Endovascular Therapy for Vascular Graft Infection After Multiple Bypass Surgeries for Aorto-Iliac Occlusive Disease.

BACKGROUND: Vascular graft infection is a very complex disease. Although complete excision of the infected grafts with extra-anatomic bypass or in situ reconstruction is a general treatment strategy, some concerns including reinfection in the new graft remain. CASE REPORT: An 88 year-old man presented to the hospital with abdominal swelling and bleeding. The patient had undergone revascularization for aorto-iliac occlusive disease twice in the past. The first procedure had been performed 15 years previously, with right ilio-femoral bypass grafting for right iliac artery occlusion and stent implantation for left iliac artery stenosis. The second procedure had been performed 10 years previously, with aorta-to-left femoral and left-to-right femoro-femoral bypass grafting because the terminal aorta, the first ilio-femoral bypass graft, and the stent of the left iliac artery had been occluded. The patient was diagnosed with vascular graft infection, and endovascular therapy was selected as the revascularization method prior to graft excision. It was successfully performed using various devices and techniques, followed by graft excision without critical limb ischemia. CONCLUSION: This case demonstrates that endovascular therapy prior to graft excision can be an alternative revascularization method for vascular graft infection after bypass surgery for aorto-iliac occlusive disease.

Rapid Formation of an Infected Coronary Artery Aneurysm With Stent Fracture.

Infected coronary artery aneurysm (ICAA) is a rare but fatal disease. We describe a case of rapid formation of ICAA with fracture of an intracoronary stent observed on coronary angiography and cardiac computed tomography. Surgery with resection of the aneurysm and coronary artery bypass grafting was performed successfully. (Level of Difficulty: Intermediate.).

Hokuriku-plus familial hypercholesterolaemia registry study: rationale and study design.

INTRODUCTION: Familial hypercholesterolaemia (FH) is an autosomal-dominant inherited genetic disease. It carries an extremely high cardiovascular risk associated with significantly elevated low-density lipoprotein (LDL) cholesterol. The diagnostic rate of this disease in some European nations is quite high, due to the presence of multiple prospective registries. On the other hand, few data-and in particular multicentre data-exist regarding this issue among Japanese subjects. Therefore, this study intends to assemble a multicentre registry that aims to comprehensively assess cardiovascular risk among Japanese FH patients while taking into account their genetic backgrounds. METHODS AND ANALYSIS: The Hokuriku-plus FH registry is a prospective, observational, multicentre cohort study, enrolling consecutive FH patients who fulfil the clinical criteria of FH in Japan from 37 participating hospitals mostly in Hokuriku region of Japan from April 2020 to March 2024. A total of 1000 patients will be enrolled into the study, and we plan to follow-up participants over 5 years. We will collect clinical parameters, including lipids, physical findings, genetic backgrounds and clinical events covering atherosclerotic and other important events, such as malignancies. The primary endpoint of this study is new atherosclerotic cardiovascular disease (ASCVD) events. The secondary endpoints are as follows: LDL cholesterol, secondary ASCVD events and the occurrence of other diseases including hypertension, diabetes and malignancies. ETHICS AND DISSEMINATION: This study is being conducted in compliance with the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects, and all other applicable laws and guidelines in Japan. This study protocol has been approved by the Institutional Review Board at Kanazawa University. We will disseminate the final results at international conferences and in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: UMIN000038210.

Huge right ventricular mass lesion associated with genital malignant tumor: a case report.

BACKGROUND: Primary heart tumors are rare, whereas metastatic heart tumors occur more frequently. CASE PRESENTATION: We report a case of a 75-year-old Japanese woman who had metastatic heart tumors of the right ventricle. Although she initially received antibiotic therapy following a diagnosis of pneumonia and pleuritis, her symptoms worsened, and she developed dyspnea and bilateral lower limb edema. Echocardiography showed a huge mass lesion occupying the entire right ventricle. Because the patient's tumor markers were elevated, we used computed tomography to search for the primary lesion, which was located in the vagina or the uterus. Histology demonstrated the presence of basaloid squamous cell carcinoma in the vaginal tissue. Chemotherapy with paclitaxel and carboplatin was initiated. CONCLUSIONS: These data suggest that the tumor in the right ventricle metastasized from the genital organs.

