What Every Physician Should Know:
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1 What Every Physician Should Know: The Canadian Heart Rhythm Society estimates that, in Canada, sudden cardiac death (SCD) is responsible for about 40,000 deaths annually; more than AIDS, breast cancer and lung cancer combined. In this article, Dr. Johri and Dr. Simpson examine SCD and provide case examples which highlight the appropriate use of implantable cardioverter defibrillators (ICD). Amer M. Johri, MD, MSc, FRCPC; and Chris Simpson, MD, FRCPC, FACC John s Case John, 70, sustained a large anterior MI in In that same year, he underwent minimally invasive coronary artery bypass surgery, with grafting of the left anterior descending coronary artery, along with an arterial graft. He did well post-operatively, although he was followed for stable, chronic New York Heart Association (NYHA) Class II heart failure. John s medications include: 75 mg of metoprolol, b.i.d., 10 mg of ramipril, q.d. and 81 mg of acetylsalicylic acid, q.d. Copyright Not for Sale or Commercial Distribution A multigated acquisition scan, conducted in 2004, showed an ejection fraction (EF) of 20%. What more can be done to further reduce his mortality risk? Chuck s Case Unauthorised use prohibited. Authorised users can download, display, view and print a single copy for personal use Chuck, 68, has no previous cardiac history and presents to the hospital following a witnessed cardiac arrest. He was found to be in ventricular fibrillation (VF) and required prolonged resuscitation, including CPR and defibrillation. Acute coronary syndrome was ruled out and non-revascularizable coronary disease was found on coronary angiography. Chuck survived this event and he had a satisfactory neurologic recovery. Should this patient receive an implantable cardioverter defibrillator (ICD)? Monica s Case Monica, 28, presents to the clinic with recurrent episodes of loss of consciousness. She is seen by a neurologist, diagnosed with a seizure disorder and is started on anti-epileptics. The episodes continued despite this treatment. On further questioning by her family physician, it was found that the episodes were triggered by ringing from a telephone, a doorbell, or an alarm clock. A family history of sudden death in young relatives was elicited. A Holter monitor was arranged, which captured a typical event immediately after waking in the morning to her alarm clock (Figure 1). She was told to come to the ED where an ECG was done (Figure 2). What is the diagnosis? Is she at risk for sudden cardiac death (SCD)? Continue reading for the answers to these questions. Perspectives in Cardiology / September
2 Figure 1. Holter monitor in a 28-year-old woman, with recurrent episodes of loss of consciousness. Figure 2. ECG of a 28-year-old woman with recurrent episodes of loss of consciousness and documented polymorphic ventricular tachycardia on Holter monitor. SCD SCD is one of the most frequent causes of death in North America, accounting for more than 40,000 deaths in Canada per year.1 The vast majority of these deaths occur in a large, low-risk subgroup of the general population for which we lack specific markers of increased risk.2 The majority (83%) of arrhythmias leading to SCD are tachyarrhythmias (Figure 3). In patients with coronary artery disease (CAD) and ischemic cardiomyopathies, medical treatment with ß-blockers, angiotensin-converting enzyme (ACE) inhibitors, statins and acetylsalicylic acid (ASA) have been shown to reduce mortality. However, even optimally treated patients may still experience ventricular arrhythmias and sudden death. Current evidence and guidelines support the use of the ICD in patients at high-risk, as an incremental reduction in mortality can be achieved. Dr. Simpson is an Associate Professor of Medicine (Cardiology), Queen s University and Medical Director, Cardiac Program at Kingston General Hospital, Kingston, Ontario. He is a Cardiac Electrophysiologist and the President of the Canadian Heart Rhythm Society. Dr. Johri is a Cardiology Resident, Queen s University, with interests in sudden cardiac death and hypertrophic cardiomyopathy, Kingston, Ontario. 30 Perspectives in Cardiology / September 2006
3 The approach to the prevention of SCD can be divided into primary and secondary prevention strategies. Secondary prevention refers to treatment to deal with a potential recurrence of a lifethreatening arrhythmic event, such as sustained ventricular tachycardia or ventricular fibrillation (VF). In these cases, implantation of an ICD confers a significant survival benefit as compared to antiarrhythmic therapy in patients with a previous potentially fatal arrhythmic event and depressed left ventricular (LV) function (Antiarrhythmics vs. Implantable Defibrillators trial [AVID] [1997], Canadian Implantable Defibrillator Study [CIDS] [2000] and Cardiac Arrest Study Hamburg [CASH] trial [2000]). 