Risk Of Inappropriate Therapy Research Articles

T-Wave Oversensing with Contemporary Implantable Cardioverter-Defibrillators.

Implantable cardioverter-defibrillators (ICDs) need to reliably detect ventricular tachycardia (VT) and ventricular fibrillation (VF) while avoiding T-wave oversensing (TWOS), which is associated with a risk of inappropriate therapies. The incidence of TWOS with endovascular ICDs appears to differ between manufacturers. We aimed to evaluate the incidence and clinical consequences of TWOS with contemporary Medtronic and Boston Scientific ICDs. Consecutive patients implanted with a recent Medtronic or Boston Scientific ICD and remotely monitored at three French centers were included. All transmitted EGMs labelled as VF, VT, non-sustained VT (NSVT), or ventricular oversensing (Medtronic) were screened for TWOS. Among 7589 transmitted episodes from 674 patients with a Boston Scientific ICD, we did not identify a single case of TWOS. Among 16,790 transmitted episodes from 1733 patients with a Medtronic ICD, we identified 60 patients (3.4%) with at least one episode of TWOS. In 46 patients, TWOS was intermittent (NSVT episodes). In the remaining 14 patients, TWOS resulted in 60 sustained episodes (completed counters). No inappropriate therapies were delivered in 12 of these patients because no therapies were programmed (in monitor zones, 11 episodes) or because therapies were inhibited by the morphology discriminator (Wavelet, 19 episodes) or by the anti-TWOS algorithm (26 episodes). Two patients received inappropriate therapies due to TWOS (0.1% of patients with Medtronic ICDs). On review of 24,379 transmitted episodes from 2407 patients with endovascular ICDs, we found no case of TWOS with Boston Scientific devices, whereas TWOS was not uncommon with Medtronic devices. However, the risk of inappropriate therapy with Medtronic ICDs was very low (0.1%) due to the often intermittent nature of this phenomenon, the morphology discriminator, and the anti-TWOS algorithm.

Exploiting SMART pass filter deactivation detection to minimize inappropriate subcutaneous implantable cardioverter defibrillator therapies: a real-world single-centre experience and management guide.

The SMART Pass™ (SP) algorithm is a high-pass filter that aims to reduce inappropriate therapy (IT) in subcutaneous internal cardiac defibrillator (S-ICD), but SP can deactivate due to low amplitude sensed R waves or asystole. The association between IT and SP deactivation and management strategies were evaluated, hypothesizing SP deactivation increases the risk of IT and device re-programming, or lead/generator re-positioning could reduce this risk. Retrospective single-centre audit of Emblem™ S-ICD devices implanted 2016 to 2020 utilizing health records and remote monitoring data. Cox regression models evaluated associations between SP deactivation and IT. A total of 348 patients (27 ± 16.6 months follow-up) were studied: 73% primary prevention. Thirty-eight patients (11.8%) received 83 shocks with 27 patients (7.8%) receiving a total of 44 IT. Causes of IT were oversensing (98%) and aberrantly conducted atrial fibrillation (2%). SP deactivation occurred in 32 of 348 patients (9%) and was significantly associated with increased risk of IT (hazard ratio 5.36, 95% CI 2.37-12.13). SP deactivation was due to low amplitude R waves (94%), associated with a higher defibrillation threshold at implant and presence of arrhythmogenic right ventricular cardiomyopathy. No further IT occurred 16 ± 15.5 months after corrective interventions, with changing the sensing vector being successful in 59% of cases. To reduce the risk of IT, the cause of the SP deactivation should be investigated, and appropriate reprogramming, device, or lead modifications made. Utilizing the alert for SP deactivation and electrograms could pro-actively prevent IT.

