Loss of Cavin-2 destabilizes PTEN and enhances Akt signaling pathway in cardiomyocytes.

AIMS: Specific cavins and caveolins, known as caveolae-related proteins, have been implicated in cardiac hypertrophy and myocardial injury. Cavin-2 forms complexes with other caveolae-related proteins, but the role of Cavin-2 in cardiomyocytes (CMs) is poorly understood. Here, we investigated an unknown function of Cavin-2 in CMs. METHODS AND RESULTS: Under cardiac stress-free conditions, systemic Cavin-2 knockout (KO) induced mild and significant CM hypertrophy. Cavin-2 KO suppressed phosphatase and tensin homolog (PTEN) associated with Akt signaling, whereas there was no difference in Akt activity between the hearts of the wild-type and the Cavin-2 KO mice under cardiac stress-free conditions. However, after swim training, CM hypertrophy was more facilitated with enhanced PI3K-Akt activity in the hearts of Cavin-2 KO mice. Cavin-2 knockdown neonatal rat CMs (NRCMs) using adenovirus expressing Cavin-2 shRNA were hypertrophied and resistant to hypoxia and H2O2-induced apoptosis. Cavin-2 knockdown increased Akt phosphorylation in NRCMs, and an Akt inhibitor inhibited Cavin-2 knockdown-induced anti-apoptotic responses in a dose-dependent manner. Cavin-2 knockdown increased PIP3 production and attenuated PTEN at the membrane fraction of NRCMs. Immunostaining and immunoprecipitation showed that Cavin-2 was associated with PTEN at the plasma membrane of NRCMs. A protein stability assay showed that Cavin-2 knockdown promoted PTEN destabilization in NRCMs. In an Angiotensin II (2-week continuous infusion)-induced pathological cardiac hypertrophy model, CM hypertrophy and CM apoptosis were suppressed in cardiomyocyte-specific Cavin-2 conditional KO (Cavin-2 cKO) mice. Because Cavin-2 cKO mouse hearts showed increased Akt activity but not decreased extracellular signal-regulated kinase activity, suppression of pathological hypertrophy by Cavin-2 loss may be due to increased survival of healthy CMs. CONCLUSIONS: Cavin-2 plays a negative regulator in the PI3K-Akt signaling in CMs through interaction with PTEN. Loss of Cavin-2 enhances Akt activity by promoting PTEN destabilization, which promotes physiological CM hypertrophy and may enhance Akt-mediated cardioprotective effects against pathological CM hypertrophy.

Edoxaban for 12 vs. 3 months in cancer-associated isolated distal deep vein thrombosis according to different doses: insights from the ONCO DVT study.

BACKGROUND: The ONCO DVT study revealed the superiority of 12-month relative to 3-month edoxaban treatment for cancer-associated isolated distal deep vein thrombosis (DVT) regarding the thrombotic risk. METHODS AND RESULTS: In this pre-specified subgroup analysis of the ONCO DVT study, we stratified the patients into those with a standard edoxaban dose (60 mg/day; N = 151) and those with a reduced edoxaban dose (30 mg/day; N = 450) and evaluated the clinical outcomes for the 12- and 3-month treatments. The cumulative 12-month incidence of symptomatic recurrent venous thromboembolism was lower in the 12-month than 3-month group for both the 60 mg (1.3% vs. 11.6%, P = 0.02; odds ratio [OR], 0.12; 95% confidence interval [CI], 0.01-0.97) and 30 mg (1.1% vs. 7.6%, P = 0.002; OR, 0.14; 95% CI, 0.03-0.60) edoxaban subgroups, which was consistent across the edoxaban doses without a significant interaction (P = 0.90). The 12-month cumulative incidence of major bleeding was higher in the 12-month group than in the 3-month group for the 60 mg edoxaban subgroup (14.3% vs. 4.4%, P = 0.046; OR, 3.61; 95% CI, 0.97-13.52), whereas it did not significantly differ between the two groups for the 30 mg edoxaban subgroup (8.7% vs. 8.6%, P = 0.89; OR, 0.97; 95% CI, 0.49-1.91), signalling there was a potential interaction (P = 0.07). CONCLUSIONS: A 12-month edoxaban regimen for cancer-associated isolated distal DVT was consistently superior to a 3-month regimen, across the edoxaban doses for the thrombotic risk. However, caution was suggested for the standard dose of edoxaban due to the potential for an increased risk of bleeding with prolonged anticoagulation therapy. TRIAL REGISTRATION NUMBER: NCT03895502 (ONCO DVT Trial): https://classic.clinicaltrials.gov/ct2/show/NCT03895502.

