Tom F. Brouwer

Long-Term Clinical Outcomes of Subcutaneous Versus Transvenous Implantable Defibrillator Therapy

BACKGROUNDnTransvenous implantable cardioverter-defibrillators (TV-ICDs) improve survival in patients at risk for sudden cardiac death, but complications remain an important drawback. The subcutaneous ICD (S-ICD) was developed to overcome lead-related complications. Comparison of clinical outcomes of both device types in previous studies was hampered by dissimilar patient characteristics.nnnOBJECTIVESnThis retrospective study compares long-term clinical outcomes of S-ICD and TV-ICD therapy in a propensity-matched cohort.nnnMETHODSnThe authors analyzed 1,160 patients who underwent S-ICD or TV-ICD implantation in 2 high-volume hospitals in the Netherlands. Propensity matching for 16 baseline characteristics, including diagnosis, yielded 140 matched pairs. Clinical outcomes were device-related complications requiring surgical intervention, appropriate and inappropriate ICD therapy, and were reported as 5-year Kaplan-Meier rate estimates.nnnRESULTSnAll 16 baseline characteristics were balanced in the matched cohort of 140 patients with S-ICDs and 140 patients with TV-ICDs (median age 41 years [interquartile range: 30 to 52 years] and 40% women). The complication rate was 13.7% in the S-ICD group versus 18.0% in the TV-ICD group (pxa0= 0.80). The infection rate was 4.1% versus 3.6% in the TV-ICD groups (pxa0= 0.36). Lead complications were lower in the S-ICD arm compared with the TV-ICD arm, 0.8% versus 11.5%, respectively (pxa0= 0.03). S-ICD patients had more nonlead-related complications than TV-ICD patients, 9.9% versus 2.2%, respectively (pxa0= 0.047). Appropriate ICD intervention (antitachycardia pacing and shocks) occurred more often in the TV-ICD group (hazard ratio [HR]: 2.42; pxa0= 0.01). The incidence of appropriate (TV-ICD HR: 1.46; pxa0=xa00.36) and inappropriate shocks (TV-ICD HR: 0.85; pxa0= 0.64) was similar.nnnCONCLUSIONSnThe complication rate in patients implanted with an S-ICD or TV-ICD was similar, but their nature differed. The S-ICD reduced lead-related complications significantly, at the cost of nonlead-related complications. Rates of appropriate and inappropriate shocks were similar between the 2 groups.

Surgical Management of Implantation-Related Complications of the Subcutaneous Implantable Cardioverter-Defibrillator

OBJECTIVESnThis study assessed outcomes in patients in whom subcutaneous implantable cardioverter-defibrillator (S-ICD) therapy was continued after implantation-related complications, in order to avoid conversion to transvenous ICD therapy.nnnBACKGROUNDnPatients at risk for sudden cardiac death benefit from ICD therapy, despite a significant risk for complications. S-ICD has a similar complication rate as transvenous ICD therapy, but the absence of transvenous leads may hold long-term benefits, especially in young ICD patients.nnnMETHODSnIn the largest single-center cohort available to date, S-ICD patients implanted between 2009 and 2015 were included.nnnRESULTSnThere were 123 patients at a median age of 40 years. During a median follow-up of 2xa0years, 10 patients (9.4%) suffered implant-related complications. There were 5 infections, 3 erosions, and 2 implant failures for which 21 surgical procedures were needed. In 9 of 10 patients, S-ICD therapy could be continued after intervention. In 6 patients, the period between extraction and reimplantation of the S-ICD system was bridged with a wearable cardioverter-defibrillator (WCD). The pulse generator was reimplanted at the original site in 5 patients and in 3xa0underneath the serratus anterior muscle. One patient was not reimplanted following extraction due to recurrent infections. Conversion to a transvenous ICD was not needed in any patient.nnnCONCLUSIONSnIn most patients with a complication, S-ICD therapy could be continued after intervention, avoiding thexa0need to convert to a transvenous system. Bridging to recovery with a WCD and submuscular implantation of the pulsexa0generator are effective treatment strategies to manage S-ICD complications.

