Silent Cerebral Events/Lesions Related to Atrial Fibrillation Ablation: A Clinical Review

Brain magnetic resonance imaging (MRI) has identified a high incidence of cerebral ischemia in asymptomatic patients after atrial fibrillation (AF) ablation (silent). Detection of cerebral ischemic events on MRI is based on acute hyperintense lesions on diffusion‐weighted imaging. In the literature, the incidence is related to specifications of MRI and depends on the definition applied. In comparative studies, silent cerebral events (SCE, diffusion‐weighted MRI [DWI] positive only) appear to be approximately 3 times more common compared to using a definition of silent cerebral lesions (SCL; without fluid attenuated inverse recovery sequence [FLAIR] positivity). Whereas the FLAIR sequence may turn positive within days after the ischemic event, SCE definition is highly sensitive for early phases of ischemic brain damage. SCE/SCL appear to represent cerebral ischemic infarcts and determine the “embolic fingerprint” of a specific ablation technology and strategy used. The optimum time point for detecting SCE is early after AF ablation (24–72 hours), whereas detection of SCL can only be performed within the first 2–7 days (due to delay of FLAIR positivity). Different technology‐, procedure‐, and patient‐related parameters have been identified to play a role in the multifactorial genesis of SCE/SCL. In recent years, evidence has been gathered that there may be differences of SCE/SCL rates depending upon the ablation technology used, but small patient numbers and a large number of potential confounders hamper all studies. As major findings of recent studies, mode of periprocedural and intraprocedural anticoagulation has been identified as a major predictor for incidences of SCE/SCL. Whereas procedural characteristics related to higher SCE/SCL‐rates may be modified, unchangeable patient‐related factors should be taken into account for future individualized risk assessment. Novel ablation devices introduced into the market should be tested for their potential embolic fingerprint and refinements of ablation procedures to reduce their embolic potential should be prompted. The knowledge of “best practice” in terms of low SCE/SCL rates has prompted changes in work‐flow, which have been implemented into ablation procedures using novel ablation devices. So far, no study has linked SCE/SCL to neuropsychological decline and the low number of AF‐ablation‐associated events needs to be weighted against the multitude of preexisting asymptomatic MRI‐detected brain lesions related to the course of AF itself. Future studies are needed to evaluate if more white matter hyperintensities due to AF may be prevented by AF ablation (producing only a small number of SCE/SCL).     

Response to Beta Blockers in Patients with Neurocardiogenic Syncope: How to Predict Beneficial Effects

Beta-Blocker Therapy for Neurocardiogenic Syncope. No definitive data are available about the possibility of predicting improvement in patients with neurocardiogenic syncope treated with beta blockers. Among 112 patients with syncope and a positive bead-up tilt test (HUT), independent predictors for prevention of symptoms with beta blockers were determined using the Cox proportional hazards model. Each patient underwent HUT at 70° for 20 minutes both in the drug-free state and during isoproterenol infusion given to increase the heart rate by at least 25%. Fifty-nine patients bad a positive HUT during isoproterenol infusion and 53 in the drug-free state. All patients were then given esmolol infusion at 500 μg/kg per minute for 3 minutes followed by 300 μg/kg per minute maintenance dose. HUT was then repeated as previously described with or without isoproterenol, depending upon the initial positive response. Regardless of the response during esmolol, all patients were treated with metoprolol 50 to 100 mg twice daily. At follow-up, 36 patients experienced symptom relapse. Four of them bad negative HUT on esmolol, whereas the remaining 32 did not respond to the acute infusion of esmolol. Only four patients with positive HUT on esmolol had a favorable response to metoprolol. Patients responding to metoprolol were older (55 ± 12 years vs 42 ± 15 years, P < 0.05). Response to metoprolol was predicted by a negative test on esmolol (P < 0.0001) and a positive HUT on isoproterenol (P < 0.001). Age older than 42 years was also associated with a higher likelihood of metoprolol success (P < 0.02). Conclusion : Acute challenge with esmolol infusion appears to be an accurate predictor of response to chronic beta blockers, together with age and a positive HUT during low-dose isoproterenol infusion.     

