Predicting electrical storms by remote monitoring of implantable cardioverter-defibrillator patients using machine learning.

AIMS: Electrical storm (ES) is a serious arrhythmic syndrome that is characterized by recurrent episodes of ventricular arrhythmias. Electrical storm is associated with increased mortality and morbidity despite the use of implantable cardioverter-defibrillators (ICDs). Predicting ES could be essential; however, models for predicting this event have never been developed. The goal of this study was to construct and validate machine learning models to predict ES based on daily ICD remote monitoring summaries. METHODS AND RESULTS: Daily ICD summaries from 19 935 patients were used to construct and evaluate two models [logistic regression (LR) and random forest (RF)] for predicting the short-term risk of ES. The models were evaluated on the parts of the data not used for model development. Random forest performed significantly better than LR (P < 0.01), achieving a test accuracy of 0.96 and an area under the curve (AUC) of 0.80 (vs. an accuracy of 0.96 and an AUC of 0.75). The percentage of ventricular pacing and the daytime activity were the most relevant variables in the RF model. CONCLUSION: The use of large-scale machine learning showed that daily summaries of ICD measurements in the absence of clinical information can predict the short-term risk of ES.

Clinical outcome in patients with implantable cardioverter-defibrillator and cancer: a nationwide study.

AIMS: Patients with cancer are insufficiently represented in randomized clinical trials investigating efficacy of implantable cardioverter-defibrillators (ICDs). We aimed to describe outcomes in patients with a pre-existing diagnosis of cancer at time of ICD implantation. METHODS AND RESULTS: We utilized Danish nationwide registries to identify primary and secondary prevention ICD implantations from 2007 to 2012. Multivariable Cox models were used to assess the risk of appropriate ICD therapy and mortality in patients with and without cancer at time of implantation. During a median follow-up of 2.1 years, 2935 primary prevention ICD and 2730 secondary prevention ICD implantations were identified. Out of these [289 (5.1%)] had pre-existing cancer [primary 140 (4.8%), secondary 149 (5.5%)]. No differential risk for appropriate ICD therapy was found between patients with or without cancer, [primary cancer: 19/140, no cancer: 380/2795, hazard ratio (HR) = 1.07 (0.67-1.69)] and [secondary cancer: 42/149, no cancer: 699/2581, HR = 1.28 (0.93-1.75)]. In primary patients, cancer was not associated with higher risk of 1-year [cancer: 10/140, no cancer: 133/2795, HR = 1.20 (0.84-2.28)] or all-time mortality [cancer: 22/140, no cancer: 339/2795, HR = 1.13 (0.74-1.75)]. In secondary patients, cancer was associated with a higher 1-year [cancer: 19/149, no cancer: 108/2581, HR = 2.62 (1.60-4.29)] and all-time mortality [cancer: 44/149, no cancer: 315/2581, HR = 2.36 (1.71-3.24)]. CONCLUSION: Implantable cardioverter-defibrillators were implanted in a minority of cancer patients. No difference in risk of appropriate therapy was observed between cancer and non-cancer patients, regardless of implant indication. Cancer was associated with increased mortality in secondary prevention ICD patients, but not in primary prevention ICD patients. In secondary prevention ICD patients, the majority of deaths were attributable to cancer.

Concerted functions of Streptococcus gordonii surface proteins PadA and Hsa mediate activation of human platelets and interactions with extracellular matrix.

A range of Streptococcus bacteria are able to interact with blood platelets to form a thrombus (clot). Streptococcus gordonii is ubiquitous within the human oral cavity and amongst the common pathogens isolated from subjects with infective endocarditis. Two cell surface proteins, Hsa and Platelet adherence protein A (PadA), in S. gordonii mediate adherence and activation of platelets. In this study, we demonstrate that PadA binds activated platelets and that an NGR (Asparagine-Glycine-Arginine) motif within a 657 amino acid residue N-terminal fragment of PadA is responsible for this, together with two other integrin-like recognition motifs RGT and AGD. PadA also acts in concert with Hsa to mediate binding of S. gordonii to cellular fibronectin and vitronectin, and to promote formation of biofilms. Evidence is presented that PadA and Hsa are each reliant on the other's active presentation on the bacterial cell surface, suggesting cooperativity in functions impacting both colonization and pathogenesis.

