Reduction of thromboembolic complications during the endovascular treatment of unruptured aneurysms by employing a tailored dual antiplatelet regimen using aspirin and prasugrel.

BACKGROUND: Thromboembolic complications (TECs) are frequent during the endovascular treatment of unruptured aneurysms. To prevent TECs, dual antiplatelet therapy using aspirin and clopidogrel is recommended for the perioperative period. In patients with a poor response, clopidogrel is a risk factor for TECs. To prevent TECs, our study assessed the stratified use of prasugrel. METHODS: Patients who underwent endovascular therapy for unruptured cerebral aneurysms from April 2017 to August 2019 were enrolled in this clinical study and given premedication with aspirin and clopidogrel for 2 weeks prior to the procedure. P2Y12 reaction units (PRU) were measured using the VerifyNow assay on the day before the procedure (tailored group). In subgroups with PRU <240, the clopidogrel dose was maintained (CPG subgroup). In subgroups with PRU ≥240, clopidogrel was changed to prasugrel (PSG subgroup). We compared the occurrence of TECs with retrospective consecutive cases from January 2015 to March 2017 without PRU assessments (non-tailored group). The frequency of TECs within 30 days was assessed as the primary endpoint. RESULTS: The tailored and non-tailored groups comprised 167 and 50 patients, respectively. TECs occurred in 11 (6.6%) and 8 (16%) patients in the tailored and non-tailored groups (P=0.048), respectively. The HR for TECs was significantly reduced in the tailored group (HR 0.3, 95% CI 0.11 to 0.81); P=0.017) compared with the non-tailored group. CONCLUSION: The results suggest that tailored dual antiplatelet therapy medication with PRU significantly reduces the frequency of TECs without increasing hemorrhagic complications.

Delayed Hemiparkinsonism Associated with Kernohan's Notch in a Patient with a Ruptured Arteriovenous Malformation.

A 24-year-old female patient was admitted for a right frontal intracranial hematoma with an uncal herniation due to a ruptured arteriovenous malformation and therefore underwent emergency surgery. Neuroimaging revealed left-sided midbrain notching against the tentorium, indicating Kernohan's notch phenomenon. She denied experiencing any short-term neurological deficits but right-sided delayed hemiparkinsonism developed 18 months later. Dopamine transporter tracer uptake was severely reduced in the left striatum, suggesting nigrostriatal degeneration secondary to Kernohan's notch. Uncal herniations are potentially fatal, but surgery can save the patient's life and improve the functional outcomes. Clinicians should therefore be aware of delayed hemiparkinsonism as a rare complication of Kernohan's notch phenomenon.

Clinical Factors Associated with a Successful Catheter Ablation Outcome in Elderly Patients with Atrial Fibrillation.

Catheter ablation is currently an established treatment for symptomatic paroxysmal atrial fibrillation (AF). We focused on elderly patients with a high prevalence of AF and attempted to identify the clinical factors associated with unsuccessful ablation outcomes.Among 735 consecutive patients who underwent AF ablation procedures, 108 (14.7%, 66 men) aged ≥ 75 years were included. Of them, 80 had paroxysmal AF, and the remaining 28 non-paroxysmal AF. All patients underwent pulmonary vein (PV) isolation and occasionally additional ablation. When AF recurred, redo ablation procedures were performed if the patient so desired.The mean number of ablation procedures was 1.1 ± 0.4 times per patient. During a mean follow-up of 38.7 ± 21.7 months, sinus rhythm was maintained in 100 patients (92.6%) without any antiarrhythmic drugs, but not in the remaining 8 (7.4%). Left atrial diameter (LAD, P < 0.001), left ventricular (LV) systolic diameter (P < 0.001), LV diastolic diameter (P = 0.001), non-PV AF foci (P = 0.036), and diabetes (P = 0.045) were associated with unsuccessful ablation procedures. Multivariate logistic regression analysis revealed a large LAD and non-PV AF foci were significant independent predictors of AF recurrences, with odds ratios of 0.76 (P = 0.019) and 0.04 (P = 0.023), respectively. In a total of 124 procedures, one major (0.8%) and 11 minor (8.9%) complications occurred.In elderly AF patients, catheter ablation of AF is effective and safe. Non-PV AF foci and a large LAD were independent clinical predictors of unsuccessful AF ablation outcomes.

