Effect of renin-angiotensin system inhibitors on pemetrexed plus platinum-induced hematological toxicities: a multicenter retrospective study using three propensity score analyses.

Hematological toxicities induced by pemetrexed plus platinum therapy remain a critical issue in clinical practice. We hypothesized that inhibition of the renin-angiotensin system (RAS) can ameliorate pemetrexed-induced hematological toxicities through drug-drug interactions involving organic anion transporters. Thus, this study aimed to clarify whether RAS inhibitors (RASIs) could prevent pemetrexed plus platinum-induced hematological toxicities. We retrospectively analyzed data from 305 consecutive patients with non-small cell lung cancer or malignant pleural mesothelioma who received their first cycle of a pemetrexed plus platinum regimen and were treated with or without RASIs. The primary endpoint was the incidence of severe myelosuppression after the first cycle. Propensity score (PS)-matched, PS-adjusted, and inverse probability of treatment weighting (IPTW) analyses were used. The number of patients with grade ≥3 hematological toxicities was 27 (8.9%). PS-matched analyses revealed that the concomitant use of RASIs was slightly associated with a lower risk of grade ≥3 hematological toxicities (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.20-2.32; p = 0.536). Additionally, sensitivity analyses using PS-adjusted and IPTW methods demonstrated similar results (OR, 0.63; 95% CI, 0.19-2.15; p = 0.463 and OR, 0.37; 95% CI, 0.11-1.29; p = 0.117, respectively). These findings suggest that RASIs might prevent pemetrexed plus platinum-induced hematological toxicities.

Single photon K(-2) and K(-1)K(-1) double core ionization in C(2)H(2n) (n=1-3), CO, and N(2) as a potential new tool for chemical analysis.

We have observed single photon double K-shell photoionization in the C(2)H(2n) (n=1-3) hydrocarbon sequence and in N(2) and CO, using synchrotron radiation and electron coincidence spectroscopy. Our previous observations of the K(-2) process in these molecules are extended by the observations of a single photon double photoionization with one core hole created at each of the two neighboring atoms in the molecule (K(-1)K(-1) process). In the C(2)H(2n) sequence, the spectroscopy of K(-1)K(-1) states is much more sensitive to the bond length than conventional electron spectroscopy for chemical analysis spectroscopy based on single K-shell ionization. The cross section variation for single photon K(-1)K(-1) double core ionization in the C(2)H(2n) sequence and in the isoelectronic C(2)H(2n), N(2) and CO molecules validates a knock-out mechanism in which a primary ionized 1s photoelectron ejects another 1s electron of the neighbor atom. The specific Auger decay from such states is clearly observed in the CO case.

Electron reemission processes following photoelectron recapture due to post-collision interaction in inner-shell photoionization of water molecules.

Electron reemission following photoelectron recapture due to post-collision interaction has been studied at 0.7 eV the inner-shell photoionization threshold of water molecules, using a multi-electron coincidence method. Electron reemissions after single Auger decay occur from O and OH fragments which are produced by the dissociations of high-n Rydberg H2O(+) states populated through photoelectron recapture. In addition, electron reemissions after double Auger decay are identified in triple coincidence events, where autoionization lines from O and O(+) fragments are observed.

Prospective randomised comparative study of visual foam sclerotherapy alone or in combination with ultrasound-guided foam sclerotherapy for treatment of superficial venous insufficiency: preliminary report.

