Search

Numerous basic studies have shown a relationship between interleukin-6 (IL-6) and the development or severity of myocarditis. However, there has been no study in which the effect of IL-6 levels in patients with myocarditis was evaluated.We enrolled control patients (n = 12) and consecutive patients with acute myocarditis (n = 13), including lymphocytic, eosinophilic, and giant cell myocarditis, and investigated the pathological and clinical effects of IL-6 on human myocarditis.The serum IL-6 level in patients with myocarditis (16.7 [9.9, 103.8] pg/mL) was significantly higher than that in the control patients (1.4 [1.0, 1.9] pg/mL) (P0.001). Immunohistochemical analysis showed that IL-6 was expressed in infiltrating inflammatory cells of endomyocardial biopsy samples from all patients with myocarditis. Moreover, the log-transformed value of serum IL-6 level showed significant positive correlations with serum creatine kinase (CK) level, CK-MB level, peak CK level, peak CK-MB level and C-reactive protein level (all P ≤ 0.005) and a negative correlation with the left ventricular (LV) ejection fraction (p = 0.014). We divided the patients with myocarditis into a low IL-6 group (9.9 [4.5, 14.2] pg/dL, n = 7) and a high IL-6 group (108.9 [51.1, 130.9] pg/dL, n = 6). The degree of infiltration of IL-6-expressing inflammatory cells in myocardial samples obtained from patients in the high IL-6 group was significantly more severe than that in samples obtained from patients in the low IL-6 group. Furthermore, patients in the high IL-6 group significantly more frequently received catecholamine therapy (P = 0.005), venoarterial extracorporeal membrane oxygenation (P = 0.029), and artificial respirator support (P = 0.021) in the acute phase of myocarditis.The results suggest that there is a strong impact of IL-6 on cardiac injury and dysfunction in patients with myocarditis.

Background Calcium channel blockers (CCB), the first accepted treatment, is effective only in a small number of idiopathic pulmonary arterial hypertension (I-PAH) patients with vasoreactivity [these patients are identified by a positive acute pulmonary vasoreactive test (AVT) response]. While the majority of I-PAH patients is non-vasoreactive and CCB non-responders, modern advanced pulmonary hypertension (PH)-specific therapies, which act on one of the three different mechanistic pathways—endothelin, nitric oxide (NO), and prostacyclin pathways, are effective. Treatment response to advanced PH-specific vasodilators in PAH patients with vasoreactivity is unknown. Case summary A 30-year-old woman with I-PAH was referred to our centre with worsening symptoms and deteriorating PH. She was being administered oral triple combination of advanced PH-specific treatment including a phosphodiesterase-5 inhibitor, an endothelin receptor antagonist, and a long-acting prostacyclin analogue. The patient showed positive AVT with NO inhalation while on these advanced PH-specific drugs. We added high-dose CCB, which dramatically normalized her pulmonary blood pressure without further symptoms, and she has remained stable for 5 years. Discussion Our case describes a PAH patient with vasoreactivity, who was resistant to three different types of advanced PH-specific vasodilators but was exclusively sensitive to CCB treatment. Some CCB responders may have a specific CCB-sensitive PAH phenotype refractory to other pulmonary vasodilators. This case highlights the role of identifying CCB responders in this era of use of modern, advanced PH-specific vasodilators. The investigation of the mechanisms underlying CCB sensitivity in PAH is necessary.

Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by chronic stenosis or obstruction of the pulmonary arteries due to thromboembolism. Although previous studies have shown untreated CTEPH has a poor prognosis, the establishment of gold-standard therapies including pulmonary endarterectomy, balloon pulmonary angioplasty (BPA), and medical therapy has improved hemodynamics and right ventricular function, leading to good long-term survival. BPA is an important therapy for patients with inoperable CTEPH, although the procedure is currently limited to specific institutions and operators. This review discusses the development of the rapidly evolving field of CTEPH that includes improvements in imaging modalities and advances in surgical and interventional techniques.

