The EP show: sudden death, part 1 Director Eric Prystowsky MD Director Clinical Electrophysiology Laboratory St Vincent Hospital, Indianapolis, IN Douglas P Zipes MD Director, Division of Cardiology and Krannert Institute of Cardiology Indiana University School of Medicine Indianapolis, IN Robert J Myerburg MD Professor of Medicine and Physiology Director, Division of Cardiology University of Miami School of Medicine Miami, FL page #9488, Interim results of ALLHAT doxazosin arm confirm excess of CVD complications compared to diuretic

Incidence of sudden cardiac death Since 1970, sudden cardiac death has been estimated to represent about 50% of all cardiovascular deaths, or 300 000 annually. Although the true incidence is not known, it is now likely to be higher given a greater number of chronic heart disease patients at risk in a growing and aging population. page #9488, Interim results of ALLHAT doxazosin arm confirm excess of CVD complications compared to diuretic

Risk categories for sudden death In the adult population, aged 35 and over, the incidence of sudden cardiac death approaches 0.1-0.2% per year or 1 in every 500-1000 individuals. In the adolescent and adult population below 30, the incidence of sudden cardiac death is approximately 1 in 100 000, and is slightly higher for athletes. page #9488, Interim results of ALLHAT doxazosin arm confirm excess of CVD complications compared to diuretic

Current intervention strategies for sudden cardiac death Other than general disease prevention measures applicable to the population at large, intervention strategies focus on patients who are post-myocardial infarction, and who have low ejection fractions and arrhythmic markers of risk. The highest risk groups have a 10-30% risk per year. Many studies are now concentrating on populations at moderate risk, eg, heart failure patients. page #9488, Interim results of ALLHAT doxazosin arm confirm excess of CVD complications compared to diuretic

Intervention strategies for the general population Most noninvasive electrophysiologic markers are not helpful in determining risk in the general population, in patients with multiple risk factors, or in low risk post-MI patients. Sudden death is the marker for coronary disease in 20-30% of sudden deaths whose etiology is ischemia. Future noninvasive risk factors may include a profile of inflammatory markers in addition to genetic profiling. page #9488, Interim results of ALLHAT doxazosin arm confirm excess of CVD complications compared to diuretic

Ischemia and sudden death It has been well documented that only about 20% of the patients who are resuscitated from ventricular fibrillation (VF) and then hospitalized evolve transmural infarction. Yet 3/4 of these patients are also found to have coronary artery disease. Also, autopsy data shows that a significant number of patients who die from VF have severe coronary disease, often with signs of recent plaque disruption. page #9488, Interim results of ALLHAT doxazosin arm confirm excess of CVD complications compared to diuretic

Precipitants of ventricular fibrillation The precipitant of VF in those patients who are found not to have an evolving infarction or ischemic markers is unknown. Several possibilities include coronary vasospasm, and transient thrombotic events in the coronary arteries which produce ischemia but not infarction. An implantable ischemic sensor device which measures wall motion abnormalities or ST-segment shifts may be useful in this regard. page #9488, Interim results of ALLHAT doxazosin arm confirm excess of CVD complications compared to diuretic

The evolution of the ambulatory CCU “But if you stop and think of how we take care of outpatients, it's much like we took care of the infarct 30 years ago. A patient comes and sees you and you write a script for whatever it is and you send the patient home. And he comes back a month or 3 months later, if he's still alive, and then you continue therapy.” Douglas P Zipes MD Indiana University School of Medicine Indianapolis, IN page #9488, Interim results of ALLHAT doxazosin arm confirm excess of CVD complications compared to diuretic

Multicenter Automatic Defibrillator Implantation Trial Prophylactic therapy with an implantable cardioverter-defibrillator was compared with conventional medical therapy in a high-risk group of 196 post-MI patients. Over an average follow-up of 27 months, therapy with the ICD led to improved survival when compared with conventional therapy (hazard ratio for overall mortality, 0.46; 95 percent confidence interval, 0.26 to 0.82; P=0.009). page #9488, Interim results of ALLHAT doxazosin arm confirm excess of CVD complications compared to diuretic Moss AJ, et al. N Engl J Med 1996;335:1933-1940  

