Atrial structural remodeling and atrial fibrillation substrate: A histopathological perspective.

Atrial fibrillation (AF) substrate progresses with the advancement of atrial structural remodeling, resulting in AF perpetuation and recurrence. Although fibrosis is considered a hallmark of atrial structural remodeling, the histological background has not been fully elucidated because obtaining atrial specimens is difficult, especially in patients not undergoing open-heart surgery. Bipolar voltage reduction evaluated using electroanatomic mapping during AF ablation is considered a surrogate marker for the progression of structural remodeling; however, histological validation is lacking. We developed an intracardiac echocardiography-guided endomyocardial atrial biopsy technique to evaluate atrial structural remodeling in patients undergoing catheter ablation for nonvalvular AF. The histological factors associated with a decrease in bipolar voltage were interstitial fibrosis, as well as an increase in myocardial intercellular space preceding fibrosis, myofibrillar loss, and a decrease in cardiomyocyte nuclear density, which is a surrogate marker for cardiomyocyte density. Cardiomyocyte hypertrophy is closely associated with a decrease in cardiomyocyte nuclear density, suggesting that hypertrophic changes compensate for cardiomyocyte loss. Electron microscopy also revealed that increased intercellular spaces indicated the leakage of plasma components owing to increased vascular permeability. Additionally, amyloid deposition was observed in 4 % of biopsy cases. Only increased intercellular space and interstitial fibrosis were significantly higher for long-standing persistent AF than for paroxysmal AF and associated with recurrence after AF ablation, suggesting that this interstitial remodeling is the AF substrate. An increase in intercellular space that occurs early in AF formation is a therapeutic target for the AF substrate, which prevents irreversible interstitial degeneration due to collagen accumulation. This endomyocardial atrial biopsy technique will allow the collection of atrial tissue from a wide variety of patients and significantly facilitate the elucidation of the mechanisms of atrial cardiomyopathy, structural remodeling, and AF substrates.

Pulmonary Vein Intervention for Severe Pulmonary Vein Stenosis After Atrial Fibrillation Ablation　- A Retrospective Cohort Study.

BACKGROUND: Pulmonary vein (PV) stenosis (PVS) is a serious complication of atrial fibrillation (AF) ablation. The objective of this study was to describe interventional treatments for PVS after AF ablation and long-term outcomes in Japanese patients.Methods and Results: This multicenter retrospective observational study enrolled 30 patients (26 [87%] male; median age 55 years) with 56 severe PVS lesions from 43 PV interventional procedures. Twenty-seven (90%) patients had symptomatic PVS and 19 (63%) had a history of a single AF ablation. Of the 56 lesions, 41 (73%) were de novo lesions and 15 (27%) were retreated. Thirty-three (59%) lesions were treated with bare metal stents, 14 (25%) were treated with plain balloons, and 9 (16%) were treated with drug-coated balloons. All lesions were successfully treated without any systemic embolic event. Over a median follow-up of 584 days (interquartile range 265-1,165 days), restenosis rates at 1 and 2 years were 35% and 47%, respectively. Multivariate Cox regression analysis revealed devices <7 mm in diameter (hazard ratio [HR] 2.52; 95% confidence interval [CI] 1.04-6.0; P=0.040) and totally occluded lesions (HR 3.33; 95% CI 1.21-9.15; P=0.020) were independent risk factors for restenosis. CONCLUSIONS: All PVS lesions were successfully enlarged by the PV intervention; however, restenosis developed in approximately half the lesions within 2 years.

Recombinant soluble thrombomodulin attenuates cisplatin-induced intestinal injury by inhibiting intestinal epithelial cell-derived cytokine secretion.

