Εμφύτευση απινιδωτών για πρωτογενή πρόληψη σε ασθενείς που δεν περιλαμβάνονται στις κλινικές μελέτες Δημήτριος M. Κωνσταντίνου Ειδικός Καρδιολόγος, MD, MSc, PhD, CCDS Πανεπιστημιακός Υπότροφος
Dr. Konstantinou has received grants from Medtronic
Level of evidence A Multiple randomized controlled clinical trials evaluated the role of ICDs in prevention of SCD in patients with ischemic heart disease & LV systolic dysfunction relative risk reduction ranges from 23 to 54%
Level of evidence B One randomized controlled clinical trial evaluated exclusively the role of ICDs in prevention of SCD in patients with non-ischemic, dilated cardiomyopathy
Level of evidence B Large non-randomized studies, including prospective registry data, are less robust but still useful for risk stratification in patients with HCM http://doc2do.com/hcm/webhcm.html 2011 ACCF/AHA Hypertrophic Cardiomyopathy Guideline 2015 ESC Guidelines
Level of evidence C Clinical reports and retrospectively analyzed series provide less rigorous evidence in support of ICD in less common conditions: Arrhythmogenic right ventricular cardiomyopathy/dysplasia Restrictive cardiomyopathy (primary/amyloidosis) Left ventricular non-compaction Myotonic dystrophy type I (Steinert disease) Laminopathies Cardiac sarcoidosis
Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D)
Ν=132 patients; 95 with a secondary prevention indication 96% actual survival vs. 72% VF-free survival at 36 months Circulation. 2003;108:3084-91 Circulation. 2004;109:1503-8
Even rapid VTs had a high likelihood of termination with ATP J Am Coll Cardiol 2014;64:119 25
Circulation. 2004;109:1503-8 Appropriate ICD intervention rate (%) Inappropriate ICD intervention rate (%) Circ Arrhythm Electrophysiol. 2013;6:562-8
Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) 2012 ACCF/AHA/HRS guidelines 2015 ESC Guidelines
Major risk factors Syncope NSVT Moderate RV/LV dysfunction RV FAC 17-24% or RVEF 36-40% or LVEF 36-45% Minor risk factors Symptoms/signs of right HF Young age Male gender Compound/digenic heterozygosity Family history of SCD VT induction during EPS Marked QRS fragmentation T wave inversion in inferior leads Late gadolinium enhancement Eur Heart J 2015;36:3227 37
Estimated risk of major arrhythmic events: high-risk category >10%/year intermediate-risk category 1-10%/year low-risk category <1%/year Eur Heart J 2015;36:3227 37
Restrictive cardiomyopathy (RCM) Non-dilated, nonhypertrophied LV Variable LV systolic function LV diastolic dysfunction Bi-atrial dilatation
Outcomes of idiopathic RCM in childhood & adulthood Circulation. 2012;126:1237-44 Circulation. 2000;101:2490-6
Facts and gaps in evidence Treatment is mostly palliative HF/AF symptoms are treated with: diuretics heart rate control to optimize LV filling anticoagulation There are no prospective data on prophylactic implantation of ICDs 2015 ESC Guidelines
Cardiac Amyloidosis Most common cause of secondary RCM in adults Two types of amyloid infiltrate the heart: Immunoglobulin lightchain (AL) amyloid Transthyretin (TTR) amyloid familial disease (misfolding of mutated TTR) Sporadic (misaggregation of wild-type TTR) Eur J Heart Fail 2007;9:617 24
ECG abnormalities in cardiac amyloidosis Eur J Heart Fail 2007;9:617 24
Electrophysiological abnormalities in cardiac amyloidosis Prolongation of the HV interval is common and may not be suspected from the surface ECG Prolongation of the HV interval was an independent predictor of SCD (HR=2.26 for each 10-ms increase in the HV interval) J Am Coll Cardiol 1997;30:1046 51
Heart Rhythm. 2014;11(1):158-62
Heart Rhythm. 2014;11(1):158-62
Stanford Amyloid Center s ICD implantation criteria Heart Rhythm. 2014;11(1):158-62
Clin Cardiol. 2009;32(8):E63-5.
