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How to detect disease at risk in asymptomatic patients Paul Erne Department of Cardiology Lucerne, Switzerland Focus of this presentation • Detection of disease at risk for sudden cardiac death (SCD) • Focus on coronary causes of SCD in young, asymptomatic patients • No conflict of interest to declare Definition of SCD • Sudden Cardiac Death is an umbrella term used for many different causes of cardiac arrest. • Sudden Cardiac Death is defined as an event that is non-traumatic, unexpected, and resulting from sudden cardiac arrest within six hours of previously witnessed normal health without other explanation. Sharma et al. Br J Sports Med 1997. Characteristics of SCD in the young • In the young <35 years: – Very low incidence: 1/200‘000 per year (≈ 0.005‰) Maron BJ et al. J Am Coll Cardiol 1998. – Usually precipitated by physical activity Maron BJ et al. JAMA 1996. – Usually no symptoms until SCD occurs Characteristics of SCD in the young – SCD still related to episodical physical activity: Dahabreh IJ et al. JAMA 2011. Age distribution of sport related SCD in the young athletes (red) and in the general population during sport (blue) Marijon E et al., Circulation 2011. Characteristics of SCD in the young- Large spectrum of disease Only in a minority of young patients dying from SCD a coronary cause may be found. Marijon E et al. Circulation 2011. Characteristics of SCD in the general population- Increasing incidence of CAD Marijon E et al. Circulation 2011. Marijon E et al., Circulation 2011. Characteristics of SCD in the young – Underlying cardiac disease causing SCD is usually atherosclerotic coronary artery disease, the remainder due to nonischemic diseases such as HCM or valvular heart disease. Corrado D et al. Cardiol Clin 2007. Magnitude of the problem • Though incidence of SCD is low in the general population, absolute numbers of SCD are highest: Myerburg RJ et al. Circulation 1992. Magnitude of the problem • Asymptomatic patients are not routinely seen by the physician. Detection of disease at risk in asymptomatic patients should start on the population level, but: Is this feasible? Technical problems • 12-lead ECG and exercise ECG – Usually do not demonstrate abnormalities in patients with coronary artery anomalies since ischemia in patients with congenital coronary artery anomalies is episodic. Basso C et al. J Am Coll Cardiol 2000. – Too many false positive findings, if used as screening instrument in a general population. Erne P et al. Eur Heart J 2007. Technical problems • Exercise ECG in SWISSI I – Subjects with silent ischaemia tzpe I above age 40 without known CAD referred for life insurance or check-up exams were eligible to examine effects of anti-ischaemic therapy. – Of 487 subjects with asymptomatic STdepression during exercise ECG, myocardial ischemia was verified by stress echocardiography or perfusion scintigraphy in only 263 patients, corresponding to a false positive rate of 46%. Erne P et al. Eur Heart J 2007. Technical problems • Signal-averaged ECG – Only evaluated in high risk populations – Available data on test characteristics suggest that SAECG is not suitable for screening in a general population: • • • • Sensitivity: Specificity: Negative predictive value: Positive predictive value: 63 – 93% 51 – 81% 96 – 99% 10 – 27% Technical problems • Coronary CT – May identify coronary anomalies: Left coronary artery arising from the right coronary sinus – High sensitivity (nearly 100%) However, costs and radiation exposure impede its use as screening instrument on the population level. Technical problems • Coronary MRI – Still not suited for the depiction of coronary arteries – MRI is expensive and availability is limited Technical problems • Echocardiography – May identify coronary anomalies – Stress echocardiography useful in detecting the extent of myocardial ischemia – However, costs and availabilty limit its use as a screening instrument on the population level Aberrant origin of the left coronary artery from the rightfacing sinus of Valsalva with intramural course Another question • If we detect coronary artery anomalies or premature CAD, would we be able to prevent SCD? SWISSI I • 54 subjects with silent ischmaemia were randomized to anti-ischaemic therapy or control of risk factors and with verified silent ischemia type I • Follow-up for 10 years Erne P et al. Eur Heart J 2007. SWISSI I • Drug therapy during study: SWISSI I • Occurrence of outcome events: SWISSI I • Occurrence of outcome events: – 2 of the 3 cardiac deaths in the risk factor control group were sudden cardiac deaths In patients with silent ischemia type I sudden cardiac death may be prevented by anti-ischemic drug therapy. SWISSI II • Included asymptomatic patients with previous myocardial infarction and silent ischemia verified by stress imaging • 201 patients were randomized to percutaneous coronary intervention or anti-ischemic drug therapy • Follow-up for 10 years Erne P et al. JAMA 2007. SWISSI II • During follow-up 12 SCD occurred • 11 SCD occurred later than 5 years after study start • 11 SCD in drug therapy group, only 1 in PCI group, though all patients but one had betablocker • 8 patients who died from SCD showed signs of residual myocardial ischemia 4 years after study start, only 4 were free of ischemia (P = 0.05) Conclusion from SWISSI I and II • Anti-ischemic therapy may prevent SCD in asymptomatic patients with myocardial ischemia Screening for coronary anomalies and premature CAD would be important for the prevention of SCD in these patients What can we do? Screening for disease at risk • As shown, screening for disease at risk on the population level, albeit desirable, is currently not feasible • However: – There is an association of SCD with physical activity – There is an association of SCD with positive family history Screening in selected populations feasible Screening for disease at risk • The ESC 2005 and International Olympic Committee 2009 recommend cardiac screening for young athletes taking part in competitive sport. • In countries such as Italy, screening participants in representative sports is mandatory. In some professions, cardiac testing is also mandatory. • If there has been sudden death under age 35 in the family, the family is entitled to be screened. The International Olympic Commitee (IOC)Consensus Statement on Periodic Health Evaluation of Elite Athletes 2009 It has been demonstrated that adding a 12-lead ECG examination to history and physical examination results in a substantial increase in the ability to identify potentially lethal heart disorders (Corrado et al 2007, Lawless and Best 2008) Conclusions • Many cardiac abnormalities predisposing young persons to SCD may be diagnosed by an ECG, but not coronary abnormalities or premature CAD. • Therefore, young persons referred for evaluation of SCD risk should be examined by echocardiography. • Screening of young physically active persons should be propagated in most countries. • A lot needs to be done: development of new technologies to better predicting SCD risk