BACKGROUND: Intestinal injury is one of the main side-effects of cisplatin chemotherapy, impairing the quality of life in patients with cancer. In this study, we investigated the protective effects of recombinant soluble thrombomodulin (rsTM), which is a potent anti-inflammatory agent, on cisplatin-induced intestinal injury. METHODS: We first evaluated the effects of rsTM on intestinal injury caused by cisplatin in mice in vivo. Disease progression was monitored by analyzing loss of body weight and histological changes in intestinal tissue. We then investigated the effects of rsTM on mouse intestinal organoid formation and growth in vitro. Gene expression levels were analyzed by quantitative real-time polymerase chain reaction and Western blotting. RESULTS: rsTM treatment significantly attenuated the loss of body weight, histological damage and gene expression levels of pro-inflammatory cytokines such as interleukin-6, tumor necrosis factor-α and high-mobility group box-1 in a cisplatin-treated mouse model. Furthermore, rsTM alleviated the inflammatory response and apoptosis in a cisplatin-treated intestinal epithelial organoid model. CONCLUSION: rsTM suppresses cisplatin-induced intestinal epithelial cell-derived cytokine production and alleviates intestinal mucositis.

Histological validation of atrial structural remodelling in patients with atrial fibrillation.

BACKGROUND AND AIMS: This study aimed to histologically validate atrial structural remodelling associated with atrial fibrillation. METHODS AND RESULTS: Patients undergoing atrial fibrillation ablation and endomyocardial atrial biopsy were included (n = 230; 67 ± 12 years old; 69 women). Electroanatomic mapping was performed during right atrial pacing. Voltage at the biopsy site (Vbiopsy), global left atrial voltage (VGLA), and the proportion of points with fractionated electrograms defined as ≥5 deflections in each electrogram (%Fractionated EGM) were evaluated. SCZtotal was calculated as the total width of slow conduction zones, defined as regions with a conduction velocity of <30 cm/s. Histological factors potentially associated with electroanatomic characteristics were evaluated using multiple linear regression analyses. Ultrastructural features and immune cell infiltration were evaluated by electron microscopy and immunohistochemical staining in 33 and 60 patients, respectively. Fibrosis, intercellular space, myofibrillar loss, and myocardial nuclear density were significantly associated with Vbiopsy (P = .014, P < .001, P < .001, and P = .002, respectively) and VGLA (P = .010, P < .001, P = .001, and P < .001, respectively). The intercellular space was associated with the %Fractionated EGM (P = .001). Fibrosis, intercellular space, and myofibrillar loss were associated with SCZtotal (P = .028, P < .001, and P = .015, respectively). Electron microscopy confirmed plasma components and immature collagen fibrils in the increased intercellular space and myofilament lysis in cardiomyocytes, depending on myofibrillar loss. Among the histological factors, the severity of myofibrillar loss was associated with an increase in macrophage infiltration. CONCLUSION: Histological correlates of atrial structural remodelling were fibrosis, increased intercellular space, myofibrillar loss, and decreased nuclear density. Each histological component was defined using electron microscopy and immunohistochemistry studies.

Interatrial conduction time is associated with left atrial low voltage area and predicts the recurrence after single atrial fibrillation ablation.

Background: Interatrial conduction time (IACT) prolongs in fibrotic left atrium. We tested the hypothesis that IACT is related to left atrial low voltage area (LVA) and predicts the recurrence after single atrial fibrillation (AF) ablation. Methods: One hundred sixty-four consecutive AF patients (79 non-paroxysmal) who underwent initial ablation in our institute were analyzed. IACT and LVA were defined as interval from the onset of P-wave to the basal left atrial appendage (P-LAA) activation, and area with bipolar electrogram < 0.5 mV covering over 5% of the total left atrial surface area during sinus rhythm, respectively. Pulmonary vein antrum isolation, non-PV foci ablation, and atrial tachycardia (AT) ablation were performed without substrate modification. Results: LVA was frequently identified in patients with prolonged P-LAA ≥ 84 ms (n  = 28) compared with patients with P-LAA < 84 ms (n  = 136). Patients with P-LAA ≥ 84 ms were older (71 ± 10 vs. 65 ± 10 years, p  = .0061), and had more frequent non-paroxysmal AF (75% vs. 43%, p  = .0018), larger left atrial diameter (43.5 ± 4.5 vs. 39.3 ± 5.7 mm, p  = .0003), and higher E/e' ratio (14.4 ± 6.5 vs. 10.5 ± 3.7, p  < .0001) compared with P-LAA < 84 ms patients. After a mean follow-up period of 665 ± 153 days, Kaplan-Meier curve analysis showed that AF/AT recurrences was more frequently observed in patients with prolonged P-LAA (Log-rank p  = .0001). Additionally, univariate analysis revealed that P-LAA prolongation (OR = 1.055 per 1 ms, 95% CI: 1.028-1.087, p  < .0001) and the existence of LVA (OR = 5.000, 95% CI: 1.653-14.485 p  = .0053) were predictors of AF/AT recurrences after single AF ablation. Conclusions: Our results suggested that prolonged IACT as measured by P-LAA was associated with LVA and predicts AT/AF recurrence after single AF ablation.

