Sudden Cardiac Death: Primary and Secondary Prevention
from Clinical Update, Summer 2005
by Tony W. Simmons, MD
Assistant Professor, Internal Medicine, Cardiology
Disclosure: Dr. Simmons is involved in research activities with Medtronic, Guidant and St. Jude.
Abstract: The magnitude of sudden cardiac deaths (SCD) exceeds the total number of deaths from AIDS, breast cancer, lung cancer and stroke annually. SCD is most commonly caused by a ventricular tachy-arrhythmia that degenerates into ventricular fibrillation. Implantable cardioverter defibrillators (ICD) have proven to be effective in primary and secondary prevention of sudden cardiac deaths. In response to studies, approved Medicare guidelines for ICD use have broadened dramatically. Now, essentially all patients with some type of organic heart disease and ejection fraction of 35% are candidates for an ICD.
It is estimated that 450,000 sudden cardiac deaths (SCD) occur annually in the United States (1). The majority of these deaths have been attributed to coronary artery disease. However, these deaths are almost always due to ventricular tachyarrhythmias in the absence of an acute myocardial infarction. Worldwide, approximately three million people a year suffer a sudden cardiac arrest with a survival rate that is estimated to be less than 1%. The Center for Disease Control (CDC) recently estimated that in the United States the survival for a sudden cardiac arrest is 5% (1). Although there has been a reduction in total cardiac mortality in the United States, the magnitude of sudden cardiac deaths still exceeds the total number of deaths from AIDS, breast cancer, lung cancer and stroke annually (2).
Sudden cardiac death most commonly occurs in patients with organic heart disease, either coronary artery disease with or without a myocardial infarction or a cardiomyopathy either dilated or hypertrophic. Primary electrical systems disease, in the form of a sodium or a potassium channel abnormality, accounts for the remainder of the deaths.
Mechanisms of Sudden Cardiac Deaths
Sudden cardiac death is most commonly caused by a ventricular tachyarrhythmia that degenerates into ventricular fibrillation. In patients with coronary artery disease, the ventricular tachyarrhythmia may be a monomorphic ventricular tachycardia that is hemodynamically unstable and then degenerates into ventricular fibrillation. Polymorphic ventricular tachycardia or ventricular fibrillation is the initial event in patients with ion channelopathies, such as the Brugada syndrome or in patients with hypertrophic cardiomyopathy. Less commonly, bradyarrhythmias are associated as the initiating event of sudden cardiac death.
Secondary Prevention of Sudden Cardiac Deaths
Initial therapies utilizing implantable cardioverter defibrillators (ICD) were aimed at preventing sudden cardiac deaths following the survival of an initial event. The implantable cardioverter defibrillators proved to be remarkably effective with the initial implant of an ICD in humans occurring in 1980. Improved technology associated with the implantation of an ICD as well as multiple studies showing dramatic success in preventing sudden cardiac deaths led to widespread acceptance of this new therapy. Implantation of ICDs increased from around 10,000 per year in 1990 up to 90,000 per year in 2000. The studies which showed dramatic success in secondary prevention of sudden cardiac deaths include: AVID (3), CASH (4), CIDS (5), etc.
Primary Prevention of Sudden Cardiac Deaths
With the widespread acceptance of the ICD as a method treating the survivors of sudden cardiac death, attention has turned to primary prevention. This is a much larger potential pool of patients. The overall survival rate for sudden cardiac death in the United States is only 5%; therefore, 95% of patients suffering their initial event fail to survive to become candidates for secondary prevention.
The earliest primary prevention trial was the Multicenter Automatic Defibrillator Implantation Trial (MADIT) (6). This trial involved a direct comparison between the ICD and the best medical management. The patients in this study had coronary artery disease with an ejection fraction less than 35% and had an abnormal electrophysiologic study. This trial was stopped early after it showed a 55% reduction in total mortality and a 75% reduction in sudden cardiac deaths.
In the Multicenter Unsustained Tachycardia Trial (MUSTT)(7), patients with an ejection fraction less than 40% and coronary artery disease were randomized to a control group with ace inhibitors and beta blockers versus best guided electrophysiologic therapy. For most of these patients the best guided therapy was with the ICD. This trial also resulted in statistically significant reduction of sudden cardiac death of 28%.
In 2002, a study similar to the MADIT study, the MADIT II trial, was published (8). This study included patients with coronary artery disease, left ventricular ejection fraction less than 30% and no other risk stratification criteria. The study enrolled 1,232 patients, 60% of whom received ICD. This trial was stopped after a follow-up period of less than 20 months when it revealed a 30% reduction of total mortality.
These trials resulted in a change in the scientific and clinical indications for ICD implantation. The Centers for Medicare and Medicaid Services (CMS) elected to fund implantation of the ICD in these primary prevention patients only if their QRS exceeded 120msec. This resulted in some controversy and left electrophysiologists with an ethical dilemma. Many physicians believed that this 120 msec restriction was an effort to control costs and was contrary to the scientific data.
