Efficacy and Safety of Appropriate Shocks and Antitachycardia Pacing in Transvenous and Subcutaneous Implantable Defibrillators: Analysis of All Appropriate Therapy in the PRAETORIAN Trial.

BACKGROUND: The PRAETORIAN trial (A Prospective, Randomized Comparison of Subcutaneous and Transvenous Implantable Cardioverter Defibrillator Therapy) showed noninferiority of subcutaneous implantable cardioverter defibrillator (S-ICD) compared with transvenous implantable cardioverter defibrillator (TV-ICD) with regard to inappropriate shocks and complications. In contrast to TV-ICD, S-ICD cannot provide antitachycardia pacing for monomorphic ventricular tachycardia. This prespecified secondary analysis evaluates appropriate therapy and whether antitachycardia pacing reduces the number of appropriate shocks. METHODS: The PRAETORIAN trial was an international, investigator-initiated randomized trial that included patients with an indication for implantable cardioverter defibrillator (ICD) therapy. Patients with previous ventricular tachycardia <170 bpm or refractory recurrent monomorphic ventricular tachycardia were excluded. In 39 centers, 849 patients were randomized to receive an S-ICD (n=426) or TV-ICD (n=423) and were followed for a median of 49.1 months. ICD programming was mandated by protocol. Appropriate ICD therapy was defined as therapy for ventricular arrhythmias. Arrhythmias were classified as discrete episodes and storm episodes (≥3 episodes within 24 hours). Analyses were performed in the modified intention-to-treat population. RESULTS: In the S-ICD group, 86 of 426 patients received appropriate therapy, versus 78 of 423 patients in the TV-ICD group, during a median follow-up of 52 months (48-month Kaplan-Meier estimates 19.4% and 17.5%; P=0.45). In the S-ICD group, 83 patients received at least 1 shock, versus 57 patients in the TV-ICD group (48-month Kaplan-Meier estimates 19.2% and 11.5%; P=0.02). Patients in the S-ICD group had a total of 254 shocks, compared with 228 shocks in the TV-ICD group (P=0.68). First shock efficacy was 93.8% in the S-ICD group and 91.6% in the TV-ICD group (P=0.40). The first antitachycardia pacing attempt successfully terminated 46% of all monomorphic ventricular tachycardias, but accelerated the arrhythmia in 9.4%. Ten patients with S-ICD experienced 13 electrical storms, versus 18 patients with TV-ICD with 19 electrical storms. Patients with appropriate therapy had an almost 2-fold increased relative risk of electrical storms in the TV-ICD group compared with the S-ICD group (P=0.05). CONCLUSIONS: In this trial, no difference was observed in shock efficacy of S-ICD compared with TV-ICD. Although patients in the S-ICD group were more likely to receive an ICD shock, the total number of appropriate shocks was not different between the 2 groups. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01296022.

Subcutaneous or Transvenous Defibrillator Therapy.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (ICD) was designed to avoid complications related to the transvenous ICD lead by using an entirely extrathoracic placement. Evidence comparing these systems has been based primarily on observational studies. METHODS: We conducted a noninferiority trial in which patients with an indication for an ICD but no indication for pacing were assigned to receive a subcutaneous ICD or transvenous ICD. The primary end point was the composite of device-related complications and inappropriate shocks; the noninferiority margin for the upper boundary of the 95% confidence interval for the hazard ratio (subcutaneous ICD vs. transvenous ICD) was 1.45. A superiority analysis was prespecified if noninferiority was established. Secondary end points included death and appropriate shocks. RESULTS: A total of 849 patients (426 in the subcutaneous ICD group and 423 in the transvenous ICD group) were included in the analyses. At a median follow-up of 49.1 months, a primary end-point event occurred in 68 patients in the subcutaneous ICD group and in 68 patients in the transvenous ICD group (48-month Kaplan-Meier estimated cumulative incidence, 15.1% and 15.7%, respectively; hazard ratio, 0.99; 95% confidence interval [CI], 0.71 to 1.39; P = 0.01 for noninferiority; P = 0.95 for superiority). Device-related complications occurred in 31 patients in the subcutaneous ICD group and in 44 in the transvenous ICD group (hazard ratio, 0.69; 95% CI, 0.44 to 1.09); inappropriate shocks occurred in 41 and 29 patients, respectively (hazard ratio, 1.43; 95% CI, 0.89 to 2.30). Death occurred in 83 patients in the subcutaneous ICD group and in 68 in the transvenous ICD group (hazard ratio, 1.23; 95% CI, 0.89 to 1.70); appropriate shocks occurred in 83 and 57 patients, respectively (hazard ratio, 1.52; 95% CI, 1.08 to 2.12). CONCLUSIONS: In patients with an indication for an ICD but no indication for pacing, the subcutaneous ICD was noninferior to the transvenous ICD with respect to device-related complications and inappropriate shocks. (Funded by Boston Scientific; PRAETORIAN ClinicalTrials.gov number, NCT01296022.).

