Clinicopathological significance of hyaluronan and hyaluronidase 2 (HYAL2) in breast cancer.

Hyaluronan (HA), as a component of extracellular matrix, has pivotal roles in both physiological and pathological condition. In breast cancer, while high molecular weight HA is produced by hyaluronan synthase, it is degraded by hyaluronidases (hyaluronidase-1 (HYAL1) and hyaluronidase-2 (HYAL2)) into low molecular weight HA (LMW HA), which is considered to have pro-tumorigenic effects in human malignancies. However, HA and HYAL2, the rate-limiting enzyme of HA degradation, have not been comprehensively examined in breast cancer and clinicopathological significance of LMW HA remains to be elucidated in breast cancer. We therefore histochemically localized HA as well as HYAL2 in 116 breast cancer tissues. In addition, we examined size-dependent function of HA on breast cancer cell proliferation and migration using MCF-7 and MDA-MB-231 breast cancer cell lines. HA was localized in both the stroma and breast carcinoma cells, while HYAL2 was predominantly localized in breast carcinoma cells. HA was significantly correlated with cell proliferation and invasion ability as well as increased risk of recurrence especially in HYAL2 positive group. On the other hand, HYAL2 was correlated with breast cancer cell proliferation and increased risk of recurrence. In addition, in vitro analyses revealed that lower molecular weight HA increased sphere forming ability and migration in MCF-7 and MDA-MB-231, whereas higher molecular weight HA inhibited them. It was concluded that HA needs to be degraded by HYAL2 to exert pro-tumorigenic effects and comprehensive HA/HYAL2 status serves as a potent prognostic factor in breast cancer.

Prevalence, Timing, and Impact of Early Recurrence of Atrial Tachyarrhythmias after Pulsed Field Ablation: A Secondary Analysis of the PULSED AF Trial.

BACKGROUND: Early recurrence of atrial tachyarrhythmias (ERATs) within three months following thermal ablation for atrial fibrillation (AF) is common and often considered transient. Pulsed field ablation (PFA) is a non-thermal energy source in which ERAT is not well described. OBJECTIVE: To analyze ERAT in AF patients undergoing PFA in the PULSED AF trial. METHODS: This analysis included 294 patients (154 paroxysmal, 140 persistent AF) that had ≥10 rhythm assessments during the 90-day blanking period. ERAT was defined as any instance of ≥30s of AF, atrial flutter, or atrial tachycardia on trans-telephonic monitoring (weekly and symptomatic) or ≥10s on ECG (at 3 months), both within 90 days. Late recurrence of atrial tachyarrhythmias (LRATs) was defined as observed atrial tachyarrhythmias between 90 days and 12 months. RESULTS: The overall prevalence of ERAT was 27.1% in paroxysmal and 31.6% in persistent AF patients. In patients with ERAT, 73% had ERAT onset within the first month post-procedure. Presence of ERAT was associated with LRAT in paroxysmal (HR 6.4 (95% c.i. 3.6-11.3)) and persistent (HR 3.8 (95% c.i. 2.2-6.6)) AF patients. Yet, in 29.4% of paroxysmal and 34.3% of persistent AF patients with ERAT, LRAT was not observed. LRAT was positively correlated with the number of ERAT observations. CONCLUSION: ERAT post PFA predicted LRAT in paroxysmal and persistent AF patients. However, the concept of a blanking period post PFA is still valid as approximately 1/3 of patients with ERAT did not continue on to LRAT during follow-up and may not need re-ablation.

Evaluating homologous recombination activity in tissues to predict the risk of hereditary breast and ovarian cancer and olaparib sensitivity.

Homologous recombination (HR) repairs DNA damage including DNA double-stranded breaks and alterations in HR-related genes results in HR deficiency. Germline alteration of HR-related genes, such as BRCA1 and BRCA2, causes hereditary breast and ovarian cancer (HBOC). Cancer cells with HR deficiency are sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors and DNA-damaging agents. Thus, accurately evaluating HR activity is useful for diagnosing HBOC and predicting the therapeutic effects of anti-cancer agents. Previously, we developed an assay for site-specific HR activity (ASHRA) that can quantitatively evaluate HR activity and detect moderate HR deficiency. HR activity in cells measured by ASHRA correlates with sensitivity to the PARP inhibitor, olaparib. In this study, we applied ASHRA to lymphoblastoid cells and xenograft tumor tissues, which simulate peripheral blood lymphocytes and tumor tissues, respectively, as clinically available samples. We showed that ASHRA could be used to detect HR deficiency in lymphoblastoid cells derived from a BRCA1 pathogenic variant carrier. Furthermore, ASHRA could quantitatively measure the HR activity in xenograft tumor tissues with HR activity that was gradually suppressed by inducible BRCA1 knockdown. The HR activity of xenograft tumor tissues quantitatively correlated with the effect of olaparib. Our data suggest that ASHRA could be a useful assay for diagnosing HBOC and predicting the efficacy of PARP inhibitors.

