Elevated INR in a COVID-19 patient after concomitant administration of favipiravir and warfarin: A case report.

WHAT IS KNOWN AND OBJECTIVE: Favipiravir is a promising treatment candidate for managing coronavirus disease 2019 (COVID-19). Warfarin has many drug interactions, but no interactions with favipiravir have been reported. CASE SUMMARY: Our patient was taking warfarin for deep vein thrombosis. The international normalized ratio (INR) was stable (1.65 to 2.0); however, it increased to 4.63 after administering favipiravir. The patient had no other factors justifying this change. WHAT IS NEW AND CONCLUSION: Favipiravir and warfarin might have previously unidentified drug interactions that elevated the INR. Therefore, INR must be closely monitored when they are concomitantly administered in COVID-19 patients.

Suturing Fenestration of the Left Subclavian Artery Orifice in Frozen Elephant Trunk Procedure.

The frozen elephant trunk (FET) procedure enables easier replacement of the entire aortic arch because it does not require reaching the distal part of the left subclavian artery (LSCA). However, it requires additional management for reconstruction of the LSCA, which is associated with bleeding events. However, the fenestrated FET technique confers a risk of endoleakage from the fenestration site. We report our unique novel technique in which the proximal side of the hybrid stent graft is cut into V-shape around the subclavian artery and sutured continuously around the orifice of the subclavian artery during aortic stump fixation.

Successful surgical treatment of cardiac metastasis from uterine leiomyosarcoma: A case report and literature review.

Uterine leiomyosarcoma is a malignant soft tissue tumor resembling uterine fibroma clinically and is difficult to diagnose preoperatively. Since metastatic cardiac tumors are very rare and asymptomatic, most cardiac metastases are detected at autopsy after death due to other diseases. A 49-year-old woman presented with menorrhagia and anemia, and a uterine tumor. Total hysterectomy was performed for the uterine tumor. Histopathological examination revealed the tumor to be a leiomyosarcoma. Postoperative computed tomography showed multiple lung metastases and a metastatic cardiac tumor. The cardiac tumor, which was located within and almost entirely occluded the right ventricle, was 49 × 26 mm. To prevent sudden death, cardiac tumorectomy was performed semi-emergently. Chemotherapy was initiated in the early postoperative period, and the patient currently maintains a complete response. Cases with lung and cardiac metastases rarely undergo surgical resection of metastatic tumors. However, emergent surgical resection of cardiac metastatic tumors should be considered to prevent sudden death.

Less Invasive Quick Open Stenting using a J Graft Open Stent for Distal Arch Aneurysms.

A new device of aortic stent graft made in Japan has been available since July 2014. Here, we describe a novel, unique surgical technique named "less invasive quick open stenting" at a rectal temperature of 28°C without any cerebral perfusion for treating distal arch aneurysms. All 12 patients were discharged from the intensive care unit within 24 hours after surgery without any complications. This technique aids in the exclusion of atherosclerotic plaques on the aortic wall and shortens the duration of circulatory arrest; moreover, it represents a very attractive option to prevent recurrent nerve injury.

Incidence of drug interaction when using proton pump inhibitor and warfarin according to cytochrome P450 2C19 (CYP2C19) genotype in Japanese.

OBJECTIVES: The US Food and Drug Administration has suggested that proton pump inhibitors (PPIs) increase the international normalized ratio (INR) when used concomitantly with warfarin (WF) because of being metabolized by cytochrome P450 2C19 (CYP2C19). We assessed whether CYP2C19 genotypes and type of PPI accentuated the drug interaction. METHODS AND RESULTS: The study group was 82 patients who needed WF after surgery and had their CYP2C19 genotypes analyzed in advance. We randomly divided them into two groups: group I (n = 41) included patients who had lansoprazole 15 mg/day and group II (n = 41) included patients who had rabeprazole 10 mg/day. The dose of WF was controlled by the doctor in charge as a target INR of 1.6 to 2.6 during the 2 months after surgery. The maximum INR was significantly higher in group I (3.36 ± 0.98) than in group II (2.29 ± 0.55, p < 0.0001). The incidence of over-INR (> 3.5) was significantly higher in group I (15 cases) than in group II (2 cases, p = 0.0001). Several bleeding events complicated 10 patients in group I, but none in group II (p = 0.015). Logistic regression analysis revealed that over-INR (odds ratio [OR] 3.58, 95% confidence interval [CI]: 3.48-368.25, p < 0.0001), and pair of lansoprazole and CYP2C19 intermediate metabolizer (OR 2.39, 95% CI: 1.108-29.491, p = 0.0009) were independent predictors of bleeding events. CONCLUSION: If a patient has had the intermediate metabolizer CYP2C19 genotype and concomitant use of WF and a PPI after open heart surgery, lansoprazole intensifies the effects of WF and is associated with bleeding events.

