[Thrombosis during thrombopoietin receptor agonist treatment for immune thrombocytopenia. A French multicentric observational study]. / Thromboses sous agonistes du récepteur de la thrombopoïétine au cours du purpura thrombopénique immunologique. Étude rétrospective multicentrique en France.

INTRODUCTION: Thrombopoietin-receptor agonists (TPO-RA) are marketed for immune thrombocytopenia (ITP). They have been associated to thrombosis occurrence in randomized controlled trials. However, the characteristics of these thromboses in the real-life practice as well as their management are poorly known. The objectives of this study were to determine the risk factors, circumstances and management of thrombosis occurring during exposure to TPO-RA in ITP. METHODS: We carried out a multicentre retrospective study in France. Moreover, all cases reported to the French pharmacovigilance system were also analyzed. RESULTS: Overall, 41 thrombosis (13 arterial) in 36 ITP patients (14 males and 22 females, mean age: 59 years) were recorded between January 2009 and October 2015. Twenty patients were treated with romiplostim, 15 with eltrombopag and 1 was treated by both medications. Thirty-three (92%) of the patients had another risk factor for thrombosis. Ten (28%) had an history of thrombosis and 13 (36%) received immunoglobulin in the month preceding the thrombotic event. Three had antiphospholipid antibodies; congenital low-risk thrombophilia was found in 4 cases; 18 patients (50%) were splenectomized. Median platelet count at the time of thrombosis was 172G/l (1-1049G/l). In 22 patients (56%), a good prognosis was associated with the thrombosis and was not linked with TPO-RA withdrawal. Bleeding events occurred in 14% of the patients treated with antiplatelet or anticoagulant drug, including 5% serious events (1 death of intracranial haemorrhage, 1 death of haemorrhagic shock). CONCLUSIONS: The thrombotic risk may be carefully assessed before starting TPO-RA in ITP patients. The impact of antiphospholipid antibodies and of congenital thrombophilia remains to be defined. Thrombosis evolution seems independent of TPO-RA management. Bleeding manifestations seem rare. Poor prognosis was mainly due to ischemic sequelae.

Quercetin induces insulin secretion by direct activation of L-type calcium channels in pancreatic beta cells.

BACKGROUND AND PURPOSE: Quercetin is a natural polyphenolic flavonoid that displays anti-diabetic properties in vivo. Its mechanism of action on insulin-secreting beta cells is poorly documented. In this work, we have analysed the effects of quercetin both on insulin secretion and on the intracellular calcium concentration ([Ca(2+)]i) in beta cells, in the absence of any co-stimulating factor. EXPERIMENTAL APPROACH: Experiments were performed on both INS-1 cell line and rat isolated pancreatic islets. Insulin release was quantified by the homogeneous time-resolved fluorescence method. Variations in [Ca(2+)]i were measured using the ratiometric fluorescent Ca(2+) indicator Fura-2. Ca(2+) channel currents were recorded with the whole-cell patch-clamp technique. KEY RESULTS: Quercetin concentration-dependently increased insulin secretion and elevated [Ca(2+)]i. These effects were not modified by the SERCA inhibitor thapsigargin (1 µmol·L(-1)), but were nearly abolished by the L-type Ca(2+) channel antagonist nifedipine (1 µmol·L(-1)). Similar to the L-type Ca(2+) channel agonist Bay K 8644, quercetin enhanced the L-type Ca(2+) current by shifting its voltage-dependent activation towards negative potentials, leading to the increase in [Ca(2+)]i and insulin secretion. The effects of quercetin were not inhibited in the presence of a maximally active concentration of Bay K 8644 (1 µmol·L(-1)), with the two drugs having cumulative effects on [Ca(2+)]i. CONCLUSIONS AND IMPLICATIONS: Taken together, our results show that quercetin stimulates insulin secretion by increasing Ca(2+) influx through an interaction with L-type Ca(2+) channels at a site different from that of Bay K 8644. These data contribute to a better understanding of quercetin's mechanism of action on insulin secretion.

Quercetin potentiates insulin secretion and protects INS-1 pancreatic ß-cells against oxidative damage via the ERK1/2 pathway.