Home Treatment for Active Cancer Patients With Low-Risk Pulmonary Embolism　- A Predetermined Companion Report From the ONCO PE Trial.

BACKGROUND: Patients with appropriately selected low-risk pulmonary embolism (PE) can be treated at home, although it has been controversial whether applies to patients with cancer, who are considered not to be at low risk.Methods and Results: The current predetermined companion report from the ONCO PE trial evaluated the 3-month clinical outcomes of patients with home treatment and those with in-hospital treatment. The ONCO PE trial was a multicenter, randomized clinical trial among 32 institutions in Japan investigating the optimal duration of rivaroxaban treatment in cancer-associated PE patients with a score of 1 using the simplified version of the Pulmonary Embolism Severity Index (sPESI). Among 178 study patients, there were 66 (37%) in the home treatment group and 112 (63%) in the in-hospital treatment group. The primary endpoint of a composite of PE-related death, recurrent venous thromboembolism (VTE) and major bleeding occurred in 3 patients (4.6% [0.0-9.6%]) in the home treatment group and in 2 patients (1.8% [0.0-4.3%]) in the in-hospital treatment group. In the home treatment group, there were no cases of PE-related death or recurrent VTE, but major bleeding occurred in 3 patients (4.6% [0.0-9.6%]), and 2 patients (3.0% [0.0-7.2%]) required hospitalization due to bleeding events. CONCLUSIONS: Active cancer patients with PE of sPESI score=1 could be potential candidates for home treatment.

The impact of renal function on clinical outcomes of patients with cancer-associated isolated distal deep vein thrombosis: Insights from the ONCO DVT study.

BACKGROUND: The multicenter, open-label, randomized clinical trial ONCO DVT compared 3-month and 12-month edoxaban treatment regimens for isolated distal deep vein thrombosis (DVT) and suggested potential benefits of prolonged edoxaban treatment in terms of thrombotic risk. However, the risk-benefit balance of prolonged edoxaban treatment in patients with renal function remains unclear. OBJECTIVES: To compare the safety and efficacy of 3-month and 12-month edoxaban treatment regimens in patients with cancer-associated isolated distal DVT and different renal functions. METHODS: This pre-specified subgroup analysis of the ONCO DVT study included 601 patients divided into subgroups according to renal function using a 50 mL/min creatinine clearance (Ccr) cutoff. The primary endpoint was symptomatic recurrent venous thromboembolism (VTE) and VTE-related death at 12 months and the major secondary endpoint was major bleeding at 12 months. RESULTS: Among the 601 patients, 131 (21.8 %) comprised the renal dysfunction subgroup. The primary endpoint occurred in 6 (9.7 %) and 1 (1.4 %) patients in the 3-month and 12-month edoxaban groups in the renal dysfunction subgroup, respectively, and in 16 (6.6 %) and 2 (0.9 %) patients in the no renal dysfunction subgroup, respectively. The major secondary endpoint occurred in 9 (14.5 %) and 7 (10.1 %) patients in the 12-month and 3-month edoxaban groups in the renal dysfunction subgroup, and in 13 (5.3 %) and 21 (9.3 %) patients in the no renal dysfunction subgroup, respectively. CONCLUSIONS: A 12-month edoxaban regiment was superior to a 3-month treatment in terms of thrombotic risk irrespective of renal function. A higher bleeding risk was not identified in patients with renal dysfunction who received prolonged edoxaban treatment.

Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis (ONCO DVT Study): An Open-Label, Multicenter, Randomized Clinical Trial.