Association between right ventricular lead position and clinical outcomes in patients with cardiac resynchronization therapy.

Aims: To evaluate the association between an apical vs. non-apical right ventricular lead position (RV-LP) and clinical outcome in a large nationwide cohort of patients treated with cardiac resynchronization therapy (CRT). Methods and results: We included consecutive Danish patients receiving a CRT device from 2008 to 2012, identified from the Danish Pacemaker and ICD Register. Endpoints were mortality, mortality or hospitalization for heart failure (HF), and clinical response (improvement ≥1 New York Heart Association class at follow-up). Subgroup analysis was made for ischaemic heart disease (IHD) and non-IHD. Cox and logistic regression analyses were used to calculate adjusted HR (aHR) and adjusted odds ratios with 95% confidence intervals (CI). A total of 2883 patients received a CRT device during the period. We excluded 301 patients that did not meet standard CRT indication. In 2391 (93%) of the remaining 2582 patients the RV-LP was defined as apical in 647 (27%) and non-apical in 1744 (73%). After mean 3.2 ± 2 years, 660 patients had died, 1275 patients were hospitalized for HF, and 1021 were responders. With a non-apical RV-LP the aHR for mortality was 0.93 (95% CI 0.0.79-1.10, P = 0.40) and the aHR for the combined endpoint of mortality or HF-hospitalization was 0.89 (95% CI 0.79-0.99, P = 0.03). These findings were significant only in patients with non-IHD. There was no association between clinical response and RV-LP. Conclusion: A non-apical RV-LP is associated with lower risk of meeting the combined endpoint of mortality or hospitalization for HF in patients with CRT. In subgroup analysis, this association was present only in patients with non-IHD.

The use of guideline recommended beta-blocker therapy in primary prevention implantable cardioverter defibrillator patients: insight from Danish nationwide registers.

Aims: We aimed to examine the use of guideline recommended beta-blocker therapy prior to and after primary prevention implantable cardioverter defibrillator (ICD) implantation in a 'real-life' setting. Methods and results: From the Danish Pacemaker and ICD Registry we identified all 1st-time primary prevention ICD and cardiac resynchronization therapy defibrillator (CRT-D) implantations in Denmark from 2007-12 (n = 2935). Use of beta-blocker, type and dose was acquired through the Danish Prescription Registry. According to guideline recommendations, we defined target daily doses as ≥50 mg carvedilol and ≥200 mg metoprolol. Prior to implantation 2427 of 2935 (83%) patients received beta-blocker therapy, with 2166 patients (89%) having initiated treatment 3 months or more prior to implantation. The majority of patients was prescribed carvedilol (52%) or metoprolol (41%). Patients on carvedilol reached target dosages more frequently than patients on metoprolol, with 39% of patients on carvedilol and 26% of patients on metoprolol at the time of implantation (P < 0.001 for all time-points). Increase in proportion of patients reaching target daily doses was observed for both carvedilol and metoprolol after ICD implantation. Carvedilol treatment was a strong predictor for being on target dose of BB at time of implant, as was treatment with angiotensin-converting enzyme inhibitors and/or spironolactone, no history of myocardial infarction, younger age and less pronounced heart failure symptoms. Conclusion: In a real-life setting of primary prevention ICD patients, 39% and 26% of patients were titrated to optimal target dose of carvedilol or metoprolol prior to implantation. A higher proportion of patients on carvedilol reached target dose, as compared with metoprolol.

Shortening of paced QRS duration after electrocardiographic optimization of left ventricular pacing vector in patients treated with Cardiac Resynchronization Therapy.

Background: Choice of left ventricular pacing vector (LVPV) affects the QRS-duration (QRSd) in patients with Cardiac Resynchronization Therapy (CRT). It is not known whether testing all LVPVs reduces QRSd compared to device-based "standard-programming". Methods: In patients implanted with CRT several ECGs were recorded for each usable LVPV (no phrenic nerve stimulation and threshold <3.5 V) and during "standard-programming" after device-based optimization of AV/VV delays. Results: 22 consecutive patients were included. Average QRSd reduction after CRT + "standard-programming" was 27.3 ±â€¯22 ms. Additional QRSd-reduction was possible in 4 patients by changing the LVPV, and in 5 other patients after optimization of AV- and VV delays without changing LVPV. Conclusions: Shortening of QRSd compared to "standard-programming" was possible approximately 40% of these patients treated with CRT by testing all LVPVs and re-optimizing AV/VV delays during follow-up. Studies of clinical effects are needed.