BACKGROUND AND PURPOSE: Quercetin lowers plasma glucose, normalizes glucose tolerance tests and preserves pancreatic ß-cell integrity in diabetic rats. However, its mechanism of action has never been explored in insulin-secreting ß-cells. Using the INS-1 ß-cell line, the effects of quercetin were determined on glucose- or glibenclamide-induced insulin secretion and on ß-cell dysfunctions induced by hydrogen peroxide (H(2)O(2)). These effects were analysed along with the activation of the extracellular signal-regulated kinase (ERK)1/2 pathway. N-acetyl-L-cysteine (NAC) and resveratrol, two antioxidants also known to exhibit some anti-diabetic properties, were used for comparison. EXPERIMENTAL APPROACH: Insulin release was quantified by the homogeneous time resolved fluorescence method and ERK1/2 activation tested by Western blot experiments. Cell viability was estimated by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) colorimetric assay. KEY RESULTS Quercetin (20 µmol·L(-1)) potentiated both glucose (8.3 mmol·L(-1))- and glibenclamide (0.01 µmol·L(-1))-induced insulin secretion and ERK1/2 phosphorylation. The ERK1/2 (but not the protein kinase A) signalling pathway played a crucial role in the potentiation of glucose-induced insulin secretion by quercetin. In addition, quercetin (20 µmol·L(-1)), protected ß-cell function and viability against oxidative damage induced by 50 µmol·L(-1) H(2)O(2) and induced a major phosphorylation of ERK1/2. In the same conditions, resveratrol or NAC were ineffective. CONCLUSION AND IMPLICATIONS: Quercetin potentiated glucose and glibenclamide-induced insulin secretion and protected ß-cells against oxidative damage. Our study suggested that ERK1/2 played a major role in those effects. The potential of quercetin in preventing ß-cell dysfunction associated with diabetes deserves further investigation.

Quadruple pads approach for external cardioversion of atrial fibrillation.

This study examined the alternative of transthoracic quadruple pads shock delivery of two simultaneous 360-J shocks to convert refractory AF in patients failing standard external cardioversion. Forty-six patients (mean age 58 +/- 11 years, 23 men) with chronic AF (duration 14 +/- 17 months, range 1-60 months) were included. The left atrial diameter was 47 +/- 7 mm. The left ventricular ejection fraction was 59 +/- 11%. Antiarrhythmic drugs had failed to convert 44 (96%) of these patients. All patients underwent conventional external transthoracic cardioversion with pads applied in the antero-apical position using energy settings of 200 and 360 J, consecutively. In all patients who failed conventional cardioversion, quadruple pads were applied. Quadruple pads consisted of four pads, two in the antero-posterior position and two in a second apex-posterior position. Standard cardioversion to sinus rhythm was successful in 19 (41%) patients after use of a single 200-J shock and an additional 8 (17%) after a single 360-J shock. The total success rate was 58% after conventional cardioversion. The quadruple pads were successful in 14 (74%) of the remaining 19 patients. Four of the five patients who failed the quadruple pads approach subsequently also failed internal cardioversion. Thus, the cardioversion success rate was increased from 48% using the conventional approach to 89% using the quadruple pads approach. Quadruple pads external cardioversion is highly effective in converting chronic AF refractory to standard shock protocols to sinus rhythm. Moreover, the failure of the quadruple pads approach seems to predict poor response to internal cardioversion.

Reducing mortality from sudden cardiac death in the community: lessons from epidemiology and clinical applications research.

The reduction of mortality from sudden cardiac death (SCD) in the community remains a challenge. Clinical-epidemiologic studies have identified a range of factors that are associated with an increased risk of SCD. While of potential etiologic and prognostic importance, these factors have limited sensitivity and a low positive predictive value for SCD. On the other hand, clinical trials have suggested that a variety of interventions, including risk factor reduction, nutritional interventions, drug therapies, cardiac procedures, and new technologies, have the potential to reduce mortality from SCD. In this review, we examine what is known about the epidemiology and clinical application of interventions to reduce mortality from SCD; and, we consider the impact of both prevention and clinical interventions on mortality from SCD from a community perspective. There is mounting evidence that supports both public health and clinical efforts to prevent the occurrence of SCD. There also is evidence suggesting that new technologies, such as automated external defibrillators, have the potential to reduce case-fatality from SCD. Further progress will depend on improved methods to identify persons-at-risk, reduction of risk factors, and application of techniques -- both simple and advanced -- to improve survival in victims of SCD.