BACKGROUND: The optimal duration of anticoagulation therapy for isolated distal deep vein thrombosis in patients with cancer is clinically relevant, but the evidence is lacking. The prolonged anticoagulation therapy could have a potential benefit for prevention of thrombotic events; however, it could also increase the risk of bleeding. METHODS: In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 60 institutions in Japan, we randomly assigned patients with cancer with isolated distal deep vein thrombosis, in a 1-to-1 ratio, to receive either a 12-month or 3-month edoxaban treatment. The primary end point was a composite of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death at 12 months. The major secondary end point was major bleeding at 12 months, according to the criteria of the International Society on Thrombosis and Haemostasis. The primary hypothesis was that a 12-month edoxaban treatment was superior to a 3-month edoxaban treatment with respect to the primary end point. RESULTS: From April 2019 through June 2022, 604 patients were randomized, and after excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group. The mean age was 70.8 years, 28% of the patients were men, and 20% of the patients had symptoms of deep vein thrombosis at baseline. The primary end point of a symptomatic recurrent VTE event or VTE-related death occurred in 3 of the 296 patients (1.0%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 0.13; 95% CI, 0.03-0.44). The major secondary end point of major bleeding occurred in 28 of the 296 patients (9.5%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 1.34; 95% CI, 0.75-2.41). The prespecified subgroups did not affect the estimates on the primary end point. CONCLUSIONS: In patients with cancer with isolated distal deep vein thrombosis, 12 months was superior to 3 months for an edoxaban treatment with respect to the composite outcome of a symptomatic recurrent VTE or VTE-related death. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03895502.

Clot-regression effects of rivaroxaban in venous thromboembolism treatment in cancer patients-a prospective interventional study.

Rivaroxaban, a direct oral anticoagulant, is effective against venous thromboembolism (VTE) recurrence without increasing the risk of major bleeding in patients with cancer-associated venous thromboembolism (CAT). However, its clot regression effects are poorly understood. This single-arm, prospective interventional study aimed to investigate the clot regression effects of rivaroxaban in 40 CAT patients, through a contrast-enhanced computed tomography at baseline, 3 weeks, and 3 months of rivaroxaban treatment. The primary endpoint was the clot-regression ratio calculated from the thrombus volumes at 3 weeks and 3 months. Compared with baseline, the total clot volume was significantly reduced at both 3 weeks and 3 months after initiation (p < 0.01). The clot-regression rates were statistically significant with 83.1% (95% confidence interval [CI], 73.8-92.3%) at 3 weeks and 98.7% (95% CI, 97.1-100.2%) at 3 months, with complete resolution in 36.1% and 80.8% of patients at 3 weeks and 3 months, respectively. One patient had recurrent VTE after dose reduction, and seven had non-fatal major bleeding. Therefore, rivaroxaban had a sufficient clot-regression effect against CAT with caution of bleeding complication.

Requirement of Cavin-2 for the expression and stability of IRß in adequate adipocyte differentiation.

OBJECTIVE: Adipogenesis plays an essential role in maintaining energy and hormonal balance. Cavin-2, one of the caveolae-related proteins, is abundant in adipocytes, the leading site of adipogenesis. However, the details of the roles of Cavin-2 in adipogenesis remain unknown. Here, we demonstrate the requirement of Cavin-2 for the expression and stability of IRß in adequate adipocyte differentiation. METHODS: Cavin-2 knockout (Cavin-2 KO) and wild-type (WT) mice were fed with a high-fat diet (HFD) for 8 weeks. We evaluated body weight, food intake, and several tissues. Glucose homeostasis was assessed by glucose and insulin tolerance tests. Insulin signaling in epididymal white adipose tissue (eWAT) was determined by Akt phosphorylation. In vitro study, we evaluated adipocyte differentiation, adipogenesis-related genes, and insulin signaling to clarify the relationship between Cavin-2 and adipogenesis under the manipulation of Cavin-2 expression. RESULTS: Caveolae structure decreased in eWAT of Cavin-2 KO mice and Cavin-2 knockdown 3T3-L1 cells. Cavin-2 enhanced the stability of insulin receptor (IR) through direct association at the plasma membrane in adipocytes, resulting in accelerated insulin/IR/Akt signaling-induced adipogenic gene expression in insulin-containing solution-stimulated 3T3-L1 adipocytes. IR-mediated Akt activation also enhanced Cavin-2 and IR expression. Cavin-2 knockout mice showed insulin resistance with dyslipidemia and pathological hypertrophic adipocytes after a HFD. CONCLUSIONS: Cavin-2 enhances IR stability through binding IR and regulates insulin signaling, promoting adequate adipocyte differentiation. Our findings highlight the pivotal role of Cavin-2 in adipogenesis and lipid metabolism, which may help to develop novel therapies for pathological obesity and adipogenic disorders.

