Risk factors of acute renal impairment after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Acute renal impairment (ARI) is a major complication after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for cancer patients with peritoneal metastases. This study aimed to investigate the incidence and identify the risk factors of post-HIPEC creatinine increased. METHODS: From April 2015 to December 2019, demographic and perioperative data of 169 patients undergoing CRS/HIPEC with a preoperative creatinine level <1.5 mg/dL were retrospectively reviewed. Renal impairment was defined according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. The risk factors of creatinine increased were analyzed using univariate and multiple logistic regression analyses. RESULTS: Among the 169 enrolled patients, 21 (12.4%) had postoperative creatinine increased (ARI group) and 148 (87.6%) did not (non-ARI group). Significantly more of the ARI group received a cisplatin HIPEC regimen than the non-ARI group (71.4 vs. 37.8%, p = 0.004). Multiple logistic regression analysis revealed that the patients who received a cisplatin HIPEC regimen (adjusted odds ratio [AOR] = 11.38, p < 0.001) and peritoneal dialysis solution as HIPEC perfusate (AOR = 7.07, p = 0.002) were more likely to develop post-HIPEC creatinine increased. CONCLUSIONS: Identifying the risk factors of post-HIPEC creatinine increased can help to improve patient selection, a dose of HIPEC regimens modification and perioperative care. We also identified the detrimental renal effect of peritoneal dialysis solution as HIPEC perfusate. More prospective studies are warranted to confirm these findings.

Diallyl trisulfide protects against high glucose-induced cardiac apoptosis by stimulating the production of cystathionine gamma-lyase-derived hydrogen sulfide.

BACKGROUND: Cystathionine-γ-lyase (CSE)-derived hydrogen sulfide (H2S) is a potent cardioprotective agent. We investigated the effects of diallyl trisulfide (DATS) on CSE expression and H2S generation in myocardium and examined whether DATS-mediated H2S generation effectively protects rat heart from diabetes-induced cardiac damage. METHODS: The correlations between the effects of hyperglycemia and diabetes on CSE expression and the effects of DATS and H2S on hyperglycemia and diabetes were examined in vitro in the cardiomyocyte cell line H9c2 and in vivo in hearts from rats with streptozotocin-induced diabetes mellitus (DM). RESULTS: Expression of CSE, a catalyst of H2S production, was suppressed in H9c2 cells treated with high glucose (33 mM) and in DM rat hearts. CSE suppression also correlated with a decrease in the activation of the pro-survival protein kinase Akt. Treatment of H9c2 cells with DATS resulted in increased CSE expression and a reduction in apoptosis via a mechanism involving IGF1R/pAkt signaling and by modulating the expression of reactive oxygen species-related enzymes. The role CSE plays in the cardioprotective effects of DATS was further confirmed by CSE inhibition assays including inhibitors and siRNA. CONCLUSION: DATS produces H2S as efficiently as NaSH and DATS-derived H2S provides effective cardioprotection. Further, our data indicate that H2S plays a major role in the protective effect of DATS against apoptosis of cardiomyocytes.

Relationship between intrinsic cardiac autonomic ganglionated plexi and the atrial fibrillation nest.

BACKGROUND: Spectral analysis of the left atrium can identify high dominant frequency (DF) sites, which might play a role in the perpetuation of atrial fibrillation (AF). Furthermore, the role of the cardiac autonomic nervous system (CANS) in the genesis of AF has been demonstrated. The relationship between CANS and the high-DF sites (AF nest) was the aim of the investigation. METHODS AND RESULTS: In 12 dogs, high frequency stimulation was applied to locate 4 major left atrial (LA) ganglionated plexi (GPs). An Ensite Array and a mapping catheter were delivered into the left atrium for electroanatomical mapping. During sinus rhythm, spectral analysis was performed on the bipolar electrograms in the left atrium before and after epicardial GP ablation. The majority of AF nests were close to the GPs (52±18% of total AF nests). After GP ablation, the mean LA DF values decreased from 54±7Hz to 49±4Hz (P=0.023), and DF values of the AF nest decreased from 93±2Hz to 87±4Hz (P=0.001). Most of the previous AF nest sites close to the GPs disappeared (85±23%). The surface area of the AF nest decreased from 9±5cm(2) to 3±2cm(2) (P=0.001). CONCLUSIONS: Catheter ablation of the GP decreased the DF values, AF nest areas and diminished the number of AF nests; particularly those close to the GPs, indicating that the CANS might play an important role in the mechanism of the AF nest.