Epicardial adipose tissue density predicts the presence of atrial fibrillation and its recurrence after catheter ablation: three-dimensional reconstructed image analysis.

Epicardial adipose tissue (EAT) induces inflammation in the atria and is associated with atrial fibrillation (AF). Several studies have examined the relationship between EAT volume (EAT-V) and density (EAT-D) and the presence of AF after catheter ablation. However, conclusions have been inconsistent. This study included 43 consecutive patients who underwent catheter ablation for AF and 30 control patients. EAT-V and EAT-D around the entire heart, entire atrium, left atrium (LA), and right atrium (RA) were measured in detail using reconstructed three-dimensional (3D) EAT images from dual-source computed tomography (CT). None of the measurements of EAT-V differed significantly between patients with AF and controls or between patients with recurrent AF and those without. On the other hand, all measurements of EAT-D were higher in patients with AF than in controls (entire atrium, p < 0.001; RA, p < 0.001; LA, p = 0.002). All EAT-D measurements were associated with the presence of AF. Among patients with AF who underwent ablation, all EAT-D measurements were higher in patients with recurrent AF than in those without. The difference was significant for EATRA-D (p = 0.032). All atrial EAT-D values predicted recurrent AF (EATRA-D: hazard ratio [HR], 1.208; 95% confidence interval [95% CI], 1.053-1.387; p = 0.007; EATLA-D: HR, 1.108; 95% CI 1.001-1.225; p = 0.047; EATatrial-D: HR, 1.174; 95% CI 1.040-1.325; p = 0.010). The most sensitive cutoffs for predicting recurrent AF were highly accurate for EATRA-D (area under the curve [AUC], 0.76; p < 0.01) and EATatrial-D (AUC = 0.75, p < 0.05), while the cutoff for EATLA-D had low accuracy (AUC, 0.65; p = 0.209). For predicting the presence of AF and recurrent AF after catheter ablation, 3D analysis of atrial EAT-D, rather than EAT-V, is useful.

Mitochondrial dynamics as a novel treatment strategy for triple-negative breast cancer.

INTRODUCTION: Triple-negative breast cancer (TNBC), recognized as the most heterogeneous type of breast cancer (BC), exhibits a worse prognosis than other subtypes. Mitochondria dynamics play a vital role as mediators in tumorigenesis by adjusting to the cell microenvironments. However, the relationship between mitochondrial dynamics and metabophenotype exhibits discrepancies and divergence across various research and BC models. Therefore, this study aims to explore the role of mitochondrial dynamics in TNBC drug resistance and tumorigenesis. METHODS: The Wst-8 test was conducted to assess doxorubicin sensitivity in HCC38, MDA-MB-231 (TNBC), and MCF-7 (luminal). Confocal microscopy and FACS were used to quantify the mitochondrial membrane potential (ΔφM), mitophagy, and reactive oxygen species (ROS) production. Agilent Seahorse XF Analyzer was utilized to measure metabolic characteristics. Dynamin-related protein-1 (DRP1), Parkin, and p62 immunohistochemistry staining were performed using samples from 107 primary patients with BC before and after neoadjuvant chemotherapy (NAC). RESULTS: MDA-MB-231, a TNBC cell line with reduced sensitivity to doxorubicin, reduced ΔφM, and enhanced mitophagy to maintain ROS production through oxidative phosphorylation (OXPHOS)-based metabolism. HCC38, a doxorubicin-sensitive cell line, exhibited no alterations in ΔφM or mitophagy. However, it demonstrated an increase in ROS production and glycolysis. Clinicopathological studies revealed that pretreatment (before NAC) expression of DRP1 was significant in TNBC, as was pretreatment expression of Parkin in the hormone receptor-negative group. Furthermore, low p62 levels seem to be a risk factor for recurrence-free survival. CONCLUSION: Our findings indicated that the interplay between mitophagy, linked to a worse clinical prognosis, and OXPHOS metabolism promoted chemotherapy resistance in TNBC. Mitochondrial fission is prevalent in TNBC. These findings suggest that targeting the unique mitochondrial metabolism and dynamics in TNBC may offer a novel therapeutic strategy for patients with TNBC.