Favorable changes of left ventricular function in the circumferential direction following transcatheter atrial septal defect closure: a strain imaging study.

To clarify the impact on left ventricular (LV) function of percutaneous atrial septal defect (ASD) closure in adult patients. Echocardiograms of 46 patients (52 ± 18 years) who underwent ASD closure with a significant left-to-right shunt obtained before and 1 month after the procedure were retrospectively analyzed. Functional parameters were obtained by 2-dimensional speckle-tracking imaging. Global longitudinal strain and strain rate at early diastole (SRe) was calculated from the three standard apical views, while circumferential and radial parameters were calculated from basal, middle, and apical LV short-axis views. Along with a diminished right ventricular (RV) volume, the LV volume and ejection fraction increased (end-diastolic volume: 61 ± 12 to 76 ± 15 mL, p < 0.001; and 63% ± 4 to 64% ± 4% p = 0.03; respectively). Both global strain and SRe was augmented only in the circumferential direction (- 16.2% ± 2.9% to - 19.8% ± 2.8%; and 1.07 ± 0.29 to 1.34 ± 0.28 s-1, both p < 0.001). Augmentation of circumferential SRe correlated with both the changes in and the pre-procedural value of diastolic LV eccentricity index (r = - 0.57, p < 0.001; and r = 0.37, p = 0.01; respectively), a morphological parameter of RV volume overload. Following ASD closure in adults, both LV systolic and diastolic function could favorably change in the circumferential direction, and the degree of diastolic functional change is associated with RV volume overload, i.e., severity of ventricular interdependence.

Two effective cases of additional pedal artery angioplasty for severe lower limb ischemia following acute thrombotic artery occlusion with hypercoagulable state diseases.

BACKGROUND: Acute limb ischemia (ALI) and critical limb ischemia (CLI) following ALI are life-threatening diseases. The rare potential causes of ALI include hypercoagulable state diseases, such as antiphospholipid syndrome (APS) and essential thrombocythemia (ET). Hypercoagulability often make revascularization for arterial occlusion, especially associated with infrapopliteal lesions, difficult. This is because the vessels have poor run-off, and elevated peripheral vascular resistance associated with microcirculation failure, due to a high thrombus burden. There is no established treatment for this issue. CASE PRESENTATION: A 45 years-old and a 56 years-old male suffered from thrombotic arterial occlusion as a first manifestation of APS and ET, respectively. Combination therapy with aggressive anti-thrombotic therapy and revascularization, such as endovascular therapy and surgical thrombectomy based on the angiosome concept, was performed. However, the high thrombus burden caused a poor pedal outflow, and significant limb ischemia remained. Additional pedal artery angioplasty was performed to improve residual limb ischemia in each case and provided sufficient blood flow to the foot. CONCLUSION: The pedal artery angioplasty for thrombotic pedal artery occlusion cases, associated with hypercoagulable state diseases, seems to be a treatment option for relieving residual limb ischemia.

Reconstruction of right ventricular outflow tract stenosis and right ventricular failure after Ross procedure - comprehensive assessment of adult congenital heart disease with four-dimensional imaging: a case report.