External cardioversion of atrial fibrillation: comparison of biphasic vs monophasic waveform shocks.

AIMS: It is well established in transthoracic ventricular defibrillation that biphasic truncated waveform shocks are associated with superior defibrillation efficacy when compared with damped sine wave monophasic waveform shocks. The aim of this study was to explore whether biphasic waveform shocks were superior to monophasic waveform shocks for external cardioversion of atrial fibrillation (AF). METHODS AND RESULTS: Fifty-seven patients in whom cardioversion of AF was indicated were randomized in this prospective study, to transthoracic cardioversion with either monophasic damped sine waveform shocks or biphasic impedance compensating waveform shocks. In the group randomized to monophasic waveform shocks (27 patients), a first shock of 150 J was delivered, followed (if necessary) by a 360 J shock. In the biphasic waveform group (30 patients), the first shock had an energy of 150 J and (if necessary) a second 150 J was delivered. All shocks were delivered in the anterolateral chest pad position. Sinus rhythm was restored in 16 patients (51%) with the first monophasic shock and in 27 patients (86%) with the first biphasic shock. The difference was statistically significant (P=0.02). After the second shock, sinus rhythm was obtained in a total of 24 patients (88%) with monophasic shocks and in 28 patients (93%) with biphasic shocks. No complication was observed in either group and cardiac enzymes (CK, CKmb, troponin I, myoglobin) did not show any significant changes. CONCLUSION: This study suggests that at the same energy level of 150 J, biphasic impedance compensating waveform shocks are superior to monophasic damped sine waveform shocks cardioversion of atrial fibrillation.

High-dose bolus lidocaine for chemical cardioversion of atrial fibrillation: a prospective, randomized, double-blind crossover trial.

BACKGROUND: Most drugs used for chemical cardioversion of atrial fibrillation have significant proarrhythmia risk and require close monitoring after administration. Lidocaine has few of the proarrhythmic concerns of most antiarrhythmic drugs and, at high bolus doses, prolongs the atrial refractory period well enough to be effective in converting atrial fibrillation to sinus rhythm. This finding has been previously demonstrated in a dog model. We sought to confirm the animal findings in human beings with lidocaine doses of 1.5 to 2.5 mg/kg. METHODS: Twenty patients with atrial fibrillation scheduled for elective cardioversion were enrolled in this study. In a randomized, double-blind, crossover study design, each patient received intravenous bolus lidocaine or saline. Patients were observed for 10 minutes after the initial bolus to assess efficacy. The second test drug was then delivered if the first was unsuccessful at cardioversion. RESULTS: All 20 patients received both lidocaine and saline placebo therapy in a crossover manner. None of the 20 patients converted to sinus rhythm with either therapy. The 95% confidence interval for effectiveness of lidocaine in this population was 0% to 14%. CONCLUSION: In this population of patients referred for elective cardioversion of atrial fibrillation, high-dose bolus lidocaine was ineffective in converting patients to sinus rhythm. Although this study was not sufficiently powered to rule out a low efficacy of lidocaine (<15%) or a higher efficacy in certain subgroups of atrial fibrillation, routine use of lidocaine for this indication is not warranted.

Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy is a genetic disease associated with a risk of ventricular tachyarrhythmias and sudden death, especially in young patients. METHODS: We conducted a retrospective multicenter study of the efficacy of implantable cardioverter-defibrillators in preventing sudden death in 128 patients with hypertrophic cardiomyopathy who were judged to be at high risk for sudden death. RESULTS: At the time of the implantation of the defibrillator, the patients were 8 to 82 years old (mean [+/-SD], 40+/-16), and 69 patients (54 percent) were less than 41 years old. The average follow-up period was 3.1 years. Defibrillators were activated appropriately in 29 patients (23 percent), by providing defibrillation shocks or antitachycardia pacing, with the restoration of sinus rhythm; the average age at the time of the intervention was 41 years. The rate of appropriate defibrillator discharge was 7 percent per year. A total of 32 patients (25 percent) had episodes of inappropriate discharges. In the group of 43 patients who received defibrillators for secondary prevention (after cardiac arrest or sustained ventricular tachycardia), the devices were activated appropriately in 19 patients (11 percent per year). Of 85 patients who had prophylactic implants because of risk factors (i.e., for primary prevention), 10 had appropriate interventions (5 percent per year). The interval between implantation and the first appropriate discharge was highly variable but was substantially prolonged (four to nine years) in six patients. In all 21 patients with stored electrographic data and appropriate interventions, the interventions were triggered by ventricular tachycardia or fibrillation. CONCLUSIONS: Ventricular tachycardia or fibrillation appears to be the principal mechanism of sudden death in patients with hypertrophic cardiomyopathy. In high-risk patients with hypertrophic cardiomyopathy, implantable defibrillators are highly effective in terminating such arrhythmias, indicating that these devices have a role in the primary and secondary prevention of sudden death.

Implantable defibrillators and antiarrhythmic drugs in patients at risk for lethal arrhythmias.

The high mortality rate and frequency of ventricular arrhythmias in patients with congestive heart failure has prompted numerous clinical trials aimed at reducing mortality by addressing arrhythmic death. Recently completed trials have suggested that for patients who have survived cardiac arrest, the preferred treatment may be an implantable cardioverter defibrillator (ICD). From the standpoint of primary prevention, implantable defibrillators and amiodarone have received the most attention. It remains unclear, however, to which patients these studies apply, and if and how the results might be generalized. No available studies confirm an additional benefit of pharmacologic or device-based antiarrhythmic therapy beyond that offered by optimal treatment with beta blockers, angiotensin-converting enzyme inhibitors, and lipid-lowering drugs in the majority of patients with cardiomyopathy. Clinical trials are ongoing to address these issues.

Comparison of naive sixth-grade children with trained professionals in the use of an automated external defibrillator.

BACKGROUND: Survival after out-of-hospital cardiac arrest (OHCA) is strongly influenced by time to defibrillation. Wider availability of automated external defibrillators (AEDs) may decrease response times but only with increased lay use. Consequently, this study endeavored to improve our understanding of AED use in naive users by measuring times to shock and appropriateness of pad location. We chose sixth-grade students to simulate an extreme circumstance of unfamiliarity with the problem of OHCA and defibrillation. The children's AED use was then compared with that of professionals. METHODS AND RESULTS: With the use of a mock cardiac arrest scenario, AED use by 15 children was compared with that of 22 emergency medical technicians (EMTs) or paramedics. The primary end point was time from entry onto the cardiac arrest scene to delivery of the shock into simulated ventricular fibrillation. The secondary end point was appropriateness of pad placement. All subject performances were videotaped to assess safety of use and compliance with AED prompts to remain clear of the mannequin during shock delivery. Mean time to defibrillation was 90+/-14 seconds (range, 69 to 111 seconds) for the children and 67+/-10 seconds (range, 50 to 87 seconds) for the EMTs/paramedics (P<0.0001). Electrode pad placement was appropriate for all subjects. All remained clear of the "patient" during shock delivery. CONCLUSIONS: During mock cardiac arrest, the speed of AED use by untrained children is only modestly slower than that of professionals. The difference between the groups is surprisingly small, considering the naïveté of the children as untutored first-time users. These findings suggest that widespread use of AEDs will require only modest training.

Analysis of defibrillation efficacy from myocardial voltage gradients with finite element modeling.

Increasing defibrillation efficacy by lowering the defibrillation threshold (DFT) is an important goal in positioning implantable cardioverter-defibrillator electrodes. Clinically, the DFT is difficult to estimate noninvasively. It has been suggested that the DFT relates to the myocardial voltage gradient distribution, but this relation has not been quantitatively demonstrated. We analyzed the relation between the experimentally measured DFT's and the simulated myocardial voltage gradients provided by finite element modeling. We performed a series of experiments in 11 pigs to measure the DFT's, and created and solved three-dimensional subject-specific finite element models to assess the correlation between the computed myocardial voltage gradient histograms and the DFT's. Our data show a statistically significant correlation between the DFT and the left ventricular voltage gradient distribution, with the septal region being more significant (correlation coefficient of 0.74) than other myocardial regions. The correlation between the DFT and the right ventricular and the atrial voltage gradient, on the other hand, is not significant.