Facts and gaps in evidence Up to 50% of cardiac amyloidosis patients die suddenly SCD often due to electromechanical dissociation Case reports/series: termination of VT/VF with ICDs NSVT in >25% of patients (prognostic significance)? Insufficient data to provide recommendations on primary prophylaxis 2015 ESC Guidelines
Left Ventricular Non Compaction (LVNC)
J Am Coll Cardiol 2000;36:493 500
J Cardiac Fail 2011;17:771-8
VS Heart 2007;93:65 71
Facts and gaps in evidence Many patients with LVNC are completely asymptomatic, but some present with HF, thromboembolism, arrhythmias or SCD A few data to suggest that LVNC by itself is an indication for an ICD The need for an ICD should be guided by the severity of LV systolic dysfunction and the presence of sustained VA using the same criteria for DCM (2015 ESC guidelines)
n=49 patients J Am Coll Cardiol 2002;40:1645 52
Severe ECG abnormalities (any of the following): 1. rhythm other than sinus 2. PR 240 ms 3. QRS duration 120 ms 4. second-degree or third-degree AV block N Engl J Med 2008;358:2688-97
The predominance of VTs after collapse lends support to the concept that ICDs could be beneficial in preventing sudden death. Mortality from progressive neuromuscular respiratory failure could limit the overall duration of benefit of ICDs... N Engl J Med 2008;358:2688-97
ECG suggesting impulse propagation abnormalities: 1. PR interval >200 ms or 2. QRS duration >100 ms Invasive strategy group: 1. patients underwent EP study (including VT stim) 2. prophylactic permanent pacing if HV interval >70ms JAMA. 2012;307(12):1292-301
Myotonic dystrophy type 1 2015 ESC Guidelines
LMNA mutations were detected in 11.5% of cases Mutations of LMNA are frequent among patients with DCM: 1. associated skeletal muscle abnormalities 2. atrial arrhythmia or 3. conduction defects subjects with LMNA mutations had a significantly worse prognosis compared with the other DCM subjects J Am Coll Cardiol 2003;41:771 80
Primary Prevention of Sudden Death in Patients with Lamin A/C Gene Mutations mean F/U 33.9 months 42% had appropriate ICD intervention 6 patients received ICD shocks for VF 2 patients received ICD shocks for VT 1 patient received ATP for VT N Engl J Med. 2006;354(2):209-10
Cumulative incidence of malignant ventricular arrhythmias was 33% J Am Coll Cardiol 2012;59:493 500
Risk factors NSVT on Holter LVEF<45% Male gender Non-missense mutations Thus, it seems prudent to consider an ICD in persons with 2 or more of the 4 risk factors identified. J Am Coll Cardiol 2012;59:493 500 2015 ESC Guidelines
Cardiac sarcoidosis
Europace 2013;15:347 54 Over mean F/U 4.2 years: 36.2% pts received appropriate ICD Tx
Predictors of appropriate ICD interventions Europace 2013;15:347 54
Circ Arrhythm Electrophysiol. 2011;4:43-8
Circ Arrhythm Electrophysiol. 2014;7:1109-15
Heart Rhythm 2014;11(7):1305-23
Take Home Messages An ICD should be considered in ARVC/D in the presence of syncope, NSVT or at least moderate RV, LV or biventricular dysfunction An ICD may be considered in cardiac amyloidosis in the presence of non-posturally mediated syncope and in the absence of NYHA class IV symptoms or expected survival <1 year In LVNC, the need for an ICD should be guided by the severity of LV systolic dysfunction The use of an ICD may be considered in myotonic dystrophy type I when there is an indication for pacing and evidence of ventricular arrhythmias
Take Home Messages Mutations of LMNA are frequent (10-20%) among patients with DCM in the presence of skeletal muscle abnormalities (e.g. Emery-Dreifuss, Limp-girdle IB) atrial arrhythmias or conduction defects An ICD should be considered in DCM patients with confirmed LMNA mutation in the presence of 2 of the following: NSVT on Holter LVEF<45% Male gender Non-missense mutations An ICD should be considered in cardiac sarcoidosis patients when there is an indication for permanent pacing
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