A Pediatric Case of Septic Pulmonary Embolism Caused by Tsukamurella paurometabola.

We herein report a three-year-old boy with septic pulmonary embolism caused by Tsukamurella paurometabola bacteremia during chemotherapy for rhabdomyosarcoma. During the interval of chemotherapy, the patient was temporarily discharged with a peripherally inserted central venous catheter but was re-admitted to the hospital with a fever on the same day. A blood culture taken at the time of re-admission showed T. paurometabola. The patient had a persistent fever, and computed tomography performed on the ninth day showed septic pulmonary embolism. We stress the importance of being aware of the possibility of septic pulmonary embolism in patients with Tsukamurella bacteremia.

Alcohol Consumption Is Associated With Postablation Recurrence but Not Changes in Atrial Substrate in Patients With Atrial Fibrillation: Insight from a High-Density Mapping Study.

Background The association between alcohol consumption, atrial substrate, and outcomes after atrial fibrillation (AF) ablation remains controversial. This study evaluated the impacts of drinking on left atrial substrate and AF recurrence after ablation. Methods and Results We prospectively enrolled 110 patients with AF without structural heart disease (64±12 years) from 2 institutions. High-density left atrial electroanatomic mapping was performed using a high-density grid multipolar catheter. We investigated the impact of alcohol consumption on left atrial voltage, left atrial conduction velocity, and AF ablation outcome. Patients were classified as abstainers (<1 drink/wk), mild drinkers (1-7 drinks/wk), or moderate-heavy drinkers (>7 drinks/wk). High-density mapping (mean 2287±600 points/patient) was performed on 49 abstainers, 27 mild drinkers, and 34 moderate-heavy drinkers. Low-voltage zone and slow-conduction zone were identified in 39 (35%) and 54 (49%) patients, respectively. There was no significant difference in the proportions of low-voltage zone and slow-conduction zone among the 3 groups. The success rate after a single ablation was significantly lower in drinkers than in abstainers (79.3% versus 95.9% at 12 months; mean follow-up, 18±8 months; P=0.013). The success rate after a single or multiple ablations was not significantly different among abstainers and drinkers. In multivariate analysis, alcohol consumption (P=0.02) and the presence of a low-voltage zone (P=0.032) and slow-conduction zone (P=0.02) were associated with AF recurrence after a single ablation, while low-voltage zone (P=0.023) and slow-conduction zone (P=0.024) were associated with AF recurrence after a single or multiple ablations. Conclusions Alcohol consumption was associated with AF recurrence after a single ablation but not changes in atrial substrate.

Atrial Structural Remodeling in Patients With Atrial Fibrillation Is a Diffuse Fibrotic Process: Evidence From High-Density Voltage Mapping and Atrial Biopsy.