Device-related complications in subcutaneous versus transvenous ICD: a secondary analysis of the PRAETORIAN trial.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is developed to overcome lead-related complications and systemic infections, inherent to transvenous ICD (TV-ICD) therapy. The PRAETORIAN trial demonstrated that the S-ICD is non-inferior to the TV-ICD with regard to the combined primary endpoint of inappropriate shocks and complications. This prespecified secondary analysis evaluates all complications in the PRAETORIAN trial. METHODS AND RESULTS: The PRAETORIAN trial is an international, multicentre, randomized trial in which 849 patients with an indication for ICD therapy were randomized to receive an S- ICD (N = 426) or TV-ICD (N = 423) and followed for a median of 49 months. Endpoints were device-related complications, lead-related complications, systemic infections, and the need for invasive interventions. Thirty-six device-related complications occurred in 31 patients in the S-ICD group of which bleedings were the most frequent. In the TV-ICD group, 49 complications occurred in 44 patients of which lead dysfunction was most frequent (HR: 0.69; P = 0.11). In both groups, half of all complications were within 30 days after implantation. Lead-related complications and systemic infections occurred significantly less in the S-ICD group compared with the TV-ICD group (P < 0.001, P = 0.03, respectively). Significantly more complications required invasive interventions in the TV-ICD group compared with the S-ICD group (8.3% vs. 4.3%, HR: 0.59; P = 0.047). CONCLUSION: This secondary analysis shows that lead-related complications and systemic infections are more prevalent in the TV-ICD group compared with the S-ICD group. In addition, complications in the TV-ICD group were more severe as they required significantly more invasive interventions. This data contributes to shared decision-making in clinical practice.

Cardiac mortality in patients randomised to elective coronary revascularisation plus medical therapy or medical therapy alone: a systematic review and meta-analysis.

AIMS: The value of elective coronary revascularisation plus medical therapy over medical therapy alone in managing stable patients with coronary artery disease is debated. We reviewed all trials comparing the two strategies in this population. METHODS AND RESULTS: From inception through November 2020, MEDLINE, EMBASE, Google Scholar, and other databases were searched for randomised trials comparing revascularisation against medical therapy alone in clinically stable coronary artery disease patients. Treatment effects were measured by rate ratios (RRs) with 95% confidence intervals, using random-effects models. Cardiac mortality was the pre-specified primary endpoint. Spontaneous myocardial infarction (MI) and its association with cardiac mortality were secondary endpoints. Further endpoints included all-cause mortality, any MI, and stroke. Longest follow-up data were abstracted. The study is registered with PROSPERO (CRD42021225598). Twenty-five trials involving 19 806 patients (10 023 randomised to revascularisation plus medical therapy and 9783 to medical therapy alone) were included. Compared with medical therapy alone, revascularisation yielded a lower risk of cardiac death [RR 0.79 (0.67-0.93), P < 0.01] and spontaneous MI [RR 0.74 (0.64-0.86), P < 0.01]. By meta-regression, the cardiac death risk reduction after revascularisation, compared with medical therapy alone, was linearly associated with follow-up duration [RR per 4-year follow-up: 0.81 (0.69-0.96), P = 0.008], spontaneous MI absolute difference (P = 0.01) and percentage of multivessel disease at baseline (P = 0.004). Trial sequential and sensitivity analyses confirmed the reliability of the cardiac mortality findings. All-cause mortality [0.94 (0.87-1.01), P = 0.11], any MI (P = 0.14), and stroke risk (P = 0.30) did not differ significantly between strategies. CONCLUSION: In stable coronary artery disease patients, randomisation to elective coronary revascularisation plus medical therapy led to reduced cardiac mortality compared with medical therapy alone. The cardiac survival benefit after revascularisation improved with longer follow-up times and was associated with fewer spontaneous MIs.

