Differences in the feasibility, anatomical parameters predicting procedural difficulty, and isolation area of a left atrial posterior wall isolation using radiofrequency versus cryoballoon catheters.

BACKGROUNDS: The difficulty and outcome of the adjunctive left atrial posterior wall isolation (LAPWI) in patients with persistent atrial fibrillation (PersAF) may be affected by the ablation energy used. This study aimed to compare the completion rate, anatomical parameters predicting procedural difficulty, and the isolation area of a LAPWI between the use of radiofrequency (RFA) and cryoballoon ablation (CBA). METHODS: We enrolled 95 and 93 patients with PersAF who underwent pulmonary vein isolation (PVI)+LAPWI using RFA (RF group) and CBA (CB group), respectively. Preoperative computed tomography was used to evaluate the anatomical features associated with an incomplete LAPWI. Post-ablation 3-dimensional maps were analyzed to quantify the isolation area. RESULTS: The completion rate of the LAPWI was significantly higher in the RF group than the CB group without touch-up RFA (88.4% vs. 72.0%; p = .005). Predictors of incomplete LAPWI were a longer left inferior pulmonary vein (LIPV)-esophageal distance (p < .001) for RFA and a steeper angle of the LAPW (p < .001) and longer transverse LAPW diameter (p = .016) for CBA. The isolated non-PV area with RFA or CBA alone was significantly greater in the CB group than the RF group (27.5 ± 9.5 cm2 vs. 22.9 ± 6.9 cm2 ; p < .001). CONCLUSION: The position of the esophagus at a distance from the LIPV was associated with an incomplete LAPWI using RFA, while a steeper angle of the LAPW and transverse enlargement of the LAPW were associated with that using CBA. The completion rate of the LAPWI was higher with RFA, but the isolation area outside of the PVs was greater with CBA.

Rationale and design of the NEO-NORMAL-AF study examination of the usefulness of implantable loop recorder for arrhythmia detection including atrial fibrillation in heart failure with non-reduced ejection fraction cases: a pilot study.

INTRODUCTION: The incidence of arrhythmia in heart failure with non-reduced ejection fraction (HFnon-rEF) in patients who have a history of hospitalisation is unclear. The aim of this study is to investigate the usefulness of an implantable loop recorder (ILR) for arrhythmia detection including atrial fibrillation (AF) in HFnon-rEF patients after discharge. METHODS AND ANALYSIS: This is a multicentre single arm study to evaluate the usefulness of ILR for detecting arrhythmia. The eligible patients are HFnon-rEF patients (left ventricular ejection fraction ≥40%) aged ≥20 years with a history of hospitalisation. The ILR will be implanted for qualified patients, and ECGs will be monitored and recorded for 1 year to check for arrhythmias. The primary endpoint is new-onset 6 min or more persistent AF detected by ILR. Secondary endpoints are 30 s or more persistent supraventricular tachycardia and ventricular tachycardia, 3 s or more persistent pause, bradycardia with 40 beats per minutes or lower heart rate, AF burden, all-cause death, cardiovascular death, hospital readmission due to exacerbation of HF, acute coronary syndrome, ischaemic or haemorrhagic stroke, non-pharmacological therapy such as pacemaker implantation and ablation. CONCLUSIONS: This study is expected to provide valuable findings regarding arrhythmia in HFnon-rEF patients, and elucidate a potential new therapeutic approach for HFnon-rEF. TRIAL REGISTRATION NUMBER: This trial has been registered in the Japan Registry of Clinical Trials (jRCT) (Trial Registration: jRCTs052210060).

Prevention of Contrast-Induced Nephropathy After Emergency Percutaneous Coronary Intervention With a Single Bolus Administration of High-Concentrate Sodium Bicarbonate　- Rationale and Design of a Single-Arm Study Compared With Historical Controls.