OBJECTIVE: The aim of the study is to compare ultrasound-guided foam sclerotherapy (UGFS: injection of foam sclerosant under ultrasound guidance) of the great saphenous vein (GSV) combined with visual foam sclerotherapy (VFS: injection of foam sclerosant under visual control) for varicose tributary veins and VFS alone in the treatment of GSV reflux. DESIGN AND METHODS: A total of 133 limbs in 97 patients with GSV reflux were randomised to receive either VFS alone or VFS combined with UGFS. In both groups, 1% polidocanol foam was used. Assessments included duplex ultrasonography, evaluation of Venous Clinical Severity Scores (VCSS) and CEAP (clinical, etiologic, anatomic, and pathophysiologic) scores. Ultrasonographic inspection of the foam in the GSV was carried out during 5 min before compression was applied. The primary 'end' point of the study was obliteration of the GSV at 6 months. RESULTS: A total of 51 limbs in 48 patients were treated with UGFS + VFS and the remaining 52 limbs in 49 patients were treated with VFS alone. There were no significant inter-group differences in patient age, male: female ratio, height, weight, body mass index, CEAP clinical scores or VCSS. The GSV diameter was 6.0 ± 1.7 mm (median ± interquartile range) in the UGFS + VFS group and 5.7 ± 1.6 mm in the VFS group (p = 0.419). The mean injected volume of foam for varicose tributary veins was 4 ± 2 ml in the UGFS + VFS group and 6 ± 2 ml in the VFS group, a significantly higher amount of foam being used in the latter (p < 0.001). However, the mean total amount of foam was greater in limbs treated with UFGS + VFS than in those treated with VFS alone (p = 0.017). Ultrasonographic inspection revealed complete vasospasm of the GSV in 37 (72.5%) limbs in the UGFS + VFS group and 29 (55.8%) in the VFS group during sclerotherapy (p = 0.097). At 6-month follow-up, complete occlusion was found in 23 limbs (45.1%) treated with UGFS + VFS and in 22 limbs (42.3%) treated with VFS. The difference between the two groups was not significant (p = 0.775). Reflux was absent in 30 limbs (58.8%) treated with UGFS + VFS and in 37 (71.2%) treated with VFS (p = 0.190). There was no inter-group difference in post-treatment VCSS (p = 0.223). CONCLUSIONS: These results show that UGFS + VFS and VFS are equally effective for the treatment of GSV reflux, despite the lower volume of foam used for VFS alone.

Communication: Formation of slow electrons in the Auger decay of core-ionized water molecules.

Double Auger decay of O1s(-1) and its satellite states in H(2)O has been studied with a multi-electron coincidence method, and a process leading to autoionizing O* fragments has been revealed. The breaking of the two O-H bonds producing the autoionizing O* fragments occurs for highly excited H(2)O(2+) populated by the initial Auger decay. The O* fragments are more favorably produced in the decay from the satellite states, resulting from the larger population of highly excited H(2)O(2+) states inheriting the valence excitation in the initial state.

Energy correlation among three photoelectrons emitted in core-valence-valence triple photoionization of Ne.

The direct observation of triple photoionization involving one inner shell and two valence electrons is reported. The energy distribution of the three photoelectrons emitted from Ne is obtained using a very efficient multielectron coincidence method using the magnetic bottle electron spectroscopic technique. A predominance of the direct path to triple photoionization for the formation of Ne3+ in the 1s 2s2 2p4 configuration is observed. It is demonstrated that the energy distribution evolves with photon energy and indicates a significant difference with triple photoionization involving only valence electrons.

Properties of hollow molecules probed by single-photon double ionization.

The formation of hollow molecules (with a completely empty K shell in one constituent atom) through single-photon core double ionization has been demonstrated using a sensitive magnetic bottle experimental technique combined with synchrotron radiation. Detailed properties are presented such as the spectroscopy, formation, and decay dynamics of the N(2)(2+) K(-2) main and satellite states and the strong chemical shifts of double K holes on an oxygen atom in CO, CO2, and O2 molecules.

Evidence of single-photon two-site core double ionization of C2H2 molecules.

We observe the formation in a single-photon transition of two core holes, each at a different carbon atom of the C2H2 molecule. At a photon energy of 770.5 eV, the probability of this 2-site core double ionization amounts to 1.6 ± 0.4% of the 1-site core double ionization. A simple theoretical model based on the knockout mechanism gives reasonable agreement with experiment. Spectroscopy and Auger decays of the associated double core hole states are also investigated.

Factors predicting development of post-thrombotic syndrome in patients with a first episode of deep vein thrombosis: preliminary report.