Validation of defibrillator lead performance registry data: insight from the Danish Pacemaker and ICD Register.

AIMS: The validity of registry data on defibrillator lead performance is described only sparsely, despite its clinical importance. This study investigated the validity of defibrillator lead performance registry data in a nationwide and population-based registry. METHODS AND RESULTS: We identified all reported surgical interventions due to defibrillator lead events in the Danish Pacemaker and ICD Register (DPIR) from 2000 to 2013. Medical records of all patients (n = 753) were examined blinded for 5 predefined intervention types and 18 reasons for lead intervention. The overall level of agreement for the types of lead intervention had a positive predictive value (PPV) of 89.4% [95% confidence interval (CI): 87.0-91.5%] and an adjusted agreement (κ value) of 0.81 (95% CI: 0.77-0.85) representing an almost perfect match. Regarding the reasons for lead intervention, the overall PPV was 63.0% (95% CI: 54.8-61.7%) with a κ value of 0.60 (95% CI: 0.55-0.64) representing a moderate match with only few subcategories having low PPV. By redistribution of the specific reasons for lead interventions into three categories commonly used to report lead performance, the overall PPV improved to 87.9% (95% CI: 85.2-90.2%) with a κ value of 0.82 (95% CI:0.78-0.86) representing an almost perfect match. CONCLUSION: The validity of data on defibrillator lead performance recorded in the DPIR is excellent for the specific types of lead intervention and good for the specific reasons for defibrillator lead intervention. The validity of the less detailed overall reasons for lead interventions commonly used to report lead performance is also excellent. These findings indicate high registry data quality appropriate for scientific analysis and industry-independent post-marketing surveillance.

Safety of magnetic resonance scanning without monitoring of patients with pacemakers.

AIMS: The objective of this study was to investigate whether it is safe to perform 1.5-Tesla magnetic resonance imaging (MRI) scans in pacemaker (PM) patients without pulse oximetry or electrocardiogram monitoring and with no special specific absorption rate (SAR) or time limits, provided that the PMs are interrogated and programmed to asynchronous mode prior to the scan. METHODS AND RESULTS: This study reports the outcome of 207 MRI scans on PM patients at Rigshospitalet, Copenhagen University Hospital from June 2010 to September 2013. All MRIs were performed with the PMs in asynchronous mode and without additional monitoring. There were no adverse events registered among the PM patients during the study period. The only statistically significant change after MRI scans was a small, but clinically insignificant increase in atrial sense. No occurrences of reprogramming to power-on-reset were registered. CONCLUSION: It is possible to perform MRI scans relatively safely in PM patients without additional monitoring or change in the normal MRI protocol, given that the PM has been assessed and reprogrammed prior to MRI. This is especially important to remember in the acute setting where MRI scans may be delayed when monitoring facilities are unavailable.

Is modification of the VVI backup mode in implantable cardioverter-defibrillators from St Jude medical required due to increased risk of inappropriate shocks?

Inappropriate implantable cardioverter-defibrillator (ICD) shock therapy is painful, stressful, and typically occurs unexpected in conscious patients and may be related to a less favourable prognosis. In our institution, we have observed four cases of multiple inappropriate ICD shocks during reset to VVI backup mode. All four patients were implanted with a St Jude Medical ICD since 2010. The reset to VVI backup mode happens as a 'safety' response when the ICD encounters errors in the software or hardware often due to electromagnetic interference. The ICD then operates in a simple mode, with only a ventricular fibrillation (VF) zone starting at 146 b.p.m., with shock therapy only and changes in sensitivity settings making the ICD more sensitive. In all cases, the reason for the multiple inappropriate shocks was that the VF zone was reached due to exercise-induced sinus tachycardia or due to oversensing during sinus rhythm. The VVI backup mode has to balance between protection from failure of ICD therapy during life-threatening ventricular arrhythmias and from inappropriate shocks. It seems the non-programmable parameters in VVI backup mode of St Jude Medical ICDs carry an unacceptable high risk of inappropriate shocks during normal rhythm as illustrated by our four cases. A higher VF zone comparable with the zones chosen by the other manufacturer would give a better balance, since it is very unlikely that a patient will need shock therapy urgently for slow ventricular tachycardia.