Background Low-voltage areas (LVAs) in the atria of patients with atrial fibrillation are considered local fibrosis. We hypothesized that voltage reduction in the atria is a diffuse process associated with fibrosis and that the presence of LVAs reflects a global voltage reduction. Methods and Results We examined 140 patients with atrial fibrillation and 13 patients with a left accessory pathway (controls). High-density bipolar voltage mapping was performed using a grid-mapping catheter during high right atrial pacing. Global left atrial (LA) voltage (VGLA) in the whole LA and regional LA voltage (VRLA) in 6 anatomic regions were evaluated with the mean of the highest voltage at a sampling density of 1 cm2. Patients with atrial fibrillation were categorized into quartiles by VGLA. LVAs were evaluated at voltage cutoffs of 0.1, 0.5, 1.0, and 1.5 mV. Twenty-eight patients with atrial fibrillation also underwent right atrial septum biopsy, and the fibrosis extent was quantified. Voltage at the biopsy site (Vbiopsy) was recorded. VGLA results by category were Q1 (<4.2 mV), Q2 (4.2-5.6 mV), Q3 (5.7-7.0 mV), and Q4 (≥7.1 mV). VRLA at any region was reduced as VGLA decreased. VGLA and VRLA did not differ between Q4 and controls. The presence of LVAs increased as VGLA decreased at any voltage cutoff. Biopsies revealed 11±6% fibrosis, which was inversely correlated with both Vbiopsy and VGLA (r=-0.71 and -0.72, respectively). Vbiopsy was correlated with VGLA (r=0.82). Conclusions Voltage reduction in the LA is a diffuse process associated with fibrosis. Presence of LVAs reflects diffuse voltage reduction of the LA.

Simple risk-score model for in-hospital major bleeding based on multiple blood variables in patients with acute myocardial infarction.

BACKGROUND: In-hospital bleeding is associated with poor prognosis in patients with acute myocardial infarction (AMI). We sought to investigate whether a combination of pre-procedural blood tests could predict the incidence of in-hospital major bleeding in patients with AMI. METHODS AND RESULTS: A total of 1684 consecutive AMI patients who underwent primary percutaneous coronary intervention (PCI) were recruited and randomly divided into derivation (n = 1010) and validation (n = 674) cohorts. A risk-score model was created based on a combination of parameters assessed on routine blood tests on admission. In the derivation cohort, multivariate analysis revealed that the following 5 variables were significantly associated with in-hospital major bleeding: hemoglobin level < 12 g/dL (odds ratio [OR], 3.32), white blood cell count >10,000/µL (OR, 2.58), platelet count <150,000/µL (OR, 2.51), albumin level < 3.8 mg/dL (OR, 2.51), and estimated glomerular filtration rate < 60 mL/min/1.73 m2 (OR, 2.31). Zero to five points were given according to the number of these factors each patient had. Incremental risk scores were significantly associated with a higher incidence of in-hospital major bleeding in both cohorts (P < 0.001). Receiver operating characteristic curve analysis of risk models showed adequate discrimination between patients with and without in-hospital major bleeding (derivation cohort: area under the curve [AUC], 0.807; 95% confidence interval [CI], 0.759-0.848; validation cohort: AUC, 0.793; 95% CI, 0.725-0.847). CONCLUSIONS: Our novel laboratory-based bleeding risk model could be useful for simple and objective prediction of in-hospital major bleeding events in patients with AMI.

Serum Albumin and Bleeding Events After Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction (from the HAGAKURE-ACS Registry).

Low serum albumin (SA) on admission in patients with acute myocardial infarction (AMI) has been reported to be associated with adverse cardiovascular events. The relation between low SA and post-AMI bleeding events is presently unknown. We analyzed 1,724 patients with AMI enrolled in the HAGAKURE-ACS registry who underwent primary percutaneous coronary intervention from January 2014 to December 2018. To assess the influence of low SA at admission, patients were divided into 3 groups according to the albumin tertiles: the low SA group (<3.8 g/100 ml), the middle SA (MSA) group (3.8 to 4.1 g/100 ml), and the normal SA (NSA) group (≥4.2 g/100 ml). The primary end point was the incidence of Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries moderate/severe bleeding. The cumulative 3-year incidence of the primary end point was significantly higher in the low SA group than in the MSA and NSA groups (30.8% and 11.9% vs 7.7%; p <0.001). In the landmark analysis at 30 days, the cumulative incidences of the primary end point were also significantly higher in the low SA group than in the MSA and NSA groups, both within and beyond 30 days (20.1% and 6.1% vs 3.5%; p <0.001, and 12.4% and 6.2% vs 4.5%; p <0.001, respectively). After adjusting for confounders, the low SA group showed excess risk of bleeding events relative to NSA (hazard ratio 1.56; 95% confidence interval 1.06 to 2.30; p = 0.026), whereas risk of bleeding was neutral in MSA relative to NSA (hazard ratio 0.94; 95% confidence interval 0.63 to 1.34; p = 0.752). In conclusion, low SA at admission was independently associated with higher risk for bleeding events in patients with AMI undergoing percutaneous coronary intervention.