3 The choice: an ICD VT 62% VT: Ventricular tachycardia Primary VF Torsades 8% de pointes 3% Figure 3. Underlying arrythmia of SCD. Bradycardia 17% As 95% of out-of-hospital cardiac arrests are fatal, most patients do not get a second chance. For this reason, investigators turned to an evaluation of ICDs in patients at high-risk for, but who have not yet had a cardiac arrest. The Multicenter Automatic Defibrillator Implantation Trial (MADIT) and Multicenter Unsustained Tachycardia Trial (MUSTT) were the initial primary prevention trials that showed improved survival with ICD implantation in patients with ischemic cardiomyopathy, spontaneous non-sustained ventricular tachycardia (NSVT) and inducible sustained ventricular tachycardia (VT) at electrophysiology study (EPS). 4,5 MADIT-II subsequently showed survival benefit from ICD implantation in post-mi patients with a LV ejection fraction (EF) 30%, regardless of the presence of NSVT and regardless of the result of EPS. 6 The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) randomized 2521 patients with chronic New York Heart Association (NYHA) Class II or Class III failure and an LVEF of 35% or less to one EF 30% EF 31% to 35% ICD EP: Electrophysiology EP Study ICD Figure 4. Current approach to the primary prevention of SCD in patients with ischemic and non-ischemic heart disease. Left ventricular ejection fraction (LVEF) measured quantitatively and at least one month post-mi and three months post-coronary revascularization procedure. A positive EP study is one in which sustained VT is induced. This identifies patients with an EF of 31% to 35%, at high-risk for SCD who should, in most cases, receive an ICD. + Perspectives in Cardiology / September
4 Table 1 Class I recommendations and levels of evidence for ICD implantation 1 Class I recommendations Level of evidence 1. Cardiac arrest due to VF or VT, not due to a transient or reversible cause A 2. Spontaneous, sustained VT in association with structural heart disease B 3. Syncope of undetermined origin, with clinically relevant, hemodynamically B significant sustained VT or VF induced at EP study 4. Spontaneous, sustained VT in patients who do not have structural heart B disease that is not amenable to other treatments 5. Patients with ischemic heart disease, with or without mild-moderate heart A failure symptoms and LVEF of 30% or less, measured at least once a month post-mi and at least three months post-coronary revascularization Class I: Conditions for which there is evidence and/or general agreement that a given procedure or treatment is useful and effective. Level of evidence A: Data are derived from multiple randomized clinical trials or meta-analyses. Level of evidence B: Data are derived from a single randomized trial, or from nonrandomized studies. of three strategies: optimal medical therapy alone, optimal medical therapy and amiodarone, or optimal medical therapy and an ICD. 7 The annual mortality rate was 7.2% in the medical therapy alone group and was unchanged with the addition of amiodarone. However, in the group receiving an ICD, there was a 23% relative reduction in total mortality over five years. Subgroup analysis suggested that the benefit was similar in patients with or without CAD, but was greatest in patients with more severe LV dysfunction. Our current approach to ICD implantation, as shown in Figure 4, is based on these studies and the recently published Canadian Cardiovascular Society/Canadian Heart Rhythm Society guidelines. 1 SCD in the young The occurrence of SCD in the young (especially in athletes) captivates the public s interest because such individuals are perceived to epitomize health and invulnerability. Nevertheless, sudden cardiac catastrophes continue to occur, usually in the absence of prior symptoms. Hypertrophic cardiomyopathy (HCM), characterized by thickening of the LV muscle, is the most common cause of SCD in the young. The disease is familial and is mainly transmitted as an autosomal dominant trait with 50% of the offspring affected. Congenital coronary artery anomalies, with abnormal origins, are the second leading cause of SCD in young athletes, accounting for approximately 14% of deaths in 32 Perspectives in Cardiology / September 2006
5 Table 2 Class IIa recommendations and levels of evidence for ICD implantation 1 Class II recommendations Level of evidence 6. Patients with ischemic heart disease and LV dysfunction (LVEF 31% B to 35%), measured at least one month post-mi and three months post-coronary revascularization procedure with inducible VF/sustained VT at EP study 7. Patients with non-ischemic cardiomyopathy present for at least nine B months with an LVEF of 30% or less and NYHA functional class II to III heart failure 8. Patients with familial or inherited conditions, including but not limited B to long QT syndrome, hypertrophic cardiomyopathy, Brugada syndrome or arrhythmogenic right ventricular cardiomyopathy and patients at high risk of life-threatening ventricular tachyarrhythmias Class IIa: Weight of the evidence/opinion is in favour of usefulness/efficacy. Class II: Conditions for which there is conflicting evidence and/or a divergence of opinion that a given procedure or treatment is useful and effective. this population. 