Recommendations for the management of sickle cell disease in South Africa.

The spectrum of sickle cell disease (SCD) encompasses a heterogeneous group of disorders that include: (I) homozygous SCD (HbSS), also referred to as sickle cell anaemia; (ii) heterozygous SCD (HbAS), also referred to as sickle cell trait; and (iii) compound heterozygous states such as HbSC disease, HbSß thalassaemia, etc. Homozygous or compound heterozygous SCD patients manifest with clinical disease of varying severity that is influenced by biological and environmental factors, whereas subject with sickle cell trait are largely asymptomatic. SCD is characterized by vaso-occlusive episodes that result in tissue ischaemia and pain in the affected region. Repeated infarctive episodes cause organ damage and may eventually lead to organ failure. For effective management, regular follow-up with support from a multidisciplinary healthcare team is necessary. The chronic nature of the disease, the steady increase in patient numbers, and relapsing acute episodes have cost implications that are likely to impact on provincial and national health budgets. Limited resources mandate local management protocols for the purposes of consistency and standardisation, which could also facilitate sharing of resources between centres for maximal utility. These recommendations have been developed for the South African setting, and it is intended to update them regularly to meet new demands and challenges.

Management of undifferentiated embryonal sarcoma of the liver in children: a case series and management review.

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare neoplasm, and the third-most common paediatric hepatic malignancy. However, no treatment guidelines exist. No randomised, controlled trials support specific combinations of therapy. OBJECTIVE: To compare presentation and management of UESL with other series, review the literature, and formulate treatment guidelines. METHODS: A retrospective chart review of all hepatic malignancies was conducted from 1996 to 2007 and 5 children with UESL were identified. Management and outcomes were documented. The literature regarding treatment modalities up to September 2012 was reviewed. RESULTS: Over a period of 11 years, 5 patients presented. All underwent surgery and 4 received chemotherapy. One received radiotherapy at relapse. Three are disease-free with follow-up of 58 - 184 months. One died after relapse, as did the patient whose family declined chemotherapy. CONCLUSION: The improved outcomes are consistent with the international experience and are probably related to combined treatment modalities and advances in supportive care. Pre-operative percutaneous biopsy provides no benefit if the lesion is resectable because it may not prove to be diagnostic, and may cause recurrence in the biopsy tract. If resectable, the recommended treatment is primary excision and adjuvant chemotherapy, with radiotherapy in selected cases. If unresectable, open biopsy is necessary to document histology, and neo- adjuvant chemotherapy is given prior to resection. If deemed unresectable, liver transplantation is considered.

Granulocytic sarcoma in children with acute myeloblastic leukemia and t(8;21).

BACKGROUND: Granulocytic sarcomas (GS) have been associated with t(8;21). The prognosis of patients with GS is generally regarded as being less favorable than of patients with acute myeloblastic leukemia (AML). GS occurs relatively commonly in Africa and has been reported to affect 10-25% of black children presenting with AML. We sought to establish the incidence of GS in our pediatric population, to determine whether an association with t(8;21) existed, and to report on the outcome of these cases in a single series. PROCEDURE: The records of consecutive pediatric patients treated for de novo AML in Johannesburg between January 1985-December 1995 were reviewed. Fifteen cases of GS among a total of 88 cases of AML presented to the Paediatric Haematology/Oncology Clinics of the Johannesburg and Baragwanath Hospitals. Fourteen (93%) of these patients were black male children. RESULTS: All 9 cases of orbital GS (60%) and almost all cases with concurrent AML M2 had t(8;21). This translocation was present in only 4 n(8.5%) of the remaining 47 AML cases without GS for which cytogenetic data were available. One case presented with a complex chromosomal translocation not previously associated with GS. The median disease-free survival of the GS patients, using conventional chemotherapy treatment protocols, was significantly better than for the patients with AML and no GS (P = 0.0004). CONCLUSIONS: Our data support a strong association between orbital GS, t(8;21), and AML M2 in the pediatric population. This entity occurred virtually exclusively in black male children at presentation. One third of these children who presented with AML had a GS. The favorable prognosis noted in our GS patients on standard induction and intensification therapy without local irradiation conflicts with some previous reports but is consistent with the favorable outcome documented in AML with t(8;21).