Clinical Features of Patients with Active Eosinophilic Granulomatosis with Polyangiitis Successfully Treated with Mepolizumab.

BACKGROUND: In some patients with eosinophilic granulomatosis with polyangiitis (EGPA), remission cannot be induced, despite treatment with corticosteroids and immunosuppressants. We evaluated the clinical features of patients with EGPA in whom mepolizumab was effective. METHODS: There were 59 EGPA patients treated at Hiratsuka City Hospital, Japan, between April 2018 and September 2020, and 30 of them received mepolizumab. Twenty (66.7%) experienced a "marked effect" (the daily dose of corticosteroid or immunosuppressant could be decreased, or the interval between intravenous immunoglobulin (IVIG) treatments could be prolonged) and 10 (33.3%) experienced a "weak effect" (these measures were not achieved). Eosinophil numbers, serum IgG levels, daily doses of corticosteroids and immunosuppressants, and the interval between IVIG treatments at diagnosis and before and after mepolizumab initiation were determined. RESULTS: Eosinophil numbers at diagnosis were significantly higher in the marked-effect group than in the weak-effect group (p < 0.05) but not before mepolizumab initiation or at the last visit. Birmingham Vasculitis Activity Scores (BVASs) before mepolizumab initiation (p < 0.05) and at last visit (p < 0.01), and frequency of relapse before treatment initiation (p < 0.05) were significantly higher, and the serum IgG level before mepolizumab treatment was significantly lower in the weak-effect group than in the marked-effect group. The weak-effect group received higher doses of corticosteroids, even if the corticosteroid dose could be reduced for a while after mepolizumab initiation. CONCLUSION: High peripheral blood eosinophil numbers at EGPA diagnosis were suggestive of a positive clinical response to mepolizumab.

Remodeling of Bone Marrow Niches and Roles of Exosomes in Leukemia.

Leukemia is a hematological malignancy that originates from hematopoietic stem cells in the bone marrow. Significant progress has made in understanding its pathogensis and in establishing chemotherapy and hematopoietic stem cell transplantation therapy (HSCT). However, while the successive development of new therapies, such as molecular-targeted therapy and immunotherapy, have resulted in remarkable advances, the fact remains that some patients still cannot be saved, and resistance to treatment and relapse are still problems that need to be solved in leukemia patients. The bone marrow (BM) niche is a microenvironment that includes hematopoietic stem cells and their supporting cells. Leukemia cells interact with bone marrow niches and modulate them, not only inducing molecular and functional changes but also switching to niches favored by leukemia cells. The latter are closely associated with leukemia progression, suppression of normal hematopoiesis, and chemotherapy resistance, which is precisely the area of ongoing study. Exosomes play an important role in cell-to-cell communication, not only with cells in close proximity but also with those more distant due to the nature of exosomal circulation via body fluids. In leukemia, exosomes play important roles in leukemogenesis, disease progression, and organ invasion, and their usefulness in the diagnosis and treatment of leukemia has recently been reported. The interaction between leukemia cell-derived exosomes and the BM microenvironment has received particular attention. Their interaction is believed to play a very important role; in addition to their diagnostic value, exosomes could serve as a marker for monitoring treatment efficacy and as an aid in overcoming drug resistance, among the many problems in leukemia patients that have yet to be overcome. In this paper, we will review bone marrow niches in leukemia, findings on leukemia-derived exosomes, and exosome-induced changes in bone marrow niches.