AP-518-01 SUBCUTANEOUS IMPLANTABLE CARDIOVERTER DEFIBRILLATOR SMART DEACTIVATION INCREASES INAPPROPRIATE SHOCKS, A REAL-WORLD SINGLE CENTRE EXPERIENCE

The SICD has been increasingly used with its addition to the HRS guidelines in 2017. A question mark remains around the burden of inappropriate therapy (IT), which, in PRETORIAN had an IT in 9.6% of patients over 4 years. Importantly, this trial was conducted using devices without the SMART pass (SP) algorithm installed. SP (Boston Scientific Corporation, Natick, MA) is a bandpass filter has been shown to reduce inappropriate therapy. However, a key area under-investigated is the algorithms’ ability to deactivate itself in community. We aimed to assess: the effect of SP, with clinical variables, on inappropriate therapies and oversensing; why the device deactivates SP and how best to manage this scenario, in a large, single centre. A retrospective audit of all Emblem S-ICD devices (A209 & A219) implanted from 2016 to 2020 using data from electronic pacing & health records and latitude remote monitoring system. The baseline clinical characteristics and SICD programming were recorded at implant and throughout follow up. A total of 322 patients were reviewed with a follow up of 27 months ± 16.6 months. 234were primary prevention (73%) and remaining 88 patients (27%) were secondary prevention. Thirty-eight (11.8%) of patients received total of 83 shocks. Twenty-four (7.5%) patients receiving IT, totalling 44 shocks. One IT was due to aberrant AF, the remaining 43 were due to oversensing. SP was a significant predictor of all therapy (p.00049) and IT (p.009). Table 1 shows rate of SP deactivation and IT rate. SP deactivation has an odds ratio of 6.45 (95% CI: 2.62 to 15.94) of IT. SP deactivation was due to low R waves in 19 patients, significant asystole in 1 patient and not available in 1 patient at the time of therapy. SP deactivation is a significant predictor and marker of IT. If the SP filter is deactivated this is likely to suggest low amplitude sensing signals. To reduce the risk of IT the cause of the SP deactivation should be investigated and sensing vector changes should be strongly considered. If the SP algorithm continues to de-activate, lead reposition should be considered, similarly to a transvenous RV ICD lead would for poor sensing. An alert for SP deactivation, R wave size and raw S-EGMs would provide clinicians with appropriate decision making to prevent IT.

A050 Defibrillator Therapy in Patients Receiving a Primary Prevention CRT-D Device: The Wellington Experience

There is no clear consensus on whether to routinely insert a primary prevention defibrillator in patients receiving CRT. Improvement of cardiac status may reduce the likelihood of ventricular arrhythmia and therefore the need for an ICD. This is especially true in patients with a non-ischaemic cardiomyopathy. The risk of inappropriate therapy must also be taken into account. Our aim was to review the incidence of appropriate and inappropriate therapy in patients undergoing CRT-D implantation under active follow up. Patients with an active CRT-D were sampled from the PaceArt database. Those who received a primary prevention device were included in the analysis. Baseline data and therapy received was collected. There were 78 patients in our analysis. 11(14%) had an ischaemic cardiomyopathy, 64 (82%) had a non-ischemic cardiomyopathy and 3(4%) were of mixed aetiology. The average age at implant was 63 years. 27(35%) were female. The mean EF at implant was 23%. In total, 19 (24%) patients received therapy. 4(5%) received inappropriate therapy, 1 received an inappropriate shock. 45% of ischaemic cardiomyopathy patients received therapy vs 22% of non-ischaemic patients. There were no cases of inappropriate therapy in ischaemic patients. The incidence of appropriate therapy is higher with ischaemic cardiomyopathy than with non-ischaemic cardiomyopathy for patients in our data set. The number of patients receiving inappropriate therapy was low. This may help with device selection and inform patients of potential risks and benefits.

