Cardiac Emergencies: Sudden Death (FL INITIAL Autonomous Practice - Differential Diagnosis)

• The Brugada syndrome is characterized by the electrocardiographic (ECG) findings of right bundle branch block and ST-segment elevation in leads V1 to V3 and an increased risk of SCD.
• Brugada syndrome is due to a functional abnormality in repolarization. There may be some overlap with an early subclinical manifestation of ARVC.
• The Brugada syndrome occurs in families, with genetic transmission consistent with autosomal dominant inheritance with variable penetrance. Mutations in the cardiac sodium channel gene, SCN5A, have been found in several families.
• A sudden unexpected nocturnal death syndrome (SUNDS) has also been described in young, apparently healthy males from Southeast Asia. This disorder is closely related and may be the same as Brugada syndrome since most affected patients have the ECG manifestations of the Brugada syndrome and the same mutations in the sodium channel gene.
• Different mutations of the same SCN5A gene have been found in a number of cardiac disorders, including the long QT syndrome, and a unique allele found in African Americans, Y1102.

• Commotio cordis is SCD secondary to VF's relatively innocent chest wall impact. Affected patients have no underlying heart disease, and there is no structural damage to the chest wall, thoracic cavity, or heart.
• Early defibrillation of victims is lifesaving, despite historical evidence that resuscitation may be more difficult in commotio cordis than in other forms of SCD.

• Early repolarization pattern on an ECG is common.
• Studies have shown a higher frequency of early repolarization in SCA survivors without apparent heart disease. These survivors tended to have increased incidences of recurrent VF compared with those SCA survivors with normal hearts and no early repolarization.
• Early repolarization in the inferior and lateral leads is associated with an increased risk of SCA.
• Early repolarization ECG pattern is especially common in athletes, and it is generally benign in these individuals. An expert consensus panel does not recommend any specific treatment for early repolarization without SCA.

• A family history of SCD in the absence of apparent structural heart disease is associated with an increased risk for primary SCD.
• The absolute increase in risk is quite small since primary SCD is rare in the general population. Genome-wide association studies have demonstrated an increased risk with several loci (Wei et al., 2016).

• If all of the above disorders are excluded, and the heart is structurally normal, primary electrical disease is diagnosed. More commonly referred to as idiopathic VF, this entity is estimated to account for 5% of cases of SCD.
• In a review of 54 published cases with presumed idiopathic VF, the mean age was 36 years with a male-to-female ratio of 2.5-to-1.30. A history of syncope preceded the episode of VF in 25%. In a meta-analysis of 639 patients with idiopathic VF from 23 studies, 80% had an ICD for secondary prevention, 31% of patients had recurrent ventricular arrhythmias over a mean follow-up of five years (Weeu & Gyabgm 2016).

• Long QT can be primary (genetic/inherited), i.e., Long QT Syndrome (LQTS) or secondary (acquired). It may be associated with a specific form of polymorphic VT called torsades de pointes. Among patients with inherited LQTS, the precipitating factors and prognosis vary with the genetic abnormality.
• The majority of secondary causes of a prolonged QT interval result from an interaction with a drug/electrolyte which interferes with an ion channel involved in repolarization, the same ion channels involved in the LQTS. Most of the pharmaceutical agents which increase the QT interval are prescription drugs such as antipsychotics, anti-emetics, quinolones, antiarrhythmics, and methadone.

• SQTS is an extremely rare inherited channelopathy associated with markedly shortened QT intervals and SCD in individuals with a structurally normal heart.
• In contrast to LQTS, ion channel defects associated with SQTS lead to an abnormal abbreviation of repolarization, predisposing affected individuals to a risk of atrial and ventricular arrhythmias.

• Acute cardiac ischemia or
  • Catecholaminergic polymorphic VT (CPVT)
• Ischemia is the cause in most of these patients, necessitating prompt evaluation for cardiac ischemia
• CPVT, an inherited channelopathy, may cause those without cardiac ischemia
  • Affected patients typically present with life-threatening VT or VF occurring during emotional or physical stress, with syncope often being the first manifestation of the disease
  • Although sporadic cases occur, this is a largely familial disease. The majority of known cases are due to mutations in the cardiac ryanodine receptor, the cardiac sarcoplasmic calcium release channel. One report suggested that this disorder may account for at least one in seven cases of sudden unexplained death

• Third Degree AV Block is defined as a blockage in the AV junction where no atrial impulses reach the ventricles.
• The potential etiologies of third-degree AV block are similar to lesser degrees of AV block and include reversible causes:
  • Pathologic causes include:
    • Cardiomyopathy (e.g., amyloidosis, sarcoidosis)
    • Endocarditis with abscess formation
    • Hyperkalemia
    • Hypervagotonia
    • Infiltrative malignancies
    • Myocardial ischemia (acute or chronic) involves the conduction system
    • Myocarditis (e.g., Lyme disease)
    • Neuromuscular diseases
  • Iatrogenic causes include:
    • Medication-related (AV nodal blocking medications)
    • Post-cardiac surgery
    • Post-catheter ablation
    • Post-transcatheter aortic valve implantation
  • Idiopathic causes include:
    • Progressive cardiac conduction disease with myocardial fibrosis or sclerosis that affects the conduction system

• Short coupled PVCs have been described as a trigger of VF. Generally, these arise from the Purkinje fibers, but PVCs from papillary muscles have also been described to trigger VF. Ablation of these triggering PVCs may eliminate recurrent episodes of VF.

• Both WPW syndrome and, very rarely, other forms of SVT can cause SCD.
• The frequency with which this occurs was assessed in a report of 290 patients with aborted SCD. The mechanism was an arrhythmia associated with the WPW syndrome in 2.1% and atrial fibrillation (AF) with a rapid ventricular response which was the most common.
• Most patients resuscitated from VF secondary to preexcitation have a history of syncope, atrioventricular reciprocating tachycardia, or AF.38 However, preexcitation and arrhythmias have been undiagnosed in up to 25% of such patients.
• Among patients with WPW syndrome who survive an episode of SCD, ablation of the accessory pathway is the treatment of choice.

• The patient (if conscious) and family should be questioned, with particular attention to the following:
  • Prior diagnoses of heart disease
  • Use of any medications, especially antiarrhythmic drugs, diuretics, and drugs that might produce LQTS
  • Ingestion of toxins or illicit drugs
  • Antecedent symptoms, especially evidence of ischemia
  • Antecedent stressful events or activities
• A coherent history may not be obtainable since the cardiac arrest is frequently unwitnessed. In addition, the patient resuscitated from VF often has retrograde amnesia and cannot remember what occurred before the cardiac arrest.