Three-year survival after surgery for primary malignant pericardial mesothelioma: report of a case.

A 59-year-old female underwent surgery for a primary malignant pericardial mesothelioma. She presented with progressive dyspnea, and several imaging studies demonstrated a 65 × 22 mm tumor in the aortopulmonary window, accompanied by massive pericardial effusion. The tumor was successfully excised with clean surgical margins under cardiopulmonary bypass, followed by patch reconstruction of the pulmonary artery, and was diagnosed as an epithelioid type of malignant pericardial mesothelioma. The patient tolerated the operation and subsequent adjuvant chemotherapy without any complications. She remained alive and asymptomatic for almost 3 years after surgery, despite the fact that the median survival of this disease is 6-10 months. This patient is the second longest postoperative survivor of this extremely rare, aggressive neoplasm.

Screening and management for ischemic heart disease in patients undergoing emergency surgery for a type A acute aortic dissection.

PURPOSE: We assessed the incidence of coronary artery disease (CAD) during hospitalization after emergency surgery for a type A acute aortic dissection. METHODS: A total of 123 patients underwent multi-slice computed tomography (MSCT) scans during an early stage after surgery. The patients were divided into two groups: group I consisted of 14 patients (11.4%) who had coronary artery stenosis of more than 75% on MSCT, and group II consisted of 109 patients (88.6%) who had no coronary lesions. RESULTS: The prevalence of diabetes, dyslipidemia and a smoking history was significantly higher in group I. Although the serum low-density lipoprotein cholesterol levels were similar, the high-density lipoprotein cholesterol (HDL) level was significantly lower in group I (36.4 ± 7.9 mg/dl) than in group II (49.6 ± 13.5 mg/dl, P = 0.0005). The maximum carotid intima-media thickness (IMT) was significantly thicker in group I (1.17 ± 0.37 mm) compared to group II (0.96 ± 0.33 mm, P = 0.0297). The logistic regression analysis detected that a carotid IMT over 1.1 mm (odds ratio 4.35, P = 0.0371) and HDL less than 40 mg/dl (odds ratio 3.90, P = 0.0482) were predictors for CAD. CONCLUSIONS: CAD screening should be recommended for patients with aortic dissection who have several atherosclerosis risk factors, even after emergency surgery.

Change in carotid intima-media thickness in a high-risk group of patients by intensive lipid-lowering therapy with rosuvastatin: subanalysis of the JART study.

Carotid intima-media thickness (IMT), a measure of atherosclerosis, is modulated by multiple risk factors. Accordingly, comprehensive control of risk factors is indispensable for management of atherosclerosis. In this study, as a posthoc analysis of the JART Study we planned two analyses. In the main analysis, we evaluated the effect of intensive lipid-lowering therapy with rosuvastatin on carotid IMT in high-risk patients. We also evaluated efficacy in the presence or absence of each risk factor using the full analysis population in the JART Study. Patients with low-density lipoprotein cholesterol (LDL-C) ≥ 140 mg/dL and max-IMT ≥ 1.1 mm were randomized to rosuvastatin or pravastatin therapy for 12 months. Dosages were allowed to increase to 10 mg/day and 20 mg/day to achieve LDL-goals (aggressive goals for rosuvastatin group and guideline goals for pravastatin group). For the main analysis, we assessed 200 high-risk patients (105 in the rosuvastatin group), as category III or secondary prevention according to the Japan Atherosclerosis Society guideline 2007, whereas we assessed 289 patients in the other analysis. Rosuvastatin significantly slowed the percentage change in mean-IMT at 12 months compared with pravastatin (1.40 ± 10.03% versus 6.43 ± 13.77%, P = 0.005). LDL-C was reduced by 48.1% in the rosuvastatin group and 27.9% in the pravastatin group. The rate of achieving the LDL-C goal was significantly greater in the rosuvastatin group compared with the pravastatin group (P < 0.001). Rosuvastatin slowed the change in mean-IMT in the presence of every risk factor. Thus, intensive lipid-lowering therapy reduced progression of carotid IMT in high-risk patients.