Oral cancer diagnosis amid COVID-19 pandemic: Identifying tell-tale signs to avoid pitfalls in general dental practice.

This article details the unusual presentation of an oral squamous cell carcinoma (SCC) referred to secondary care during the COVID-19 pandemic. The patient's chief complaints were trismus and pain from a lower left partially erupted third molar, which was assumed to be pericoronitis-related on referral. Intra-oral examination was difficult due to the patient's symptoms, but radiographic assessment of an orthopantomogram (OPG) showed a pathological fracture and poorly defined radiolucency in the lower left third molar region. Oral SCC was diagnosed after biopsy, and surgery and radiotherapy were swiftly carried out despite COVID-19 restrictions. General dental practitioners (GDPs) remain the frontline healthcare professionals in the screening and detection of oral cancer through detailed history taking and examinations. Primary care dental practitioners should always remain vigilant with patients at risk of oral cancer. Prompt referral to secondary care for further investigations and management should be made when a suspicion of oral malignancy is raised, to ensure a better treatment outcome. Video consultations have had their merits in dentistry amid the coronavirus pandemic, but face-to-face consultations are essential to establish quality patient care.

Mechanism of outside-in {alpha}IIb{beta}3-mediated activation of human platelets by the colonizing Bacterium, Streptococcus gordonii.

OBJECTIVE: To better understand the mechanism of platelet recruitment and activation by Streptococcus gordonii. The oral bacterium Streptococcus gordonii, is amongst the most common pathogens isolated from infective endocarditis patients, and has the property of being able to activate platelets, leading to thrombotic complications. The mechanism of platelet recruitment and activation by S. gordonii is poorly understood. METHODS AND RESULTS: Infective endocarditis is a bacterial infection of the heart valves that carries a high risk of morbidity and mortality. The oral bacterium, S gordonii, is among the most common pathogens isolated from patients with infective endocarditis and is able to activate platelets, leading to thrombotic complications. Platelets interact with S gordonii via glycoprotein Ibα- and α(IIb)ß(3)-recognizing S gordonii surface proteins haemaglutitin salivary antigen (Hsa) and platelet adherence protein A, respectively. The inhibition of glycoprotein Ibα or α(IIb)ß(3) using blocking antibodies or deletion of S gordonii Hsa or platelet adherence protein A significantly reduces platelet adhesion. Immunoreceptor tyrosine-based activation motif (ITAM)-containing proteins have recently played a role in transmitting activating signals into platelets. Platelet adhesion to immobilized S gordonii resulted in tyrosine phosphorylation of the ITAM-bearing receptor, FcγRIIa, and phosphorylation of downstream effectors (ie, spleen tyrosine kinase [Syk] and phospholipase C [PLC]-γ2). Tyrosine phosphorylation of FcγRIIa resulted in platelet-dense granule secretion, filopodial and lamellipodial extension, and platelet spreading. Inhibition of FcγRIIa ablated both dense granule release and platelet spreading. CONCLUSIONS: Streptococcus gordonii binding to the α(IIb)ß(3)/FcγRIIa integrin/ITAM signaling complex results in platelet activation that likely contributes to the thrombotic complications of infective endocarditis.

Human platelets recognize a novel surface protein, PadA, on Streptococcus gordonii through a unique interaction involving fibrinogen receptor GPIIbIIIa.