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.

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.

Low-energy impedance-compensating biphasic waveforms terminate ventricular fibrillation at high rates in victims of out-of-hospital cardiac arrest. LIFE Investigators.

INTRODUCTION: New automatic external defibrillators (AEDs), which are smaller, lighter, easier to use, and less costly make the goal of widespread AED deployment and early defibrillation for out-of-hospital cardiac arrest feasible. The objective of this study was to observe the performance of a low-energy impedance-compensating biphasic waveform in the out-of-hospital setting on 100 consecutive victims of sudden cardiac arrest. METHODS AND RESULTS: AEDs incorporating a 150-J impedance-compensating biphasic waveform were used by 12 EMS systems. Data were obtained from the AED PC card reporting system. Defibrillation was defined as conversion to an organized rhythm or to asystole. Endpoints included: defibrillation efficacy for ventricular fibrillation (VF); restoration of an organized rhythm at the time of patient transfer to an advanced life support (ALS) team or to the emergency department (ED); and time from AED power-on to first defibrillation. The AED correctly identified 44 of 100 patients presenting in VF as requiring a shock (100% sensitivity) and 56 of 100 patients not in VF as not requiring a shock (100% specificity). The time from 911 call to first shock delivery averaged 8.1 +/- 3.0 minutes. A single 150-J biphasic shock defibrillated the initial VF episode in 39 of 44 (89%) patients. The average time from power-on to first defibrillation was 25 +/- 17 seconds. At patient transfer to ALS or ED care, an organized rhythm was present in 34 of 44 (77%) patients presenting with VF. Asystole was present in 7 (16%) and VF in 3 (7%). CONCLUSIONS: Low-energy impedance-compensating biphasic waveforms terminate long-duration VF at high rates in out-of-hospital cardiac arrest. Use of this waveform allows AED device characteristics consistent with widespread AED deployment and early defibrillation.

Prospective evaluation of eligibility for thrombolytic therapy in acute myocardial infarction.

OBJECTIVES: To determine the proportion of patients presenting with acute myocardial infarction who are eligible for thrombolytic therapy. DESIGN: Cohort follow up study. SETTING: The four coronary care units in Auckland, New Zealand. SUBJECTS: All 3014 patients presenting to the units with suspected myocardial infarction in 1993. MAIN OUTCOME MEASURES: Eligibility for reperfusion with thrombolytic therapy (presentation within 12 hours of the onset of ischaemic chest pain with ST elevation > or = 2 mm in leads V1-V3, ST elevation > or = 1 mm in any other two contiguous leads, or new left bundle branch block); proportions of (a) patients eligible for reperfusion and (b) patients with contraindications to thrombolysis; death (including causes); definite myocardial infarction. RESULTS: 948 patients had definite myocardial infarction, 124 probable myocardial infarction, and nine ST elevation but no infarction; 1274 patients had unstable angina and 659 chest pain of other causes. Of patients with definite or probable myocardial infarction, 576 (53.3%) were eligible for reperfusion, 39 had definite contraindications to thrombolysis (risk of bleeding). Hence 49.7% of patients (537/1081) were eligible for thrombolysis and 43.5% (470) received this treatment. Hospital mortality among patients eligible for reperfusion was 11.7% (55/470 cases) among those who received thrombolysis and 17.0% (18/106) among those who did not. CONCLUSIONS: On current criteria about half of patients admitted to coronary care units with definite or probable myocardial infarction are eligible for thrombolytic therapy. Few eligible patients have definite contraindications to thrombolytic therapy. Mortality for all community admissions for myocardial infarction remains high.

Management of ventricular fibrillation with transvenous defibrillators without baseline electrophysiologic testing or antiarrhythmic drugs.

