currently , the selection of candidates for implantable cardioverter defibrillator ( icd ) implantation for primary prevention of sudden cardiac death relies mainly on left ventricular ejection fraction ( lvef ) evaluation at the time of pre - implantation screening . previous studies have shown that a proportion of patients implanted for primary prevention of sudden death improve their lvef after icd implantation , , , , , especially if treated with cardiac resynchronization therapy icd ( crt - d ) . as a substantial proportion of icd recipients outlive their first device and must undergo generator replacement , some authors questioned the appropriateness of icd replacement when primary prevention indication does not persist and no ventricular arrhythmias were documented during follow - up . we hypothesized that patients without persistent icd indication at device replacement could be at lower risk of icd therapies after replacement . we sought to determine the persistence of icd indication at the time of generator replacement in patients who had received an icd for primary prevention of sudden cardiac death , and to measure the rate of icd therapies after replacement . in addition , we investigated the existence of predictors of appropriate therapies after generator replacement . the study was approved by our internal committee for human research . at the time of implantation , patients gave informed consent for future use of de - identified data . we prospectively collected data about all consecutive adult patients who underwent icd implantation from 2000 to 2015  at our hospital . for the aim of present analysis , we retrospectively evaluated patients who received icd for primary prevention of sudden cardiac death . all patients were implanted according to the then contemporary international guidelines and underwent a trial of optimized medical therapy and revascularization before receiving ad icd . thus , we identified patients with lvef 35% and no documentation of previous arrhythmias or unexplained syncope at the time of implantation . of them , we included in analysis all patients who outlived their first device and underwent generator replacement . data about delivery of appropriate therapies for ventricular arrhythmia were collected from device interrogation records . spontaneous arrhythmic episodes detected by the device were validated by 2 independent electrophysiologists blinded to the patient outcome . if a consensus could not be reached , a third electrophysiologist was involved in episode review . device implantation and replacement were performed according to standard clinical practice and optimization of icd parameters and pharmacological treatments were based on clinical evaluation by the attending physicians . during follow - up , patients underwent standard transthoracic echocardiographic examination every 6 months and before device replacement . we measured the proportion of patients with persistent icd indication at the time of generator replacement . in particular , we identified those patients with lvef 35% or who received appropriate icd therapies before replacement . differences between mean data were compared by a t - test for gaussian variables and by the mann - whitney - wilcoxon nonparametric test for non - gaussian variables . cox regression was used to analyze possible predictors of appropriate icd therapies or shocks after replacement . the rates of events were analyzed by using the comparison of incidence rates ( large sample ) test . all statistical analyses were performed by means of statistica software , version 7.1 ( statsoft , inc . ) . we prospectively collected data about all consecutive adult patients who underwent icd implantation from 2000 to 2015  at our hospital . for the aim of present analysis , we retrospectively evaluated patients who received icd for primary prevention of sudden cardiac death . all patients were implanted according to the then contemporary international guidelines and underwent a trial of optimized medical therapy and revascularization before receiving ad icd . thus , we identified patients with lvef 35% and no documentation of previous arrhythmias or unexplained syncope at the time of implantation . of them , we included in analysis all patients who outlived their first device and underwent generator replacement . data about delivery of appropriate therapies for ventricular arrhythmia were collected from device interrogation records . spontaneous arrhythmic episodes detected by the device were validated by 2 independent electrophysiologists blinded to the patient outcome . if a consensus could not be reached , a third electrophysiologist was involved in episode review . device implantation and replacement were performed according to standard clinical practice and optimization of icd parameters and pharmacological treatments were based on clinical evaluation by the attending physicians . during follow - up , patients underwent standard transthoracic echocardiographic examination every 6 months and before device replacement . we measured the proportion of patients with persistent icd indication at the time of generator replacement . in particular , we identified those patients with lvef 35% or who received appropriate icd therapies before replacement . differences between mean data were compared by a t - test for gaussian variables and by the mann - whitney - wilcoxon nonparametric test for non - gaussian variables . cox regression was used to analyze possible predictors of appropriate icd therapies or shocks after replacement . the rates of events were analyzed by using the comparison of incidence rates ( large sample ) test . all statistical analyses were performed by means of statistica software , version 7.1 ( statsoft , inc . ) . from 2000 to 2015 , 1130 consecutive patients underwent icd implantation at our hospital . of them , 166 underwent one or more generator replacements during follow - up and had lvef 35% and no documentation of previous arrhythmias or unexplained syncope at the time of first implantation ( fig .  