The Lectin-Like Domain of Thrombomodulin Inhibits ß1 Integrin-Dependent Binding of Human Breast Cancer-Derived Cell Lines to Fibronectin.

Thrombomodulin is a molecule with anti-coagulant and anti-inflammatory properties. Recently, thrombomodulin was reported to be able to bind extracellular matrix proteins, such as fibronectin and collagen; however, whether thrombomodulin regulates the binding of human breast cancer-derived cell lines to the extracellular matrix remains unknown. To investigate this, we created an extracellular domain of thrombomodulin, TMD123-Fc, or domain deletion TM-Fc proteins (TM domain 12-Fc, TM domain 23-Fc) and examined their bindings to fibronectin in vitro by ELISA. The lectin-like domain of thrombomodulin was found to be essential for the binding of the extracellular domain of thrombomodulin to fibronectin. Using a V-well cell adhesion assay or flow cytometry analysis with fluorescent beads, we found that both TMD123-Fc and TMD12-Fc inhibited the binding between ß1 integrin of human breast cancer-derived cell lines and fibronectin. Furthermore, TMD123-Fc and TMD12-Fc inhibited the binding of activated integrins to fibronectin under shear stress in the presence of Ca2+ and Mg2+ but not under strong integrin-activation conditions in the presence of Mg2+ without Ca2+. This suggests that thrombomodulin Fc fusion protein administered exogenously at a relatively early stage of inflammation may be applied to the development of new therapies that inhibit the binding of ß1 integrin of breast cancer cell lines to fibronectin.

Evaluation of Retinal Function and Pathology After Intravitreal Injection of Povidone-Iodine and Polyvinyl Alcohol-Iodine in Rabbits.

Purpose: This study compared intraocular toxicity of intravitreally injected povidone-iodine (PI) and polyvinyl alcohol-iodine (PAI) in rabbits. Methods: In each rabbit, 0.1 mL of PI or PAI solution was injected intravitreally into one eye and saline was injected into the other. PI was tested at available iodine concentrations of 0.05%, 0.1%, 0.2%, and 0.5%, and PAI at 0.05%, 0.1%, and 0.2% (n = 6 each). Electroretinograms were recorded before injection and 1, 7, and 14 days after injection. Pathological examinations of eyeballs were performed on day 15. Results: Mean b-/a-wave ratios of the electroretinograms did not change in eyes injected with 0.05%, 0.1%, or 0.2% PI (PI-0.05, PI-0.1, and PI-0.2, respectively) or in eyes injected with 0.05% or 0.1% PAI (PAI-0.05 and PAI-0.1, respectively) compared to saline-injected eyes, but was transiently impaired on day 1 in PAI-0.2 eyes. Histopathologically, no retinal abnormalities were observed in PI-0.05, PAI-0.05, or PAI-0.1 eyes. One PI-0.1 eye first showed localized inflammatory cell infiltration in the inferior retinal region. Two PI-0.2 eyes and one PAI-0.2 eye had retinal degeneration and inflammatory cell infiltration. In the PI-0.5 group, extensive inflammatory cell infiltration was observed in six eyes and inferior retinal detachment in five eyes. Conclusions: PI and PAI have equivalent retinal toxicity profiles, and retinal toxicity first affects the inner retinal layer in the inferior region. The highest non-retinotoxic vitreous concentration is 0.0033% available iodine from intravitreal injection of PI or PAI containing 0.05% available iodine. Translational Relevance: Low concentrations of PI or PAI can be used to wash the ocular surface during surgery or intravitreal injection to prevent endophthalmitis.

Impact of Renal Dysfunction on Left Atrial Structural Remodeling and Recurrence After Catheter Ablation for Atrial Fibrillation　- A Propensity Score Matching Analysis.