P2277Utility of cardiovascular implantable electronic device (CIED)-derived patient activity, a novel digital biomarker, to predict inappropriate therapy

Abstract Background The role of cardiovascular implantable electronic device (CIED)-derived activity to predict inappropriate implantable cardioverter-defibrillator (ICD) therapy is not known. The Multicenter Automatic Defibrillator Implantation Trial – Reduce Inappropriate Therapy (MADIT-RIT) enrolled 1500 patients with contemporary indication for an ICD or a CRT-D. We aimed to identify whether activity, as a digital biomarker, predicted inappropriate therapy. Methods In 1500 patients enrolled in MADIT-RIT, CIED-derived patient activity was acquired daily. CIED-derived activity was averaged for the first 30 days following randomization and utilized in this study to predict inappropriate therapy post- 30-day. Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression models were used to evaluate first inappropriate therapy by 30-day CIED-derived patient activity quintiles, and by 30-day device derived patient activity as a continuous measurement. Results There were a total of 1463 patients with activity data available (90%), 135 patients received at least one inappropriate therapy during the post-30 day follow-up period. Patients in the highest quintile (Q5) of CIED-derived activity (more active) were younger, more often males and more likely to have had a prior ablation of an atrial arrhythmia. Patients in the highest quintile of 30-day CIED-derived median activity had the highest risk of receiving inappropriate therapy, 21% at 2 years as compared 7–11% in the other four quintiles (Figure, p<0.001 for the overall duration). Patients with the highest level of 30-day median patient activity (Q5) had 1.75 times higher risk of any inappropriate therapy as compared with lower levels of activity, Q1-Q4 (HR=1.75, 95% CI: 1.23–2.50, p<0.002). Each 10% increase in CIED-derived 30-day median patient activity was associated with a significant, 73% increase in risk of receiving inappropriate therapy (HR=1.73, 95% CI: 1.17–2.54, p=0.005). Patients in the highest quintile for activity had a 68% increase in the risk of SVT excluding atrial fibrillation, atrial flutter or atrial tachycardia (HR=1.69, 95% CI: 1.26–2.25, p=0.004), despite 96% receiving beta-blocker medications. Inappropriate ICD Therapies by Activity Conclusions CIED-derived 30-day median patient activity predicted subsequent inappropriate therapy in ICD and CRT-D patients enrolled in MADIT-RIT. Patients with high levels of 30-day CIED-derived median patient activity were at a significantly higher risk of receiving inappropriate therapy. Activity, as a digital biomarker, may have utility in predicting and managing the risk of inappropriate therapy in this population. Acknowledgement/Funding Boston Scientific

Implantable cardioverter-defibrillator therapy and device-related complications in young patients with inherited cardiomyopathies or channelopathies: a 17-year cohort study.

To quantify appropriate and inappropriate therapy and complications related to implantable cardioverter-defibrillator (ICD) treatment in young patients receiving an ICD for a hereditary cardiomyopathy or channelopathy. This was a retrospective study including 117 consecutive patients who had received an ICD at Aarhus University Hospital, Denmark from 1 January 1999 to 31 December 2015. Patients were followed from the date of ICD implantation until migration, death, heart transplantation, or end of follow-up on 1 February 2017. Mean age at implantation was 30.5 ± 12.8 years, and the patients were followed for a mean period of 7.1 ± 4.4 years. The cumulative incidence at 1, 5, and 10 years was 17%, 29%, and 48% for appropriate ICD therapy, 6%, 13%, and 20% for inappropriate ICD therapy, and 7%, 18%, and 33% for device-related complications, respectively. Patients with an ICD implanted for secondary prevention had a higher risk of appropriate therapy compared with patients implanted for primary prevention [adjusted hazard ratio (HR) 5.18, 95% confidence interval (CI) 2.22-12.09; P < 0.01]. There was no difference in the risk of inappropriate therapy (adjusted HR 1.58, 95% CI 0.55-4.56; P = 0.40) or device-related complications (adjusted HR 1.22, 95% CI 0.56-2.68; P = 0.62) between patients with primary and secondary preventive indication. We observed high absolute risk estimates for appropriate ICD therapy in young patients with an ICD indicated by a hereditary cardiomyopathy or channelopathy. Also risks for inappropriate ICD therapy and device-related complications were significant.

