Cardiac Arrhythmias

Prognosis of Ventricular Arrhythmias

General Therapy

Underlying causes of complex VA should be treated when possible. Treatment of congestive heart failure (CHF), LV dysfunction, digitalis toxicity, hypokalemia, hypomagnesemia, myocardial ischemia (by antiischemic drugs such as β-blockers or by coronary revascularization), hypertension, LV hypertrophy, hypoxia, and other conditions may eliminate or reduce the severity of complex VA. Such patients should not smoke or drink alcohol and should avoid drugs that may cause or increase complex VA.

All older adults with CAD should be treated with aspirin, β-blockers, angiotensin-converting enzyme (ACE) inhibitors, and statins unless there are contraindications to these drugs.

Age-related physiologic changes may affect absorption, distribution, metabolism, and excretion of cardiovascular drugs. Numerous physiologic changes that occur with aging affect pharmacodynamics, resulting in changes in end-organ responsiveness to cardiovascular drugs. Drug interactions between antiarrhythmic drugs and other cardiovascular drugs are common, especially in older adults. Important drug-disease interactions also occur in older adults. Class I antiarrhythmic drugs are more proarrhythmic than class III antiarrhythmic drugs. Except for β-blockers, all antiarrhythmic drugs can cause torsade de pointes VT (polymorphous appearance associated with a prolonged QT interval).

Class I Antiarrhythmic Drugs

Class I antiarrhythmic drugs are sodium channel blockers. Class Ia antiarrhythmic drugs have intermediate channel kinetics and prolong repolarization; these drugs include disopyramide, procainamide, and quinidine. Class Ib antiarrhythmic drugs have rapid channel kinetics and shorten repolarization slightly; these drugs include lidocaine, mexiletine, phenytoin, and tocainide. Class Ic antiarrhythmic drugs have slow channel kinetics and have little effect on repolarization; these drugs include encainide, flecainide, lorcainide, moricizine, and propafenone. None of the class I antiarrhythmic drugs have been demonstrated in controlled, clinical trials to decrease sudden cardiac death, total cardiac death, or total mortality.

Table 44-1 shows the effect of class I antiarrhythmic drugs on mortality in patients with heart disease and complex VA. A meta-analysis of six double-blind studies of patients with chronic atrial fibrillation who underwent direct-current cardioversion to sinus rhythm showed that the mortality rate at 1 year was higher in patients treated with quinidine (2.9%) than in patients treated with a placebo (0.8%).

Of 1330 patients in the Stroke Prevention in Atrial Fibrillation (SPAF) study, 127 were treated with quinidine, 57 with procainamide, 34 with flecainide, 20 with encainide, and 7 with amiodarone. The adjusted relative risk of cardiac mortality was increased 1.8 times and the adjusted relative risk of arrhythmic death was increased 2.1 times in patients receiving antiarrhythmic drugs versus no antiarrhythmic drugs. In patients with a history of CHF, the adjusted relative risk of cardiac death was increased 3.3 times and the adjusted relative risk of arrhythmic death was increased 5.8 times in patients taking antiarrhythmic drugs versus no antiarrhythmic drugs.

An analysis was made of 59 randomized, controlled clinical trials including 23,229 patients that investigated the use of class I antiarrhythmic drugs after myocardial infarction (MI). The class I antiarrhythmic drugs investigated included aprindine, disopyramide, encainide, flecainide, imipramine, lidocaine, mexiletine, moricizine, phenytoin, procainamide, quinidine, and tocainide. Mortality was increased in patients receiving class I antiarrhythmic drugs versus patients receiving no antiarrhythmic drugs (OR = 1.14). None of the 59 studies showed that the use of a class I antiarrhythmic drug decreased mortality in patients after MI.

On the basis of the available data, none of the class I antiarrhythmic drugs should be used to treat VT or complex VA in older adult or younger patients with heart disease.

Calcium Channel Blockers

Calcium channel blockers are not useful in the therapy of complex VA. Although verapamil can terminate a left septal VT, hemodynamic collapse can occur if intravenous verapamil is given to patients with the more common forms of VT. An analysis was made of randomized, controlled clinical trials (N = 20,342) that investigated the use of calcium channel blockers after MI. Mortality was insignificantly increased in patients receiving calcium channel blockers than in patients receiving no antiarrhythmic drugs (odds ratio [OR] = 1.04).

On the basis of the available data, none of the calcium channel blockers should be used to treat VT or complex VA in older adult or younger patients with heart disease.

β-Blockers

An analysis of 55 randomized, controlled clinical trials including 53,268 patients that investigated the use of β-blockers after MI showed that mortality was decreased in patients who received β-blockers versus a placebo (OR = 0.81). β-Blockers caused a greater decrease in mortality in older patients than in younger patients. Table 44-2 indicates the effect of β-blockers on mortality in patients with heart disease and complex VA.