The early and long-term outcomes after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) have been established by several high-volume centers, but the impact of postoperative residual pulmonary hypertension affecting postoperative clinical parameters remains unclear. This study aims to investigate the institutional surgical results of PEA and to evaluate the efficacy of additional balloon pulmonary angioplasty (BPA) for residual pulmonary hypertension.We retrospectively reviewed 222 patients (57.7 ± 12.9 years old, 141 female) who underwent PEA for CTEPH at the National Cerebral and Cardiovascular Center between 2000 and 2020.The preoperative mean pulmonary artery pressure (mPAP) was 45.6 ± 9.7 mmHg and pulmonary vascular resistance (PVR) was 1062 ± 451 dyne*sec/cmPEA provided immediate and substantial improvements in pulmonary hemodynamics and favorable long-term survival. In addition, postoperative BPA improved postoperative clinical parameters for eligible patients regardless of the presence of residual PH.

Introduction: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by arteriopathy in the small to medium-sized distal pulmonary arteries, often accompanied by infiltration of inflammatory cells. Aryl hydrocarbon receptor (AHR), a nuclear receptor/transcription factor, detoxifies xenobiotics and regulates the differentiation and function of various immune cells. However, the role of AHR in the pathogenesis of PAH is largely unknown. Hypothesis: We hypothesized that AHR has a role in PAH pathogenesis both in human and animal models. Methods: Wild type (WT) and Ahr -knockout ( Ahr -/- ) rats were either treated with AHR agonists or VEGFR2 inhibitors or fed a diet containing a Chinese herbal drug Qing-Dai, which may cause drug-induced PAH, in combination with hypoxia, and then subjected to hemodynamic analysis. Histological characteristics were analyzed in the lungs of these rats and patients with idiopathic PAH. RNA-seq and qRT-PCR were performed on specimens from SU5416/Hypoxia (SuHx) rats, including lungs and the peripheral blood mononuclear cells (PBMCs), and PBMCs of PAH patients. AHR agonistic activity in serum was judged by luciferase reporter assay. Results: WT rats treated with the potent endogenous AHR agonist (6-formylindolo[3,2-b]carbazole) in combination with hypoxia, developed severe pulmonary hypertension (PH) with plexiform-like lesions, whereas WT rats treated with the potent VEGFR2 inhibitors (KI8751 and TAK-593) did not. Ahr -/- rats did not develop PH in the SuHx rats. A diet containing Qing-Dai in combination with hypoxia led to development of PH in Ahr +/+ rats, but not in Ahr -/- rats. Several inflammatory signaling pathways were up-regulated in endothelial cells and PBMCs, which led to infiltration of CD4 + IL-21 + T cells and MRC1 + macrophages into vascular lesions in an AHR-dependent manner. AHR agonistic activity in serum was significantly higher in PAH patients than in healthy volunteers and was associated with poor prognosis of PAH. The expression of several AHR-related genes were changed in PBMCs of PAH patients. Conclusions: AHR plays crucial roles in the development and progression of PAH, indicating that this receptor is a potential target for both diagnosis and treatment of PAH.

Background Balloon pulmonary angioplasty (BPA) has shown beneficial effects for chronic thromboembolic pulmonary hypertension (CTEPH). However, previous studies have shown less cardiac output improvement and symptoms remaining after BPA, implying poor right ventricular (RV) function recovery. Therefore, we investigated the residual RV dysfunction after BPA to reveal risk factors, clinical effects, and possible underlying histopathological mechanisms. Methods and results We investigated 61 consecutive CTEPH patients who underwent cardiovascular magnetic resonance before and 3 and 12 months after BPA series. Residual dysfunction (RD) of RV was defined as RV end-diastolic volume index >100 ml/m2 or RV ejection fraction (EF) Compared with the ND group, the RD group had significantly worse World Health Organization (WHO) functional class at follow-up. No significant hemodynamic differences were observed between the groups. On multivariable logistic regression analysis, male sex (odds ratio [OR] 12.5, p = 0.004) and prolonged QRS duration (OR 1.08, p = 0.029) were independently associated with residual RV dysfunction. Additionally, RV histopathology in 11 CTEPH autopsy cases showed that QRS duration was correlated with RV fibrosis area. Conclusions Relatively high percentage (44%) of residual RV dysfunction with worse WHO functional class was observed in CTEPH patients even after BPA. Prolonged QRS duration may predict poor recovery in RV function after BPA.