Effect of long-term intensive lipid-lowering therapy with rosuvastatin on progression of carotid intima-media thickness--Justification for Atherosclerosis Regression Treatment (JART) extension study.

BACKGROUND: Recently, it was reported from the Justification for Atherosclerosis Regression Treatment (JART) Study that intensive therapy with rosuvastatin significantly slowed progression of carotid intima-media thickness (IMT) compared with conventional therapy with pravastatin at 12 months. To assess the long-term efficacy of intensive therapy, the present extension study was conducted. METHODS AND RESULTS: Subjects in the intensive therapy group of the JART Study were asked to participate in the extension study and to continue rosuvastatin treatment. A total of 113 subjects were enrolled into the extension study and were included in the analysis. At 24 months, the mean daily dose of rosuvastatin (±SD) was 7.9±2.9 mg. Mean change in mean IMT was -0.005 mm (range, -0.024 to 0.015 mm) at 24 months (P=0.633, compared with baseline). Rosuvastatin lowered low-density lipoprotein cholesterol (mean±SD) by 46.4±13.8% and elevated high-density lipoprotein cholesterol (mean±SD) by 8.9±24.0% at 24 months compared with baseline. Gray scale median was measured in 25 subjects. It increased by 16.93±33.12 (mean±SD) % at 12 months and by 22.50±52.83% at 24 months from baseline (P=0.017, P=0.044, respectively). CONCLUSIONS: Two-year treatment with rosuvastatin inhibited progression of carotid IMT. Rosuvastatin also improved the plaque composition, and this qualitative change occurred relatively early after starting therapy.

Comparison of febuxostat and allopurinol for hyperuricemia in cardiac surgery patients (NU-FLASH Trial).

BACKGROUND: Febuxostat has been reported to have a stronger effect on hyperuricemia than allopurinol. METHODS AND RESULTS: Cardiac surgery patients with hyperuricemia (n=141) were randomized to a febuxostat group or an allopurinol group. The study was single-blind, so the treatment was not known by the investigators. The primary endpoint was serum uric acid (UA) level. Secondary endpoints included serum creatinine, urinary albumin, cystatin-C, oxidized low-density lipoprotein (LDL), eicosapentaenoic acid/arachidonic acid ratio, total cholesterol, triglycerides, LDL, high-density lipoprotein, high-sensitivity C-reactive protein, blood pressure, heart rate, pulse wave velocity (PWV), ejection fraction, left ventricular mass index (LVMI), and adverse reactions. UA level was significantly lower in the febuxostat group than the allopurinol group from 1 month of treatment onward. Serum creatinine, urinary albumin, cystatin-C and oxidized LDL were also significantly lower in the febuxostat group. There were no significant changes in systolic blood pressure, PWV, and LVMI in the allopurinol group, but these parameters all had a significant decrease in the febuxostat group. CONCLUSIONS: Febuxostat was effective for high-risk cardiac surgery patients with hyperuricemia because it reduced UA more markedly than allopurinol. Febuxostat also had a renoprotective effect, inhibited oxidative stress, showed anti-atherogenic activity, reduced blood pressure, and decreased PWV and LVMI.

Long-term outcomes of patients undergoing extracorporeal membrane oxygenation for refractory postcardiotomy cardiogenic shock.