Effect of Adding Ticagrelor to Standard Aspirin on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting (POPular CABG): A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Approximately 15% of saphenous vein grafts (SVGs) occlude during the first year after coronary artery bypass graft surgery (CABG) despite aspirin use. The POPular CABG trial (The Effect of Ticagrelor on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting Surgery) investigated whether ticagrelor added to standard aspirin improves SVG patency at 1 year after CABG. METHODS: In this investigator-initiated, randomized, double-blind, placebo-controlled, multicenter trial, patients with ≥1 SVGs were randomly assigned (1:1) after CABG to ticagrelor or placebo added to standard aspirin (80 mg or 100 mg). The primary outcome was SVG occlusion at 1 year, assessed with coronary computed tomography angiography, in all patients that had primary outcome imaging available. A generalized estimating equation model was used to perform the primary analysis per SVG. The secondary outcome was 1-year SVG failure, which was a composite of SVG occlusion, SVG revascularization, myocardial infarction in myocardial territory supplied by a SVG, or sudden death. RESULTS: Among 499 randomly assigned patients, the mean age was 67.9±8.3 years, 87.1% were male, the indication for CABG was acute coronary syndrome in 31.3%, and 95.2% of procedures used cardiopulmonary bypass. Primary outcome imaging was available in 220 patients in the ticagrelor group and 223 patients in the placebo group. The SVG occlusion rate in the ticagrelor group was 10.5% (51 of 484 SVGs) versus 9.1% in the placebo group (43 of 470 SVGs), odds ratio, 1.29 [95% CI, 0.73-2.30]; P=0.38. SVG failure occurred in 35 (14.2%) patients in the ticagrelor group versus 29 (11.6%) patients in the placebo group (odds ratio, 1.22 [95% CI, 0.72-2.05]). CONCLUSIONS: In this randomized, placebo-controlled trial, the addition of ticagrelor to standard aspirin did not reduce SVG occlusion at 1 year after CABG. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02352402.

Cardiac Troponin Composition Characterization after Non ST-Elevation Myocardial Infarction: Relation with Culprit Artery, Ischemic Time Window, and Severity of Injury.

BACKGROUND: Troponin composition characterization has been implicated as a next step to differentiate among non-ST elevation myocardial infarction (NSTEMI) patients and improve distinction from other conditions with troponin release. We therefore studied coronary and peripheral troponin compositions in relation to clinical variables of NSTEMI patients. METHODS: Samples were obtained from the great cardiac vein (GCV), coronary sinus (CS), and peripheral circulation of 45 patients with NSTEMI. We measured total cTnI concentrations, and assessed both complex cTnI (binary cTnIC + all ternary cTnTIC forms), and large-size cTnTIC (full-size and partially truncated cTnTIC). Troponin compositions were studied in relation to culprit vessel localization (left anterior descending artery [LAD] or non-LAD), ischemic time window, and peak CK-MB value. RESULTS: Sampling occurred at a median of 25 hours after symptom onset. Of total peripheral cTnI, a median of 87[78-100]% consisted of complex cTnI; and 9[6-15]% was large-size cTnTIC. All concentrations (total, complex cTnI, and large-size cTnTIC) were significantly higher in the CS than in peripheral samples (P < 0.001). For LAD culprit patients, GCV concentrations were all significantly higher; in non-LAD culprit patients, CS concentrations were higher. Proportionally, more large-size cTnTIC was present in the earliest sampled patients and in those with the highest CK-MB peaks. CONCLUSIONS: In coronary veins draining the infarct area, concentrations of both full-size and degraded troponin were higher than in the peripheral circulation. This finding, and the observed associations of troponin composition with the ischemic time window and the extent of sustained injury may contribute to future characterization of different disease states among NSTEMI patients.

Meta-analysis of controlled studies on minimally interrupted vs. continuous use of non-vitamin K antagonist oral anticoagulants in catheter ablation for atrial fibrillation.