ObjectivePulmonary arterial hypertension (PAH), caused by pulmonary artery remodelling and increased pulmonary vascular resistance (PVR) due to an unknown mechanism, is an intractable disease with a poor prognosis. The recent development of PAH-specific treatment medications may allow for higher PVR reduction than previously achieved. This study aimed to identify the prognostic significance of follow-up PVR levels achieved shortly after the initiation of targeted treatment in patients with idiopathic/heritable pulmonary arterial hypertension (I/H-PAH).MethodsWe analysed the data of all patients with I/H-PAH admitted to our hospital between 1998 and 2019. We collected data at baseline and during the first invasive haemodynamic evaluation. The primary outcome was death or lung transplantation.ResultsOf the 133 treatment-naïve patients enrolled in this study, 47 experienced adverse events during a median follow-up period of 6.4 (IQR 3.5–11.5) years. The median time interval to first follow-up from diagnosis was 162 (IQR 117–253) days. Incidence of the primary outcome was significantly lower in patients who achieved low PVR at follow-up. Of risk factors evaluated at follow-up, the multivariate Cox regression analysis revealed PVR as an independent predictor of the primary outcome (HR 1.103, 95% CI 1.029 to 1.183; p=0.006). The results were consistent across risk profiles according to the simplified risk stratification recommended by the European Society of Cardiology and European Respiratory Society guidelines.ConclusionFollow-up PVR was an independent predictor of transplant-free survival in patients with I/H-PAH. Evaluation of haemodynamic status shortly after initiating treatment may help predict long-term prognosis.

In patients with an atrial septal defect (ASD) and left ventricular (LV) dysfunction associated with coronary artery disease (CAD), to avoid the development of acute left heart failure (HF) and an increase in myocardial oxygen consumption following ASD closure, it is conceivable that coronary artery revascularization should be performed prior to ASD closure. We report the case of a 67-year-old man with a large secundum ASD and LV ejection fraction of 15.6% resulting from severe ischemic cardiomyopathy and triple-vessel CAD, both of which contributed to biventricular HF characterized by high left-to-right shunt (Qp:Qs of 7.1:1) and low systemic cardiac output. After evaluating his hemodynamics and biventricular function with cardiac catheterization and cardiovascular magnetic resonance imaging, we successfully conducted an inverse, stepwise strategy of transcatheter ASD closure using anti-congestive therapies, intraaortic balloon pumping, and subsequent balloon occlusion testing, followed by on-pump beating-heart coronary artery bypass grafting.

Systemic right ventricular (RV) failure in patients with congenitally corrected transposition of the great arteries (ccTGA), a major cause of mortality in the long-term follow-up, is usually induced by concomitant severe morphologically tricuspid regurgitation (TR) with/without Ebstein's anomaly or progressive conduction tissue disturbances. However, whether or not myocardial fibrosis is a common cause of systemic RV failure in patients with ccTGA remains unclear. Here, we describe an 82-year-old man who had been diagnosed previously as having uncomplicated ccTGA and situs inversus and recently developed systemic RV failure, which was neither associated with severe TR nor advanced conduction tissue abnormalities. Cardiovascular magnetic resonance (CMR) with delayed-enhancement imaging clearly detected extensive myocardial scars (presumably fibrosis) in the RV wall as well as prominent dilatation, hypertrophy, and systolic dysfunction of the systemic RV. These findings suggest that myocardial fibrosis can cause systemic RV failure in elderly patients with uncomplicated ccTGA despite the absence of severe TR or advanced conduction tissue abnormalities and that CMR may be a useful examination to accurately detect systemic RV failure associated with myocardial fibrosis and to subsequently clarify the prognosis in these patients.

A 45-year-old man, who was implanted with an inferior vena cava (IVC) filter in his infrarenal IVC, had a complication of deep vein thrombosis (DVT) propagation from the IVC, beyond the IVC filter, to the right calf and left external iliac veins. The entire IVC filter was covered with a massive thrombus. We first decided to retrieve the IVC filter itself, which was suspected of causing metallic allergy. The thrombotic IVC filter was successfully retrieved using multi-step catheter intervention. To our knowledge, this is the first case report to describe successful multi-step catheter intervention for retrieval of an IVC filter covered with a massive thrombus.