Impact of combined lipid lowering and blood pressure control on coronary plaque: myocardial ischemia treated by percutaneous coronary intervention and plaque regression by lipid lowering and blood pressure controlling assessed by intravascular ultrasonography (MILLION) study.

The aim of the study was to elucidate the aggressive reduction of both low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) reduced coronary atherosclerotic plaque volume compared with a standard treatment of LDL-C and BP in Japanese patients with coronary artery disease (CAD). This study is a prospective, randomized, and open-labelled with a blind-endpoint evaluation study. A total of 97 patients (81 men, mean age 62.0 ± 9.6) with CAD undergoing intravascular ultrasonography (IVUS)-guided percutaneous coronary intervention (PCI) were randomized, and 68 patients had IVUS examinations at baseline and at 18-24 months follow-up. Patients were randomly assigned to standard or aggressive strategies targeting LDL-C and a BP of 100 mg/dL and 140/90 mmHg vs. 70 mg/dL and 120/70 mmHg, respectively. The primary endpoint was the percent change in coronary plaque volume. Both standard and aggressive strategies succeeded to achieve target levels of LDL-C and BP; 74.9 ± 14.7 vs. 63.7 ± 11.9 mg/dL (NS) and 124.1 ± 9.4/75.8 ± 7.7 vs. 113.6 ± 9.6/65.8 ± 9.4 mmHg (systolic BP; NS, diastolic BP; p < 0.05), respectively. Both groups showed a significant reduction in the coronary plaque volume of -9.4 ± 10.7% and -8.7 ± 8.6% (NS) in standard and aggressive therapies, respectively. Both standard and aggressive intervention significantly regressed coronary plaque volume by the same degree, suggesting the importance of simultaneous reductions of LDL-C and BP for prevention of CAD.

Impact of combined lipid lowering with blood pressure control on coronary plaque regression: rationale and design of MILLION study.

A line of epidemiological studies suggests that the accumulation of coronary risk factors promotes the progression of coronary atherosclerosis. Recent clinical studies showed that aggressive low-density lipoprotein (LDL) cholesterol-lowering therapy using statins could regress coronary atheroma and reduce major cardiovascular events. Additionally, therapy that controlled amlodipine-based blood pressure reduced major cardiovascular events in patients with hypertension compared with an atenolol-based regimen. An open-label randomized multicenter study is primarily planned to evaluate the changes in coronary atheroma volume using intravascular ultrasonography 18-24 months after intensive lowering of LDL-cholesterol and blood pressure compared with a standard therapy indicated by current guidelines in Japanese patients with coronary artery disease (CAD). The secondary endpoints include changes in serum lipid levels, inflammatory markers, glucose markers and blood pressure. In total, 100 subjects with CAD who are undergoing percutaneous coronary intervention will be tested. The MILLION study will provide new evidence and therapeutic standards for the prevention of CAD in Japanese patients by controlling both LDL-C levels and blood pressure.

A novel mutation in the transmembrane nonpore region of the KCNH2 gene causes severe clinical manifestations of long QT syndrome.