The concept of an infectious agent playing a role in cardiovascular disease is slowly gaining attention. Among several pathogens identified, the oral bacterium Streptococcus gordonii has been implicated as a plausible agent. Platelet adhesion and subsequent aggregation are critical events in the pathogenesis and dissemination of the infective process. Here we describe the identification and characterization of a novel cell wall-anchored surface protein, PadA (397 kDa), of S. gordonii DL1 that binds to the platelet fibrinogen receptor GPIIbIIIa. Wild-type S. gordonii cells induced platelet aggregation and supported platelet adhesion in a GPIIbIIIa-dependent manner. Deletion of the padA gene had no effect on platelet aggregation by S. gordonii but significantly reduced (>75%) platelet adhesion to S. gordonii. Purified N-terminal PadA recombinant polypeptide adhered to platelets. The padA mutant was unaffected in production of other platelet-interactive surface proteins (Hsa, SspA, and SspB), and levels of adherence of the mutant to fetuin or platelet receptor GPIb were unaffected. Wild-type S. gordonii, but not the padA mutant, bound to Chinese hamster ovary cells stably transfected with GPIIbIIIa, and this interaction was ablated by addition of GPIIbIIIa inhibitor Abciximab. These results highlight the growing complexity of interactions between S. gordonii and platelets and demonstrate a new mechanism by which the bacterium could contribute to unwanted thrombosis.

Oral splints for temporomandibular disorder or bruxism: a systematic review.

Objectives To evaluate the clinical-effectiveness of oral splints for patients with TMD or bruxism for the primary outcomes: pain (TMD) and tooth wear (bruxism).Data sources Four databases including MEDLINE and EMBASE were searched from inception until 1 October 2018.Data selection and extraction Randomised controlled trials comparing all types of splints versus no/minimal treatment for patients with TMD or bruxism were eligible. Standard Cochrane review methods were used. Standardised mean differences (SMD) were pooled for the primary outcome of pain, using random effects models in TMD patients.Data synthesis Thirty-seven trials were included and the evidence identified was of very low certainty using GRADE assessments. When all subtypes of TMD were pooled into one global TMD group, there was no evidence that splints reduced pain: SMD (up to 3 months) -0.18 (95% CI -0.42 to 0.06); 13 trials, 1,076 participants. There was no evidence that any other outcomes improved when using splints. There was no evidence of adverse events associated with splints, but reporting was poor regarding this outcome. No trials measured tooth wear in patients with bruxism. There was a large variation in diagnostic criteria, splint types and outcome measures used and reported. Sensitivity analyses based on these factors did not indicate a reduction in pain.Conclusions The very low-certainty evidence identified did not demonstrate that splints reduced pain in TMD as a group of conditions. There is insufficient evidence to determine whether splints reduce tooth wear in patients with bruxism.

Oral splints for patients with temporomandibular disorders or bruxism: a systematic review and economic evaluation.

BACKGROUND: Splints are a non-invasive, reversible management option for temporomandibular disorders or bruxism. The clinical effectiveness and cost-effectiveness of splints remain uncertain. OBJECTIVES: The objectives were to evaluate the clinical effectiveness and cost-effectiveness of splints for patients with temporomandibular disorders or bruxism. This evidence synthesis compared (1) all types of splint versus no/minimal treatment/control splints and (2) prefabricated versus custom-made splints, for the primary outcomes, which were pain (temporomandibular disorders) and tooth wear (bruxism). REVIEW METHODS: Four databases, including MEDLINE and EMBASE, were searched from inception until 1 October 2018 for randomised clinical trials. The searches were conducted on 1 October 2018. Cochrane review methods (including risk of bias) were used for the systematic review. Standardised mean differences were pooled for the primary outcome of pain, using random-effects models in temporomandibular disorder patients. A Markov cohort, state-transition model, populated using current pain and Characteristic Pain Intensity data, was used to estimate the incremental cost-effectiveness ratio for splints compared with no splint, from an NHS perspective over a lifetime horizon. A value-of-information analysis identified future research priorities. RESULTS: Fifty-two trials were included in the systematic review. The evidence identified was of very low quality with unclear reporting by temporomandibular disorder subtype. When all subtypes were pooled into one global temporomandibular disorder group, there was no evidence that splints reduced pain [standardised mean difference (at up to 3 months) -0.18, 95% confidence interval -0.42 to 0.06; substantial heterogeneity] when compared with no splints or a minimal intervention. There was no evidence that other outcomes, including temporomandibular joint noises, decreased mouth-opening, and quality of life, improved when using splints. Adverse events were generally not reported, but seemed infrequent when reported. The most plausible base-case incremental cost-effectiveness ratio was uncertain and driven by the lack of clinical effectiveness evidence. The cost-effectiveness acceptability curve showed splints becoming more cost-effective at a willingness-to-pay threshold of ≈£6000, but the probability never exceeded 60% at higher levels of willingness to pay. Results were sensitive to longer-term extrapolation assumptions. A value-of-information analysis indicated that further research is required. There were no studies measuring tooth wear in patients with bruxism. One small study looked at pain and found a reduction in the splint group [mean difference (0-10 scale) -2.01, 95% CI -1.40 to -2.62; very low-quality evidence]. As there was no evidence of a difference between splints and no splints, the second objective became irrelevant. LIMITATIONS: There was a large variation in the diagnostic criteria, splint types and outcome measures used and reported. Sensitivity analyses based on these limitations did not indicate a reduction in pain. CONCLUSIONS: The very low-quality evidence identified did not demonstrate that splints reduced pain in temporomandibular disorders as a group of conditions. There is insufficient evidence to determine whether or not splints reduce tooth wear in patients with bruxism. There remains substantial uncertainty surrounding the most plausible incremental cost-effectiveness ratio. FUTURE WORK: There is a need for well-conducted trials to determine the clinical effectiveness and cost-effectiveness of splints in patients with carefully diagnosed and subtyped temporomandibular disorders, and patients with bruxism, using agreed measures of pain and tooth wear. STUDY REGISTRATION: This study is registered as PROSPERO CRD42017068512. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 7. See the NIHR Journals Library website for further project information.