OBJECTIVE: To investigate the indicative parameters reflecting the progression of post-thrombotic syndrome (PTS) in patients with a first episode of deep vein thrombosis (DVT). DESIGN AND METHODS: The patients' initial risk factors were assessed at presentation. Venous occlusion, and reflux and reflux parameters were evaluated at 6 months using venous duplex scanning. Near-infrared spectroscopy (NIRS) was also used to measure calf muscle deoxygenated haemoglobin levels at 6 months. Clinical manifestations were categorised using the clinical, etiologic, anatomic and pathophysiologic (CEAP) classification for chronic venous insufficiency (CVI), and the patients were divided into those having no PTS (C(0-3S),E(s),A(s,d,p),P(r,o)) and those having PTS (C(4-6S),E(s),A(s,d,p),P(r,o)). RESULTS: Of the 121 patients evaluated, 25 (21%) developed PTS with a mean follow-up period of 66 months. At initial presentation, ilio-femoral DVT (odds ratio (OR) 3.4, 95% confidence interval (CI) 1.4-8.6) was associated with development of PTS. At 6 months, venous occlusion combined with reflux (OR 4.4, 95% CI 2.9-20.7), peak reflux velocity >29.7 cm s(-1) (OR 13.7, 95% CI 4.1-45.7) and mean reflux velocity >8.6 cm s(-1) (OR 4.4, 95% CI 1.5-12.9) in the popliteal vein detected by duplex scanning were strong predictors of PTS. NIRS-derived retention index >3.5 was the strongest predictor of PTS at 6 months (OR 67.4, 95% CI 14.3-318.1). CONCLUSIONS: Ilio-femoral DVT is associated with the development of PTS at initial presentation. By contrast, occlusion and reflux, high reflux velocity in the popliteal vein and increased NIRS-derived retention index are important time-course predictors of PTS progression.

Advanced chronic venous insufficiency is associated with increased calf muscle deoxygenation.

OBJECTIVE: To determine the temporal relationship between changes in calf muscle deoxygenated haemoglobin (HHb) measured by near-infrared spectroscopy (NIRS) during light-intensity exercise and clinical stages of chronic venous insufficiency (CVI). DESIGN AND METHODS: Calf muscle HHb level was obtained in 168 limbs of 158 patients with various clinical stages of CVI. Clinical manifestations were categorised according to the CEAP classification (CEAP, clinical, etiological, anatomical and pathophysiological), and the patients were divided into two groups: early CVI (C(0-3),E(p)(,s),A(s)(,d,p),P(r)(,o)) and advanced CVI (C(4-6),E(p)(,s), A(s)(,d,p),P(r)(,o)). Calf venous blood-filling index (FI-HHb) was calculated on standing, then the calf venous ejection index (EI-HHb) was obtained after one tiptoe movement and the venous retention index (RI-HHb) after 10 tiptoe movements. RESULTS: A total of 116 limbs had early, and 52 had advanced CVI. FI and RI were significantly increased in patients with advanced CVI compared with those with early CVI (P = 0.003, 0.0001, respectively). Similarly, RI was significantly greater in patients who had superficial, combined with deep and/or perforator, insufficiency than in patients with superficial insufficiency alone (P = 0.002). RI showed the strongest correlation with duplex-derived peak reflux velocity in the popliteal vein (r = 0.78, P < 0.0001). Combination of an optimal cut-off point of 0.2 for FI and 2.9 for RI improved the ability to discriminate early from advanced CVI, with a sensitivity of 94% and a specificity of 86%. CONCLUSIONS: These results suggest that FI and RI, as measured by NIRS, may be promising parameters for discriminating early CVI from advanced CVI.

Great saphenous vein sparing surgery by angioscopic valvuloplasty combined with axial transposition of a competent tributary vein--5-year follow-up.

OBJECTIVE: To evaluate the efficacy and haemodynamic effects of great saphenous vein (GSV) sparing surgery--valvuloplasty combined with axial transposition of a competent tributary vein (A-VACT). MATERIALS AND METHODS: Eighty-five limbs in 74 patients with isolated GSV incompetence were selected for GSV sparing surgery. After angiographic valvuloplasty, the competent tributary vein was exposed and cut 1.5 cm distal to its insertion point on the GSV. The transected vein was anastomosed end-to-side to the GSV, which was ligated between the tributary insertion site and the anastomosis. Venous valve competence were screened by serial postoperative duplex examination, and venous haemodynamic changes were analyzed using venous filling index (VFI) measured by air plethysmograph pre- and postoperatively. The follow-up period was 5-years. RESULTS: Sixty-seven patients were included in whom 76 limbs were treated. There was a statistically significant reduction in the vein diameter at the SFJ after 5-years (0.83 S.D. 0.29 cm to 0.46 S.D. 0.12 cm, p=0.0002, Wilcoxon). Similarly, significant reduction was found in the GSV at the 5-year follow-up point (0.63 S.D. 0.19 cm to 0.39 S.D. 0.11 cm, p<0.0001, Wilcoxon). On the other hand, there was significant increase in the diameter of the competent tributary vein postoperatively (0.22 S.D. 0.13 cm to 0.31 S.D. 0.12 cm, p<0.0001, Wilcoxon). Duplex scanning demonstrated reflux at the SFJ in 12 limbs (16%). Similarly, in the GSV, venous reflux was found in 13 limbs (17%). Reflux in the transposed tributary vein was found in 20 limbs (26%). But only 7 limbs (9%) had minor varicose veins' recurrence. VFI remained normal during the follow-up examination. The preoperative VFI confirmed the presence of venous reflux, but there were significant improvement in the VFI values at all postoperative examinations. CONCLUSIONS: A-VACT procedure improves venous function, resolves varicose veins at 5-years follow-up as well as preserving the GSV for future grafting.

