Performance and outcomes of the SAPIEN 3 Ultra RESILIA transcatheter heart valve in the OCEAN-TAVI registry.

BACKGROUND: Data on the performance of the latest-generation SAPIEN 3 Ultra RESILIA (S3UR) valve in patients who undergo transcatheter aortic valve replacement (TAVR) are scarce. AIMS: We aimed to assess the clinical outcomes, including valve performance, of the S3UR. METHODS: Registry data of 618 consecutive patients with S3UR and of a historical pooled cohort of 8,750 patients who had a SAPIEN 3 (S3) valve and underwent TAVR were collected. The clinical outcomes and haemodynamics, including patient-prosthesis mismatch (PPM), were compared between the 2 groups and in a propensity-matched cohort. RESULTS: The incidence of in-hospital death, vascular complications, and new pacemaker implantation was similar between the S3UR and the S3 groups (allp>0.05). However, both groups showed significant differences in the degrees of paravalvular leakage (PVL) (none-trivial: 87.0% vs 78.5%, mild: 12.5% vs 20.5%, ≥moderate: 0.5% vs 1.1%; p<0.001) and the incidence of PPM (none: 94.3% vs 85.1%, moderate: 5.2% vs 12.8%, severe: 0.5% vs 2.0%; p<0.001). The prevalence of a mean pressure gradient ≥20 mmHg was significantly lower in the S3UR group (1.6% vs 6.2%; p<0.001). Better haemodynamics were observed with the smaller 20 mm and 23 mm S3UR valves. The results were consistent in a matched cohort of patients with S3UR and with S3 (n=618 patients/group). CONCLUSIONS: The S3UR has equivalent procedural complications to the S3 but with lower rates of PVL and significantly better valve performance. The better valve performance of the S3UR, particularly in smaller valve sizes, overcomes the remaining issue of balloon-expandable valves after TAVR.

Rationale and design of Non-antithrombotic Therapy After Transcatheter Aortic Valve Implantation (NAPT) Trial.

BACKGROUND: Despite the wide implementation of transcatheter aortic valve implantation (TAVI), the optimal antithrombotic therapy after TAVI has not been established yet. Owing to the accumulating evidence supporting the efficacy and safety of single antiplatelet therapy (SAPT) over dual antiplatelet therapy, the latest guideline recommends life-long SAPT. However, there is scarce evidence supporting SAPT compared with non-antithrombotic therapy. Given the vulnerability of patients undergoing TAVI in terms of high bleeding risk, the benefit of SAPT may be canceled out by its potential increased bleeding risk. STUDY DESIGN AND OBJECTIVES: Non-antithrombotic Therapy After Transcatheter Aortic Valve Implantation (NAPT) Trial is a prospective, randomized controlled, open-label blinded endpoint multicenter trial conducted in Japan, testing the non-inferiority of non-antithrombotic therapy compared with aspirin monotherapy in patients who underwent TAVI and had no indications for long-term oral anticoagulation therapy (OAC). Patients who successfully underwent trans-femoral TAVI for severe aortic stenosis with either balloon-expandable or self-expandable valves are eligible for inclusion. Key exclusion criteria are (i) occurrence of perioperative complications (ii) indications of taking antithrombotic drugs for other reasons; (iii) eGFR <30 ml/min/1.73 m2 or hemodialysis or peritoneal dialysis. A total of 360 patients will be randomized (1:1) to aspirin monotherapy vs. non-antithrombotic therapy. The primary outcome is a composite of all-cause mortality, myocardial infarction, stroke, and bleeding. All bleeding events based on the Valve Academic Research Consortium 3 are included as a component of the primary outcome. CONCLUSION: The NAPT trial will determine the non-inferiority of a non-antithrombotic therapy compared with aspirin monotherapy after TAVI.

Edoxaban vs. Vitamin K Antagonist for Atrial Fibrillation After Transcatheter Aortic Valve Replacement in Japanese Patients　- A Subanalysis of the ENVISAGE-TAVI AF Trial.