Recent Primary Prevention Trials
In 2004 and early 2005, several trials were published involving the primary prevention of SCD in patients with coronary artery disease as well as patients with non-ischemic dilated cardiomyopathy.
The COMPANION trial (9), which was the comparison of medical therapy, pacing and defibrillation in patients with chronic congestive heart failure, involved patients with both coronary artery disease and dilated cardiomyopathy with ejection fractions less than 30% and QRS width greater than 120msec. Patients were then randomized to best medical management versus a cardiac resynchronization defibrillator. In this trial, there was a 28% reduction in the risk of death or hospitalization after one year. There was a 36% reduction in all cause mortality and this therapy held true for both dilated cardiomyopathy and coronary artery disease patients.
The Sudden Cardiac Death in Heart Failure (SCD-HeFT) trial involved 2,521 patients followed for a minimum of 45.5 months (10). These patients were randomized for best medical therapy, Amiodarone or ICD. There was a significant reduction in all cause mortality over a placebo or Amiodarone by 23%.
New Medicare Guidelines for the Primary Prevention of Sudden Cardiac Death Based on the recently published primary prevention trials, CMS published a decision memorandum on January 27, 2005(11). In this decision summary, the approved Medicare guidelines for ICD implantation have dramatically changed. This decision was based primarily on the SCD-HeFT, Companion and MADIT II data.
CMS has determined that patients with coronary artery disease and an ejection fraction of less than or equal to 35% are now indicated for an ICD. This decision increases the lower limit of the qualifying ejection fraction from 30 to 35% and eliminates the need for secondary indicators of risks. Previously needed secondary indicators were electrophysiologic studies, T-wave Alternans, heart rate variability, etc.
CMS has also approved a new diagnosis for primary prevention which includes nonischemic dilated cardiomyopathy with New York Heart Association Class II and III. Therefore, patients with idiopathic dilated cardiomyopathy and other forms of cardiomyopathy with ejection fraction of 35% or less are now indicated for an ICD. The only caveat is that this diagnosis must be in place for at least nine months. If the diagnosis has been in place from three to nine months, the patients can have an ICD but they will need to be entered into a special registry, either an independent registry from each institution approved by the Institutional Review Board (IRB) or a yet to be established ACC/Heart Rhythm Society Registry.
In addition, New York Heart Association Class IV patients are now indicated for an ICD if they meet the requirements for cardiac resynchronization therapy.
Essentially all patients with some type of organic heart disease and ejection fraction of 35% are now qualified for an ICD. These patients should be considered for referral to an institution capable of implanting these devices. These institutions should have a low complication rate and high rate of successful ICD implantation and provide a patient registry as required by CMS. This decision by CMS has removed many of the ethical and financial concerns regarding indications for ICD implantation making it easier for physicians to provide the medical care that is proven to be necessary.
Heart Center physicians may be consulted by calling PAL® at 1-800-277-7654.
- Zhi-Jie Z, Croft JB, Giles WH, et al: Sudden cardiac death in the United States, 1989-1998. Circulation, 2001; 104:2158-2163.
- Myerburg RJ, Castellanos A;Cardiac arrest in sudden cardiac death. In: Braunwald E, Zipes DP, Libby P, eds. Heart Disease: A Textbook of Cardiovascular Medicine, 6th ed., Philadelphia: WB Saunders; 2001:890-931.
- The Antiarrhythmics Versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J of Med. 1997; 337:1576-1584.
- Kuck KH, Cappato R, Siebels J, Reppel R for the CASH investigators. Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest. Circulation, 2000; 102:748-754.
- Connolly SJ, Gent M, Roberts RS, et al: Canadian implantable defibrillator study (CIDS): a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation, 2000; 101:1297-1302.
- Moss AJ, Hall WJ, Cannom DS, Daubert JP, Higgins SL, Klein H, et al: Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J of Med. 1996; 335:1933-1940.
- Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN, Hafley G: A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J of Med. 1999;341:1882-1890.
- Moss AJ, Zareba W, Hall WJ, et al: Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J of Med. 2002; 346:877-883.
- Salukhe TV, Francis DP, Sutton R; Comparision of medical therapy, pacing and defibrillation in heart failure (COMPANION) close trial terminated early; combined biventricular pacemaker defibrillators reduced all-cause mortality and hospitalization. Int J of Cardiol, 2003:87:119-120.
- Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, et al: Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J of Med. 2005:352:225-237.
- Centers for Medicare and Medicaid services. Administrative file CAG: decision memorandum: implantable cardioverter defibrillators (# 00157R3). January 27, 2005. Available at: http:// www.cms.hhs.gov.