Treatment of underlying atrial fibrillation: paced rhythm obscures recognition.

OBJECTIVES: The purpose of this study was to evaluate the rate of recognition of atrial fibrillation (AF), use of warfarin and prevalence of cerebrovascular accident (CVA) in paced versus unpaced patients during admission to a tertiary care teaching hospital. BACKGROUND: The presence of AF underlying a continuously paced rhythm may be under recognized and result in a lower rate of anticoagulation and higher incidence of CVA. METHODS: The identification of AF on 12 lead electrocardiogram (ECG) and telemetry, "optimal use" of anticoagulants that is, warfarin or aspirin, when warfarin is contraindicated and history of prior CVA was studied in three groups: 1) group A with continuously paced rhythm on ECG and telemetry (n = 30), 2) group B with intermittently paced rhythm on ECG and telemetry (n = 59), and 3) group C with persistent AF and no permanent pacemaker (n = 50). RESULTS: The identification and documentation of AF was significantly lower in the continuously paced group A (20%) versus the intermittently paced group B (44%). Both groups A and B were substantially lower than unpaced controls. "Optimal use" of anticoagulants was significantly lower in group A (40%) compared with groups B (78%) and C (72%) but was not different between groups B and C. The prevalence of prior CVA was not significantly different between the three groups. CONCLUSIONS: All ECGs in patients with paced rhythm should be examined closely for underlying AF to prevent under-recognition and under-treatment with anticoagulants.

Prophylactic oral amiodarone compared with placebo for prevention of atrial fibrillation after coronary artery bypass surgery.

BACKGROUND: Postoperative atrial fibrillation occurs in 20% to 40% of patients undergoing coronary artery bypass grafting (CABG) and contributes to delayed recovery, increased length of stay, and increased hospital cost. Measures at preventing postoperative atrial fibrillation have had mixed results. We report a double-blind trial comparing oral amiodarone with placebo for the prevention of atrial fibrillation after CABG. METHODS AND RESULTS: All patients undergoing CABG were considered eligible. Exclusion criteria included bradycardia (<50 beats/min), prior Atrial fibrillation, concurrent therapy with antiarrhythmic drugs, or concomitant valve surgery. Patients were given 2 g of amiodarone (73 patients) or placebo (70 patients) in divided doses 1 to 4 days before surgery and 400 mg daily for 7 days postoperatively. Atrial fibrillation occurred in 24.7% (18 of 43) of patients receiving amiodarone and 32. 8% (23 of 70) of patients receiving placebo (P =.30). Heart rate at onset of atrial fibrillation was 133.4 +/- 26.6 beats/min for amiodarone compared with 152.9 +/- 31.6 beats/min for placebo (P =. 04). Duration of atrial fibrillation was 10.2 +/- 8.1 hours for amiodarone compared with 16.2 +/- 27.5 hours for placebo (P =.67). Patients receiving both beta-blockade and amiodarone had a 16.7% incidence of atrial fibrillation compared with 31.9% in the remaining patients (P =.10). Atrial fibrillation was associated with an increased cost of $7011 compared with those who remained in sinus rhythm ($23,869 +/- $20,894 vs $16,857 +/- $5401 in sinus rhythm). Hospital cost of those taking amiodarone was $18,895 +/- $13,267 compared with $18,839 +/- $11,537.18 for placebo (P =.42). CONCLUSION: Postoperative CABG atrial fibrillation is associated with prolonged hospital stay and increased cost. Prophylactic oral amiodarone did not statistically alter the incidence or duration of atrial fibrillation after CABG, although favorable trends were noted. Hospital cost was not affected by therapy with amiodarone.

A prospective randomized trial of prevention measures in patients at high risk for contrast nephropathy: results of the P.R.I.N.C.E. Study. Prevention of Radiocontrast Induced Nephropathy Clinical Evaluation.