Remote monitoring and inappropriate therapies in ICD patients: The THORN registry

Inappropriate shocks (IS) are a major side effect of implantable cardioverter defibrillators (ICD). Remote monitoring (RM) may reduce inappropriate diagnoses (ID) and subsequent inappropriate therapies (IT). The purpose of THORN study was to determine the ability of ICD RM to early identify ID of ventricular arrhythmias and prompt physician reaction, in order to reduce the risk of recurrent IT. THORN is an observational multicenter study of RM ICD patients, separated in a retrospective cohort (R), issued from a large RM database collected since 2007 by Biotronik SE & Co.KG and a prospective cohort (P) of patients implanted since 2012. The primary objective was to determine: 1/in the retrospective cohort, the relative proportion of patients experiencing at least one IT during a 15-month follow-up period, and, 2/in the prospective cohort, the medical reaction time (MRT) and ID recurrence after an initial ID. A total of 1891 patients (R: 1379, P: 512), implanted with a CRT-D (28.1%) or conventional ICD, (single chamber: 45.1%; dual chamber: 26.8%) were enrolled (83.6% men, 62.9 ± 12.8 y), 31.8% in primary prevention. During 13.7 ± 3.5 months of follow-up, 8.6% (R: 9.2%, P: 6.9%, P = 0.05) of the patients experienced at least one ID, of whom, 75.3% suffered at least one IT (R: 74%, P: 80%, P = NS) and 35.8% at least one IS. The median MRT was 9 days (0 to 145 days). It was 4 times longer for ID due to supraventricular tachyarrhythmias (16 days) compared to those due to abnormal sensing (4 days) ( P = 0.04). ID recurrence occurred in 37% of ID patients, with a substantial part (25.7%) within the MRT. Among the 6.5% of patients experiencing at least one IT, 36.1% had an IT recurrence. The rate of patients experiencing ID/IT and recurrences seems to decrease over time. Though RM is intended to take action earlier, the MRT is sometimes long and could be reduced as ID/IT recurrences are not infrequent within the MRT period.

Heart failure severity, inappropriate ICD therapy, and novel ICD programming: a MADIT-RIT substudy.

The effects of heart failure (HF) severity on risk of inappropriate implantable cardioverter-defibrillator (ICD) therapy have not been thoroughly investigated. We aimed to study the association between HF severity and inappropriate ICD therapy in MADIT-RIT. MADIT-RIT randomized 1,500 patients to three ICD programming arms: conventional (Arm A), high-rate cut-off (Arm B: ≥200beats/min), and delayed therapy (Arm C: 60-second delay for ≥170beats/min). We evaluated the association between New York Heart Association (NYHA) class III (n=256) versus class I-II (n=251) and inappropriate ICD therapy in Arm A patients with ICD-only and cardiac resynchronization therapy with defibrillator (CRT-D). We additionally assessed benefit of novel ICD programming in Arms B and C versus Arm A by NYHA classification. In Arm A, the risk of inappropriate therapy was significantly higher in those with NYHA III versus NYHA I-II for both ICD (hazard ratio [HR]=2.55, confidence interval [CI]: 1.51-4.30, P<0.001) and CRT-D patients (HR=3.73, CI: 1.14-12.23, P=0.030). This was consistent for inappropriate ATP and inappropriate ICD therapy<200beats/min, but not for inappropriate shocks. Novel ICD programming significantly reduced inappropriate therapy in patients with both NYHA III (Arm B vs Arm A: HR=0.08, P<0.001; Arm C vs Arm A: HR=0.17, P<0.001) and NYHA I-II (Arm B vs Arm A: HR=0.25, P<0.001; Arm C vs Arm A: HR=0.28, P<0.001). Patients with more severe HF are at increased risk for inappropriate ICD therapy, particularly ATP due to arrhythmias<200beats/min. Novel programming with high-rate cut-off or delayed detection reduces inappropriate ICD therapies in both mild and moderate HF.

