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Notes: Interest in development of mechanical cardiac support has grown out of the realization of the enormous impact of heart failure-related mortality, the limited potential to provide cardiac transplantation (approximately 2000 patients/year in the USA), and the long waiting period required, even in appropriately selected patients. Both left ventricular assist devices (LVADs) and total artificial hearts (TAHs) have been developed to assist in addressing these needs. This review focuses on TAH development. The first bridging TAH was implanted in 1969, and the first permanent device in 1982 with a patient survival of 112 days. Since that time, evolution of device design and manufacture, patient selection, and ancillary therapies have occurred. Worldwide clinical application now spans 27 years and includes experience with TAH implantation in 311 patients, with eight different pneumatically driven devices implanted either as permanent devices (N = 5) or as temporary, bridging therapy to transplantation (N = 306), with all but four implanted after 1984. Utah-developed TAHs represent the largest source of this experience (N = 287). In the earlier (Symbion manufactured) TAH series (N = 204, 1985–1992), 42% of implanted patients and 59% of transplanted patients were discharged alive from the hospital, and average support time was 24 days. In the current (Cardio West manufactured) series (N = 78, 1993–1996), 67% of implanted patients and 94% of transplanted patients were discharged alive, and average support time is 30 days. Of transplanted and discharged patients, 98% remain alive. With improvements in device design and manufacture, as well as anticoagulant regimens, the incidence of stroke with long-term deficits has decreased from 3 out of 7 in 1984-1985 to 1 out of 61 in 1988, with no permanent deficits since then. Infection rates have also decreased. Only one implanted patient died of TAH mechanical failure (an early experience). Based on this evolving experience, use of the TAH as a bridge to transplantation in selected patients who are not appropriate for an LVAD has become a viable current therapeutic option. Further TAH development and application is anticipated.

Notes: Background: Spontaneous variability of ventricular arrhythmia has been described in patients with chronic stable ventricular arrhythmias and in patients with chronic heart failure. However, no data are available on spontaneous variability in patients with sustained ventricular tachyarrhythmias. Thus, the present study was designed to prospectively determine the extent of spontaneous variability of ventricular arrhythmia in patients with sustained ventricular tachyarrhythmias and in survivors of cardiac arrest.Methods: Ventricular arrhythmia variability was determined in 470 patients (413 men, 57 women), age (mean ± SD) 64.6 ± 9.5 years with documented ventricular tachycardia (VT), cardiac arrest, or syncope who were prospectively enrolled in a randomized trial of the comparison of electrophysiological testing with Holter monitoring to predict antiarrhythmic drug efficacy. Coronary artery disease was present in 398 (85%) patients, and the mean left ventricular ejection fraction was 0.32 ± 0.13. They underwent two 24-hour ambulatory recordings separated by 1 day. Spontaneous variability was determined for total premature ventricular complexes (PVCs), pairs, and VT events.Results: Arithmetic mean of hourly total PVCs on day 1 was 315 ± 425. The 95% confidence limit of spontaneous reduction in total PVC count was 71%. Corresponding values for pairs, VT events of 3–15 beats, 〈 15 beats, or 〈 15 seconds were 72%, 80%, 94%, and 95%, respectively. The percentage increases in total PVCs, pairs, and VT events 3–15 beats, 〈 15 beats, and 〈 15 seconds were 243%, 259%, 397%, 1553%, and 1756%, respectively. The percentage reduction required to show a true drug effect was 63% for patients with an ejection fraction 〉 0.32 and 76% for those with an ejection fraction ltm 0.32 (P = 0.024). Patients who presented with unmonitored syncope showed less spontaneous variability than either patients with documented, sustained VT or cardiac arrest.Conclusions: Marked spontaneous variability of ventricular arrhythmias is observed in patients with sustained ventricular tachyarrhythmias. Variability is affected by the degree of left ventricular dysfunction. The lowest variability was observed in patients presenting with unmonitored syncope. Thus, large changes in arrhythmia frequency must be observed in this population, as in others, to be ascribed to drug effect.

Notes: Endomyocardial biopsy is a reliable and reproducible technique to confirm or establish a clinical diagnosis in many cases of idiopathic heart muscle disease. Our overall experience of 243 consecutive nontransplant related biopsy procedures (combined experience of previously reported and current series) comparing a new femoral venous (n = 94) with a standard internal jugular venous (n = 149) approach is reviewed. In the current series, the femoral (n = 59) and the internal jugular (n = 80) approaches, performed on 139 consecutive nontransplant-related procedures (466 myocardial samples), were compared. Vascular access was achieved in all femoral procedures; the internal jugular vein could not be located in 4% (three) of neck approaches (P = NS). Myocardial sampling was sufficient in all internal jugular procedures; sampling was adequate in all femoral procedures except two (3%, P = NS). Two cases of hematoma were observed after an internal jugular approach. Pericardial effusion was observed in one patient after femoral and in one patient after internal jugular approaches (P = NS), and in the latter case, tamponade developed requiring intervention. Transient atrioventricular block (complete in 2 and 2:1 in 1) developed in three patients (femoral procedures), but all of these patients had shown predisposing complete left bundle branch block on their electrocardiogram. No difference in vascular access, sampling efficiency and complication rate between our previous and current series regarding the internal jugular and femoral approaches was observed. Our overall experience with the femoral and internal jugular approaches was similar for complication rate (1% in both). Vascular access was better overall with the femoral approach (100% vs 93%, P 〈0. 01), reflecting more difficulty with internal jugular access in the first series. Thus, the femoral venous approach described is comparable in efficacy and safety to the standard internal jugular approach and may be especially useful as an alternative to right ventricular biopsy when the internal jugular vein cannot be successfully cannulated or when a cardiac catheterization from the femoral area is being performed at the same time for other reasons.