Treatment options for people experiencing temporomandibular disorders (pain and/or restricted movement in and around the jaw joint) include splints, which are removable appliances, often similar to a mouthguard. They are provided to patients to help ease pain in the mouth, face or jaws. They are also used to manage the symptoms of temporomandibular disorders, such as frequent headaches/migraines, clicking jaws, restricted mouth-opening or tooth wear from the grinding of teeth (bruxism). There are many types of splints. This research looked at the evidence addressing the primary question of whether or not splints work (regardless of type of splint) in reducing the pain associated with temporomandibular disorders and/or tooth wear, and if they offered value for money. Patients were involved in the research to ensure that the question and the outcomes that were measured were appropriate. A systematic review of the literature was undertaken to find all randomised controlled trials including patients with temporomandibular disorders or bruxism. Online databases of research publications were searched, and these searches were checked, to identify relevant trials. All stages of the review process were undertaken to the highest standards by two people, independently and in duplicate, using well-respected and recognised Cochrane methods. We conducted a value-for-money assessment, comparing the trial data with the costs of splints to see if splints are a cost-effective use of NHS funding. There was no evidence that splints reduced pain when compared with not wearing a splint or when compared with a minimal treatment (like jaw exercises, advice or education) in patients with temporomandibular disorders. The evidence was assessed as being of very low quality; therefore, it remains unclear whether or not splints are good value for money, or if they should be paid for by the NHS. This research showed that more well-conducted trials on temporomandibular disorder patients are needed.

Impact of device programming on the success of the first anti-tachycardia pacing therapy: An anonymized large-scale study.

BACKGROUND: Antitachycardia pacing (ATP) is an effective treatment for ventricular tachycardia (VT). We evaluated the efficacy of different ATP programs based on a large remote monitoring data set from patients with implantable cardioverter-defibrillators (ICDs). METHODS: A dataset from 18,679 ICD patients was used to evaluate the first delivered ATP treatment. We considered all device programs that were used for at least 50 patients, leaving us with 7 different programs and a total of 32,045 episodes. We used the two-proportions z-test (α = 0.01) to compare the probability of success and the probability for acceleration in each group with the corresponding values of the default setting. RESULTS: Overall, the first ATP treatment terminated in 78.4%-97.5% of episodes with slow VT and 81.5%-91.1% of episodes with fast VT. The default setting of the ATP programs with the number of sequences S = 3 was applied to treat 30.1% of the slow and 36.6% of the fast episodes. Reducing the maximum number of sequences to S = 2 decreased the success rate for slow VT (P < 0.0001, h = 0.38), while the setting S = 4 resulted in the highest success rate of 97.5% (P < 0.0001, h = 0.27). CONCLUSION: While the default programs performed well, we found that increasing the number of sequences from 3 to 4 was a promising option to improve the overall ATP performance.

