Dutch Outcome in Implantable Cardioverter-Defibrillator Therapy:Implantable Cardioverter-Defibrillator-Related Complications in a Contemporary Primary Prevention Cohort

Background One third of primary prevention implantable cardioverter-defibrillator patients receive appropriate therapy, but all remain at risk of defibrillator complications. Information on these complications in contemporary cohorts is limited. This study assessed complications and their risk factors after defibrillator implantation in a Dutch nationwide prospective registry cohort and forecasts the potential reduction in complications under distinct scenarios of updated indication criteria. Methods and Results Complications in a prospective multicenter registry cohort of 1442 primary implantable cardioverter-defibrillator implant patients were classified as major or minor. The potential for reducing complications was derived from a newly developed prediction model of appropriate therapy to identify patients with a low probability of benefitting from the implantable cardioverter-defibrillator. During a follow-up of 2.2 years (interquartile range, 2.0-2.6 years), 228 complications occurred in 195 patients (13.6%), with 113 patients (7.8%) experiencing at least one major complication. Most common ones were lead related (n=93) and infection (n=18). Minor complications occurred in 6.8% of patients, with lead-related (n=47) and pocket-related (n=40) complications as the most prevailing ones. A surgical reintervention or additional hospitalization was required in 53% or 61% of complications, respectively. Complications were strongly associated with device type. Application of stricter implant indication results in a comparable proportional reduction of (major) complications. Conclusions One in 13 patients experiences at least one major implantable cardioverter-defibrillator-related complication, and many patients undergo a surgical reintervention. Complications are related to defibrillator implantations, and these should be discussed with the patient. Stricter implant indication criteria and careful selection of device type implanted may have significant clinical and financial benefits

Recombinant human collagen-based microspheres mitigate cardiac conduction slowing induced by adipose tissue-derived stromal cells

Background Stem cell therapy to improve cardiac function after myocardial infarction is hampered by poor cell retention, while it may also increase the risk of arrhythmias by providing an arrhythmogenic substrate. We previously showed that porcine adipose tissue-derived-stromal cells (pASC) induce conduction slowing through paracrine actions, whereas rat ASC (rASC) and human ASC (hASC) induce conduction slowing by direct coupling. We postulate that biomaterial microspheres mitigate the conduction slowing influence of pASC by interacting with paracrine signaling. Aim To investigate the modulation of ASC-loaded recombinant human collagen-based microspheres, on the electrophysiological behavior of neonatal rat ventricular myocytes (NRVM). Method Unipolar extracellular electrograms, derived from microelectrode arrays (8x8 electrodes) containing NRVM, co-cultured with ASC or ASC loaded microspheres, were used to determine conduction velocity (CV) and conduction heterogeneity. Conditioned medium (Cme) of (co)cultures was used to assess paracrine mechanisms. Results Microspheres did not affect CV in control (NRVM) monolayers. In co-cultures of NRVM and rASC, hASC or pASC, CV was lower than in controls (14.4+/-1.0, 13.0+/-0.6 and 9.0+/-1.0 vs. 19.5+/-0.5 cm/s respectively, p Conclusion The application of recombinant human collagen-based microspheres mitigates indirect paracrine conduction slowing through interference with a secondary autocrine myocardial factor

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Microvolt T-wave alternans during exercise and pacing are not comparable

The absence of microvolt T-wave alternans (MTWA) identifies a group of patients who are at low risk for ventricular arrhythmia or sudden cardiac death. However, in exercised assessed MTWA, 20-40% of all test results are indeterminate. We hypothesised that MTWA during pacing would yield less indeterminate results. Thirty patients with ischaemic cardiomyopathy and prior dual chamber implantable cardioverter defibrillator implantation were enrolled. All patients underwent sequential MTWA testing using an exercise (E), atrial-paced (A), and atrioventricular-paced (AV) protocol. The number of indeterminate tests was lower during pacing (A: 17%; AV: 3%) compared with exercise (37%) (E vs. A: P = 0.015, E vs. AV: P = <0.001). When positive and indeterminate test results were grouped as non-negative, the concordance rates between E and A, E and AV, and A and AV were 60% (kappa = 0.17), 57% (kappa = 0.058), and 70% (kappa = 0.348), respectively. If indeterminate results were excluded, agreements were 60% (kappa = 0.19), 50% (kappa = 0.129) and 67% (kappa = 0.33), respectively. Indeterminate test results are less common during pacing. However, there is a low concordance rate between test results using different protocols. This necessitates further study to determine the predictive value of each method in high risk patients with ischaemic cardiomyopath

Experimental Validation of Noninvasive Epicardial and Endocardial Activation Imaging