Presence of lower limb deep vein thrombosis and prognosis in patients with symptomatic pulmonary embolism: preliminary report.

OBJECTIVES: To investigate the presence of lower limb deep vein thrombosis (DVT) and prognosis in patients with symptomatic pulmonary embolism (PE). MATERIALS AND METHODS: A total of 203 consecutive referral patients with PE were included. The distribution of DVT was evaluated with compression ultrasound (CUS), and all patients were then followed for 12 months for investigation of recurrence of venous thromboembolism (VTE) and fatal events as adverse outcome. RESULTS: The mean age of the patients was 62.8 years, and 78 (38.4%) were males. DVT was found in 118 (58.1%) patients. Of these patients, 61 (30.0%) had proximal DVT. Multivariate analysis demonstrated that active cancer, inadequate anticoagulation, leg symptoms, male gender, presence of DVT, presence of proximal DVT, and previous DVT were independent risk factors for adverse outcome. A clinical risk score ranging from 0 to 10 points was generated on the basis of multivariate regression coefficients. Receiver operating characteristic curve analysis showed that an appropriate cut-off point for discriminating between the presence and the absence of an adverse event was 4. Using this category, 166 (81.8%) patients were classified as low risk and 37 (18.2%) as high risk for adverse outcome. The adverse event rates were 6.0% for the low-risk group and 59.5% for the high-risk group. CONCLUSIONS: This study has confirmed the clinical significance of surveillance CUS in patients with a first episode of PE. Furthermore, a simple risk score on the basis of available variables can identify patients at risk of an adverse outcome in patients with PE.

Multiple small-dose injections can reduce the passage of sclerosant foam into deep veins during foam sclerotherapy for varicose veins.

OBJECTIVE: To compare the proportion of foam sclerosant that enters deep veins between multiple injections of <0.5 ml foam per injection and a few injections of >0.5 ml foam per injection. DESIGN & METHODS: One hundred and seven patients with superficial venous incompetence were randomised to receive either multiple injections of <0.5 ml 1% polidocanol (POL) -foam (multiple injections) or a few injections of >0.5 ml 1% POL-foam per injection (few injections) for the treatment of varicose tributaries. All patients then received ultrasound-guided foam sclerotherapy for refluxing great saphenous vein (GSV) using 3% POL-foam. Only a single session was allowed per patient in order to standardise treatment. Qualitative ultrasonographic inspection of the foam was carried out during a 5-min period before compression was applied. Post-sclerotherapy surveillance was done at day 3, 2 weeks, 1 month, 3 months, and 6 months. RESULTS: Fifty-six limbs in 53 patients were treated with multiple injections and the remaining 56 limbs in 54 patients were treated with a few injections. There were no significant differences in age or male:female ratio between the groups. The mean volume of 1% POL-foam was 2.2 S.D. 0.6 ml (range: 0.7-4.0 ml) in the multiple injections group and 2.5 S.D. 0.6 ml (range: 1.0-4.0 ml) in the few injections group (p=0.003). The mean volume of 3% POL was 1.5 ml (range: 0.7-3.0 ml) and 1.4 ml (range: 0.7-3.0 ml), respectively (p=0.137). Ultrasonographic inspection immediately after sclerotherapy demonstrated that foam was distributed significantly more commonly in the deep veins of patients treated with a few injections (p=0.0003). Two (4%) of the patients treated with a few injections developed migraine during the procedure, but recovered quickly with no further complications. There was no significant difference in the success rate between the groups at 6 months (p=0.257). CONCLUSIONS: These findings suggest that multiple small-dose injections can reduce the amount of foam sclerosant and the risk of foam sclerosant entering the deep veins in patients with superficial venous insufficiency.