Prosthesis Used in Microvascular Decompressions: A Multicenter Survey in Japan Focusing on Adverse Events.

OBJECTIVE: To investigate the characteristics of materials used as prostheses for microvascular decompression surgery (MVDs) in Japan and their possible adverse events (AEs) to determine preferable materials for MVDs. METHODS: A questionnaire was sent to all members of the Japanese Society for MVDs, and answers were obtained from 59 institutions. RESULTS: Among a total of 2789 MVDs, 1088 operations for trigeminal neuralgia, 1670 for hemifacial spasm, and 31 others, including 117 reoperations, were performed between April 2011 and March 2014. Nonabsorbable material was used in 96.5% of MVDs, including polytetrafluoroethylene (PTFE) (80.5%), polyurethane (11.9%), expanded PTFE (2.1%), and silk thread (1.47%). The use of absorbable materials, including fibrin glue (87.5%), cellulose (13.5%), gelatin (4,77%), and collagen (1.76%), was reported. The major combinations were PTFE with fibrin glue (58.7%) followed by PTFE alone (7.60%). Eighty-eight AEs in 85 (3.2%) cases were reported among 2672 first operations. AEs included 51 central nervous system dysfunctions, 15 wound infections/dehiscence, and 10 others, which were presumed to be related to the intraoperative procedure. Among relatively high-, moderate-, and low-volume centers, there were no significant differences in the frequency of AEs (P = 0.077). Tissue-prosthesis adhesion and/or granuloma formation were reported in 13 cases of 117 reoperations. The incidence of adhesion-related recurrence was 11.1% of all reoperations. CONCLUSIONS: The number of AEs was quite low in this survey, and intradural use of any prosthesis reported in this paper might be justified; however, further development of easily handled and less-adhesive prosthesis materials is awaited.

Bleeding with oral anticoagulant dabigatran is highly associated with occult cancers in atrial fibrillation patients.

AIM: The aim of this study was to examine cancer and bleeding in atrial fibrillation patients administered with dabigatran. MATERIALS & METHODS: This study enrolled 509 consecutive nonvalvular atrial fibrillation patients who received dabigatran. The mean administration period was 14.8 ± 15.7 months. We investigated the prevalence and new development of cancers. Further, the relation between cancer and adverse events was evaluated. RESULTS: In the 509 patients, major bleeding occurred in 2.6% and dyspepsia in 8.4%. Further, 16.9% patients had a history of cancer and 3.9% developed new cancers. These adverse events developed in 45% patients who developed new cancers. The cancer (hazard ratio: 6.30; p = 0.003) was a significant predictor of major bleeding. CONCLUSION: Bleeding was associated with the presence of cancer.

Assessment of drug-induced proarrhythmias due to pilsicainide in patients with atrial tachyarrhythmias.

BACKGROUND: Pilsicainide, a pure Na+ channel blocker, is a popular antiarrhythmic drug for the management of atrial tachyarrhythmias (AT), in Japan. However, serious drug-induced proarrhythmias (DIPs) may unexpectedly occur. We assessed the clinical background of AT patients presenting with DIPs caused by pilsicainide. METHODS: This study retrospectively enrolled 874 consecutive patients (543 men, 63.6±15.3 years old, and 57.9±16.5 kg of body weight), who were orally administered pilsicainide for AT management. We evaluated the relationship between DIPs and serum pilsicainide concentration, renal dysfunction (estimate glomerular filtration rate, eGFR), and electrocardiogram (ECG) parameters. RESULTS: Among the patients, 154 (17.6%) had renal dysfunction (eGFR<50 mL/min), including 12 (1.4%) on hemodialysis. DIPs were present in 10 patients (1.1%): all had renal dysfunction, and one was on hemodialysis. The eGFR in DIP patients was significantly lower than that in the non-DIP patients (32.2±15.1 vs. 68.4±22.1 mL/min, p<0.001). Among the clinical factors measured, only renal dysfunction (eGFR<50 mL/min) was significantly associated with DIPs (OR 44.6; 95% CI 5.61-335.0, p<0.001). Interestingly, among the ECG parameters, the corrected QT (QTc) intervals in DIP patients were longer than those in non-DIP patients (555.8±37.6 vs. 430.7±32.6 ms, p<0.001). As pilsicainide concentration increased, both QRS and QTc intervals prolonged. The latter were improved by discontinuing pilsicainide administration, and additional treatments. CONCLUSIONS: DIPs caused by pilsicainide administration were strongly associated with renal dysfunction. Hence, confirmation of renal function would be necessary prior to and/or during the pilsicainide administration.

