Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkins disease

BACKGROUND: Faced with unsatisfactory results of treatment for advanced Hodgkin's disease, we investigated three combinations of chemotherapy. METHODS: From 1993 to 1998, 1201 eligible patients 15 to 65 years of age who had newly diagnosed Hodgkin's disease in unfavorable stage IIB or IIIA or stage IIIB or IV were randomly assigned to receive eight cycles of cyclophosphamide, vincristine, procarbazine, and prednisone alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (COPP-ABVD); bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP); or increased-dose BEACOPP, each followed by local radiotherapy when indicated. Enrollment in the COPP-ABVD group was stopped in 1996 owing to inferior results. RESULTS: For the final analysis, 1195 of 1201 patients could be evaluated: 260 in the COPP-ABVD group, 469 in the BEACOPP group, and 466 in the increased-dose BEACOPP group; the median follow-up was 72, 54, and 51 months, respectively. The rate of freedom from treatment failure at five years was 69 percent in the COPP-ABVD group, 76 percent in the BEACOPP group, and 87 percent in the increased-dose BEACOPP group (P=0.04 for the comparison of the COPP-ABVD group with the BEACOPP group and P<0.001 for the comparison of the increased-dose BEACOPP group with the COPP-ABVD group and with the BEACOPP group), and the five-year rates of overall survival were 83 percent, 88 percent, and 91 percent, respectively (P=0.16 for the comparison of the COPP-ABVD group with the BEACOPP group, P=0.06 for the comparison of the BEACOPP group with the increased-dose BEACOPP group, and P=0.002 for the comparison of the COPP-ABVD group with the increased-dose BEACOPP group). Rates of early progression were significantly lower with increased-dose BEACOPP than with COPP-ABVD or standard BEACOPP. CONCLUSIONS: Increased-dose BEACOPP resulted in better tumor control and overall survival than did COPP-ABVD

Cause-of-death analysis in patients with cardiac resynchronization therapy with or without a defibrillator: A systematic review and proportional meta-analysis

AIMS: The additional benefit of a defibrillator in cardiac resynchronization therapy (CRT) patients is a matter of debate. Cause-of-death analysis in a CRT population has been recently proposed as a useful approach to gain insight into this problem. We performed a systematic review and meta-analysis looking at cause of death in studies involving CRT subjects with (CRT-D) or without (CRT-P) a defibrillator. METHODS AND RESULTS: Literature search performed from inception to 31 March 2016 for relevant studies. Proportional and conventional meta-analyses were performed to obtain and compare causes of death in CRT-D vs. CRT-P patients, including sudden cardiac death (SCD), all-cause mortality, heart failure, cardiovascular, and non-cardiovascular mortalities. The systematic review included a total of 44 studies and 18 874 patients (13 248 receiving CRT-D and 5626 receiving CRT-P), representing 48 504 patient-years of follow-up. CRT-D recipients were younger, more often male, had lower NYHA class, less atrial fibrillation, more ischaemic heart disease and were more often on beta-blockers than those receiving CRT-P. There were an additional 42 deaths per 1000 patient-years in the CRT-P group compared with CRT-D (97 ± 9, 95% CI 79-115 vs. 55 ± 5, 95% CI 44-65, respectively), of which 35.7% were due to SCD (20 ± 2, 95% CI 15-24 vs. 5 ± 1, 95% CI 3-6) and the remaining 64.3% due to non-SCD. Of all deaths reported in CRT-D and CRT-P patients, 9.1% and 20.6% were due to SCD, respectively. The extent of SCD in CRT-P patients significantly increased in studies with higher percentage of males, ischaemic cardiomyopathy and NYHA class 3. CONCLUSION: Overall, compared with CRT-D patients, unadjusted mortality rate was almost two-fold higher in CRT-P recipients, with SCD representing one third of the excess mortality. Rate of SCD was significantly higher in certain subgroups (males, ischaemic cardiomyopathy, NYHA class 3), where a CRT-D may be of more pronounced benefit. This deserves further focused investigation

