A randomized phase III study evaluating the efficacy of single-dose NEPA, a fixed antiemetic combination of netupitant and palonosetron, versus an aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC).

Background: Co-administration of multiple antiemetics that inhibit several molecular pathways involved in emesis is required to optimize chemotherapy-induced nausea and vomiting (CINV) control in patients receiving highly emetogenic chemotherapy (HEC). NEPA, a fixed combination of a highly selective NK1 receptor antagonist, netupitant (300 mg), and the pharmacologically distinct 5-HT3RA, palonosetron (PALO 0.50 mg), has shown superior CINV prevention compared with PALO in cisplatin and anthracycline/cyclophosphamide-based settings. This study is the first head-to-head comparison of NEPA versus an aprepitant (APR)/granisetron (GRAN) regimen. Patients and methods: This randomized, double-blind phase III study conducted in Asia was designed with the primary objective to demonstrate non-inferiority of a single oral dose of NEPA compared with a 3-day oral APR/GRAN regimen in chemotherapy-naïve patients receiving cisplatin-based HEC. All patients also received oral dexamethasone (DEX) on days 1-4. The primary efficacy endpoint was complete response (CR: no emesis/no rescue medication) during the overall (0-120 h) phase. Non-inferiority was defined as a lower 95% CI greater than the non-inferiority margin set at - 10%. Secondary efficacy endpoints included no emesis, no rescue medication, and no significant nausea (NSN). Results: Treatment groups were comparable for the 828 patients analyzed: predominantly male (71%); mean age 54.5 years; ECOG 0-1 (98%); lung cancer (58%). NEPA demonstrated non-inferiority to APR/GRAN for overall CR [NEPA 73.8% versus APR/GRAN 72.4%, 95% CI (-4.5%, 7.5%)]. No emesis [NEPA 75.0% versus APR/GRAN 74.0%, 95% CI (-4.8%, 6.9%)] and NSN rates [NEPA 75.7% versus APR/GRAN 70.4%, 95% CI (-0.6%, 11.4%)] were similar between groups, but significantly more NEPA patients did not take rescue medication [NEPA 96.6% versus APR/GRAN 93.5%, 95% CI (0.2%, 6.1%)]. NEPA was well tolerated with a similar safety profile to APR/GRAN. Conclusions: In this first study comparing NK1RA regimens and DEX, NEPA administered only on day 1 was non-inferior to a 3-day oral APR/GRAN regimen in preventing CINV associated with HEC.

Radiofrequency application to the posteroseptal region alters retrograde accessory pathway activation.

INTRODUCTION: Radiofrequency applications to the posteroseptal region can ablate the atrioventricular accessory pathway residing in this area. In conjunction with the adjacent anatomic structures, however, ablative lesions which do not effectively ablate the accessory pathway could markedly alter retrograde atrial activation sequence and confound interpretation of further mapping of an accessory pathway. METHODS AND RESULTS: Electrophysiologic studies, endocardial activation mapping and radiofrequency catheter ablation were undertaken in three patients with recurrent supraventricular tachycardia. Patients were initially thought to have a single posteroseptal accessory pathway; earliest ventrioatrial activation during tachycardias and during ventricular pacing was at the coronary sinus ostium, but initial radiofrequency applications were unsuccessful to ablate the pathway. After initial radiofrequency applications to the posteroseptal region, the earliest retrograde atrial activation changed to the right atrial free wall in two patients. Additional radiofrequency application to the posteroseptal area was able to ablate the single posteroseptal accessory pathway in one patient. Radiofrequency application to the right atrial free wall was required to stop tachycardia initiation in other patient. The third patient was suspected of having a slow-slow atrioventricular nodal reentry tachycardia. Radiofrequency application to the posteroseptal area changed the earliest retrograde atrial activation to the distal coronary sinus recording site, mimicking an accessory pathway at the left atrial free wall. Radiofrequency application to the anteroseptum was able to ablate the concealed accessory pathway. CONCLUSION: Radiofrequency applications to the posteroseptal region can markedly alter retrograde atrial activation, thereby confounding further mapping of the accessory pathway.

Thromboembolism in chronic atrial flutter: is the risk underestimated?

OBJECTIVES: We sought to evaluate the risk of thromboembolic events in the presence of chronic atrial flutter and to determine the impact of anticoagulation therapy, if any, on this risk. BACKGROUND: Thromboembolic events are thought to be rare after cardioversion of atrial flutter. METHODS: This study was a retrospective analysis of 110 consecutive patients referred to the electrophysiology laboratory for cardioversion of chronic atrial flutter from 1986 to 1996. Atrial flutter was present for at least 6 months. Of the 110 patients reviewed, 100 had adequate information available regarding the effectiveness of anticoagulation (mean age 64 years, range 27 to 86; 75 men, 25 women; mean left ventricular ejection fraction 42%). RESULTS: Thirteen patients (13%) had a thromboembolic event. Of these, seven were attributable to causes other than atrial flutter. In the remaining six patients (6%), thromboembolic events occurred during a rhythm of atrial flutter or after cardioversion to sinus rhythm. Other causes of thromboembolism were excluded. Effective anticoagulation was associated with a decreased risk of thromboembolism (p = 0.026). CONCLUSIONS: Patients with chronic atrial flutter are at an increased risk of thromboembolic events. Effective anticoagulation may decrease this risk.

Symptomatic atrioventricular block in an atriofascicular pathway inserting into the left bundle branch without apparent atrioventricular node function.

We report a patient with symptomatic AV block associated with conduction solely through an atriofascicular pathway that inserted into the left bundle branch. There was no apparent conduction present through the AV node. There was, however, passive activation through the His-Purkinje system. His-bundle pacing demonstrated normal conduction through both right and left bundles. This is the first report of such a case.

Teletronics 330-801 atrial lead extraction via the subclavian approach.

BACKGROUND: The Telectronics 330-801 atrial J (801) lead was recalled after reports implicated lead fracture/retention wire protrusion in patient mortality and morbidity. Recent reports suggest that 801 lead extraction may be associated with substantial morbidity and, possibly, excess mortality. We hypothesized that the 801 lead could be extracted using the subclavian approach with a high success rate and acceptable morbidity. METHODS: We analyzed the clinical outcomes in 60 consecutive patients who underwent 801 lead extraction. RESULTS: Sixty patients (34 women) with a mean age of 67 +/- 14.8 years had 18 class I, 13 class II, and 29 class III fractures. The lead age was 39 +/- 17 months. The subclavian approach was successful in 58 of 60 patients (96%). Complications, three major and eight minor, occurred in 10 of 60 patients (16%). All complications were successfully treated. There were no deaths. Only concurrent ventricular lead extraction was associated with complications (p = 0.008 by Fisher's exact test). CONCLUSIONS: Telectronics 801 leads can be successfully extracted using the subclavian approach with acceptable short-term morbidity, low mortality, and excellent long-term results.