9 Arrhythmogenic right ventricular cardiomyopathy (ARVC) is another important cause, characterized by myocyte death and fibrofatty tissue infiltration of the myocardium, leading to ventricular dysrhythmia. The cause of ARVC is not clear, but familial involvement is common. Approximately 2% of young athletes with sudden death have no evidence of structural heart disease at autopsy and it is thought that primary electrical disorders are the cause. Primary cardiac electrical disorders include: long QT syndrome (LQTS), Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT). ICDs are commonly implanted in patients with these conditions who have either survived a cardiac arrest, or who have been diagnosed with one of these conditions and are felt to be at high-risk for SCD. Case resolutions John s case is an example of a patient with ischemic heart disease and a LVEF 30% who fulfills the NYHA Class I recommendations for ICD implantation (level of evidence A, Table 1). This patient was referred to the Cardiac Rhythm Device Clinic and subsequently underwent implantation of an ICD for primary prevention of SCD in the setting of ischemic cardiomyopathy. Approximately two months after implantation, he experienced an episode of rapid VT which was successfully terminated by the device. Perspectives in Cardiology / September
6 John s case illustrates the benefit of ICD implantation for the primary prevention of SCD, in patients who are clinically stable even several years following coronary revascularization. Simply having an EF 30% is sufficient to recommend the implantation of an ICD in this individual. Chuck s case is an example of a patient who survived a witnessed cardiac arrest and who clearly fulfills the criteria for the NYHA Class I (level of evidence A) recommendation for ICD, that is cardiac arrest due to VF or VT and not due to a transient or reversible cause. Subgroup analysis has shown that patients with an LVEF < 35% derive the greatest benefit from ICD therapy for the secondary prevention of SCD. In the final case, Monica is suffering from an inherited disorder (LQTS) that can lead to SCD in a young person. The management recommendations for this patient with symptomatic LQTS includes: ß-blockers, cessation of competitive sports and an ICD implant (Table 2). Other first-degree family members should be screened for these inherited heart rhythm disorders. Further management of this condition includes careful monitoring by a cardiologist and avoidance of triggers. Monica proceeded have an ICD implanted and several months later she developed polymorphic VT triggered by her doorbell ringing in the middle of the night (Figure 4). The life-threatening arrhythmia was terminated by the ICD (Figure 5). Summary SCD is a leading cause of mortality in our society. While ß-blockers, ACE inhibitors, ASA and revascularization are important treatments that have been shown to reduce mortality, the ICD has now been shown to significantly reduce mortality risk, not just in cardiac arrest survivors, but also in patients with significant LV dysfunction who have never had an arrhythmia. Patients with a LVEF of 30% or less should be referred to an arrhythmia specialist for consideration of an ICD implant. Atrial electrogram Ventricular electrogram Shock delivered Figure 5. Polymorphic ventricular tachycardia/vf in a patient with LQTS triggered by a doorbell ringing and subsequent termination of the arrhythmia by the ICD (electrograms stored in the ICD memory). 34 Perspectives in Cardiology / September 2006
7 While rare, inherited heart rhythm disorders, such as LQTS, Brugada s syndrome, CPVT and the inherited structural heart diseases with proarrhythmic potential (ARVC, HCM) should be considered in the differential diagnosis of young patients with worrisome syncope. These heart rhythm disorders require evaluation by a cardiologist. PCard References 1. Tang AS, Ross H, Simpson CS, et al: Canadian Cardiovascular Society/Canadian Heart Rhythm Society position paper on implantable cardioverter defibrillator use in Canada. Can J Cardiol 2005; 21(Suppl A):11A-18A. 2. Huikuri HV, Castellanos A, Myerburg RJ: Sudden death due to cardiac arrhythmias. N Engl J Med 2001; 345(20): Spector PS: Diagnosis and management of sudden cardiac death. Heart 2005; 91(3): Moss AJ, Hall WJ, Cannom DS, et al: Improved survival with an implantable defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med 1996; 335(26): Buxton AE, Lee KL, Fisher JD, et al: A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Eng J Med 1999; 341(25): Moss AJ, Zareba W, Hall WJ, et al: Multicenter Automatic Defibrillator Implantation Trial II Investigators. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002; 346(12): Bardy GH, Lee KL, Mark DB, et al: Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Eng J Med 2005; 352(3): Bayes de Luna A, Coumel P, Leclercq JF: Ambulatory sudden cardiac death: Mechanisms of production of fatal arrhythmias on the basis of data from 157 cases. Am Heart J 1989; 117(1): Maron BJ: Sudden death in young athletes. New Engl J Med 2003; 349(11): Perspectives in Cardiology / September
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