Background: Contrast-induced nephropathy (CIN) is clinically important because of its poor prognosis. The incidence of CIN is higher in emergency than elective percutaneous coronary intervention (PCI) because there is no established method to prevent CIN. The aim of this study is to evaluate whether bolus administration of a concentrated solution of sodium bicarbonate can prevent CIN in patients undergoing emergency PCI. Methods and Results: This multicenter prospective single-arm trial with historical controls will include patients who are aged ≥20 years and will undergo cardiac catheterization for suspected acute myocardial infarction (AMI). Patients will receive an intravenous bolus administration of concentrated sodium bicarbonate solution (7% or 8.4%, 20 mEq) and will be observed for 72±12 h. Data for the control group, comprising all patients who underwent PCI for AMI between January 1, 2020 and December 31, 2020 across participating hospitals, will be extracted. The primary endpoint is the incidence of CIN, defined as an increase in serum creatinine of >0.5 mg/dL or >25% from baseline within 48±12 h. We will evaluate the endpoints in the prospective group and compare them with those in the historical control group. Conclusions: This study will evaluate whether a single bolus administration of concentrated sodium bicarbonate can prevent CIN after emergency PCI.

The Efficacy of Acute Myocardial Infarction Intensive Care Unit Management with a Collaborative Intensivists and Cardiologists in Japan: A Retrospective Observational Study.

Objective Dedicated intensive care unit (ICU) physician staffing is associated with a reduction in ICU mortality rates in general medical and surgical ICUs. However, limited data are available on the role of intensivists in ICU for cardiac disease, especially in Japan. This study investigated the association of collaborative intensivists and cardiologist care with clinical outcomes in patients with acute myocardial infarction (AMI) admitted to the ICU. Methods This study analyzed 106 patients admitted to the ICU at Nara Prefecture General Medical Center in Nara, Japan, from April 2017 to April 2019. Eligible patients were divided into either the high-intensity ICU management group (n=51) or the low-intensity ICU management group (n=55). The primary outcome of in-hospital mortality was compared in the two groups. Results The high-intensity ICU group was found to be associated with a lower mortality rate in a multivariate analysis than the low-intensity group [7.8% vs. 16.4%; odds ratio (OR): 0.07; 95% confidence interval (CI): 0.01-0.54; p=0.01]. There were no significant differences in the length of either the ICU stay or hospital stay or the hospital costs between the two groups. A subgroup analysis revealed that the in-hospital mortality rate was lower in the high-intensity ICU group than in the low-intensity ICU group among patients with Killip class IV (16.7% vs. 34.6%; OR, 0.08; 95% CI, 0.01-0.67; p=0.02). Conclusion The presence of dedicated intensivists in high-intensity ICU collaborating with cardiologists might reduce in-hospital mortality in patients with Killip class IV AMI who require critical care.

Comparative evaluation of chlorous acid and sodium hypochlorite activity against SARS-CoV-2.

A novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), suddenly emerged in China in 2019, spread globally and caused the present COVID-19 pandemic. Therefore, to mitigate SARS-CoV-2 infection effective measures are essential. Chlorous acid (HClO2) has been shown to be an effective antimicrobial agent. However, at present there is no experimental evidence showing that HClO2 can inactivate SARS-CoV-2. Therefore, in this study, we examined the potential of HClO2 to inactivate SARS-CoV-2 in presence or absence of organic matter and the results were compared with that of sodium hypochlorite (NaClO), another potent antimicrobial agent. When concentrated SARS-CoV-2 was incubated with 10 ppm HClO2 for 10 s, viral titre was decreased by 5 log of 50% tissue culture infective dose per mL (TCID50 ml-1). However, the same concentration of NaClO could not inactivate SARS-CoV-2 as effectively as HClO2 did even after incubation for 3 min. Furthermore, 10 ppm HClO2 also inactivated more than 4.0 log of TCID50 within 10 s in the presence of 5 % fetal bovine serum used as mixed organic matters. Our results obtained with HClO2 are more effective against SARS-CoV-2 as compared to NaClO that can be used for disinfectant against SARS-CoV-2 .

Efficacy and Safety of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure (EARLIER trial): a multicentre, randomized, double-blind, placebo-controlled trial.