Noninvasive imaging of cardiac activation before ablation of the arrhythmogenic substrate can reduce electrophysiological procedure duration and help choosing between an endocardial or epicardial approach. A noninvasive imaging technique was evaluated that estimates both endocardial and epicardial activation from body surface potential maps. We performed a study in isolated and in situ pig hearts, estimating activation from body surface potential maps during sinus rhythm and localizing endocardial and epicardial stimulation sites. From 3 Langendorff-perfused pig hearts, 180 intramural unipolar electrograms were recorded during sinus rhythm and ectopic activation, together with pseudo-body surface potential map ECGs in 2 of them. From 4 other anesthetized pigs, 64-lead body surface potential maps were recorded during sinus rhythm and ventricular stimulation from 27 endocardial and epicardial sites. The ventricular activation pattern was computed from the recorded QRS complexes. For both Langendorff-perfused hearts, the calculated epicardial and endocardial activation patterns showed good qualitative correspondence to the patterns obtained with needle electrodes. Absolute timing difference for sinus rhythm was 10±5 and 11±8 ms respectively, and for ectopic activation 6±5 and 7±6 ms, respectively. Calculated activation for the in situ hearts in sinus rhythm was similar to patterns recorded in Langendorff-perfused hearts. During stimulation, the distance between the stimulation site and calculated site of earliest activation was 18 (15-27) mm, and 23 of 27 stimulation sites were correctly mapped to either endocardium or epicardium. Noninvasive activation imaging is able to determine earliest ventricular activation and discriminate endocardial from epicardial origin of activation with clinically relevant accurac

Documented atrial fibrillation recurrences after pulmonary vein isolation are associated with diminished quality of life

Pulmonary vein isolation (PVI) aims at eliminating symptomatic atrial fibrillation. In this regard, the most relevant indication for this procedure is the reduction of symptoms and improvement of quality of life (QoL) in patients who remain symptomatic despite antiarrhythmic drug treatment. We investigated the relation between documented atrial fibrillation recurrences and QoL in patients after PVI. One hundred and six PVIs were performed in 99 patients. Follow-up was mainly performed at referring hospitals. Short Form 36 (SF-36) QoL questionnaires were completed before and 1 year after PVI. Electrocardiographic recordings from the first postprocedural year were retrospectively collected, 3 months blanking excluded. Atrial fibrillation recurrence was defined as any recurrence of atrial arrhythmia documented on ECG or 24-h-Holter. Before PVI, patients had lower QoL than the general Dutch population in 7/8 SF-36 questionnaire subscales (sumQoL 419.4 ± 161 vs. 617.9, P  < 0.001). Atrial fibrillation recurred in 52 (49%) patients. In these patients, four subscales increased following PVI (physical functioning P  < 0.001, role physical P = 0.006, bodily pain P = 0.011 and social functioning P = 0.047). SumQoL remained lower than the general Dutch population (546.7 ± 157, P = 0.003). In patients without documented recurrences, QoL improved to a level similar to that of the general Dutch population (602.9 ± 148; P = 0.46). The number of electrocardiographic recordings was lower in the group without documented recurrences (2.5 ± 1.8 vs. 3.8 ± 1.7, P = 0.002). In patients without documentation of atrial fibrillation, QoL increased up to the level of the general population after PVI, but it remained lower in patients with recurrences. In the latter group more ECGs were done, suggesting that QoL relates particularly to symptomatic episodes. Improvement of QoL is therefore an important attribute of PV

The ICD for Primary Prevention in Patients With Inherited Cardiac Diseases Indications, Use, and Outcome: A Comparison With Secondary Prevention

Background- Indications for prophylactic implantable cardioverter-defibrillator (ICD) therapy in patients with inherited cardiac diseases stem from observational studies and are uncertain. This study evaluates the efficacy and harm rate of ICD implantations for primary prevention compared with secondary prevention in inherited cardiac diseases. Methods and Results- Between January 1, 1993, and April 1, 2011, 354 patients with inherited cardiac diseases were treated with ICDs. Incidence rates of appropriate shocks in primary prevention patients with arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy were 4.2 to 6.7/100 patient-years, whereas the risk for appropriate shocks in primary prevention patients with Brugada syndrome, long QT syndrome, or carrying the DPP6 haplotype approached zero. Conversely, in secondary prevention patients there was a considerably higher incidence rate of appropriate shocks. None of the indications for primary prevention were associated with appropriate shock therapy. One hundred twenty-three patients (35%) experienced ICD-related adverse events. Conclusions- For Brugada syndrome, long QT syndrome, and DPP6 the efficacy of an ICD for primary prevention contrasts with the amount of harm, and factors that formed the indication for ICD implantation do not relate to the occurrence of appropriate shocks. The higher appropriate discharge rates in arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy compared with primary electric diseases might result from a more advanced risk stratification scheme in these inherited cardiomyopathie

Value of Serial Heart Rate Variability Measurement for Prediction of Appropriate ICD Discharge in Patients with Heart Failure