High peak reflux velocity in the proximal deep veins is a strong predictor of advanced post-thrombotic sequelae.

BACKGROUND: The presence of reflux in the femoral vein (FV) and popliteal vein (POPV) after acute deep vein thrombosis (DVT) is considered to contribute to the development of advanced post-thrombotic syndrome (PTS). However, a quantification of reflux has yet to be determined. The purpose of study was to determine the indicative parameters reflecting the progression of PTS. METHODS: Venous abnormalities were evaluated in 131 limbs out of 130 patients who completed a six-year follow-up after an acute DVT. Clinical manifestations were categorized according to the clinical, etiologic, anatomic, and pathophysiologic (CEAP) classification, and the patients were divided into two groups at a six-year follow-up point: group I, C(0-3)E(s),A(s,d,p),P(r,o), early chronic venous insufficiency (CVI); group II, C(4-6)E(s),A(s,d,p),P(r,o), advanced CVI. Venous segments were examined whether they were occluded or recanalized. The reflux parameters assessed were the diameter (cm), the reflux time (RT; s), the peak reflux velocity (PRV; cm s(-1)), and total refluxed volume, and these parameters were assessed especially in the FV and POPV at the two-year (early phase) and subsequent six-year (late phase) follow-up points after DVT. RESULTS: There were 98 limbs in group I and 33 in group II. The frequency of venous reflux was significantly higher in group II (<0.0001). In contrast, the proportion of occlusion did not differ between the groups (P = 0.138). The proportions of FV and POPV incompetence were significantly higher in group II (P < 0.0001 and P < 0.0001, respectively). In these veins, the RT did not improve the discrimination power between the two groups. In contrast, the PRV had significant discrimination power in these veins at both the two- and six-year follow-up points. In the superficial venous system, there were no significant differences in any of the determined parameters between the groups. In group II, 19 patients (58%), who had early symptoms of CVI at the two-year follow-up point, subsequently developed advanced symptoms of PTS. After calculating a suitable cutoff point using receiver operating characteristic curves analysis at the two-year follow-up point, multivariable analysis showed that a PRV of >25.4 cm s(-1) in the POPV was the strongest independent predictor of advanced CVI [odds ratio (OR) 60.32; 95% confidence interval (95CI) 43.1-1238.97, P < 0.0001]. Similarly, in the FV, a PRV of >24.5 cm s(-1) was found to be a strong predictor of advanced CVI (OR 25.77, 95CI 10.56-331.12, P < 0.0001). CONCLUSIONS: These findings suggest that the presence of a high PRV in the proximal deep veins is an independent predictor of advanced symptoms of PTS.

Force-induced IL-8 from periodontal ligament cells requires IL-1beta.

During orthodontic tooth movement, mechanical stresses induce inflammatory reactions in the periodontal ligament (PDL). We hypothesized that chemokines released from PDL cells under mechanical stress regulate osteoclastogenesis, and investigated the profiles and mechanisms of chemokine expression by human PDL cells in response to mechanical stress. In vitro, shear stress and pressure force rapidly increased the gene and protein expressions of IL-8/CXCL8 by PDL cells. Consistently, amounts of IL-8 in the gingival crevicular fluid of healthy individuals increased within 2 to 4 days of orthodontic force application. The PDL cells constitutively expressed low levels of IL-1beta, which were not further increased by mechanical stress. Interestingly, neutralization of IL-1beta abolished IL-8 induction by mechanical stresses, indicating that IL-1beta is essential for IL-8 induction, presumably though autocrine or paracrine mechanisms. Finally, experiments with signal-specific inhibitors indicated that MAP kinase activation is essential for IL-8 induction.

Harvesting epithelial keratinocyte sheets from temperature-responsive dishes preserves basement membrane proteins and improves cell survival in a skin defect model.

