Proarrhythmia, cardiac arrest and death in young patients receiving encainide and flecainide. The Pediatric Electrophysiology Group

The potential for proarrhythmic responses to the class IC sodium channel-blocking drugs encainide and flecainide has not been well described in young patients. Therefore, data were retrospectively collected from 36 institutions regarding 579 young patients who were administered encainide or flecainide for treatment of supraventricular tachycardias (encainide 86 patients, flecainide 369 patients) or ventricular arrhythmias (encainide 21 patients, flecainide 103 patients) to assess the frequency of proarrhythmia, cardiac arrest and death during therapy (adverse events). The two drugs were similar in regard to efficacy (flecainide 71.4%, encainide 59.8%) and rate of proarrhythmic responses (flecainide 7.4%; encainide 7.5%). However, patients receiving encainide more frequently experienced cardiac arrest (encainide 7.5% vs. flecainide 2.3%, p less than 0.05) or died during treatment (encainide 7.5% vs. flecainide 2.1%, p less than 0.05). Detailed data were provided for 44 patients experiencing one or more adverse events. Patient age, previous drug trials, concomitant therapy and days of inpatient monitoring were similar for patients receiving encainide or flecainide. However, echocardiographic left ventricular shortening before treatment was lower among patients receiving encainide (0.23 +/- 0.09) than among those receiving flecainide (0.34 +/- 0.06, p less than 0.05). Plasma drug concentrations were rarely elevated. Cardiac arrest (12 patients) and deaths (13 patients) occurred predominantly among patients with underlying heart disease, particularly among patients receiving flecainide for supraventricular tachycardia (8.3% vs. 0.3%, p less than 0.001). Fifteen patients with an ostensibly normal heart and normal ventricular function experienced proarrhythmia during treatment for supraventricular tachycardia, but only 3 of the 15 had a cardiac arrest or died. The relatively high incidence of adverse events should be considered when contemplating treatment with encainide or flecainide, particularly among patients with underlying heart disease.     

Effects of interleukin-11 on the proliferation and cell cycle status of myeloid leukemic cells

Interleukin-11 (IL-11) is a pleiotropic cytokine with effects on many different targets. Within the hematopoietic system, the effects of IL- 11 are largely manifest only through combination with other cytokines, including IL-3 and Steel factor (SF). In the present study, we addressed the question of IL-11 responsiveness within the different types of human leukemic cells, as well as the mechanism of action of IL- 11 at the cellular level. Analysis of a panel of samples from different patients with acute myeloblastic leukemia (AML) and myeloid leukemic cell lines indicated that IL-11 alone was ineffective in supporting myeloid leukemic cell growth but frequently enhanced growth supported by IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), or SF. In contrast, three acute pre-B lymphocytic leukemia (pre-B-ALL) and two acute T lymphocytic leukemia (T-ALL) lines failed to respond to IL- 11 alone or when combined with other cytokines. The growth enhancement of IL-11 among the AML patient samples was dose dependent and remarkably constant with half-efficient concentrations in the range of 0.3 to 0.4 ng/mL. The thymidine suicide studies with the patient samples revealed that 40% to 50% of the blast cells were in S-phase when exposed for 16 hours to IL-3 and this level was increased to 70% to 90% in response to either IL-11 or IL-6. Our data suggest that the latter two interleukins act synergistically with the direct mitogenic factor, IL-3, in triggering AML blast-cell proliferation. Detailed analysis with several patient samples further revealed that SF and IL- 11 both enhance IL-3-supported clonogenic growth of AML blasts and the combination of all three growth factors yields optimal growth. In contrast, IL-6 does not further enhance the effect of IL-11. These results indicate that SF and IL-11 enhance IL-3-dependent clonogenic growth through two distinct pathways, whereas IL-6 and IL-11 may trigger the same pathway.     

Type A dissection following endovascular thoracic aortic stent-graft repair.

PURPOSE: To describe our experience with endovascular stent-graft repairs in the thoracic aorta focusing on the secondary complication of type A dissection. METHODS: Between January 1996 and April 2004, 73 patients were treated for traumatic thoracic aortic rupture (n=15), type B dissection (n=22), or atherosclerotic descending thoracic aortic aneurysms (TAA, n=36). A retrospective review of the records found 5 (6.8%) patients (3 men; median age 64 years, range 43-87) who experienced a type A dissection at a median 20 days (range 2-124) after thoracic stent-graft repair for 3 type B dissections, 1 TAA, and a late type I endoleak that appeared 28 months after initial stent-graft repair of a traumatic dissection. RESULTS: In 3 patients (2 dissections, 1 endoleak), a tear in the aortic wall at the proximal stent-graft was responsible for a retrograde type A dissection. Underlying disease was the cause of the type A dissection in the 2 other patients (1 dissection, 1 TAA) and was unrelated to the stent-grafts. Three patients underwent open surgery at 3, 26, and 124 days after stent-graft placement; 2 procedures were successful, but the third patient died 3 months later due to multiorgan failure. Two type A dissections were untreated: one patient died from cardiac tamponade 14 days after successful stent-graft exclusion of the type I endoleak; the other patient refused further treatment and survived. The procedure-related mortality following acute retrograde type A dissection was 40%. CONCLUSIONS: Endovascular stent-graft repair of the thoracic aorta is associated with lower morbidity and mortality rates than surgical repair, although potentially lethal complications, acute or delayed, may occur.     

