Adjuvant Antiarrhythmic Therapy in Patients With ICDs
Adjuvant Antiarrhythmic Therapy in Patients With ICDs
The risk of sudden cardiac death from ventricular fibrillation (VF) or ventricular tachycardia (VT) in patients with cardiomyopathy related to structural heart disease has been favorably impacted by the wide adaptation of implantable cardioverter defibrillators (ICDs) for both primary and secondary prevention. As such, the number of ICD implantations has increased significantly in the last decade. This trend is in direct opposition to a general decline in stand-alone antiarrhythmic drugs for ventricular indications. Not all of the trends are driven by the efficacy of ICDs in the prevention of arrhythmia, as ICD therapies for recurrent arrhythmias are common, and added drug therapy over time to reduce arrhythmic events in ICD patients for secondary prevention may be efficacious. In addition, randomized clinical trials have not supported prophylactic antiarrhythmic drug therapy for sudden death prevention because of either risk of proarrhythmia or incomplete suppression of ventricular arrhythmias.
In patients who receive an ICD, the risk of future arrhythmias that will require a shock or antitachycardia pacing (ATP) is high. The estimated risk of an inappropriate shock is 20–25 % and of an appropriate shock up to 35 %. Often appropriate therapies for VT or VF outnumber sudden deaths in ICD trials on a magnitude of 2–3 to 1. The structural heart disease that drives this risk also increases long-term mortality risk. These risks are particularly apparent in those patients who received an ICD for secondary prevention of arrhythmias in the setting of structural heart disease. Although ICD shocks for tachyarrhythmias can be life-saving, there are several reasons to prevent them. First, an ICD shock can be physically painful. This can lead to emotional distress and symptoms of sadness, depression, anxiety, and in some cases posttraumatic stress disorder. Unfortunately, a majority of patients report that they were ill-informed about the psychological impact of ICD shocks at the time they made their decision to have a device. Second, although ICDs are highly effective in terminating ventricular tachyarrhythmias, there is a delay from onset of the arrhythmia to treatment. This obligatory delay occurs while the device analyzes the arrhythmia and charges its highvoltage capacitors. During this time, which is required for the ICD to appropriately diagnose, charge, and treat the ventricular tachyarrhythmia, patients can experience significant symptoms, including lightheadedness, chest pain, dyspnea, palpitations, and syncope; this last can lead to significant secondary harm (e.g., as may occur during driving). Finally, ICD shocks are associated with increased mortality despite termination of the acute event. In this regard, ventricular tachyarrhythmias are typically treated only if they are sustained and/or rapid enough to lead to probable cardiac instability, adverse symptoms, or neurologic compromise. This diversion of ICD shocks is done in primary prevention patients through specific ICD tachycardia therapy programming criteria .
There are four primary reasons for concomitant or adjuvant antiarrhythmic drug therapy in patients with an ICD ( Table 1 ). The most common reason is to reduce the frequency or recurrence of ventricular tachyarrhythmias that are increasing in length or burden or have already triggered ATP therapies or ICD shocks. In the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial, a study of secondary prevention of ventricular tachyarrhythmias, the primary reason to start antiarrhythmic drugs after ICD implantation (64 % of crossover patients) was due to subsequent ICD shocks. In addition to prevention of subsequent ICD therapies, a high burden of ventricular arrhythmias can negatively impact cardiac function and heart failure status. Minimizing this negative impact is also an important consideration in the treatment of ventricular arrhythmias even if they fall below the threshold of activating ATP therapies or ICD shocks.
The next reason is to suppress or treat supraventricular arrhythmias, most commonly atrial fibrillation, that can lead to inappropriate ICD shocks. Inappropriate shocks can occur in up to 18–29 % of patients with an ICD and heart failure, and they have similar adverse morbidity and mortality consequences to ICD therapies for ventricular tachyarrhythmias. In patients who experience one inappropriate shock, the increased risk of mortality increases significantly [hazard ratio (HR) 1.6, P = 0.01]. The HR increases substantially to 3.7 in patients who receive five or more shocks.
Finally, antiarrhythmic drugs can be used to slow a ventricular tachyarrhythmia to make it more amenable to ATP therapy or to lower defibrillation thresholds in those with high thresholds that exceed ICD capabilities. These last reasons for antiarrhythmic therapy are very seldom used in isolation.