AIMS: A mineralocorticoid receptor antagonist (MRA) is effective in patients with chronic heart failure; however, the effects of the early initiation of an MRA in patients with acute heart failure (AHF) have not been elucidated. METHODS AND RESULTS: In this multicentre, randomized, double-blind, placebo-controlled, parallel-group study, we focused on the safety and effectiveness of the treatment with eplerenone, a selective MRA in 300 patients with AHF, that is, 149 in the eplerenone group and 151 in the placebo group in 27 Japanese institutions. The key inclusion criteria were (i) patients aged 20 years or older and (ii) those with left ventricular ejection fraction of ≤40%. The primary outcome was a composite of cardiac death or first re-hospitalization due to cardiovascular disease within 6 months. The mean age of the participants was 66.8 years, 27.3% were women, and the median levels of brain natriuretic peptide were 376.0 pg/mL. The incidences of the primary outcome were 19.5% in the eplerenone group and 17.2% in the placebo group [hazard ratio (HR): 1.09, 95% confidence interval (CI): 0.642-1.855]. In prespecified secondary outcomes, HR for the composite endpoint, cardiovascular death, or first re-hospitalization due to heart failure within 6 months was 0.55 (95% CI: 0.213-1.434). The safety profile for eplerenone was as expected. CONCLUSION: The early initiation of eplerenone in patients with AHF could safely be utilized. The reduction of the incidence of a composite of cardiovascular death or first re-hospitalization for cardiovascular diseases by eplerenone is inconclusive because of inadequate power.

Adenosine-sensitive atrial tachycardia originating from the para-Hisian region with a slow conduction zone in the anteroseptal left atrium.

Adenosine-sensitive atrial tachycardias (ATs) originating from the para-Hisian region have been reported, and the responsible mechanism is considered to be reentry. As an alternative strategy to ablation at the earliest activation site (EAS) close to the atrioventricular node, previous reports safely eliminated these ATs at the entrance of the slow conduction zone, indicated by a manifest entrainment-guided strategy, but no report has successfully ablated those ATs using the same strategy in the left atrium. We describe a case of adenosine-sensitive AT originating from the para-Hisian region that could be eliminated at a remote site from the EAS indicated by the demonstration of manifest entrainment from the high anteroseptal left atrium. .

Effect of the Sodium-Glucose Cotransporter 2 Inhibitor Canagliflozin for Heart Failure With Preserved Ejection Fraction in Patients With Type 2 Diabetes.

Background: The efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in elderly patients with heart failure with preserved ejection fraction (HFpEF) remains unclear. Methods and Results: In a multicenter, controlled trial, the CANONICAL study, we enrolled 82 HFpEF (left ventricular ejection fraction [LVEF] ≥50%) patients with type 2 diabetes (T2D) aged ≥65 years, with plasma B-type natriuretic peptide (BNP) ≥100 pg/mL or plasma N-terminal pro BNP (NT-proBNP) ≥400 pg/mL or history of HF. Patients were randomly assigned to 2 groups and were administered either the SGLT2 inhibitor canagliflozin (100 mg/day) for 24 weeks or standard therapy. The primary endpoints were changes in body weight (BW) and BNP concentrations. Mean (±SD) patient age, body mass index, and LVEF were 75.7±6.5 years, 25.0±3.6 kg/m2 and 61.5±7.6%, respectively. At 24 weeks, BW was significantly lower in the canagliflozin than standard therapy group. The extent of BNP reductions at 4 weeks was significantly greater in the canagliflozin than standard therapy group (P<0.05), but at 24 weeks there was no significant difference between the 2 groups. Conclusions: In this study, canagliflozin treatment reduced BW, but did not significantly reduce plasma BNP concentrations compared with standard therapy after 24 weeks treatment in T2D patients with HFpEF. Further large-scale randomized studies are needed to conclude the beneficial effects of canagliflozin in T2D patients with HFpEF.

Immunoglobulin G4-related masses surrounding coronary arteries: a case report.

BACKGROUND: Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition with high serum IgG4 levels affecting various organs, such as the pancreas, lacrimal and salivary glands, thyroid, kidney, and lung. Typical cardiovascular manifestations of IgG4-RD include periaortitis, coronary arteritis, and pericarditis. However, reports of IgG4-RD associated with coronary arteritis are rare. Here, we report a case of IgG4-related masses surrounding the coronary arteries. CASE SUMMARY: A 59-year-old man was referred to our hospital because of mediastinal masses detected by computed tomography (CT). Coronary CT angiography revealed masses surrounding the right coronary artery and the left anterior descending coronary artery. An elevated serum level of IgG4 and histological findings led to the diagnosis of IgG4-related coronary arteritis with mass formation. Coronary angiography showed numerous feeding arteries to the masses, which were demonstrated as multiple microchannels in the intravascular ultrasound (IVUS) images. DISCUSSION: IgG4-RD involving the cardiovascular system has been reported. However, coronary artery disease associated with IgG4-RD is very rare, and the mechanism of mass formation in IgG4-related coronary arteritis is unclear. In our case, within the cardiovascular system, IgG4-RD was limited to the coronary arteries, suggesting that the affected coronary arteries may provide the necessary blood supply to the mass, thus, aiding its growth. These findings were supported by the images from coronary angiography and IVUS.

