Impact of Sleep Apnea on Nocturnal Parasympathetic Activity in Atrial Fibrillation Patients After Catheter Ablation　- Implications for Heart Rate Variability Analysis.

BACKGROUND: The impact of sleep apnea (SA) on heart rate variability (HRV) in atrial fibrillation (AF) patients has not been investigated. METHODS AND RESULTS: Of 94 patients who underwent AF ablation between January 2021 and September 2022, 76 patients who had a nocturnal Holter electrocardiography and polysomnography conducted simultaneously were included in the analysis. A 15-min duration of HRV, as determined by an electrocardiogram during apnea and non-apnea time, were compared between patients with and without AF recurrence at 12 months' postoperatively. Patients had a mean age of 63.4±11.6 years, 14 were female, and 20 had AF recurrence at 12 months' follow-up. The root mean square of the difference between consecutive normal-to-normal intervals (RMSSD, ms) an indicator of a parasympathetic nervous system, was more highly increased in patients with AF recurrence than those without, during both apnea and non-apnea time (apnea time: 16.7±4.5 vs. 13.5±3.3, P=0.03; non-apnea time: 20.9±9.5 vs. 15.5±5.9, P<0.01). However, RMSSD during an apneic state was decreased more than that in a non-apneic state in both groups of patients with and without AF recurrence (AF recurrence group: 16.7±4.5 vs. 20.9±9.5, P<0.01; non-AF recurrence group; 13.5±3.3 vs. 15.5±5.9, P=0.03). Consequently, the effect of AF recurrence on parasympathetic activity was offset by SA. Similar trends were observed for other parasympathetic activity indices; high frequency (HF), logarithm of HF (lnHF) and the percentage of normal-to-normal intervals >50 ms (pNN50). CONCLUSIONS: Without considering the influence of SA, the results of nocturnal HRV analysis might be misinterpreted. Caution should be taken when using nocturnal HRV as a predictor of AF recurrence.

Early high-dose intravenous immunoglobulin for refractory heparin-induced thrombocytopenia with stroke: Two case reports.

BACKGROUND: High-dose intravenous immunoglobulin (IVIg) can be effective for patients with refractory autoimmune heparin-induced thrombocytopenia (HIT). We report two patients with autoimmune HIT (aHIT) successfully treated with early high-dose IVIg. CASE DESCRIPTION: Case 1 was a 48-year-old male who had persisting HIT with recurrent ischemic stroke after mitral valve replacement. Case 2 was a 71-year-old male who had flush heparin HIT with cerebral venous thrombosis after total hip arthroplasty. High-dose IVIg was administered 6 and 4 days after starting argatroban due to non-improved thrombocytopenia and persistently high D-dimer values, respectively. Both patients achieved favorable functional recovery at discharge as well as improvements of thrombocytopenia and hypercoagulation. CONCLUSIONS: Early high-dose IVIg may be effective for patients with aHIT and hypercoagulability.

An Autopsy Case of Severe COVID-19 Pneumonia Complicated by Intrapulmonary Thrombosis in Myelodysplastic/Myeloproliferative Neoplasm With Ring Sideroblasts and Thrombocytosis.

Patients with coronavirus disease 2019 (COVID-19) pneumonia are prone to intrapulmonary thrombosis owing to excessive inflammation and platelet activation. Myelodysplastic/myeloproliferative neoplasm (MDS/MPN) with ring sideroblasts and thrombocytosis (RS-T) is a rare disease in MDS/MPN overlap entities. Patients with MDS/MPN RS-T are known to be at a high risk of thrombosis, and platelet count control with drug therapy does not necessarily reduce this risk. Here, we report the autopsy case of an older male patient with MDS/MPN RS-T and severe COVID-19 pneumonia complicated by intrapulmonary thrombosis. His platelet count had been controlled in the normal range after treatment with hydroxyurea and 5-aza-2'-deoxycytidine. On admission day, he rapidly developed respiratory distress and tested positive on a polymerase chain reaction test for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). After admission, he received supplemental oxygen and was administered remdesivir and dexamethasone; however, his respiratory and circulatory status did not improve. The patient died on day 4 of illness. Autopsy findings revealed massive thrombi within blood vessels and diffuse alveolar damage in both lungs, which were determined to be the cause of death. In patients with MDS/MPN RS-T combined with COVID-19 pneumonia, clinicians may need to pay close attention to the risk of pulmonary thrombosis.

