Ventricular Arrhythmias During Acute Mi

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The metabolic sequelae of ischemia, including intracellular hypercalcemia and acidosis, anaerobic lipid metabolism, and free-radical production, may contribute to arrhyth-mogenesis during AMI (3). Rapid efflux of intracellular potassium, leading to membrane depolarization, may be the most important of these effects. In addition, increased sympathetic tone augments electrical instability, provoking both ventricular and supra-ventricular tachyarrhythmias. Enhanced parasympathetic tone, usually occurring in the setting of acute inferior infarction, predisposes to bradyarrhythmias but may be protective against VF.

Ventricular arrhythmias may be temporarily divided into three phases: prehospital, CCU, and late. Prehospital (or early CCU phase) arrhythmias, most notably VF, probably result from chaotic reentry arising in the region of infarction. After several hours, progressive myocardial damage compromises intramyocardial conduction so that these reentrant arrhythmias occur less frequently (4). Six to eight hours after the onset of infarction, Purkinje fibers in the infarct zone may develop abnormal automaticity, leading to the second phase of arrhythmogenesis (5). This CCU phase lasts approx 48 h. When late ventricular arrhythmias—typically monomorphic ventricular tachycardia (VT) occur more than 24-48 h into the infarct, they may reflect the development of an anatomic substrate (scar) which supports reentry, suggesting a risk of recurrent ventricular arrhythmias after discharge.

Ventricular Fibrillation

Untreated VF (see Fig. 1) is generally lethal, and is the cause of most prehospital deaths in AMI. Rare cases of spontaneous reversion of VF have been reported, however. Primary VF is distinguished from secondary VF, which occurs in the setting of significant congestive heart failure (CHF) or cardiogenic shock. Late VF occurs more than 48 h after the onset of an acute MI.

Graphs Arrhythmia

Fig. 2. These graphs show the timing of VF after symptom onset in patients admitted with AMI early in the CCU era. The top graph reflects primary VF, and the bottom reflects complicating, or secondary, VF. Note the clustering of events in the first few hours after onset of symptoms. (Reprinted from Lawrie DM, Higgins MR, Godman MJ, et al. Ventricular fibrillation complicating acute myocardial infarction. Lancet 1968;2:525.)

Fig. 2. These graphs show the timing of VF after symptom onset in patients admitted with AMI early in the CCU era. The top graph reflects primary VF, and the bottom reflects complicating, or secondary, VF. Note the clustering of events in the first few hours after onset of symptoms. (Reprinted from Lawrie DM, Higgins MR, Godman MJ, et al. Ventricular fibrillation complicating acute myocardial infarction. Lancet 1968;2:525.)

Incidence

The incidence of VF is highest in the first few hours of an AMI, and declines sharply thereafter (5) (see Fig. 2). In GISSI-2, the incidence of primary VF in the first 4 h after presentation was 3.1%, and in hours 4-48 the incident was only 0.6% (6). Clinical studies have shown that the incidence of both primary (7-9) and secondary (10) VF are proportional to the extent of infarction, measured either enzymatically or in terms of left ventricular ejection fraction (LVEF). VF occurs rarely in the setting of non-Q-wave MI (NQMI) (11). In inferior MI, VF occurs more frequently with concomitant right ventricular infarction (12,13). In GISSI-1, the incidences of primary and secondary VF were 2.8% (14) and 2.7% (15), respectively; thrombolytic therapy with streptokinase reduced the frequency of secondary but not primary VF. A meta-analysis (16) suggested that the incidence of primary VF has been decreasing since 1970 (see Fig. 3), probably because of improvements in the overall management of AMI. In contrast, a retrospective review of patients with AMI admitted to community hospitals between 1975 and 1990 suggested that the rate of primary VF remained constant at 5.1% during this period (17). Late VF—occurring more than 48 h into the infarct—is rare, but tends to occur following large anterior MI, particularly when complicated by CHF and/or bundlebranch block (BBB) (18).

Fig. 3. Patients in randomized clinical trials of lidocaine in AMI who experienced VF as a function of the year the study was published. In both the control and lidocaine groups, the incidence of VF appears to be decreasing with time. (Reprinted from Antman EM, Berlin JA. Declining incidence of ventricular fibrillation in myocardial infarction: Implications for the prophylactic use of lidocaine. Circulation 1992;86:770.)

Fig. 3. Patients in randomized clinical trials of lidocaine in AMI who experienced VF as a function of the year the study was published. In both the control and lidocaine groups, the incidence of VF appears to be decreasing with time. (Reprinted from Antman EM, Berlin JA. Declining incidence of ventricular fibrillation in myocardial infarction: Implications for the prophylactic use of lidocaine. Circulation 1992;86:770.)