BACKGROUND: Long QT syndrome (LQTS) is characterized by prolonged ventricular repolarization and variable clinical course with arrhythmia-related syncope and sudden death. Mutations in the nonpore region of the LQTS-associated KCNH2 gene (also known as hERG) are mostly associated with coassembly or trafficking abnormalities, resulting in haplotype insufficiency and milder clinical phenotypes compared with mutations in the pore domain. OBJECTIVE: To investigate the effect of a nonpore mutation on the channel current, which was identified from an LQTS family with severe clinical phenotypes. METHODS: Two members of a Japanese family with LQTS were searched for mutations in KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, and KCNJ2 genes by using automated DNA sequencing. We characterized the electrophysiological properties and glycosylation pattern of the mutant channels by using patch clamp recording and Western blot analysis. RESULTS: In the LQTS patient with torsades de pointes and cardiopulmonary arrest, we identified the novel T473P mutation in the transmembrane nonpore region of KCNH2. The proband's father carried the same mutation and showed prolonged corrected QT interval and frequent torsades de pointes in the presence of hypokalemia following the administration of garenoxacin. Patch clamp analysis in heterologous cells showed that hERG T473P channels generated no current and exhibited a dominant negative effect when coexpressed with wild-type protein. Only incompletely glycosylated hERG T473P channels were observed by using Western blot analysis, suggesting impaired trafficking. CONCLUSIONS: These results demonstrated that a trafficking-deficient mutation in the transmembrane nonpore region of KCNH2 causes a dominant negative effect and a severe clinical course in affected patients.

Impact of out-stent plaque volume on in-stent intimal hyperplasia: results from serial volumetric analysis with high-gain intravascular ultrasound.

BACKGROUND: Changes in out-stent plaque volume can be related to in-stent intimal hyperplasia. However, few data exist regarding the impact of out-stent plaque volume on in-stent intimal hyperplasia. METHODS: We prospectively performed volumetric intravascular ultrasound in 46 stable coronary patients (34 males, mean age of 66 years) immediately as well as 18 months after stenting. From the high-gain ultrasound images, out-stent plaque volume was calculated by extracting the stent volume from the external elastic membrane volume. Volumes of in-stent intimal hyperplasia and reference plaque were also evaluated. RESULTS: Out-stent plaque volume increased from 177.3 ± 100.8mm(3) to 190.7 ± 111.1mm(3) (p<0.05) in correlation with increases in-stent intimal hyperplasia (r=0.536, p<0.05). Under these conditions, changes in reference plaque volume correlated with those in LDL-C, which decreased from 121.2 ± 48.0mg/dl to 103.3 ± 48.9 mg/dl (r=0.43, p<0.05). Interestingly, increases in out-stent plaque volume in the silorimus-eluting stent (2.7 ± 1.2%) were lesser than those in the bare-metal stent (14.0 ± 11.0%, p<0.05). CONCLUSIONS: These results indicate that irrespective of LDL-C level, changes in out-stent plaque volume correlate with those in in-stent intimal hyperplasia. We suggest that silorimus-eluting stent can suppress in-stent intimal hyperplasia partially by affecting out-stent plaque, although further large-scale studies are required to define the role of out-stent plaque in the occurrence of in-stent intimal hyperplasia.

Pulmonary hypertension associated with veno-occlusive disease in systemic sclerosis: Insight into the mechanism of resistance to vasodilator.

We report a case with pulmonary veno-occlusive disease (PVOD) associated with systemic sclerosis which exhibits strong resistance to pulmonary vasodilator. A 55-year-old female with severe pulmonary hypertension was admitted to our hospital to be introduced to epoprostenol infusion therapy. She was diagnosed as having pulmonary arterial hypertension (PAH) associated with systemic sclerosis at the age of 51. Several aggressive treatments with pulmonary vasodilators, including oral prostaglandin, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors, failed to improve her symptoms. We introduced continuous intravenous epoprostenol therapy from 2 µg/kg/min for her. However, pulmonary edema appeared and worsened in a dose-dependent manner. We made a diagnosis of PVOD clinically at that time. Thereafter, pulmonary edema gradually disappeared consistent with the reduction of the dose of epoprostenol infusion. She died of renal failure and infection 4 months after the introduction of epoprostenol infusion therapy. A histological examination revealed severe stenosis and occlusions of pulmonary veins as well as pulmonary arteries over a wide area. We suggest that prevalence of veno-occlusive type of disease could be one of the major mechanisms of less responsive or even refractory to pulmonary vasodilator therapies in patients with PAH associated with connective tissue disease.