PURPOSE: Postcardiotomy cardiogenic shock is still associated with a poor prognosis. We reviewed patients undergoing extracorporeal membrane oxygenation (ECMO) support for postcardiotomy cardiogenic shock and assessed their long-term outcomes. METHODS: The subjects were 47 patients who received ECMO support for cardiogenic shock after open heart surgery. We analyzed the long-term survival and risk factors for early or late death. RESULTS: Twenty-nine patients were weaned off ECMO support, but 15 of these patients died during their hospital stay. An independent predictor of mortality during ECMO support was incomplete sternum closure (OR 4.089, 95 % CL 1.003-16.67, p = 0.049) and a predictor of mortality after weaning off ECMO was more than 48 h of support (OR 8.975, 95 % CL 1.281-62.896, p = 0.027). Fourteen patients were discharged from hospital, but seven of these patients died during the follow-up period owing to cardiac events (n = 2) or non-cardiac causes (n = 5). The actuarial survival rates were 34.0 % at 30 days, 29.8 % at 1 year, and 17.6 % at 10 years. CONCLUSION: Although postcardiotomy cardiogenic shock requiring ECMO support is associated with high morbidity and mortality, the long-term survival rate is acceptable.

Intensive lipid-lowering therapy for slowing progression as well as inducing regression of atherosclerosis in Japanese patients: subanalysis of the JART study.

This paper describes a subanalysis of the JART Study comparing rosuvastatin and pravastatin treatment. A total of 314 subjects were analyzed in this subanalysis, 282 of whom were eligible for evaluation of the relationship between LDL-C and carotid mean-IMT change. In the subanalysis, we evaluated the extent to which intensive lipid-lowering therapy slowed the mean-IMT progression by a correlation analysis between LDL-C and mean-IMT change after 12 months of statin treatment. Nearly half were male (49.4%) and elderly (49.7%). The majority (84.4%) were treated for primary prevention. Patients with hypertension and diabetes mellitus accounted for 65.3% and 44.0%, respectively. At the 12-month measurement point, mean-IMT change was correlated with LDL-C (R = 0.187; P = 0.0016), LDL-C/ HDL-C ratio (R = 0.152; P = 0.0105), and non-HDL-C (R = 0.132; P = 0.0259). Mean-IMT after 12 months was divided into 4 subgroups by LDL-C at 12 months; < 80, ≥ 80 to < 100, ≥ 100 to < 120, and ≥ 120 mg/dL. A trend analysis using the Jonckheere-Terpstra test showed statistical signifi cance (P = 0.0002). Even for prevention in Japanese patients who have lower risk of atherosclerotic disease than Western patients, lowering the LDL-C level to below the therapeutic target prevented mean-IMT progression after 12 months more strongly. These findings suggest that more intensive control of LDL-C to levels lower than those in current JAS guidelines should be required to achieve slowing of progression as well as induction of regression of atherosclerosis.

Effect of intensive lipid-lowering therapy with rosuvastatin on progression of carotid intima-media thickness in Japanese patients: Justification for Atherosclerosis Regression Treatment (JART) study.

BACKGROUND: A recent trial in Western countries has shown that rosuvastatin slows progression of carotid intima-media thickness (IMT) in patients with modest carotid IMT thickening and elevated levels of low-density lipoprotein cholesterol (LDL-C). We conducted a prospective, randomized, open-label, blinded-endpoint trial to determine whether rosuvastatin is more effective than pravastatin in slowing progression of carotid IMT in Japanese patients. METHODS AND RESULTS: Adult patients with hypercholesterolemia who had a maximum IMT ≥1.1mm were randomly assigned to receive rosuvastatin or pravastatin. The primary endpoint was the percent change in the mean-IMT, which was measured by a single observer who was blinded to the treatment assignments. The trial was stopped on April 2011 according to the recommendation by the data and safety monitoring committee. A total of 348 patients (173 rosuvastatin; 175 pravastatin) were enrolled and 314 (159 rosuvastatin; 155 pravastatin) were included in the primary analysis. Mean (SD) percentage changes in the mean-IMT at 12 months were 1.91% (10.9) in the rosuvastatin group and 5.8% (12.0) in the pravastatin group, with a difference of 3.89% (11.5) between the groups (P=0.004). At 12 months, 85 patients (59.4%) in the rosuvastatin group achieved a LDL-C/high-density lipoprotein cholesterol ratio ≤1.5 compared with 24 patients (16.4%) in the pravastatin group (P<0.0001). CONCLUSIONS: Rosuvastatin significantly slowed progression of carotid IMT at 12 months compared with pravastatin.