Prognosis

Traditionally, it has been taught that patients successfully resuscitated from primary VF have a good short-term prognosis. Recent studies (14,19), however, suggest that primary VF is associated with a significantly increased in-hospital mortality, which may be as high as 10-20%. It remains unclear whether the episode of VF is a significant cause of, or is simply a marker for, the high mortality. Notably, patients with primary VF who survive until hospital discharge have the same medium-term prognosis as patients who do not experience VF (6-9,19,20). Compared with primary VF, patients who have secondary VF have a much higher (38-56%) in-hospital mortality (10,15). Survivors of secondary VF appear to have the same medium-term prognosis as patients with similar degrees of left ventricular impairment who did not have VF (10,15).

Prophylaxis

Lidocaine had traditionally been used prophylactically to prevent primary VF. Early randomized trials (21,22) demonstrated a significant reduction in primary VF in patients treated with lidocaine. Overviews (23,24) of randomized trials documented a reduction in VF by about one-third, as well as an increased mortality in lidocaine-treated patients with suspected AMI. These meta-analyses included trials conducted largely in the pre-reperfusion therapy era. A more recent study, in which patients were randomized to prophylactic lidocaine and thrombolytic therapy in factorial design, yielded similar results (25). The mechanism of this excess mortality is not entirely clear; asystole, bradyarrhythmias, heart failure, and proarrhythmic effects may all play contributing roles. Of note, lidocaine was not associated with an increased mortality in GUSTO-I and II-b, although lidocaine use in these trials was by physician preference and not randomized (26).

Prophylactic lidocaine administered via intramuscular (im) injection prior to hospital arrival has also been considered. Some randomized trials have shown efficacy in reducing VF (27,28), and others have not (29-31). Inability to achieve therapeutic serum levels after im injection may have led to the lack of efficacy in these trials.

Meta-analyses have suggested a trend toward less VF (23) in patients who received prehospital im lidocaine, but no mortality advantage or disadvantage (23,24).

Efforts to define a high-risk population who might benefit from lidocaine prophylaxis have been unsuccessful. Initial enthusiasm regarding "warning arrhythmias" (>5 ventricular premature beats (VPBs) per minute, R on T (early phase) VPBs, multifocal VPBs, couplets, and salvos) waned when careful studies (32,33) revealed poor sensitivity (58-60%), specificity (41-45%), and positive predictive value (4-8%) for VF. Not surprisingly, a randomized study comparing "selective" and "broad" lidocaine prophylaxis showed no significant difference in the incidence of VF. Thus, prophylactic lidocaine should not be used routinely in AMI (34).

Fewer data are available regarding prophylactic amiodarone. The GEMICA trial in Argentina randomized patients within the first few hours of AMI to either intravenous (iv) and oral amiodarone or placebo (35). Treatment continued for 6 mo. Total mortality with the original "high-dose" regimen was higher than with placebo, although it is not clear how much of this excess mortality occurred during the index hospitalization compared with during follow-up. The protocol was modified, and there was no significant difference in mortality between the "lower-dose" regimen and placebo. Amiodarone was not associated with a significant decrease in the risk of sudden death. Amiodarone-treated patients had more adverse effects than placebo patients, including hypotension in the "high-dose" group. Thus, there is no indication for amiodarone prophylaxis with AMI.

Studies in the pre-thrombolytic era consistently documented that early iv betablockade reduced mortality in AMI (36); a portion of this benefit is attributable to an antifibrillatory effect. A single iv dose of propranolol, followed by oral therapy, markedly reduced the incidence of VF in a randomized trial of 735 patients (37). In the Goteburg metoprolol trial, a double-blind, randomized study, 15 mg of iv metoprolol (administered 5 mg every 2 min for three doses) reduced the incidence of VF from 2.4%-0.9% (38). Atenolol, administered intravenously (5 mg) and then orally, reduced the incidence of cardiac arrest in a randomized study involving 477 patients (39). An overview of 28 randomized trials, including ISIS-1, revealed a significant decrease in VF or cardiac arrest in patients treated with iv beta-blockade (40). It remains unclear whether this effect of beta-blockers is directly antifibrillatory, anti-ischemic, anti-adrenergic, or caused by infarct-size limitation or another factor.

There are fewer data for patients treated with thrombolytic therapy (41) or direct angioplasty. In fact, the routine use of iv beta-blockade seems to be decreasing in AMI as well as in other settings (42). In the Fourth International Study of Infarct Survival (ISIS-4), only 9% of the 58,050 received iv beta-blockers (43). The National Registry of MI confirmed a low utilization of iv beta-blockade in the United States, particularly in patients receiving thrombolytic therapy (44). The Thrombolysis in Myocardial Infarction (TIMI) II trial evaluated early iv metoprolol vs delayed oral therapy following treatment with recombinant tissue-type plasminogen activator (rt-PA) for AMI (45). Although there was no reduction of VF in the patients treated early, this therapy was safe, and conferred a mortality benefit in low-risk patients. A subsequent study revealed no excess of clinically significant bradyarrhythmias or tachyarrhythmias in patients who received both iv atenolol and rt-PA (46). In a nonrandomized analysis from the GUSTO study, patients treated with early iv atenolol had more complications, despite more favorable baseline characteristics than the group treated with later oral atenolol (47).