INTRODUCTION: Baseline electrophysiologic study (EPS) is routinely performed in patients resuscitated from ventricular fibrillation (VF) to risk stratify and select patients for chronic antiarrhythmic drug therapy. The role of EP testing prior to insertion of a multiprogrammable implantable cardioverter defibrillator (ICD), however, is unclear. METHODS AND RESULTS: This study was a retrospective review of outcome in 66 survivors of an initial episode of out-of-hospital VF not associated with a Q wave myocardial infarction or reversible causes, treated with transvenous ICDs as first-line therapy. Patients were excluded from the study if they had a previous history of monomorphic ventricular tachycardia (VT), a clinical history suggestive of supraventricular tachycardia, or had undergone preoperative EP testing. Fifty-two of the patients (79%) were male with an average age of 58 +/- 11 years. Coronary artery disease was present in 43 patients (66%), cardiomyopathy in 15 patients (23%), and valvular heart disease in 1 patient (1.5%). Seven patients (11%) had no detectable structural heart disease. The mean left ventricular ejection fraction was 0.40 +/- 0.16. With an average follow-up of 25 +/- 12 months, survival free of death from any cause was 100%. Twenty-three patients (35%) experienced 48 episodes of recurrent rapid VT or VF (average cycle length: 236 +/- 47 msec) treated by their device. The mean time to first therapy was 223 +/- 200 days. Only one of these patients also received antitachycardia pacing for two episodes of VT. One patient (1.5%) temporarily received amiodarone after removal of an infected device that was subsequently replaced. No other patient received antiarrhythmic drug therapy. CONCLUSION: After a cardiac arrest due to primary VF, select patients treated with multiprogrammable ICDs can be managed successfully without baseline EPS or antiarrhythmic drug therapy.

A prospective randomized comparison in humans of 90-mu F and 120-mu F biphasic pulse defibrillation using a unipolar defibrillation system.

INTRODUCTION: Capacitance is known to influence defibrillation. Optimal biphasic waveform capacitance for transvenous unipolar defibrillation systems in man is currently being defined. In an effort to improve defibrillation efficacy, we examined the relative defibrillation efficacy of a 65% tilt biphasic pulse from a 90-mu F capacitor compared to a 65% tilt biphasic pulse from a 120-mu F capacitor in a prospective, randomized fashion in 16 consecutive cardiac arrest survivors undergoing defibrillator surgery. METHODS AND RESULTS: The transvenous unipolar pectoral defibrillation system uses a single endocardial RV anodal defibrillation coil and the shell of an 80-cc volume (88 cm2 surface area) pulse generator (Medtronic Model 7219C PCD "active CAN") as the cathode for the first phase of the biphasic shock: RV+ --> CAN-. Defibrillation thresholds for each capacitance were determined prospectively in a randomized fashion. The defibrillation threshold results for the 90-mu F capacitance were: leading edge voltage 383 +/- 132 V; stored energy 7.4 +/- 5.0 J; and resistance 57 +/- 10 omega. The results for the 120-mu F capacitance were: leading edge voltage 315 +/- 93 V (P = 0.002); stored energy 6.5 +/- 3.7 J (P = 0.21); and resistance 57.0 +/- 11 omega (P = 0.87). CONCLUSIONS: We conclude that 90-mu F, 65% tilt biphasic pulses used with unipolar pectoral defibrillation systems have equivalent stored energy defibrillation efficacy compared to 120-mu F, 65% tilt pulses. Use of lower capacitance is possible in present implantable defibrillators without compromising defibrillation.

Anatomical findings in patients having had a chronically indwelling coronary sinus defibrillation lead.

