute coronary syndrome.

The number of very elderly patients with acute coronary syndrome (ACS) is increasing. Therefore, owing to the need for evidence-based treatment decisions in this population, this study aimed to examine the clinical outcomes during 1 year after percutaneous coronary intervention (PCI) in very elderly patients with ACS. This prospective multicenter observational study comprised 1337 patients with ACS treated with PCI, classified into the following four groups according to age: under 60, <60 years; sexagenarian, ≥60 and <69 years; septuagenarian, ≥70 and <80 years; and very elderly, ≥80 years. The primary endpoint was a composite of the first occurrence of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and bleeding within 1 year after PCI. We used the sexagenarian group as a reference and compared outcomes with those of the other groups. The incidence of the primary endpoint was significantly higher in the very elderly group than in the sexagenarian group (36 [12.7%] vs. 24 [6.9%], respectively; hazard ratio, 1.94; 95% confidence interval: 1.16-3.26; p = 0.012). The higher incidence of the primary endpoint was primarily driven by a higher incidence of all-cause death. When the multivariable analysis was used to adjust for patient characteristics and comorbidities, no difference was observed in the primary endpoint between the very elderly and sexagenarian groups (p = 0.96). The incidence of adverse events after PCI, particularly all-cause death, in very elderly patients with ACS was high. However, if several confounders are adjusted, comparable outcomes may be expected within 1 year after PCI among this population.

Clinical conditions and risk factors for inhibitor-development in patients with haemophilia: A decade-long prospective cohort study in Japan, J-HIS2 (Japan Hemophilia Inhibitor Study 2).

BACKGROUND: Inhibitor-development is a serious complication in patients with haemophilia (PwH). Previous studies reported that therapeutic and genetic factors could be associated with these alloantibodies. Relevant clinical features such as genetic-background and different treatment regimens in Japan remain unclear, however. AIMS: To analyse a nation-wide Japanese registry for PwH, and to examine risk factors for inhibitor-development. METHODS AND RESULTS: Newly diagnosed patients with haemophilia A (PwHA) or haemophilia B (PwHB) without inhibitors after 2007, and with treatment records traceable from 0 to 75 exposure days (ED), were enrolled in the Japan Hemophilia Inhibitor Study 2 (J-HIS2) initiated in 2008. Of 417 patients (340 PwHA, 77 PwHB) from 46 facilities, 83 (76 PwHA, 7 PwHB) were recorded with inhibitors by July 2020. Inhibitors were observed in 31.0% of severe PwHA, 8.0% moderate and 1.6% mild and in 17.1% of severe PwHB. The majority of inhibitors (89.7% in severe PwHA and 71.4% in severe PwHB) were detected on or before 25ED (median 12ED in PwHA and 19ED in PwHB). Genotyping in these severe patients identified an association between inhibitor-development and null variants of F8 (P < .01) or F9 (P < .05). A lower incidence of inhibitors was recorded in severe PwHA treated with prophylaxis than in those treated on-demand (P < .01). A past-history of intracranial-haemorrhage appeared to be associated with inhibitor-development, while FVIII-concentrates infusion and routine vaccination on the same day was not related to inhibitor-development. CONCLUSION: The J-HIS2 study has identified significant clinical variables associated with inhibitor-development in Japanese PwH, consistent with other global studies.

Favorable prognosis of vaccine-associated immune thrombocytopenia in children is correlated with young age at vaccination: Retrospective survey of a nationwide disease registry.

Childhood vaccine-associated immune thrombocytopenia (ITP) has a mostly favorable prognosis. To identify factors associated with prognosis, a retrospective survey was conducted with children with ITP who were registered in the Japanese Society of Pediatric Hematology/Oncology registry from 2008 to 2011. A total of 477 patients were categorized into four groups by event preceding ITP onset: vaccine-precedence (VP; n = 43), vaccine/infection-precedence (VIP; n = 34), infection-precedence (IP; n = 162), and no vaccine/infection-precedence (NVI; n = 238). Compared to IP and NVI, VP and VIP were significantly younger at diagnosis, with the age distribution peaking at infancy, and more frequently had favorable prognosis. Time to platelet recovery to 100 × 103/µL was significantly faster for VP and VIP than NVI. Multivariate Cox regression analysis with sex, age at diagnosis, infection-precedence, and vaccine-precedence as variables revealed age < 36 months (HR 0.992, 95% CI 0.989-0.995; p < 0.001) and male sex (HR 0.770, 95% CI 0.623-0.952; p = 0.015) as associated factors, but not infection-precedence (p = 0.149) or vaccine-precedence (p = 0.650). In subgroup analysis in patients < 36 months, age at diagnosis (p < 0.001) was the only associated factor. Favorable prognosis of childhood vaccine-associated ITP is correlated with young age at vaccination, but not with vaccination itself.