Patients upgraded to cardiac resynchronization therapy due to pacing-induced cardiomyopathy are at low risk of life-threatening ventricular arrhythmias: A long-term cause-of-death analysis

AIMS: Upgrade to cardiac resynchronization therapy (CRT) should be offered to patients who have developed pacing-induced cardiomyopathy with conventional right ventricular pacing. The extent to which these patients would also benefit from defibrillator back-up at the time of CRT upgrade is, however, unknown. METHODS AND RESULTS: Retrospective observational cohort study of 199 patients with pacing-induced cardiomyopathy and no history of sustained ventricular arrhythmia, including 104 upgraded to CRT-Pacemaker (CRT-P) and 95 upgraded to CRT-Defibrillator (CRT-D). The incidence of ventricular arrhythmias and the risk of sudden arrhythmic death obtained through a cause-of-death analysis based on clinical data and necropsy results were assessed and compared between the two groups. During a mean follow-up of 66 ± 24 months, 40 (38.5%) CRT-P patients died: three from primary arrhythmic death, while the remaining died of different causes (especially progressive heart failure), giving an incidence of 6.2 sudden arrhythmic deaths per 1000 patient-years. No episode of sustained VT was observed in the study group. There were no sudden arrhythmic deaths in the CRT-D group during a shorter follow-up, but the small and non-significant difference in all-cause mortality between CRT-Pacemaker (CRT-P) and CRT-D groups was mostly accounted for by an increase in non-sudden death. Women upgraded to CRT were at particularly low risk of all-cause mortality compared with men (HR 0.232, P = 0.048). CONCLUSION: Our findings suggest that patients who develop pacing-induced cardiomyopathy and are upgraded to CRT may not derive any significant benefit from the addition of the defibrillator in the absence of a history of ventricular arrhythmias

Long-Term Impact of Body Mass Index on Survival of Patients Undergoing Cardiac Resynchronization Therapy: A Multi-Centre Study

Obesity is a risk factor for heart failure (HF), but its presence among HF patients may be associated with favorable outcomes. We investigated the long-term outcomes across different body mass index (BMI) groups, after cardiac resynchronization therapy (CRT), and whether defibrillator back-up (CRT-D) confers survival benefit. One thousand two-hundred seventy-seven (1,277) consecutive patients (mean age: 67.0 ± 12.7 years, 44.1% women, and mean BMI: 28.3 ± 5.6 Kg/m2) who underwent CRT implantation in 5 centers between 2000-2014 were followed-up for a median period of 4.9 years (IQR 2.4 to 7.5). More than 10% of patients had follow-up for ≥10 years. Patients were classified according to BMI as normal: 75% of patients, but were used less frequently in obese individuals. The composite endpoint of all-cause mortality or cardiac transplant/left ventricular assist device (LVAD) occurred in 50.9% of patients. At 10-year follow-up, less than a quarter of patients in the lowest and highest BMI categories were still alive and free from heart transplant/LVAD. After adjustment BMI of 25 to 29.9 Kg/m2 (HR = 0.73 [95%CI 0.56 to 0.96], p = 0.023) and use of CRT-D (HR = 0.74 [95% CI 0.55 to 0.98], p = 0.039) were independent predictors of survival free from LVAD/heart transplant. BMI of 25 to 29.9 Kg/m2 at the time of implant was independently associated with favourable long-term 10-year survival. Use of CRT-D was associated with improved survival irrespective of BMI class

Dual-site right ventricular pacing in patients undergoing cardiac resynchronization therapy: Results of a multicenter propensity-matched analysis