Identifying the chloroperoxyl radical in acidified sodium chlorite solution.

The present study identified the active radical species in acidic sodium chlorite and investigated the feasibility of quantifying these species with the diethylphenylenediamine (DPD) method. Electron spin resonance (ESR) spectroscopy was used to identify the active species generated in solutions containing sodium chlorite (NaClO2). The ESR signal was directly observed in an acidified sodium chlorite (ASC) aqueous solution at room temperature. This ESR signal was very long-lived, indicating that the radical was thermodynamically stable. The ESR parameters of this signal did not coincide with previously reported values of the chlorine radical (Cl●) or chlorine dioxide radical (O = Cl●-O and O = Cl-O●). We refer to this signal as being from the chloroperoxyl radical (Cl-O-O●). Quantum chemical calculations revealed that the optimal structure of the chloroperoxyl radical is much more thermodynamically stable than that of the chlorine dioxide radical. The UV-visible spectrum of the chloroperoxyl radical showed maximum absorbance at 354 nm. This absorbance had a linear relationship with the chloroperoxyl radical ESR signal intensity. Quantifying the free chlorine concentration by the DPD method also revealed a linear relationship with the maximum absorbance at 354 nm, which in turn showed a linear relationship with the chloroperoxyl radical ESR signal intensity. These linear relationships suggest that the DPD method can quantify chloroperoxyl radicals, which this study considers to be the active species in ASC aqueous solution.

Effects of Fatty Acid Therapy in Addition to Strong Statin on Coronary Plaques in Acute Coronary Syndrome: An Optical Coherence Tomography Study.

BACKGROUND Vascular healing response associated with adjunctive n-3 polyunsaturated fatty acid therapy therapy in patients receiving strong statin therapy remains unclear. The aim of this study was to evaluate the effect of polyunsaturated fatty acid therapy with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) in addition to strong statin therapy on coronary atherosclerotic plaques using optical coherence tomography. METHODS AND RESULTS This prospective multicenter randomized controlled trial included 130 patients with acute coronary syndrome treated with strong statins. They were assigned to either statin only (control group, n=42), statin+high-dose EPA (1800 mg/day) (EPA group, n=40), statin+EPA (930 mg/day)+DHA (750 mg/day) (EPA+DHA group, n=48). Optical coherence tomography was performed at baseline and at the 8-month follow-up. The target for optical coherence tomography analysis was a nonculprit lesion with a lipid plaque. Between baseline and the 8-month follow-up, fibrous cap thickness (FCT) significantly increased in all 3 groups. There were no significant differences in the percent change for minimum FCT between the EPA or EPA+DHA group and the control group. In patients with FCT <120 µm (median value), the percent change for minimum FCT was significantly higher in the EPA or EPA+DHA group compared with the control group. CONCLUSIONS EPA or EPA+DHA therapy in addition to strong statin therapy did not significantly increase FCT in nonculprit plaques compared with strong statin therapy alone, but significantly increased FCT in patients with thinner FCT. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN 000012825.

Number of Board-Certified Cardiologists and Acute Myocardial Infarction-Related Mortality in Japan　- JROAD and JROAD-DPC Registry Analysis.