Study on the Causes, Types, and Mechanisms of Childhood Injuries-Age and Disease Specificity.

INTRODUCTION: To clarify the causes, types, and mechanisms of injuries in children, we collected injury cases and analyzed their causes. METHODS: During the 3-year period from 2013, we collected injury cases from three sources: nursery schools and kindergartens (A), emergency clinics of hospitals (B), and schools and a clinic for the developmentally disabled (C), using a format designed by Safe Kids Japan. RESULTS: In all, 383 cases were collected during the 3-year period. The causes of the injuries in group A were crashes, falls, and so on. The types of injuries were cuts, bruises, fractures, injuries of teeth, etc. Dislocations and abrasions were prominent in nursery school children (aged less than 3 years) and bone fractures were prominent in kindergarten children aged more than 3 years.Group B consisted of 144 cases. The most common causes of injuries were falls, traffic accidents, and so on, and the types of injuries were fractures, abrasions, sprains, etc. The incidence of fractures was particularly high and 50% of the accidents were bicycle accidents.Group C consisted of 41 cases. Although the age distribution was similar to that of group B, the types of accidents and injuries were similar to those of group A.The Bodygraphic Injury Surveillance System (BISS) analysis showed that groups A and C were similar, that is, injuries occurred mainly to the head, whereas in group B, the extremities were mainly affected. CONCLUSIONS: We analyzed the causes, types, and mechanisms of childhood injuries. The BISS may help to clarify the mechanisms of injuries in childhood.

Detailed analysis of anti-emicizumab antibody decreasing drug efficacy, using plasma samples from a patient with hemophilia A.

BACKGROUND: Emicizumab is a humanized bispecific monoclonal antibody that bridges activated factor IX (FIXa) and factor X (FX) to mimic the function of factor VIII (FVIII). It suppresses the bleeding tendency in hemophilia A patients with or without FVIII inhibitors. A case of an adult FVIII inhibitor-positive hemophilia A patient in whom treatment with emicizumab was discontinued owing to the repeated bleeding events and prolonged activated partial thromboplastin time. OBJECTIVE: To analyze the mechanisms of decreased efficacy of emicizumab. METHODS: Residual plasma samples were used to measure the following: emicizumab concentration in plasma, measured by enzyme-linked immunosorbent assay; titer of anti-drug antibody (ADA) against emicizumab, measured by electrochemiluminescence; and neutralizing activity against emicizumab, measured by Bethesda method modified by using emicizumab-spiked FVIII-deficient plasma. RESULTS: At week 31, emicizumab concentration was 15.0 µg/ml, and ADAs were measured as positive. Emicizumab concentration continued to decrease until emicizumab discontinuation point at week 49, and after week 50, emicizumab concentrations were below the limitation of quantification. The ADA titer increased transiently from week 31, even past the emicizumab discontinuation point at week 49. The ADA titer then gradually decreased until the last sampling point at week 93. Neutralizing activity against emicizumab was detected after emicizumab discontinuation. Epitope analysis showed that the ADAs recognize the anti-FIXa and anti-FX Fab arms of emicizumab, but not the Fc region. CONCLUSION: The appearance of ADAs with emicizumab-neutralizing activity and potential to accelerate emicizumab clearance decreased the efficacy of emicizumab.

Clinical characteristics of hospitalized heart failure patients with preserved, mid-range, and reduced ejection fractions in Japan.