Prevalence, characteristics, mapping, and catheter ablation of potential rotors in nonparoxysmal atrial fibrillation.

BACKGROUND: Identification of critical atrial substrates in patients with nonparoxysmal atrial fibrillation (AF) failing to respond to pulmonary vein isolation is important. This study investigated the signal characteristics, substrate nature, and ablation results of rotors during AF. METHODS AND RESULTS: In total, 53 patients (age=55±8), 31 with persistent AF and 22 with long-lasting AF, underwent pulmonary vein isolation and substrate modification of complex fractionated atrial electrograms. Small-radius-reentrant rotors were identified from signal analyses of the dominant frequency and fractionation interval and nonlinear analyses (newly developed, beat-to-beat nonlinear measurement of the repetitiveness of the electrogram morphology>6 seconds). In 15% of the patients, activation maps demonstrated occurrences of rotor-like small-radius reentrant circuits (n=9; 1.1 per patient; cycle length=110±21 ms; diameter=11±6 mm) with fibrillation occurring outside these areas. Rotors were identified by conventional point-by-point mapping and signal analyses and were subsequently eradicated by catheter ablation in these patients. Persistent AF for <1 year, a smaller left atrial size, substrates with higher mean voltages and shorter total activation durations predicted a higher incidence of rotors (all P<0.05). In the multivariable model, areas of reentrant circuits exhibited a higher dominant frequency, kurtosis, and higher degree of a beat-to-beat electrogram similarity than areas without or outside the rotors (all P<0.05). CONCLUSIONS: Rotor-like re-entry with fibrillatory conduction was found in a limited number of patients with nonparoxysmal AF after pulmonary vein isolation. Those areas were characterized by rapid repetitive activity with a high degree of electrogram similarity.

Sinus node dysfunction in atrial fibrillation patients: the evidence of regional atrial substrate remodelling.

AIMS: It remains unclear as to whether regional atrial substrates of certain areas of the atrium in patients with atrial fibrillation (AF) can be related to sinoatrial node dysfunction. We investigated the relationship between the biatrial substrate characteristics and sinus node function in these patients. METHODS AND RESULTS: The study enrolled 34 patients (aged 57 ± 11 years old; 20 males) who underwent catheter ablation for symptomatic paroxysmal AF. Sinus node dysfunction was defined as having corrected sinus node recovery time longer than 550 ms. Atrial substrate analyses of both atria and atrial conductive properties were investigated in patients with (Group 1) and without sinus node dysfunction (Group 2). The mean global bipolar voltage of both atria and the atrial refractory period were similar between the two groups. Regional analysis showed that the mean bipolar voltage for patients in Group 1 was lower than in Group 2 (1.0 ± 0.3 vs. 2.1 ± 0.7 mV, P < 0.001) only in the sinus node region, while the electrophysiological properties were similar for both groups in other anatomic regions of both atria. The right atrial total activation time was significantly longer (97 ± 9 vs. 89 ± 10 ms, P = 0.023) and the conduction velocity along the crista terminalis was significantly slower (1.0 ± 0.2 vs. 1.2 ± 0.3 m/s, P = 0.019) in Group 1 patients than in Group 2 patients. CONCLUSION: In patients with AF, regional atrial remodelling near the sinus node area was associated with sinus node dysfunction.

Nonlinear analysis of fibrillatory electrogram similarity to optimize the detection of complex fractionated electrograms during persistent atrial fibrillation.

