Keith H. Newby

Sustained Ventricular Arrhythmias in Patients Receiving Thrombolytic Therapy Incidence and Outcomes

BACKGROUND Sustained ventricular tachycardia (VT) and fibrillation (VF) occur in up to 20% of patients with acute myocardial infarction (MI) and have been associated with a poor prognosis. The relationships among the type of arrhythmia (VT versus VF or both), time of VT/VF occurrence, use of thrombolytic agents, and eventual outcome are unclear. METHODS AND RESULTS In the GUSTO-I study, we examined variables associated with the occurrence of VT/VF and its impact on mortality. Of the 40 895 patients with ventricular arrhythmia data, 4188 (10.2%) had sustained VT, VF, or both. Older age, systemic hypertension, previous MI, Killip class, anterior infarct, and depressed ejection fraction were associated with a higher risk of sustained VT and VF (P<0.001). In-hospital and 30-day mortality rates were higher among patients with sustained VT/VF than among patients without sustained ventricular arrhythmias (P<0.001). Both early (<2 days) and late (>2 days) occurrences of sustained VT and VF were associated with a higher risk of later mortality (P<0. 001). In addition, patients with both VT and VF had worse outcomes than those with either VT or VF alone (P<0.001). Among patients who survived hospitalization, no significant difference was found in 30-day mortality between the VT/VF and no VT/VF groups. However, after 1 year, the mortality rate was significantly higher in the VT alone and VT/VF groups (P<0.0001). CONCLUSIONS Despite the use of thrombolytic therapy, both early and late occurrences of sustained VT or VF continue to have a negative impact on patient outcome; patients with both VT and VF had the worst outcome; and among patients who survived hospitalization, the 1-year mortality rate was significantly higher in those who experienced VT alone or VT and VF.

Implantable Cardioverter-Defibrillators and Pregnancy A Safe Combination?

BACKGROUND The purpose of this investigation was to evaluate the outcome of pregnancy in women with implantable cardioverter-defibrillators (ICDs). METHODS AND RESULTS A multicenter retrospective analysis was performed on women with an ICD who became pregnant. Data were collected on 44 patients. The mean age and ejection fraction at the time of the initial ICD implant were 25.6+/-4.9 years and 49.8+/-9.7%, respectively. The mean follow-up after the ICD implant was 4.8+/-2.8 years. Forty-two women had abdominally implanted generators, and 2 had a prepectoral device. Thirty had epicardial lead sensing systems, and 14 had transvenous. Thirty-six (82%) experienced no complications, and 8 (18%) had a medical or device-related complication. The ICD-related problems included tenderness at the ICD pocket scar (2 patients), generator migration (1), and pericarditis secondary to the epicardial patches (1). Medical complications were pulmonary embolism (1), therapeutic abortion (1), worsening hyperthyroidism (1), congestive heart failure (1), and weight loss (1). Thirty-seven women delivered vaginally, and 7 underwent cesarean section. Thirty-nine babies were born healthy, 1 was stillborn, 2 were small for gestational age, 1 had transient hypoglycemia, and 1 woman had a therapeutic abortion unrelated to the ICD. During pregnancy, 33 women received no ICD therapy, 8 had 1 shock, 1 had 5 discharges, 1 had 11 shocks, and 1 had 5 shocks. The total number of shocks during pregnancy ranged from 0 to 11, with an average of 0.66+/-1.9 discharges. Five women had 7 additional pregnancies without an ICD shock. CONCLUSIONS The mere presence of an ICD should not defer a women from becoming pregnant unless she has an underlying structural cardiac disease that is considered a contraindication. Pregnancy does not increase the risk of major ICD-related complications or result in a high number of ICD discharges.

Incidence and Clinical Relevance of the Occurrence of Bundle-Branch Block in Patients Treated With Thrombolytic Therapy

BACKGROUND Whether thrombolytic therapy alters the incidence and clinical outcome of bundle-branch block is unclear. METHODS AND RESULTS We examined the occurrence of new-onset bundle-branch block, both transient and persistent, in 681 patients with acute myocardial infarction enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction 9 and Global Utilization of Streptokinase and t-PA for Occluded Arteries 1 protocols. Each patient underwent continuous 12-lead ECG monitoring for 36 to 72 hours with the Mortara ST monitoring system. Bundle-branch block was characterized as right, left, alternating, transient, or persistent. The overall incidence of bundle-branch block was 23.6% (n = 161), with transient block in 18.4% (n = 125) and persistent block in 5.3% (n = 36). Right bundle-branch block was found in 13% (n = 89) of the population; left bundle-branch block was found in 7% (n = 48). Alternating bundle-branch block was seen in 3.5% (n = 24) of patients. Left anterior descending artery infarcts accounted for most bundles (54%, n = 79). Patients with bundle-branch block had lower ejection fractions, higher peak creatine phosphokinase levels (P < .0001), and more diseased vessels (P < .019). Mortality rates in patients with and without bundle-branch block were 8.7% and 3.5%, respectively (P < .007). A higher mortality rate was observed in the presence of persistent (19.4%) versus transient (5.6%) or no (3.5%) bundle-branch block (P < .001). CONCLUSIONS Thrombolytic therapy reduces the overall mortality rate associated with persistent bundle-branch block. However, persistent bundle-branch block remains predictive of a higher mortality rate than either transient or no bundle-branch block. Continuous 12-lead ECG monitoring provides an accurate characterization of the incidence and type of conduction disturbances after acute myocardial infarction.