Although further investigation is needed, early aggressive beta-blockade is still recommended in patients treated with thrombolytic therapy or direct angioplasty (41,48).

Hypokalemia, commonly observed upon admission to the CCU, has been associated with increased frequency of ventricular ectopy (49), VF (50), ventricular tachycardia (VT) (51), and cardiac arrest (7) (see Fig. 4). Although no data exist confirming that potassium supplementation lowers the risk of ventricular arrhythmias, vigorous repletion to maintain a serum level of at least 4.5 meq/L is recommended in patients with AMI.

Magnesium metabolism may also be important in the AMI setting (52). A number of studies (53), including LIMIT-2, suggested a striking mortality reduction in patients given iv magnesium supplementation, although the effect on ventricular arrhythmia has not been consistent (54). This benefit seemed attributable to a protective effect on the myocardium rather than a primary reduction in VT and VF. Accordingly, in LIMIT-2, the magnesium-treated patients had an improved long-term (55) as well as short-term prognosis. The ISIS-4 megatrial, however, showed no advantage with respect to ventricular arrhythmias or mortality in AMI patients randomized to high-dose magnesium supplementation (43). This lack of effect may be attributed to the late administration of magnesium in this relatively low-risk cohort of patients (56). A more recent trial conducted in high-risk patients who were considered unsuitable for thrombolysis revealed a significant mortality advantage with aggressive iv magnesium supplementation (57). Early magnesium supplementation in high-risk AMI patients is currently being studied in the MAGIC trial.

Although they improve the long-term survival in AMI patients, angiotensin-converting enzyme (ACE) inhibitors have not been proven to reduce the incidence of ventricular arrhythmias during the acute phase of MI. In ISIS-4, there was no significant difference in the rates of VF or cardiac arrest in patients randomized to early captopril or placebo (43). However, there was a reduction in sudden death in long-term follow-up in MI survivors with left ventricular dysfunction treated with captopril in the SAVE study (58). A similar effect was noted in a meta-analysis of studies utilizing ACE inhibitors post-infarct (59). This may be mediated by the salutory effect of ACE inhibitors on left ventricular remodeling (60).

Although the widespread use of thrombolytic therapy has raised concerns of "reperfusion arrhythmias," clinical studies have not confirmed the dramatic increase in VF and VT following reperfusion in animal models (61). In fact, GISSI-1 (62) and ISIS-2 (63) demonstrated a slight reduction of VF in patients given thrombolytic therapy. A recent meta-analysis (64) of these and other randomized controlled trials showed no increased risk of early VF—in fact, there was a lower incidence of late VF in patients who received thrombolytic therapy. In the EMIP trial, however, a temporal relationship was noted between the infusion of thrombolytic therapy and VF (65). Finally, in the PAMI trial (66), there was a higher incidence of VF in patients treated with angioplasty compared with thrombolytic therapy. Thus, it remains possible that malignant reperfusion arrhythmias may follow revascularization therapy—particularly primary angio-plasty.

Early beta-blockade and potassium repletion may reduce the risk of VF in patients with AMI. Lidocaine should not be administered prophylactically to all patients admitted to the CCU with AMI, but rather reserved as treatment for those who manifest VF or sustained VT. Short-term lidocaine prophylaxis may be a good choice for patients for whom prompt defibrillation would not be possible, but this has not been studied

Acute Atrial Fibrillation

Fig. 4. Risk of developing VF (A) and VT (B) as a function of serum potassium level. (Reprinted from Nordrehaug JE, von der Lippe G. Hypokalemia and ventricular fibrillation in acute myocardial infarction. Br Heart J 1983;50:526 and Nordrehaug JE, Johannessen K-A, von der Lippe G. Serum potassium concentration as a risk factor of ventricular arrhythmia early in acute myocardial infarction. Circulation 1985;71:647.)

Fig. 4. Risk of developing VF (A) and VT (B) as a function of serum potassium level. (Reprinted from Nordrehaug JE, von der Lippe G. Hypokalemia and ventricular fibrillation in acute myocardial infarction. Br Heart J 1983;50:526 and Nordrehaug JE, Johannessen K-A, von der Lippe G. Serum potassium concentration as a risk factor of ventricular arrhythmia early in acute myocardial infarction. Circulation 1985;71:647.)

Table 2

Antiarrhythmic Agents for use in Ventricular Arrhythmias

Table 2

Antiarrhythmic Agents for use in Ventricular Arrhythmias

Drug

Loading dose

Infusion rate

Comments

Lidocaine

1.0-1.5 mg/kg

2-4 mg/min

Rebolus with 0.5-0.75 mg/kg every 5-10 min as needed, maximum load 3 mg/kg.

Amiodarone

150 mg

1 mg/min for 6 h, then 0.5 mg/min

Load over 10 min; monitoring blood pressure. Rebolus with 50-100 mg as needed.

Bretylium tosylate*

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  • Jorma Raila
    What arrhythmia accounts for more deaths during AMI?
    7 years ago

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