BACKGROUND: Renal dysfunction coexists with other known risk factors of left atrial (LA) structural remodeling, expressed as low-voltage zones (LVZs), and the recurrence of atrial fibrillation (AF) after ablation. This study aimed to determine whether renal dysfunction had an independent effect on the presence of LVZs and recurrence after AF ablation, using propensity score (PS) matching analysis.Methods and Results:448 consecutive patients who underwent their initial AF ablation were enrolled. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, with 126 (28%) patients having CKD. Using PS matching analysis, new subsets (CKD and non-CKD group, n=103 each) were obtained, matched for age, sex, AF type, and LA volume. The presence of LVZs defined as bipolar voltage <0.5 mV was higher in the CKD group than in the non-CKD group (31% vs. 17%, P=0.034). Multivariate analysis showed eGFR was an independent predictor of the presence of LVZs (odds ratio 1.31 per 10-mL/min/1.73 m2decrease, P=0.029). AF-free survival rate was significantly lower in the CKD patients during 20±9 months of follow-up (63% vs. 82%, P=0.019), and eGFR was shown to be an independent predictor of recurrence (hazard ratio 1.29 per 10-mL/min/1.73 m2decrease, P=0.006), but the presence of LVZs did not predict recurrence. CONCLUSIONS: Renal dysfunction independently predicted not only the recurrence of AF after ablation but also the presence of LVZs.

Catheter ablation of atrial fibrillation reduces heart failure rehospitalization in patients with heart failure with preserved ejection fraction.

BACKGROUND: Atrial fibrillation (AF) is associated with heart failure (HF) rehospitalization in patients with heart failure with preserved ejection fraction (HFpEF). OBJECTIVE: We tested the hypothesis that catheter ablation of AF could reduce HF rehospitalization compared with conventional pharmacotherapy in patients with HFpEF. METHODS: Eighty-five consecutive HFpEF (EF ≥ 50% and a history of HF hospitalization) patients diagnosed as AF by 12-lead electrocardiogram were retrospectively analyzed. Thirty-five patients who received catheter ablation (ABL group) were compared with 50 patients treated by antiarrhythmic drugs and/or beta-blockers (CNT group). The primary endpoint was rehospitalization due to HF. RESULTS: The patients characteristics did not differ between the two groups including, age (71 ± 8 vs 71 ± 13 years; P = .637), female sex (34% vs 36%; P = .870), mean plasma brain natriuretic peptide (145 ± 112 vs 195 ± 153 pg/mL; P = .111), mean left ventricular ejection fraction (62% ± 8% vs 61% ± 9%; P = .624), and type of AF (nonparoxysmal AF 60% vs 62%; P = .852). Amiodarone was continued 40% (14 out of 35) and 40% (20 out of 70) in ABL and CNT groups, respectively (P = 1.000). Neither major complication nor major side effect was observed during the follow-up period. During a mean follow-up period of 792 ± 485 days, Kaplan-Meier curve analysis showed that significantly more patients in the ABL group were free from HF rehospitalization (log-rank P = .0039). Additionally, multivariate analysis revealed that catheter ablation of AF was the only preventive factor of HF rehospitalization (OR = 0.15; 95% CI: 0.04-0.46; P < .001). CONCLUSIONS: Catheter ablation of AF reduced HF rehospitalization compared with conventional pharmacotherapy in patients with HFpEF in our institute. Multicenter randomized study is warranted to confirm the result.

Left atrial functional and structural changes associated with ablation of atrial fibrillation - Cardiac magnetic resonance study.