Pitfalls and tips for lumenless lead extraction inserted deep within the ventricular septum.

Key Clinical Message: This case highlights the pitfalls and provides tips for the extraction of deeply implanted lumenless leads, and encourages careful lead selection in the current era of widespread left bundle branch area pacing. Abstract: The extraction of cardiovascular implantable electronic device leads is sometimes complicated. We describe a case with difficult but successful extraction of SelectSecure, a lumenless permanent pacemaker lead, implanted deep in the ventricular septum, highlighting its pitfalls and tips in the current era of left bundle branch area pacing.

The relationship between neurological worsening and lesion patterns in patients with acute middle cerebral artery stenosis.

BACKGROUND: Intracranial atherosclerotic disease is one of the most common causes of ischemic stroke especially in Asians, Hispanics and blacks. Although middle cerebral artery (MCA) stenosis is increasingly being recognized with the advent of magnetic resonance angiography (MRA) or transcranial Doppler ultrasonography, few studies have focused on acute neurological worsening (NW) in patients with MCA stenosis. We investigated the relationship between NW and lesion patterns detected by diffusion-weighted imaging (DWI). METHODS: We studied 44 consecutive patients out of a total of 2,863 consecutive patients who had symptomatic lesions in the territory of the MCA and in whom MRA and/or conventional angiography showed isolated MCA stenosis ≥50% in the MCA trunk. Acute DWI lesion patterns were classified as follows: (1) pial artery territory infarcts (PAI); (2) small cortical and/or subcortical infarcts (SCS); (3) deep penetrating artery territory infarcts (DPI); (4) cortical border zone infarcts (CBZ), and (5) internal border zone infarcts (IBZ). NW was defined as worsening by ≥2 points on the National Institutes of Health Stroke Scale (NIHSS) during the first 7 days. Functional outcome was assessed by the modified Rankin Scale (mRS) at 3 months after stroke onset. Poor outcome was defined as ≥3 on the mRS. The severity of MCA stenosis on MRA was further categorized as 50-75% (moderate) and >75% or focal signal loss with the presence of distal MCA signal (severe). RESULTS: There were 14 patients (31.8%) who showed NW and 16 patients (36.3%) who showed poor outcomes. Nine of the 14 patients with NW showed poor outcomes (64.2%). The most frequent lesions in the present study were SCS (n = 16, 36.3%), followed by IBZ (n = 12, 27.2%) and DPI (n = 11, 25.0%). Prevalence of IBZ was significantly higher in the group with NW compared to that without NW (p = 0.0081), while the prevalence of SCS, DPI, PAI and CBZ did not differ between the two groups. Logistic regression analysis showed significantly high age- and sex-adjusted odds ratios (ORs) for NW only for IBZ (OR 10.9, p = 0.0051). The degree of stenosis did not correlate with NW and lesion patterns. CONCLUSIONS: Only IBZ among various lesion patterns correlated strongly with NW. IBZ are considered to be more associated with hemodynamic compromise, while embolic pathogeneses contribute more to CBZ or SCS. Early interventional medical treatments such as thrombolytic or anti-platelet therapy or stenting should be considered in cases of IBZ in MCA stenosis.

Speech disturbance at stroke onset is correlated with stroke early mortality.