AIMS: There are regional differences in the patient characteristics, management, and outcomes of hospitalized patients with heart failure (HF). The aim of this study was to evaluate the clinical characteristics and outcomes of Japanese patients who are hospitalized with HF on the basis of the left ventricular ejection fraction (LVEF) stratum. METHODS AND RESULTS: We retrospectively conducted a multicentre cohort study of 1245 hospitalized patients with decompensated HF between 2013 and 2014. Of these patients, 36% had an LVEF < 40% [HF with reduced ejection fraction (HFrEF), median age 72 years, 71% male], 21% had an LVEF 40-49% [HF with mid-range EF (HFmrEF), 77 years, 56% male], and 43% had an LVEF ≥ 50% [HF with preserved EF (HFpEF), 81 years, 44% male]. The primary outcome was death from any cause, and the secondary outcomes were cardiac death and re-hospitalization due to worsened HF after hospital discharge. There were high proportions of non-ischaemic cardiomyopathy (32%) in HFrEF patients, coronary artery disease (44%) in HFmrEF patients, and valvular disease (39%) in HFpEF patients. The frequencies of intravenous diuretic and natriuretic peptide administration during hospitalization were 66% and 30%, respectively. The median hospital stay for the overall population was 19 days, and the length of stay was >7 days for >90% of patients. In-hospital mortality was 7%, but was not different among the LVEF groups (HFrEF 7%, HFmrEF 6%, and HFpEF 8%). After a median follow-up of 19 months (range, 3-26 months), 192 (17%) of the 1156 patients who were discharged alive died, and 534 (46%) were re-hospitalized after hospital discharge. There were no significant differences in mortality after hospital discharge among the three LVEF groups (HFrEF 18%, HFmrEF 16%, and HFpEF 16%). There were no differences in cardiac death or re-hospitalization due to worsened HF after hospital discharge among the LVEF groups (cardiac death: HFrEF 8%, HFmrEF 7%, and HFpEF 7%; re-hospitalization due to worsened HF: HFrEF 19%, HFmrEF 16%, and HFpEF 17%). Multivariable-adjusted analyses showed that the HFmrEF and HFrEF groups, compared with the HFpEF group, were not associated with an increased risk for in-hospital death or death after hospital discharge. Non-cardiac causes of death and re-hospitalization after hospital discharge accounted for 35% and 38%, respectively. CONCLUSIONS: Our results revealed different clinical characteristics but similar mortality rates in the HFrEF, HFmrEF, and HFpEF groups. The most common cause of death and re-hospitalization after hospital discharge was HF, but non-cardiac causes also contributed to their prognosis. Integrated management approaches will be required for HF patients.

Baseline serum sitosterol level as predictor of adverse clinical events in acute coronary syndrome patients with dyslipidaemia: A sub-analysis of HIJ-PROPER.

BACKGROUND AND AIMS: We aimed to examine the effect of serum sitosterol, a cholesterol absorption marker, on clinical outcomes in acute coronary syndrome patients with dyslipidaemia. METHODS: This is a sub-analysis of the HIJ-PROPER trial that assesses the effect of aggressive low-density lipoprotein cholesterol (LDL-C) lowering treatment with pitavastatin + ezetimibe in 1734 acute coronary syndrome (ACS) patients with dyslipidaemia. Patients were divided into two groups based on sitosterol level at enrolment (cut-off value was 2.2 µg/mL; a median of baseline sitosterol level), and clinical outcomes were examined. RESULTS: The mean LDL-C level after 3 years in the low sitosterol group was 84.8 ± 20.1 mg/dL with pitavastatin-monotherapy and 64.6 ± 20.3 mg/dL with pitavastatin + ezetimibe, while corresponding values in the high sitosterol group were 91.0 ± 22.9 mg/dL and 71.1 ± 23.3 mg/dL, respectively. In the high sitosterol group, the Kaplan-Meier event rate for the primary endpoint at 3 years was 26.0% in the pitavastatin + ezetimibe group, as compared with 34.3% in the pitavastatin-monotherapy group (hazard ratio, 0.71; 95% confidence interval, 0.56-0.91; p = 0.006, p-value for interaction = 0.010). However, in the low sitosterol group, there was no significant reduction of the primary endpoint by pitavastatin + ezetimibe therapy. CONCLUSIONS: Aggressive lipid-lowering treatment with ezetimibe had a positive effect on clinical outcomes in the high sitosterol subset of ACS patients with dyslipidaemia, but not in the low sitosterol subset. This effect was independent of LDL-C reduction and suggests that sitosterol measurement on admission in ACS patients might contribute to a "personalised" lipid-lowering approach.