• Immediate evaluation should include standard laboratory testing to exclude electrolyte abnormalities and, in many cases, an arterial blood gas to exclude acidosis. Any reversible metabolic abnormalities should be identified and corrected, particularly hypokalemia and hypomagnesemia, which can predispose to ventricular tachyarrhythmias.
• Two important limitations should be considered when interpreting the test results:
  • Electrolyte abnormalities during and shortly after resuscitation may be secondary to cardiac arrest and hypoperfusion rather than a cause of SCD.
  • Electrolyte abnormalities by themselves are usually insufficient to cause SCD. Clinical settings that increase the proarrhythmic effect of hypokalemia and hypomagnesemia include acute myocardial infarction, overt HF, and LQTS.
• Unless compelling evidence of an association, it is potentially hazardous to ascribe a cardiac arrest to an electrolyte or metabolic derangement alone. Mistaken attribution of a significant arrhythmia to an innocent or merely potentiating laboratory abnormality can place the patient at high risk if appropriate therapy to prevent recurrent SCD is delayed or not given. Importantly, electrolyte and pH abnormalities may be secondary to the arrhythmia itself.
• This risk was illustrated in a review of 169 patients treated with an ICD for sustained ventricular arrhythmia. The plasma potassium concentration was measured on the day of the arrhythmia. The likelihood of a recurrent sustained ventricular arrhythmia was 82% at five years. The long-term risk was similar in patients with low, normal, and high plasma potassium concentrations at presentation.

• An ECG can reveal evidence of both acute abnormalities and chronic conditions. It should be part of the immediate evaluation and repeated as necessary once the patient's cardiac, hemodynamic, and metabolic condition stabilizes. The ECG should be evaluated for evidence of the following:
  • Ongoing ischemia or prior myocardial infarction
  • Conduction system disease, including bundle branch block, second-degree heart block, and third-degree heart block
• Less common abnormalities that also may be evident include:
  • ARVC is suggested by VT or ventricular ectopy with a left bundle branch block configuration and an inferior axis. In addition, abnormalities of the baseline QRS may be present, including an epsilon wave in the right precordial leads
  • Brugada syndrome, evidenced by a pseudo-RBBB and persistent ST-segment elevation in V1 to V3
  • Hypertrophic cardiomyopathy
  • LQTS, possibly with torsades de pointes
  • WPW syndrome, evidenced by a short PR interval and a slurred QRS complex upstroke known as a delta wave

• Coronary angiography is performed in most survivors of SCD for one of two indications:
  • Management of an ACS
    • SCD may be the presenting manifestation of an ACS. Among patients with an ACS, malignant arrhythmias are significantly more common in an acute ST elevation MI (STEMI) setting. Still, they are also seen in approximately 2% of patients with a non-ST elevation MI (NSTEMI). In patients with an ACS and ischemia, the arrhythmia is usually polymorphic VT, rapid ventricular flutter, or VF.
    • Any patient with evidence of a confirmed or suspected STEMI or NSTEMI following resuscitation from SCD should undergo urgent cardiac catheterization and primary percutaneous coronary intervention (PCI) or, in some cases, surgical revascularization as appropriate.
    • Patients who experience SCD during the first 48 hours after a STEMI have higher in-hospital mortality compared with STEMI patients who do not experience sustained VT or VF. However, there is little or no difference in mortality among patients who survive hospital discharge at one to two years.
  • Diagnosis of chronic CHD
    • Diagnostic angiography
      • In SCD survivors without an ACS, angiography is still considered to exclude stable, chronic CHD, which is the leading cause of SCD. Malignant arrhythmias and SCD occur in such patients, usually those who have had a prior infarction with residual myocardial scarring. In contrast to patients with an ACS, the culprit arrhythmia is usually scar-related monomorphic VT, which is not the result of ischemia. However, monomorphic VT can ultimately degenerate to VF, particularly if the arrhythmia induces ischemia. Because SCD may be the first clinical evidence of chronic CHD, most SCD survivors undergo diagnostic angiography before discharge.
    • Even for patients arriving at the hospital in refractory VT/VF who are receiving ongoing CPR, immediate coronary angiography appears beneficial in a carefully selected group of patients (18 to 75 years of age with VT/VF as initial rhythm who received three shocks and amiodarone loading dose and who can be in the catheterization lab in <30 minutes post-arrest) (Yannopoulos et al., 2017).
    • Diagnostic coronary angiography may not be necessary for selected patients without signs or symptoms of CHD if another clear cause for SCD is identified (e.g., LQTS, WPW, Brugada, HCM, left ventricular noncompaction, or ARVC).
    • Angiography is suggested in younger patients without an apparent cause for SCD, in whom angiography may also detect an anomalous origin of a coronary artery. Among competitive athletes under age 35, anomalous origin of a coronary artery was present in 13% of SCD survivors in one series.
    • Patients with stable CHD who experience an episode of primary SCD without evidence of simultaneous ischemia are at high risk for recurrent malignant arrhythmias, even after percutaneous or surgical revascularization. As a result, such patients are treated with an ICD.

• Echocardiography can detect abnormalities that suggest or confirm the diagnosis of many of the important causes of SCD. Since global left ventricular dysfunction due to myocardial stunning can be induced by cardiac arrest, and cardiopulmonary resuscitation, evaluation of left ventricular function should be performed at least 48 hours after resuscitation.
• Potential causes of SCD that can be detected with echocardiography include the following:
  • Aortic stenosis
  • ARVC
  • CHD – Left ventricular dysfunction with wall motion abnormalities suggest prior myocardial infarction. Dyskinetic wall motion is consistent with an aneurysm
  • Dilated cardiomyopathy
  • HCM

• CMR is indicated for selected patients whose diagnosis is uncertain after the evaluation.
• CMR is useful in the evaluation of the following disorders:
  • ARVC
  • Cardiac amyloidosis
  • Cardiac sarcoidosis
  • Congenital heart disease, including the anomalous origin of coronary arteries
  • Dilated cardiomyopathy
  • HCM
  • Myocarditis
• The utility of CMR angiography as an alternative to invasive coronary angiography is not well defined. Alternatively, cardiac computed tomography angiography may be used to assess both congenital and acquired coronary abnormalities.