BACKGROUND: Speech disturbance is a common symptom of stroke and is important as a prompt identifier of the event. The frequency of the symptom among each stroke subtype, differences between patients with and without speech disturbance and its correlation to early mortality remain unclear. METHODS: The Kyoto prefecture of Japan has established a registry to enroll new stroke patients in cooperation with the Kyoto Medical Association and its affiliated hospitals. It is named the Kyoto Stroke Registry (KSR). We confirmed the existence or absence of speech disturbance in 1693 stroke patients registered to the KSR and investigated associations between speech disturbance and other characteristics. RESULTS: Speech disturbance was observed in 52.6% of cerebral infarction (CI), 47.5% of cerebral hemorrhage (CH), and 8.0% of subarachnoid hemorrhage (SAH) cases. Characteristics showing statistically significant differences between patients with and without speech disturbance and patients were age, blood pressure, history of hypertension, arrhythmia and diabetes mellitus, habit of tobacco and alcohol, and paresis. Mortality rates of patients with/without speech disturbance were 5.2%/1.2% for CI, 12.5% /4.1% for CH, and 62.5%/ 9.0% for SAH. Adjusted hazard ratios were 2.63 (1.14-6.13, p = 0.024) in CI, 4.15 (1.41-12.23, p = 0.010) in CH, and 20.46 (4.40-95.07, p < 0.001) in SAH). CONCLUSION: Speech disturbance was frequently observed in stroke patients at the onset and therefore could be useful to identify the problem at the earliest stage. Hazard ratio for death was higher in stroke patients with speech disturbance than patients without. Speech disturbance is a prompt predictor of stroke early mortality.Hiromi Nakano, Yoshiyuki Watanabe, Tatsuyuki Sekimoto, Kouichiro Shimizu, Akihiko Nishizawa, Atsushi Okumura and Masahiro Makino contributed equally to this work.

Vomiting should be a prompt predictor of stroke outcome.

BACKGROUND: To predict the outcome of stroke at an acute stage is important but still difficult. Vomiting is one of the commonest symptoms in stroke patients. The aim of this study is threefold: first, to examine the percentage of vomiting in each of the three major categories of strokes; second, to investigate the association between vomiting and other characteristics and third, to determine the correlation between vomiting and mortality. METHODS: We investigated the existence or absence of vomiting in stroke patients in the Kyoto prefecture cohort. We compared the characteristics of patients with and without vomiting. We calculated the HR for death in both types of patients, adjusted for age, sex, blood pressure, arrhythmia, tobacco and alcohol use and paresis. RESULTS: Of the 1968 confirmed stroke patients, 1349 (68.5%) had cerebral infarction (CI), 459 (23.3%) had cerebral haemorrhage (CH) and 152 (7.7%) had subarachnoid haemorrhage (SAH). Vomiting was seen in 14.5% of all stroke patients. When subdivided according to stroke type, vomiting was observed in 8.7% of CI, 23.7% of CH and 36.8% of SAH cases. HR for death and 95% CI were 5.06 and 3.26 to 7.84 (p<0.001) when all stroke patients were considered, 5.27 and 2.56 to 10.83 (p<0.001) in CI, 2.82 and 1.33 to 5.99 (p=0.007) in CH and 5.07 and 1.87 to 13.76 (p=0.001) in SAH. CONCLUSIONS: Compared with patients without vomiting, the risk of death was significantly higher in patients with vomiting at the onset of stroke. Vomiting should be an early predictor of the outcome.

A Case of Cardiogenic Stroke With a Novel LMNA Variant (c. 1135C>A; p.Leu379Ile).

Laminopathy is muscular dystrophy caused by an LMNA gene mutation. It is characterized by cardiac disease such as atrial fibrillation. We report a case of laminopathy in a 49-year-old woman who presented with cardiogenic stroke. She had experienced weakness in her limb-girdle muscles since childhood, atrial fibrillation, cardiomyopathy, and mild contracture of the ankle joints, and had a familial history of heart disease. Gene analysis identified a novel heterozygous variant, c. 1135C>A (p.Leu379Ile), in the LMNA gene. Laminopathy can be an underlying disease in ischemic stroke, especially in young to middle age.

Prediction model for the new onset of atrial fibrillation combining features of 24-hour Holter electrocardiogram with 12-lead electrocardiogram.