BACKGROUND: The appropriate number of board-certified cardiologists (BCC) for the treatment of acute myocardial infarction (AMI) has not been thoroughly examined in Japan. This study investigated whether the number of BCC/50 cardiovascular beds affects acute outcome in AMI treatment. Methods and Results: Data on 751 board-certified teaching hospitals and 63,603 patients with AMI were obtained from the Japanese Registry Of All cardiac and vascular Diseases (JROAD) and JROAD Diagnosis Procedure Combination (JROAD-DPC) databases between 1 April 2012 and 31 March 2014. The hospitals were categorized into 3 groups based on the median number of BCC/50 cardiovascular beds: first tertile, 5.0 (IQR, 4.0-5.7); second, 8.3 (IQR, 7.4-9.8); third, 15.3 (IQR, 12.5-22.7), and the patients with AMI admitted to the categorized hospitals were compared (first tertile, 12,002 patients; second, 23,930; third, 27,671). On hierarchical logistic modeling, the adjusted OR for 30-day mortality were 0.86 (95% CI: 0.74-1.00) for the second tertile and 0.75 (95% CI: 0.65-0.88) for the third tertile. CONCLUSIONS: Patients with AMI admitted to hospitals with a large number of BCC/50 cardiovascular beds had a lower 30-day mortality rate. This tendency was independent of patient and hospital characteristics. This is the first study to provide new information on the association between the number of BCC and in-hospital AMI-related mortality in Japan.

Alteration of ß-Adrenoceptor Signaling in Left Ventricle of Acute Phase Takotsubo Syndrome: a Human Study.

Accumulating evidence indicates alteration of the ß-adrenoceptor (AR), such as desensitization and subtype switching of its coupling G protein, plays a role in the protection against catecholamine toxicity in heart failure. However, in human takotsubo syndrome (TTS), which is associated with a surge of circulating catecholamine in the acute phase, there is no histologic evidence of ß-AR alteration. The purpose of this study was to investigate the involvement of alteration of ß-AR signaling in the mechanism of TTS development. Left ventricular (LV) biopsied samples from 26 patients with TTS, 19 with normal LV function, and 26 with dilated cardiomyopathy (DCM) were studied. G protein-coupled receptor kinase 2 (GRK2) and ß-arrestin2, which initiate the alteration of ß-AR signaling, were more abundantly expressed in the myocardium in acute-phase TTS than in those of DCM and normal control as indicated by immunohistochemistry. The percentage of cardiomyocytes that showed positive membrane staining for GRK2 and ß-arrestin2 was also significantly higher in acute-phase TTS. Sequential biopsies in the recovery-phase for two patients with TTS revealed that membrane expression of GRK2 and ß-arrestin2 faded over time. This study provided the first histologic evidence of the involvement of alteration of ß-ARs in the development of TTS.

Prognostic Value of Urinary Neutrophil Gelatinase-Associated Lipocalin on the First Day of Admission for Adverse Events in Patients With Acute Decompensated Heart Failure.

BACKGROUND: Urinary neutrophil gelatinase-associated lipocalin (U-NGAL) is an early predictor of acute kidney injury and adverse events in various diseases; however, in acute decompensated heart failure patients, its significance remains poorly understood. This study aimed to investigate the prognostic value of U-NGAL on the first day of admission for the occurrence of acute kidney injury and long-term outcomes in acute decompensated heart failure patients. METHODS AND RESULTS: We studied 260 acute decompensated heart failure patients admitted to our department between 2011 and 2014 by measuring U-NGAL in 24-hour urine samples collected on the first day of admission. Primary end points were all-cause death, cardiovascular death, and heart failure admission. Patients were divided into 2 groups according to their median U-NGAL levels (32.5 µg/gCr). The high-U-NGAL group had a significantly higher occurrence of acute kidney injury during hospitalization than the low-U-NGAL group (P=0.0012). Kaplan-Meier analysis revealed that the high-U-NGAL group exhibited a worse prognosis than the low-U-NGAL group in all-cause death (hazard ratio 2.07; 95%CI 1.38-3.12, P=0.0004), cardiovascular death (hazard ratio 2.29; 95%CI 1.28-4.24, P=0.0052), and heart failure admission (hazard ratio 1.77; 95%CI 1.13-2.77, P=0.0119). The addition of U-NGAL to the estimated glomerular filtration rate significantly improved the predictive accuracy of all-cause mortality (P=0.0083). CONCLUSIONS: In acute decompensated heart failure patients, an elevated U-NGAL level on the first day of admission was related to the development of clinical acute kidney injury and independently associated with poor prognosis.

Microbicidal effects of weakly acidified chlorous acid water against feline calicivirus and Clostridium difficile spores under protein-rich conditions.