• Approximately 5 to 10% of SCD survivors have no evidence of a noncardiac etiology or structural heart disease after the above evaluation. Such patients are considered to have a primary electrical disorder.
• The majority of these patients do not have "normal" hearts, but historically diagnostic tools have been unable to identify the structural or functional derangement. In the past, the etiology of many of these deaths was unknown and termed "idiopathic." Subsequent discoveries have identified the cause of death in many of these patients (Wei et al., 2016). As understanding the mechanisms of primary electrical disorders has improved, so have diagnostic capabilities, with important benefits for both the victims of SCD and their families.
• Characteristic changes on an ECG often detect these disorders.
• Several of the disorders that cause SCD in the absence of structural heart disease are due to abnormalities of cardiac ion channels, including the following:
  • Brugada syndrome
  • CPVT
  • LQTS
  • SQTS
• Disorders associated with SCD that are not due to ion channel abnormalities include:
  • WPW syndrome
  • Commotio cordis
• Patients without evidence of any of the above structural or electrical abnormalities have idiopathic VF or primary electrical disease.
• Identification of a primary electrical disorder in an SCD survivor has two important benefits:
  • Directing medical treatment to prevent arrhythmia recurrence (e.g., beta-blockers for CPVT). Although medical therapy alone is now uncommon in SCD survivors, adjunctive medical therapy can reduce the frequency of ICD shocks.
  • Guiding the evaluation and management of family members.

• EP testing is not usually performed in patients with an established etiology of SCD. However, an EP study can be valuable in those whose initial evaluation reveals no etiology and in selected patients with a previously identified disorder.
• In SCD survivors with a normal heart, EP testing may reveal the following:
  • Abnormalities of atrioventricular conduction.
    • The presence of severe conducting system disease suggests that a serious bradyarrhythmia may have contributed to the SCD event.
    • These patients, though, typically present with syncope rather than SCD.
    • Furthermore, VT/VF may be the culprit even when conduction disease is identified, and ventricular stimulation to induce ventricular arrhythmias may be warranted.
  • An accessory pathway in patients with WPW syndrome.
    • An accessory pathway can rapidly conduction supraventricular arrhythmia, primarily AF, producing a rapid ventricular rate that can degenerate to VF.
    • Such patients usually have evidence of preexcitation on their ECG. If preexcitation is evident on an ECG in a survivor of SCD, EP study and ablation of the accessory pathway are usually indicated.
  • Inducible ventricular arrhythmias.
    • VT and VF may be induced in patients with several underlying cardiac abnormalities. The prognostic value of inducible arrhythmias is best established in patients with prior myocardial infarction and reduced left ventricular (LV) systolic function.
    • There is evidence that inducible VF, particularly when repeatedly induced with nonaggressive protocols, suggests the diagnosis of idiopathic VF and may predict recurrent arrhythmic events.
    • In a literature review, 69% of patients with idiopathic VF had sustained ventricular tachyarrhythmia induced with a nonaggressive protocol. The induced arrhythmia was generally polymorphic in configuration and poorly tolerated.
    • In some other conditions, it is unclear whether inducible VT or VF has prognostic significance (e.g., Brugada syndrome, infiltrative diseases, HCM. Furthermore, aggressive stimulation protocols can induce polymorphic VT or VF in some individuals without cardiac disease. Thus, inducible arrhythmias can be a nonspecific finding. For this reason, the significance of inducible ventricular arrhythmias in patients with apparently normal hearts is unclear. On the other hand, the absence of inducible VT/VF may not preclude ICD implantation since lack of inducibility does not predict low risk.
  • Myocardial scar
    • Substrate mapping may identify areas of scar indicating abnormal substrate and a predisposition to ventricular arrhythmias. These abnormalities are more commonly seen in patients with CHD, HCM, ARVC, or infiltrative diseases and occur in some idiopathic VF cases.
    • In addition, some patients with idiopathic VF have other electrophysiologic abnormalities, including areas of slow conduction, regionally delayed repolarization, or dispersion in repolarization.
  • Supraventricular arrhythmias
    • Patients in whom VT or VF was not well documented at SCD may have another culprit arrhythmia, usually an SVT. In such patients, SVT may be inducible during the EP study.

• Exercise testing is not usually part of the CHD evaluation in SCD survivors since most undergo coronary angiography. However, the provocation of ischemia with exercise, independently of coronary anatomy, is important in evaluating the SCD survivor. Although angiography alone does not prove a causal relationship to SCD or the presence of ischemia, the observation that revascularization appears to improve outcomes means that a negative exercise test in a patient with a significant coronary disease on angiography is not likely to affect the decision on revascularization. Also of great importance is the provocation of VT or VF in these patients, which would predict a higher recurrence rate. It is also a target for adjunctive antiarrhythmic therapy in addition to an ICD. While VT (often scar mediated and provoked by catecholamines) may be provoked during exercise, VF most commonly occurs after exercise in the recovery period (when ischemia is more common).
• In patients with apparently normal hearts, exercise testing can assist in diagnosing LQTS and CPVT. It is also useful in patients with WPW patterns as the resolution of the delta wave with exercise generally correlates with a low likelihood of a rapid ventricular rate with AF, which is the etiology for VF and SCD in these patients.

• In patients without a clear etiology for SCD, ambulatory monitoring may reveal recurrent sustained or nonsustained arrhythmias. However, most patients without an established diagnosis will have an ICD placed before discharge, and the memory features in these devices may preclude the need for ambulatory monitoring.

• Some primary electrical disorders may still be present despite no abnormalities on any of the proceeding tests. ECG abnormalities may be intermittent or latent, and genetic testing is not comprehensive enough to exclude all possible disorders.
• Investigators have evaluated pharmacologic challenge's role in eliciting diagnostic ECG changes or arrhythmias in selected SCD survivors. One report included 18 SCD survivors with no evidence of structural heart disease. All patients had a normal ECG, echocardiogram, coronary angiography, and CMR. Patients were infused with epinephrine (0.05 to 0.5 micron/kg per minute) and then procainamide (1 g over 30 minutes). Epinephrine was intended to induce CPVT and procainamide to induce the characteristic ECG abnormalities of Brugada syndrome.
• The following findings were noted:
  • Ten patients were diagnosed with CPVT based upon an abnormal response to an epinephrine infusion (frequent or polymorphic ventricular ectopy, nonsustained VT, or sustained VT). Four of these patients had ventricular ectopy during exercise testing, but none had sustained or nonsustained VT.
  • Two patients were diagnosed with Brugada syndrome.
  • Six patients were left with a diagnosis of idiopathic VF.
  • Among 55 family members who were tested, eight affected members from one family were diagnosed with CPVT, and one relative was diagnosed with Brugada syndrome.
• In summary, two-thirds of patients whose standard evaluation provided no etiology for SCD had a diagnosis established with provocative pharmacologic testing. This allowed for the addition of appropriate adjunctive therapy (beta-blockers for CPVT) and the identification of nine additional affected family members.