INTRODUCTION: Currently, the identification of complex fractionated atrial electrograms (CFEs) in the substrate modification is mostly based on cycle length-derived algorithms. The characteristics of the fibrillation electrogram morphology and their consistency over time are not clear. The aim of this study was to optimize the detection algorithm of crucial CFEs by using nonlinear measure electrogram similarity. METHODS AND RESULTS: One hundred persistent atrial fibrillation patients that underwent catheter ablation were included. In patients who required CFE ablation (79%), the time-domain fibrillation signals (6 seconds) were acquired for a linear analysis (mean fractionation interval and dominant frequency [DF]) and nonlinear-based waveform similarity analysis of the local electrograms, termed the similarity index (SI). Continuous CFEs were targeted with an endpoint of termination. Predictors of the various signal characteristics on the termination and clinical outcome were investigated. Procedural termination was observed in 39% and long-term sinus rhythm maintenance in 67% of the patients. The targeted CFEs didn't differ based on the linear analysis modalities between the patients who responded and did not respond to CFE ablation. In contrast, the average SI of the targeted CFEs was higher in termination patients, and they had a better outcome. Multivariate regression analysis showed that a higher SI independently predicted sites of termination (≥ 0.57; OR = 4.9; 95% CI = 1.33-18.0; P = 0.017). CONCLUSIONS: In persistent AF patients, a cycle length-based linear analysis could not differentiate culprit CFEs from bystanders. This study suggested that sites with a high level of fibrillation electrogram similarity at the CFE sites were important for AF maintenance.

Long-term outcome of catheter ablation in patients with atrial fibrillation originating from nonpulmonary vein ectopy.

INTRODUCTION: Data regarding the long-term outcome of catheter ablation in patients with nonpulmonary vein (NPV) ectopy initiating atrial fibrillation (AF) are limited. We aimed to evaluate the long-term result of patients with AF who had NPV triggers and underwent catheter ablation. METHODS AND RESULTS: The study included 660 consecutive patients (age 54 ± 11 years old, 477 males) who had undergone catheter ablation for AF. Group 1 consisted of 132 patients with AF initiating from the NPV, and group 2 consisted of 528 patients with AF initiating from pulmonary vein (PV) triggers only. Patients from Group 1 were younger than those from Group 2 (51 ± 12 years old vs 54 ± 11 years old, P = 0.001) and were more likely to be females (34.4% vs 25.8%, P = 0.049). The incidences of nonparoxysmal AF (36.4% vs 16.3%, P < 0.001) and right atrial (RA) enlargement (31.3% vs 19%, P = 0.004) were higher, and the biatrial substrates were worse in Group 1 than those in Group 2 (left atrial voltage 1.5 ± 0.7 mV vs 1.9 ± 0.7 mV, P < 0.001, RA voltage 1.6 ± 0.5 mV vs 1.8 ± 0.6 mV, P = 0.014). During a follow-up period of 46 ± 23 months, there was a higher AF recurrence rate in Group 1 than in Group 2 (57.6% vs 38.8%, P < 0.001). The independent predictors of AF recurrence were NPV trigger (P < 0.001, HR 2, 95% CI 1.4-2.85), nonparoxysmal AF (P = 0.021, HR 1.55, 95% CI 1.07-2.24), larger left atrial diameter (P = 0.002, HR 1.04, 95% CI 1.02-1.07) and worse left atrial substrate (P = 0.028, HR 1.3, 95% CI 1.03-1.64). CONCLUSION: Compared to AF originating from the PV alone, AF originating from the NPV ectopy showed a worse outcome.

Relationship between the CHADS(2) score and risk of very late recurrences after catheter ablation of paroxysmal atrial fibrillation.

BACKGROUND: Catheter ablation of paroxysmal atrial fibrillation has been performed for more than 10 years. However, data about the long-term results were limited. OBJECTIVES: To evaluate the long-tem efficacy following paroxysmal atrial fibrillation ablation and to investigate whether there were different patterns of recurrences in patients with different CHADS(2) scores. METHODS: A total of 238 patients with paroxysmal atrial fibrillation who received a catheter ablation from 2004 to 2007 were enrolled. Free of recurrence was defined as the absence of atrial arrhythmias without using any antiarrhythmic agents after ablation. RESULTS: There were 121 patients (50.8%) suffering from recurrences after the first ablation procedure during a median follow-up period of 5 years. The CHADS(2) score and left atrial diameter were significant predictors of recurrences in the multivariate analysis. Different patterns of recurrence were observed in different groups of patients categorized on the base of CHADS(2) score. Among patients with a CHADS(2) score of ≥3 without recurrences at 2 years postablation, 63.6% experienced episodes of arrhythmias during the subsequent follow-up period. In contrast, in patients with a CHADS(2) score of 0 without recurrences at 2 years postablation, the future recurrence rate was only 2.7%. CONCLUSIONS: After a successful ablation, recurrences may continue to occur without reaching a plateau during the long-term follow-up, especially in patients with a high CHADS(2) score. The optimal follow-up strategy may differ and should be individualized for patients with different scores.