HRV and Appropriate ICD Shock in Heart Failure Introduction Decreased heart rate variability (HRV) is associated with adverse outcomes in patients with heart failure. Our objective was to examine whether decreased HRV predicts appropriate implantable cardioverter defibrillator (ICD) shocks. Methods and Results In 105 patients with a Boston Scientific Contak Renewal, Cognis or Energen device implanted for either primary (73.3%) or secondary prevention (26.7%), time domain HRV variables standard deviation of averages of normal beat-to-beat interval (SDANN) and footprint percentage (FPP) were collected at baseline and during follow-up. In case of appropriate shock, HRV before shock was assessed. Using time-dependent Cox regression models, the relation between median-based dichotomized SDANN or FFP and appropriate shock was investigated. Baseline characteristics between patients with or without shocks were similar, with exception of secondary prevention patients using more often antiarrhythmic drugs. During follow-up (median 451, IQR 202-1,460 days), appropriate shocks occurred in 20 (19%) patients. SDANN and FPP did not differ significantly at baseline between patients with or without shocks (respectively, P = 0.18 and P = 0.78). However, time-dependent Cox regression analysis showed a trend that patients were at lower risk for appropriate shock (SDANN: HR 0.43, 95% CI [0.18-1.05], P = 0.06 and FPP: HR 0.49, 95% CI [0.20-1.20], P = 0.12) when HRV values were above median baseline value during follow-up. Conclusions These results imply that HRV could be an independent predictor for appropriate shocks. Therefore, low HRV could be of additional use in predicting imminent appropriate shocks and could possibly guide concomitant medical therap

Left atrial pressure reduction for mitral stenosis reverses left atrial direction-dependent conduction abnormalities

Left atrial (LA) stretch-associated electrophysiological changes in patients with mitral stenosis (MS) predispose to atrial fibrillation. We hypothesized that the normalization of the pressure gradient by percutaneous transvenous mitral balloon valvotomy (PTMV) affects LA but not right atrial (RA) conduction, depending on the site of stimulation. Because direction-dependent (asymmetric) changes of conduction may contribute to arrhythmogenesis, we assessed conduction symmetry in MS patients and tested whether it is restored by PTMV. In nine patients with MS, atrial effective refractory period and local activation times (ATs) were determined during stimulation before and after PTMV, with up to four decapolar catheters (LA and RA). Eight patients with ventricular pre-excitation served as controls. ATs at basic cycle length were similar before and after PTMV. With stimulation from either atrium, they were about 45 ms in the ipsilateral atrium and about 115 ms in the contralateral atrium. With premature stimulation, ATs increased dramatically. The shortest ATs were found in the RA with RA stimulation (78 +/- 9 and 80 +/- 6 ns, before and after PTMV). PTMV caused a shortening in LA-ATs (following LA stimulation) from 118 +/- 14 to 82 +/- 5 ms (before and after; P <0.05). Asymmetry in conduction properties was therefore normalized by PTMV. PTMV led to a decrease in RA-ATs (following LA stimulation) from 196 +/- 11 to 174 +/- 13 ms (P <0.02). In addition, following RA stimulation, the dispersion in ATs in the LA decreased significantly by PTMV (from 66 +/- 10 to 34 +/- 7 ms; P <0.02). MS is associated with LA conduction delay, increased LA dispersion of conduction, and conduction asymmetry. These changes are immediately reversible by PTMV

Right ventricular pacing and the risk of heart failure in implantable cardioverter-defibrillator patients

BACKGROUND Right ventricular (RV) pacing in implantable cardioverter-defibrillator (ICD) patients may have detrimental effects on morbidity and mortality, in particular by inducing heart failure (HF). OBJECTIVE We investigated whether RV pacing increases the risk of HF in an asymptomatic ICD population. METHODS We evaluated all patients without symptomatic HF who received an ICD. The primary endpoint was the occurrence of HF, which was defined as new HF, hospitalization for HF, or death due to HF. The secondary endpoint was appropriate shocks. RESULTS The study population consisted of 456 patients with mean left ventricular ejection fraction (LVEF) 40% +/- 13%. Mean follow-up was 31 +/- 22 months. Because of the bimodal distribution of pacing, patients were divided into two groups: paced 50% (median 96%; n = 143). HF occurred more often in the paced >50% group (20% versus 9%; P 50% (adjusted hazard ratio [HR] 1.85; 95% confidence interval [0] 1.08-3.15; P = .03), baseline LVEF 50% patients versus 20% of paced 50% also independently predicted appropriate shocks (adjusted HR 1.50; 95% CI 1.02-2.20; P = .04). CONCLUSION RV pacing was associated with an increased risk of HF in asymptomatic ICD patients, particularly in those with preexistent left ventricular dysfunction