Reperfusion of Infarct Related Artery Achieved by Direct Percutaneous Transluminal Coronary Angioplasty Counteracts Left Ventricular Remodeling after Acute Myocardial Infarction More Than Thrombolysis

The purpose of this study was to compare the effect of direct percutaneous transluminal coronary angioplasty (PTCA) and intravenous recombinant tissue plasminogen activator (rt-PA) on left ventricular remodeling in patients with acute myocardial infarction (AMI). To address this issue, patients with AMI randomly assigned to direct PTCA or intravenous rt-PA as part of a large multicenter study (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO] IIb Angioplasty Substudy) were evaluated with two-dimensional echocardiography at predischarge. An echocardiographic infarct size index and the end-diastolic and end-systolic left ventricular volumes were computed. Patients with an infarct size index equal to or higher than the mean value were considered to have a large infarction. Of 26 enrolled patients, 13 were assigned to PTCA (9 successfully reperfused: i.e., TIMI-3 flow after PTCA) and 13 to rt-PA (10 successfully reperfused: i.e., ST resolution after rt-PA). In patients considered successfully reperfused, end-systolic volumes tended to be lower in PTCA patients than in rt-PA patients (43 ± 17 cc vs 59 ± 21 cc, P = 0.09), although there were no differences in infarct size index (7.3 ± 2.8 vs 7.0 ± 2.8) and ejection fraction (52%± 10% vs 46%± 12%). End-systolic volume depended on infarct size index in the overall patient population (r = 0.60, P = 0.007) and in rt-PA patients (r = 0.80, P =0.005), while no correlation was found in PTCA patients. Considering patients with large AMIs, end-systolic volumes were higher in the four patients treated with rt-PA than in the four patients treated with direct PTCA (P < 0.01). Considering all the 26 enrolled patients, these differences were also present, but they did not reach statistical significance. In conclusion, our results suggest that, in patients with large AMIs, adequate reperfusion obtained by direct PTCA has a more marked effect in counteracting ventricular remodeling than that obtained by systemic rt-PA. This beneficial effect of direct PTCA, independent of any reduction in regional wall-motion abnormalities, should be taken into account when comparing the clinical value of direct PTCA with that of systemic thrornbolysis in the treatment of AMI.     

EXTRAPERITONEAL LAPAROSCOPIC PYELOPLASTY: A MULTICENTER STUDY OF 55 PROCEDURES

PURPOSE: We assessed the feasibility, reproducibility and morbidity of retroperitoneal laparoscopic pyeloplasty for ureteropelvic junction obstruction. MATERIALS AND METHODS: A total of 55 retroperitoneal laparoscopic pyeloplasties were performed at 3 institutions between September 1996 and May 2000 in 33 women and 21 men. Results were analyzed in regard to radiological assessment by excretory urography at 3 months, complications and hospital stay. RESULTS: We performed dismembered pyeloplasty in 48 cases and Fenger plasty in 7 cases. Crossing vessels were noted in 23 patients. The conversion rate was 5.4%. Mean operative time was 185 minutes (range 100 to 260), mean hospital stay was 4.5 days (range 1 to 14) and mean followup was 14.4 months (range 6 to 43.6). The overall complication rate was 12.7%. Complications in 7 patients included hematoma in 3, urinoma in 1, severe pyelonephritis in 1 and anastomotic stricture in 2 requiring open pyeloplasty at 3 weeks and delayed balloon incision at 13 months, respectively. Excretory urography in 50 patients and ultrasound in 4 showed decreased hydronephrosis in 88.9% at 3 months. Normal physical activity and absent pain were reported by 47 patients (87%) 1 month after surgery. CONCLUSIONS: Retroperitoneal laparoscopic pyeloplasty seems to be a valuable alternative to open pyeloplasty for ureteropelvic junction obstruction. The long-term outcome must be assessed before this procedure may be definitively validated.     