Successful Catheter Ablation as a Substitute for Cardiac Resynchronization Therapy in Patient with an Accessory Pathway-induced Cardiomyopathy.

A 50-year-old man presented with exertional dyspnea and orthopnea. An electrocardiogram showed a delta wave and a wide QRS complex, similar to left bundle branch block. Cardiac echocardiography revealed diffuse severe hypokinesis and dyssynchrony. The patient was diagnosed with congestive heart failure. We considered that the patient's condition was caused by an accessory pathway-induced cardiomyopathy after heart failure compensation with guideline-oriented medical therapy. We therefore performed catheter ablation for right-sided pre-excitation syndrome as cardiac resynchronization therapy. The left ventricular dyssynchrony was resolved immediately after the procedure, and the patient's ventricular contraction improved, with a reduced cardiac volume at 6 months after the procedure-thus suggesting that the accessory pathway had affected the patient's cardiac function.

Evaluation of the association between sleep apnea and polyunsaturated fatty acids profiles in patients after percutaneous coronary intervention.

The long-term outcome is poor in patients with sleep apnea and cardiovascular disease. Polyunsaturated fatty acid (PUFA) is also known as an independent predictor for adverse clinical events. However, the profile of PUFA in sleep apnea patients with coronary artery disease (CAD) is still unclear. This study aimed to clarify the association between sleep apnea and PUFA profiles in patients with CAD. Two hundred seventy-four consecutive patients undergoing percutaneous coronary intervention (PCI) were screened for sleep apnea using nocturnal oximetry. Oxygen desaturation index down to 4% (4%ODI) ≥5 was used as an indicator of sleep apnea. Baseline characteristics, including PUFA profiles, were compared between patients with and without sleep apnea. Among 243 enrolled patients, 134 (55%) had sleep apnea. The sleep apnea group included a significantly higher rate of patients with obesity, insulin-requiring diabetes, peripheral artery disease (PAD), and a higher C-reactive protein level than the non-sleep apnea group. The sleep apnea group had a significantly lower eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio than the non-sleep apnea group (0.33 vs. 0.44, respectively, p = 0.024). Additionally, EPA value and EPA/AA ratio were significantly correlated with 4%ODI (r = -0.15, p = 0.028; r = -0.16, p = 0.019, respectively). Results of logistic regression analysis indicated that the comorbidities of obesity, PAD, heart failure and EPA/AA ratio had a significant association with sleep apnea. Our results suggested that patients with sleep apnea who underwent PCI had a lower EPA/AA ratio than those without sleep apnea, and EPA value and EPA/AA ratio were significantly correlated with 4%ODI.

Low-density lipoprotein cholesterol targeting with pitavastatin + ezetimibe for patients with acute coronary syndrome and dyslipidaemia: the HIJ-PROPER study, a prospective, open-label, randomized trial.