MCG simulations of myocardial infarctions with a realistic heart-torso model.

Data from simulations of the anterior myocardial infarction (AMI) and inferior myocardial infarction (IMI) are presented. One infarct located in the anterior section of the left ventricle and a second one in the inferior wall of the left ventricle were modeled. A high-resolution finite element model of a heart and torso was used in this study. Differences in the normal and infarcted fields were computed. Our data suggest that the infarcted region contribution to the total magnetic field can be accounted for by an equivalent current dipole. It might also be possible to detect an infarct from these difference fields constructed for different cases of myocardial infarction. More simulations are needed to determine the relations between infarct sizes and locations and magnetic fields. These relations might then be used to detect various cases of myocardial infarction.

MCG simulations with a realistic heart-torso model.

Magnetocardiograms (MCG's) simulated with a high-resolution heart-torso model of an adult subject were compared with measured MCG's acquired from the same individual. An exact match of the measured and simulated MCG's was not found due to the uncertainties in tissue conductivities and cardiac source positions. However, general features of the measured MCG's were reasonably represented by the simulated data for most, but not all of the channels. This suggests that the model accounts for the most important mechanisms underlying the genesis of MCG's and may be useful for cardiac magnetic field modeling under normal and diseased states. MCG's were simulated with a realistic finite-element heart-torso model constructed from segmented magnetic resonance images with 19 different tissue types identified. A finite-element model was developed from the segmented images. The model consists of 2.51 million brick-shaped elements and 2.58 million nodes, and has a voxel resolution of 1.56 x 1.56 x 3 mm. Current distributions inside the torso and the magnetic fields and MCG's at the gradiometer coil locations were computed. MCG's were measured with a Philips twin Dewar first-order gradiometer SQUID-system consisting of 31 channels in one tank and 19 channels in the other.

Treatment of out-of-hospital cardiac arrest with a low-energy impedance-compensating biphasic waveform automatic external defibrillator. The LIFE Investigators.

Few victims of sudden cardiac arrest survive. A new generation of automatic external defibrillators (AEDs), smaller, lighter, easier to use, and less costly, makes the goal of widespread AED deployment and early defibrillation feasible. A low-energy impedance-compensating biphasic waveform allows AED device characteristics more suitable to the goal of early defibrillation than high-energy waveforms. This study observed the performance of such a biphasic waveform in the out-of-hospital setting on 100 consecutive victims of sudden cardiac arrest treated by a wide range of first-responders. AEDs incorporating 150-J impedance-compensating biphasic waveforms were placed into service of 34 EMS systems. Data were obtained from the AED PC data card-recording system. The first endpoint was to determine the effectiveness of this waveform in terminating ventricular fibrillation (VF). The second endpoint was to determine whether or not the use of such an AED culminated in an organized rhythm at the time of patient transfer to an advanced life support (ALS) team or emergency department (ED). The third endpoint was to assess the efficiency of the human-factors design of the AED by measuring user time intervals. The 34 sites provided data from 286 consecutive AED uses, 100 from SCA victims with VF as their initial rhythm upon attachment of the AED. All 286 patients were correctly identified by the AED as requiring a shock (100% sensitivity for the 100 VF patients) or not (100% specificity to the 186 patients not presenting in VF). Times from emergency call to first shock delivery averaged 9.1 +/- 7.3 minutes. A single 150-J biphasic shock defibrillated the initial VF episode in 86% of patients. For all 450 episodes of VF in these 100 patients, an average of 86% +/- 24% of VF episodes were terminated with a single biphasic shock. Of the 449 VF episodes that received up to three shocks, 97% +/- 11% were terminated with three shocks or fewer. The average number of shocks per VF episode was 1.3 +/- 0.7. The average time from AED power-on and pads attached to first defibrillation was 25 +/- 23 sec. At the time of patient transfer, an organized rhythm was present in 65% of the VF patients; asystole was the result in 25%, and VF was in progress in 10%. It is concluded that low-energy impedance-compensating biphasic waveforms terminate long-duration VF at high rates in out-of-hospital cardiac arrest and provide defibrillation rates exceeding those previously achieved with high-energy shocks. Use of this waveform allows AED device characteristics consistent with widespread AED deployment and early defibrillation.

