Catheter-based ultrasound renal denervation in patients with resistant hypertension: the randomized, controlled REQUIRE trial.

Renal denervation is a promising new non-pharmacological treatment for resistant hypertension. However, there is a lack of data from Asian patients. The REQUIRE trial investigated the blood pressure-lowering efficacy of renal denervation in treated patients with resistant hypertension from Japan and South Korea. Adults with resistant hypertension (seated office blood pressure ≥150/90 mmHg and 24-hour ambulatory systolic blood pressure ≥140 mmHg) with suitable renal artery anatomy were randomized to ultrasound renal denervation or a sham procedure. The primary endpoint was change from baseline in 24-hour ambulatory systolic blood pressure at 3 months. A total of 143 patients were included (72 renal denervation, 71 sham control). Reduction from baseline in 24-hour ambulatory systolic blood pressure at 3 months was not significantly different between the renal denervation (-6.6 mmHg) and sham control (-6.5 mmHg) groups (difference: -0.1, 95% confidence interval -5.5, 5.3; p = 0.971). Reductions from baseline in home and office systolic blood pressure (differences: -1.8 mmHg [p = 0.488] and -2.0 mmHg [p = 0.511], respectively), and medication load, did not differ significantly between the two groups. The procedure-/device-related major adverse events was not seen. This study did not show a significant difference in ambulatory blood pressure reductions between renal denervation and a sham procedure in treated patients with resistant hypertension. Although blood pressure reduction after renal denervation was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. This unexpected blood pressure reduction in the sham control group highlights study design issues that will be addressed in a new trial. CLINICAL TRIAL REGISTRATION: NCT02918305 ( http://www.clinicaltrials.gov ).

New-onset Takayasu's Arteritis as Acute Myocardial Infarction.

We herein report the case of a 25-year-old Japanese woman with left-main-trunk acute myocardial infarction (LMT-AMI). She had cardiogenic shock, so emergency percutaneous intervention was performed. Intravascular ultrasound of LMT-AMI showed that the three-layered structure of the intima, tunica media, and adventitia was not clearly visible, and the vessel was concentrically thickened; unstable plaque and calcification were not seen. AMI is rarely seen in young women, but Takayasu's arteritis is one major cause. If a young woman complaining of typical chest pain as acute coronary syndrome is encountered, systemic diseases must be considered.

Isolated Cardiac Sarcoidosis Mimicking Arrhythmogenic Right Ventricular Cardiomyopathy.

The diagnosis of cardiac sarcoidosis (CS) has become easier due to advances in imaging modalities, but we sometimes encounter difficult-to-diagnose patients. We herein report the case of a 60-year-old Japanese woman who was diagnosed with isolated CS, although she also met the diagnostic criteria of arrhythmogenic right ventricular cardiomyopathy (ARVC). A histological examination by an endomyocardial biopsy of the right ventricle revealed the typical findings of granulomatous change for CS. Although she did not show any characteristics of systemic sarcoidosis, oral prednisolone treatment was introduced, and she achieved a good response. This case shows that the characteristics of CS can overlap with the diagnostic criteria of ARVC, and that a histological examination is essential for the correct diagnosis of CS.

Venous Thromboembolism Due to Oral Contraceptive Intake and Spending Nights in a Vehicle -A Case from the 2016 Kumamoto Earthquakes.

A 40-year-old woman experiencing sudden dyspnea went to her personal doctor for advice. She was previously diagnosed with endometriosis and prescribed oral contraceptives for treatment. During earthquakes, she spent 7 nights sleeping in a vehicle. The patient had swelling and pain in her left leg and high D-dimer concentration levels. A contrast-enhanced computed tomography scan revealed a contrast deficit in the bilateral pulmonary artery and in the left lower extremity. She was diagnosed with pulmonary thromboembolism (PTE), and anticoagulation therapy was initiated. This present case is the first report of PTE attributed to the use of oral contraceptives after earthquakes.

Life- and limb-saving endovascular therapy in a patient with acute abdominal aortic occlusion.

A 79-year-old man developed severe bilateral ischemic symptoms in the lower limbs. Chest-abdominal-pelvic contrast computed tomography (CT) showed acute occlusion involving the abdominal aorta, and endovascular therapy (EVT) was used as emergency treatment. Two self-expandable stents placed in the thrombus area resulted in restoration of blood flow to the lower limbs, despite limited stent expansion, and movement of these limbs. Follow-up CT showed good stent expansion. The patient had a favorable recovery without additional surgery. This case suggests that EVT might be an additional option for acute abdominal aortic occlusion if surgery or thrombolytic therapies are not possible.

Efficient distal tip size of primary guidewire for antegrade percutaneous coronary intervention in chronic total occlusion: The G-FORCE study.