AIMS: At present, there are no guideline recommendations for minimally interrupted use of non-vitamin K antagonist oral anticoagulants (mi-NOAC) during catheter ablation (CA) for atrial fibrillation (AF). Current evidence is predominantly based on observational studies, with continuous use of vitamin K antagonist in the control arm. This quantitative summary reflects the first high-level evidence on contemporary regimens, with continuous NOAC use (c-NOAC) as the current gold standard. METHODS AND RESULTS: Meta-analysis (Pubmed, Embase, and Web of Science) on prospective, controlled studies comparing contemporary mi-NOAC (without bridging) with c-NOAC. Net adverse clinical events (major bleeding, thrombo-embolic events) were the primary outcome. In addition, we analysed total bleeding, minor bleeding, and silent cerebral embolism. Eight studies (six randomized, two observational) with 2168 patients were summarized. The primary endpoint occurred in 1.0% (18/1835): 1.1% (11/1005) vs. 0.8% (7/830) for the mi-NOAC and c-NOAC groups, respectively; odds ratio (OR) 1.20 [95% confidence interval (CI) 0.49-2.92, P = 0.64]. The OR for total bleeding on mi-NOAC was 1.26 (95% CI 0.97-1.63, P = 0.07). ORs for minor bleeding and silent cerebral embolism were 1.17 (95% CI 0.80-1.70, P = 0.34) and 2.62 (95% CI 0.54-12.61, P = 0.12), respectively. CONCLUSION: This synopsis provides a quantitative synthesis of high-level evidence on a contemporary strategy of mi-NOAC in CA for AF, and overall clinical outcomes were not different from continuous NOAC use. Despite preprocedural interruption, there was no sign of lower bleeding rates. Additional higher volume datasets are warranted for more precise treatment effect estimations of this everyday alternative anticoagulation strategy in AF ablation.

Development and external validation of prediction models to predict implantable cardioverter-defibrillator efficacy in primary prevention of sudden cardiac death.

AIMS: This study was performed to develop and externally validate prediction models for appropriate implantable cardioverter-defibrillator (ICD) shock and mortality to identify subgroups with insufficient benefit from ICD implantation. METHODS AND RESULTS: We recruited patients scheduled for primary prevention ICD implantation and reduced left ventricular function. Bootstrapping-based Cox proportional hazards and Fine and Gray competing risk models with likely candidate predictors were developed for all-cause mortality and appropriate ICD shock, respectively. Between 2014 and 2018, we included 1441 consecutive patients in the development and 1450 patients in the validation cohort. During a median follow-up of 2.4 (IQR 2.1-2.8) years, 109 (7.6%) patients received appropriate ICD shock and 193 (13.4%) died in the development cohort. During a median follow-up of 2.7 (IQR 2.0-3.4) years, 105 (7.2%) received appropriate ICD shock and 223 (15.4%) died in the validation cohort. Selected predictors of appropriate ICD shock were gender, NSVT, ACE/ARB use, atrial fibrillation history, Aldosterone-antagonist use, Digoxin use, eGFR, (N)OAC use, and peripheral vascular disease. Selected predictors of all-cause mortality were age, diuretic use, sodium, NT-pro-BNP, and ACE/ARB use. C-statistic was 0.61 and 0.60 at respectively internal and external validation for appropriate ICD shock and 0.74 at both internal and external validation for mortality. CONCLUSION: Although this cohort study was specifically designed to develop prediction models, risk stratification still remains challenging and no large group with insufficient benefit of ICD implantation was found. However, the prediction models have some clinical utility as we present several scenarios where ICD implantation might be postponed.

Uninterrupted Dabigatran versus Warfarin for Ablation in Atrial Fibrillation.