Biphasic transthoracic defibrillation causes fewer ECG ST-segment changes after shock.

STUDY OBJECTIVE: Electrocardiographic abnormalities are common after transthoracic defibrillation. ECG ST-segment changes are especially problematic after defibrillation and may indicate ischemic or shock-induced cardiac dysfunction after resuscitation. Biphasic defibrillation waveforms, compared with monophasic waveforms, diminish shock-induced cardiac dysfunction in laboratory preparations. This effect has not been validated in human subjects. We therefore evaluated in a prospective, blinded fashion the effect of biphasic and monophasic transthoracic defibrillation on the ECG ST segment in 30 consecutive patients during surgery for the implantation of a cardioverter-defibrillator. METHODS: In each patient two low-energy truncated biphasic transthoracic defibrillation shocks (115 and 130 J) were compared with a standard clinical 200 J monophasic damped-sine wave shock. The biphasic shocks and the damped-sine wave shock have been demonstrated to have equal defibrillation efficacy of 97%. Fifteen-second ECG signals recorded across transthoracic defibrillation electrodes were digitized before ventricular fibrillation induction and immediately after each defibrillation attempt. The ST segments 80 msec after the J point were analyzed in a blinded fashion by two reviewers. The ST-segment deflection, QRS-interval duration, QT interval, and heart rate after each therapy were compared with baseline values. RESULTS: ECG ST-segment elevation was significantly greater with the 200-J damped-sine waveform than with either biphasic waveform. The ECG ST-segment levels were -.55 +/- .36 at baseline, -.76 +/- .36 mm after internal shock, -.02-.36 mm after 115-J biphasic shock, .21 +/- .38 mm after 130-J biphasic shock, and 2.09 +/- .37 mm after 200-J damped-sine wave shock (P<.0001). QRS-interval duration, QT interval, and heart rate did not change significantly with any waveform. CONCLUSION: Transthoracic defibrillation with biphasic waveforms results in less postshock ECG evidence of myocardial dysfunction (injury or ischemia) than standard monophasic damped sine waveforms without compromise of defibrillation efficacy.

Prospective evaluation of the effect of biphasic waveform defibrillation on ventricular pacing thresholds.

INTRODUCTION: Significant increases in ventricular pacing threshold have been observed following monophasic waveform ventricular defibrillation shocks. High-output pacing is recommended to ensure consistent capture, particularly in pacemaker-dependent patients who are likely to be defibrillated. Whether biphasic waveform defibrillation compounds this problem is not known. The purpose of this prospective study was to examine serial changes in ventricular pacing thresholds following single, multiple, low- and high-energy biphasic defibrillation shocks from an implanted defibrillator. METHODS AND RESULTS: Bipolar pacing thresholds before and after defibrillation, and the adequacy of pacing capture at three times preshock threshold in the immediate aftermath of ventricular defibrillation, were prospectively evaluated in 67 consecutively tested recipients of a biphasic implanted cardioverter defibrillator. Overall, serial pacing thresholds following successful defibrillation were completely unchanged after 141 of 177 (80%) ventricular fibrillation inductions. In no case did the threshold pulse width increment > 0.06 msec from its baseline value after shock, nor did pacing at a pulse width of three times preshock threshold from dedicated bipolar pacing electrodes fail to result in successful ventricular capture. Changes in threshold were not related to when measured from the time of shock, defibrillation energy, number of shocks, electrode system, chronicity of leads, shock orientation, or to clinical factors. CONCLUSIONS: No clinically important changes in pacing threshold were observed after biphasic waveform defibrillation. Bradycardia pacing at conventional pacemaker outputs of three times baseline pulse width threshold from bipolar electrodes dedicated exclusively to pacing or sensing (but not defibrillation) consistently allowed for an adequate safety margin following defibrillation.