1 ) . the patients in analysis underwent generator replacement for battery depletion after a mean follow - up of 59    20 months . twenty patients previously implanted with single- or dual - chamber icd developed crt indications and received a crt - d device at replacement . at the time of device removal , icd interrogations revealed appropriate therapies for ventricular arrhythmia in 48 patients ( 0.74 events / year in the overall group ) . in particular , 28 patients had received appropriate shock therapies ( 0.13 events / year ) . moreover , 21 patients had received inappropriate therapies ( 0.03 events / year ) ( fig .  2 ) . at the time of replacement , the mean lvef was 33    11% and 64 patients showed lvef > 35% ( mean 44    7% in this subgroup ) . in particular , 9 patients showed lvef > 50% , and 20% of patients with icd alone ( no crt ) showed a marked increase in ef ( from 27    5% to 43    6% , p  <  0.001 ) . we therefore identified a persistent icd indication for prevention of sudden death in 114 ( 69% ) patients . the clinical parameters of patients with persistent and non - persistent icd indication are reported in table  2 . more frequently , patients with persistent icd indication were male , had ischemic disease , and did not receive crt - d . persistent icd indications were reported in 57 ( 60% ) patients initially implanted with crt - d devices , and in 57 ( 80% ) patients initially implanted with single- or dual - chamber icds ( p  =  0.005 ) . after icd replacement , patients were followed for a mean period of 25    23 months . in this second phase , appropriate therapies for ventricular arrhythmia were delivered in 42 patients ( 0.86 events / year in the overall group ) , and 21 patients received appropriate shock therapies ( 0.17 events / year ) . moreover , 7 patients received inappropriate therapies ( 0.02 events / year ) . in particular , appropriate therapies were delivered in 30 ( 26% ) patients with persistent icd indication and in 12 ( 23% ) of the remaining patients ( p  =  0.656 ) . nonetheless , the annual rate of therapies was higher in the first group : 1.08 events / year versus 0.53 events / year ( p  <  0.001 ) . appropriate shock therapies were delivered in 14 ( 12% ) patients with persistent icd indication and in 7 ( 13% ) of the remaining patients ( p  =  0.832 ) . the annual rate of shock was comparable between groups ( 0.17 events / year versus 0.17 events / year ; p  =  0.971 ) , while the rate of inappropriate therapies was higher in the first group ( 0.03 events / year versus 0 events / year ; p  =  0.031 ) . in particular , appropriate icd therapies were reported in 3 patients with lvef > 50% at replacement . the kaplan  meier analysis of time from generator replacement to first appropriate therapy , stratified by persistence or non - persistence of indication to icd , showed no differences between groups ( fig . ( table  3 ) , the only independent predictor of appropriate icd therapies after replacement was the rate of shocks received before replacement ( hazard ratio : 1.41 ; 95% confidence interval : 1.011.96 ; p  =  0.041 ) . from 2000 to 2015 , 1130 consecutive patients underwent icd implantation at our hospital . of them , 166 underwent one or more generator replacements during follow - up and had lvef 35% and no documentation of previous arrhythmias or unexplained syncope at the time of first implantation ( fig .  1 ) . the patients in analysis underwent generator replacement for battery depletion after a mean follow - up of 59    20 months . twenty patients previously implanted with single- or dual - chamber icd developed crt indications and received a crt - d device at replacement . at the time of device removal , icd interrogations revealed appropriate therapies for ventricular arrhythmia in 48 patients ( 0.74 events / year in the overall group ) . in particular , 28 patients had received appropriate shock therapies ( 0.13 events / year ) . moreover , 21 patients had received inappropriate therapies ( 0.03 events / year ) ( fig .  