Background: Several factors that predict new-onset atrial fibrillation (AF) have been investigated using the 24-hour Holter electrocardiogram (ECG) and 12-lead ECG; however, these have been based on each test independently. The aim of this study was to combine findings from the two tests to create a comprehensive, easy-to-use score and to examine its validity. Methods and Results: A total of 502 patients underwent 24-hour Holter ECG and 12-lead ECG were followed up for 6.2 ± 3.5 years, and 66 patients developed new-onset AF. Multivariate Cox regression analyses revealed that total number of supraventricular extrasystoles (SVEs) ≥ 100 beats/day and SVE's longest run ≥ 3 beats on 24-hour Holter ECG and PR interval ≥ 185 ms, amplitude ratio of P wave (aVR/V1) < 1.0 and amplitude of RV5 + SV1 ≥ 2.2 mV on 12-lead ECG were significant independent predictors for developing AF (all p < 0.01). Using these cut-off points, the PAAFS (acronym for risk factors) score was constructed by adding one point for each parameter if the patient met each of the criteria. The area under the curve (AUC) of the PAAFS score was 0.80, compared to the AUCs of 24-hour Holter ECG-only factors (0.73) and 12-lead ECG-only factors (0.72), indicating an improvement in score. The annual incidence of AF for each PAAFS score were 0.0%, 0.2%, 0.7%, 1.9%, 5.6%, and 11.1%/year for scores 0 to 5, respectively. Conclusion: The PAAFS score, which combines findings from 24-hour Holter ECG and 12-lead ECG, was superior to 24-hour Holter ECG and 12-lead ECG alone in predictive accuracy for new-onset AF.

Late onset of coronary ostial stenosis following surgical aortic valve replacement in a patient with anomalous origin of the right coronary artery.

Surgical aortic valve replacement (SAVR) in patients with anomalous origination of a coronary artery from the opposite sinus is associated with risk for myocardial ischemia during the perioperative period. [1] However, iatrogenic coronary ostial stenosis (ICOS) generally occurs within the first 6 months after SAVR. We present an unusual case of a 74-year-old man with anomalous origination of the right coronary artery from the left coronary sinus, who developed effort angina due to ICOS 19 months following SAVR and ascending aorta replacement. Angiography and computed tomography were utilized to perform a comparison before and after the procedure. From the results, it was evident that the flattened mild stenosis preoperatively was caused by anomalous origination of a coronary artery from the opposite sinus and progressed to severe stenosis by ICOS after the procedure. The patient was successfully treated with percutaneous coronary intervention. .

Persistent microscopic active inflammatory lesions in the central nervous system of a patient with neuromyelitis optica treated with oral prednisolone for more than 40 years.

We have reported an autopsy case of neuromyelitis optica (NMO) that exhibited persisting active inflammatory lesions in the central nervous system (CNS) despite a 45-year-long treatment with oral corticosteroids. To our knowledge, our case had received the longest course of maintenance treatment. This case study suggests that the current treatment of NMO with immunosuppressive agents may offer a good prospect for improving life expectancy. On the other hand, it also suggest that microscopic active lesions which were clinically silent and difficult to detect by neurological examination or MRI studies may persist in the CNS in patients with NMO, despite prolonged and continuous immunosuppressive treatment.

[Case of baroreflex failure after bilateral revascularization of the cervical carotid artery].

We report a patient of baroreflex failure two years after bilateral cervical internal carotid artery (ICA) revascularization. A 76-year-old hypertensive man was admitted to our hospital after suffering multiple syncopal events for the past 2 years prior to admission. He received bilateral surgical and endovascular revascularization for stenotic lesions of the ICA orifices 4 years ago. Intervention consisted of carotid endarterectomy and carotid stenting for the right and left ICAs, respectively. Head T2-weighted magnetic resonance images demonstrated multiple high intensity signals in the basal ganglia bilaterally. To investigate his autonomic function, head-up tilt test, 24-hour ambulatory blood pressure measurements, and Valsalva's maneuver were performed. The patient demonstrated marked orthostatic hypotension without increment of heart rate, increased variability of blood pressure and abnormal hypertensive surges in a single 24 hour period, and abnormal response of heart rate during Valsalva's maneuver. These findings were indicative of impaired baroreflex-mediated vasomotor and heart rate control. Other examinations involving hematological analysis, cardiac function assessment, and scintigraphy for pheochromocytoma were within normal limits except for a marked increase in plasma norepinephrine during hypertensive surge. We therefore considered that he had baroreflex failure resulting from previous bilateral ICA orifice revascularization. The patient was given diazepam during hospitalization. After then, his blood pressure stabilized somewhat and syncopal attacks were controlled. Our case suggests that patients, who undergo bilateral ICA orifice revascularization and present with syncopal attacks, should be considered baroreflex failure even if the patient is post-operative several years. Long-term follow up should therefore be necessitated in patients who undergo bilateral carotid revascularization.

Ischemic stroke with vertebrobasilar artery dissection extended to posterior cerebral artery.