BACKGROUND: Catheter ablation of atrial fibrillation is typically performed with uninterrupted anticoagulation with warfarin or interrupted non-vitamin K antagonist oral anticoagulant therapy. Uninterrupted anticoagulation with a non-vitamin K antagonist oral anticoagulant, such as dabigatran, may be safer; however, controlled data are lacking. We investigated the safety of uninterrupted dabigatran versus warfarin in patients undergoing ablation of atrial fibrillation. METHODS: In this randomized, open-label, multicenter, controlled trial with blinded adjudicated end-point assessments, we randomly assigned patients scheduled for catheter ablation of paroxysmal or persistent atrial fibrillation to receive either dabigatran (150 mg twice daily) or warfarin (target international normalized ratio, 2.0 to 3.0). Ablation was performed after 4 to 8 weeks of uninterrupted anticoagulation, which was continued during and for 8 weeks after ablation. The primary end point was the incidence of major bleeding events during and up to 8 weeks after ablation; secondary end points included thromboembolic and other bleeding events. RESULTS: The trial enrolled 704 patients across 104 sites; 635 patients underwent ablation. Baseline characteristics were balanced between treatment groups. The incidence of major bleeding events during and up to 8 weeks after ablation was lower with dabigatran than with warfarin (5 patients [1.6%] vs. 22 patients [6.9%]; absolute risk difference, -5.3 percentage points; 95% confidence interval, -8.4 to -2.2; P<0.001). Dabigatran was associated with fewer periprocedural pericardial tamponades and groin hematomas than warfarin. The two treatment groups had a similar incidence of minor bleeding events. One thromboembolic event occurred in the warfarin group. CONCLUSIONS: In patients undergoing ablation for atrial fibrillation, anticoagulation with uninterrupted dabigatran was associated with fewer bleeding complications than uninterrupted warfarin. (Funded by Boehringer Ingelheim; RE-CIRCUIT ClinicalTrials.gov number, NCT02348723 .).

Two-year safety evaluation of a biodegradable polymer sirolimus-eluting stent with increased drug elution and polymer absorption kinetics in complex patient and lesion cohort.

OBJECTIVES: The aim of the present report was to compare 2-year safety outcomes of two biodegradable polymer (BP) sirolimus-eluting stents (SESs) with different drug eluting and polymer absorption kinetics in a subgroup of complex patients and lesions. BACKGROUND: The previously published PANDA III study showed the BuMA BP SES, with faster drug elution and polymer absorption, was non-inferior to the Excel SES in target lesion failure (TLF). METHODS: In PANDA III trial, patients who fulfilled one or more of the following criteria were included: Small vessel disease (reference vessel diameter ≤ 2.5 mm); long lesion (lesion length ≥ 20 mm); chronic total occlusion lesion; and diabetic patients. RESULTS: Among 2,348 patients randomly assigned to treatment with BuMA (n = 1,174) or Excel SES (n = 1,174) in the PANDA III study, 858 in the BuMA group and 855 in the Excel group satisfied the inclusion criteria. At 2-year follow-up, the incidence of definite/probable stent thrombosis (ST) was significantly lower with BuMA SES as compared with Excel SES (0.7% vs. 1.9%, p = 0.03). This difference was mainly caused by decreased subacute stent thrombosis rate (0% vs. 0.6%, p = 0.03). In patients who did not fulfill the complex patient and lesion criteria, there were no between-group difference in ST (0.7% vs. 0%, p = 0.50). Myocardial infarction and TLF rates were similar (5.7% vs. 6.0%, p = 0.79 and 8.8% vs. 7.5%, p = 0.34, respectively), whereas patient-oriented composite endpoint was higher with BuMA SES mainly due to high risk of revascularization (15.6% vs. 11.4%, p = 0.01; 8.4% vs. 4.6%, p < 0.01). CONCLUSIONS: Two-year subgroup analysis of the all-comer PANDA III trial revealed the increased safety benefit of the BuMA SES is more prominently seen in complex patient and lesion population. CLINICAL TRIAL: ClinicalTrial.gov, Identifier-NCT02017275.

Outcomes of apixaban versus warfarin in patients with atrial fibrillation and multi-morbidity: Insights from the ARISTOTLE trial.