BACKGROUND: Japanese patients undergoing transcatheter aortic valve replacement (TAVR) are often female and have a small body size, potentially impacting bleeding risk with antithrombotic therapy. Outcomes of direct oral anticoagulant use in these patients with atrial fibrillation (AF) need to be clarified.Methods and Results: This prespecified analysis included Japanese patients from ENVISAGE-TAVI AF, a prospective, randomized, open-label, adjudicator-masked trial that compared treatment with edoxaban and vitamin K antagonists (VKAs) in patients with AF after TAVR. The primary efficacy and safety outcomes were net adverse clinical events (NACE; composite of all-cause death, myocardial infarction, ischemic stroke, systemic embolic event, valve thrombosis, and International Society on Thrombosis and Haemostasis [ISTH]-defined major bleeding) and ISTH-defined major bleeding, respectively. Intention-to-treat (ITT) and on-treatment analyses were performed. Overall, 159 Japanese patients were enrolled (edoxaban group: 82, VKA group: 77) and followed for on average 483 days. Mean patient age was 83.8 years; 52.2% were female. In the ITT analysis, NACE rates were 10.9%/year with edoxaban and 12.5%/year with VKA (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.38-1.90); major bleeding occurred in 8.9%/year and 7.3%/year, respectively (HR, 1.17; 95% CI, 0.45-3.05). In edoxaban- and VKA-treated patients, rates of ischemic stroke were 1.8%/year and 1.0%/year, respectively; fatal bleeding rates were 0.9%/year and 2.0 %/year. On-treatment results were similar to ITT. CONCLUSIONS: In Japanese patients with AF after successful TAVR, edoxaban and VKA treatment have similar safety and efficacy profiles.

Revisiting the Aortic Valve Calcium Score in Evaluating the Severity of Aortic Stenosis in Japanese Patients　- A Single-Center Study.

Background: In patients with aortic stenosis (AS), measurement of aortic valve calcification (AVC) using computed tomography (CT) is recommended in cases where echocardiographic measurements are inconclusive. However, sex-specific AVC thresholds proposed in the guidelines for predicting severe AS (women: 1,200 arbitrary units [AU]; men: 2,000 AU) are based on studies from Western countries. Methods and Results: We retrospectively included 512 Japanese patients with at least moderate AS who underwent transthoracic echocardiography and CT. AVC was quantified using the Agatston method. AVC was positively correlated with peak aortic jet velocity and mean transvalvular gradient (mPG), and negatively correlated with aortic valve area (AVA) and the AVA index (AVAi). In 257 patients with concordant AS grading (152 severe AS [AVAi ≤0.6 cm2/m2, mPG ≥40 mmHg], 105 moderate AS [AVAi >0.6 cm2/m2, mPG <40 mmHg]), receiver operating characteristic curve analysis of AVC predicting severe AS yielded an area under the curve of 0.91 (95% confidence interval [CI] 0.87-0.95; P<0.001) in women and 0.86 (95% CI 0.75-0.98; P<0.001) in men. The optimal thresholds (women: 1,379 AU; men: 1,802 AU) were close to those proposed in the guidelines. The diagnostic accuracy of the thresholds in the guidelines was similar to that of the optimal thresholds. Conclusions: The sex-specific AVC thresholds proposed in international guidelines can be applied to Japanese AS patients, yielding similar diagnostic accuracy as the optimal cut-off derived from the study patients.

Peripartum myocardial infarction associated with coronary spasm and acquired protein S deficiency: A case report.