Concurrence of Aneurysmal Subarachnoid Hemorrhage and Stanford Type A Acute Aortic Dissection.

We report a rare case of concurrent aneurysmal subarachnoid hemorrhage (SAH) and acute aortic dissection (AAD). A 38-year-old man visited our hospital complaining of severe headache, and brain computed tomography (CT) revealed the presence of SAH. Thoracic to neck computed tomography angiography (CTA), performed in addition to brain CTA, suggested a tear in the aortic arch, and subsequent CT aortography established the diagnosis of Stanford type A AAD. The AAD in our patient, who reported no episodes of chest or back pain, was detected incidentally by thoracic to neck CTA. The imaging study has rarely been indicated for SAH except that it provides additional anatomical information in patients for whom extracranial-intracranial bypass surgery or endovascular treatment is considered. Nevertheless, our experience may highlight additional diagnostic value of thoracic to neck CTA in SAH patients.

Antifibrotic response of cardiac fibroblasts in hypertensive hearts through enhanced TIMP-1 expression by basic fibroblast growth factor.

BACKGROUND: Cardiac fibroblasts (CFs) play a pivotal role in the development of myocardial fibrosis. We previously demonstrated that direct injection of basic fibroblast growth factor (bFGF) into the hypertensive Dahl salt-sensitive (DS) rat heart prevented systolic dysfunction and left ventricular dilation effectively. However, the precise role played by bFGF in fibrotic response of CFs remains unclear. We suggested potential effects of bFGF on the fibrotic response of CFs in vitro. METHODS AND RESULTS: Histopathologic assessment of cardiac fibrosis demonstrated a marked decline in the extent of perivascular and interstitial fibrosis in bFGF-injected hypertensive DS rat hearts. CFs harvested from the hearts of noninjected DS rats demonstrated a significantly increased messenger RNA (mRNA) expression of matrix metalloproteinase (MMP)-2, MMP-9, and both collagen I and III. In contrast, bFGF treatment in the CFs induced a marked increase in tissue inhibitor of MMP (TIMP)-1 expression and a marked decline in MMP-9 activation. bFGF also induced a decline in α-smooth muscle actin and collagen I and III mRNA expression in the CFs accompanied by inhibited differentiation of CFs into myofibroblasts. Small interfering RNA targeting FGF receptor 1 confirmed a specific interference of the mRNA expression changes elicited by bFGF. In vivo examination confirmed many TIMP-1-positive CFs in perivascular spaces of bFGF-injected hearts. CONCLUSIONS: Up-regulated TIMP-1 expression and down-regulated MMP-9 activation by bFGF in CFs could prevent excessive ECM degradation and collagen deposition in perivascular spaces effectively, leading to prevention of cardiac fibrosis during hypertensive heart failure. SUMMARY: Cardiac fibroblasts (CFs) play a pivotal role in myocardial fibrosis. The precise role of CFs in fibrotic response played by growth factors remains unclear. Our results indicates that basic fibroblast growth factor could up-regulate TIMP-1 expression and down-regulate MMP-9 activation in CFs in perivascular spaces, leading to inhibited progression of cardiac fibrosis during hypertensive heart failure.

Overshoot phenomena of respiratory gas variables during exercise recovery in cardiac patients.

BACKGROUND: Transient increases (overshoot) in respiratory gas variables have been observed during exercise recovery, but their clinical significance is not clearly understood. Our group evaluated the relationship between the presence of overshoot of respiratory gas variables and the parameters obtained from cardiopulmonary exercise testing (CPX). METHODS AND RESULTS: In total, 227 patients with various cardiac diseases underwent CPX. The overshoot phenomena of O2 uptake (·VO2), ·VO2/heart rate (O2-pulse), and CO2 output (·VCO2) were analyzed by respiratory gas analysis during recovery after maximal exercise. The overshoot of ·VO2, O2-pulse, and ·VCO2 were recognized in 11 (5%), 43 (19%), and 12 (5%) patients, respectively. Compared with the patients without a ·VO2 overshoot, those with a ·VO2 overshoot had a significantly lower peak ·VO2 (12.3±3.7 vs. 17.9±6.2ml·min⁻¹·kg⁻¹, P=0.003), lower anaerobic threshold (9.4±1.7 vs. 12.4±3.3 ml·min⁻¹·kg⁻¹, P=0.001), higher ·VE-·VCO2 slope (38.0±5.2 vs. 33.2±9.6, P=0.013), and lower left ventricular ejection fraction (LVEF) (39.9±22.8 vs. 55.8±16.8%, P=0.003). Similar findings were obtained for the patients with an O2-pulse overshoot and those with a ·VCO2 overshoot. CONCLUSIONS: The overshoot phenomena of respiratory gas variables during recovery after maximal exercise are correlated with impaired cardiopulmonary function during exercise in cardiac patients.