Sanitation of environmental surfaces with chlorine based-disinfectants is a principal measure to control outbreaks of norovirus or Clostridium difficile. The microbicidal activity of chlorine-based disinfectants depends on the free available chlorine (FAC), but their oxidative potential is rapidly eliminated by organic matter. In this study, the microbicidal activities of weakly acidified chlorous acid water (WACAW) and sodium hypochlorite solution (NaClO) against feline calcivirus (FCV) and C. difficile spores were compared in protein-rich conditions. WACAW inactivated FCV and C. difficile spores better than NaClO under all experimental conditions used in this study. WACAW above 100 ppm FAC decreased FCV >4 log10 within 30 sec in the presence of 0.5% each of bovine serum albumin (BSA), polypeptone or meat extract. Even in the presence of 5% BSA, WACAW at 600 ppm FAC reduced FCV >4 log10 within 30 sec. Polypeptone inhibited the virucidal activity of WACAW against FCV more so than BSA or meat extract. WACAW at 200 ppm FAC decreased C. difficile spores >3 log10 within 1 min in the presence of 0.5% polypeptone. The microbicidal activity of NaClO was extensively diminished in the presence of organic matter. WACAW recovered its FAC to the initial level after partial neutralization by sodium thiosulfate, while no restoration of the FAC was observed in NaClO. These results indicate that WACAW is relatively stable under organic matter-rich conditions and therefore may be useful for treating environmental surfaces contaminated by human excretions.

Salt accelerates aldosterone-induced cardiac remodeling in the absence of guanylyl cyclase-A signaling.

AIMS: Excess sodium causes the development of cardiovascular diseases in conjunction with enhancing renin-angiotensin-aldosterone system (RAAS). Natriuretic peptides are sodium regulators and prevent pathological cardiac alterations by counteracting RAAS. However, it is unknown whether natriuretic peptides inhibit the sodium effect in adverse cardiac alterations. Here, we investigated whether excess salt intake could exacerbate cardiac remodeling in mice with impaired natriuretic peptide signaling. MATERIALS AND METHODS: Mice lacking the gene encoding the natriuretic peptide receptor, guanylyl cyclase-A (GC-A), and wild-type mice were administered with either a vehicle substance or a subpressor dose of aldosterone (100ng/kg/min), alongside low salt (0.001% NaCl), normal salt (0.6% NaCl), or high salt diets (6.0% NaCl) for four weeks. Mice were then sacrificed and the hearts were evaluated by histology and RT-PCR. KEY FINDINGS: Salt load did not induce cardiac changes in vehicle and aldosterone groups in wild-type mice. On the other hand, cardiac hypertrophy and interstitial fibrosis were significantly exacerbated in a salt dependent manner in GC-A knockout (KO) mice administered aldosterone, and were associated with enhanced gene expression relevant to hypertrophy, fibrosis, and oxidative stress conditions. Of note, excess salt intake increased the expression of Sgk1, serum and glucocorticoid responsive kinase-1, in aldosterone-administered GC-A KO mice. These molecular changes were not observed in wild-type mice. SIGNIFICANCE: The results of the present study demonstrate that excess salt intake induced cardiac remodeling in conjunction with aldosterone administration in GC-A KO mice, indicating that GC-A signaling attenuated the deleterious salt effect in aldosterone-induced cardiac remodeling.

Suppressed Production of Soluble Fms-Like Tyrosine Kinase-1 Contributes to Myocardial Remodeling and Heart Failure.

Soluble fms-like tyrosine kinase-1 (sFlt-1), an endogenous inhibitor of vascular endothelial growth factor and placental growth factor, is involved in the pathogenesis of cardiovascular disease. However, the significance of sFlt-1 in heart failure has not been fully elucidated. We found that sFlt-1 is decreased in renal failure and serves as a key molecule in atherosclerosis. In this study, we aimed to investigate the role of the decreased sFlt-1 production in heart failure, using sFlt-1 knockout mice. sFlt-1 knockout mice and wild-type mice were subjected to transverse aortic constriction and evaluated after 7 days. The sFlt-1 knockout mice had significantly higher mortality (52% versus 15%; P=0.0002) attributable to heart failure and showed greater cardiac hypertrophy (heart weight to body weight ratio, 8.95±0.45 mg/g in sFlt-1 knockout mice versus 6.60±0.32 mg/g in wild-type mice; P<0.0001) and cardiac dysfunction, which was accompanied by a significant increase in macrophage infiltration and cardiac fibrosis, than wild-type mice after transverse aortic constriction. An anti-placental growth factor-neutralizing antibody prevented pressure overload-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction. Moreover, monocyte chemoattractant protein-1 expression was significantly increased in the hypertrophied hearts of sFlt-1 knockout mice compared with wild-type mice. Monocyte chemoattractant protein-1 inhibition with neutralizing antibody ameliorated maladaptive cardiac remodeling in sFlt-1 knockout mice after transverse aortic constriction. In conclusion, decreased sFlt-1 production plays a key role in the aggravation of cardiac hypertrophy and heart failure through upregulation of monocyte chemoattractant protein-1 expression in pressure-overloaded heart.