Unipolar pectoral defibrillation systems.

Over the past 15 years, the implantation of automatic defibrillations has evolved from an obscure, impractical, and often morbid procedure to nearly a routine therapy. Initial large abdominally implanted generators with multiple epicardial leads have given way to much smaller, pectorally implanted systems utilizing only a single lead. These systems are better accepted by physicians and patients and rival recent-generation pacemakers in their implantation simplicity. Outcomes with single lead defibrillator implantation have been excellent. They are 99% effective at eliminating sudden death in large cohorts of patients, with overall survival of 94.4% at 18 months. Previously significant perioperative complications and mortality associated with epicardial systems have been virtually eliminated. Transvenous single lead systems now provide defibrillation efficacy at a level that makes epicardial leads unnecessary in most patients. Although inappropriate shocks are not a morbid complication, they still occur in approximately 15%-30% of patients. This is an area for improvement in defibrillator therapy, which, though invisible in total mortality statistics, is significant in terms of patient comfort and acceptance. Incremental improvements in pulse generator design and defibrillator lead technology are being made. Perhaps the most interesting new development will be the dual chamber device, incorporating and atrial electrode for sensing, pacing, and perhaps, atrial defibrillation. Such improvements will continue to make device therapy of all arrhythmias more versatile and improve patient comfort both in terms of device size and inappropriate shocks. It is unlikely, however, that further technological advances can further diminish the already small complication rate or improve the already excellent efficacy of current single lead systems. Defibrillator technology has already reached a maturity where technological improvements are less significant than efforts to better define the patient population who will benefit from the therapy.

Malignant sustained ventricular tachyarrhythmias in women: characteristics and outcome of treatment with an implantable cardioverter defibrillator.

Clinical rhythm, heart disease, ejection fraction, defibrillation threshold, recurrent arrhythmias, and mortality were compared in 268 consecutive recipients (213 men and 55 women) of their first implantable cardioverter defibrillator for life-threatening ventricular tachycardia or fibrillation. Women were younger than men, less likely to have structural heart disease, and more likely to have clinical ventricular fibrillation, a higher ejection fraction, and a lower defibrillation threshold. Complications of defibrillator placement were similar in both sexes. Unadjusted survival tended to be higher in women than in men (97% vs 90%, respectively, at 2 years, P = 0.08), largely due to fewer deaths from noncardiac causes or cardiac causes other than arrhythmia (P = 0.04). Women also tended to be at lower, albeit still substantial, risk for recurrent arrhythmias during follow-up (37% vs 52% in men at 2 years, P = 0.11). After adjustment for baseline differences, overall survival, arrhythmia death-free survival, nonarrhythmia death-free survival, and frequency of recurrent arrhythmias were not found to be gender related. Despite their apparent "lower risk" status on initial presentation, women remained at substantial risk for recurrent arrhythmias. This underscores the need to avoid being unduly biased by the "appearance" of health in managing women with malignant arrhythmias. That survival and other clinical endpoints were all ultimately independent of gender emphasizes the importance of other clinical variables in assessing risk from ventricular tachyarrhythmias.

A multicenter, randomized trial comparing an active can implantable defibrillator with a passive can system. Jewel Active Can Investigators.

Replacing one defibrillation electrode lead by the defibrillator can may simplify implantation of the ICD. In this multicenter study, 304 patients were randomized to receive either the biphasic active can (AC) (model 7219C system, Medtronic, Inc.) or the passive can (PC) (model 7219D system). The AC and PC systems were compared with respect to their ability to meet the implant defibrillation criterion and to defibrillate VF, and to DFTs, implant time, patient adverse events, and survival rates. A higher percentage fulfilled the implant defibrillation criterion on the first configuration with the AC (86.3% vs 75.9% for PC; P = 0.023), and the first shock success for terminating induced VF was 94% for AC compared to 89% for PC (P = 0.026). DFTs were significantly lower (10.9 vs 12.7 J; P = 0.031), and implant time was significantly shorter for the AC patients (99.2 vs 112.0 min; P = 0.002). The two groups showed no significant differences in 3-month adverse event rates, 3-month survival, and hospital stay.