OBJECTIVES: This study was done to test the hypothesis that a forced diuresis with maintenance of intravascular volume after contrast exposure would reduce the rate of contrast-induced renal injury. BACKGROUND: We have previously shown a graded relationship with the degree of postprocedure renal failure and the probability of in-hospital death in patients undergoing percutaneous coronary intervention. Earlier studies of singular prevention strategies (atrial natriuretic factor, loop diuretics, dopamine, mannitol) have shown no clear benefit across a spectrum of patients at risk. METHODS: A prospective, randomized, controlled, single-blind trial was conducted where 98 participants were randomized to forced diuresis with intravenous crystalloid, furosemide, mannitol (if pulmonary capillary wedge pressure <20 mm Hg), and low-dose dopamine (n = 43) versus intravenous crystalloid and matching placebos (n = 55). RESULTS: The groups were similar with respect to baseline serum creatinine (2.44+/-0.80 and 2.55+/-0.91 mg/dl), age, weight, diabetic status, left ventricular function, degree of prehydration, contrast volume and ionicity, and extent of peripheral vascular disease. The forced diuresis resulted in higher urine flow rate (163.26+/-54.47 vs. 122.57+/-54.27 ml/h) over the 24 h after contrast exposure (p = 0.001). Two participants in the experimental arm versus five in the control arm required dialysis, with all seven cases having measured flow rates <145 ml/h in the 24 h after the procedure. The mean individual change in serum creatinine at 48 h, the primary end point, was 0.48+/-0.86 versus 0.51+/-0.87, in the experimental and control arms, respectively, p = 0.87. There were no differences in the rates of renal failure across six definitions of renal failure by intent-to-treat analysis. However, in all participants combined, the rise in serum creatinine was related to the degree of induced diuresis after controlling for baseline renal function, r = -0.36, p = 0.005. The rates of renal failure in those with urine flow rates greater than 150 ml/h in the postprocedure period were significantly lower, 8/37 (21.6%) versus 28/61 (45.9%), p = 0.03. CONCLUSIONS: Forced diuresis with intravenous crystalloid, furosemide, and mannitol if hemodynamics permit, beginning at the start of angiography provides a modest benefit against contrast-induced nephropathy provided a high urine flow rate can be achieved.

Worsening of ventricular tachycardia by amiodarone.

The details of worsening of ventricular tachycardia in 8 (4.1%) of 194 patients receiving treatment with amiodarone are reported. Two forms of amiodarone-induced tachycardia were recognized: first, the development of new tachycardias (three patients) and second, a change in the pattern of recurrence of clinical tachycardia (five patients). In retrospect, the time from the initiation of amiodarone to the initial documentation of worsening ranged from 1 to 23 days (mean +/- SD, 9.4 +/- 8.2 days) and the time from the initiation of therapy to the recognition of worsening ranged from 6 to 26 days (14.6 +/- 10.1 days). Seven patients survived the worsening of tachycardia and one died. The total dose of amiodarone received and the duration of administration did not correlate with time to manifestation or time to resolution of worsening. This report emphasizes that worsening of ventricular tachycardia as a result of amiodarone is often difficult to differentiate from inadequate drug loading or early recurrence of 2 patient's clinical tachycardia. Further, because of the pharmacokinetics of the drug, the manifestations of worsening may be prolonged. In the cases reported, it ranged from 2 to 26 days (7.9 +/- 8.3 days), which is longer than previously reported. Because of the potential for amiodarone to cause life-threatening worsening of ventricular tachycardia and in accordance with current results, a period of in-hospital monitoring of at least 10 days at the start of therapy with amiodarone is recommended.

Discrimination of anterograde from retrograde atrial electrograms for physiologic pacing.

The morphology of bipolar electrograms recorded in the right atrium was examined in nine patients in an attempt to discriminate retrograde from anterograde atrial signals to an extent that would be useful for physiologic pacing. Peak-to-peak amplitude, duration, square root of energy (energy), maximum slew rate, mean slew rate, and polarity were examined in the time domain. Maximum frequency, half-power frequency, Fourier amplitude peak, and frequency of peak were measured in the frequency domain. There was a significant difference between anterograde and retrograde signals for all variables related to amplitude; these variables are peak-to-peak amplitude, energy, Fourier amplitude peak, maximum slew rate and mean slew rate. In seven of nine patients there was at least one variable sufficiently discriminating to insure reliable detection of anterograde signals while systematically rejecting retrograde signals. However, no individual variable was able to effect this discrimination in more than four patients and at least three variables were needed for all seven patients: maximum frequency, one of either energy and Fourier amplitude peak, and one of either frequency of peak or half-power frequency (six possible combinations). Thus, although differences between anterograde and retrograde atrial activity can be demonstrated in most patients, no single parameter displays sufficient discriminating power to facilitate physiologic pacing in patients exhibiting retrograde activity.