BACKGROUND: Although several new techniques have been introduced for CTO such as the retrograde approach, the fundamental question of what type of guidewire is the most appropriate as a primary guidewire in the antegrade approach has not been answered. METHODS: The G-FORCE study was designed as a prospective multicenter randomized controlled trial to determine the efficient primary guidewire in antegrade approach for chronic total occlusion (CTO). The first guidewire was randomly assigned to a regular size distal tip group (0.014in. size) or tapered tip group (0.010in. or less). The primary endpoint was defined as successful lesion penetration by the first guidewire into distal true lumen. This study was registered at ClinicalTrials.gov with identifier NCT00987610. RESULTS: A total of 260 patients were enrolled, with an average age of 66±11years and 16% were female. The average J-CTO score was 1.8±1.1. The primary endpoint was achieved in 38% and 32% of patients using tapered and regular distal tip guidewires, respectively (P=0.80). The final PCI success rate was 81% vs. 85%, respectively (P=0.57). Easy CTO lesions with a J-CTO score=0 exhibited a primary endpoint significantly different between tapered and regular distal tip primary guidewires (79% vs. 40%; P=0.046). Guidewire distal coating or distal tip load did not relate with primary guidewire success rate. CONCLUSION: Tapered and regular distal tip guidewires are equivalent as a first choice for CTO. Tapered guidewires are superior for CTO lesions with a J-CTO score=0.

The dawn of a new era in onco-cardiology: The Kumamoto Classification.

The term "onco-cardiology" has been used in reference to cardiotoxicity in the treatment of malignant disease. In actual clinical situations, however, cardiovascular disease (CVD) associated with malignant disease and the concurrence of atherosclerotic disease with malignant disease are commonly observed, complicating the course of treatment. Patients with malignant disease associated with coronary artery disease often die from the cardiovascular disease, so it is essential to classify these disease states. Additionally, the prevalence of these classifications makes it easy to manage patients with malignant disease and coronary artery disease. We divided the broad field of onco-cardiology into 4 classifications based on clinical scenarios (CSs): CS1 represents the so-called paraneoplastic syndrome. CS2 represents cardiotoxicity during treatment of malignant diseases. CS3 represents the concurrence of atherosclerotic disease with malignant disease, and CS4 represents cardiovascular disease with benign tumors. This classification facilitates the management of patients with malignant disease and coronary artery disease by promoting not only the primary but also the secondary prevention of CVD.

Impact of Introducing Catheter-based Renal Denervation into Japan for Hypertension Management: Estimation of Number of Target Patients and Clinical Relevance of Ambulatory Blood Pressure Reduction.

BACKGROUND: New medical approaches to the autonomic nervous system, such as catheterbased renal denervation, have been introduced into clinical practice in the recent years for patients who have resistant hypertension. OBJECTIVES AND METHODS: We estimate the number of subjects in Japan who would benefit from renal denervation when this treatment is introduced into Japan, based on data from the Jichi Medical University clinical trials. We also discuss the logical basis of changing the formerly used primary endpoint, i.e., office BP, to 24-hr ambulatory BP in future clinical trials. RESULTS: Among JAMP registry data, the total number of hypertensives was 5,858 and the patients who were prescribed ≥ 3 drugs including diuretics were 749. The poorly controlled hypertension rate was 32% in the group prescribed ≥ 3 drugs including diuretics and it constitutes 4.1% of the total hypertensive patients. We also analyzed the data of JMS ABPM cohort study wave 1 (811 patients). The hazard ratios (HRs) for each 10-mmHg increase in BP was 1.38 (95%CI 1.17-1.63, p<0.001) for 24-hr BP and 1.18 (95%CI 1.05-1.33, p=0.006) for office BP. However, the significance for office BP was lost once the 24-hr, daytime and nighttime ambulatory BP data were added to the covariates. CONCLUSION: The prevalence of resistant hypertensive patients among all of the hypertensive patients is 4.1%. Based on this prevalence, the number of resistant hypertensive individuals in Japan would be 1,870,000 patients. In future renal denervation clinical studies in Japan, we should set the primary endpoint as a 24-hr systolic BP reduction measured by ABPM.

Thrombus just beneath a retrievable inferior vena cava filter in a pregnant woman with deep vein thrombosis: its removal requiring catheter thrombus fragmentation with fibrinolysis.

Recently, transient inferior vena cava (IVC) filters have been employed to protect against pulmonary embolism (PE) in pregnant women with deep vein thrombosis. A 34-year-old primiparous Japanese woman with a history of myomectomy was diagnosed with deep vein thrombosis by ultrasound at 27 weeks of gestation. Unfractionated heparin was administered, which soon ameliorated swelling in the right thigh. A transient IVC filter was implanted just before cesarean section. An enhanced computed tomography scan 2 days after cesarean section revealed a wide thrombus just distal to the filter. We performed catheter thrombus fragmentation with fibrinolysis just before the removal of the IVC filter, resulting in re-canalization of blood flow. No significant PE occurred. Although a transient IVC filter may work well for the prophylaxis of PE during labor and delivery, catheter fragmentation with fibrinolysis may become necessary at removal of the filter.

High-sensitivity troponin T is a prognostic marker for patients with aortic stenosis after valve replacement surgery.