Evaluation of blood requisition and utilization practices at a tertiary care hospital blood bank in Islamabad, Pakistan

Introduction: The significance of appropriate completion of blood request forms (BRFs) is frequently underrated by the clinicians which results in wastage and increased risk of inappropriate therapy. The judicious use of blood components can be assessed by the crossmatch-to-transfusion ratio (C:T), transfusion probability (%T), and transfusion index (TI). The current study assessed the standard of completion of BRFs and blood components utilization at a Tertiary Care Hospital Blood Bank. Materials and Methods: This was a cross-sectional, prospective study conducted at the Department of Blood Transfusion Services, Shaheed Zulfiqar Ali Bhutto Medical University Hospital, Islamabad, from January to April 2016. A total of 5957 BRFs received between January and April 2016 were reviewed. The data were entered in SPSS version 20.0 (IBM SPSS Statistics for Windows, IBM Corp., Armonk, NY, USA) and analyzed for completeness, legibility, and blood component utilization through calculation of key indicators including C:T ratio, transfusion probability (%T), and TI. Results: Out of the 5957 request forms reviewed, only 12.7% forms were completed in full. The overall C:T ratio, %T, and TI were 1.52, 65.38, and 0.65, respectively. The same indicators for the Maternal and Child Health Centre (MCHC) were 10.7, 9.32, and 0.09. Conclusion: Incomplete blood transfusion request forms create difficulties for the blood bank staff in comprehending the requests which may compromise patient safety. Similarly, the efficiency of MCHC blood transfusion services is far from optimum. The Hospital Transfusion Committee can play a key role in solving this problem and thus improving the standards of Patient Blood Management.

Relationship between age and inappropriate implantable cardioverter-defibrillator therapy in MADIT-RIT (Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy)

There is limited data regarding the relationship between age and inappropriate therapy among patients with an implantable cardioverter-defibrillator (ICD) and resynchronization therapy. We aimed to investigate this relationship and the effect of ICD programming on inappropriate therapy by age. In the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) 1500 patients were randomized to 3 ICD programming arms: (A) conventional with ventricular tachycardia (VT) therapy ≥170; (B) high-rate cutoff with VT therapy ≥200, and (C) prolonged 60-second delay for VT therapy ≥170. We investigated the relationship between age, the risk of inappropriate ICD therapy (including antitachycardia pacing [ATP] or shock), and ICD programming. Cumulative incidence function Kaplan-Meier graphs showed an inverse relationship between increasing quartiles of age (Q1: ≤55, Q2: 56-64, Q3: 65-71, and Q4: ≥72 years) and the risk for inappropriate therapy. Multivariate analyses showed that each increasing decade of life was associated with 34% (P < .001), 27% (P < .001), and 26% (P < .001) reduction in the risk of inappropriate shock, inappropriate ATP, and any inappropriate therapy, respectively. Treatment arms B and C as compared with arm A were associated with a significant reduction in the risk of inappropriate therapies across all age quartiles (P < .001 for all). Among patients with a primary prevention indication for an ICD, there is an inverse relationship between age and inappropriate ICD therapy. Innovative ICD programming of high-rate cutoff or prolonged delay for VT therapy is associated with significant reductions in inappropriate therapy among all age groups.

Cardiac resynchronization therapy is associated with reductions in left atrial volume and inappropriate implantable cardioverter-defibrillator therapy in MADIT-CRT

There are no prior studies assessing the relationship between left atrial volume (LAV) and inappropriate implantable cardioverter-defibrillator (ICD) therapy following treatment with cardiac resynchronization therapy. The purpose of this study was to investigate the hypothesis that patients randomized to cardiac resynchronization therapy with defibrillator (CRT-D) in the Multicenter Automatic Defibrillator Trial-Cardiac Resynchronization Therapy (MADIT-CRT) who had significant LAV reductions would have reduced risks of inappropriate ICD therapy. Cardiac resynchronization remodeling was assessed by measuring LAV change between baseline and 12-month echocardiograms in 751 CRT-D treated patients. Patients were stratified into quartiles based on percent reduction of LAV change. High LAV responders were those in the highest 3 quartiles of LAV reduction (LAV reduction ≥21%). Low LAV responders were those in the lowest quartile of LAV reduction (LAV reduction <21%). Clinical factors associated with ≥21% reduction in LAV were evaluated by linear regression analysis. In Cox proportional hazards regression analyses, high LAV responders had a 39% reduction in the risk of inappropriate therapy (hazard ratio 0.61, P = .04) and left bundle branch block patients exhibited an even greater risk reduction in inappropriate therapy (hazard ratio 0.51, P = .02) compared to low LAV responders during follow-up extending up to 3 years after the 12-month echocardiogram. High LAV responders also had a significantly lower risk of heart failure or death during follow-up than did low LAV responders. A ≥21% reduction in LAV with cardiac resynchronization therapy is associated with significant reductions in inappropriate ICD therapy and in heart failure or death during a 3-year follow-up.