Hemorrhage vs rethrombosis after thrombolysis for acute myocardial infarction.

To determine whether or not the timing of heparin infusion affects either bleeding or reocclusion following intracoronary streptokinase for acute myocardial infarction, heparin was infused immediately after streptokinase in 89 patients and was delayed for 12 hours in the subsequent 93. Bleeding occurred in 22 immediate-heparin patients and was major in five (one fatal); there were 14 hemorrhages in the delayed-heparin group, all minor. At discharge, reocclusions were observed in 18% (12/68) of immediate-heparin patients, and 11% (3/27) of the latter. Bioassayed fibrinogen levels displayed sustained depression regardless of bleeding for 20 hours after streptokinase; however, defibrinogenation measured by immunoassay was much less striking. This suggests that high levels of fibrinogen degradation products spuriously affect the bioassay of fibrinogen. We conclude that bleeding is related to the anticoagulant effects of fibrinogen degradation products interacting with heparin, and may be largely independent of hypofibrinogenemia. Delaying heparin for 12 hours may decrease the risk of bleeding while little affecting the risk of reocclusion.

The influence of infarction site and size on the ventricular response to coronary thrombolysis.

To test the hypothesis that myocardial infarction (MI) size rather than location determines the ventricular response to reperfusion, we studied 69 patients receiving intracoronary streptokinase within five hours of chest pain onset who displayed sustained reperfusion at 8.4 +/- 3.4 (SD) days. Twenty reperfusion failures served as controls. There were 31 patients with anterior MIs, 18 of which were estimated to be large based on an ejection fraction (EF) at reperfusion of less than 50%; 14 of 38 patients with inferior MIs also had large MIs. The EF increased at follow-up by 6.4% +/- 2.6% in patients with large anterior MIs and by 8.2% +/- 2.5% in those with large inferior MIs; in contrast, it increased by only 1.8% +/- 2.6% in patients with small anterior MIs and significantly decreased by 5.8% +/- 1.9% in patients with small inferior MIs. Six controls with large MIs (four anterior) displayed no change in EF; in 14 with small MIs (ten inferior), it fell slightly. There were no significant group differences in the number of diseased vessels, residual stenosis, or collaterals. It is concluded that MI size, not site, largely determines the ventricular functional response to early reperfusion; thus, patients with inferior MIs cannot be disqualified on this basis alone for thrombolytic therapy.

Sequelae of left ventricular electrical endocardial ablation.

The endomyocardial residual effects of left ventricular endocardial electrical ablation utilizing unipolar and bipolar electrode catheters were studied in 15 dogs. Histopathologic techniques specific for contraction band necrosis revealed that the mean maximal depth and breadth of necrosis was 0.63 +/- 0.44 and 1.23 +/- 0.82 cm, respectively. The dimensions of necrosis were significantly increased when utilizing larger energy discharges, especially through unipolar electrodes. Four dogs died during the procedure, three from ventricular fibrillation and one from asystole, and two died suddenly within the succeeding 24 hours. Endocardial thrombi were noted at necropsy in two dogs. In conclusion, transcatheter endocardial electrical ablation may destroy a sufficient mass of myocardium to interrupt arrhythmogenic conduction tissue, especially when larger currents are delivered through unipolar electrodes. However, serious ventricular arrhythmias and endocardial thrombi should be anticipated.

The effect of electrode position on atrial sensing for physiologically responsive cardiac pacemakers.