Angiogenic Factors and Risks of Technique Failure and Cardiovascular Events in Patients Receiving Peritoneal Dialysis.

BACKGROUND: Placental growth factor (PlGF) is a member of the vascular endothelial growth factor family that acts as a pleiotropic cytokine capable of stimulating angiogenesis and accelerating atherogenesis. Soluble fms-like tyrosine kinase-1 (sFlt-1) antagonizes PlGF action. Higher levels of PlGF and sFlt-1 have been associated with cardiovascular events in patients with chronic kidney disease, yet little is known about their relationship with adverse outcomes in patients on peritoneal dialysis (PD). The aim of this study was to investigate the association of PlGF and sFlt-1 with technique survival and cardiovascular events. METHODS: We measured serum levels of PlGF and plasma levels of sFlt-1 in 40 PD patients at Nara Medical University. RESULTS: PlGF and sFlt-1 levels were significantly correlated with the dialysate-to-plasma ratio of creatinine (r = 0.342, p = 0.04 and r = 0.554, p < 0.001) although PlGF and sFlt-1 levels were not correlated with total creatinine clearance and total Kt/V. Additionally, both PlGF and sFlt-1 levels were significantly higher in patients with high transport membranes compared to those without (p = 0.039 and p < 0.001, respectively). Patients with PlGF levels above the median had lower technique survival and higher incidence of cardiovascular events than patients with levels below the median, with hazard ratios of 11.9 and 7.7, respectively, in univariate Cox regression analysis. However, sFlt-1 levels were not associated with technique survival or cardiovascular events (p = 0.11 and p = 0.10, respectively). CONCLUSION: Elevated PlGF and sFlt-1 are significantly associated with high transport membrane status. PlGF may be a useful predictor of technique survival and cardiovascular events in PD patients.

Thin-cap fibroatheroma and large calcification at the proximal stent edge correlate with a high proportion of uncovered stent struts in the chronic phase.

OBJECTIVE: A high proportion of uncovered stent struts is associated with late stent thrombosis after drug-eluting stent (DES) implantation, which frequently results in myocardial infarction or death. However, the predictors of uncovered stent struts remain unknown. Here, using optical coherence tomography (OCT), we studied the baseline tissue characteristics of the target coronary segment and evaluated their influence on the neointimal coverage of the strut in the chronic phase. METHODS: We analyzed 118 coronary lesions treated with OCT-guided DES implantation. OCT examinations of target lesions were performed before and after DES implantation, and tissue characteristics were evaluated within 5 mm outer segment of both stent edges. At follow-up, stent strut coverage was assessed within 5 mm inner segment from each stent edge. On the basis of the proportion of uncovered stent struts in the chronic phase, target segments were divided into poorly covered (the highest quartile with % uncovered struts, n=29) and well-covered (the remaining lower quartiles with % uncovered struts, n=89) groups. RESULTS: Clinical parameters were similar between the two groups. On baseline OCT images, thin-cap fibroatheroma (TCFA) and large calcification were more frequently observed in the poorly covered group than the well-covered group (10.3 vs. 0.0%, P=0.0032, and 27.6 vs. 9.0%, P=0.017, respectively). Furthermore, multivariable analysis showed TCFA and large calcification at the proximal edge, but not at the distal edge, were predictors of uncover stent struts. CONCLUSION: TCFA and large calcification at the proximal stent edge are strong predictors of uncovered stent struts. OCT is useful for selecting stent landing sites in terms of future occurrence of uncovered stent struts.