Combining thrombolysis with the platelet glycoprotein IIb/IIIa inhibitor lamifiban: Results of the platelet aggregation receptor antagonist dose investigation and reperfusion gain in myocardial infarction (PARADIGM) trial

OBJECTIVES The trial was designed to assess the safety, pharmacodynamics and effects on reperfusion of the platelet glycoprotein (GP) IIb/IIIa inhibitor lamifiban when given with thrombolysis to patients with ST segment elevation acute myocardial infarction. BACKGROUND Studies of fibrinolytic agents in acute myocardial infarction have demonstrated a direct relationship between early complete reperfusion and survival. Blockade of the platelet GP IIb/IIIa receptor complex inhibits platelet aggregation and may speed reperfusion when given in conjunction with thrombolysis to patients with acute myocardial infarction. METHODS Patients with ST segment elevation presenting within 12 h of symptom onset who were treated with either tissue-plasminogen activator or streptokinase were enrolled in this three-part Phase II dose exploration study. In Part A, all patients received the GP IIb/IIIa inhibitor lamifiban in an open-label, dose escalation scheme. Parts B and C were a randomized, double-blind comparison of a bolus plus 24-h infusion of lamifiban versus placebo with patients randomized in a 2:1 ratio. The goal was to identify a dose(s) of lamifiban that provided >85% adenosine diphosphate (ADP)-induced platelet aggregation inhibition. A composite of angiographic, continuous electrocardiographic and clinical markers of reperfusion was the primary efficacy end point, and bleeding was the primary safety end point. RESULTS Platelet aggregation was inhibited by lamifiban in a dose-dependent manner with the highest doses exceeding 85% ADP-induced platelet aggregation inhibition. There was more bleeding associated with lamifiban (transfusions in 16.1% lamifiban-treated vs. 10.3% placebo-treated patients). Lamifiban induced more rapid reperfusion as measured by all continuous electrocardiographic (ECG) parameters. CONCLUSIONS Lamifiban given with thrombolytic therapy appears to be associated with more rapid and complete reperfusion than placebo. As expected in this small sample, there were no obvious clinical benefits to lamifiban over placebo. Reconciliation of ECG monitoring with clinical outcomes will require a larger, adequately powered clinical trial.

Impact on ventricular function and quality of life of transcatheter ablation of the atrioventricular junction in chronic atrial fibrillation with a normal ventricular response

We assessed left ventricular function and quality of life after atrioventricular junction ablation and pacemaker implant in 14 patients with chronic atrial fibrillation and normal ventricular response. A significant improvement in left ventricular ejection fraction, fractional shortening, and functional capacity were observed at follow-up, suggesting that in patients with chronic atrial fibrillation a regular heart beat may be preferable over rate control.

Testing different biphasic waveforms and capacitances: Effect on atrial defibrillation threshold and pain perception

OBJECTIVES The goal of this study was to compare the effect of different tilts and capacitances for biphasic shocks on atrial defibrillation efficacy and pain threshold. BACKGROUND Although biphasic shocks have been shown to be superior to monophasic shocks, the effect of tilt and capacitance on atrial defibrillation success and pain perception has not been studied in patients. METHODS Atrial defibrillation threshold (DFT) testing was performed using a right atrial appendage/coronary sinus lead configuration in 38 patients with a history of paroxysmal atrial fibrillation undergoing an invasive electrophysiologic study. Biphasic waveforms with 40%, 50%, 65%, 80%, 30%/50% and 40%/50% were tested randomly in 22 patients (Group 1). In 16 patients (Group 2), a 65% tilt waveform with 50- and 120-microF capacitance was tested. Before sedation, pain sensation was graded by 15 patients in Group 1 after delivery of a 0.5-J shock and by 10 patients in Group 2 after two 1.5-J shocks with 50- and 120-microF capacitance were delivered. RESULTS The DFT energy for the 50% tilt waveform was significantly lower than the 65%, 80% and 30%/50% tilt waveforms. The 40%/50% tilt waveform provided slightly lower energy requirements than the 50% tilt waveform. Nine patients (60%) described the 0.5-J shock as very painful, and four (26.6%) complained of slight pain. The 50-microF capacitor lowered energy requirements compared with the 120-microF capacitor. Six patients (60%) perceived the 1.5-J 50-microF capacitor shock as more painful, whereas three (30%) perceived both shocks as equally painful. CONCLUSIONS Biphasic waveforms with 50% tilt in both phases and a smaller tilt in the positive phase than that in the negative phase (40%/50%) provided a decrease in energy requirements at atrial DFT. In addition, stored energy was reduced by biphasic shocks with 50-microF capacitance compared with 120-microF capacitance. Despite the reduction in energy requirements, shocks < 1 J continued to be perceived as painful in the majority of patients.