BACKGROUND: Patients with atrial fibrillation (AF) often have multi-morbidity, defined as ≥3 comorbid conditions. Multi-morbidity is associated with polypharmacy, adverse events, and frailty potentially altering response to anticoagulation. We sought to describe the prevalence of multi-morbidity among older patients with AF and determine the association between multi-morbidity, clinical outcomes, and the efficacy and safety of apixaban compared with warfarin. METHODS: In this post-hoc subgroup analysis of the ARISTOTLE trial, we studied enrolled patients age ≥ 55 years (n = 16,800). Patients were categorized by the number of comorbid conditions at baseline: no multi-morbidity (0-2 comorbid conditions), moderate multi-morbidity (3-5 comorbid conditions), and high multi-morbidity (≥6 comorbid conditions). Association between multi-morbidity and clinical outcomes were analyzed by treatment with a median follow-up of 1.8 (1.3-2.3) years. RESULTS: Multi-morbidity was present in 64% (n = 10,713) of patients; 51% (n = 8491) had moderate multi-morbidity, 13% (n = 2222) had high multi-morbidity, and 36% (n = 6087) had no multi-morbidity. Compared with the no multi-morbidity group, the high multi-morbidity group was older (74 vs 69 years), took twice as many medications (10 vs 5), and had higher CHA2DS2-VASc scores (4.9 vs 2.7) (all P < .001). Adjusted rates per 100 patient-years for stroke/systemic embolism, death, and major bleeding increased with multi-morbidity (Reference no multi-morbidity; moderate multi-morbidity 1.42 [1.24-1.64] and high multi-morbidity 1.92 [1.59-2.31]), with no interaction in relation to efficacy or safety of apixaban. CONCLUSIONS: Multi-morbidity is prevalent among the population with AF; efficacy and safety of apixaban is preserved in this subgroup supporting extension of trial results to the most complex AF patients.

Observed survival benefit of mild therapeutic hypothermia reanalysing the Circulation Improving Resuscitation Care trial.

BACKGROUND: Mild therapeutic hypothermia is argued being beneficial for outcome after cardiac arrest. MATERIALS AND METHODS: Retrospective analysis of Circulation Improving Resuscitation Care (CIRC) trial data to assess if therapeutic cooling to 33 ± 1 °C core temperature had an association with survival. Of 4231 adult, out-of-hospital cardiac arrests of presumed cardiac origin initially enrolled, eligibility criteria for therapeutic hypothermia were met by 1812. Logistic regression was undertaken in a stepwise fashion to account for the impact on outcome of each significant difference and for the variable of interest between the groups. RESULTS: Out-of- and in-hospital cooled were 263 (15%), only after admission cooled were 230 (13%) and not cooled were 357 (20%) patients. The group cooled out of- and in hospital had 98 (37%) survivors as compared to the groups cooled in hospital only [80 (35%)] and of those not cooled [68 (19%)]. After adjusting for known covariates (sex, age, witnessed cardiac arrest, no- and low-flow time, shockable initial rhythm, random allocation, bystander cardiopulmonary resuscitation and percutaneous coronary intervention), the odds ratio for survival comparing no cooling to out-of- plus in-hospital cooling was 0·53 [95% confidence interval (CI): 0·46-0·61, P < 0·001], and comparing to in-hospital cooling only was 0·67 (95% CI: 0·50-0·89, P = 0·006). CONCLUSION: Mild therapeutic hypothermia initiated out of hospital and/or in hospital was associated with improved survival within this secondary analysis of the CIRC cohort compared to no therapeutic hypothermia.

Randomized evaluation of short-term dual antiplatelet therapy in patients with acute coronary syndrome treated with the COMBO dual therapy stent: rationale and design of the REDUCE trial.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients treated with drug eluting stents (DES) is still under debate. Recent meta-analyses on ≤6months versus 12months DAPT suggest that bleeding rates can be reduced, without a higher rate of thrombotic complications. In particular, the COMBO dual therapy stent, being associated with early re-endothelialization, may allow for a reduction of the duration of DAPT without increasing the thrombotic risk, while reducing the risk of bleeding complications. AIM: The aim of the REDUCE trial is to demonstrate the non-inferiority of a combined efficacy and safety endpoint of a short-term 3months DAPT strategy as compared to standard 12-month DAPT strategy in ACS patients treated with the COMBO stent. DESIGN: A prospective, multicenter, randomized study designed to enroll 1500 patients with ACS treated with the COMBO stent. Patients will be randomized before discharge in a 1:1 fashion to either 3 or 12months of DAPT. A clinical follow-up is scheduled at 3, 6, 12, and 24months. The primary endpoint is the time to event as defined by the occurrence of one of the following: all cause mortality, myocardial infarction, stent thrombosis, stroke, target vessel revascularization or bleeding (Bleeding Academic Research Council type II, III and V) within 12months. The study has recruited patients since July 2014, and the results are expected in 2017. SUMMARY: A reduction of the DAPT duration in ACS patients after PCI without affecting the thrombotic risk is an attractive option with regard to the associated bleeding risk. The REDUCE trial will be the first to investigate the efficacy and safety of a 3-month DAPT strategy compared to a 12-month DAPT strategy in an ACS only population treated with the COMBO stent.