• During the cardiac evaluation, minor cardiac abnormalities are often detected that do not have a clear causal relationship to SCD. These findings do not preclude the diagnosis of idiopathic VF. However, their severity must be considered, and monitoring is warranted since these disorders may be the initial manifestations of underlying structural heart disease that will become clinically apparent later.
  • Examples of such disorders which do not exclude idiopathic VF are:
    • First degree atrioventricular (AV) block
    • Transient second-degree Mobitz type II AV block without bradycardia
    • Isolated bundle branch block

• Some causes of SCD are familial, including a genetic predisposition to premature CHD. The risk of cardiovascular disease appears significantly higher in first- and second-degree relatives of the SCD victims, particularly young victims.
  • In a nationwide Danish study from 2000 to 2006, 470 victims of SCD were identified who were 35 years of age or younger. Among a cohort of 3,073 first- and second-degree relatives of the SCD victims who were followed for up to 11 years, CVD was significantly more likely to be present than in the general population. In contrast, there was no difference in CVD rates compared with the general population among relatives of elderly (> 60 years of age) victims of SCD.
• A general cardiologic evaluation of first- and second-degree relatives of victims of unexplained SCD can yield the diagnosis of heritable disease in up to 40% of families, as illustrated by the following observations.
  • In a study of 32 families of victims of unexplained SCD, a general cardiologic evaluation (ECG, echocardiogram, Holter monitor and, less commonly, stress testing) was completed in 107 first-degree relatives. Seven families (22%) were diagnosed with a heritable disease: four with LQTS, one with nonstructural cardiac disease, one with myotonic dystrophy, and one with HCM.
  • These findings were extended in a second report that evaluated 43 families with 183 surviving first- and second-degree relatives of victims of unexplained SCD at age ≤40. Careful history identified 26 additional cases of unexplained SCD at age ≤40. Cardiology evaluation included ECG, echocardiogram, exercise tolerance testing (ETT), and measurement of serum lipids. Additional testing, as indicated, included a flecainide challenge for suspected Brugada syndrome or cardiac MR for suspected ARVC.
• Genetic testing for the suspected disease was performed when a clinical diagnosis was established. A genetic abnormality was confirmed, additional screening was done in another 150 family members. The following findings were noted:
  • A heritable disease was identified in 17 families (40%): five with CPVT, four with LQTS, two with Brugada syndrome, one with Brugada/LQTS, three with ARVC, one with HCM, and one with familial hypercholesterolemia. Genetic analysis confirmed the diagnosis in 10 families.
  • An average of 8.9 asymptomatic carriers per family was identified through secondary genetic analysis.
  • Identifying a specific disease was more likely if ≥2 unexplained SCD events occurred in the family and more family members underwent evaluation.
  • The increased yield in the second study may reflect the more extensive evaluation, including ETT, and the inclusion of more family members.
• Consistent with these findings, it has been recommended that first-degree family members of patients with SCD in the absence of structural heart disease be informed of the potentially increased risk. An assessment should be offered at a center with experience diagnosing and managing inherited cardiac diseases. Routine genetic screening for inherited disorders is not feasible, although, in an identifiable condition, the genetic evaluation of family members may be undertaken at some centers.

The main indications for the use of an ICD can be divided into two groups (Russo et al., 2013):

• Secondary Prevention
  • Implantation of an ICD is recommended for the secondary prevention of SCD due to life-threatening VT/VF in the following settings:
    • Patients with a prior episode of resuscitated VT/VF or sustained hemodynamically unstable VT in whom a completely reversible cause cannot be identified. This includes patients with various underlying heart diseases and idiopathic VT/VF and congenital LQTS, but not patients who have VT/VF limited to the first 48 hours after an acute MI.
    • Patients with episodes of spontaneous sustained VT in the presence of heart disease (valvular, ischemic, hypertrophic, dilated, or infiltrative cardiomyopathies) and other settings (e.g., channelopathies).
    • A key issue is the prevention of total mortality (not arrhythmic or sudden death). Simply correcting VT/VF may not improve overall mortality. Therefore, patient selection for ICD implantation should consider the known risk of SCD due to VT/VF for a specific condition and the risk of total mortality from underlying medical conditions.
• Primary Prevention
  • Implantation of an ICD is recommended for the primary prevention of SCD due to life-threatening VT/VF in patients who have received optimal medical management (including the use of beta-blockers and angiotensin-converting enzyme [ACE] inhibitors) yet remain at high risk of SCD, including:
    • Patients with a prior MI (at least 40 days ago) and left ventricular ejection fraction (LVEF) ≤30%.
    • Patients with cardiomyopathy, New York Heart Association (NYHA) functional class II to III (Table 2), and LVEF ≤35%.

• ICD therapy is not recommended in the following settings:
  • Patients with ventricular tachyarrhythmias due to a completely reversible disorder in the absence of structural heart disease (e.g., electrolyte imbalance, drugs, or trauma).
  • Patients do not have a reasonable expectation of survival with an acceptable functional status for at least one year, even if they otherwise meet ICD implantation criteria.
  • Patients with incessant VT or VF in whom other therapies (e.g., catheter ablation) should be considered first.
  • Patients with severe psychiatric illnesses that may be aggravated by device implantation. This situation is rarely encountered in clinical practice and may apply more to primary prevention than secondary prevention settings.
  • Patients with NYHA Class IV HF are refractory to optimal medical treatment and are not candidates for cardiac transplantation or CRT.
  • Patients with syncope without inducible ventricular tachyarrhythmias and structural heart disease.
  • Patients with VF or VT amenable to surgical or catheter ablation in whom the risk of SCD is normalized after successful ablation (e.g., atrial arrhythmias associated with the WPW syndrome, RV or LV outflow tract VT, idiopathic VT, or fascicular VT in the absence of structural heart disease).
  • ICD implantation should be delayed in patients with active infections or other acute medical issues. If necessary, the patient can be bridged with a wearable cardioverter-defibrillator (WCD) until ICD implantation can be carried out.