RATIONALE: Coronary angiography (CAG) findings of acute myocardial infarction (AMI) in pregnant women are characterized by a high incidence of normal coronary arteries. This is the first report of AMI with normal coronary arteries during pregnancy, showing coronary spasm and pregnancy-related acquired protein S (PS) deficiency. PATIENT CONCERNS: A 30-year-old Japanese woman was admitted to an emergency department. One hour before admission, she developed sudden onset of precordial discomfort, back pain, and dyspnea. She was a primigravida at 39 weeks' gestation and had no abnormality in the pregnancy thus far. She had no history of heart disease, diabetes, hypertension, dyslipidemia, deep vein thrombosis (DVT), smoking, or oral contraceptive use and no family history of ischemic heart disease, hemostasis disorder, or DVT. She did not take any medication. DIAGNOSIS: Electrocardiography showed ST-segment elevations in leads II, III, aVF, and V2-V6. Heart-type fatty acid-binding protein was positive. Echocardiography showed hypokinesis of the anterior interventricular septum and inferior wall. Continuous intravenous infusion of isosorbide dinitrate was initiated. Coronary computed tomography angiography revealed diffuse narrowing of the apical segment of the left anterior descending coronary artery. Three hours after admission, troponin T became positive, and the following enzymes reached their peak levels: creatine kinase (CK), 1,886 U/L; CK-muscle/brain, 130 U/L. She was diagnosed with transmural AMI due to severe coronary spasm and administered benidipine hydrochloride. Five hours after admission, premature membrane rupture occurred. INTERVENTIONS: Emergency cesarean section was performed. There were no anesthetic or obstetrical complications during the operation. On postpartum day 1, the free PS antigen level was low (29%). On postpartum day 18, she was discharged with no reduction in physical performance. OUTCOMES: Four months after the infarction, CAG showed normal coronary arteries. Acetylcholine provocation test showed diffuse vasospasm in the coronary artery. She was advised that her next pregnancy should be carefully planned. Two years after delivery, free PS antigen level was within normal range, at 86%. She had not experienced recurrence of angina during the 2-year period. Her child was also developing normally. LESSONS: In addition to coronary spasm, pregnancy-related acquired PS deficiency may be involved in AMI etiology.

Clinical Utility of Intraoperative Motor-Evoked Potential Monitoring to Prevent Postoperative Spinal Cord Injury in Thoracic and Thoracoabdominal Aneurysm Repair: An Audit of the Japanese Association of Spinal Cord Protection in Aortic Surgery Database.

BACKGROUND: Spinal cord ischemic injury is the most devastating sequela of descending and thoracoabdominal aortic surgery. Motor-evoked potentials (MEPs) have been used to intraoperatively assess motor tract function, but it remains unclear whether MEP monitoring can decrease the incidence of postoperative motor deficits. Therefore, we reviewed multicenter medical records of patients who had undergone descending and thoracoabdominal aortic repair (both open surgery and endovascular repair) to assess the association of MEP monitoring with postoperative motor deficits. METHODS: Patients included in the study underwent descending or thoracoabdominal aortic repair at 12 hospitals belonging to the Japanese Association of Spinal Cord Protection in Aortic Surgery between 2000 and 2013. Using multivariable mixed-effects logistic regression analysis, we investigated whether intraoperative MEP monitoring was associated with postoperative motor deficits at discharge after open and endovascular aortic repair. RESULTS: We reviewed data from 1214 patients (open surgery, 601 [49.5%]; endovascular repair, 613 [50.5%]). MEP monitoring was performed in 631 patients and not performed in the remaining 583 patients. Postoperative motor deficits were observed in 75 (6.2%) patients at discharge. Multivariable logistic regression analysis revealed that postoperative motor deficits at discharge did not have a significant association with MEP monitoring (adjusted odds ratio [OR], 1.13; 95% confidence interval [CI], 0.69-1.88; P = .624), but with other factors: history of neural deficits (adjusted OR, 6.08; 95% CI, 3.10-11.91; P < .001), spinal drainage (adjusted OR, 2.14; 95% CI, 1.32-3.47; P = .002), and endovascular procedure (adjusted OR, 0.45; 95% CI, 0.27-0.76; P = .003). The sensitivity and specificity of MEP <25% of control value for motor deficits at discharge were 37.8% (95% CI, 26.5%-49.5%) and 95.5% (95% CI, 94.7%-96.4%), respectively. CONCLUSIONS: MEP monitoring was not significantly associated with motor deficits at discharge.