AIMS: To elucidate the effects of intensive LDL-C lowering treatment with a standard dose of statin and ezetimibe in patients with dyslipidaemia and high risk of coronary events, targeting LDL-C less than 70 mg/dL (1.8 mmol/L), compared with standard LDL-C lowering lipid monotherapy targeting less than 100 mg/dL (2.6 mmol/L). METHODS AND RESULTS: The HIJ-PROPER study is a prospective, randomized, open-label trial to assess whether intensive LDL-C lowering with standard-dose pitavastatin plus ezetimibe reduces cardiovascular events more than standard LDL-C lowering with pitavastatin monotherapy in patients with acute coronary syndrome (ACS) and dyslipidaemia. Patients were randomized to intensive lowering (target LDL-C < 70 mg/dL [1.8 mmol/L]; pitavastatin plus ezetimibe) or standard lowering (target LDL-C 90 mg/dL to 100 mg/dL [2.3-2.6 mmol/L]; pitavastatin monotherapy). The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina, and ischaemia-driven revascularization. Between January 2010 and April 2013, 1734 patients were enroled at 19 hospitals in Japan. Patients were followed for at least 36 months. Median follow-up was 3.86 years. Mean follow-up LDL-C was 65.1 mg/dL (1.68 mmol/L) for pitavastatin plus ezetimibe and 84.6 mg/dL (2.19 mmol/L) for pitavastatin monotherapy. LDL-C lowering with statin plus ezetimibe did not reduce primary endpoint occurrence in comparison with standard statin monotherapy (283/864, 32.8% vs. 316/857, 36.9%; HR 0.89, 95% CI 0.76-1.04, P = 0.152). In, ACS patients with higher cholesterol absorption, represented by elevated pre-treatment sitosterol, was associated with significantly lower incidence of the primary endpoint in the statin plus ezetimibe group (HR 0.71, 95% CI 0.56-0.91). CONCLUSION: Although intensive lowering with standard pitavastatin plus ezetimibe showed no more cardiovascular benefit than standard pitavastatin monotherapy in ACS patients with dyslipidaemia, statin plus ezetimibe may be more effective than statin monotherapy in patients with higher cholesterol absorption; further confirmation is needed. TRIAL NO: UMIN000002742, registered as an International Standard Randomized Controlled Trial.

Association of New York Heart Association functional class IV symptoms at admission and clinical features with outcomes in patients hospitalized for acute heart failure syndromes.

BACKGROUND: It remains unclear whether there are subgroups of acute heart failure syndromes (AHFS) patients in whom New York Heart Association (NYHA) class IV symptoms at admission is related to a higher risk of mortality because of the heterogeneity of this patient population. The aim of this study was to evaluate the association of NYHA class IV symptoms at baseline with in-hospital mortality in subgroups of patients with AHFS. METHODS AND RESULTS: Of the 4842 patients enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, 4786 patients were included in this analysis. The primary endpoint was in-hospital all-cause death. NYHA class IV at baseline was detected in 44.3% of the patients. The all-cause death rate was significantly higher in patients with NYHA class IV than in those with NYHA class II or III (9.0% vs. 4.3%, P<0.001). To examine the heterogeneity of the association between NYHA class IV symptoms at baseline and in-hospital mortality, subgroup analyses were performed. As a result, the presence of NYHA class IV symptoms on admission was associated with a significantly higher risk of all-cause death in patients aged ≥75years, female patients, patients without an idiopathic dilated etiology, and patients with preserved ejection fraction (EF). CONCLUSIONS: This study demonstrated that an age≥75years, female gender, the absence of idiopathic dilated etiology, and a preserved EF should be considered when assessing the clinical significance of NYHA class IV symptoms in relation to the risk of in-hospital mortality in patients hospitalized for AHFS.

The use of a cutting balloon in contemporary reverse controlled antegrade and retrograde subintimal tracking (reverse CART) technique.

The key concept of reverse controlled antegrade and retrograde tracking (CART) technique is retrograde puncture with a tapered wire to an antegrade balloon (contemporary reverse CART) or new connections between the antegrade and retrograde subintimal space (classical reverse CART). In our case, a 75-year-old man with severe chronic total occlusion of the right coronary artery, reverse CART with conventional balloons could not be accomplished. Externalization wiring was completed by contemporary reverse CART using a cutting balloon as an antegrade balloon to improve the fenestration force of the retrograde guidewire. Thus, the use of a cutting balloon for contemporary reverse CART might be promising.

External and internal compressions to retrieve a kinked catheter in the right brachial artery.

Kinking of the catheter due to excessive rotation is not a rare complication. However, percutaneous retrieval of a kinked catheter can be difficult. The key to bailout is fixation of the catheter tip. Herein, we present a 78-year-old woman who had this complication during transradial angiography. Retrieval using several previously reported techniques was unsuccessful. We finally retrieved the kinked catheter by fixing the tip of the catheter, using external and internal compressions. The former comprises manual compression on the axillary artery, while the latter comprises deployment of a balloon catheter via another puncture site.