Background
The risk of sudden cardiac death from ventricular fibrillation (VF) or ventricular tachycardia (VT) in patients with cardiomyopathy related to structural heart disease has been favorably impacted by the wide adaptation of implantable cardioverter defibrillators (ICDs) for both primary and secondary prevention. As such, the number of ICD implantations has increased significantly in the last decade. This trend is in direct opposition to a general decline in stand-alone antiarrhythmic drugs for ventricular indications. Not all of the trends are driven by the efficacy of ICDs in the prevention of arrhythmia, as ICD therapies for recurrent arrhythmias are common, and added drug therapy over time to reduce arrhythmic events in ICD patients for secondary prevention may be efficacious. In addition, randomized clinical trials have not supported prophylactic antiarrhythmic drug therapy for sudden death prevention because of either risk of proarrhythmia or incomplete suppression of ventricular arrhythmias.
In patients who receive an ICD, the risk of future arrhythmias that will require a shock or antitachycardia pacing (ATP) is high. The estimated risk of an inappropriate shock is 20–25 % and of an appropriate shock up to 35 %. Often appropriate therapies for VT or VF outnumber sudden deaths in ICD trials on a magnitude of 2–3 to 1. The structural heart disease that drives this risk also increases long-term mortality risk. These risks are particularly apparent in those patients who received an ICD for secondary prevention of arrhythmias in the setting of structural heart disease. Although ICD shocks for tachyarrhythmias can be life-saving, there are several reasons to prevent them. First, an ICD shock can be physically painful. This can lead to emotional distress and symptoms of sadness, depression, anxiety, and in some cases posttraumatic stress disorder. Unfortunately, a majority of patients report that they were ill-informed about the psychological impact of ICD shocks at the time they made their decision to have a device. Second, although ICDs are highly effective in terminating ventricular tachyarrhythmias, there is a delay from onset of the arrhythmia to treatment. This obligatory delay occurs while the device analyzes the arrhythmia and charges its highvoltage capacitors. During this time, which is required for the ICD to appropriately diagnose, charge, and treat the ventricular tachyarrhythmia, patients can experience significant symptoms, including lightheadedness, chest pain, dyspnea, palpitations, and syncope; this last can lead to significant secondary harm (e.g., as may occur during driving). Finally, ICD shocks are associated with increased mortality despite termination of the acute event. In this regard, ventricular tachyarrhythmias are typically treated only if they are sustained and/or rapid enough to lead to probable cardiac instability, adverse symptoms, or neurologic compromise. This diversion of ICD shocks is done in primary prevention patients through specific ICD tachycardia therapy programming criteria .
There are four primary reasons for concomitant or adjuvant antiarrhythmic drug therapy in patients with an ICD ( Table 1 ). The most common reason is to reduce the frequency or recurrence of ventricular tachyarrhythmias that are increasing in length or burden or have already triggered ATP therapies or ICD shocks. In the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial, a study of secondary prevention of ventricular tachyarrhythmias, the primary reason to start antiarrhythmic drugs after ICD implantation (64 % of crossover patients) was due to subsequent ICD shocks. In addition to prevention of subsequent ICD therapies, a high burden of ventricular arrhythmias can negatively impact cardiac function and heart failure status. Minimizing this negative impact is also an important consideration in the treatment of ventricular arrhythmias even if they fall below the threshold of activating ATP therapies or ICD shocks.
The next reason is to suppress or treat supraventricular arrhythmias, most commonly atrial fibrillation, that can lead to inappropriate ICD shocks. Inappropriate shocks can occur in up to 18–29 % of patients with an ICD and heart failure, and they have similar adverse morbidity and mortality consequences to ICD therapies for ventricular tachyarrhythmias. In patients who experience one inappropriate shock, the increased risk of mortality increases significantly [hazard ratio (HR) 1.6, P = 0.01]. The HR increases substantially to 3.7 in patients who receive five or more shocks.
Finally, antiarrhythmic drugs can be used to slow a ventricular tachyarrhythmia to make it more amenable to ATP therapy or to lower defibrillation thresholds in those with high thresholds that exceed ICD capabilities. These last reasons for antiarrhythmic therapy are very seldom used in isolation.
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