The purpose of this report is to review the gross and histological cardiac anatomical findings in patients with chronically indwelling coronary sinus leads at the time of autopsy or cardiac transplantation. Transvenous cardioverter defibrillators offer effective protection against sudden death. The use of a coronary sinus electrode has been shown in some patients to decrease the defibrillation threshold. The anatomical consequences of chronically indwelling coronary sinus cardioversion/defibrillation electrodes in patients having transvenous implantable cardioverter defibrillators is unknown. The hearts of seven patients with chronically indwelling coronary sinus electrodes were evaluated following autopsy (n = 2) or cardiac transplantation (n = 5). The coronary sinus electrode in each case was a 6.5 French silicone lead with a 5-cm long defibrillation coil (Medtronic CS lead model 6933) that was positioned as distally as possible within the coronary sinus at the time of implantable cardioverter defibrillator surgery. The seven hearts examined were derived from patients whose age ranged between 49 and 69 (mean 56 +/- 7 years). Six had coronary artery disease and one had idiopathic dilated cardiomyopathy. The time from implant to death or cardiac transplantation was 8 +/- 6 months, range 1-18 months. In all seven patients, there was no evidence of any significant damage from the presence of the coronary sinus lead. The only finding in each case was the scattered presence of a thin white fibrous sheath over the lead that intermittently adhered to the coronary sinus endothelium and, in the two patients transplanted 1-3 months after implantable cardioverter defibrillator insertion, a mild inflammation reaction adjacent to the leads in the coronary sinus endothelium. There was no evidence of coronary sinus occlusion, adjacent coronary artery injury, coronary sinus perforation, coronary sinus burn, or myocardial injury adjacent to the lead. Cause of death was due to end-stage congestive heart failure and thrombotic stroke, respectively, in the two patients examined at autopsy. Coronary sinus defibrillation leads can be used safely without harmful anatomical effect.

A prospective randomized evaluation of implantable cardioverter-defibrillator size on unipolar defibrillation system efficacy.

BACKGROUND: The active can unipolar implantable cardioverter-defibrillator (ICD) has been shown to defibrillate efficiently, but its current 80-cc size limits use in the pectoral position in many patients. Decreasing can size will facilitate pectoral insertion and will soon be feasible as an inevitable consequence of technological advancements. However, decreasing the can size has the potential to compromise unipolar defibrillation efficacy. It is the purpose of this study, therefore, to prospectively and randomly compare unipolar defibrillation efficacy with 80-cc, 60-cc, and 40-cc can sizes in patients immediately before ICD surgery in anticipation of advances in technology that will make smaller ICDs possible. METHODS AND RESULTS: Twenty-four consecutive patients underwent prospective, randomized evaluation of the effect of ICD can size on defibrillation efficacy during standard ICD surgery. Each patient had the unipolar defibrillation threshold (DFT) measured with 80-cc, 60-cc, or 40-cc active can placed in the left subcutaneous infraclavicular region. The system included a 10.5F tripolar right ventricular electrode that served as the shock anode. The shock waveform used in each instance was a single capacitor biphasic 65% pulse delivered from a 120-microF capacitor. Stored energy at the DFT for the 80-cc, 60-cc, and 40-cc cans were 8.1 +/- 4.7 J, 8.7 +/- 5.8 J, and 9.5 +/- 4.8 J, respectively. There was no statistical significant difference between the DFTs for the three unipolar can electrodes (P = 39). Leading edge voltage also did not differ significantly among the three unipolar cans (356 +/- 92 V, 365 +/- 110 V, and 387 +/- 94 V, respectively, P = .29). There was, however, a slight progressive increase in resistance with decreasing can size (57 +/- 7 omega, 60 +/- 9 omega, and 65 +/- 9 omega, respectively, P < .001). CONCLUSIONS: Decreasing can volume from 80 cc to 60 cc to 40 cc does not compromise unipolar defibrillation efficacy despite a slight rise in shock resistance. These findings indicate that technological advances that allow for smaller-volume ICDs will not compromise defibrillation efficacy for unipolar systems.

Mechanical complications after implantation of multiple-lead nonthoracotomy defibrillator systems: implications for management and future system design.

Nonthoracotomy lead system (NTL) implantable cardioverter defibrillators (ICDs) provide excellent protection against sudden death from ventricular tachyarrhythmias. However, these devices have unique mechanical complications and management issues. We reviewed the major complications occurring in 159 patients who underwent attempted implantation of a multilead NTL system. Successful implantation was obtained in 98% of patients. Two-year, all-cause actuarial survival on an intention-to-treat basis was 94%. Major complications occurred in 28 (17.6%) patients over a follow-up period of 21 +/- 10 months. Complications included 11 (6.9%) lead dislodgements, 10 (5.7%) lead fractures in 9 patients, 2 (1.3%) pocket infections, 1 frozen shoulder, 1 right ventricular perforation, 1 pneumothorax, 1 bleed requiring transfusion, 1 thromboembolism, and 1 "twiddle"-induced torsion of leads. Most of the lead dislodgements and fractures were identified by routine x-ray surveillance. Single-lead systems may significantly reduce complication rates in the future and maintain excellent survival rates.