Influence of prior atrial arrhythmias on the effects of innovative programming in reducing inappropriate therapy and death in MADIT-RIT

Background: The impact of prior atrial arrhythmias on the effects of innovative programming and subsequent outcome has not yet been evaluated. Methods: The MADIT-RIT trial randomized ICD patients to three programming arms: conventional programming with a VT zone ≥170 bpm (Arm A), high-rate cut-off with a VT zone ≥200 bpm (Arm B), or 60-sec delayed therapy in the VT zone 170-199 bpm (Arm C). The effects of programming on inappropriate therapy and death were assessed in multivariate Cox models stratified by prior atrial arrhythmias (atrial arrhythmia prior to enrollment). Results: In patients with prior atrial arrhythmias (n=203, 14%) there was a significantly higher risk of inappropriate therapy (HR=2.10, 95% CI: 1.38-3.20, p 0.10) (Figure). High-rate cut-off programming (Arm B) was associated with a significant reduction in the risk of all-cause mortality in patients without prior atrial arrhythmias (HR=0.48, 95% CI: 0.25-0.93, p=0.03), and similar, but not significant reduction in those with prior atrial arrhythmias (HR=0.33, 95% CI: 0.08-1.34, p=0.12, interaction p-value=0.645). ![Figure][1] Figure Conclusion: Novel ICD programming reduces inappropriate therapy in those with or without prior atrial arrhythmias. There was a beneficial reduction in all-cause mortality in those programmed to high-rate therapy (Arm B), particularly in those with a history of prior atrial arrhythmias. [1]: pending:yes

Clinical characteristics and treatment of short QT syndrome

Short QT syndrome is a new inherited disorder associated with familial atrial fibrillation and/or sudden death or syncope. To date, three different mutations in genes encoding cardiac ion channels (KCNH2, KCNQ1 and KCNJ2) have been identified as causing short QT syndrome. All mutations lead to a gain in function of the affected current (IKr, IKs and IK1). The syndrome is characterized in the few patients identified so far by a shortened QT interval of less than 300–325 ms after correction for heart rate at rates below 80 beats per minute. However, no boundary or limit for the QT interval can yet be determined, as more knowledge about this disease is still restricted to a small patient population. Furthermore, the QT interval lacks adaptation to heart rate. The majority of patients exhibit shortened atrial and ventricular effective refractory periods and inducibility of ventricular fibrillation. Death already occurs in newborns, so the short QT syndrome may also account for deaths classified as sudden infant death syndrome. The therapy of choice in families with a history of sudden death or syncope seems to be the implantable cardioverter-defibrillator. Whether patients without a family history of sudden death or symptoms need a defibrillator cannot yet be answered, and requires further investigation. Pharmacologic treatment has only been investigated in patients with a mutation in KCNH2 (HERG), and it could be demonstrated that the mutant currents may be insufficiently suppressed by drugs that are targeted to block the specific current (e.g., sotalol or ibutilide) in patients with a mutation in the IKr-coding gene KCNH2 (HERG). Interestingly, in this specific patient population, quinidine proved to be efficient in prolonging the QT interval and normalizing the effective refractory periods. Implantable cardioverter-defibrillator therapy is associated with an increased risk of inappropriate therapies for T-wave oversensing, although this risk can be resolved by reprogramming implantable cardioverter-defibrillator detection algorithms.

Toxic risks of inappropriate therapy

Drug therapy may produce toxicity. Patient individuality or drug interactions account for many cases of poisoning, but other factors such as genetic predisposition, drug contamination or human error are also known causes. Examples of various types of drug poisoning are given, illustrating the role of the clinical chemist in minimizing or studying drug toxicity.