Fully automatic pacing systems rely on accurate identification of spontaneous atrial signals for physiologically responsive pacing. These signals must be discriminated from far-field ventricular activity, which might otherwise be sensed in the atrium. To amplify on the previously reported superiority of bipolar signals and high-impedance circuitry for atrial sensing, we studied the effects of various intraatrial electrode positions on the atrial and ventricular contribution to electrograms recorded in this chamber. Compared with other intraatrial endocardial sites, right atrial signals were greatest in amplitude and slew rate in the appendage (RAA), averaging 3.3 +/- 0.41 mV and 1.15 +/- 0.16 V/sec (mean +/- SEM), respectively. These values were substantially higher than in the low atrium (p less than 0.001 and 0.0005 for amplitude and slew rate, respectively) and the high lateral atrium (p less than 0.05 for slew rate). Appendage atrial electrograms also had significantly higher amplitude and slew rate than far-field R waves recorded here (p less than 0.0001 for both). Additionally, the greatest difference in spectral content between atrial and far-field ventricular signals was also observed in the RAA. Thus, parameters in the domain of both time and frequency identified the RAA as the superior location for atrial sensing. Except for phrenic nerve problems with pacing, the HRA also appears to be a suitable electrode location for sensing. These considerations are germane in light of a growing number of atrial active and passive fixation leads now being employed for physiologic pacing.

Prevalence and significance of ventriculoatrial conduction.

Because retrograde atrioventricular conduction may predispose to pacemaker-induced tachycardia when DDD pacing is employed, we assessed ventriculo-atrial conduction in 117 patients undergoing electrophysiologic studies. Ventriculo-atrial conduction was present in 40% with a mean (+/- sem) conduction time of 205 +/- 12 ms. The maximum VA conduction time following minimum extrastimulus intervals averaged 258 +/- 14 ms. Antegrade AV nodal properties predicted VA conduction in only 67% by using stepwise discriminant analysis. Only the PR interval, AH interval, and AV nodal effective refractory periods were helpful in predicting ventriculo-atrial conduction. Although ventriculo-atrial conduction time increased on most antiarrhythmic drugs, it was infrequently eliminated.

Hemorrhage and the products of fibrinogen digestion after intracoronary administration of streptokinase.

Hemorrhage was prospectively identified in 26 of 116 consecutive patients (23%) who were receiving intracoronary streptokinase for occlusive coronary thrombi producing infarction. Bleeding was not influenced by the dose of streptokinase or the method of cardiac catheterization. Before treatment, prothrombin time and partial thromboplastin time were normal in both bleeders and nonbleeders. Fibrinogen levels measured by bioassay after streptokinase (mean +/- SEM) were 62 +/- 29 mg/dl in patients with major bleeding, 111 +/- 26 mg/dl in patients with minor bleeding, and 109 +/- 13 mg/dl in nonbleeders (p = NS). The regression slope b calculated from poststreptokinase fibrinogen time-concentration data in 71 patients was 4.7 mg/dl/hr. However, mean fibrinogen concentrations calculated at sequential 5 hr intervals revealed no net regeneration for the first 20 hr after thrombolysis. The apparent fibrinogen regeneration rate was less than normal (31 mg/kg/day) for more than 10 hr but subsequently increased to 94 +/- 10 mg/kg/day by the second day. The initial apparent latency of fibrinogen regeneration paralleled the sharp rise in fibrinogen degradation products, which began to decline after 20 hr of treatment but remained elevated well into the second day. Because of their anticoagulant effects, these products may interfere with the fibrinogen assay, causing spuriously low results. Thus, whether the early delay in fibrinogen regeneration is real or simply a reflection of the effects of fibrinogen degradation products on the bioassay, it signals the time for caution in initiating systemic heparin therapy.

The significance of surface changes on explanted polyurethane pacemaker leads.

Although over 140,000 polyurethane leads have been implanted in humans, a controversy has recently arisen dealing with the significance of frequently detected irregularities on explanted insulator surfaces by scanning electron microscopy (SEM), and their relationship with lead failure. We therefore implanted ten, 6 Fr atrial polyurethane leads and an equal number of 4 Fr ventricular leads in dogs for a mean 26 +/- 2 and 29 +/- 2 weeks, respectively. Fourteen leads were removed utilizing metered force. The remaining leads were removed surgically without force at the termination of the study. Specimens were stored in saline prior to physical testing (tensile strength and elongation) of intravascular and extravascular lead segments. Similarly stored samples were prepared for SEM analysis. The polyurethane insulator disconnected from the electrode on forcible removal in three atrial and two ventricular leads (concordant connected from the electrode on forcible removal in three atrial and two ventricular leads (concordant for two pairs). There was no significant relationship between the results of physical testing and extraction force, lead size, integrity on removal, sample location or SEM scores. Chemical analysis of surface changes employing both x-ray and electron emission spectroscopy failed to reveal evidence of protein adsorption or liquid impregnation. Samples soaked in sodium hydroxide displayed the same SEM irregularities. The combined effects of fissuring and fluid absorption by polyurethane did not affect chronic anodal or cathodal thresholds. In conclusion, a clear relationship between chronic surface irregularities and the insulator function of polyurethane, its relationship between chronic surface irregularities and the insulator function of polyurethane, its integrity in situ, or its strength at explant has not been established by this relatively short-term study. On the other hand, a potential time-dependent impact of these changes on lead performance has not been excluded. Moreover, only a single species of medical grade polyurethane has been clinically evaluated. Thus, the ultimate place of polyurethane leads in pacing systems has yet to be determined.