Polymorphic ventricular tachycardia in a patient with hypertrophic cardiomyopathy and digitalis intoxication.

We report the case of a 74-year-old woman who presented with recurrent episodes of polymorphic ventricular tachycardia (PVT) with a normal QT interval due to digitalis intoxication (serum digoxin concentration, 5.0 ng/mL) and severe hyperkalemia (serum potassium level, 8.3 mEq/L). In addition, laboratory data showed elevated levels of blood urea nitrogen (54 mg/dL) and serum creatinine (1.57 mg/dL), suggesting dehydration. She had been treated with a combination of digoxin and eplerenone for atrial fibrillation and heart failure. The PVT resolved after treatment for hyperkalemia. Cardiac magnetic resonance imaging and left ventriculography showed left ventricular hypertrophy predominantly in the apex, suggesting apical hypertrophic cardiomyopathy (HCM). We presume that the presence of HCM was related to the occurrence of PVT in this patient with digitalis intoxication and hyperkalemia. .

Multiple noncoding exons 1 of nuclear receptors NR4A family (nerve growth factor-induced clone B, Nur-related factor 1 and neuron-derived orphan receptor 1) and NR5A1 (steroidogenic factor 1) in human cardiovascular and adrenal tissues.

OBJECTIVE: Nuclear receptors are involved in a wide variety of functions, including aldosteronogenesis. Nuclear receptor families NR4A [nerve growth factor-induced clone B (NGFIB), Nur-related factor 1 (NURR1) and neuron-derived orphan receptor 1 (NOR1)] and NR2F [chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TFI), COUP-TFII and NR2F6) activate, whereas NR5A1 [steroidogenic factor 1 (SF1)] represses CYP11B2 (aldosterone synthase) gene transcription. The present study was undertaken to elucidate the mechanism of differential regulation of nuclear receptors between cardiovascular and adrenal tissues. METHODS: We collected tissues of artery (n = 9), cardiomyopathy muscle (n = 9), heart muscle (noncardiomyopathy) (n = 6), adrenal gland (n = 9) and aldosterone-producing adenoma (APA) (n = 9). 5'-rapid amplification of cDNA ends (RACE) identified transcription start sites. Multiplex reverse-transcription PCR (RT-PCR) determined use of alternative noncoding exons 1 (ANEs). RESULTS: In adrenocortical H295R cells, angiotensin II, KCl or cAMP, all stimulated CYP11B2 transcription and NR4A was upregulated, whereas NR2F and NR5A1 were downregulated. 5'-RACE and RT-PCR revealed four ANEs of NGFIB (NR4A1), three of NURR1 (NR4A2), two of NOR1 (NR4A3) and two of SF1 (NR5A1) in cardiovascular and adrenal tissues. Quantitative multiplex RT-PCR showed NR4A and NR5A1 differentially employed multiple ANEs in a tissue-specific manner. The use of ANEs of NGFIB and NURR1 was significantly different between APA and artery. Changes in use of ANEs of NGFIB and NOR1 were observed between cardiomyopathy and noncardiomyopathy. The NR4A mRNA levels in artery were high compared with cardiac and adrenal tissues, whereas the NR5A1 mRNA level in adrenal tissues was extremely high compared with cardiovascular tissues. CONCLUSION: NR4A and NR5A1 genes are complex in terms of alternative promoter use. The use of ANEs may be associated with the pathophysiology of the heart and adrenal gland.

A KCR1 variant implicated in susceptibility to the long QT syndrome.