BACKGROUND: Aortic stenosis (AS) is recognized as a cause of sudden cardiac death. Recently, the measurement of high-sensitivity troponin T (hs-TnT) has become possible. Several studies have clarified that hs-TnT is a marker to indicate mortality of cardiovascular diseases. OBJECTIVES: To examine whether hs-TnT can be used as a prognostic marker to predict the operative outcome of AS. METHODS: We enrolled 60 patients with AS (mean age=68.7 ± 9.6 years, male/female=30/30). Cardiac catheterization and echocardiography were performed to evaluate the severity of AS. Aortic valve replacement surgery was performed in all patients. We defined major adverse cardiac events (MACE) as composite events of heart failure, fatal arrhythmia, and all causes of death. RESULTS: We followed up the patients for 922 ± 800 days. Mean left ventricular ejection fraction was 60.0 ± 1.8%. Mean aortic valve area was 0.61 ± 0.03 cm(2). MACE occurred in 11 patients (18%), including 5 sudden cardiac deaths. We divided the patients into three groups based on the percentile of the plasma levels of hs-TnT. Kaplan-Meier curve revealed a statistically significant difference in MACE rate among the groups (log-rank test, χ(2)=13.0, p=0.002). We conducted a Cox proportional hazard analysis with a model including age, sex, estimated glomerular filtration rate, and hs-TnT tertile as explanatory variables to predict MACE. We found that hs-TnT tertile to be a significant factor to predict MACE (hazard ratio: 3.71, p=0.03). CONCLUSIONS: hs-TnT can be a prognostic marker for patients with AS after valve replacement surgery.

Minimizing the inhibitory effect of neutralizing antibody for efficient gene expression in the liver with adeno-associated virus 8 vectors.

Neutralizing antibodies (NAbs) against adeno-associated viruses (AAVs) are known to interfere with AAV vector-mediated gene transfer by intravascular delivery. Evading the inhibitory effects of antibodies against AAV vectors is necessary for efficient transfer of therapeutic genes clinically. For this purpose, we tested the efficacy of saline flushing in order to avoid contact of vectors with NAbs present in blood. Direct injection of the AAV8 vector carrying the factor IX (FIX) gene into the portal vein of macaques using saline flushing achieved transgene-derived FIX expression (4.7 ± 2.10-10.1 ± 5.45% of normal human FIX concentration) in the presence of NAbs. Expression was as efficient as that (5.43 ± 2.59-12.68 ± 4.83%) in macaques lacking NAbs. We next tested the efficacy of saline flushing using less invasive balloon catheter-guided injection. This approach also resulted in efficient expression of transgene-derived FIX (2.5 ± 1.06-9.0 ± 2.37%) in the presence of NAbs (14-56× dilutions). NAbs at this range of titers reduced the efficiency of transduction in the macaque liver by 100-fold when the same vector was injected into mesenteric veins without balloon catheters. Our results suggest that portal vein-directed vector delivery strategies with flushing to remove blood are efficacious for minimizing the inhibitory effect of anti-AAV antibodies.

S100A12 as a marker to predict cardiovascular events in patients with chronic coronary artery disease.

BACKGROUND: S100A12, a calgranulin family protein released from white blood cells, is involved in inflammatory cardiovascular disease. It was hypothesized that the plasma level of S100A12 can be used to predict outcome in patients with chronic coronary artery disease (CAD). The purpose of this study was to clarify the clinical significance of S100A12 in patients with stable CAD. METHODS AND RESULTS: A total of 652 patients with stable CAD were studied. All patients underwent percutaneous coronary intervention and successful revascularization. Major adverse cardiovascular events (MACE) were defined as a composite of events of CHF, recurrence of angina pectoris, acute myocardial infarction, stroke, critical arrhythmia, intervention to peripheral arteries and cardiac death. The mean follow-up period was 973±639 days. MACE occurred in 108 patients (16.6%). Plasma S100A12 level had a significant positive correlation with high-sensitivity C-reactive protein (hs-CRP) level. On Kaplan-Meier curve analysis the incidence of MACE was significantly different among S100A12 quartiles (P=0.026). The highest S100A12 quartile (Q4) had a significantly higher MACE rate than the lowest quartile (Q1) (P=0.002). In contrast, hs-CRP was not significant for predicting MACE in the present subjects (P=0.074). A Cox proportional hazard model showed that S100A12 was an independent factor for predicting MACE in multivariate models. CONCLUSIONS: S100A12 could be a novel biomarker for predicting cardiovascular events for predicting MACE in patients with stable CAD.

A case of Takayasu arteritis with repeated coronary artery restenosis after drug-eluting stent implantation successfully treated with a combination of steroids.

A 52-year-old woman with Takayasu arteritis developed acute coronary syndrome and received percutaneous coronary intervention (PCI). The patient experienced restenosis three times even with drug-eluting stent (DES) implantation. We started steroid administration after the fourth PCI to reduce inflammation due to autoimmunity. With DES and a steroid combination, the patient remained free of chest pain, and a follow-up angiography demonstrated good patency of the stent site. Since in-stent restenosis may result from a complicated combination of neointimal proliferation and autoimmune mechanisms, physicians should consider a combination of DES and a steroid for the treatment of coronary artery disease in Takayasu arteritis.