J Curve in Patients Randomly Assigned to Different Systolic Blood Pressure Targets: An Experimental Approach to an Observational Paradigm

Background: Low systolic blood pressure (SBP) values are associated with an increased risk of cardiovascular events, giving rise to the so-called J-curve phenomenon. We assessed the association between on-treatment SBP levels, cardiovascular events, and all-cause mortality in patients randomized to different SBP targets. Methods: Data from 2 large randomized trials that randomly allocated hypertensive patients at high risk for cardiovascular disease to intensive (SBP<120 mmu2009Hg) or conventional (SBP<140 mmu2009Hg) treatment were pooled and harmonized for outcomes and follow-up duration. Using natural cubic splines, we plotted the hazard ratio for all-cause mortality and cardiovascular events against the mean on-treatment SBP per treatment group. Results: The pooled data consisted of 194u2009875 on-treatment SBP measurements in 13u2009946 patients (98.9%). During a median follow-up of 3.3 years, cardiovascular events occurred in 1014 patients (7.3%), and 502 patients died (3.7%). For both blood pressure targets, an identical shape of the J curve was present, with a nadir for cardiovascular events and all-cause mortality just below the SBP target. Patients in the lowest SBP stratum were older, had a higher body mass index, smoked more often, and had a higher frequency of diabetes mellitus and cardiovascular events. Conclusions: Low on-treatment SBP levels are associated with increased cardiovascular events and all-cause mortality. This association is independent of the attained blood pressure level because the J curve aligns with the SBP target. Our results suggest that the benefit or risk associated with intensive blood pressure–lowering treatment can be established only via randomized clinical trials. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01206062 and NCT00000620.

Intensive Blood Pressure Lowering in Patients With and Patients Without Type 2 Diabetes: A Pooled Analysis From Two Randomized Trials

OBJECTIVE The Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD-BP) study did not find a significant beneficial effect of intensive systolic blood pressure (SBP) lowering on cardiovascular events in hypertensive patients with type 2 diabetes mellitus (T2DM), while the Systolic Blood Pressure Intervention Trial (SPRINT) did find a significant beneficial effect in patients without T2DM. The objective of this analysis was to assess the effect of both T2DM and baseline cardiovascular disease risk on the treatment effect of intensive blood pressure lowering. RESEARCH DESIGN AND METHODS The individual patient data from the ACCORD-BP and SPRINT studies were pooled and follow-up durations harmonized. Both studies randomized hypertensive patients to an SBP target of <120 mmHg or a target of <140 mmHg. The composite primary end point consisted of unstable angina, myocardial infarction, acute heart failure, stroke, and cardiovascular death. The interaction between intensive blood pressure lowering and both T2DM and 10-year cardiovascular risk was assessed using Cox proportional hazards models. RESULTS The cohort consisted of 14,094 patients with mean age 66 ± 8.9 years and mean baseline SBP 139.5 ± 15.6 mmHg; 33.6% had T2DM. The hazard ratio for the primary composite end point was 0.82 (95% CI 0.73–0.93), P = 0.0017. The interaction between intensive blood pressure lowering and T2DM was nonsignificant (P = 0.13). The 10-year cardiovascular risk was higher in primary prevention patients with T2DM, but risk did not interact with the treatment effect (P = 0.84). CONCLUSIONS Intensive blood pressure lowering may have a similar favorable effect and appears to decrease cardiovascular events in both patients with and patients without T2DM.

Prospective blinded evaluation of a novel sensing methodology designed to reduce inappropriate shocks by the subcutaneous implantable cardioverter-defibrillator