Coronary artery bypass grafting with internal thoracic arteries may cause bilateral brachiocephalic vein occlusion, complicating pacemaker implantation.

The number of patients with arrhythmia and ischaemic heart diseases is increasing. Patients with pacemaker implantation sometimes have brachiocephalic vein occlusion, and several aetiologies have been reported. However, coronary artery bypass grafting using the internal thoracic arteries is not fully discussed in the literature. We present a case of failed percutaneous pacemaker implantation due to bilateral brachiocephalic vein occlusion 8 years after coronary artery bypass grafting using the bilateral internal thoracic arteries. There were rich collateral veins consisting of hemiazygos and azygos veins. We then performed surgical implantation instead. Contrast CT or venography for such patients might be considered.

Efficacy of extracorporeal ultrafiltration in patients with diuretic-resistant heart failure.

Renal congestion contributes to the cardiorenal syndrome. There are some heart failure cases that are refractory to diuretic therapy. If the dose of diuretics is titrated, it leads to irreversible renal dysfunction. Early administration of tolvaptan is effective in treating fluid retention and congestion. However, in case of tolvaptan resistance, starting extracorporeal ultrafiltration (ECUM) at an early stage should be considered. Tolvaptan has been proven efficient, and we believe it should be incorporated with the classical method, ECUM. Herein, we present a case of successful application of ECUM to a heart failure patient refractory to any diuretics and tolvaptan.

Successful Retrieval of a Dismembered Central Venous Catheter Stuck to the Right Pulmonary Artery Using a Stepwise Approach.

Recent advances in anticancer chemotherapy have resulted in an increase in the number of patients requiring a central venous port catheter, and the incidence of catheter pinch-off syndrome has been increasing. Catheter pinch-off syndrome is a rare and unusual complication. It is difficult to retrieve dislodged catheters from the pulmonary artery, especially if the catheter is stuck to the peripheral pulmonary artery. We herein describe the successful removal of a catheter stuck in the pulmonary artery with a stepwise approach. First, a pigtail catheter was used to tug the dislodged catheter in order to free the unilateral end. Then, a gooseneck snare was used to catch and pull the catheter out of the patient. The key to success is to free the end of the catheter.

Thyroid Echography-induced Thyroid Storm and Exacerbation of Acute Heart Failure.

Hyperthyroidism and thyroid storm affect cardiac circulation in some conditions. Several factors including trauma can induce thyroid storms. We herein describe the case of a 57-year-old woman who experienced a thyroid storm and exacerbation of acute heart failure on thyroid echography. She initially demonstrated a good clinical course after medical rate control for atrial fibrillation; however, thyroid echography for evaluating hyperthyroidism led to a thyroid storm and she collapsed. A multidisciplinary approach stabilized her thyroid hormone levels and hemodynamics. Thus, the medical staff should be prepared for a deterioration in the patient's condition during thyroid echography in heart failure patients with hyperthyroidism.

The Differentiation of Giant Right Atrial Myxoma from Metastatic Cancer with the Use of Multiple Imaging Modalities.

Whether a cardiac tumor is primary or metastatic strongly influences the therapeutic strategy. We herein present a case of a cardiac tumor that occupied most of the right atrium which required immediate treatment in a patient with breast cancer. Multiple imaging modalities, especially computed tomography and cardiac magnetic resonance imaging, provided a precise preoperative diagnosis. We performed cardiac surgery prior to breast cancer surgery because the cardiac tumor was thought to be a myxoma rather than a metastatic cancer.

The usefulness of a perfusion balloon in a case of late stent thrombosis that caused simultaneous double vessel occlusion.

Simultaneous stent thrombosis in different coronary arteries requires rapid management. A 70-year-old man experienced simultaneous stent thrombosis at the left anterior descending and circumflex arteries. We used a perfusion balloon to prevent thrombus production at the left anterior descending artery, and completed percutaneous coronary intervention at the left circumflex artery in 10 min. The perfusion balloon was dilated during the procedure. In both vessels, Thrombolysis in myocardial infarction flow grade 3 was achieved after balloon deflation. Thus, use of a perfusion balloon for simultaneous double vessel occlusion helped avoid the need for redundant stent placement and shortened the procedure time.