2 ) . at the time of replacement , the mean lvef was 33    11% and 64 patients showed lvef > 35% ( mean 44    7% in this subgroup ) . in particular , 9 patients showed lvef > 50% , and 20% of patients with icd alone ( no crt ) showed a marked increase in ef ( from 27    5% to 43    6% , p we therefore identified a persistent icd indication for prevention of sudden death in 114 ( 69% ) patients . the clinical parameters of patients with persistent and non - persistent icd indication are reported in table  2 . more frequently , patients with persistent icd indication were male , had ischemic disease , and did not receive crt - d . persistent icd indications were reported in 57 ( 60% ) patients initially implanted with crt - d devices , and in 57 ( 80% ) patients initially implanted with single- or dual - chamber icds ( p  =  0.005 ) . after icd replacement , patients were followed for a mean period of 25    23 months . in this second phase , appropriate therapies for ventricular arrhythmia were delivered in 42 patients ( 0.86 events / year in the overall group ) , and 21 patients received appropriate shock therapies ( 0.17 events / year ) . moreover , 7 patients received inappropriate therapies ( 0.02 events / year ) . in particular , appropriate therapies were delivered in 30 ( 26% ) patients with persistent icd indication and in 12 ( 23% ) of the remaining patients ( p  =  0.656 ) . nonetheless , the annual rate of therapies was higher in the first group : 1.08 events / year versus 0.53 events / year ( p  <  0.001 ) . appropriate shock therapies were delivered in 14 ( 12% ) patients with persistent icd indication and in 7 ( 13% ) of the remaining patients ( p  =  0.832 ) . the annual rate of shock was comparable between groups ( 0.17 events / year versus 0.17 events / year ; p  =  0.971 ) , while the rate of inappropriate therapies was higher in the first group ( 0.03 events / year versus 0 events / year ; p  =  0.031 ) . in particular , appropriate icd therapies were reported in 3 patients with lvef > 50% at replacement . the kaplan  meier analysis of time from generator replacement to first appropriate therapy , stratified by persistence or non - persistence of indication to icd , showed no differences between groups ( fig . the only independent predictor of appropriate icd therapies after replacement was the rate of shocks received before replacement ( hazard ratio : 1.41 ; 95% confidence interval : 1.011.96 ; p  =  0.041 ) . in the present study we demonstrated that the icd indication for prevention of sudden cardiac death persisted at the time of generator replacement in 69% of patients who had received a primary prevention icd in the setting of heart failure with reduced lvef . nonetheless , the persistence of indication was not associated with a higher risk of further appropriate icd therapies . indeed , the recurrence of arrhythmic events was only associated with a higher rate of shocks delivered before replacement . currently , the selection of icd candidates relies mainly on lvef evaluation at the time of pre - implantation screening , as reduced lvef was the principal inclusion criterion in trials for primary prevention of sudden cardiac death . nonetheless , although no other strong and reliable tools are available at the moment , in the last ten years growing evidence is accumulating that lvef is not an optimal risk discriminator . indeed , lvef has a limited specificity for the underlying risk , meaning that a reduced lvef is a risk factor not only for sudden but also for non - sudden death , . moreover , only relatively few patients with reduced lvef benefit from an icd , and indeed the number of icds needed to prevent a death over 45 months of observation was estimated to be approximately 14 . in addition , strong evidences are missing about patients with ef recovery after optimal therapy ; in this setting icd implantation is not usually recommended ( a waiting time of 13months is usually warranted before scd prophylaxis ) , because early icd implantation showed no benefit on overall mortality . however , some authors proposed early implantation or bridge therapy with wearable defibrillator in patients at  high risk  ( a poorly defined category ) because scd is not null and , after ef recovery or when a borderline ef is observed , a residual risk may persist in selected patients ( e.g. the ones with anatomical substrate for ventricular arrhythmias ) . our analysis confirmed that lvef alone is a poor risk stratifier and that , even in the absence of documented ventricular arrhythmias , a subsequent life threatening arrhythmic event can not be excluded in patients with improved lvef at follow - up ( and , maybe , even before primary prevention implant ) . we identified a large proportion of patients implanted for primary prevention of sudden cardiac death who had no icd interventions and who improved their lvef to more than 35% at the time of generator replacement . although we noticed a lower rate of appropriate icd therapies in this group after replacement , the proportion of patients with events was comparable in the two groups , and we also reported arrhythmic events among patients who showed full recovery of lvef ( i.e. > 50% ) . therefore , although the discontinuation of icd therapy in these patients may be tempting from an economic point of view , as well as the possibility of downgrading a crt - d to a crt pacemaker in patients requiring biventricular pacing , the risk of sudden cardiac death remains not null . nonetheless , although the potential complications associated with the replacement procedure are not negligible , we showed a lower rate of inappropriate therapies in patients with no persistent icd indication , and thus a potentially lower negative impact