Desflurane inhalation before ischemia increases ischemia-reperfusion-induced vascular leakage in isolated rabbit lungs.

BACKGROUND: Isoflurane and sevoflurane protect lungs with ischemia-reperfusion (IR) injury. We examined the influence of desflurane on IR lung injury using isolated rabbit lungs perfused with a physiological salt solution. METHODS: The isolated lungs were divided into three groups: IR, desflurane-treated ischemia-reperfusion (DES-IR), and ventilation/perfusion-continued control (Cont) groups (n = 6 per group). In the DES-IR group, inhalation of desflurane at 1 minimum alveolar concentration (MAC) was conducted in a stable 30-min phase. In the IR and DES-IR groups, ventilation/perfusion was stopped for 75 min after the stable phase. Subsequently, they were resumed. Each lung was placed on a balance, and weighed. Weight changes were measured serially throughout this experiment. The coefficient of filtration (Kfc) was determined immediately before ischemia and 60 min after reperfusion. Furthermore, bronchoalveolar lavage fluid (BALF) was collected from the right bronchus at the completion of the experiment. After the completion of the experiment, the left lung was dried, and the lung wet-to-dry weight ratio (W/D) was calculated. RESULTS: The Kfc values at 60 min after perfusion were 0.40 ± 0.13 ml/min/mmHg/100 g in the DES-IR group, 0.26 ± 0.07 ml/min/mmHg/100 g in the IR group, and 0.22 ± 0.08 (mean ± SD) ml/mmHg/100 g in the Cont group. In the DES-IR group, the Kfc at 60 min after the start of reperfusion was significantly higher than in the other groups. In the DES-IR group, W/D was significantly higher than in the Cont group. In the DES-IR group, the BALF concentrations of nitric oxide metabolites were significantly higher than in the other groups. In the DES-IR group, the total amount of vascular endothelial growth factor in BALF was significantly higher than in the Cont group. CONCLUSIONS: The pre-inhalation of desflurane at 1 MAC exacerbates pulmonary IR injury in isolated/perfused rabbit lungs.

Phosphoenolpyruvate administration protects ischemia-reperfusion injury in isolated rabbit lungs.

Phosphoenolpyruvate (PEP) is an intermediate metabolite of the glycolytic pathway and an in vivo high-energy phosphate compound. We have examined the protective effects of PEP on ischemia-reperfusion lung injury in isolated rabbits lungs perfused with a physiological salt solution. The lungs were divided into three treatment groups: (1) ischemia-reperfusion (IR), (2) ischemia-reperfusion with PEP treatment (PEP-IR), in which 1 mM PEP was pre-administered into the perfusate during the stable period, and (3) ventilation-perfusion continued without interruption (Cont). In the IR and PEP-IR groups, ventilation-perfusion was discontinued for about 60 min after a 30-min stable period and then restarted. The capillary filtration coefficients (K fc) and pyruvate concentration in the perfusate were determined immediately before ischemia and 30 and 60 min after reperfusion. The left lungs were dried at the end of the experiment to calculate the tissue wet-to-dry weight ratio (W/D). The K fc values after reperfusion were significantly higher in the IR group than in the other two groups. Pyruvate concentrations were significantly higher at three time-points in the PEP-IR group than in the other two groups. The W/D was significantly higher in the IR group than in the other two groups. Based on these results, we conclude that the administration of PEP prior to lung ischemia alleviates lung ischemia-reperfusion injury.

[Multiple cerebral infarction by air embolism associated with remarkable low BIS value during lung segmentectomy with video assisted thoracic surgery (VATS) technique: a case report].