Catheter ablation approach on the right side only for paroxysmal atrial fibrillation therapy: long-term results.

We report the long‐term follow‐up of a right side only catheter ablation approach for paroxysmal AF. Eighteen patients with AF refractory to drugs entered the study. Ablation was attempted in the right atrium only by creating linear lesions based on a specific design including from two to four linear lesions. Induction of AF was attempted before ablation and after placement of the lesions. A septal lesion was performed in nine patients. In ten patients atrial defibrillation thresholds (ADFTs) before ablation and following creation of the linear lesions were compared. After a mean follow‐up of 22±11 months, seven patients had recurrence of AF, and another nine patients experienced atria flutter or atrial tachycardia. Five patients remained in sinus rhythm without medications and four required the use of drugs. Three patients had sporadic AF and six were in chronic AF. The recurrence rate was similar in patients with and without the septal lesion. However, a cure with right side ablation appeared to be predicted by the presence of disorganized and earlier activity in the high right atrium and crista terminalis. Linear lesions in the right atrium were associated with a lower ADFT (pre 2.6 ± 04 J vs post 1.7 ± 0.6 J). In conclusion, in a small number of patients, control of AF can be obtained with a right side only approach. Certain activation patterns may identify patients suitable to this approach. No specific lesion pattern appeared more effective. Eight atrial linear lesions resulted in lower ADFT.

Recurrence of neurocardiogenic syncope without pharmacologic interventions

In 54 patients with positive tilt and who refused medical therapy, we observed a significant decrease in the frequency of syncopal spells after diagnosis and counseling. However, symptoms were reported at follow-up by 64.8% of the patients and were predicted by the frequency and total number of syncope episodes before upright tilt.

Use of sublingual nitroglycerin during head-up tilt-table testing in patients >60 years of age.

Previous work had demonstrated a reduced specificity associated with head-up tilt protocols using high-dose isoproterenol in patients between 20 and 50 years of age. We evaluated the specificity of head-up tilt testing using different isoproterenol infusion doses and administration of nitroglycerin in patients aged >60 years. In addition, whether the same protocols have impact on the sensitivity of the test was also assessed. One hundred sixty subjects were included in this study. Seventy-six were volunteers randomized to either head-up tilt test with low-dose, 3- and 5-microg/min of isoproterenol (group I) or to a protocol including 0.4 mg of sublingual nitroglycerin (group II). In addition, after an upright tilt drug-free state, 58 patients with a history of syncope underwent repeat head-up tilt with increasing doses of isoproterenol infusion, followed by sublingual nitroglycerin if the test result remained negative. The remaining 33 patients were subjected to the nitroglycerin protocol after the drug-free state phase. In the control groups, the incidence of false-positive responses was 88% and 95%, respectively. In patients with syncope after a negative test result during 5 microg of isoproterenol infusion, nitroglycerin administration increased the number of positive responses from 45% to 79%. The percentage of positive tilt in patients undergoing nitroglycerin administration after the drug-free state part of the protocol was 78%. Administration of nitroglycerin was the most significant predictor of a positive upright tilt in patients with syncope. In subjects aged >60 years, head-up tilt protocols with high-dose isoproterenol infusion and nitroglycerin maintained an adequate specificity. In this subset of patients, nitroglycerin seemed to provide a better sensitivity than isoproterenol.

Prospective Evaluation of New and Old Criteria to Discriminate Between Supraventricular and Ventricular Tachycardia in Implantable Defibrillators

This study was designed to evaluate the ability to distinguish between supraventricular tachycardias (SVTs) and ventricular tachycardias (VTs) based on onset, stability, and width criteria in an implantable defibrillator. Inappropriate detection of atrial fibrillation and sinus tachycardia is a common problem in patients with implantable defibrillators. The onset, stability, and width criteria were studied in 17 patients who underwent implantation of a Medtronic 7218C implantable defibrillator by inducing sinus tachycardia and atrial fibrillation. Additional data on the width criteria was obtained by pacing at separate sites in both the left and right ventricle. Patients were studied at different times for up to 6 months to determine any changes in the criteria. The onset and stability criteria caused inappropriate detections in 36% and 12% of the episodes, respectively. The addition of the width criteria decreased the inappropriate detection using the onset and stability criteria to 5% and 2%, respectively. Pacing from the RV apex, RV outflow tract, and LV apex was appropriately detected as wide in 76%, 41%, and 94%, respectively. The width criteria changed over time in individual patients, but was stable by 6 months in all but one patient. No single criterion is satisfactory for distinguishing between SVT and VT in this patient population, but the combination of criteria seems to provide better discrimination. The width criteria can change dramatically over time and needs to be monitored carefully. Newer algorithms will need to be developed to allow better detection of supraventricular tachycardias.