Coronary microvessel endothelial dysfunction and nitric oxide (NO) depletion contribute to elevated passive tension of cardiomyocytes, diastolic dysfunction and predispose the heart to heart failure with preserved ejection fraction. We examined if diastolic dysfunction at the level of the cardiomyocytes precedes coronary endothelial dysfunction in prediabetes. Further, we determined if myofilaments other than titin contribute to impairment. Utilizing synchrotron microangiography we found young prediabetic male rats showed preserved dilator responses to acetylcholine in microvessels. Utilizing synchrotron X-ray diffraction we show that cardiac relaxation and cross-bridge dynamics are impaired by myosin head displacement from actin filaments particularly in the inner myocardium. We reveal that increased PKC activity and mitochondrial oxidative stress in cardiomyocytes contributes to rho-kinase mediated impairment of myosin head extension to actin filaments, depression of soluble guanylyl cyclase/PKG activity and consequently stiffening of titin in prediabetes ahead of coronary endothelial dysfunction.

Objective To determine safety and efficacy of cardiac rehabilitation (CR) initiated immediately following balloon pulmonary angioplasty (BPA) in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) who presented with continuing exercise intolerance and symptoms on effort even after a course of BPA; 2–8 sessions/patient. Methods Forty-one consecutive patients with inoperable CTEPH who underwent their final BPA with improved resting mean pulmonary arterial pressure of 24.7±5.5 mm Hg and who suffered remaining exercise intolerance were prospectively studied. Participants were divided into two groups just after the final BPA (6.8±2.3 days): patients with (CR group, n=17) or without (non-CR group, n=24) participation in a 12-week CR of 1-week inhospital training followed by an 11-week outpatient programme. Cardiopulmonary exercise testing, haemodynamics, and quality of life (QOL) were assessed before and after CR. Results No significant between-group differences were found for any baseline characteristics. At week 12, peak oxygen uptake (VO2), per cent predicted peak VO2 (70.7±9.4% to 78.2±12.8%, p

Inferior vena cava (IVC) stenosis is a well-known complication of the IVC filter. However, there are no previous reports of IVC stenosis caused by a temporary IVC filter. In this case report, we describe the case of a 35-year-old man who was referred to our center for the treatment of recurrent proximal deep vein thrombosis (DVT) and severe IVC stenosis that occurred after retrieval of a temporary IVC filter. We performed a catheter-directed thrombolysis and balloon angioplasty. DVT resolved effectively, and his leg symptoms resolved. .

Although several tissue-Doppler imaging (TDI) models for pulmonary capillary wedge pressure (PCWP) estimation have been reported, their reliability remains uncertain. Our previous theoretical and experimental analyses suggest that right atrial pressure (RAP) corrected by tissue-Doppler imaging tricuspid/mitral annular peak systolic velocities (ST/SM) (RAP × ST/SM) reliably predicts elevated PCWP. We sought to investigate its clinical usefulness for predicting elevated PCWP in heart failure (HF) patients. Ninety-eight patients admitted with HF who underwent right heart catheterization were prospectively studied. RAP and PCWP were measured by right heart catheterization. Simultaneously, ST/SM, early diastolic transmitral flow velocity to mitral annular velocity ratio (E/Ea), and diameter of inferior vena cava at inspiration (IVCDi), a noninvasive surrogate for RAP, were measured by echocardiography. RAP correlated with IVCDi (R2 = 0.57). A significantly stronger correlation was observed between IVCDi corrected by ST/SM (IVCDi × ST/SM) and PCWP than between E/Ea and PCWP (R2 = 0.47 vs 0.18). Receiver-operating characteristic analyses indicated that IVCDi × ST/SM >16 mm predicted PCWP >18 mm Hg with 90% sensitivity and 77% specificity, and the area under the curve was 0.86, which was significantly larger than that of E/Ea (area under the curve=0.72). In conclusions, IVCDi × ST/SM is a new useful noninvasive model to predict elevated PCWP in HF patients.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating but potentially reversible complication of chronic pulmonary thromboembolic disease characterized by progressive right heart dysfunction secondary to pulmonary arterial stenosis or occlusion. Balloon pulmonary angioplasty (BPA) has recently emerged as an alternative intervention for non-surgical candidates with CTEPH. Modern reperfusion angioplasty techniques relieve sequela of chronic pulmonary hypertension, ameliorate right ventricular failure, and improve functional status. This article will discuss the diagnosis and treatment of patients with CTEPH and the current state of endovascular management with BPA.