The decrease in mortality as a result of the use of β-blockers in older adults with heart disease and complex VA is due more to an antiischemic effect than to an antiarrhythmic effect. β-Blockers also abolish the circadian distribution of sudden cardiac death or fatal MI, markedly decrease the circadian variation of complex VA, and abolish the circadian variation of myocardial ischemia. Based on the available data, β-blockers should be used to treat older and younger patients with heart disease and complex VA if there are no contraindications to the use of β-blockers.

Angiotensin-Converting Enzyme Inhibitors

ACE inhibitors have been demonstrated to reduce sudden cardiac death in some studies of patients with CHF. ACE inhibitors should be used to reduce total mortality in older and younger patients with CHF, an anterior MI, and an LV ejection fraction of 40% after MI. ACE inhibitors should be administered to treat older adult and younger patients with CHF with abnormal LV ejection fraction or with normal LV ejection fraction.

On the basis of the available data, ACE inhibitors should be used to treat older and younger patients with VT or complex VA associated with CHF, an anterior MI, or an LV ejection fraction of 40% after MI if there are no contraindications to the use of ACE inhibitors. β-Blockers should be administered in addition to ACE inhibitors in treating these patients.

Class III Antiarrhythmic Drugs

Class III antiarrhythmic drugs are potassium channel blockers, which prolong repolarization manifested by an increase in QT interval on the ECG. These drugs are effective in suppressing complex VA, including nonsustained VT, by increasing the refractory period. However, antiarrhythmic aggravation can occur, especially torsade de pointes.

Table 44-3 shows the effect of class III antiarrhythmic drugs on mortality in patients with heart disease. None of the class III antiarrhythmic drugs have been found in a double-blind, randomized, placebo-controlled clinical trial to decrease mortality in patients with heart disease and complex VA.

In 481 patients with VT, d , l -sotalol caused torsade de pointes (12 patients) or an increase in VT episodes (11 patients) in 23 patients (5%). On the basis of the available data, β-blockers are preferred to the use of d , l -sotalol in treating older adult and younger patients with heart disease and VT or complex VA.

Amiodarone is very effective in suppressing VT and complex VA associated with heart disease. However, the incidence of adverse effects from amiodarone approaches 90% after 5 years of therapy. In the Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation study, the incidence of pulmonary toxicity was 10% at 2 years in patients receiving 158 mg of amiodarone daily. Amiodarone can also cause hyperthyroidism, hypothyroidism, and cardiac, dermatologic, gastrointestinal, hepatic, neurologic, and ophthalmologic adverse effects.

Because amiodarone has not been demonstrated to reduce mortality in older adult or younger patients with VT or complex VA associated with prior MI or CHF and has a very high incidence of toxicity, β-blockers are preferred to the use of amiodarone in treating these patients. Some data suggest that patients receiving amiodarone plus β-blockers have a better survival time than patients receiving amiodarone.

Invasive Intervention

If patients have life-threatening VT or VF resistant to antiarrhythmic drugs, invasive intervention should be conducted. Patients with critical CAD and severe myocardial ischemia should undergo coronary artery bypass graft surgery to reduce mortality.

Surgical ablation of the arrhythmogenic focus in patients with life-threatening VT can be curative. This treatment includes aneurysmectomy or infarctectomy and endocardial resection with or without adjunctive cryoablation based on activation mapping in the operating room. However, the perioperative mortality rate is high. Endoaneurysmorrhaphy with a pericardial patch combined with mapping-guided subendocardial resection frequently cures recurrent VT with a low operative mortality and improvement of LV systolic function. Radiofrequency catheter ablation of VT has also been beneficial in the management of selected patients with arrhythmogenic foci of monomorphic VT.

Automatic Implantable Cardioverter-Defibrillator

The automatic implantable cardioverter-defibrillator (AICD) is the most effective treatment for patients with life-threatening VT or VF. Table 44-4 indicates the effect of the AICD on mortality in patients with ventricular tachyarrhythmias. Tresch and colleagues showed in retrospective studies that the AICD was very effective in treating life-threatening VT in older adult and younger patients. The Canadian Implantable Defibrillator study found that patients most likely to benefit from an AICD were those with two of the following factors: age (70 years), LV ejection fraction (35%), and New York Heart Association (NYHA) function class III or IV.

In MADIT-II, the reduction in sudden cardiac death in patients treated with an AICD was significantly reduced: by 68% in 574 patients younger than 65 years, by 65% in 455 patients aged 65 to 74 years, and by 68% in 204 patients aged 75 years. The median survival in 348 octogenarians treated with AICD therapy was greater than 4 years.