A 45-year-old woman was admitted with headache following sudden disturbance of consciousness that occurred two hours beforehand. A neurological examination identified disorientation, left homonymous hemianopia, left hemiplegia, and sensory disturbance in the left limbs. Brain MRI DWI showed acute infarcts in the right occipital lobe and bilateral thalami, and MRA poorly depicted right vertebral artery and right posterior cerebral artery. Anticoagulation was started to treat acute ischemic stroke, but her consciousness level deteriorated at 12 hours after onset. MRI revealed a double lumen in the basilar artery, indicating a diagnosis of vertebrobasilar artery dissection. Serial MRA findings showed that images of the basilar artery and posterior cerebral artery changed over time, suggesting vertebral artery dissection extension to the posterior cerebral artery.

Distinct molecular mechanisms of HTRA1 mutants in manifesting heterozygotes with CARASIL.

OBJECTIVE: To elucidate the molecular mechanism of mutant HTRA1-dependent cerebral small vessel disease in heterozygous individuals. METHODS: We recruited 113 unrelated index patients with clinically diagnosed cerebral small vessel disease. The coding sequences of the HTRA1 gene were analyzed. We evaluated HTRA1 protease activities using casein assays and oligomeric HTRA1 formation using gel filtration chromatography. RESULTS: We found 4 heterozygous missense mutations in the HTRA1 gene (p.G283E, p.P285L, p.R302Q, and p.T319I) in 6 patients from 113 unrelated index patients and in 2 siblings in 2 unrelated families with p.R302Q. The mean age at cognitive impairment onset was 51.1 years. Spondylosis deformans was observed in all cases, whereas alopecia was observed in 3 cases; an autopsied case with p.G283E showed arteriopathy in their cerebral small arteries. These mutant HTRA1s showed markedly decreased protease activities and inhibited wild-type HTRA1 activity, whereas 2 of 3 mutant HTRA1s reported in cerebral autosomal-recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) (A252T and V297M) did not inhibit wild-type HTRA1 activity. Wild-type HTRA1 forms trimers; however, G283E and T319I HTRA1, observed in manifesting heterozygotes, did not form trimers. P285L and R302Q HTRA1s formed trimers, but their mutations were located in domains that are important for trimer-associated HTRA1 activation; in contrast, A252T and V297M HTRA1s, which have been observed in CARASIL, also formed trimers but had mutations outside the domains important for trimer-associated HTRA1 activation. CONCLUSIONS: The mutant HTRA1s observed in manifesting heterozygotes might result in an impaired HTRA1 activation cascade of HTRA1 or be unable to form stable trimers.

Effect of intravenous gadolinium-DTPA on diffusion-weighted images: evaluation of normal brain and infarcts.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) is usually done before administration of intravenous contrast agents. Repetition of DWI is occasionally necessary after administration, but the effects of contrast material on DWI and apparent diffusion coefficient (ADC) values have not yet been fully examined. The present study assesses whether administration of gadolinium-based contrast material significantly affects DWI and ADC values. METHODS: We examined DWI data from 39 patients (mean age, 67.9 years; range, 34 to 87 years) who were evaluated with a stroke protocol at our institute. All patients were scanned at the acute or subacute stages of infarct from 3 hours to 5 days after symptom onset. We obtained DWI images using single-shot echo-planar imaging with a b value of 1000 s/mm2. Patients were injected with 0.1 mmol gadopentetate dimeglumine per 1 kg body weight. We examined the signal-to-noise ratio of the normal brain and the infarct and evaluated the contrast-to-noise ratio of each lesion. In addition, we compared the ADC values calculated from the DWI images before and after administration of contrast. The statistical significance of differences between precontrast and postcontrast administration was determined by use of a paired t test. RESULTS: The signal-to-noise and contrast-to-noise ratios of the DW images were not significantly different before and after administration of contrast agent. The ADC values were slightly lower after administration of contrast agent for both normal brain (P=0.0011) and infarcts (P=0.038). The estimated differences in the ADC values were approximately 1.3% and 3.5% for normal brain and infarcts, respectively. CONCLUSIONS: The lack of a significant difference between the signal-to-noise and contrast-to-noise ratios of DW images before and after administration of contrast agent indicates the feasibility of postcontrast DWI.

Fiber-tracking method reveals sensorimotor pathway involvement in stroke patients.