Potential role of Fbxo22 in resistance to endocrine therapy in breast cancer with invasive lobular carcinoma.

BACKGROUND: Invasive lobular carcinoma (ILC) is distinct from invasive ductal carcinoma (IDC) in terms of their hormonal microenvironments that may require different therapeutic strategies. We previously reported that selective estrogen receptor modulator (SERM) function requires F-box protein 22 (Fbxo22). Here, we investigated the role of Fbxo22 as a potential biomarker contributing to the resistance to endocrine therapy in ILC. METHODS: A total of 302 breast cancer (BC) patients including 150 ILC were recruited in the study. Fbxo22 expression and clinical information were analyzed to elucidate whether Fbxo22 negativity could be a prognostic factor or there were any correlations among clinical variables and SERM efficacy. RESULTS: Fbxo22 negativity was significantly higher in ILC compared with IDC (58.0% vs. 27.0%, P < 0.001) and higher in postmenopausal patients than premenopausal patients (64.1% vs. 48.2%, P = 0.041). In the ILC cohort, Fbxo22-negative patients had poorer overall survival (OS) than Fbxo22-positive patients, with 10-year OS rates of 77.4% vs. 93.6% (P = 0.055). All patients treated with SERMs, Fbxo22 negativity resulted in a poorer outcome, with 10-year OS rates of 81.3% vs. 92.3% (P = 0.032). In multivariate analysis regarding recurrence-free survival (RFS) in ILC patients, Fbxo22 status was independently predictive of survival as well as lymph node metastasis. CONCLUSION: Fbxo22 negativity significantly impacts on survival in BC patients with IDC and ILC, and the disadvantage was enhanced among ILC postmenopausal women or patients treated with SERMs. The findings suggest that different therapeutic strategies might be needed according to the different histopathological types when considering adjuvant endocrine therapy.

Phrenic nerve injury after atrial fibrillation ablation: different recovery courses among cryoballoon, laser balloon, and radiofrequency ablation.

BACKGROUND: Phrenic nerve injury (PNI) is one of the common complications in atrial fibrillation (AF) ablation, which often recovers spontaneously. However, the course of its recovery has not been examined fully, especially in regard to the different ablation methods. We sought to compare the recovery course of PNI in cryoballoon, laser balloon, and radiofrequency ablation. METHODS: This multicenter retrospective study analyzed 355 patients who suffered from PNI during AF ablation. PNI occurred during cryoballoon ablation (CB group) and laser balloon ablation (LB group) for a pulmonary vein isolation in 288 and 20 patients, and radiofrequency ablation for a superior vena cava (SVC) isolation (RF-SVC group) in 47 patients, respectively RESULTS: There was a significant difference in the estimated probability of PNI recovery after the procedure between the methods (p = 0.01). PNI recovered significantly earlier in the CB group, especially within 24 h and 3 months post-procedure (the percentage of the recovery within 24 h and 3 months: 49.7% and 71.5% in the CB group, 15.0% and 22.2% in the LB group, and 23.4% and 41.9% in the RF-SVC group, respectively). Persistent PNI after 12 months was observed in only seven patients in the CB group, one in the LB group, and four in the RF-SVC group, respectively. CONCLUSION: PNI rarely persists over 12 months after AF ablation; however, there is a difference in the timing of its recovery. PNI recovers quicker with cryoballoon ablation than with laser balloon ablation or radiofrequency ablation of the SVC.

Changes in cell-free DNA after short-term palbociclib and fulvestrant treatment for advanced or metastatic hormone receptor-positive and human epidermal growth factor 2-negative breast cancer.

PURPOSE: Here, we investigated the potential predictive and elucidating efficacy of cell-free DNA (cfDNA) changes on clinical outcomes and biological effects, respectively, after short-term palbociclib and fulvestrant treatment for patients with hormone receptor (HR)-positive and human epidermal growth factor 2 (HER2)-negative advanced or metastatic breast cancer (ABC). METHODS: In this secondary analysis of the Japan Breast Cancer Research Group-M07 (FUTURE) trial, blood cfDNA was obtained before palbociclib treatment and on day 15 of cycle one (28-day cycle). Target enrichment was performed using next-generation sequencing; progression-free survival (PFS) was compared based on cfDNA changes between baseline and day 15 of cycle one after combination therapy. RESULTS: Fifty-six patients (112 paired blood samples) were examined. The median follow-up time was 8.9 months. PIK3CA (30.4%, 17/56), FOXA1 (30.4%, 17/56), and ESR1 (28.6%, 16/56) were most frequently mutated at baseline. The number of mutated genes was significantly decreased on day 15 compared with that at baseline (paired t test: P value = 0.025). No significant difference was observed in PFS (decrease group, 7.9 m vs the others, 9.3 m; log-rank P value = 0.75; hazard ratio, 1.13; 95% confidence interval, 0.53-2.41). Among patients without previous aromatase inhibitor treatment (n = 15), three (20%) had ESR1 mutations after progression to fulvestrant. CONCLUSION: No significant association was observed between changes in mutated genes after short-term palbociclib and fulvestrant treatment and disease progression; a significant reduction in cfDNA mutation level was observed on day 15 of cycle one. Clinical meanings of cfDNA should be investigated in the future trials.

Treatment with catheter ablation for patients with arrhythmia-induced cardiomyopathy caused by atrial fibrillation promises a good prognosis.

Clinical outcomes after catheter ablation in patients with reduced left ventricular (LV) ejection fraction (EF) and atrial fibrillation (AF) remain unclear. This study aimed to explore the clinical outcomes of patients with arrhythmia-induced cardiomyopathy (AIC) and the influence of pharmacological treatment on clinical outcomes in patients with AIC after the procedure. Ninety-six patients with AF with a reduced LVEF (LVEF < 50%, 66.7 ± 10.9 years; 72 males) underwent AF ablation. AIC was defined as patients whose LVEF recovered ≥ 50% after catheter ablation (n = 67) and patients whose LVEF remained reduced were defined as non-AIC (n = 29). During a median follow-up of 25 (13-40) months, Kaplan-Meier analysis demonstrated that patients with AIC were associated with less frequent cardiovascular death (p = 0.025) and hospitalization for worsening heart failure (p < 0.001) than those without AIC. Freedom from AF recurrence was similar between the two groups (p = 0.47). In multivariate analysis, the LV end-diastolic diameter (p = 0.0002) and the CHA2DS2-VASc scores (p = 0.0062) were independent predictors of AIC. Among the 67 patients with AIC, no significant differences in baseline characteristics, except for LV chamber size and cryoballoon use, were observed between patients with AIC with (n = 31) and without renin-angiotensin system (RAS) inhibitors (n = 36). In the Kaplan-Meier analysis, cardiovascular death, hospitalization for worsening heart failure, and AF recurrence after catheter ablation did not differ between patients treated with and without RAS inhibitors (all p > 0.05). Catheter ablation in patients with AIC due to AF is associated with a good post-procedural prognosis.IRB information The study was approved by the Research Ethics Committee of the University of Fukui (No. 20220151) and clinical trial registration (UMIN000050391).

Symptomatic periesophageal vagal nerve injury by different energy sources during atrial fibrillation ablation.

Background: Symptomatic gastric hypomotility (SGH) is a rare but major complication of atrial fibrillation (AF) ablation, but data on this are scarce. Objective: We compared the clinical course of SGH occurring with different energy sources. Methods: This multicenter study retrospectively collected the characteristics and clinical outcomes of patients with SGH after AF ablation. Results: The data of 93 patients (67.0 ± 11.2 years, 68 men, 52 paroxysmal AF) with SGH after AF ablation were collected from 23 cardiovascular centers. Left atrial (LA) ablation sets included pulmonary vein isolation (PVI) alone, a PVI plus a roof-line, and an LA posterior wall isolation in 42 (45.2%), 11 (11.8%), and 40 (43.0%) patients, respectively. LA ablation was performed by radiofrequency ablation, cryoballoon ablation, or both in 38 (40.8%), 38 (40.8%), and 17 (18.3%) patients, respectively. SGH diagnoses were confirmed at 2 (1-4) days post-procedure, and 28 (30.1%) patients required re-hospitalizations. Fasting was required in 81 (92.0%) patients for 4 (2.5-5) days; the total hospitalization duration was 11 [7-19.8] days. After conservative treatment, symptoms disappeared in 22.3% of patients at 1 month, 48.9% at 2 months, 57.6% at 3 months, 84.6% at 6 months, and 89.7% at 12 months, however, one patient required surgery after radiofrequency ablation. Symptoms persisted for >1-year post-procedure in 7 patients. The outcomes were similar regardless of the energy source and LA lesion set. Conclusions: The clinical course of SGH was similar regardless of the energy source. The diagnosis was often delayed, and most recovered within 6 months, yet could persist for over 1 year in 10%.

Contrast-enhanced computed tomography in the venous rather than the arterial phase is essential for the evaluation of the right phrenic nerve.

BACKGROUND: Preprocedural detection of the running course of the right pericardiophrenic bundles (PBs) is considered to be useful in preventing phrenic nerve (PN) injury during catheter ablation for atrial fibrillation (AF). However, previous studies using the arterial phase of contrast-enhanced computed tomography (CT) reported a relatively low right PBs detection rate. METHODS: This study included 63 patients with AF who underwent catheter ablation and preoperative contrast-enhanced CT imaging of the venous and arterial phases (66.7 ± 10.2 years; 44 male). The venous phase of contrast-enhanced CT significantly improved the detection rate of PBs compared to the arterial phase (96.8% vs. 60.3%, p < .001), and PBs were detected in the venous phase only in 23 (36.7%) patients. No significant differences were observed between the right PBs detection rate using non-contrast CT versus the arterial phase of contrast-enhanced CT (p = .37). Patients without visualization of the right PBs during the arterial phase had a higher frequency of chronic heart failure (p = .0083), lower left ventricular ejection fraction (p = .021), and a higher CHADS2 score (p = .048) than those with visualization. In five patients whose right PBs could only be detected during the venous phase of contrast-enhanced CT, the reconstructed running course of the right PBs corresponded with the PN generated by electrical high-output pacing. CONCLUSION: Contrast-enhanced CT images of the venous phase, rather than the arterial phase, are useful in detecting the right PBs, especially in patients with heart failure or reduced left ventricular ejection fraction.

Immunolocalization of Cytoplasmic ER in ER-negative Breast Carcinoma as a Potent Favorable Prognostic Predictor.

It is known that estrogen receptor (ER) has extranuclear signaling functions in addition to classical genomic pathway, and estrogenic actions have been reported in ER-negative breast carcinoma cells. However, significance of cytoplasmic-ER immunoreactivity has not been reported in ER-negative breast carcinoma tissues. We immunolocalized cytoplasmic ER in 155 ER-negative breast carcinoma tissues and evaluated its clinicopathological significance including the prognosis. As a comparative cohort set, we also used 142 ER-positive breast carcinomas. Cytoplasmic-ER immunoreactivity was detected in the carcinoma cells, but not in the non-neoplastic mammary epithelium. Cytoplasmic-ER immunoreactivity was positive in the 35 out of 155 (23%) ER-negative breast carcinoma cases, whereas it was detected only in 2 out of 142 (1.4%) ER-positive cases. Cytoplasmic ER status was positively associated with cytoplasmic-PR status, but inversely associated with Ki67 labeling index or distant free-relapse survival rate. Moreover, cytoplasmic-ER status turned out to be an independent good prognostic factor for both distant relapse-free survival and breast cancer specific survival. These findings suggested that cytoplasmic ER plays important roles in the ER-negative breast carcinoma, and cytoplasmic ER is a potent good prognostic factor. Among the ER-negative breast cancer patients, clinical benefit of chemotherapy may be limited in the cytoplasmic-ER positive cases.

Effects of door-to-tolvaptan time on short-term clinical outcome in patients with acute heart failure.

AIMS: We investigated the effects of door-to-tolvaptan (D2T) time on short-term urine volume and in-hospital clinical outcomes in patients with acute heart failure (AHF). METHODS AND RESULTS: Patients with AHF, treated with tolvaptan at two hospitals, were enrolled in this retrospective observational study. The D2T time was defined as the time elapsed from the arrival of a patient at a participating hospital to the first administration of tolvaptan. The group with the D2T time within 6 h was defined as the 'early group'. The primary outcome was 48-h urine volume. The secondary outcomes were in-hospital death, length of hospital stay, and worsening renal function (WRF) incidence. A restricted cubic spline model was used to evaluate the presence of a nonlinear association between the D2T time and 48-h urine volume and the odds ratio of WRF incidence. Our study included a total of 138 patients with AHF who were started on tolvaptan after hospitalization. The median D2T time was 5.3 h (interquartile range: 3.0-31.9 h). Seventy-four patients (53.6%) were classified to be in the early group. Baseline characteristics were similar in the two groups: mean age (85.4 ± 9.6 years vs. 84.5 ± 9.5 years; P = 0.59) and male sex (n = 22 [33.3%] vs. n = 29 [46%]; P = 0.16), except that patients in the early group had higher systolic blood pressure than those in the delayed group (138.2 ± 22.9 vs. 125.7 ± 21.7; P = 0.001). The initial tolvaptan dose in the delayed group was much lower than that in the early group (7.5 [7.5, 7.5] vs. 7.5 [5.6, 7.5] mg; P = 0.01). Total urine volume in 48 h did not differ in the early and delayed groups (4113 ± 1758 mL vs. 4201 ± 1893 mL; P = 0.80). The relationship between D2T time and total urine volume within 48 h increased slightly, with a peak at a D2T time of 15 h, and gradually decreased, thereafter. In-hospital death and the length of hospital stay did not differ significantly between the two groups (n = 1, 1.3% vs. n = 4, 6.3%; P = 0.18, and 5.0 [12.0, 30.0] vs. 22.0 [14.5, 30.0] days; P = 0.17, respectively). Notably, the restricted cubic spline model for the odds ratio of WRF incidence increased as the D2T time was delayed (P for effect<0.01). CONCLUSIONS: The shorter D2T time did not affect the short-term urine volume and in-hospital outcomes but reduced the risk of WRF incidence in patients with AHF.

Atrial fibrillation activation patterns predict freedom from arrhythmias after catheter ablation: utility of ExTRa mapping™.

Background: Mechanisms underlying atrial fibrillation (AF) are widely complex and vary tremendously among individuals. Objectives: This retrospective study aimed to investigate the association between AF activation patterns and clinical outcomes post-ablation. Methods: Fifty-five AF patients (64.0 ± 12.9 years; 41 men; 17 paroxysmal) underwent bi-atrial endocardial driver mapping during AF pre-ablation with a real-time phase mapping system (ExTRa Mapping). The nonpassively activated ratio (%NP) of meandering rotors and multiple wavelets relative to the recording time was evaluated in 26 atrial segments [15 in the left atrium (LA) and 11 in the right atrium]. Irrespective of the mapping results, all patients underwent standard AF ablation via cryoballoons and/or radiofrequency catheters. Results: In a median follow-up interval of 27(14-30) months, 69.1% of patients were free from recurrent arrhythmias and antiarrhythmic drugs at one year post-procedure. Patients with recurrent AF were more likely to have non-paroxysmal AF, a significantly larger LA size, and higher LA maximal %NP(LAmax%NP) and LA anterior wall %NP(LAAW%NP) than those without recurrent AF. A multivariate Cox regression analysis showed that both an LAmax%NP (hazard ratio [HR] = 1.075; 95% confidence interval [CI] = 1.02-1.14, p = 0.012) and LAAW%NP (HR = 1.061; 95% CI = 1.01-1.11, p = 0.013) were independent predictors of atrial arrhythmia recurrence. The optimal cutoff points for the LAmax%NP and LAAW%NP for predicting AF recurrence were 64.5% and 60.0%, respectively. A Kaplan-Meier analysis demonstrated that both an LAmax%NP > 64.5% (p = 0.0062) and LAAW%NP > 60.0% (p = 0.014) were associated with more frequent AF recurrences. Conclusion: Baseline AF activation pattern mapping may aid in predicting freedom from arrhythmias after standard AF ablation procedures.

The R Wave Amplitude in Lead aVL Could Predict Successful Catheter Ablation of Ventricular Arrhythmias Originating below the His Bundle Region of the Right Ventricle.