BACKGROUND: Re-intervention after Ross procedure into the right ventricular outflow tract might be needed in patients in the long term. However, right ventricular outflow tract re-intervention indications are still unclear. Comprehensive assessment of total hemodynamics is needed. A 42-year-old Japanese woman was referred to our hospital for moderately severe pulmonary regurgitation and severe tricuspid regurgitation after a Ross-Konno procedure. Thirteen years after surgery, she developed atrial fibrillation and atrial flutter and complained of dyspnea. Electrophysiological studies showed re-entry circuit around the low voltage area of the lateral wall on the right atrium. Four-dimensional flow magnetic resonance imaging revealed moderate pulmonary regurgitation, severe tricuspid regurgitation, and a dilated right ventricle. Flow energy loss in right ventricle calculated from four-dimensional flow magnetic resonance imaging was five times higher than in normal controls, suggesting an overload of the right-sided heart system. Her left ventricular ejection fraction was almost preserved. Moreover, the total left interventricular pressure difference, which shows diastolic function, revealed that her sucking force in left ventricle was preserved. After the comprehensive assessments, we performed right ventricular outflow tract reconstruction, tricuspid valve annuloplasty, and right-side Maze procedure. A permanent pacemaker with a single atrial lead was implanted 14 days postoperatively. She was discharged 27 days postoperatively. Echocardiography performed 3 months later showed that the size of the dilated right ventricle had significantly reduced. DISCUSSION: A four-dimensional imaging tool can be useful in the decision of re-operation in patients with complex adult congenital heart disease. The optimal timing of surgery should be considered comprehensively.

Clot regression effects of rivaroxaban in the treatment of venous thromboembolism in patients with cancer (CRERIT-VTE cancer): study protocol.

INTRODUCTION: Anticoagulant therapy in patients with cancer with venous thromboembolism (VTE) increases the risk of both VTE recurrence and haemorrhagic complication. Direct oral anticoagulants (DOACs) have been shown to be effective in preventing VTE recurrence, and comparable to conventional therapy in preventing VTE recurrence in patients with advanced cancer. Rivaroxaban is a DOAC that causes thrombus regression, possibly through a profibrinolytic effect. Thrombus regression with initial treatment is essential for VTE patients. However, the thrombolytic effect of DOAC for VTE patients with cancer has not been fully examined. Therefore, in this study, we investigate the thrombolytic effect of rivaroxaban in patients with cancer who develop VTE. METHODS AND ANALYSIS: This study is a single-arm, open-label, prospective interventional study. Forty patients aged from 20 to 75 years old at the time of consent who have been diagnosed with acute VTE and have active cancer are included. Patients are excluded if they have received thrombolytic therapy, have creatinine clearance of less than 30 mL/min, have expected a life expectancy of less than 6 months or have deep vein thrombosis limited to the distal lower leg. Eligible patients receive standard treatment with rivaroxaban (15 mg two times daily for 3 weeks, followed by 15 mg QD). The primary study endpoint is clot regression ratio as evaluated by contrast-enhanced CT imaging. CT imaging is obtained at baseline, 21±4 and 90±14 days after the start of rivaroxaban treatment. Secondary endpoints are the recurrence of VTE and haemorrhagic complications. ETHICS AND DISSEMINATION: This study was approved by the institutional review board of the Kyoto Prefectural University of Medicine. Study results will be disseminated through peer-reviewed journals.Trial registration numberUMIN000027793.

Systems Network Genomic Analysis Reveals Cardioprotective Effect of MURC/Cavin-4 Deletion Against Ischemia/Reperfusion Injury.