Prospective randomized comparison of biphasic waveform tilt using a unipolar defibrillation system.

BACKGROUND: A unipolar defibrillation system using a single right ventricular (RV) electrode and the active shell or container of an implantable cardioverter defibrillator situated in a left infraclavicular pocket has been shown to be as efficient in defibrillation as an epicardial lead system. Additional improvements in this system would have favorable practice implications and could derive from alterations in pulse waveform shape. The specific purpose of this study is to determine whether defibrillation efficacy can be improved further in humans by lowering biphasic waveform tilt. METHODS: We prospectively and randomly compared the defibrillation efficacy of a 50% and a 65% tilt asymmetric biphasic waveform using the unipolar defibrillation system in 15 consecutive cardiac arrest survivors prior to implantation of a presently available standard transvenous defibrillation system. The RV defibrillation electrode has a 5-cm coil located on a 10.5 French lead and was used as the anode. The system cathode was the active 108 cm2 surface area shell (or "CAN") of a prototype titanium alloy pulse generator placed in the left infraclavicular pocket. The defibrillation pulse derived from a 120-microF capacitor and was delivered from RV-->CAN, with RV positive with respect to the CAN during the initial portion of the cycle. Defibrillation threshold (DFT) stored energy, delivered energy, leading edge voltage and current, pulse resistance, and pulse width were measured for both tilts examined. RESULTS: The unipolar single lead system, RV-->CAN, using a 65% tilt biphasic pulse resulted in a stored energy DFT of 8.7 +/- 5.7 J and a delivered energy DFT of 7.6 +/- 5.0 J. In all 15 patients, stored and delivered energy DFTs were < 20 J. The 50% tilt biphasic pulse resulted in a stored energy DFT of 8.2 +/- 5.4 J and a delivered energy DFT of 6.1 +/- 4.0 J; P = 0.69 and 0.17, respectively. As with the 65% tilt pulse, all 15 patients had stored and delivered energy DFTs < 20 J. CONCLUSION: The unipolar single lead transvenous defibrillation system provides defibrillation at energy levels comparable to that reported with epicardial lead systems. This system is not improved by use of a 50% tilt biphasic waveform instead of a standard 65% tilt biphasic pulse.

Clinical predictors of the defibrillation threshold with the unipolar implantable defibrillation system.

OBJECTIVES: The purpose of this study was to determine the relation between clinical variables and the defibrillation threshold by using a standardized testing protocol and a uniform implantable defibrillator system. BACKGROUND: Past studied have not revealed useful correlations between clinical variables and the energy required to terminate ventricular fibrillation. Most of these studies did not use a uniform implantable defibrillator system or a standardized protocol to measure the defibrillation threshold and, thus, did not control for the influence of these technical influences. We postulated that defibrillator and defibrillation threshold measurement-based sources of variability overshadowed important clinical predictors. METHODS: The defibrillation threshold was measured by using a standardized protocol in 101 consecutive patients. We used a transvenous unipolar pectoral defibrillation system that employed a single endocardial right ventricular defibrillation coil as the anode and the shell of an 80-cm3 pulse generator as the cathode to deliver a 65% tilt biphasic pulse. RESULTS: Several clinical variables were found to be significantly associated with the defibrillation threshold: patient gender, height, weight, body surface area, heart rate at rest, QRS and corrected QT (QTc) intervals, left ventricular mass and several measures of heart and chest size by chest roentgenogram. None of these variables had a correlation coefficient > 0.45 with the defibrillation threshold. On multivariate analysis, left ventricular mass and heart rate at rest were the only independent predictors of the defibrillation threshold and explained only 25% of the observed variability. CONCLUSIONS: Despite the use of a uniform transvenous defibrillation system and a standardized protocol to measure the defibrillation threshold, no clinically relevant correlation was found between clinical variables and the defibrillation threshold. The defibrillation threshold is probably a function of a complex interaction of anatomic, physiologic and cellular variables that are not adequately represented by easily obtainable clinical information. It is probably not possible to predict defibrillation outcome from standard clinical variables.