BACKGROUNDnMost inappropriate shocks from the subcutaneous implantable cardioverter-defibrillator (S-ICD) are caused by cardiac oversensing. A novel sensing methodology, SMART Pass (SP; Boston Scientific Corporation, Natick, MA), aims to reduce cardiac oversensing.nnnOBJECTIVEnThe purpose of this study was to evaluate the effect of SP on shocks in ambulatory patients with S-ICD.nnnMETHODSnPatients implanted in 2015-2016 and enrolled in a remote patient monitoring system were included and followed for 1 year. Shocks were adjudicated by 3 independent blinded reviewers as appropriate or inappropriate. Shock incidence was calculated for patients with SP programmed enabled or disabled at implantation, censoring patients when SP programming changed or at the last transmission. The SP setting (enabled vs disabled) was modeled as a time-dependent Cox regression variable.nnnRESULTSnThe cohort consisted of 1984 patients, and a total of 880 shocks were adjudicated. At implantation, SP was enabled in 655 patients (33%) and disabled in 1329 patients (67%). SP reduced the risk for the first inappropriate shock by 50% (P < .001) and the risk for all inappropriate shocks by 68% (P < .001) in multivariate analysis adjusted for age and device programming. The incidence of inappropriate shocks was 4.3% in the SP enabled arm vs 9.7% in the SP disabled arm. The incidence of appropriate shocks was similar (5.2% vs 6.6%; P = .18) along with the time to treat the first appropriate shock (17.4 seconds vs 16.7 seconds; Pxa0=xa0.92) for SP enabled vs disabled, respectively.nnnCONCLUSIONnThis prospective blinded evaluation of the SP filter demonstrates that enabling the SP filter results in a significant reduction of inappropriate shocks by the S-ICD without a negative effect on appropriate shocks.

Propensity score matched comparison of subcutaneous and transvenous implantable cardioverter-defibrillator therapy in the SIMPLE and EFFORTLESS studies

AimsnComparison of outcomes between subcutaneous and transvenous implantable cardioverter-defibrillator (S-ICD and TV-ICD) therapy is hampered by varying patient characteristics and complication definitions. The aim of this analysis is to compare clinical outcomes of S-ICD and TV-ICD therapy in a matched cohort.nnnMethods and resultsnPatients implanted with de novo implantable cardioverter-defibrillators without need for pacing were selected from two studies: SIMPLE (nu2009=u20091091 single and nu2009=u2009553 dual chamber TV-ICDs) and EFFORTLESS (nu2009=u2009798 S-ICDs). Subcutaneous implantable cardioverter-defibrillator patients were 1:1 matched on propensity score to TV-ICD patients. Propensity scores were calculated using 15 baseline characteristics including diagnosis. The Kaplan-Meier estimates for complications requiring invasive intervention, appropriate shocks, and inappropriate shocks were calculated at 3 years follow-up. The primary analysis yielded 391 patients pairs with balanced baseline characteristics, with mean age 55u2009±u200914u2009years, 49% ischaemic cardiomyopathy, mean left ventricular ejection fraction 40%, 71% primary prevention, and 89% of TV-ICDs were single chamber. Follow-up was mean 2.9u2009years in the S-ICD arm vs. 3.3 in the TV-ICD arm. All-cause complications occurred in 9.0% of S-ICD vs. 6.5% of TV-ICD patients, Pu2009=u20090.29. Appropriate shocks occurred in 9.9% of S-ICD vs. 13.8% in TV-ICD patients, Pu2009=u20090.03 and inappropriate shocks in 11.9% in S-ICD vs. 8.9% in TV-ICD patients (Pu2009=u20090.07). Total shock burden (20 vs. 31, Pu2009=u20090.05) and appropriate shock burden per 100 patients years (9 vs. 18, Pu2009=u20090.02) were lower for S-ICD patients, while inappropriate shock burden was equal (11 vs. 13, Pu2009=u20090.56).nnnConclusionnThe earliest experience of the S-ICD demonstrates similar outcomes as contemporary TV-ICD therapy in a matched comparison with predominately single-chamber devices at 3 years follow-up.

Assessment of the Extravascular Implantable Defibrillator: Feasibility of Substernal Ventricular Pacing: Substernal Pacing in Humans

The objective of this study was to assess feasibility of ventricular pacing and thresholds from within the substernal space to examine a new extravascular ICD configuration with pacing capabilities.