The acquired long QT syndrome (aLQTS) is frequently associated with extrinsic and intrinsic risk factors including therapeutic agents that inadvertently inhibit the KCNH2 K(+) channel that underlies the repolarizing I(Kr) current in the heart. Previous reports demonstrated that K(+) channel regulator 1 (KCR1) diminishes KCNH2 drug sensitivity and may protect susceptible patients from developing aLQTS. Here, we describe a novel variant of KCR1 (E33D) isolated from a patient with ventricular fibrillation and significant QT prolongation. We recorded the KCNH2 current (I(KCNH2)) from CHO-K1 cells transfected with KCNH2 plus wild type (WT) or mutant KCR1 cDNA, using whole cell patch-clamp techniques and assessed the development of I(KCNH2) inhibition in response to well-characterized KCNH2 inhibitors. Unlike KCR1 WT, the E33D variant did not protect KCNH2 from the effects of class I antiarrhythmic drugs such as quinidine or class III antiarrhythmic drugs including dofetilide and sotalol. The remaining current of the KCNH2 WT+KCR1 E33D channel after 100 pulses in the presence of each drug was similar to that of KCNH2 alone. Simulated conditions of hypokalemia (1mM [K(+)](o)) produced no significant difference in the fraction of the current that was protected from dofetilide inhibition with KCR1 WT or E33D. The previously described α-glucosyltransferase activity of KCR1 was found to be compromised in KCR1 E33D in a yeast expression system. Our findings suggest that KCR1 genetic variations that diminish the ability of KCR1 to protect KCNH2 from inhibition by commonly used therapeutic agents constitute a risk factor for the aLQTS.

Coronary arteriovenous fistulas complicated by complete atrioventricular block: A case report.

We report the case of a patient with bilateral coronary arteriovenous fistulas (CAVFs) connecting the right coronary artery and left circumflex coronary artery with the right atrium who had progression of first-degree atrioventricular (AV) block to complete AV block during a 4-year period. The His bundle electrogram revealed that the complete AV block was the result of a block at the level of the AV node. Dipyridamole stress thallium-201 myocardial imaging showed decreased perfusion in the inferoapical wall. Coronary angiography and computed tomography showed fistulas that arose from the AV nodal branch of the right coronary artery and from the distal portion of the circumflex coronary artery and drained into the right atrium. Because the fistulas were small, they were not repaired surgically, and a permanent pacemaker was implanted to treat the complete AV block. We presumed that the complication by complete AV block was due to abnormalities of the arteries feeding the AV node and chronic ischemia resulting from a coronary steal associated with the fistulas. To the best of our knowledge, this is the first report of CAVF complicated by complete AV block.

An enhanced device for transluminal retrieval of vascular stents without surgical procedures: experimental studies.

BACKGROUND: Although efforts have been focused on developing endovascular procedures by which intravascular devices such as stents could be effectively deployed, few data exist regarding devices for the nonsurgical retrieval of deployed stents. Therefore, we designed to enable retrieval of deployed stents without a surgical procedure. METHODS: The device consisted of four components: ultra-low profile forceps with 2.0 mm in diameter, conducting shaft with 1.8 mm in diameter, control handle by which the forceps is opened or closed, and a covering sheath. This device was designed to advance into the vessel lumen along a 0.014-inch guidewire by over the wire fashion. RESULTS: The forceps could firmly catch nonexpanded as well as expanded tubular-type stents with open cells in an in vitro model that was 4.0 mm in diameter. Then, we used this device in porcine renal arteries with 2.5-5.0 mm in diameter. At first, a fragmented 0.014-inch guidewire could be safely removed without vessel damage that was confirmed by intravascular ultrasound. This device could successfully remove four of five inappropriately and 11 of 14 appropriately deployed stents. Under these conditions, intravascular ultrasound demonstrated minor vessel wall dissection in two-third of cases. CONCLUSIONS: These results demonstrate that the present device can be used for transluminal removal of foreign bodies such as nonexpanded as well as expanded stents in acute phase. Further miniaturization may enable using this type of device in the renal as well as coronary arteries.

