CONGRESSO REGIONALE ANMCO TOSCANA Contradditori ICD: uso restrittivo Massimo Milli UTIC S. Maria Nuova Azienda Sanitaria di Firenze Viareggio Centro Congressi Stabilimento Principe di Piemonte 7-8 Ottobre 2011

Temporal Changes in Non–Evidence-Based Implantable Cardioverter-Defibrillators (ICDs) Sana M. Al-Khatib, MD, MHS JAMA. 2011;305(1):43-49

In-hospital Outcomes Non–Evidence-Based ICD Implantations in the United States Sana M. Al-Khatib, MD, MHS JAMA. 2011;305(1):43-49 In-hospital Outcomes

Limitazioni riconosciute della terapia con ICD Costi del Device Complicanze legate alla procedura dell’intervento e di possibili malfunzionamenti del device Effetti e risultati di shock appropriati ed inappropriati Soluzioni proposte: Migliore selezione dei pazienti Migliore programmazione del device Ottimizzazione della terapia medica Ablazione del substrato aritmico

Shock inappropriati: problema di quale dimensioni ? Despite the technological evolution of ICD systems, more than 20% of shocks are triggered by supraventricular arrhythmia; thus, they are inappropriate (Rosenqvist 1998, Nanthakumar 2000, Dorian, 2004) Principali cause di shock inappropriati The most common cause of inappropriate ICD shocks was: atrial fibrillation (44%) other supraventricular tachycardias, including sinus tachycardia (36%) abnormal sensing (20%) (Daubert, 2008)

Conseguenze di shock non appropriati Adverse psychological consequences: The ICD shocks are perceived as awfully painful. After an ICD shock, the patient may become immobilized, fearing that any movement or activity might activate another shock. Individuals who experience an ICD shock exhibit higher levels of psychological distress, anxiety, anger, and depression than those who do not. (Dunbar, 1993; Dougherty, 1995, Ahmad, 2000). The level of anxiety, depression, and poor quality of life is comparable in incidence to patients resuscitated from cardiac arrest and cardiopulmonary bypass surgery (Bostwick, 2007) ICD implantation is associated with neuropsychological impairment that significantly affects acute and long-term cognitive function (Hallas, 2010).

Tachicardia e/o FA responsabili per se dell’aumento di mortalità ? Conseguenze di shock non appropriati Adverse medical consequences: Higher mortality than patients who did not suffer inappropriate shocks, with a hazard ratio of 2.29 (p=0.025) (Daubert & Zareba, 2008) Predictors of inappropriate shocks: - age > 70 years (hazard ratio 1.9) history of atrial fibrillation (hazard ratio 2.0) The occurrence of only one inappropriate shock showed an all-cause mortality hazard ratio of 1.6. Each additional inappropriate shock corresponded to a hazard ratio of 1.4 , such that the risk is more than triple after a total of five shocks (Johanes, 2011). in the MADIT II population, although both appropriate and inappropriate shocks were associated with an increased total mortality, appropriate and inappropriate antitachycardia pacing was not. In fact, having only antitachycardia pacing episodes and no shocks was associated with a trend toward lower mortality. Tachicardia e/o FA responsabili per se dell’aumento di mortalità ?

Possibili meccanismi dell’aumento di mortalità nei pz con shock non appropriati Direct myocardium damage: The immediacy of post shock electromechanical dissociation suggests that necrosis is not the cause of the phenomenon Animal models have demonstrated a vast array of potentially deleterious effects of DC shocks including alterations in cellular morphology, biochemical function, electrophysiologic function, and hemodynamic function (Tedeschi, 1954; Van Vleet, 1977; Babbs, 1980; Jones, 1980; Wilson, 1988; Trouton, 1992). Non-direct myocardium damage: Adverse psychological effects of ICD shocks (anxiety and depression) can set off a cascade of events, including poor compliance to medical therapy, that culminates in an increased risk of death in patients with congestive heart failure.

Soluzioni proposte: Migliore selezione dei pazienti B) Migliore programmazione del device C) Ottimizzazione della terapia medica D) Ablazione del substrato aritmico There is a 4 deaths excess every 1000 ICD implanted when the device is implanted outside the guidelines. (Kadish, 2011). In the MADIT II trial, AF was the most common cause of inappropriate shocks. Patients provided with the stability detection algorithm programmed on their ICDs, which is designed to prevent shocks for atrial fibrillation, were less likely to have inappropriate shocks (Daubert, 2008). The Pain Free II study, showed that aggressive use of antitachycardia pacing, even for very fast episodes of ventricular tachycardia, was effective and reduced the risk of shocks (Wathen, 2004). It is less clear whether medical therapy can reduce the risk of ICD shocks. Prophylactic radiofrequency catheter ablation of arrhythmogenic substrate in patients with a previous myocardial infarction in preventing ICD therapy SMASH-VT trial: Catheter ablation resulted in reduced appropriate ICD therapy from 33 to 12% VTACH trial: Catheter ablation significantly prolonged time to first ventricular TV/FV from 5.9 to 18.6 months. The benefit was more pronounced in pts with left ventricular ejection fraction > 30%