Background Ischemia/reperfusion (I/R) injury is a critical issue in the development of treatment strategies for ischemic heart disease. MURC (muscle-restricted coiled-coil protein)/Cavin-4 (caveolae-associated protein 4), which is a component of caveolae, is involved in the pathophysiology of dilated cardiomyopathy and cardiac hypertrophy. However, the role of MURC in cardiac I/R injury remains unknown. Methods and Results The systems network genomic analysis based on PC-corr network inference on microarray data between wild-type and MURC knockout mouse hearts predicted a network of discriminating genes associated with reactive oxygen species. To demonstrate the prediction, we analyzed I/R-injured mouse hearts. MURC deletion decreased infarct size and preserved heart contraction with reactive oxygen species-related molecule EGR1 (early growth response protein 1) and DDIT4 (DNA-damage-inducible transcript 4) suppression in I/R-injured hearts. Because PC-corr network inference integrated with a protein-protein interaction network prediction also showed that MURC is involved in the apoptotic pathway, we confirmed the upregulation of STAT3 (signal transducer and activator of transcription 3) and BCL2 (B-cell lymphoma 2) and the inactivation of caspase 3 in I/R-injured hearts of MURC knockout mice compared with those of wild-type mice. STAT3 inhibitor canceled the cardioprotective effect of MURC deletion in I/R-injured hearts. In cardiomyocytes exposed to hydrogen peroxide, MURC overexpression promoted apoptosis and MURC knockdown inhibited apoptosis. STAT3 inhibitor canceled the antiapoptotic effect of MURC knockdown in cardiomyocytes. Conclusions Our findings, obtained by prediction from systems network genomic analysis followed by experimental validation, suggested that MURC modulates cardiac I/R injury through the regulation of reactive oxygen species-induced cell death and STAT3-meditated antiapoptosis. Functional inhibition of MURC may be effective in reducing cardiac I/R injury.

Evaluation using a four-dimensional imaging tool before and after pulmonary valve replacement in a patient with tetralogy of Fallot: a case report.

BACKGROUND: Pulmonary regurgitation is a common complication after tetralogy of Fallot repair, resulting in right ventricular dysfunction, arrhythmia, and sudden death. However, the indications and optimal timing for pulmonary valve replacement are not fully known. We describe a case in which a four-dimensional imaging tool was useful in the decision to re-operate, thus resulting in decreased energy loss and improved right ventricular function after the re-operation for tetralogy of Fallot. CASE PRESENTATION: A 54-year-old Japanese woman visited our hospital due to palpitations and wide QRS tachycardia with persistent tiredness for several months. She underwent repair of tetralogy of Fallot when she was 2-years old. An electrocardiogram showed prolonged QRS duration (199 msec) with a complete right bundle branch block and an echocardiograph demonstrated that her right ventricle was highly enlarged and had poor contraction, and severe pulmonary valve regurgitation with one leaflet flail. Four-dimensional flow magnetic resonance imaging demonstrated that regurgitant volumes and regurgitant fractions of pulmonary regurgitation were calculated as 63.12 ml and 54.0%, respectively. Right ventricular end-diastolic/end-systolic volume index was 169.54/99.76 mL/m2, and the cardiac index was 1.78 L/minute per m2. Flow energy loss was 2.93 mW, which is estimated to be three times higher than normal controls. An electrophysiological study showed an intact anterior internodal pathway and a slow pathway just through the outside of the right atriotomy line scar, which is supposed to cause a re-entry circuit. We decided to perform a pulmonary valve replacement and a right maze procedure. A 27 mm bioprosthetic valve was implanted in the native pulmonary annulus with a supra-annular position. Concomitantly, the right maze procedure was performed. A four-dimensional flow magnetic resonance imaging done 3 months later showed that right ventricular end-diastolic/end-systolic volume index had significantly reduced to 85.24/55.41 mL/m2 and the cardiac index had increased from 1.78 to 2.58 L/minute per m2. Energy loss had greatly improved from 2.93 to 1.48 mW. CONCLUSIONS: A four-dimensional imaging tool was useful in the decision to re-operate, thus resulting in decreased energy loss and improved right ventricular function after the re-operation for tetralogy of Fallot.

In-stent Massive Thrombi Formation During Primary Percutaneous Coronary Intervention in a Patient with Acute Myocardial Infarction Complicated with Essential Thrombocythemia.

A 61-year-old man with essential thrombocythemia (ET) presented with acute myocardial infarction (AMI) and underwent primary percutaneous coronary intervention. After stent deployment from the left main (LM) to the left anterior descending artery, intravascular ultrasound revealed thrombi formation in the whole stent. Two days later, optical frequency domain imaging confirmed stent malapposition and thrombi remaining in only the LM. The stent malapposition and ET might have contributed to this phenomenon. He underwent an additional stent expansion and aggressive anti-thrombotic regimen. AMI complicated with ET carries increased risks of in-stent thrombi formation and requires careful revascularization and aggressive pharmacotherapy.