Ventricular arrhythmias detected after transvenous defibrillator implantation in patients with a clinical history of only ventricular fibrillation. Implications for use of implantable defibrillator.

BACKGROUND: Patients with a history of ventricular fibrillation (VF) have been shown to have a clinical profile, response to electrophysiological testing (EPS), and response to antiarrhythmic therapy that distinguishes them from patients with a history of sustained monomorphic ventricular tachycardia (MVT). Despite these differences, it is not clear whether VF in these patients is triggered by MVT or occurs de novo. The incidence of MVT and VF in such patients after their index VF event has important implications for therapeutic decisions regarding implantable defibrillator selection and programming. METHODS AND RESULTS: The records of 111 consecutive patients who had undergone transvenous cardioverter/defibrillator (ICD) implantation for malignant ventricular arrhythmias were reviewed retrospectively. For each patient, all device tachyarrhythmia detections were examined and classified as VF, MVT, rapid polymorphic VT, or other. The number of events, time to first arrhythmia detection, and cycle length of MVTs were recorded. There were 55 patients with a history of only VF and 56 with a history that included an episode of MVT. Over 14 months of follow-up, with all patients initially off of antiarrhythmic medications, MVT was detected by only 18% of patients with a history of only VF compared with 54% of those with a history that included MVT (P = .002). Among patients who did detect MVT, those with a history of only VF had fewer episodes (7 +/- 7 versus 20 +/- 31, P = .001) and a shorter mean MVT cycle length (279 versus 314 ms, P = .03) than those with a clinical history of MVT. Abrupt onset of VF not preceded by MVT was detected in 11% of patients with VF only. In addition to a history of MVT, male sex, age < 60 years, and MVT inducible on EPS were all significantly associated with an increased likelihood of MVT detection. On multivariate analysis, the inducibility of MVT was the primary independent predictor of MVT detection but was of minimal incremental predictive value in the subgroup of patients with a history of only VF. When EPS results were not considered, arrhythmia history was the primary independent predictor of MVT detection. CONCLUSIONS: Patients with a history of only VF infrequently have MVT detected by their defibrillators. When these patients do detect MVT, it is faster than that detected in patients with a clinical history of MVT before ICD surgery. A significant percentage of VF survivors detected the abrupt onset of VF not preceded by MVT, suggesting that the deterioration of rapid MVT to VF is not the only clinically important mechanism of VF induction. These findings may have important implications for the understanding of the mechanism of VF induction and for use of an implantable defibrillator.

Truncated biphasic pulses for transthoracic defibrillation.

BACKGROUND: Early defibrillation is the single most important factor for improving out-of-hospital ventricular fibrillation resuscitation rates. To achieve the earlier response times required for survival, typically < 6 minutes from time of collapse, it will be necessary to equip a far wider network of first responders (firefighters, police, and other individuals with responsibility for public safety) with small, lightweight, and inexpensive automatic external defibrillators (AEDs). An important step in reducing the size and cost of AEDs will be to improve defibrillation efficacy. Because biphasic waveform defibrillation has had a favorable impact on implantable cardioverter-defibrillators (ICDs), there are reasons to believe that biphasic waveforms would also improve transthoracic defibrillators. Our purpose, therefore, was to examine the efficacy of two different low-energy biphasic truncated waveforms referenced to a standard damped sine waveform for transthoracic defibrillation in humans. METHODS AND RESULTS: We prospectively and randomly compared the transthoracic defibrillation efficacy of two different truncated biphasic waveforms, 115 J (70 microF) and 130 J (105 microF), with that of a standard 200-J (36-microF, 28-mH) damped sine wave pulse using right anterior and left lateral thoracic pads (R2 Medical Systems) in 30 cardiac arrest survivors during transvenous ICD surgery. The right anterior patch electrode was used as the cathode and the left lateral thoracic pad as the anode. Transthoracic ventricular defibrillation rescue shocks were tested after a failed transvenous defibrillation shock delivered in the course of ICD testing. Each of the three different rescue shocks was tested in random order in each patient. All shocks were delivered at end expiration. The investigators responsible for determining transthoracic shock efficacy were blinded throughout the study to the transthoracic rescue waveform used. A total of 33 patients were considered for study, but three patients failed to satisfy all entry criteria or did not have a sufficient number of ventricular fibrillation inductions to allow for testing of all three waveforms. Percent efficacy for the three waveforms was then compared in the 30 patients who satisfied entry criteria and completed the protocol. The study population had a mean age of 61 +/- 11 years, with 22 (73%) being men. The mean left ventricular ejection fraction was 0.39 +/- 0.14. Coronary artery disease was present in 22 (73%). The 115-J (70-microF) biphasic pulse, the 130-J (105-microF) biphasic pulse, and the 200-J (36-microF, 28-mH) damped sine wave pulse were equally effective, resulting in a 97% first-shock ventricular defibrillation efficacy rate. Each waveform failed to defibrillate once, with each waveform failing in a different patient. CONCLUSIONS: The results of this study suggest that biphasic truncated transthoracic shocks of low energy (115 and 130 J) are as effective as 200-J damped sine wave shocks used in standard transthoracic defibrillators. This finding may contribute significantly to the miniaturization and cost reduction of transthoracic defibrillators, which could enable the development of a new generation of AEDs appropriate for an expanded group of out-of-hospital first responders and, eventually, layperson use.