INTRODUCTION: Left atrial (LA) volumes are related to success of atrial fibrillation (AF) ablation, but the relation to other functional and structural parameters is less well understood. Our goal was to detect potential functional and structural predictors of arrhythmia recurrence after ablation using cardiac magnetic resonance imaging (CMRi) and to non-invasively assess the relation between LA functional and structural remodeling pre- and post-ablation. METHODS: A total of 55 patients (38 male, age 67 ± 10 years) underwent CMRi prior to and then within 24-h and 3-months after ablation. LA volumes (LAV) and function (as assessed by ejection fraction and peak longitudinal atrial strain (PLAS)) were measured by feature-tracking CMRi, and LA fibrosis/scarring was quantified using late­gadolinium enhancement (LGE) imaging. RESULTS: Atrial function was lower acutely in patients with recurrence versus those with non-recurrence: [R vs NR: EFTotal 27.8 ± 10.3% vs 38.1 ± 11% p = 0.002; EFActive 10.5 ± 8% vs 19.1 ± 12% p = 0.007; EFPassive 19.4 ± 8 vs 25.8 ± 10 p = 0.021; PLAS 13 ± 5.9% vs 20.2 ± 7% p = 0.004]. With univariate analysis, baseline minimum volume (MinLAV, MinLAVi), several baseline functional parameters (EFTotal, EFPassive, EFActive, PLAS), and LA-LGE were predictors of recurrence [all p < 0.05]. Acute function (EFTotal, EFPassive, EFActive, PLAS) also predicted recurrence (p < 0.01). Lower pre-ablation EFTotal, EFPassive, and PLAS correlated with higher amount of pre-ablation LA-LGE (p < 0.05). In a multivariate model including MinLAV, EFActive and LA-LGE (all at baseline), LA-LGE was the only independent predictor of recurrence (p = 0.0322). CONCLUSION: Pre-ablation function inversely correlated with LA-LGE and was related to success of AF ablation. Multi-parametric and longitudinal assessment of LA function and structure could be helpful in selection of optimal treatment strategies for AF patients by predicting outcomes.

The long-term prognosis of nephropathy in operated reflux.

OBJECTIVE: To investigate the postoperative long-term prognosis and the factors predicting the renal function of patients with reflux nephropathy. As the serum creatinine (s-Cr) level tends to increase during infancy, the degree of reflux and renal parenchymal damage are thought to be more important factors in pediatric patients than in older patients. MATERIALS AND METHODS: This study examined s-Cr, urinary protein, and blood pressure of patients who underwent anti-reflux surgery 10 years before. It also calculated the postoperative estimated glomerular filtration rate (eGFR) and examined the correlation between the eGFR and preoperative factors (age, gender, number of urinary tract infections [UTIs], primary diagnosis, reflux grade, percentage of dimercaptosuccinic acid uptake, degree of renal parenchymal damage, s-Cr abnormality, proteinuria, and hypertension), and analyzed the factors associated with the long-term prognosis. RESULTS: The study population was 51 infants (37 boys and 14 girls). The mean age of the patients before surgery and at the follow-up examination was 3.41 ± 3.61 and 14.63 ± 3.74 years, respectively. After surgery, the s-Cr, urinary protein, and blood pressure values showed (44.7%, 26.7%, and 18.2%, respectively) were abnormal. The postoperative eGFR was a mean 90.27 ± 20.42 ml/min/1.73 m2 and primary correlated with an older age (P = 0.0361), no UTI at the primary diagnosis (P = 0.0044), reflux grade ≥8 (P = 0.0180), degree of renal parenchymal damage (group ≥2b, P < 0.0001), s-Cr abnormality (P < 0.0001), and proteinuria (P = 0.0001) at baseline. A total of 20 patients had chronic kidney disease (CKD; Fig. 1). The multiple regression analysis of these factors revealed that an older age (P = 0.0021), reflux grade ≥8 (P = 0.0134), and degree of renal parenchymal damage (group ≥2b, P < 0.0001) were significantly associated with the long-term postoperative prognosis of reflux nephropathy. Using these three factors, this study derived a multiple regression equation estimating eGFR in the 10th year after surgery (Fig. 1). DISCUSSION: In this study, severe vesico-ureteral reflux (reflux grade ≥8) and severe renal parenchymal damage (group ≥2b) were associated with a long-term decrease in the eGFR. In particular, renal parenchymal damage was closely correlated with the postoperative eGFR; thus, this was clearly a critical factor. The age at surgery showed a better correlation with the postoperative eGFR in the multiple regression analysis; thus, age was regarded as an independent prognostic factor. CONCLUSIONS: The age, reflux grade, and degree of renal parenchymal damage at baseline were factors that affected the long-term postoperative prognosis of reflux nephropathy. Patients with high-grade reflux and severe renal parenchymal damage were more likely to show a reduced CKD level at 10 years after anti-reflux surgery.