Abnormal end-tidal PO(2) and PCO(2) at the anaerobic threshold correlate well with impaired exercise gas exchange in patients with left ventricular dysfunction.

BACKGROUND: The aim of the present study was to compare the end-tidal O(2) pressure (PETO(2)) to end-tidal CO(2) pressure (PETCO(2)) in cardiac patients during rest and during 2 states of exercise: at anaerobic threshold (AT) and at peak. The purpose was to see which metabolic state, PETO(2) or PETCO(2), best correlated with exercise limitation. METHODS AND RESULTS: Thirty-eight patients with left ventricular (LV) ejection fraction <40% underwent cardiopulmonary exercise testing (CPX). PETO(2) and PETCO(2) were measured during CPX, along with peak O(2) uptake (VO(2)), AT, slope of the increase in ventilation (VE) relative to the increase in CO(2) output (VCO(2)) (VE vs. VCO(2) slope), and the ratio of the increase in VO(2) to the increase in work rate (ΔVO(2)/ΔWR). Both PETO(2) and PETCO(2) measured at AT were best correlated with peakVO(2), AT, ΔVO(2)/ΔWR and VE vs. VCO(2) slope. PETO(2) at AT correlated with reduced peak VO(2) (r=-0.60), reduced AT (r=-0.52), reduced ΔVO(2)/ΔWR (r=-0.55) and increased VE vs. VCO(2) slope (r=0.74). PETCO(2) at AT correlated with reduced peak VO(2) (r=0.67), reduced AT (r=0.61), reduced ΔVO(2)/ΔWR (r=0.58) and increased VE vs. VCO(2) slope (r=-0.80). CONCLUSIONS: PETCO(2) and PETO(2) at AT correlated with peak VO(2), AT and ΔVO(2)/ΔWR, but best correlated with increased VE vs. VCO(2) slope. PETO(2) and PETCO(2) at AT can be used as a prime index of impaired cardiopulmonary function during exercise in patients with LV failure.

Basic fibroblast growth factor inhibits ventricular remodeling in Dahl salt-sensitive hypertensive rats.

OBJECTIVE: Basic fibroblast growth factor (bFGF) inhibits the progression of ventricular remodeling in ischemic and hypertensive heart diseases (HHDs). Recent studies have revealed that bFGF induces the transition from myofibroblasts to fibroblasts with decreased expression of alpha-smooth muscle actin (alpha-SMA). To clarify the mechanisms underlying the reduced ventricular remodeling in hypertensive heart diseases caused by bFGF, we examined the degree of interstitial fibrosis associated with alpha-smooth muscle actin expression and matrix metalloproteinase activity in hypertensive heart diseases. METHODS: Dahl salt-sensitive rats were fed with a high-salt diet from 6 to 18 weeks of age and injected with a single dose of bFGF (100 microg) into the left myocardium at 15 weeks. Others were administered PBS without bFGF. Control age-matched Dahl salt-sensitive rats were fed with a low-salt diet. RESULTS: Cardiac systolic function was well preserved and decompensation of heart failure was prevented at 18 weeks in the rats treated with bFGF at 15 weeks. The bFGF-treated rats had significantly fewer interstitial alpha-SMA-positive myofibroblasts and significantly decreased prolyl 4-hydroxylase expression. Increased matrix metalloproteinase-9 gelatinase activity correlated with the downregulation of transforming growth factor-beta1 by bFGF, suggesting that inhibited extracellular matrix deposition is associated with a decreased number of myofibroblasts induced by bFGF. CONCLUSION: bFGF can inhibit the progression of ventricular remodeling by inhibiting interstitial fibrosis and promoting angiogenesis without decreasing blood pressure in hypertensive heart disease.