Leadless pacemaker versus transvenous single-chamber pacemaker therapy: A propensity score-matched analysis

BACKGROUNDnThe recent introduction of leadless pacemakers (PMs) was aimed to eliminate transvenous lead- and pocket-related complications. While the initial results with the leadless PMs seem promising, the nonrandomized nature, limited implant experience of operators, and short follow-up period of these studies preclude a simple comparison to transvenous PMs.nnnOBJECTIVESnThe objective of this study was to provide a balanced comparison of leadless and transvenous single-chamber PM therapies through a propensity score-matched analysis.nnnMETHODSnLeadless patients from 3 experienced leadless implant centers were propensity score-matched to VVI-R patients from a contemporary prospective multicenter transvenous PM registry. The primary outcome was device-related complications that required invasive intervention during mid-term follow-up. Separate analyses including and excluding PM advisory-related complications were performed.nnnRESULTSnA total of 635 patients were match-eligible (leadless: nxa0=xa0254; transvenous: n = 381), of whom 440 patients (median age 78 years; interquartile range 70-84 years; 61% men) were successfully matched (leadless: n = 220 vs transvenous: n = 220). The complication rate at 800 days of follow-up was 0.9% (95% confidence interval [CI] 0%-2.2%) in the leadless group vs 4.7% (95% CI 1.8%-7.6%) in the transvenous group when excluding PM advisory-related complications (P = .02). When including these PM advisory-related complications, the complication rate at 800 days increased to 10.9% (95% CI 4.8%-16.5%) in the leadless group vs 4.7% (95% CI 1.8%-7.6%) in the transvenous group (P = .063).nnnCONCLUSIONnThis study reveals favorable complication rates for leadless compared to transvenous single-chamber pacing therapy at mid-term follow-up in a propensity score-matched cohort. When including PM advisory-related complications, this advantage is no longer observed.

A novel tool to evaluate the implant position and predict defibrillation success of the subcutaneous implantable defibrillator: the PRAETORIAN score

BACKGROUNDnSuboptimal positioning of the subcutaneous implantable cardioverter-defibrillator (S-ICD) increases the defibrillation threshold and risk of conversion failure.nnnOBJECTIVEnOur objective is to develop a tool to evaluate the implant position and predict defibrillation success of the S-ICD: the PRAETORIAN score.nnnMETHODSnThe PRAETORIAN score is based on clinical and computer modeling knowledge of determinants affecting the defibrillation threshold: subcoil fat, subgenerator fat, and anterior positioning of the S-ICD generator. The score evaluates these determinants on the postoperative anterior-posterior and lateral chest radiographs and has 3 categories: 30-<90 points representing a low risk, 90-<150 points representing an intermediate risk, and ≥150 points representing a high risk of conversion failure. The score was developed using 2 separate S-ICD data sets for derivation and validation. The performance metrics are the positive and negative predictive values.nnnRESULTSnThe development data set consisted of 181 patients with S-ICD, and the validation cohort consisted of 321 patients from the S-ICD Investigational Device Exemption trial. The distribution of scores was 93%-98% low risk (<90 points), 2%-5% intermediate risk (90-<150 points), and 1% high risk (≥150 points). The positive predictive value for an intermediate or high PRAETORIAN score for a failed conversion test was 51%, while a low PRAETORIAN score predicted a successful conversion in 99.8% of patients.nnnCONCLUSIONnThe PRAETORIAN score allows the identification of patients with high defibrillation thresholds by using the routine chest radiograph and provides feedback to implanters on S-ICD positioning. The PRAETORIAN-DFT trial will prospectively validate the score by randomizing to standard conversion testing vs using the score without conversion testing.

An Overview of Clinical Outcomes in Transvenous and Subcutaneous ICD Patients

Purpose of ReviewClear guidelines on when to select a subcutaneous ICD (S-ICD) over a transvenous ICD (TV-ICD) are lacking. This review will provide an overview of the most recent clinical data on S-ICD and TV-ICD therapy by pooling comparison studies in order to aid clinical decision making.Recent FindingsPooling of observational-matched studies demonstrated an incidence rate ratio (IRR) for device-related complication of 0.90 (95% CI 0.58–1.42) and IRR for lead-related complications of 0.15 (95% CI 0.06–0.39) in favor of S-ICD. The IRR for device infections was 2.00 (95% CI 0.95–4.22) in favor of TV-ICD. Both appropriate shocks (IRR 0.67 (95% CI 0.42–1.06)) and inappropriate shocks (IRR 1.17 (95% CI 0.77–1.79)) did not differ significantly between both groups.SummaryWith randomized data underway, the observational data demonstrate that the S-ICD is associated with reduced lead complications, but this has not yet resulted in a significant reduction in total number of complications compared to TV-ICDs. New technologies are expected to make the S-ICD a more attractive alternative.