Feasibility and Safety of Reverse Catheterization Technique of the Superficial Femoral Artery in Single-Stage Endovascular Treatment of Bilateral Infrainguinal Diseases.

PURPOSE:: We evaluated the feasibility and safety of the reverse catheterization technique of the superficial femoral artery (ReCAT) for single-stage endovascular treatment (EVT) in patients with bilateral infrainguinal diseases. MATERIALS AND METHODS:: We retrospectively evaluated 24 consecutive patients (overall median age: 79 years; male patients: 21 [87.5%]) who underwent EVT for bilateral infrainguinal diseases. The objective of ReCAT was to perform single-stage EVT in patients with bilateral infrainguinal diseases with a one-time unilateral femoral artery puncture. The main outcomes were the incidence of puncture site complications, including major bleeding or hematoma requiring transfusion, pseudoaneurysm, and arteriovenous fistula, and ReCAT procedure-related arterial dissection or perforation, which were assessed by ultrasonography on the day after the procedure. The secondary outcome measures were in-hospital mortality and in-hospital amputation. RESULTS:: Reverse catheterization technique of the superficial femoral artery was successful in 23 (95.8%) of the 24 patients; it failed in 1 patient due to severe calcification and a previously implanted stent in the ipsilateral iliac artery. The median operation time, radiation time, and the volume of contrast media used were 108 (84-142) minutes, 37 (27-55) minutes, and 111 (80-157) mL, respectively. There were no incidences of puncture site complications and arterial dissection related to the ReCAT procedure. One case of vessel perforation in a branch of the ipsilateral superficial femoral artery occurred due to flipped guidewire injury. CONCLUSION:: Reverse catheterization technique of the superficial femoral artery is safe and effective in performing single-stage EVT for bilateral infrainguinal diseases. It might also reduce the number of EVTs and complications due to multiple femoral artery punctures.

Angioscopic Evaluation During Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disorder with a poor prognosis. Recently, balloon pulmonary angioplasty (BPA) has been reported to be an effective treatment for inoperable patients with CTEPH. However, this catheter-based treatment has potentially life-threatening vascular complications. To improve the efficacy and safety of BPA, we assessed the morphological evaluation of organised thrombus and the vascular injury by BPA procedure. METHODS: In this study, we assessed the morphology of organised thrombi and the vascular injury observed by angioscopy during BPA in 28 lesions from nine CTEPH patients. RESULTS: Angioscopy visualised various forms of organised thrombi such as 'Mesh', 'Slit', 'Flap' and 'Mass' and allowed for a detailed evaluation of organised thrombus that was difficult to do by conventional contrast angiography. In addition, after balloon dilation for BPA, angioscopy revealed a haemorrhage due to a vessel wall injury caused by wiring and/or ballooning. CONCLUSIONS: Assessment of organised thrombus and vascular injury by angioscopy might contribute to improving the treatment of the patients with CTEPH.

Brachial-Ankle Pulse Waves Reflect the Hemodynamics of Valvular Heart Disease.

BACKGROUND: Brachial-ankle pulse wave (ba-PW) analysis is an established technique for assessing arterial stiffness and cardiovascular risk. The peripheral arterial pulse wave configuration may be useful for valvular heart disease (VHD) detection because it is closely related to the physical signs of VHD; however, few reports have been made assessing the efficacy of ba-PW analysis for VHD screening. METHODS: Consecutive VHD patients scheduled for valve surgery were enrolled in the study. These included 58 patients with aortic stenosis (AS) (mean age 74 ± 1.1 years), 67 with aortic regurgitation (AR) (mean age 59 ± 1.9 years), and 65 with mitral regurgitation (MR) (mean age 62 ± 1.6 years). Ba-PW analysis was conducted using the VaSera VS-1500 screening system before and after surgery. Upstroke time (UT), ejection time (ET), pre-ejection period (PEP), PEP/ET ratio, mean arterial pressure (%MAP), and cardio-ankle vascular index (CAVI) were compared with a control group (n = 65; mean age 69 ± 1.5 years) without VHD. RESULTS: The UT was significantly shorter in the AR group (132.9 ± 4.0 ms) and MR group (134.5 ± 2.5 ms), but significantly longer in the AS group (178.2 ± 2.8 ms) compared to controls (149.6 ± 3.6 ms; all p <0.01). The ET was significantly longer in the AS group (318.5 ± 7.4 ms) and AR group (320.0 ± 4.6 ms), but significantly shorter in the MR group (289.0 ± 3.8 ms) compared to controls (305.3 ± 3.4 ms; all p <0.05). In ROC analyses of each group compared to controls, areas under the curve of UT, corrected (c)UT, ET and cET in the AS group, UT/ET ratio in the AR group, and PEP/UT ratio in the MR group were all >0.7. CONCLUSIONS: Multiple pulse wave parameters reflect VHD hemodynamics and may be useful for screening for the condition.