Intracoronary streptokinase in clinical practice.

The candidacy for streptokinase (SK) infusion was studied in 95 patients displaying ECG evidence of acute or impending infarction who were catheterized within 5 hours of the onset of chest pain. Intracoronary SK was administered to 84 patients in whom occlusions of the infarct-related vessel were identified, with early recanalization having been achieved in 74 (88%). Because of completeness of studies, a data base of 72 patients was employed for further analysis. Recanalization was sustained at follow-up in 45 of 55 patients (82%). Spontaneous thrombolysis was demonstrated at follow-up in five patients (8%) initially resistant to SK, and rethrombosis occurred in 10 patients (18%). Preservation of R waves relative to Q wave depth was limited to patients with less than 90% residual stenosis. Eight of nine patients with continuing thrombolysis and patients with recanalized occlusions of the left anterior descending coronary artery displayed more impressive increases in mean (+/- SEM) ejection fraction (47% +/- 4% to 53% +/- 5% [p less than 0.05], and 47% +/- 3% to 52% +/- 5, respectively). The ejection fraction also increased significantly in 15 patients with pre-SK values of less than 50% (41% +/- 2% to 48% +/- 3%; p less than 0.05). Ventricular function deteriorated in SK failures. Reperfusion arrhythmias occurred in 28 of 62 recanalized patients (45%). Minor bleeding tendencies were displayed in 18 of 72 patients (25%). Major hemorrhages, one of which may have been fatal, occurred in four patients (5.6%). Of 84 patients, four (4.7%) died, two of whom were in cardiogenic shock when first seen. In contrast, there were 11 deaths (11.8%) in a consecutive simultaneously enrolled series of 93 control patients with similar entry criteria (p less than 0.05). Two additional SK-treated patients died, 16 and 30 days after treatment, both more than a week after surgical revascularization. It is concluded that SK recanalization is a promising new therapy that may decrease mortality and preserve myocardial function in certain circumstances. Its efficacy in a setting closer to the mainstream of cardiologic practice extends the favorable experience issuing from earlier clinical investigations.

Percutaneous intraaortic balloon counterpulsation. Clinical effectiveness and hazards.

Because of its greater ease and rapidity of insertion, the percutaneous intraaortic balloon in many institutions has become the primary method for implementing counterpulsation. We report the results and complications of 113 attempted procedures in a variety of clinical settings. We had a high (93.8 percent) insertion success rate. However, our 18.6 complication rate was similar to the experience reported for the surgical method of insertion. Thus, the original anticipation of reduced complications with this method has not been realized in this and other recent reports.

Limitations of exercise testing in critical left coronary artery disease.

Exercise testing was evaluated in 51 patients with critical left coronary artery disease (LCA) documented by coronary arteriography within two weeks of their bicycle ergometer (26 patients) or treadmill (25 patients) electrocardiographic study. Adequate tests, as defined by the patient having reached 85% of predicted maximum heart rate, were achieved in only 16 patients on the ergometer (62%) and in 21 (84%) on the treadmill. Nevertheless mean maximum double product (220 vs 232) and mean exercise time (4.6 min vs 5.0 min.) were similar (p:NS). The sensitivity for ergometry and treadmill testing was 75 and 62% respectively. If however we include those negative studies in which for various reasons patients were unable to achieve 85% of their predicted maximal heart rate (i.e., inadequate studies), sensitivity was only 46 and 52% respectively. Thus a sizable group of patients with critical LCA disease cannot adequately perform exercise tests especially on the ergometer; and over half of all such patients studied will be found for one reason or another to respond negatively, regardless of exercise protocol.