Rapid aortic enlargement requiring surgery in patients with chronic type B aortic dissection.

We report the relationship between rapid aortic enlargement of chronic type B aortic dissection and sleep disorder due to anxiety after Tohoku disaster. Five patients underwent surgical procedures due to rapid aortic enlargement after the earthquake disaster. They reported that their morning blood pressure increased to approximately 190 mm Hg after the disaster. They were troubled with severe insomnia due to anxiety about the continuing aftershocks. In primary care for patients with mental stress after a big disaster, it is important to keep a careful monitoring of blood pressure besides assessment of anxiety and sleep.

The effect of combined treatment with Impella(®) and landiolol in a swine model of acute myocardial infarction.

Cardiogenic shock is associated with a high mortality rate in patients with acute myocardial infarction (AMI). We developed a new treatment approach named heart rest therapy (HRT) for complete revascularization in the early stage of AMI using an ultra-short-acting ß-blocker (landiolol) and an Impella(®) left ventricular assist device and verified the effect of this therapy in a swine model. In 18 male pigs, AMI was induced by left anterior descending coronary artery occlusion at the level of the second diagonal branch for 120 min, followed by 240 min of reperfusion. The animals were divided into three groups: group A had no support, group B was supported with the Impella(®), and group C was treated with HRT from 90 min after ischemia to 240 min after reperfusion. Infarct ratio (percentage of the infarct area relative to the area at infarct risk) was significantly reduced in group C (group A 65.38 ± 6.07, group B 39.66 ± 11.16, group C 21.78 ± 7.29), with a significant difference between groups A and B (P < 0.001), A and C (P < 0.001), and B and C (P = 0.006). Heart rates were significantly lower in group C at 30 min (P = 0.01), 60 min (P = 0.022), and 240 min (P = 0.032) after reperfusion compared with group B, without development of hypotension. HRT at the early stage in AMI stabilized the hemodynamic conditions and reduced infarct size and complications in a swine model. These results suggest that HRT can improve the prognosis of patients with AMI.

Concomitant aortic valve and ascending aorta replacement with moderate hypothermic circulatory arrest to treat an aortic bicuspid valve with post-stenotic dilatation.

We recommend concomitant surgery for aortic valve replacement (AVR) and ascending aortic replacement using moderate hypothermic circulatory arrest (CA) for post-stenotic dilatation complicated by an aortic bicuspid valve. Cardiopulmonary bypass (CPB) was established from the right atrium to the dilated ascending aorta. As soon as the rectal temperature decreased to 28 °C, CA was commenced and the open distal anastomosis of a polyester prosthesis, without any cerebral perfusion, was completed. AVR was then carried out during rapid re-warming with CPB using a side arm of the prosthesis. This procedure exhibited safe and satisfactory results. There are many benefits of carrying out the procedure in this way; it avoids the requirement for cannulation to a calcified aortic arch, provides a good operative field, for an easier distal anastomosis and suturing at the valve site, and reduces the risk of further dilatation or dissection of the residual ascending aorta in the later phase.

Sleep disorders and aortic dissection in a working population.

The aim of the present study was to assess the relationship between acute aortic dissection (AAD) and sleep disorders in a working population. Seventy (50.4%) of 139 younger subjects with AAD suffered from sleep disorders. Insomnia was reported by 35 patients (50%), sleep deprivation by 31 patients (44.3%), and sleep apnea syndrome was present in 43 patients (61.4%). The average apnea-hypopnea index was 22.0 ± 7.5 points, requiring appropriate treatment. Most of these patients had irregular daily schedules due to job pressure. Sixty-six (94.3%) complained of severe mental and physical stress in daily life. Sleep disorders are considered one of the risk factors for the occurrence of AAD at younger active ages. In primary care for patients with mental or physical stress due to their daily life, it is important to assess these individuals for the presence of sleep disorders.

Is prophylactic intravenous administration of a proton pump inhibitor necessary for perioperative management of cardiac surgery?