Idiopathic dissection from left subclavian artery to brachial artery: Spontaneous repair with conservative management.

We report an unusual case of a 58-year-old female with idiopathic dissection of the left subclavian artery to the brachial artery which provoked vessel narrowing in the acute phase and was spontaneously repaired without surgical procedures in the chronic phase. We describe the serial imaging findings of the angiography and ultrasonography which demonstrate restoration of the dissection. In carefully selected patients, conservative management could be an alternative treatment to surgery or stenting with an excellent outcome.

Long QT syndrome and associated gene mutation carriers in Japanese children: results from ECG screening examinations.

LQTS (long QT syndrome) is caused by mutations in cardiac ion channel genes; however, the prevalence of LQTS in the general population is not well known. In the present study, we prospectively estimated the prevalence of LQTS and analysed the associated mutation carriers in Japanese children. ECGs were recorded from 7961 Japanese school children (4044 males; mean age, 9.9+/-3.0 years). ECGs were examined again for children who had prolonged QTc (corrected QT) intervals in the initial ECGs, and their QT intervals were measured manually. An LQTS score was determined according to Schwartz's criteria, and ion channel genes were analysed. In vitro characterization of the identified mutants was performed by heterologous expression experiments. Three subjects were assigned to a high probability of LQTS (3.5< or = LQTS score), and eight subjects to an intermediate probability (1.0< LQTS score < or =3.0). Genetic analysis of these II subjects identified three KCNH2 mutations (M124T, 547-553 del GGCGGCG and 2311-2332 del/ins TC). In contrast, no mutations were identified in the 15 subjects with a low probability of LQTS. Electrophysiological studies showed that both the M124T and the 547-553 del GGCGGCG KCNH2 did not suppress the wild-type KCNH2 channel in a dominant-negative manner. These results demonstrate that, in a random sample of healthy Japanese children, the prevalence of a high probability of LQTS is 0.038% (three in 7961), and that LQTS mutation carriers can be identified in at least 0.038% (one in 2653). Furthermore, large-scale genetic studies will be needed to clarify the real prevalence of LQTS by gene-carrier status, as it may have been underestimated in the present study.

Impact of QT variables on clinical outcome of genotyped hypertrophic cardiomyopathy.

BACKGROUND: Although QT variables such as its interval and/or dispersion can be clinical markers of ventricular tachyarrhythmia, few data exist regarding the role of QT variables in genotyped hypertrophic cardiomyopathy (HCM). Therefore, we analyzed QT variables in genotyped subjects with or without left ventricular hypertrophy (LVH). METHODS: QT variables were analyzed in 111 mutation and 43 non-mutation carriers who were divided into three groups: A, those without ECG abnormalities and echocardiographically determined LVH (wall thickness > or =13 mm); B, those with ECG abnormalities but LVH; and C, those with ECG abnormalities and LVH. We also examined clinical outcome of enrolled patients. RESULTS: Maximal LV wall thickness in group C (19.0 +/- 4.3 mm, mean +/-SD) was significantly greater than that in group A (9.2 +/- 1.8) and group B (10.4 +/- 1.8). Under these conditions, maximum QTc interval and QT dispersion were significantly longer in group C than those in group A (438 +/- 38 ms vs 406 +/- 30 and 64 +/- 31 vs 44 +/- 18, respectively; P < 0.05). QTc interval and QT dispersion in group B (436 +/- 50 and 64 +/- 22 ms) were also significantly greater than those in group A. During follow-up periods, four sudden cardiac deaths and one ventricular fibrillation were observed in group C, and two nonlethal ventricular tachyarrhythmias were observed in group B. CONCLUSIONS: Patients with HCM-related gene mutation accompanying any ECG abnormalities frequently exhibited impaired QT variables even without LVH. We suggest that careful observation should be considered for those genotyped subjects.