Cultured epithelial autograft (CEA) therapy has been used in clinical applications since the 1980s. However, there are some issues related to this treatment that still remain unsolved. Enzymatic treatment is typically used in the collection of epithelial keratinocyte sheets, but it tends to break the adhesion and basement membrane proteins. It is thought that the loss of proteins after enzymatic treatment is responsible for the poor survival of transplanted cell sheets. Our laboratory has developed a temperature-responsive culture dish that does not require enzymatic treatment to harvest the cells. In this study, we compare morphological and survival results from rat epithelial keratinocyte cell sheets harvested by temperature-reducing treatment (TT sheets) against cell sheets harvested by enzymatic (dispase) treatment (DT sheets). TT sheets preserve keratin structure in better conditions and express higher levels of collagen IV and laminin 5 than DT sheets. In order to evaluate cell sheet survival after transplantation, we created an in vivo transplant model. Keratinocyte sheets obtained from GFP-positive animals were transplanted into athymic rats. The survival rate 7 days after transplantation of TT sheet was higher than that of DT sheets. Collagen IV and Laminin 5 expression was observed in the TT sheet transplantation group. These results indicate that the remaining basement membrane proteins are important for initial attachment and cell survival. We believe that the cell sheet harvesting method using temperature-responsive culture dishes provides superior cell survival and can solve one of the roadblocks in CEA therapy. Copyright © 2016 John Wiley & Sons, Ltd.

The utility of quantitative calf muscle near-infrared spectroscopy in the follow-up of acute deep vein thrombosis.

BACKGROUND: To investigate patterns of venous insufficiency and changes in calf muscle deoxygenated hemoglobin (HHb) levels after an acute deep vein thrombosis (DVT). METHODS: A total of 78 limbs with an acute DVT involving 156 anatomic segments were evaluated with duplex scanning and near-infrared spectroscopy (NIRS) at 1, 3, 6 and 12 months. Venous segments were examined whether they were occluded, partially recanalized, and totally recanalized, and the development of venous reflux was noted. The NIRS was used to measure calf muscle HHb levels. Calf venous blood filling index (HHbFI) was calculated on standing, then the calf venous ejection index (HHbEI), and the venous retention index (HHbRI) were obtained after exercise. RESULTS: The segments investigated were the common femoral vein (CFV; 38 segments), femoral vein (FV; 37), popliteal vein (POPV; 44), and calf veins (CV; 37). At 1 year, thrombi had fully resolved in 67% of the segments, 27% remained partially recanalized, 6% were occluded. The venous occlusion was predominant in the FV (24%) at 1 year. On the contrary, rapid recanalization was obtained in CV than proximal veins at each examination (P < 0.01). Venous reflux was predominant in POPV (55%), followed by FV (19%), and no reflux was found in CV. At 1 year, the HHbFI in POPV reflux patients was significantly higher than those with resolution (0.19 +/- 0.14, 0.11 +/- 0.05 microm s, P = 0.009, respectively). Similarly, there was a significant difference in the HHbRI between the two groups (3.08 +/- 1.91, 1.42 +/- 1.56, P = 0.002, respectively). In patients with FV occlusion, the value of HHbRI was significantly higher than those with complete resolution (2.59 +/- 1.50, 1.42 +/- 1.56, P = 0.011, respectively). CONCLUSIONS: The lower extremity venous segments show different proportions of occlusion, partial recanalization, and total recanalization. The CV shows more rapid recanalization than proximal veins. The NIRS-derived HHbFI and HHbRI could be promising parameters as the overall venous function in the follow-up of acute DVT. These findings might be very helpful for physician in detecting patients who require much longer follow-up studies.

Catheter ablation in patients with multiple and unstable ventricular tachycardias after myocardial infarction: short ablation lines guided by reentry circuit isthmuses and sinus rhythm mapping.

BACKGROUND: Extensive lines of radiofrequency (RF) lesions through infarct (MI) can ablate multiple and unstable ventricular tachycardias (VTs). Methods for guiding ablation that minimize unnecessary RF applications are needed. This study assesses the feasibility of guiding RF line placement by mapping to identify a reentry circuit isthmus. METHODS AND RESULTS: Catheter mapping and ablation were performed in 40 patients (MI location: inferior, 28; anterior, 7; and both, 5) with an electroanatomic mapping system to measure the infarct region and ablation lines. The initial line was placed in the MI region either through a circuit isthmus identified from entrainment mapping or a target identified from pace mapping. A total of 143 VTs (42 stable, 101 unstable) were induced. An isthmus was identified in 25 patients (63%; 5 with only stable VTs, 5 with only unstable VTs, and 15 with both VTs). Inducible VTs were abolished or modified in 100% of patients when the RF line included an isthmus compared with 53% when RF had to be guided by pace mapping (P=0.0002); those with an isthmus identified received shorter ablation lines (4.9+/-2.4 versus 7.4+/-4.3 cm total length, P=0.02). During follow-up, spontaneous VT decreased markedly regardless of whether an isthmus was identified. VT stability and number of morphologies did not influence outcome. CONCLUSIONS: A 4- to 5-cm line of RF lesions abolishes all inducible VTs in more than 50% of patients. Less ablation is required if a reentry circuit isthmus is identified even when multiple and unstable VTs are present.