INTERLEUKIN 6 GENE-TRANSFECTED MOUSE MAMMARY ADENOCARCINOMA: TUMOUR CELL GROWTH AND METASTATIC POTENTIAL

Cells from the spontaneous metastatic TSA mammary adenocarcinoma of BALB/C mouse were transfected with the murine (interleukin-6) IL6 gene. The clone (TSA-IL6) secreting the largest amount of IL6 displayed an in vitro increased growth rate compared with that of TSA cells transfected with the neomycin resistance gene only (TSA-neo). TSA-IL6 cell colonies consisted mainly of fusiform cells and TSA-neo colonies of polygonal cells. When subcutaneously (s.c.) injected in syngeneic mice, TSA-IL6 cells gave rise to tumours that grew significantly slower than TSA-neo cell tumours. Microscopically, TSA-IL6 tumours displayed a fascicular pattern of growth, associated with a very scanty macrophage infiltrate. S.c. TSA-IL6 tumours were significantly less metastatic than TSA-neo tumours. By contrast, following intravenous (i.v.) challenge, TSA-IL6 cells produced 5–7 times more lung metastases than TSA-neo cells. The i.v. TSA-IL6 cell lung metastases showed a marked macrophage infiltrate and a rich vascularization. The high in vitro TSA-IL6 cell growth rate is attributable to the IL6-induced production of growth factors, some of which possess heparin-binding properties, such as amphiregulin. The differences in vascularization and macrophage infiltrate may underlie the observed differences between s.c. TSA-IL6 tumour growth with low spontaneous metastatic potential and the widespread growth of i.v. metastasis. © 1997 John Wiley & Sons, Ltd.     

COMBINED POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION AND RESECTION OF CHEST TUMOR UNDER THE SAME ANESTHETIC IS APPROPRIATE BASED ON MORBIDITY AND TUMOR PATHOLOGY

Purpose

We determine if post-chemotherapy resection of residual retroperitoneal and chest tumor under the same anesthetic is reasonable based on tumor pathology and morbidity, and if the finding of necrosis in the abdomen allows observation of chest tumor.

Materials and Methods

We retrospectively reviewed 143 post-chemotherapy patients who underwent resection of residual retroperitoneal and chest disease under the same anesthetic.

Results

Retroperitoneal pathology was generally predictive of chest pathology. Concordance existed in 77.5% of patients with necrosis, 70% with teratoma and 69% with cancer of the abdomen. However, the correlation was much stronger (86%) in predicting necrosis/fibrosis if cases were categorized as uncomplicated by Indiana University criteria. Although the morbidity of the combined approach is higher than that of standard post-chemotherapy retroperitoneal lymph node dissection, it was acceptable.

Conclusions

The morbidity of post-chemotherapy retroperitoneal lymph node dissection and resection of chest disease under the same anesthetic is acceptable. Retroperitoneal pathology generally predicts chest pathology but this correlation is much stronger if the case is uncomplicated based on our criteria. In an uncomplicated case the discovery of necrosis of the abdomen allows observation of chest tumor.     

LOCAL MICROWAVE HYPERTHERMIA AND INTRAVESICAL CHEMOTHERAPY AS BLADDER SPARING TREATMENT FOR SELECT MULTIFOCAL AND UNRESECTABLE SUPERFICIAL BLADDER TUMORS

Purpose

The role of a combined regimen of local hyperthermia and topical chemotherapy in patients with multifocal and recurrent superficial bladder tumors not curable by transurethral resection was evaluated in a neodjuvant organ sparing clinical study.

Materials and Methods

A total of 19 patients with multifocal, superficial grades 1 to 3 bladder tumors that recurred after intravesical chemoprophylaxis or immunoprophylaxis underwent local combined administration of microwave induced hyperthermia and intravesical chemotherapy as a debulking approach. Due to extensive superficial involvement of the bladder walls complete transurethral resection of all tumors seemed technically unfeasible in all cases and radical cystectomy was considered the treatment of choice. Endovesical hyperthermia at 42.5 to 46C was delivered using the SB-TS 101 system,* based on a microwave transurethral applicator that irradiates the bladder filled with a circulating solution of mitomycin C. Patients underwent 8 weekly 1-hour sessions on an outpatient basis without anesthesia. When possible, after treatment patients underwent transurethral resection of residual tumors and all suspicious areas.*Boston Scientific Corp., Natick, Massachusetts.

Results

After treatment transurethral resection appeared to be feasible and curative in 16 patients (84%). Histological study revealed complete and partial responses in 9 (47%) and 7 (37%) cases, respectively. Due to extensive residual tumors radical cystectomy was performed in 3 patients (16%). At a median 33-month followup 8 superficial transitional tumor recurrences were documented and easily eradicated by transurethral resection or laser therapy in patients in whom the bladder had been saved.

Conclusions

Microwave induced hyperthermia combined with intravesical mitomycin C seems to be a feasible, safe and elective approach for conservative treatment of multifocal and recurrent superficial bladder tumors when other treatment strategies have failed.