Precision of automated QRS duration measurement in patients treated with cardiac resynchronization therapy.

PURPOSE: Shortening of the QRS duration (QRSd) is often used to guide device optimization and reprogramming in patients with cardiac resynchronization therapy (CRT). Detecting the small changes expected during reprogramming requires that the QRSd can be measured with high precision, but this has never been studied in patients with CRT. In this study, we wanted to assess the precision of automated QRSd measurement in patients treated with CRT using two commonly available electrocardiographs. METHODS: Patients treated with CRT were recruited during routine follow-up in our pacemaker clinic. In all participants, a number of immediate successive ECGs were recorded with the GE MAC 5500 (Mac55) and the GE MAC 1600 (Mac16). Data were analyzed with a linear mixed model. RESULTS: A total of 785 12-lead ECGs were recorded in 36 patients with an average of 11.2 and 10.6 ECGs per patient with the Mac55 and Mac16, respectively. The Mac55 measured the QRSd longer by 10.3 milliseconds (ms) (95% CI 7.1-13.5 ms, p < 0.001) and with significantly smaller standard deviation for repeated measurements (6.3 vs. 10.4 ms, p < 0.001). Limits of agreement were ± 17.5 and ± 28.8 ms for the Mac55 and Mac16, respectively. CONCLUSIONS: Automated measurement of QRSd in patients with CRT shows low precision with limits of agreement of ± 17.5 and ± 28.8 ms for repeated measurements in two commercially available electrocardiographs. Device programming solely by QRSd changes should be done with caution, and clinical effects should be demonstrated in future trials. Device programming based on QRSd changes should be done with caution until the ability of this measure to predict clinical outcome can be demonstrated in prospective study.

The impact of co-morbidity burden on appropriate implantable cardioverter defibrillator therapy and all-cause mortality: insight from Danish nationwide clinical registers.

AIMS: In a nationwide cohort of primary (PP-ICD) and secondary prevention (SP-ICD) implantable cardioverter defibrillator (ICD) patients, we aimed to investigate the association between co-morbidity burden and risk of appropriate ICD therapy and mortality. METHODS AND RESULTS: We identified all patients >18 years, implanted with first-time PP-ICD (n = 1873) or SP-ICD (n = 2461) in Denmark from 2007 to 2012. Co-morbidity was identified in administrative registers of hospitalization and drug prescription from pharmacies. Co-morbidity burden was defined as the number of pre-existing non-ICD indication-related co-morbidities including atrial fibrillation, diabetes, chronic obstructive pulmonary disease, chronic renal disease, liver disease, cancer, chronic psychiatric disease, and peripheral and/or cerebrovascular disease, and divided into four groups (co-morbidity burden 0, 1, 2, and ≥3). Through Cox models, we assessed the impact of co-morbidity burden on appropriate ICD therapy and mortality. Increasing co-morbidity burden was not associated with increased risk of appropriate therapy, irrespective of implant indication [all hazard ratios (HRs) 1.0-1.4, P = NS]. Using no co-morbidities as reference, increasing co-morbidity burden was associated with increased mortality risk in PP-ICD patients (co-morbidity burden 1, HR 2.1; comorbidity burden 2, HR 3.7; co-morbidity burden ≥3, HR 6.6) (all P < 0.001) and SP-ICD patients (co-morbidity burden 1, HR 2.2; co-morbidity burden 2, HR 3.8; co-morbidity burden ≥3, HR 5.8). With increasing co-morbidity burden, an increasing frequency of patients died without having utilized their device, with 72% PP-ICD and 45% SP-ICD patients with co-morbidity burden ≥3 dying without prior appropriate ICD therapy. CONCLUSION: Increasing co-morbidity burden was not associated with increased risk of appropriate ICD therapy. With increasing co-morbidity burden, mortality increased, and a higher proportion of patients died, without ever having utilized their device.

Single-coil and dual-coil defibrillator leads and association with clinical outcomes in a complete Danish nationwide ICD cohort.