Late-onset Mitochondrial Cardiomyopathy Triggered by Anticancer Treatment.

We report the case of a 62-year-old woman with a history of bilateral hearing impairment, who developed mitochondrial cardiomyopathy after chemotherapy. The patient underwent postoperative cisplatin chemotherapy after the surgical treatment of cervical cancer. The systolic function of her left ventricle decreased significantly. A tissue examination of the left ventricle revealed mitochondrial cardiomyopathy. Genetic testing revealed mutations in mitochondrial 3,243 A→G. Nine hundred fifty-five individual mutations were identified by next-generation sequencing. Since cardiovascular complications are the second leading cause of morbidity and mortality in patients undergoing cancer treatment, mitochondrial cardiomyopathy should be considered a potential cause of heart failure.

Usefulness of peripheral arterial signs in the evaluation of aortic regurgitation.

BACKGROUND: Early diagnosis and optimal timing of surgical repair for chronic aortic regurgitation (AR) are topics of interest, because left ventricular compensation delays the clinical signs of the early stages of left ventricular dysfunction. Various physical signs have been described as indicators of chronic AR, but AR screening can be difficult depending on the proficiency of primary care providers. The recent use of the cardio-ankle vascular index (CAVI) measurement to assess peripheral atherosclerosis may detect AR objectively and simply because its arterial pulse wave configuration is closely related to the physical signs of AR. METHODS: CAVI measurements include pulse pressure (PP), the difference in blood pressures between upper and lower limbs (ABD), ankle-brachial index (ABI), ejection time (ET), and upstroke time (UT). We evaluated the differences in CAVI parameters between AR group and age-matched control group, the relationships between CAVI parameters and the echocardiographic semi-quantitative measurements of AR severity such as left ventricular dimensions (Dd, Ds) and vena contracta (VC), and between the changes in CAVI parameters before and after aortic valve replacement. RESULTS: ABD, PP, ET, ankle systolic pressure and ABI in the AR group were significantly higher than that in the control group. Brachial diastolic pressure and CAVI in the AR group were significantly lower than that in the control group. UT was lower than that in the control group (p=0.05). PP did not correlate with the semi-quantitative AR severity, but ABD was correlated with Dd, Ds, and VC and was negatively correlated with UT. The exaggerated ABD, PP, ET, and ABI were moderated after surgery. CONCLUSIONS: CAVI parameters could be useful in the screening and serial follow-up of AR patients.

Angioscopic observation in chronic thromboembolic pulmonary hypertension before and after balloon pulmonary angioplasty.

: We here report the angioscopic assessment of inoperable peripheral chronic thromboembolic pulmonary hypertension in an 81-year-old man who was previously diagnosed with the disease. To assess the pathological morphology of the web lesion, pouch defect and band lesion, we used two types of angioscopic catheter: blood flow-maintaining type and blood flow-blocking type. Angioscopy revealed a heterogeneous thrombus that contained white organized thrombus, red fragile thrombus and yellowish thrombus. After three sessions of balloon pulmonary angioplasty, his pulmonary arterial pressure decreased and his symptom of dyspnea on exertion and desaturation were improved. Angioscopy displayed various forms of organized thrombus, and also allowed the detailed observation of lesions that were difficult to be observed by angiography.