A prospective randomized comparison in humans of biphasic waveform 60-microF and 120-microF capacitance pulses using a unipolar defibrillation system.

BACKGROUND: Improving unipolar implantable cardioverter-defibrillator (ICD) effectiveness has favorable implications for ICD safety, efficacy, and size. Advances in defibrillation efficacy would accelerate ICD ease of use by decreasing device size and by minimizing morbidity and mortality related to an improved defibrillation safety margin. The specific purpose of the present study was to determine whether unipolar defibrillation efficacy could be improved further in humans by lowering biphasic waveform capacitance. METHODS AND RESULTS: We prospectively and randomly compared the defibrillation efficacy of a 60-microF and a 120-microF capacitance asymmetrical 65% tilt biphasic waveform using a unipolar defibrillation system in 38 consecutive cardiac arrest survivors before implantation of a presently available standard transvenous defibrillation system. The right ventricular defibrillation electrode had a 5-cm coil located on a 10.5F lead and was used as the anode. The system cathode was the electrically active 108-cm2 surface area shell (or "can") of a prototype titanium alloy pulse generator placed in a left infraclavicular pocket. The defibrillation pulse was derived from either a 60-microF or a 120-microF capacitance and was delivered from RV-->CAN. Defibrillation threshold (DFT) stored energy, delivered energy, leading-edge voltage and current, pulse resistance, and pulse width were measured for both capacitances examined. The 60-microF capacitance biphasic pulse resulted in a stored-energy DFT of 8.5 +/- 4.1 J and a delivered-energy DFT of 8.4 +/- 4.0 J. In 34 of 38 patients (89%), the stored-energy DFT was < 15 J. Leading-edge voltage at the DFT was 517 +/- 128 V. Mean pulse impedance for the 60-microF waveform was 60.6 +/- 7.1 omega. The 120-microF capacitance biphasic pulse resulted in a stored-energy DFT of 10.1 +/- 7.4 J and a delivered-energy DFT of 10.0 +/- 7.2 J (P = .13 and .13, respectively). In 28 of 38 patients (74%), the stored-energy DFT was < 15 J (P = .052). Leading-edge voltage at the DFT with the 120-microF capacitance pulse was 386 +/- 142 (P < .00001). Mean pulse impedance for the 120-microF waveform was 60.7 +/- 7.0 omega (P = .80). CONCLUSIONS: The results of the present study suggest that a relatively small capacitance, 60 microF, can be used for unipolar defibrillation systems without compromising defibrillation energy requirements compared with more typical ICD capacitance values, but this will require a higher circuit voltage. The use of lower capacitance also provides a modest increase in the percent of patients who have very low energy defibrillation requirements, an important issue should maximum ICD energy be decreased from the present level of 34 J. Such a move to smaller output devices could allow significant decreases in device size, a necessary feature of making cardioverter-defibrillator implantation comparable to that of standard pacemaker surgery.