Do-not-resuscitate and do-not-hospitalize directives of persons admitted to skilled nursing facilities under the Medicare benefit

OBJECTIVES: To determine prevalence and factors associated with do-not-resuscitate (DNR) and do-not-hospitalize (DNH) directives of residents admitted under the Medicare benefit to a skilled nursing facility (SNF). To explore geographic variation in use of DNR and DNH orders. DESIGN: Retrospective cohort study. SETTING: Nursing homes in the United States. PARTICIPANTS: Medicare admissions to SNFs in 2001 (n=1,962,742). MEASUREMENTS: Logistic regression was used to select factors associated with DNR and DNH directives and state variation in their use. RESULTS: Thirty-two percent of residents had DNR directives, whereas less than 2% had DNH directives. Factors associated with having a DNR or DNH directive at the resident level included older age, cognitive impairment, functional dependence, and Caucasian ethnicity. African-American, Hispanic, Asian, and North American Native residents were all significantly less likely than Caucasian residents to have DNR (adjusted odds ratio (OR)=0.35, 0.51, 0.61, and 0.62, respectively) or DNH (adjusted OR=0.26, 0.41, 0.43, and 0.67, respectively) directives. In contrast, residents in rural and government facilities were more likely to have DNR or DNH directives. After controlling for resident and facility characteristics, significant variation between states existed in the use of DNR and DNH directives. CONCLUSION: Ethnic minorities are less likely to have DNR and DNH directives even after controlling for disease status, demographic, facility, and geographic characteristics. Wide variation in the likelihood of having DNR and DNH directives between states suggests a need for better-standardized methods for eliciting the care preferences of residents admitted to SNFs under the Medicare benefit.     

First human case of retrograde transcatheter implantation of an aortic valve prosthesis

The transcatheter route is an emerging approach to treating valvular disease in high-risk patients. The 1st clinical antegrade transcatheter placement of an aortic valve prosthesis was reported in 2002. We describe the first retrograde transcatheter implantation of a new aortic valve prosthesis, in a 62-year-old man with inoperable calcific aortic stenosis and multiple severe comorbidities. Via the right femoral artery, a Cook introducer was advanced into the abdominal aorta. The aortic valve was crossed with a straight wire, and a pigtail catheter was advanced into the left ventricle to obtain pressure-gradient and anatomic measurements. An 18-mm valvuloplasty balloon was then used to predilate the aortic valve. Initial attempts to position the prosthetic valve caused a transient cardiac arrest. Implantation was achieved by superimposing the right coronary angiogram onto fluoroscopic landmarks in the same radiographic plane. A balloon-expandable frame was used to deliver the valve. After device implantation, the transvalvular gradient was <5 mmHg. The cardiac output increased from 1 to 5 L/min, and urine production increased to 200 mL/h. The patient was extubated on the 2nd postimplant day. Twelve hours later, he had to be reintubated because of respiratory distress and high pulmonary pressures. His condition deteriorated, and he died of biventricular failure and refractory hypotension on day 5. Despite the severe hypotension, valve function was satisfactory on echo-Doppler evaluation. In our patient, retrograde transcatheter implantation of a prosthetic aortic valve yielded excellent hemodynamic results and paved the way for further use of this technique in selected high-risk patients.     

Steroid-eluting epicardial pacing leads in pediatric patients: encouraging early results.

OBJECTIVES. This study evaluated the pacing and sensing characteristics of a new porous-tipped steroid-eluting epicardial lead in a group of pediatric patients. BACKGROUND. Pacing in children may be complicated by small patient size, patient growth and the prevalence of structural congenital heart disease in children requiring pacing. Epicardial pacing has been associated with a high incidence of problems with sensing and capture, prompting the use of transvenous endocardial pacing when possible. In some children, epicardial pacing may still be desirable because of small patient size, potential for caval obstruction, previous cardiac surgery limiting transvenous access to the heart, or the need to repair congenital heart disease at the time of pacemaker insertion. METHODS. Twelve patients aged 3 weeks to 18 years underwent placement of 23 epicardial pacing leads (8 atrial, 15 ventricular). Pulse width thresholds, sensing thresholds and lead impedance were measured weekly for 6 weeks, then at 3, 6, 12 and 18 months after pacemaker implantation. The median duration of follow-up was 12 months. RESULTS. Ventricular pulse width thresholds did not change over time, whereas atrial pulse width thresholds improved significantly. At 6 months, the mean pulse width threshold at 2.5 V for the atrial and ventricular leads was 0.10 +/- 0.03 and 0.19 +/- 0.09 ms, respectively. The thresholds were slightly lower at 12 and 18 months. At the most recent follow-up, all atrial leads sensed appropriately at 2.5 mV and all ventricular leads at 5 mV. CONCLUSIONS. These encouraging early results suggest that steroid-eluting epicardial pacing leads may be an attractive option for children needing epicardial pacing. Their excellent pacing and sensing characteristics may allow reliable dual-chamber pacing in infants who are too small for transvenous pacing.