Radiofrequency catheter ablation (RFCA) to treat ventricular arrhythmias (VAs) originating below the His bundle (HB) region of the right ventricular (RV) septum could impair the atrioventricular node conduction. This study aimed to clarify the parameters of the 12-lead electrocardiography that predict successful RFCA of VAs originating from this region. This study included 20 consecutive patients (13 men; mean age, 68 ± 7 years) with monomorphic VAs in whom the earliest ventricular activation during the VA was below the HB region of the RV septum. According to the ablation results, the patients were divided into two groups: successful ablation (S-group; n = 10) and failed ablation groups (F-group; n = 10). The electrocardiographic parameters during the VAs and RFCA results were assessed. The R wave amplitudes in leads aVL (P = 0.001) and I (P = 0.010) in the S-group were both smaller than those in the F-group. In addition, the S-group had smaller negative deflection amplitudes in leads III (P = 0.002) and aVF (P = 0.003) than the F-group. According to the receiver operating characteristic curve analysis, the most useful electrocardiographic parameter for predicting successful ablation was the R wave amplitude in lead aVL (area under the curve, 0.895; P < 0.001); a cutoff value of < 1.3 mV predicted a successful RFCA with the highest accuracy (sensitivity, 90%; specificity, 80%; positive predictive value, 82%; negative predictive value, 89%). The R wave amplitude in lead aVL was the most useful parameter for predicting a successful RFCA to treat VAs originating below the HB region of the RV septum.

Clinical Significance of ABCG2/BCRP Quantified by Fluorescent Nanoparticles in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy.

Breast cancer resistance protein (BCRP), also known as ATP-binding cassette transporter G2 (ABCG2), is associated with chemotherapy resistance. BCRP is also implicated in breast cancer stem cells, and is reported as a poor prognostic factor. However, the relationship of BCRP levels in breast cancer tissues with chemotherapy resistance and prognosis has not been clarified. We aimed to evaluate the correlation between BCRP expression and prognosis in breast cancer using immunohistochemistry with fluorescent phosphor-integrated dots (IHC-PIDs). A total of 37 breast cancer patients with residual cancer in the primary tumor and axillary lymph nodes were evaluated. BCRP levels in breast cancer tissue and metastatic lymph nodes were quantitatively detected after neoadjuvant chemotherapy (NAC). Among these 37 patients, 24 had corresponding core needle biopsies obtained before NAC. Biomarker assay with IHC-PIDs showed high accuracy for the quantitative assessment of BCRP with low expression. High BCRP expression in the primary tumor and metastatic lymph nodes after preoperative chemotherapy was associated with worse overall survival. In conclusion, high BCRP levels may be associated with poor prognosis in patients with breast cancer, having residual tumors within the primary tumor and lymph nodes after preoperative chemotherapy. These findings provide a basis for further appropriate adjuvant therapy in these patients.

Influence of monitoring and atrial arrhythmia burden on quality of life and health care utilization in patients undergoing pulsed field ablation: A secondary analysis of the PULSED AF trial.

BACKGROUND: Freedom from atrial arrhythmia (AA) recurrence ≥30 seconds after pulsed field ablation (PFA) in patients with atrial fibrillation (AF) was reported in PULSED AF (Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF; ClinialTrials.gov Identifier: NCT04198701). AA burden may be a more clinically meaningful endpoint. OBJECTIVE: The purpose of this study was to determine the influence of monitoring strategies on AA detection and AA burden association with quality of life (QoL) and health care utilization (HCU) after PFA. METHODS: Patients underwent 24-hour Holter monitoring at 6 and 12 months and weekly, and symptomatic transtelephonic monitoring (TTM). AA burden post-blanking was calculated as the greater of (1) percentage of AA on total Holter time; or (2) percentage of weeks with ≥1 TTM with AA out of all weeks with ≥1 TTM. RESULTS: Freedom from all AAs varied by >20% when differing monitoring strategies were used. PFA resulted in zero burden in 69.4% of paroxysmal atrial fibrillation (PAF) and 62.2% of persistent atrial fibrillation (PsAF) patients. Median burden was low (<9%). Most PAF and PsAF patients had ≤1 week of AA detection on TTM (82.6% and 75.4%) and <30 minutes of AA per day of Holter monitoring (96.5% and 89.6%), respectively. Only PAF patients with <10% AA burden averaged a clinically meaningful (>19 point) QoL improvement. PsAF patients experienced clinically meaningful QoL improvements irrespective of burden. Repeat ablations and cardioversions significantly increased with higher AA burden (P <.01). CONCLUSION: The ≥30-second AA endpoint is dependent on the monitoring protocol used. PFA resulted in low AA burden for most patients, which was associated with clinically relevant improvement in QoL and reduced AA-related HCU.