BACKGROUND Post-thrombotic syndrome (PTS), the most common complication of deep venous thrombosis (DVT), develops in ≥50% of patients with iliofemoral DVT. However, the benefit of endovascular treatment in Japanese patients with chronic DVT and PTS remains unclear. Methods and Results: Between June 2014 and May 2016, endovascular treatment was performed in 11 consecutive Japanese patients with chronic iliofemoral DVT and PTS refractory to anticoagulant therapy and elastic compression stockings. We evaluated the technical success rate, complications, patency, Villalta score, calf circumference, and popliteal vein reflux in both the acute stage (the day following endovascular treatment) and chronic stage (after 6 months). Imaging follow-up included venous duplex scanning and/or magnetic resonance venography. The technical success rate was 81.8%, without complications. In patients with successful intervention, the Villalta score improved significantly, from 9.0±3.7 preoperatively to 3.6±2.5 in the acute phase (P

We previously demonstrated the usefulness of temporary inferior vena cava filters (t-IVCFs) to prevent pulmonary thromboembolism in pregnant women with deep venous thrombosis (DVT). However, there is currently no consensus on the indications for intrapartum t-IVCF in pregnant women with DVT. In this study, we re-evaluated the safety and usefulness of t-IVCF inserted in this condition.A retrospective evaluation in a single center was performed of 45 Japanese patients (54 pregnancies) with DVT between 1989 and 2014. Intrapartum t-IVCF insertion was indicated in patients who had or might have had extensive DVT located in iliofemoral veins and who had floating thrombi in the veins of their lower limbs.Eighteen patients (40%) had thrombophilias. Onset of DVT and delivery occurred at 17 ± 9 weeks and 37 ± 2 weeks of gestation, respectively. Twenty pregnant women underwent placement of an intrapartum t-IVCF. All t-IVCFs were successfully placed in the suprarenal inferior vena cava before delivery. Filter-related complications occurred in two cases (10%). One was an allergic reaction to the lidocaine used at the insertion, and another was dislocation of the t-IVCF to the right atrium. The t-IVCFs were placed for more acute DVT compared with the 34 pregnancies without t-IVCF; the onset of DVT with t-IVCF was significantly later (22 vs 12 weeks; P = .002), and the duration of unfractionated heparin therapy was significantly shorter (16 vs 28 weeks; P.001). There was no case of clinical pulmonary embolism in the perinatal period. Thrombus was detected macroscopically at the removed t-IVCF in 15 cases; however, almost all were minute pieces. In only one case with protein S deficiency and placental abruption was a large thrombus captured in the t-IVCF, which was considered to have prevented a clinically relevant pulmonary embolus.Placement of a t-IVCF appears to be safe for pregnant women. However, intrapartum t-IVCF insertion is considered to be unnecessary for pregnant women with DVT who have received anticoagulation therapy at early onset of gestation and long term before delivery. Patients with thrombophilia and at high risk of hemorrhage may represent a subgroup of women who would benefit from t-IVCF placement, but larger prospective multicenter evaluations are required to establish that fact.

It had been reported that BPA significantly improved pulmonary artery hypertension, New York Heart Association (NYHA) class and 6-minute walk distances (6MWD), in patients whose mean pulmonary arterial pressure (mPAP) >30mmHg. However, CTEPH patients with mPAP ≤30mmHg still have the symptom such

Right ventricular (RV) function is an important predictor in the course of chronic thromboembolic pulmonary hypertension (CTEPH). Recently, balloon pulmonary angioplasty (BPA) has been reported to improve hemodynamics and functional capacity in patients with CTEPH. However, there are no reports