Risk Factors for Inadequate Defibrillation Safety Margins Vary With the Underlying Cardiac Disease: Implications for Selective Testing Strategies.

INTRODUCTION: In view of the shift from routine toward no or selective defibrillation testing, optimization of the current risk stratification for inadequate defibrillation safety margins (DSMs) could improve individualized testing decisions. Given the pathophysiological differences in myocardial substrate between ischemic and nonischemic heart disease (IHD/non-IHD) and the accompanying differences in clinical characteristics, we studied inadequate DSMs and their predictors in relation to the underlying etiology. METHODS AND RESULTS: Cohort of routine defibrillation tests (n = 785) after first implantable cardioverter defibrillator (ICD)-implantations at the Radboud UMC (2005-2014). A defibrillation threshold >25 J was regarded as an inadequate DSM. In total, 4.3% of patients had an inadequate DSM; in IHD 2.5% versus 7.3% in non-IHD (P = 0.002). We identified a group of non-IHD patients at high risk (13-42% inadequate DSM); the remainder of the cohort (>70%) had a risk of only 2% (C-statistic entire cohort 0.74; C-statistic non-IHD 0.82). This was based upon two identified interaction terms: (1) non-IHD and age (aOR 0.94 [95% CI 0.91-0.97]); (2) non-IHD and the indexed left ventricular (LV) internal diastolic diameter (aOR 3.50 [95% CI 2.10-5.82]). CONCLUSION: The present study on risk stratification for an inadequate DSM not only confirms the importance of making a distinction between IHD and non-IHD, but also shows that risk factors in an entire cohort (LV dilatation, age) may only apply to a subgroup (non-IHD). Appreciation of this concept could favorably affect current risk stratification. If confirmed, our approach may be used to optimize individualized testing decisions in an upcoming era of non-routine testing.

Manual Cardiopulmonary Resuscitation Versus CPR Including a Mechanical Chest Compression Device in Out-of-Hospital Cardiac Arrest: A Comprehensive Meta-analysis From Randomized and Observational Studies.

STUDY OBJECTIVE: Mechanical chest compression devices have been developed to facilitate continuous delivery of high-quality cardiopulmonary resuscitation (CPR). Despite promising hemodynamic data, evidence on clinical outcomes remains inconclusive. With the completion of 3 randomized controlled trials, we conduct a meta-analysis on the effect of in-field mechanical versus manual CPR on clinical outcomes after out-of-hospital cardiac arrest. METHODS: With a systematic search (PubMed, Web of Science, EMBASE, and the Cochrane Libraries), we identified all eligible studies (randomized controlled trials and nonrandomized studies) that compared a CPR strategy including an automated mechanical chest compression device with a strategy of manual CPR only. Outcome variables were survival to hospital admission, survival to discharge, and favorable neurologic outcome. RESULTS: Twenty studies (n=21,363) were analyzed: 5 randomized controlled trials and 15 nonrandomized studies, pooled separately. For survival to admission, the pooled estimate of the randomized controlled trials did not indicate a difference (odds ratio 0.94; 95% confidence interval 0.84 to 1.05; P=.24) between mechanical and manual CPR. In contrast, meta-analysis of nonrandomized studies demonstrated a benefit in favor of mechanical CPR (odds ratio 1.42; 95% confidence interval 1.21 to 1.67; P<.001). No interaction was found between the endorsed CPR guidelines (2000 versus 2005) and the CPR strategy (P=.27). Survival to discharge and neurologic outcome did not differ between strategies. CONCLUSION: Although there are lower-quality, observational data that suggest that mechanical CPR used at the rescuer's discretion could improve survival to hospital admission, the cumulative high-quality randomized evidence does not support a routine strategy of mechanical CPR to improve survival or neurologic outcome. These findings are irrespective of the endorsed CPR guidelines during the study periods.