on the outcome and the quality of life . in the perspective of discontinuing icd therapy , one additional open question concerns the management of the depleted device : leaving it in place , removing the generator or the complete system , using the icd lead for right ventricular pacing in case of concomitant crt or pacing indications . every option is associated with different potential risks and should be carefully evaluated . of course , the adoption of modern technologies , such as the totally subcutaneous icd , would allow an easier management of possible system removal . looking at the question from a different perspective , the problem of changes in indication at the time of icd replacement can be solved by decreasing the proportion of icd recipients who outlive their first device . in our study , the mean longevity of icds implanted over the last 15 years was approximately 5 years . as hauser suggested in 2005 , a 10-years battery would allow to provide an icd that lasts a lifetime in the majority of patients , and recent data seem to show that modern battery technology ( e.g. high capacity cells , highly efficient chemistry ) has finally reached this goal . thirdly , several clinical variables or comorbid conditions at baseline and at replacement were not considered in our analysis of potential predictors . fourthly , the long duration of the enrollment period may have impacted the results , as the implantation criteria and the icd programming may have changed over time . however , the study was carried out in a single center , the operators in charge of patient selection , device implantation and clinical management did not change during the study period . lastly , the therapies delivered by the icd are only a surrogate endpoint and may not be necessarily considered as prevented sudden cardiac death , as episodes of nonsustained ventricular tachycardia frequently terminate spontaneously . however , this approach was previously adopted by other authors ,   and , in our opinion , is the only feasible in a retrospective setting . the first limitation of the present study is the retrospective design of the analysis . however , all the patients included were consecutive . secondly , the number of patients in analysis was relatively small . thirdly , several clinical variables or comorbid conditions at baseline and at replacement were not considered in our analysis of potential predictors . fourthly , the long duration of the enrollment period may have impacted the results , as the implantation criteria and the icd programming may have changed over time . however , the study was carried out in a single center , the operators in charge of patient selection , device implantation and clinical management did not change during the study period . lastly , the therapies delivered by the icd are only a surrogate endpoint and may not be necessarily considered as prevented sudden cardiac death , as episodes of nonsustained ventricular tachycardia frequently terminate spontaneously . however , this approach was previously adopted by other authors ,   and , in our opinion , is the only feasible in a retrospective setting . in our study we did not find sensitive predictors of recurrent arrhythmias after generator replacement , in patients who had received an icd for primary prevention of sudden death in the setting of heart failure with reduced lvef . therefore , although current criteria for icd indication did not persist at the time of replacement in about 30% of patients , in our opinion icd therapy discontinuation seems not perfectly safe . larger prospective trials are needed to identify reliable risk factors at the time of first icd implantation and replacement .
backgroundindication to implantable cardioverter defibrillator ( icd ) for primary prevention of sudden death relies on left ventricular ejection fraction ( lvef ) . 
 we measured the proportion of patients in whom indication to icd persisted at the time of generator replacement ( gr ) and searched for predictors of appropriate therapies after gr.methodswe identified all consecutive patients who had received an icd at our hospital , for lvef 35% and no previous arrhythmias or unexplained syncope . 
 then , we included the 166 patients who outlived their first device and underwent gr.resultsat the time of gr ( mean follow - up 59    20 months ) , icd indication ( i.e. lvef 35% or previously treated ventricular arrhythmias ) persisted in 114 ( 69% ) patients . 
 after gr , appropriate icd therapies were delivered in 30 ( 26% ) patients with persistent icd indication and in 12 ( 23% ) of the remaining patients ( p  =  0.656 ) . 
 nonetheless , the annual rate of therapies was higher in the first group ( 1.08 versus 0.53 events / year ; p  <  0.001 ) , as well as the rate of inappropriate therapies ( 0.03 versus 0 events / year ; p  =  0.031 ) . the only independent predictor of appropriate icd therapies after gr was the rate of shocks received before replacement ( hazard ratio : 1.41 ; 95% confidence interval : 1.011.96 ; p  =  0.041).conclusionin heart failure with reduced lvef , icd indication persisted at the time of gr in 69% of patients . 
 however , even in the absence of persistent icd indication at gr , the risk of recurrence of arrhythmic events was not null .