BACKGROUND AND PURPOSE: We tested the feasibility of a new MRI technique that provides visualization of the sensorimotor tracts in vivo in a group of stroke victims. SUMMARY OF REPORT: Fourteen patients with small infarctions involving the white matter of the supratentorial brain were evaluated. Sensorimotor tracts on the lesional and contralesional sides were successfully depicted in all cases. The position of the sensorimotor tracts relative to the infarct was in good agreement with clinical symptoms. The overall sensitivity and specificity for sensorimotor tract involvement were 100% and 77%, respectively. CONCLUSIONS: Our proposed fiber-tracking method was shown to be a clinically feasible technique that correlates well with clinical symptoms.

Voltammetric study of the transfer of polyammonium ions at nitrobenzene / water interface.

The transfer of polyammonium ions, poly[(dimethylimino)-1,6-hexanediyl] (n = 140, n being the degree of polymerization) ion and poly[(dimethylimino)(2-oxo-1,2-ethanediyl)imino-alpha,omega-alkanediylimino(1-oxo-1,2-ethanediyl)(dimethylimino)-alpha',omega'-alkanediyl] ([-N+ (CH3)2CH2CONH(CH2)x NHCOCH2N+ (CH3)2(CH2)y-]n, x = 2, 3, 4, or 6, y = 3 or 6, and n = 30-130) ions, at a polarizable nitrobenzene / water interface has been studied by normal pulse voltammetry and cyclic voltammetry. Despite the polydispersity of the preparations, by normal pulse voltammetry, an S-shaped current-potential curve with a well-defined limiting current, and, by cyclic voltammetry, a pair of anodic and cathodic peak currents due to the transfer of polyammonium ions across the interface were observed within the potential window. The voltammetric behavior is described. Also, the effect of ion-pair formation of the polyammonium ions with supporting electrolyte anions in nitrobenzene- and water-phases on the half-wave or midpoint potential of the ion-transfer, and the relation between the structure of the polyammonium ions and the transfer potentials are discussed.

Fermentative l-(+)-lactic acid production from non-sterilized rice washing drainage containing rice bran by a newly isolated lactic acid bacteria without any additions of nutrients.

A newly isolated lactic acid producing bacterium Lactobacillus rhamnosus M-23, from a rice washing drainage storage tank was found to produce l-(+)-lactic acid from a non-sterilized mixture of rice washing drainage and rice bran without any additions of nutrients under the simultaneous saccharification and fermentation (SSF) process. The maximum lactate yield attained was 59 g/l with a productivity of 1.23 g/l/h and a product optical purity of 95% corresponding to a conversion of 0.85 g of lactic acid per gram of sugar equivalent.

Prediction of dysphagia severity: an investigation of the dysphagia patterns in patients with lateral medullary infarction.

OBJECTIVE: In order to identify the factors that influence the swallowing function in patients who develop Wallenberg syndrome (WS) following lateral medullary infarction (LMI), we examined various patient characteristics, including the passage pattern abnormality (PPA) of a bolus through the upper esophageal sphincter (UES). METHODS: Fifty-four pure LMI patients with dysphagia participated in this study. PPA, defined as the failure of bolus passage through the UES corresponding to the intact side of the medulla, was identified during videofluorographic swallowing evaluations of each patient. On brain magnetic resonance imaging, the subjects' lesions were classified vertically into three levels and horizontally into seven levels in relation to the involvement of the ambiguous and/or solitary nuclei. Logistic regression analyses were performed for age, sex, PPA and the vertical and horizontal sites of the lesions. RESULTS: In terms of severity, 15 subjects were categorized as having mild dysphagia, 26 subjects were categorized as having moderate dysphagia and 13 were categorized as having severe dysphagia. Subjects with cephalic lesions, greater vertical spread of the lesion and PPA were more likely to have severe dysphagia. PPA and a greater vertical spread of the lesion were related to the severity of the functional outcome (p<0.01). The horizontal extent of the lesion was not strongly related to the prognosis. CONCLUSION: The presence of PPA in LMI patients is suggestive of abnormalities in the swallowing pattern and, in turn, damage to the medullary central pattern generator. The presence of PPA and a greater vertical spread of the lesion can be useful predictors of severe dysphagia.