BACKGROUND: Mortality from gastrointestinal (GI) hemorrhage caused by antiplatelet or anticoagulant therapy (or both) is quite high after cardiac surgery. We previously reported that proton pump inhibitor (PPI) therapy is indispensable in preventing postoperative GI complications. PPIs are usually administered intravenously immediately after surgery and subsequently by oral formulations. We conducted a prospective study to evaluate whether intravenous PPI followed by oral administration is more efficient as prophylaxis than oral-only administration. METHODS AND RESULTS: We enrolled 40 patients scheduled to undergo coronary artery bypass grafting with cardiopulmonary bypass and randomly assigned them to receive oral PPIs alone (group 1) or intravenous PPI followed by oral administration (group 2). Postoperative upper GI endoscopy evaluations showed no evidence of GI bleeding. Only gastritis, esophagitis, and hiatal hernia were observed at similar incidences in the groups. Mean hospital stays were also similar, but the cost of PPI treatment was significantly lower in group 1. CONCLUSION: No additional benefits of intravenous PPIs over oral formulations were demonstrated. Oral PPIs alone were effective and economical as prophylaxis against GI complications. Intravenous PPIs might be unnecessary in selected patients after cardiac surgery.

Long-term patency rate for radial artery vs. saphenous vein grafts using same-patient materials.

BACKGROUND: The aim of the present study was to assess the long-term graft patency rate of the radial artery (RA), in comparison to the saphenous vein (SV) in patients harvested for both vessels. METHODS AND RESULTS: RA and SV were concomitantly used for coronary artery bypass grafting in 318 patients in an 8-year period from January 2002 to March 2010. During follow-up, graft patency was assessed on angiography or multi-slice computed tomography in 192 of these patients. Cumulative graft patency rates were compared between RA and SV. Independent predictors for graft failure were examined for both vessels. Cumulative graft patency rates at 8 years were 74.3% in RA and 64.7% in SV, respectively. There was no significant difference between these types of grafts. Independent predictors of late RA graft failure were native coronary stenosis <75% and peripheral vascular disease (PVD). Independent predictors of late SV graft failure were use of only one anti-platelet agent and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio >2.5. Cardiovascular event-free and actuarial survival rates at 8 years in this series were 81.2% and 89.7%, respectively. CONCLUSIONS: Cumulative graft patency rates between RA and SV were similar at 8 years. RA performed more poorly in patients with target vessel stenosis <75% and in those complicated by PVD. Aggressive anti-platelet therapy and strict lipid control may be important in maintaining long-term patency of SV.

Myocardial protective effect of human atrial natriuretic Peptide in cardiac surgery. -hANP Shot" in clinical safety trial-.

BACKGROUND: We studied low-dose human atrial natriuretic peptide (hANP) infusion therapy during cardiac surgery and reported the cardiac and renal protective effects. The efficacy of a bolus injection of hANP (the "hANP shot") simultaneously with induction of cardioplegia has been proven in animal experiments. In the present study the clinical effects of this "hANP shot" were examined. METHODS AND RESULTS: The subjects were 67 patients undergoing Coronary artery bypass grafting. At the time of inducing cardioplegia, 1 group received a simultaneous bolus injection of 100 µg of hANP (hANP group) and the other group received an injection of physiological saline (placebo group). The primary endpoints were (1) operative mortality and complications, and (2) the creatine kinase isoenzyme MB (CPK-MB), troponin-I, and human heart fatty acid binding protein (H-FABP) levels. The secondary endpoints were (1) the incidence of arrhythmia, and levels of (2) atrial and B-type natriuretic peptides, and cyclic guanosine monophosphate (cGMP), and (3) renin, angiotensin II, and aldosterone. Postoperative CPK-MB, troponin-I, and H-FABP levels were significantly lower in the hANP group than in the placebo group. Postoperative arrhythmia was significantly less frequent in the hANP group than in the placebo group. CONCLUSIONS: It is possible to achieve cardioprotective effects based on the safety of the "hANP shot", as well as from biomarkers of ischemia and results related to arrhythmia. The "hANP shot" should also be evaluated as a safer and new cardioprotective method for cardiac surgery.