Notes: The results of an overview of early (90–240 min) and late (24 hours or more) patency and of stroke rates for each of the three commercially available thrombolytic agents, streptokinase, alteplase, and anistreplase are presented. Studies included in this analysis are all those published between 1985 and March 1992 and focus on the licensed dosage regimens of each agent. The rates of early and late patency for streptokinase were 64.7% and 80.8%; for alteplase, 66.6% and 73.7%; and for anistreplase, 72.1% and 84.5%. The rates of total and hemorrhagic stroke for streptokinase were 0.69% and 0.17%; for alteplase, 1.27% and 0.50%; and for anistreplase, 0.91% and 0.38%. These results provided evidence that the rates of early and late patency appeared to be greatest for anistreplase and that the rates of stroke are within “acceptable” ranges for all three thrombolytic agents with streptokinase affording the lowest rate.

Notes: Trials during the 1980s established that thrombolytic therapy restores coronary blood flow rapidly and reduces mortality compared to control or placebo therapy in acute myocardial infarction. Comparative studies have generated controversy, however, in that the newer agents tissue plasminogen activator (tPA) and anistreplase (APSAC), shown to open arteries more rapidly than streptokinase (SK), achieve no greater mortality reductions. In these trials, tPA may have been disadvantaged because adjunctive IV heparin therapy was not given. This possibility is being explored in the Global Utilization of Streptokinase and tPA for Occluded Coronary Arteries (GUSTO) study. However, heparin may not entirely explain the discrepancy because (1) among patients in International Studies of Infarct Survival (ISIS-3) given IV heparin out of protocol, no difference in mortality between tPA and SK was observed; (2) reinfarction was actually slightly less after tPA; and (3) APSAC, longer acting and more efficient than SK and not requiring early IV heparin, achieved no greater mortality reductions. Another explanation for the discrepancy between 90-minute patency and mortality effects among agents is that benefit in the usual time frame of treatment (2–6 hours after onset of symptoms) depends more on diastolic effects (improved healing with preserved diastolic size, shape) than on systolic effects (reduction in infarct size) and is less time-dependent. A similar survival outcome is then consistent with the observation that all three agents lead to similar plateau patency rates at ≥ 3 hours. Prehospital throtnbolysis trials are exploring the possibility that greater functional and mortality benefits are associated with therapy given very early (within 1–2 hours). Differential benefits might be seen when regimens with differing thrombolytic efficiencies are given within 1–2 hours of symptom onset, but this possibility must be established by direct comparative trials. Future trials should emphasize improved myocardial salvage by more rapid delivery of thrombolytic therapy as well as the use of more efficient thrombolytic regimens.

Notes: Trials in Ventricular Tachycardias. Recent clinical trials in patients with ventricular tachycardia (VT) or fibrillation (VF) have occurred in the setting of the disappointing results of postinfarction secondary prevention studies using Class I antiarrhythmics (e.g., CAST). ESVEM addressed in a randomized trial whether electrophysiologic study (EPS) or Hotter monitoring (HM) is a more accurate predictor of long-term antiarrhythmic drug efficacy in VT/VF patients (N = 486) and what the relative efficacy of various antiarrhythmic agents is for VT/VF. Surprisingly, arrhythmia recurrence rates were not significantly different by the method of determining an efficacy prediction. However, arrhythmia recurrence and mortality were lower (by about 50% at 1 year) in patients treated with sotalol (a mixed Class II/III agent) than with other drugs (Class I). CASCADE evaluated empiric amiodarone versus guided (EPS or HM) standard (Class I) therapy in survivors of out-of-hospital cardiac arrest due to VF. The primary endpoint of cardiac death, resuscitated VF, or syncopal shock (in ICD patients) was reduced by amiodarone compared with conventional therapy (9% vs 23% at 1 year). An interim report of the ongoing CASH study suggested in 230 survivors of cardiac arrest that propafenone (Class IC) provided less effective prophylaxis (approximately 20% 1-year mortality) compared with randomly assigned therapies with amiodarone, metoprolol, or an ICD (approximately 14% mortality rates) and was excluded from further study. These studies have led to a paradigm shift in the approach to antiarrhythmic therapy of VT/VF: drugs with antisympathetic plus Class III (refractoriness prolonging) action (i.e., sotalol, amiodarone) are superior to traditional drugs with Class I (conduction slowing) effects, even when guided by EPS or HM.