At 26-month follow-up, survival was 91% for patients treated with metoprolol plus an AICD versus 83% for patients treated with d , l -sotalol plus an AICD. An observational study in 78 patients with CAD and life-threatening VA treated with an AICD showed at the 490-day follow-up that the use of lipid-lowering drugs reduced recurrences of life-threatening VA. At the 33-month follow-up of 1038 patients (mean age, 70 years) who had AICDs, use of β-blockers significantly reduced the frequency of appropriate AICD shocks. At the 32-month follow-up of 965 of these patients, all-cause mortality was significantly reduced: 46% by use of β-blockers, 42% by use of statins, and 29% by use of ACE inhibitors or angiotensin receptor blockers. These data support the use of β-blockers, statins, and ACE inhibitors or angiotensin receptor blockers in the treatment of patients with AICDs.

The American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend that class I indications for treatment with an AICD are (1) cardiac arrest due to VT or VF not caused by a transient or reversible cause; (2) spontaneous sustained VT; (3) syncope of undetermined origin with clinically relevant, hemodynamically significant sustained VT or VF induced at electrophysiologic study when drug therapy is ineffective, not tolerated, or not preferred; (4) nonsustained VT with CAD, prior MI, LV systolic dysfunction, and inducible VF or sustained VT at electrophysiologic study that is not suppressed by a class I antiarrhythmic drug; (5) patients with prior MI (at least 40 days previously) with an LV ejection fraction less than or equal to 35% who are in NYHA class II or III; (6) patients with prior MI (at least 40 days previously) with an LV ejection fraction less than 30% who are in NYHA class I; and (7) patients with nonischemic dilated cardiomyopathy with an LV ejection fraction less than or equal to 35% who are in NYHA class II or III.

The 2009 updated ACC/AHA guidelines for treatment of CHF with class I indications recommend use of an AICD in (1) patients with current or prior symptoms of CHF and reduced LV ejection fraction with a history of cardiac arrest, VF, or hemodynamically destabilizing VT; (2) patients with CAD at least 40 days after MI, an LV ejection fraction equal to or less than 35%, NYHA class II or III symptoms on optimal medical therapy, and an expected survival greater than 1 year; and (3) patients with nonischemic cardiomyopathy, an LV ejection fraction equal to or less than 35%, NYHA class II or III symptoms on optimal medical therapy, and an expected survival greater than 1 year; and (4) may be used in patients receiving cardiac resynchronization therapy for NYHA class II or ambulatory class IV symptoms despite recommended optimal medical therapy.

ACC/AHA class IIa indications for treatment with an AICD are (1) unexplained syncope, significant LV dysfunction, and nonischemic cardiomyopathy; (2) sustained VT and normal or near normal LV function; (3) hypertrophic cardiomyopathy with one or more major risk factors for sudden cardiac death; (4) prevention of sudden cardiac death in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy who have one or more risk factors for sudden cardiac death; (5) reduction of sudden cardiac death in patients with long-QT syndrome who have syncope and/or VT while using β-blockers; (6) nonhospitalized patients awaiting cardiac transplantation; (7) Brugada syndrome with syncope; (8) Brugada syndrome with documented VT that has not resulted in cardiac arrest; (9) patients with catechol­aminergic polymorphic VT with syncope and/or documented sustained VT on β-blockers; and (10) cardiac sarcoidosis, giant cell myocarditis, or Chagas disease.

During 1243 days mean follow-up of 549 patients, mean age 74 years, who had an AICD for CHF, 163 (30%) had appropriate AICD shocks, 71 (13%) had inappropriate AICD shocks, and 63 (12%) died. Stepwise logistic regression analysis showed that significant independent prognostic factors for appropriate AICD shocks were smoking (OR = 3.7) and statins (OR = 0.54) , for inappropriate AICD shocks were atrial fibrillation (OR = 6.2) and statins (OR = 0.52), and for time to mortality were age (hazard ratio [HR] = 1.08 per 1-year increase), ACE inhibitors or angiotensin receptor blockers (HR = 0.25), AF (HR = 4.1), right ventricular pacing (HR = 3.6), digoxin (HR = 2.9), hypertension (HR = 5.3), and statins (HR = 0.32).

During implantation and during the 38-month follow-up observation of 1,060 patients (mean age, 70 years) who had AICDs, complications occurred in 60 patients (5.7%). In a registry of 5,399 AICD recipients for primary or secondary prevention, rates of appropriate AICD shocks were similar among patients aged 18 to 49, 50 to 59, 60 to 69, 70 to 79, and 80 years and older.