Design of the Park-in-Shape study: a phase II double blind randomized controlled trial evaluating the effects of exercise on motor and non-motor symptoms in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder with a wide range of motor and non-motor symptoms. Despite optimal medical management, PD still results in a high disability rate and secondary complications and many patients lead a sedentary lifestyle, which in turn is also associated with a higher co-morbidity and mortality. Exercise has been explored as a strategy to reduce secondary complications and results suggests that it not only provides general health benefits, but may also provide symptomatic relief. If this holds true exercise would be a very attractive addition to the therapeutic arsenal in PD. The supportive evidence remains incomplete. Here, we describe the design of the Park-in-Shape study, which primarily aims to evaluate whether aerobic exercise affords clinically relevant improvements in motor symptoms in sedentary PD patients. A specific new element is the introduction of gaming to optimize compliance to the exercise intervention. METHODS/DESIGN: The Park-in-Shape study is a randomized controlled, assessor- and patient-blinded single center study. Two parallel groups will include a total of 130 patients, receiving either aerobic exercise on a home trainer equipped with gaming elements ("exergaming"), or a non-aerobic intervention (stretching, flexibility and relaxation exercises). Both groups are supported by a specifically designed motivational app that uses gaming elements to stimulate patients to exercise and rewards them after having completed the exercise. Both interventions are delivered at home at least 3 times a week for 30-45 minutes during 6 months. Eligible patients are community-dwelling, sedentary patients diagnosed with mild-moderate PD. The primary outcome is the MDS-UPDRS motor score (tested in the off state) after 6 months. Secondary outcomes include various motor and non-motor symptoms, quality of life, physical fitness, and adherence. DISCUSSION: This Park-in-Shape study is anticipated to answer the question whether high intensity aerobic exercise combined with gaming elements ("exergaming") provides symptomatic relief in PD. Strong elements include the double-blinded randomized controlled trial design, the MDS-UPDRS as valid primary outcome, the large sample size and unique combination of home-based pure aerobic exercise combined with gaming elements and motivational aspects. TRIAL REGISTRATION: Dutch trial register NTR4743.

Automated cardiac arrest detection using a photoplethysmography wristband: algorithm development and validation in patients with induced circulatory arrest in the DETECT-1 study.

BACKGROUND: Unwitnessed out-of-hospital cardiac arrest is associated with low survival chances because of the delayed activation of the emergency medical system in most cases. Automated cardiac arrest detection and alarming using biosensor technology would offer a potential solution to provide early help. We developed and validated an algorithm for automated circulatory arrest detection using wrist-derived photoplethysmography from patients with induced circulatory arrests. METHODS: In this prospective multicentre study in three university medical centres in the Netherlands, adult patients (aged 18 years or older) in whom short-lasting circulatory arrest was induced as part of routine practice (transcatheter aortic valve implantation, defibrillation testing, or ventricular tachycardia induction) were eligible for inclusion. Exclusion criteria were a known bilateral significant subclavian artery stenosis or medical issues interfering with the wearing of the wristband. After providing informed consent, patients were equipped with a photoplethysmography wristband during the procedure. Invasive arterial blood pressure and electrocardiography were continuously monitored as the reference standard. Development of the photoplethysmography algorithm was based on three consecutive training cohorts. For each cohort, patients were consecutively enrolled. When a total of 50 patients with at least one event of circulatory arrest were enrolled, that cohort was closed. Validation was performed on the fourth set of included patients. The primary outcome was sensitivity for the detection of circulatory arrest. FINDINGS: Of 306 patients enrolled between March 14, 2022, and April 21, 2023, 291 patients were included in the data analysis. In the development phase (n=205), the first training set yielded a sensitivity for circulatory arrest detection of 100% (95% CI 94-100) and four false positive alarms; the second training set yielded a sensitivity of 100% (94-100), with six false positive alarms; and the third training set yielded a sensitivity of 100% (94-100), with two false positive alarms. In the validation phase (n=86), the sensitivity for circulatory arrest detection was 98% (92-100) and 11 false positive circulatory arrest alarms. The positive predictive value was 90% (95% CI 82-94). INTERPRETATION: The automated detection of induced circulatory arrests using wrist-derived photoplethysmography is feasible with good sensitivity and low false positives. These promising findings warrant further development of this wearable technology to enable automated cardiac arrest detection and alarming in a home setting. FUNDING: Dutch Heart Foundation (Hartstichting).