Esistono differenze di outcome in base al sesso per le procedure elettrofisiologiche ed in particolare per l’impianto di ICD ? (J Cardiovasc Electrophysiol, Vol. 22, pp. 605-612, May 2011) Similarly to ICD trials, women were significantly underrepresented also in CRT trials, being approximately one-third of the total population enrolled. In the contrary with ICD studies, subgroup analyses of CRT trials suggest that women may have a better response to CRT, although different studies showed conflicting results. Donne/CRT CARE HF - COMPANION Donne/CRT MIRACLE - MADIT CRT Meta-analysis of primary prevention ICD studies (MADITII, MUSTT, SCD-HeFT, DEFINITE, COMPANION) The number of ICD needed to prevent one death in women was nearly double than in men

Esistono differenze di outcome in base all’ età per le procedure elettrofisiologiche ed in particolare per l’impianto di ICD ? Ann Intern Med. 2010;153:592-599. In primary prevention ICD trials, which constitute the basis for current clinical practice, more than 50% of enrolled pts were younger than 60 yrs . In real-world practice, nearly 70% of ICDs are implanted in pts older than 60 yrs, and more than 40% are implanted in pts older than 70 yrs .

Sensitivity of EF in predicting sudden death La Frazione d’Eiezione (EF) è un parametro sensibile e specifico per la corretta indicazione ad impianto di ICD ? Sensitivity of EF in predicting sudden death Autonomic Tone and Reflexes After Myocardial Infarction study (La Rovere et al.) The study enrolled 1284 pts with a recent myocardial infarction of whom 49 died suddenly during a mean follow up of 21 months. Of these, only 22 (44%) had an EF of 35%, thus suggesting a low sensitivity of EF alone in predicting SCD. EF was significantly associated with major arrhythmic events only when associated with evidence of cardiac autonomic dysfunction, such as depressed heart rate variability and low baroreflex sensitivity. Maastricht Circulatory Arrest Registry (Gorgels et al) Rate and total number of sudden cardiac deaths (SCD) according to ejection fraction

patients compared to non-diabetic ones (15 vs 11 ICD respectively). La Frazione d’Eiezione (EF) è un parametro sensibile e specifico per la corretta indicazione ad impianto di ICD ? Specificity of EF in predicting sudden death MUSTT: Relation between ejection fraction (EF) and mode of death in 1791 patients with coronary artery disease. Total mortality in black and arrhythmic mortality in grey. (Buxton et al) Although low EF was associated with higher mortality, the degree of left ventricular dysfunction did not predict the mode of death, as approximately half of the deaths occurred suddenly both in patients with EF <30% and in those with EF 30% Also patients with low EF and diabetes seem to earn a smaller benefit from prophylactic ICD therapy. In the MADIT II study, the number of ICD needed to implant to prevent one death was nearly 40% higher in diabetic patients compared to non-diabetic ones (15 vs 11 ICD respectively). Conclusions: The current EF-based guidelines do result in a significant number of unnecessary ICD implants. This is because EF alone lacks sufficient sensitivity and specificity in identifying patients at risk of SCD. Future studies should be focused on the discovery and validation of newer arrhythmic risk markers, in order to improve the predictive value of EF alone.

CONCLUSIONI Un approccio non “restrittivo” ma ragionato all’impianto di ICD deve tener conto di: Necessità di attenersi strettamente alle linee guida soprattutto per quanto riguarda la tempistica dopo IMA o dopo la diagnosi di scompenso cardiaco. Gli impianti outlayers sono gravati da una mortalità e complicanze maggiori statisticamente significative Accertarsi di aver veramente raggiunto una terapia medica ottimale sia in termini di principi attivi che di dosi (in questo caso una discreta fetta di pz esce dai criteri di eligibilità all’impianto in prevenzione primaria per sostanziale miglioramento della funzione sistolica) Valutare la possibilità di effettuare soprattutto nei pz ischemici una terapia ablativa dell’aritmia che può per se risolvere il problema o comunque ridurre la possibilità di attivazione dell’ICD. Nel caso di pz con FA può essere utile in tal senso abbinare una modulazione del nodo AV

CONCLUSIONI Un approccio non “restrittivo” ma ragionato all’impianto di ICD deve tener conto di: I risultati dei trial clinici fanno riferimento a pz che nel 50% dei casi avevano età < 60 aa. Nei pz > 65 aa con severa disfunzione sistolica non sembrano esserci risultati certi di superiorità in termini di mortalità, del trattamento con ICD e terapia medica Nelle donne l’efficacia dell’ICD in prevenzione primaria è minore di quella degli uomini La frazione d’eiezione, pur rimanendo nella pratica il parametro più utilizzato soprattutto ai fini dell’indicazione in prevenzione primaria, è comunque dotato di una sensibilità e specificità piuttosto scarse

GRAZIE PER L’ATTENZIONE

Ruth England, Tim England, and John Coggon The ethical and legal implications of deactivating an implantable cardioverter‐defibrillator in a patient with terminal cancer Ruth England, Tim England, and John Coggon J Med Ethics. 2007 September; 33(9): 538–540. 10.1136/jme.2006.017657 Decisions about deactivation of ICDs will become increasingly common in clinical practice We propose that ICDs be treated as integral devices rather than as external machines or parts of the body An integral device, though not organic, is part of the patient. We suggest that where technology has been integrated into the physical being, a patient should retain stronger autonomy than he does with external mechanical devices Nonetheless, an integral device is not truly a part of the body. Thus, deactivation should be permitted in some circumstances. Furthermore, a patient should have the right to demand that his ICD be disabled, even against medical advice, just as he would have the right to refuse external defibrillation in advance