• The ICD system is comprised of the following elements (Picture 1):
  • Pacing/sensing electrodes
    • Pacing and sensing functions require a pair of electrodes. Contemporary pacemakers and defibrillators usually use leads with two electrodes on the ventricular lead: the distal electrode at the tip of the lead and a second electrode in the shape of a ring, several millimeters back from the tip (i.e., true bipolar leads). These bipolar leads provide accurate sensing, with high amplitude, narrow electrograms. Some ICD leads utilize integrated bipolar sensing in which the bipole consists of a single tip electrode and the distal shocking coil electrode. In addition to improved sensing capabilities, bipolar leads reduce the risk of extraneous interference, leading to inappropriate device function (e.g., inappropriate shocks delivered due to sensing of muscular activity).
  • Defibrillation electrode
    • The defibrillation function of the electrodes requires a relatively large surface area and positioning of the lead to maximize the density of current flow through the ventricular myocardium. Contemporary ICD systems use a "coil" of wire that extends along with the ventricular lead as the primary defibrillation electrode. Thus, a single transvenous lead can accomplish all pacing, sensing, and defibrillation functions.
    • Additional defibrillation electrodes improve defibrillation efficacy and reduce the defibrillation threshold. Most contemporary ICD systems have two or three defibrillation electrodes. Along with the distal coil in the RV on the transvenous lead, some ICD leads have a second defibrillation coil proximal to the RV coil. In addition, with "active can" technology, the metal housing of the ICD serves as one of the shocking electrodes. This configuration requires that the pulse generator be implanted in the pectoral region. The active can and transvenous lead systems can be combined to achieve adequate defibrillation thresholds (minimum energy required for successful defibrillation, which should generally be 10 joules less than the device's maximum output).
    • There are three types of pacing offered by current transvenous systems.
      • Single-chamber systems have only an RV lead.
      • Dual-chamber systems have right atrial (RA), and RV leads.
      • CRT, also called biventricular systems, has RA, RV, LV leads, or RV and LV leads in some patients with permanent atrial fibrillation.
  • Pulse generator
    • The pulse generator contains the sensing circuitry and the high voltage capacitors and battery.
    • Placement:
      • The development of small pulse generators (e.g., thickness ≤15 mm) has permitted placement in the infraclavicular region of the anterior chest wall in nearly all patients. The majority are placed in a:
        • Prepectoral (i.e., subcutaneous) position
        • Subpectoral position is advantageous. Most patients with the pulse generator in this location transmit the impulses generated to the myocardium via transvenous leads. Epicardial systems are still available and may be necessary due to anatomical limitations to placing a transvenous lead(s). Additionally, a subcutaneous ICD (S-ICD) system is now available in which the pulse generator is placed overlying the left lower lateral ribs.
        • A pulse generator will last for five or more years in most patients.

Implantable Cardioverter Defibrillator (ICD)
When the ICD senses an abnormal heart rhythm, it delivers an electrical shock to reset the heart to a normal rhythm.

• Before implanting an ICD, the healthcare provider must determine the optimal position to place the leads and the pulse generator. Most current ICD systems utilize one or two transvenous leads placed via the axillary, subclavian, or cephalic vein, attaching to a pulse generator in the subcutaneous tissue in the infraclavicular anterior chest wall. In more recent years, there has been a trend toward single coils rather than dual coils, which were favored earlier in the era of transvenous ICD systems. The rationale for this is that a proximal coil is rarely needed for defibrillation and that single-coil leads are less difficult to extract in the future if lead removal is necessary. If necessary, an additional defibrillation lead can be placed in the azygos vein, coronary sinus, or subcutaneous tissue.
• Choosing the optimal pulse generator location
  • Modern devices are small enough to be implanted in the pectoral region of the anterior chest wall, either subcutaneously or submuscularly, similar to pacemaker implantation.
  • Transvenous devices placed in the pectoral region are associated with fewer perioperative complications, shorter procedure time, shorter hospital stays, lower hospitalization costs, and lower total costs.
  • Although implantation on the left side is preferred, a right-sided implant can be performed. The left pectoral position is usually chosen for two reasons: defibrillation energy requirement is usually lower on the left because of the location of the heart in the left chest, and there is a small risk of arm swelling due to venous occlusion, which would impact fewer people on the left as the majority of patients are right-handed.
  • Additionally, an S-ICD system is available that allows for defibrillation (though no backup pacing or anti-tachycardia pacing) without inserting a transvenous lead. The pulse generator for the S-ICD system is implanted in a subcutaneous pocket in the left lateral, mid-axillary thoracic position.
• Choosing the optimal lead placement
  • In most new ICD implantations, the lead with the pace/sense electrodes is placed transvenously, with the distal electrode positioned on the RV apical endocardium. RV septal lead placement is also an option. In rare cases, usually due to limitations of the venous anatomy or a high risk of bacteremia and endovascular infection, the pace/sense electrodes are placed on the epicardium during surgery. The electrodes should record a ventricular electrogram of at least 5 mV. These signals should be sufficiently large for the detection of VT and VF.
  • Dual-chamber ICDs have an additional lead with another pair of pace/sense electrodes in the right atrium for atrial sensing and pacing.
  • An S-ICD has been developed with no leads placed in the heart. The subcutaneous lead, which toward its terminal end contains an 8-cm shocking coil electrode, is tunneled from the pulse generator in the left axilla to a position along the left parasternal margin. The S-ICD can sense VT/VF and deliver therapeutic shocks but cannot deliver anti-tachycardia pacing or pacing for bradycardias.

• DFT testing has historically been performed at device implantation, although the necessity for this evaluation with the current generation of devices has been questioned (Wikoff et al., 2015).
• DFT testing is generally performed in patients receiving an S-ICD.
• DFT testing is not required and can be omitted in patients undergoing a left pectoral transvenous ICD implantation with an RV apical lead functioning appropriately.
• DFT testing is reasonable in patients undergoing a right pectoral ICD implantation or ICD pulse generator changes (on either right or left side). The rationale for testing right-sided implants is that defibrillation may be more difficult with a right pectoral pulse generator, given that the heart lies in the left chest. There may be concerns about the integrity of the chronic leads for generator changes.
• DFT testing should not be performed in patients with a documented nonchronic cardiac thrombus, atrial fibrillation/flutter without adequate anticoagulation, severe aortic stenosis, unstable angina, recent stroke or transient ischemic attack, or hemodynamic instability. Many centers avoid DFT testing in patients with very low LVEFs (<15%) or severe pulmonary hypertension.
• Some electrophysiologists feel that universally omitting DFT testing might compromise the safety of certain patients, especially those with high DFTs who would benefit from a higher energy device or additional leads.
• However, a distinction should be made between DFT testing at initial implantation and at the time of generator replacement. DFT testing at the time of generator replacement is useful in subsets of patients with leads that have a hazard alert or in patients at higher risk of DFT changes (e.g., obese patients, patients with HF symptoms, patients on amiodarone, etc.) (Phan et al., 2015).
• Early ICD systems frequently required lead system adjustment at the time of implantation to achieve an adequate safety margin (arbitrarily set at 10 joules or greater). As technology improved, thresholds were substantially reduced. As a result, it is now unusual for the standard triad defibrillation system (two shock coils and an active can) to require modification at the time of implantation. Data regarding DFT testing on the more modern single-coil systems are limited since the available cohort and registry data predate the development of single-coil systems. On average, omitting the proximal coil in a single-coil system likely increases the DFT a few joules, which usually does not impact the safety margin but could be significant in some patients.
• Several studies have illustrated the impact of DFT testing at the time of ICD implantation with the current generation of devices, generally showing no significant difference in outcomes (arnson et al., 2014). In a systematic review and meta-analysis of 13 studies involving 9,740 patients undergoing initial ICD implantation, there was no significant difference in mortality or adverse outcomes between patients with and without DFT testing (Phan et al., 2016).

• Nearly all patients who undergo ICD implantation will have the device placed using local anesthesia at the site of the pulse generator insertion, with intravenous sedation provided for patients who experience significant anxiety or pain by nurse anesthetists or anesthesiologists.
• Following ICD implantation:
  • A posteroanterior (PA) and lateral chest x-ray should be obtained to establish the position of the pulse generator and the associated lead(s) and exclude any apparent complications, including pneumothorax and lead dislodgment.
  • Patients should also have a 12-lead ECG recorded during pacing to document the ECG appearance of the QRS complex.

• There are a variety of potential complications associated with ICDs, both at and around the time of implantation and long-term over the life of the patient and their device.
• Periprocedural complications include:
  • Bleeding
  • Cardiac perforation
  • Infection
  • Perioperative mortality (rare)
  • Shoulder related problems include:
    • Decreased shoulder mobility
    • Pain
    • Reduced function
    • Insertion tendonitis
  • Long-term complications include:
    • Lead-related problems
      • Increased defibrillation threshold
      • Infection
      • Lead failure (resulting in failure to pace, failure to shock, or inappropriate shocks)
      • Tricuspid valve damage
      • Venous thrombosis
    • Pulse generator complications
      • Electronic circuit damage
      • Electromagnetic interference
      • Skin erosion due to the size and weight of the generator and infection of the pulse generator pocket
      • Twiddler’s Syndrome is a condition in which twisting or rotating the pulse generator within its pocket results in lead dislodgement and device malfunction.
    • Arrhythmia-related problems
      • Appropriate shocks can have an adverse effect on the quality of life, including emotional problems and driving restrictions.
      • Inappropriate shocks
      • "Phantom" shocks
    • Miscellaneous complications
      • HF
      • Quality of life -The ICD is often associated with deleterious psychosocial effects, with as many as 50% of recipients reporting elevated levels of anxiety and depression resulting from the fear of receiving a shock, device failure, decrease in physical activity, and negative lifestyle changes (such as the inability to drive or to return to work). Some patients develop severe psychiatric problems after receiving appropriate shocks.

• Many ICD pulse generators have useful battery life remaining at the time of a patient's death or when the ICD is explanted due to infection or device upgrade.
• Because of concerns regarding the transmission of infectious disease from patient to patient and the lack of data regarding device reliability when used in such a fashion, reuse of explanted ICDs has not been approved by any governing or regulatory body.
• However, due to the large numbers of patients in resource-limited settings who have indications for an ICD but cannot afford the device, there is a potential for compassionate reuse of ICDs if sterility and reliability can be assured.

• ECG monitoring and storage
  • Contemporary ICDs have more extensive storage and monitoring capacities, allowing more expedient patient management, often without requiring a face-to-face visit. Some examples include:
    • Recording and displaying stored electrograms from tachyarrhythmia events, thus allowing for the detection of "silent" or asymptomatic arrhythmias where patient management is likely to change (e.g., AF).
    • Telemetry capabilities permit easier analysis when patients receive shocks.
    • Remote monitoring capabilities via telephone or internet allow healthcare providers to review ICD parameters and events without requiring the patient to come to the office or hospital.
  • Antitachycardia pacing
    • VT, particularly reentrant VT associated with the scar from a prior MI, can sometimes be terminated by pacing the ventricle at a rate slightly faster than tachycardia. When a paced impulse enters the reentrant circuit during a tachycardia, it can depolarize a segment of the circuit, leaving that segment refractory when the reentrant wave returns, thus terminating the tachycardia.
    • Antitachycardia pacing, or overdrive pacing, refers to the delivery of short bursts (e.g., eight beats) of rapid ventricular pacing to terminate VT. Although a variety of algorithms exist, antitachycardia pacing is usually programmed to be delivered at a slightly faster rate (e.g., at a cycle length 10 to 12% shorter) than the rate of the detected tachycardia.
    • S-ICDs cannot pace for bradycardia or antitachycardic pacing.
    • Though employed substantially less frequently, antitachycardia pacing can also terminate some atrial tachyarrhythmias, and these features have been incorporated in some contemporary ICD systems.
  • Cardioversion/defibrillation
    • A synchronized shock to be delivered at the peak of the R wave is referred to as cardioversion.
    • Because VT is an organized electrical rhythm, delivering an electrical shock during the vulnerable period of repolarization can cause VT to degenerate into VF.
    • Synchronized cardioversion prevents shock delivery during the vulnerable period. Although ICDs can be programmed to deliver synchronized shocks at a range of energies up to the device's maximum output (usually 30 to 35 joules), synchronized cardioversion can often terminate VT with relatively low energy (e.g., 10 joules or less).
    • An unsynchronized shock (i.e., a shock delivered randomly during the cardiac cycle) is called defibrillation. Healthcare providers can program ICDs to deliver unsynchronized shocks for very rapid ventricular arrhythmias (e.g., heart rate greater than 200 beats/min). Because VF is not an organized rhythm, synchronized cardioversion is neither possible nor necessary. Similarly, it can be difficult to synchronize with very rapid VTs, and such rapid rhythms are unlikely to be hemodynamically tolerated.
    • ICDs are typically programmed to deliver synchronized shocks at energies approaching the device's maximum output (usually 30 to 35 joules).
  • Bradycardia pacing
    • All contemporary transvenous ICDs can pace, although S-ICDs cannot deliver pacing therapies.
    • Many patients with an ICD have a conventional indication for cardiac pacing.
    • Separate ICDs and pacemakers can produce device-to-device interactions, particularly with older models, potentially resulting in inappropriate shocks and underdetection of VT/VF.
    • Patients should have only one transvenous or epicardial device with rare exceptions, although the combined use of a leadless pacemaker with an S-ICD is under investigation.
    • Generally, however, when a patient with a pacemaker develops an indication for ICD implantation, the pacemaker is removed and replaced with an ICD.
    • The device will be programmed accordingly for patients with known AV block or sinus node dysfunction or those receiving LV pacing as part of CRT.
    • For those without pre-existing AV block or sinus node dysfunction and who presumably do not require regular ventricular pacing, the ICD will typically be programmed to minimize the amount of pacing provided (e.g., pace only for intrinsic rates less than 40 beats/min).
    • In addition to the usual indications for pacing, the ability to provide pacing also protects against bradyarrhythmias that can follow a tachycardia or shock and against ventricular arrhythmias that are bradycardia-dependent. Because of the unique physiology following a ventricular tachyarrhythmia and device shock, ICDs allow for distinct post-shock pacing programming (usually at higher outputs).
  • Cardiac resynchronization therapy (CRT)
    • CRT, which utilizes biventricular pacing, is an effective treatment for symptomatic HF in some patients with LV dyssynchrony.
    • CRT is currently recommended in patients with advanced HF (usually NYHA class III or IV), severe systolic dysfunction (LV ejection fraction ≤35%), and intraventricular conduction delay (QRS >120 milliseconds).
    • The evidence of benefit is greatest in patients with left bundle branch block and a QRS duration >150 milliseconds.
    • Pacing of the LV is most frequently achieved by transvenous insertion of an electrode into a cardiac vein via the coronary sinus.
    • Surgical placement of an epicardial lead is also an option in patients following failed efforts at transvenous lead placement or in patients undergoing cardiac surgery for another reason.
    • Improvement in HF can reduce the frequency of ventricular arrhythmias, raising the possibility that biventricular pacing may have an adjunctive role with an ICD by reducing the need for ICD therapy.
  • Perioperative ICD functioning
    • During surgical procedures, the function of ICDs may be affected by electromagnetic interference (EMI), most commonly due to the use of an electrosurgery unit (ESU).
    • ICDs with integrated bipolar sensing configuration may be more susceptible to EMI than true bipolar sensing.
    • Very rarely, direct damage from cautery to the ICD may alter its delivery of pacing or shocks or reset the ICD to an alternate or backup mode. The more common concern is that the device might misinterpret the cautery as tachyarrhythmia, which leads to withholding bradycardia pacing and perhaps inappropriate ICD shocks.

• Some patients at risk for SCD do not meet established criteria for implantation of an ICD or may require only short-term protection (such as patients awaiting subsequent ICD insertion or cardiac transplantation).
• A wearable WCD may be preferable to either ICD insertion or bystander resuscitation in such settings.

• Some patients who are at risk for SCD and require an ICD will have compelling reasons for avoiding the indwelling transvenous leads associated with a standard ICD (e.g., other indwelling leads or catheters, high risk for systemic infection, relatively young age at implant with numerous device implants anticipated over a lifetime, etc.).
• An entirely S-ICD has been developed to provide an effective alternative means of defibrillation, albeit without some of the standard capabilities of a traditional transvenous ICD (i.e., no antitachycardia pacing or backup bradycardia pacing).

• Nearly all survivors of SCA without a reversible cause should be evaluated for placement of an ICD. Because an ICD treats but does not prevent arrhythmias, patients with symptoms or device discharges may require adjunctive antiarrhythmic therapy.
• In addition to ICD therapy for survivors of SCA, there are three main indications for concomitant antiarrhythmic drug therapy:
  • To reduce the frequency of ventricular arrhythmias in patients with frequent ICD shocks. In one analysis, the occurrence of frequent ICD shocks was the primary reason for adding an antiarrhythmic drug (64%).
  • To suppress supraventricular arrhythmias that may cause symptoms or interfere with ICD function, potentially resulting in "inappropriate" shocks.
    • "Inappropriate" shocks result from non-life-threatening arrhythmias which meet the programmed parameters for ICD therapy, primarily based upon rate (e.g., AF with a rapid ventricular response exceeding the programmed threshold for delivering a shock).
    • "Inappropriate" shocks have been reported in up to 29% of ICD patients and can have a substantial impact on the patient’s quality of life.
      • These shocks are caused by various arrhythmias, including sinus tachycardia, AF, and NSVT.
      • More sophisticated programming features of current-generation ICDs may allow the device to ignore clinically unimportant and non-life-threatening arrhythmias rather than delivering an unnecessary shock.
  • To reduce the ventricular rate of VT so that it is better tolerated hemodynamically or more amenable to termination by anti-tachycardia pacing or low energy cardioversion.

• Medications used to manage cardiac arrhythmias (Table 3):

• Empiric pharmacologic therapy for SCA survivors, primarily with beta-blockers or an antiarrhythmic drug, is an effective approach for survivors of SCA. They have refused ICD placement or are not candidates for an ICD.
• Beta-blockers have some efficacy with relatively few side effects, while for most patients, amiodarone is the most efficacious antiarrhythmic drug for preventing recurrent ventricular arrhythmias.
• However, in current practice, when pharmacologic therapy is administered to a patient with or without (because of refusal or noncandidacy for) an ICD, empiric treatment with beta-blockers or amiodarone is the preferred approach.
  • Other antiarrhythmic drugs (for example, mexiletine or sotalol) are considered if there is recurrent arrhythmia despite therapy with amiodarone or a beta-blocker.

• Nearly all patients who have survived SCA should receive a beta-blocker as part of their therapy.
• Beta-blockers are not generally considered adequate monotherapy and should be used with an antiarrhythmic drug for most patients resuscitated from SCA due to VT or VF. However, the associated anti-adrenergic effects of beta-blockers may effectively reduce arrhythmias and SCA when no specific antiarrhythmic treatment is given.
  • In an analysis from the AVID trial, patients discharged from the hospital on a beta-blocker had a mortality reduction compared with those not receiving a beta-blocker.
• Most SCA survivors will have multiple indications for a beta-blocker (e.g., post-myocardial infarction, HF, etc.) from which they derive clinical benefit.
  • Beta-blockers reduce the incidence of sudden death and total mortality in patients with a recent myocardial infarction and those with symptomatic HF or congenital LQTS.
  • Beta-blockers should be used as part of the medical regimen following SCA due to VT/VF, even in the absence of any additional indications.
• Beta-blockers can potentiate the effects of class I antiarrhythmic drugs by preventing the effect of sympathetic stimulation on reversing the depressant effect on slowing conduction. They can also potentiate the action of class III antiarrhythmic drugs by preventing the sympathetic effect of shortening repolarization.

• Amiodarone is the most effective for preventing recurrent ventricular tachyarrhythmias, although mexiletine, sotalol, and dofetilide are also useful in reducing recurrent ventricular arrhythmias.
  • Empiric therapy with amiodarone is preferred for immediately following SCA in patients with recurrent ventricular tachyarrhythmias and those who have refused (or are not candidates for) ICD placement.
  • Following patient stabilization, if there are concerns about potential toxicity related to amiodarone, particularly for anticipated long-term use, mexiletine, sotalol, or dofetilide may be considered.

• Several clinical trials and systematic reviews have evaluated the efficacy of antiarrhythmic drugs as adjuvant therapy in ICD patients. There were significant differences in trial methodologies, which limit direct comparisons. Amiodarone has generally been the most effective antiarrhythmic drug for preventing ventricular arrhythmias (and associated ICD shocks).
  • There was significant heterogeneity among the trials in one systematic review that included eight randomized trials involving 1,889 patients. Key findings included:
    • Amiodarone in combination with a beta-blocker significantly reduced the incidence of shocks compared with the beta-blocker alone.
    • Sotalol reduced the incidence of ICD shocks when compared with a placebo. There was also a trend toward fewer shocks in patients treated with sotalol versus another beta-blocker.
    • Treatment with either azimilide or dofetilide resulted in nonsignificant trends towards reduction in total ICD shocks compared with placebo. However, the incidence of appropriate ICD therapies (shocks plus antitachycardia pacing) was significantly reduced by azimilide.
    • Another major advantage of amiodarone is its very low frequency of proarrhythmia. Although amiodarone can prolong the QT interval, torsades de pointes are rare. Caution is necessary when amiodarone is given with other drugs that can prolong the QT interval or therapy is complicated by hypokalemia or hypomagnesemia.

• When patients are started on an antiarrhythmic drug, a baseline ECG should be obtained before drug initiation and then serial ECGs obtained for the first two to three days, particularly to monitor heart rate and assess for any significant QT interval prolongation.
• Amiodarone
  • The initial dosing of amiodarone will vary depending on the route (IV or oral), as well as the clinical situation:
    • For patients with electrical storm or incessant VT, amiodarone IV (150 mg IV push, followed by 1 mg/minute IV infusion for six hours, followed by 0.5 mg/min IV infusion for 18 additional hours) is the initial antiarrhythmic agent.
    • For patients who have been on IV therapy for more than two weeks, oral maintenance amiodarone at a dose of 200 to 400 mg/day is begun.
    • For patients who have been on IV therapy for one to two weeks, an intermediate maintenance oral amiodarone dose of 400 to 800 mg/day is begun. This should be continued until a total loading dose of 10 to 15 grams has been received, then the dose should be reduced to the usual maintenance dose of 200 to 400 mg/day. As oral amiodarone is only approximately 50% bioavailable, a total of 20 to 30 grams needs to be administered.
    • For patients who have been on IV therapy for one week or less, a full oral amiodarone loading dose of 400 to 1200 mg/day (typically in two divided doses) is started. This should be continued until a total loading dose of 10 to 15 grams has been received (and a total of 20 to 30 grams administered due to the reduced oral bioavailability), then the dose should be reduced to the usual maintenance dose of 200 to 400 mg/day.
• Sotalol
  • Sotalol is not universally available in intravenous form. Bradycardic and proarrhythmic events can occur after the initiation of sotalol therapy and with each upward dosing adjustment. As a result, sotalol should be initiated, and doses increased in a hospital with cardiac rhythm monitoring and assessment facilities.
  • Sotalol is started at a dose of 80 mg twice daily, with dose adjustments at three-day intervals once steady-state plasma concentrations have been achieved and the QT interval reviewed on an ECG. Patients with renal insufficiency require a modification of the dosing interval.
• Dofetilide
  • Dofetilide is only available in oral form and is not universally available in all countries.
• Mexiletine
  • Mexiletine, a lidocaine-like antiarrhythmic drug, is only available for oral use.
  • It is often used with or without amiodarone for treating patients with an ICD who have ventricular arrhythmias that are of concern.
  • The usual dose is 200 to 400 mg PO three times daily.

• Patients with recurrent, or breakthrough, arrhythmias resulting in repeat ICD shocks or SCA despite therapy with a beta-blocker or antiarrhythmic drug represent a significant clinical challenge. As with the occurrence of any ventricular arrhythmia, any identifiable reversible causes (e.g., myocardial ischemia, electrolyte disturbances, etc.) should be corrected.
• In the absence of any reversible causes, treatment should be approached as follows:
  • For patients who are taking only a beta-blocker, an antiarrhythmic drug, ideally amiodarone, should be added.
  • A beta-blocker should be added for patients taking only an antiarrhythmic drug.
  • For patients who are taking both a beta-blocker and an antiarrhythmic drug, treatment options include:
    • Upward titration of either or both existing drugs or,
    • Discontinuation of the current antiarrhythmic drug in favor of an alternative antiarrhythmic drug.
    • First, increasing the beta blocker's dose and the current antiarrhythmic drug to the maximum recommended dose (or maximum tolerated dose if side effects arise) is preferred. If this approach is ineffective and the patient continues to have recurrent ventricular arrhythmias and shocks, the current antiarrhythmic drug should be stopped and treatment initiated with another agent.
    • Another important option for patients with recurrent arrhythmia despite amiodarone and a beta-blocker is adding a class I antiarrhythmic agent that does not alter the QT interval (i.e., mexiletine or propafenone).

• The primary goal of using beta-blockers or antiarrhythmic drugs in patients with an ICD is to minimize the frequency of recurrent ventricular arrhythmias, thereby decreasing the likelihood of receiving additional ICD shocks.
• Beyond reducing the likelihood of ICD shocks, however, antiarrhythmic drug therapy may impact the efficacy of ICD therapies by potentially altering defibrillation thresholds and slowing the ventricular rates of any recurrent sustained tachyarrhythmias.

• Any antiarrhythmic drug can potentially alter the DFT. However, the effect has been most pronounced with amiodarone and its major metabolite, desethylamiodarone, increasing the DFT dose-dependent.
• DFT testing has historically been performed at the time of ICD implantation, although the routine necessity for this evaluation with the current generation of ICDs has been questioned. However, repeat DFT testing may be warranted after the initiation of amiodarone if there is concern about rising DFT thresholds (as may occur in certain clinical situations, including AF, hypertension, and left ventricular hypertrophy).
• The report on the efficacy of routine ICD testing is discussed above (Yannopoulos et al., 2017). patients had an ICD test due to the initiation or dose-adjustment of an antiarrhythmic drug (primarily amiodarone or sotalol), and the ICD failed to defibrillate only two patients.

• In patients receiving chronic antiarrhythmic drug therapy, the rate of recurrent VT is often slower than the rate seen during the index arrhythmia. This slower ventricular rate can have both positive and negative impacts on the delivery of ICD therapy:
  • Antitachycardia pacing is often more effective for the treatment of VT with a slower ventricular rate. When antitachycardia pacing effectively terminates the VT, the ICD does not deliver a shock, and many patients will not know about the event.
  • Slower ventricular rates during VT may result in the VT falling below the previously defined rate thresholds for the ICD to detect and treat the arrhythmia. As a result, if no ICD programming changes are made, and the VT is hemodynamically significant (i.e., resulting in syncope, palpitations, chest pain, dyspnea, or even SCA), the patient may not receive an appropriately-indicated therapy.
  • Consequently, lowering the VT detection cutoff is common when initiating antiarrhythmic drug therapy. The specific detection threshold is individualized based on the specific data from prior events in the individual patient.