A novel finding of the atrial substrate properties and long-term results of catheter ablation in chronic atrial fibrillation patients with left atrial spontaneous echo contrast.

BACKGROUND: The atrial substrate in chronic atrial fibrillation (AF) patients with a left atrial spontaneous echo contrast (LASEC) has not been previously reported. The aim of this study was to investigate the atrial substrate properties and long-term follow-up results in the patients who received catheter ablation of chronic AF. METHODS: Of 36 consecutive patients with chronic AF who received a stepwise ablation approach, 18 patients with an LASEC (group I) were compared with 18 age-gender-left atrial volume matched patients without an LASEC (group II). The atrial substrate properties including the weighted peak-to-peak voltage, total activation time during sinus rhythm (SR), dominant frequency (DF), and complex fractionated electrograms (CFEs) during AF in the bi-atria were evaluated. RESULT: The left atrial weighted bipolar peak-to-peak voltage (1.0 ± 0.6 vs 1.6 ± 0.7 mV, P = 0.04), total activation time (119 ± 20 vs 103 ± 13 ms, P < 0.001) and DF (7.3 ± 1.3 vs 6.6 ± 0.7 Hz, P < 0.001) differed between group I and group II, respectively. Those parameters did not differ in the right atrium. The bi-atrial CFEs (left atrium: 89 ± 24 vs 92 ± 25, P = 0.8; right atrium: 92 ± 25 vs 102 ± 3, P = 0.9) did not differ between group I and group II, respectively. After a mean follow-up of 30 ± 13 month, there were significant differences in the antiarrhythmic drugs (1.1 ± 0.3 vs 0.7 ± 0.5, P = 0.02) needed after ablation, and recurrence as persistent AF (92% vs 50%, P = 0.03) between group I and group II, respectively. After multiple procedures, there were more group II patients that remained in SR, when compared with group I (78% vs 44%, P = 0.04). CONCLUSION: There was a poorer atrial substrate, lesser SR maintenance after catheter ablation and need for more antiarrhythmic drugs in the chronic AF patients with an LASEC when compared with those without an LASEC.

Postmarketing surveillance of acarbose treatment in Taiwanese patients with type 2 diabetes mellitus.

OBJECTIVE: This postmarketing surveillance (PMS) study was conducted to assess the efficacy, safety and acceptance of acarbose treatment in patients with type 2 diabetes mellitus. METHODS: Patients were recruited in this open, prospective, uncontrolled, non-randomised multicentre study by 159 physicians throughout Taiwan, following the guidelines of the Bureau of National Health Insurance (BNHI) of Taiwan. Primary efficacy parameters were changes in fasting blood glucose, postprandial blood glucose and glycosylated haemoglobin (HbA(1c)) values during treatment with acarbose. RESULTS: The majority of the 1558 enrolled patients received acarbose 50 mg three times daily, had previously been treated with a sulphonylurea and/or biguanide, and were observed for a mean period of 13.9 weeks. Most patients (91.8%) received concomitant oral antihyperglycaemic agents. Acarbose reduced fasting blood glucose concentrations by 32.0 mg/dL and 2-hour postprandial blood glucose levels by 52.2 mg/dL. HbA(1c) was reduced by 1.0% from 9.9% to 8.9%, and bodyweight remained stable. The attending physicians assessed that acarbose was associated with 'very good' or 'good' general efficacy in 46.0% of patients, 'very good' or 'good' tolerability in 60.6% and 'very good' or 'good' patient acceptance in 63.4%. These ratings were higher for patients receiving acarbose monotherapy compared with those taking other antihyperglycaemic therapies in addition to acarbose. Only 2.0% of all patients experienced drug-related adverse events. CONCLUSION: Acarbose treatment provides an efficacious, safe and well accepted alternative for metabolic improvement in Taiwanese patients with type 2 diabetes under daily-life treatment conditions.