A 64-year-old woman (151 cm, 43 kg) with well controlled hypertension was diagnosed as having right lung cancer at S8 segment. She underwent right S8 segmentectomy by video assisted thoracic surgery (VATS) under general anesthesia combined with epidural anesthesia. Her vital signs were stable and BIS value was around 45 before the surgeon injected the air using a syringe with a 22 G needle to confirm the lesion resected. After the injection of air, her systolic blood pressure rapidly increased from 120 to 170 mmHg and the BIS value suddenly decreased to 5. Blood propofol concentration was reduced from 3 microg x ml(-1) to 2 microg x ml(-1) in the target-controlled infusion technique, and thereby the BIS value increased slowly. She did not wake up nor maintain sufficient spontaneous breathing even 2 hours after the discontinuation of opioids, and was transferred to ICU with tracheal intubation. In ICU, she showed clonic convulsions. Urgent CT and MRI confirmed cerebral air embolism. Her vital signs were too unstable to choose hyperbaric oxygen therapy as her first treatment. Her consciousness was recovered and her trachea was extubated on 11th postoperative day. She was discharged with left hemiparalysis from hospital.

Effect of intraoperative acetated Ringer's solution with 1% glucose on glucose and protein metabolism.

PURPOSE: To investigate the effects of the intraoperative administration of Ringer's solution with 1% glucose on the metabolism of glucose, lipid and muscle protein during surgery. METHODS: Thirty-one adult patients, American Society of Anesthesiologists physical status I or II, undergoing elective otorhinolaryngeal, head and neck surgeries were randomly assigned to one of two patient groups: those receiving acetated Ringer's solution with 1% glucose (Group G) or those receiving acetated Ringer's solution without glucose (Group R) throughout the surgical procedure. Plasma glucose was measured at anesthetic induction (T0), artery 1 h (T1), 2 h (T2), 3 h after anesthetic induction (T3) and at the end of surgery (T4). Plasma ketone bodies, insulin and 3-methylhistidine were measured at T0 and T4. RESULTS: The intravenous infusion for patients in Group G and R was 6.1 + or - 0.8 and 6.3 + or - 1.7 ml/kg/h, respectively, with Group G patients receiving a dose of 4.1 g/h glucose. Plasma glucose levels were significantly higher in Group G than in Group R patients at T1, T2, T3 and T4; however, plasma glucose remained <150 mg/dl in both groups. The plasma concentration of ketone bodies was significantly higher (P < 0.05) in Group R than in Group G patients at T4. Changes in plasma 3-methylhistidine concentration was significantly lower in Group G than in Group R patients. These results indicate that acetated Ringer's solution with 1% glucose decreased protein catabolism without hyperglycemia among the Group G patients. CONCLUSION: The infusion of a small dose of glucose (1%) during minor otorhinolaryngeal, head and neck surgeries may suppress protein catabolism without hyperglycemia and hypoglycemia.

Caudal blockade shortens the time to walking exercise in elderly patients following low back surgery.

PURPOSE: We conducted a randomized, double-blinded study to test our hypothesis that caudal blockade as preemptive analgesia for low back surgery might accelerate time to walking exercise following surgery and reduce postoperative analgesics, thereby attaining faster recovery of cognitive function. METHODS: Our study included 51 elderly patients >70 years with American Society of Anesthesiologists (ASA) physical status 1-3, who underwent lumbosacral surgery under general anesthesia. After anesthetic induction and tracheal intubation, patients in the study group (group B) were injected with simple 0.5% bupivacaine [10 ml x height (m)] as a caudal block 15 min before surgical incision, whereas patients in the control group (group C) received normal saline. After surgery, patients had access to intravenous patient-administered analgesia (IV PCA), fentanyl, for postoperative pain relief. We assessed Mini-Mental State Examination (MMSE) scores before and after the surgery, values of visual analog scale (VAS) for postoperative analgesic status, fentanyl consumption during and for 3 days after surgery, and time to begin walking exercise after surgery. RESULTS: VAS value of group B patients was significantly lower than those in group C throughout the postoperative 48-h period (p < 0.005), and group B patients began walking exercise significantly earlier than those in group C [mean +/- standard deviation (SD) 70.2 (14.3) in group C, and 61.9 (7.6) in group B; p = 0.0133]. Cognitive function level was higher in group B than in group C patients 24 h after operation. CONCLUSIONS: Caudal blockade as preemptive analgesia shortened the time to start walking exercise after surgery and accelerated recovery of postoperative cognitive function.