BACKGROUND: Dual-site right ventricular pacing (Dual RV) has been proposed as an alternative for patients with heart failure undergoing cardiac resynchronization therapy (CRT) with a failure to deliver a coronary sinus (CS) lead. Only short-term hemodynamic and echocardiographic results of Dual RV are available. We aimed to assess the long-term results of Dual RV and its impact on survival. METHODS: Multicenter retrospective assessment of all CRT implants during a 12-year period. Patients with failed CS lead implantation, treated with Dual RV, were followed and assessed for the primary endpoint of all-cause mortality and/or heart transplant. A control group was obtained from contemporary patients using propensity matching for all available baseline variables. RESULTS: Ninety-three patients were implanted with Dual RV devices and compared with 93 matched controls. During a median of 1,273 days (interquartile range 557-2,218), intention-to-treat analysis showed that all-cause mortality and/or heart transplant was higher in the Dual RV group (adjusted hazard ratio [HR] = 1.66, 95% confidence interval [CI] 1.12-2.47, P = 0.012). As-treated analysis yielded similar results (HR = 1.97, 95% CI 1.31-2.96, P = 0.001). Cardiac device-related infections occurred seven times more frequently in the Dual RV site group (HR = 7.60, 95% CI 1.51-38.33, P = 0.014). Among Dual RV nonresponders, four had their apical leads switched off, five required an epicardial LV lead insertion, a transseptal LV lead was implanted in two, and in nine patients, after reviewing the CS venogram, a new CS lead insertion was successfully attempted. CONCLUSION: Dual RV pacing is associated with worse clinical outcomes and higher complication rates than conventional CRT

Device complications with addition of defibrillation to cardiac resynchronisation therapy for primary prevention

Objective: In patients indicated for cardiac resynchronisation therapy (CRT), the choice between a CRT-pacemaker (CRT-P) versus defibrillator (CRT-D) remains controversial and indications in this setting have not been well delineated. Apart from inappropriate therapies, which are inherent to the presence of a defibrillator, whether adding defibrillator to CRT in the primary prevention setting impacts risk of other acute and late device-related complications has not been well studied and may bear relevance for device selection. // Methods: Observational multicentre European cohort study of 3008 consecutive patients with ischaemic or non-ischaemic dilated cardiomyopathy and no history of sustained ventricular arrhythmias, undergoing CRT implantation with (CRT-D, n=1785) or without (CRT-P, n=1223) defibrillator. Using propensity score and competing risk analyses, we assessed the risk of significant device-related complications requiring surgical reintervention. Inappropriate shocks were not considered except those due to lead malfunction requiring lead revision. // Results: Acute complications occurred in 148 patients (4.9%), without significant difference between groups, even after considering potential confounders (OR=1.20, 95% CI 0.72 to 2.00, p=0.47). During a mean follow-up of 41.4±29 months, late complications occurred in 475 patients, giving an annual incidence rate of 26 (95% CI 9 to 43) and 15 (95% CI 6 to 24) per 1000 patient-years in CRT-D and CRT-P patients, respectively. CRT-D was independently associated with increased occurrence of late complications (HR=1.68, 95% CI 1.27 to 2.23, p=0.001). In particular, when compared with CRT-P, CRT-D was associated with an increased risk of device-related infection (HR 2.10, 95% CI 1.18 to 3.45, p=0.004). Acute complications did not predict overall late complications, but predicted device-related infection (HR 2.85, 95% CI 1.71 to 4.56, p<0.001). // Conclusions: Compared with CRT-P, CRT-D is associated with a similar risk of periprocedural complications but increased risk of long-term complications, mainly infection. This needs to be considered in the decision of implanting CRT with or without a defibrillator

Biomedical applications of fast neutron radiography

Also published in Supplement to Atomkernenergie Kerntechnik (1984) v. 44 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Fast neutron radiography (FNR) with track etch technique

SIGLESpecial print from: J.P. Barton, G. Farny, J.L. Person, H. Roettger (eds.): Neutron Radiography, Proceedings of the Second World Conference, p. 639-646. Dordrecht: Reidel, 1986 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman