Sudden death prevention

Overview
The optimal approach to prevention of SCD following ST elevation MI (STEMI) has been evaluated in multiple randomized trials. In general, post-STEMI patients should be treated with evidenced based therapies that have been associated with a reduction in SCD including beta-blockers, ACE-inhibitors (or ARBs in patients who are ACE intolerant) and statins. In patients who have symptomatic congestive heart failure (CHF), an aldosterone antagonist may be a reasonable additional therapy. Despite the intuitive benefits of anti-arrhythmics, amiodarone and sotalol have not been shown to reduce all cause mortality following STEMI, although amiodarone may be useful in reducing the frequency of shocks in patients with ICDs who have unacceptably high rates of shock. In general terms, ICD placement is indicated in those patients with a reduced left ventricular ejection fraction at 40 days post MI and / or 3 months following revascularization (PCI or CABG) for STEMI given the survival benefits in this population.

Timing of Sudden Cardiac Death Following ST elevation MI
Patients with STEMI are at risk of sudden cardiac death. The timing of sudden cardiac death following STEMI is as follows:


 * In the first 3 months after STEMI one quarter of sudden cardiac deaths occur. This statistic is critical in so far as implantable cardiac defibrillators are often not implanted in the first three months. It is for this reason that wearable defibrillators are sometimes used in patients with a large MI and reduced ejection fraction.


 * In the first year following STEMI one half of the sudden cardiac deaths occur.


 * Beyond one year, there is still an increased risk of sudden cardiac death for a prolonged period of time.

Medical Therapy to Prevent Sudden Death Following STEMI
Therapies aimed to reduce disease progression, stabilize plaque, improve left ventricular function, and reduce ischemia may minimize the risk of sudden cardiac death. These therapies include beta blockade, ACE inhibition, and statins.

Beta Blockers
Beta blocker administration has been associated with a reduction in sudden cardiac death from 5.0% to 3.3% in a review of 13 trials. The reduction in SCD was greatest among patients with congestive heart failure. Among patients with an ICD, beta blocker administration has been associated with an additional reduction in mortality in MADIT II (hazard ratio of 0.42 to 0.44) and a lower frequency of ICD discharge (hazard ratio of 0.48).

ACE inhibition
ACE inhibitor administration has been associated with a 20% relative and a 1.4% absolute reduction in the risk of SCD in a metanalysis of randomized trials.

Angiotensin II receptor blockers (ARBs)
If a patient is intolerant to ACE inhibitor, an ARB can be administered. Valsartan is non-inferior to captopril in reducing post MI mortality, and may therefore confer similar benefits in SCD.

Statin Therapy
Among patients with an ICD implanted, statin administration has been associated with a reduction in documented arrhythmias post-MI in observation studies.

Aldosterone antagonists
In the EPHESUS trial, among the specific subgroup of post MI patients who have left ventricular dysfunction and / or diabetes, eplerenone administration was associated with reduction in all cause and SCD mortality (4.9% vs 6.1%).

Anti-arrhythmics
Despite the intuitive benefits of anti-arrhythmic treatments, anti-arrhythmics have not shown a reduction in all cause mortality in the management of post MI SCD. Amiodarone was associated with a reduction in arrhythmic death among patients with an LVEF of <40% following STEMI, but all cause mortality was not improved in the CAMIAT trial. Anti-arrhythmics such as amiodarone may be useful in reducing the frequency of shocks in patients with an ICD who have excessively frequent shocks. Flecainide and propafenone should not be administered as these Class I C agents are proarrhythmic in patients with coronary artery disease.

Overview
In general terms, ICD placement is indicated in those patients with a reduced left ventricular ejection fraction at 40 days post MI and / or 3 months following revascularization (PCI or CABG) for STEMI given the survival benefits in this population. Patients should also be treated with evidence based therapies including beta-blockers, ACE inhibitors and statins. Patients undergoing ICD implantation should not have a limited life expectancy due to non-cardiovascular causes.

Consensus and CMS Indications for ICD Placement
The following are clear Grade 1 A or CMS supported recommendations for placement of an ICD:
 * Based upon the MADIT II study entry criteria, patients with a prior MI and an LVEF of < 30% should be treated with an ICD after 40 days. This is true whether or not the patient is inducible on electrophysiologic testing.
 * Based upon the SCD-Heft study entry criteria, patients with an ischemic cardiomyopathy who are symptomatic with NYHA grade II or III CHF with an LVEF < 35%. Again, This is true whether or not the patient is inducible on electrophysiologic testing.
 * Some patients will not have an LVEF as low as < 30% as in MADIT II or as low as an LVEF < 35% as in SCD-HeFT, but if they have an LVEF < 40%, and non sustained ventricular tachycardia on Holter monitoring and are inducible on EP testing, then they are appropriate candidates for ICD placement based upon the MUSTT and MADIT I trials.
 * Based upon the MADIT I study entry criteria, patients with a history of MI with an LVEF < 35% who have inducible VT or VF on electrophysiologic testing at least 4 weeks after STEMI.
 * Patients who meet the COMPANION criteria who have an indication for a cardiac resynchronization (CRT) device and have NYHA class IV congestive heart failure (CHF)

Timing of ICD Placement
Despite the fact that the highest risk of SCD is in the first 3 months after STEMI, the DINAMIT and IRIS trials did not show a benefit of ICD placement during the first 3 months after STEMI. Likewise, it should be noted that MADITT II excluded patients who had an MI or revascularization within the preceding 40 days. The results of DINAMIT and IRIS form the basis for the guidelines recommendation that ICD implantation be deferred until 40 days following STEMI. In DINAMIT, 332 patients were enrolled if they had an MI in the previous 6 to 40 days (the average time of implantation was 18 days following MI) and their LVEF was < 35%. A heart rate > 80 beats per minute or a reduced heart rate variability was required. At 30 days of follow-up, the all cause mortality was 7.5% in ICD patients and 6.9% in placebo patients (p=NS). Non-arrhythmic deaths were more common in the ICD arm, and arrhythmic deaths were more common in the placebo arm. Similar trends in mortality were observed in the subsequent IRIS trial, which enrolled a larger number of patients (n=898), during a similar period following STEMI (5 to 31 days) with 37 months of follow-up.

There are some differences in society and CMS recommendations regarding the timing of ICD placement. CMS recommends that LVEF be assessed at 3 months following the most recent revascularization. In contrast to the CMS guidance, the 2008 American College of Cardiology / American Heart Association /Heart Rhythm Society guidelines recommend a 40 day delay following a STEMI and there is no recommendation regarding a 3 month delay following revascularization.

Management of the Patient While Awaiting ICD Placement
Evidence based treatment with beta-blockers, statins, and ACE-inhibitors should be administered to patients while they await placement of an ICD at 40 days to 3 months following STEMI. An external cardiac defibrillator vest can be prescribed in high risk patients with a low ejection fraction while the patient is awaiting assessment of their LVEF at 3 months.

Role of Electrophysiology Testing
Inducibiity and pharmacologic suppression of VT/VF on electrophysiologic studies is no longer deemed to be relevant based upon the MUSTT study and the MADITT I study. Importantly, lack of inducibility on electrophysiologic testing should not preclude implantation of an ICD.

ICD Implantation in Patients with Chronic Stable Symptomatic Congestive Heart Failure: The SCD-HeFT Trial
While the previous trials such as MADITT, MUST, IRIS and DANIMIT focused on post MI patients, the SCD-HeFT trial instead focused on a different population, namely patients with chronic stable symptomatic congestive heart failure (CHF) due to either ischemic or nonischemic cardiomyopathy [25]. In contrast to previous studies where only a reduced ejection fraction was required, in SCD-HeFT symptoms of CHF (NYHA class II or III) were required along with an LVEF of < 35%. For instance, it should be noted that only about two thirds of patients in MADIT II had symptoms of heart failure. ICD implantation was associated with a reduction in mortality at 5 years versus placebo (29% versus 36%), with similar benefits observed both in patients with ischemic and non-ischemic cardiomyopathy. The third arm, amiodarone therapy, was not associated with a reduction in mortality. Based upon SCD-HeFT, an ICD is indicated in patients with an ischemic cardiomyopathy with NYHA class II – III CHF and an LVEF < 35%.

The Benefit of ICD Implantation May Be Greater in Patients with a QRS Duration > 120 msec
In both SCD-HeFT and MADIT II, the reduction in SCD was greater in patients with a QRS duration > 120 msec.

Wearable Defibrillators
In patients with a large MI with a low EF who are awaiting permanent ICD implantation, use of a wearable defibrillator is a reasonable strategy.

Cardiac resynchronization therapy (CRT) Combined with ICD Placement
Patients with congestive heart failure following MI may have dyssynchrony or a loss of coordinated contraction in the left ventricle. Restoration of synchronous contraction can improve patient symptoms and may improve left ventricular function and even mortality in appropriate patients. It is notable that the indications for CRT placement are similar to those for ICD placement, and some patients may benefit from a combined device that functions in both capacities.

Although there are no clear guidelines recommendations, based upon the results of the COMPANION trial it is reasonable to place a combined ICD / CRT device in patients with the following:
 * Symptomatic NYHA Class III or IV congestive heart failure
 * A left ventricular ejection fraction < 35%
 * Evidence of left ventricular dyssynchrony with a QRS > 120 msec

==ACC / AHA Guidelines- Recommendations for Implantable Cardioverter Defibrillators (DO NOT EDIT) == {{cquote|

Class I
1. ICD therapy is indicated in patients who are survivors of cardiac arrest due to VF or hemodynamically unstable sustained VT after evaluation to define the cause of the event and to exclude any completely reversible causes. (Level of Evidence: A)

2. ICD therapy is indicated in patients with structural heart disease and spontaneous sustained VT, whether hemodynamically stable or unstable. (Level of Evidence: B)

3. ICD therapy is indicated in patients with syncope of undetermined origin with clinically relevant, hemodynamically significant sustained VT or VF induced at electrophysiological study. (Level of Evidence: B)

4. ICD therapy is indicated in patients with LVEF less than 35% due to prior MI who are at least 40 days post-MI and are in NYHA functional Class II or III. (Level of Evidence: A)

5. ICD therapy is indicated in patients with nonischemic DCM who have an LVEF less than or equal to 35% and who are in NYHA functional Class II or III. (Level of Evidence: B)

6. ICD therapy is indicated in patients with LV dysfunction due to prior MI who are at least 40 days post-MI, have an LVEF less than 30%, and are in NYHA functional Class I. (Level of Evidence: A)

7. ICD therapy is indicated in patients with nonsustained VT due to prior MI, LVEF less than 40%, and inducible VF or sustained VT at electrophysiological study. (Level of Evidence: B)

Class IIa
1. ICD implantation is reasonable for patients with unexplained syncope, significant LV dysfunction, and nonischemic DCM. (Level of Evidence: C)

2. ICD implantation is reasonable for patients with sustained VT and normal or near-normal ventricular function. (Level of Evidence: C)

3. ICD implantation is reasonable for patients with HCM who have 1 or more major{dagger} risk factors for SCD. (Level of Evidence: C)

4. ICD implantation is reasonable for the prevention of SCD in patients with ARVD/C who have 1 or more risk factors for SCD. (Level of Evidence: C)

5. ICD implantation is reasonable to reduce SCD in patients with long-QT syndrome who are experiencing syncope and/or VT while receiving beta blockers. (Level of Evidence: B)

6. ICD implantation is reasonable for non hospitalized patients awaiting transplantation. (Level of Evidence: C)

7. ICD implantation is reasonable for patients with Brugada syndrome who have had syncope. (Level of Evidence: C)

8. ICD implantation is reasonable for patients with Brugada syndrome who have documented VT that has not resulted in cardiac arrest. (Level of Evidence: C)

9. ICD implantation is reasonable for patients with catecholaminergic polymorphic VT who have syncope and/or documented sustained VT while receiving beta blockers. (Level of Evidence: C)

10. ICD implantation is reasonable for patients with cardiac sarcoidosis, giant cell myocarditis, or Chagas disease. (Level of Evidence: C)

Class IIb
1. ICD therapy may be considered in patients with nonischemic heart disease who have an LVEF of less than or equal to 35% and who are in NYHA functional Class I. (Level of Evidence: C)

2. ICD therapy may be considered for patients with long-QT syndrome and risk factors for SCD. (Level of Evidence: B)

3. ICD therapy may be considered in patients with syncope and advanced structural heart disease in whom thorough invasive and noninvasive investigations have failed to define a cause. (Level of Evidence: C)

4. ICD therapy may be considered in patients with a familial cardiomyopathy associated with sudden death. (Level of Evidence: C)

5. ICD therapy may be considered in patients with LV noncompaction. (Level of Evidence: C)

Class III
1. ICD therapy is not indicated for patients who do not have a reasonable expectation of survival with an acceptable functional status for at least 1 year, even if they meet ICD implantation criteria specified in the Class I, IIa, and IIb recommendations above. (Level of Evidence: C)

2. ICD therapy is not indicated for patients with incessant VT or VF. (Level of Evidence: C)

3. ICD therapy is not indicated in patients with significant psychiatric illnesses that may be aggravated by device implantation or that may preclude systematic follow-up. (Level of Evidence: C)

4. ICD therapy is not indicated for NYHA Class IV patients with drug-refractory congestive heart failure who are not candidates for cardiac transplantation or CRT-D. (Level of Evidence: C)

5. ICD therapy is not indicated for syncope of undetermined cause in a patient without inducible ventricular tachyarrhythmias and without structural heart disease. (Level of Evidence: C)

6. ICD therapy is not indicated when VF or VT is amenable to surgical or catheter ablation (e.g., atrial arrhythmias associated with the Wolff-Parkinson-White syndrome, RV or LV outflow tract VT, idiopathic VT, or fascicular VT in the absence of structural heart disease). (Level of Evidence: C)

7. ICD therapy is not indicated for patients with ventricular tachyarrhythmias due to a completely reversible disorder in the absence of structural heart disease (e.g., electrolyte imbalance, drugs, or trauma). (Level of Evidence: B)}}

==ACC / AHA Guidelines- Recommendations for Implantable Cardioverter-Defibrillators in Pediatric Patients and Patients With Congenital Heart Disease (DO NOT EDIT) == {{cquote|

Class I
1. ICD implantation is indicated in the survivor of cardiac arrest after evaluation to define the cause of the event and to exclude any reversible causes. (Level of Evidence: B)

2. ICD implantation is indicated for patients with symptomatic sustained VT in association with congenital heart disease who have undergone hemodynamic and electrophysiological evaluation. Catheter ablation or surgical repair may offer possible alternatives in carefully selected patients. (Level of Evidence: C)

Class IIa
1. ICD implantation is reasonable for patients with congenital heart disease with recurrent syncope of undetermined origin in the presence of either ventricular dysfunction or inducible ventricular arrhythmias at electrophysiological study. (Level of Evidence: B)

Class IIb
1. ICD implantation may be considered for patients with recurrent syncope associated with complex congenital heart disease and advanced systemic ventricular dysfunction when thorough invasive and noninvasive investigations have failed to define a cause. (Level of Evidence: C)

Class III
1. All Class III recommendations found in Section 3, "Indications for Implantable Cardioverter-Defibrillator Therapy," apply to pediatric patients and patients with congenital heart disease, and ICD implantation is not indicated in these patient populations. (Level of Evidence: C) }}

Unresolved Questions in Identifying the Optimal Patients for ICD Implanatation Following STEMI
The benefits of ICD placement in those patients over the age of 75 and in those with impaired renal function is not well defined, but post-hoc analyses from randomized trials suggest a lack of benefit in these populations. Non-sustained VT on Holter monitoring, an abnormal signal averaged EKG, and abnormal micro T wave alternans are associated with an increased risk of SCD, however, it is not known if ICD therapy is of benefit in these populations.