Multicenter Unsustained Tachycardia Trial: protocol Electrophysiologic studies Registry (n=1435) sustained VT not inducible Randomization (n=704) sustained VT inducible Conservative therapy (n=353) ACE-inhibitors and beta-blockers EP-guided therapy (n=351) ACE-inhibitors and beta-blockers Buxton AE, et al. N Engl J Med 1999;341:1882-1890

MUSTT results EP guided therapy showed a reduction in primary endpoints: 27% reduction in arrhythmic death and cardiac arrest trend toward overall reduction in mortality (20% risk reduction) The entire benefit derived from EP-guided therapy was due to treatment with implantable defibrillators. Buxton AE, et al. N Engl J Med 1999;341:1882-1890

Secondary prevention of sudden cardiac death: CASH The Cardiac Arrest Study, Hamburg Survivors of cardiac arrest secondary to documented ventricular arrhythmias were randomized to an ICD or medical antiarrhythmic therapy (288 patients total). There was a nonsignificant trend toward higher survival in patients assigned to ICD therapy. page #9488, Interim results of ALLHAT doxazosin arm confirm excess of CVD complications compared to diuretic Kuck KH, et al. Circulation 2000; 102(7):748-754

Secondary prevention of sudden cardiac death: CIDS The Canadian Implantable Defibrillator Study 659 patients with resuscitated VF, ventricular tachycardia (VT), or unmonitored syncope were randomized to ICD or amiodarone therapy. Nonsignificant relative risk reductions of 20% and 33% were found to occur in all-cause mortality and arrhythmic mortality in the ICD group compared to amiodarone. page #9488, Interim results of ALLHAT doxazosin arm confirm excess of CVD complications compared to diuretic Connolly SJ, et al. Circulation 2000; 101(11):1297-1302

Secondary prevention of sudden cardiac death: AVID Antiarrhythmics Versus Implantable Defibrillators study 1016 survivors of VF or VT were randomly assigned to either ICD or antiarrhythmic-drug therapy. Over three years, statistically significant relative reductions in mortality from 27-39% were seen in the ICD group. page #9488, Interim results of ALLHAT doxazosin arm confirm excess of CVD complications compared to diuretic The Antiarrhythmics Versus Implantable Defibrillators (AVID) Investigators. N Engl J Med 1997;337:1576–1583

AVID data and heart failure Combined data from secondary prevention trials, and AVID data alone, show that patients with ejection fractions above 35% did not receive additional benefit from an ICD compared to amiodarone alone. The 2 therapies offered have equal outcomes. page #9488, Interim results of ALLHAT doxazosin arm confirm excess of CVD complications compared to diuretic Domanski MJ, et al. J Am Coll Cardiol 1999;34:1090-1095

AVID data and mortality risk AVID registry data suggests that there is a high mortality rate for patients with VF and VT thought due to reversible factors, and for patients who manifest only asymptomatic VT. This mortality rate is similar to the rate for more high-risk ventricular arrhythmias and suggests that clinical judgment regarding reversibility and recurrence risk is not very accurate. page #9488, Interim results of ALLHAT doxazosin arm confirm excess of CVD complications compared to diuretic Anderson JL, et al. Circulation 1999;99:1692-1699

Persistence of reversibility Early studies attributing sudden cardiac death to MI relied on the presence of enzymes, new Q waves and a clinical history of pain preceding the onset of cardiac arrest. New data are highlighting the distinction between reversibility and persistence of reversibility in cardiac arrest survivors. For example, active plaque pathophysiology in cardiac arrest victims (present in 40-70%) may be reversible, but not permanently reversible. page #9488, Interim results of ALLHAT doxazosin arm confirm excess of CVD complications compared to diuretic