Saline-cooled versus standard radiofrequency catheter ablation for infarct-related ventricular tachycardias.

BACKGROUND: Saline cooling of the electrode during radiofrequency (RF) ablation increases lesion size in animal models. If cooled RF also increases lesion size in human infarcts, it should facilitate the termination of ventricular tachycardia (VT). METHODS AND RESULTS: In 66 patients with VT due to prior infarction, 366 ablation sites, which were classified by entrainment and isolated potentials followed by ablation during VT with either standard RF energy (247 sites) or cooled RF (119 sites), were retrospectively reviewed to compare the efficacy for terminating VT. RF energy was applied at 259 isthmus sites, 62 bystander sites, 28 inner loop sites, and 17 outer loop sites. Compared with standard RF, cooled RF terminated VT more frequently at isthmus sites where an isolated potential was present (89% versus 54%, P=0.003), isthmus sites without an isolated potential (36% versus 21%, P=0.04), and at inner loop sites (60% versus 22%, P=0.04). Termination rates were similarly low for cooled and standard RF at bystander sites (14% versus 9%, P=0.56) and outer loop sites (13% versus 11%, P=0.93). CONCLUSIONS: Greater efficacy of cooled RF for terminating VT is consistent with the production of a larger lesion in human infarctions, which should facilitate successful ablation.

Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome.

OBJECTIVES: We examined the modulatory effects of autonomic nervous system and antiarrhythmic drugs on the ST segment in patients with Brugada syndrome to gain an insight into the mechanism of ST segment elevation. BACKGROUND: Right bundle branch block, ST segment elevation and ventricular tachyarrhythmias define a distinct clinical and electrocardiographic (ECG) syndrome (Brugada syndrome). However, the mechanism of ST segment elevation and the causes of this syndrome are unknown. METHODS: The study included four patients in whom structural heart or coronary artery disease was excluded by noninvasive and invasive tests. High take-off ST segment elevation of either the coved or saddle-back type in precordial leads V1, V2 and V3 was seen in all patients. Three patients experienced recurrent episodes of syncope or aborted sudden cardiac death, and the remaining patient had palpitation. Autonomic receptor stimulation and blockade and intravenous administration of antiarrhythmic drugs were performed during sinus rhythm while the 12-lead ECG was recorded. Metaiodobenzylguanidine (MIBG) scanning and Holter monitoring were also performed. RESULTS: Beta-adrenoceptor stimulation by intravenous isoproterenol consistently reduced (> or = 0.1 mV) ST segment elevation at or 80 ms after the J point in all four patients. Selective alpha-adrenoceptor stimulation by intravenous norepinephrine in the presence of propranolol or by intravenous methoxamine consistently augmented, whereas alpha-adrenoceptor blockade reduced, ST segment elevation in three patients. Intracoronary acetylcholine or intravenous edrophonium or neostigmine augmented ST segment elevation without inducing coronary spasm in three of four patients. Class IA antiarrhythmic drugs also consistently augmented (three patients), whereas class IB drugs had no effect on (two patients) ST segment elevation. No abnormality was found on MIBG imaging or heart rate variability in three patients, suggesting that autonomic dysfunction is not a primary disease process. Class IA drugs had no effect on ST segment in three control patients, suggesting that the ST segment elevation seen in patients with Brugada syndrome in response to the drugs is not a nonspecific response. CONCLUSIONS: ST segment elevation in patients with Brugada syndrome was augmented by selective stimulation of alpha-adrenoceptors or muscarinic receptors or by class IA drugs but was mitigated by beta-adrenoceptor stimulation or alpha-adrenoceptor blockade. These responses might be explained by postulating the presence of an area of early repolarization or a local "depolarized" area in the ventricle causing ST segment elevation in this syndrome. Because only a small number of patients were studied, these possibilities need further evaluation.