BACKGROUND: The best choice of defibrillator lead in patients with routine implantable cardioverter-defibrillator (ICD) is not settled. Traditionally, most physicians prefer dual-coil leads but the use of single-coil leads is increasing. OBJECTIVE: The purpose of this study was to compare clinical outcomes in patients with single- and dual-coil leads. METHODS: All 4769 Danish patients 18 years or older with first-time ICD implants from 2007 to 2011 were included from the Danish Pacemaker and ICD Register. Defibrillator leads were 38.9% single-coil leads and 61.1% dual-coil leads. The primary end point was all-cause mortality. Secondary end points were lowest successful energy at implant defibrillation testing, first shock failure in spontaneous arrhythmias, structural lead failure, and lead extraction outcomes. RESULTS: Single-coil leads were associated with lower all-cause mortality with an adjusted hazard ratio of 0.85 (95% confidence interval 0.73-0.99; P = .04). This finding was robust in a supplementary propensity score-matched analysis. However, dual-coil leads were used in patients with slightly higher preimplant morbidity, making residual confounding by indication the most likely explanation for the observed association between lead type and mortality. The lowest successful defibrillation energy was higher using single-coil leads (23.2 ± 4.3 J vs 22.1 ± 3.9 J; P < .001). No significant differences were observed for other secondary end points showing high shock efficacies and low rates of lead failures and extraction complications. CONCLUSION: Shock efficacy is high for modern ICD systems. The choice between single-coil and dual-coil defibrillator leads is unlikely to have a clinically significant impact on patient outcomes in routine ICD implants.

An anterior left ventricular lead position is associated with increased mortality and non-response in cardiac resynchronization therapy.

BACKGROUND: Non-response to cardiac resynchronization therapy (CRT) might be due to insufficient resynchronization as a result of a sub-optimal left ventricular lead positon (LV-LP). OBJECTIVE: To evaluate the impact of different LV-LPs on mortality and symptomatic improvement in a large cohort of patients treated with CRT. METHODS: We performed a nationwide cohort study on consecutive patients receiving a CRT device from 1997 to 2012 registered in the Danish pacemaker and ICD register. The LV-LP was defined clockwise in a left anterior oblique (LAO) view and categorized as anterior (≤2 o'clock), lateral (2 to 4 o'clock) or posterior (>4 o'clock), and as basal, mid-ventricular, or apical in a right anterior oblique (RAO) view. Outcomes were all cause mortality and clinical response (improvement in NYHA class). Adjusted hazard ratio (aHR) and odds ratio (aOR) with 95% confidence intervals (CI) were calculated using Cox and logistic regression analysis. RESULTS: A total of 2594 patients were included. A lateral LV-LP, (aHR 0.77, 95% CI 0.64-0.92, p=0.004), and a posterior LV-LP, (aHR 0.71 95% CI 0.53-0.97, p=0.029) were associated with lower mortality as compared to an anterior LV-LP. A lateral LV-PV was associated with higher clinical response rate as compared to an anterior LV-LP (aOR 1.37, 1.03-1.83, p=0.032). No statistically significant associations were observed between LV-LP in the RAO view and mortality or clinical response. CONCLUSION: An anterior left ventricular lead position is associated with increased all-cause mortality and lower clinical response rate in patients treated with CRT and should be avoided.

The patient perspective on the Riata defibrillator lead advisory: a Danish nationwide study.

BACKGROUND: The St Jude Medical Riata lead advisory was issued owing to insulation failures. The impact of this advisory on patients' well-being is unknown. OBJECTIVES: The objectives of this study were to describe the acute impact of the Riata advisory on patients' well-being and psychological functioning and to examine changes over time. METHODS: Patients with active Riata leads completed standardized and validated patient-reported outcomes (PROs) in connection with a nationwide fluoroscopic screening with 12-month follow-up. They were matched (1:1) on age, sex, and implant indication with nonadvisory controls for baseline comparisons. Cohen's effect size d was used to determine the clinical relevance of the estimated adjusted mean differences (small, d = 0.20; moderate, d = 0.50; large, d ≥ 0.80). RESULTS: Of all Riata patients, 86% (256 of 299) completed baseline PROs and 70% (210 of 299) follow-up PROs. Riata patients reported poorer device acceptance (d = -0.28; P = .001) and increased device-related concerns (d = 0.29; P < .001) as compared with matched nonadvisory controls. There were no differences in symptoms of depression (d = 0.13; P = .13). Female sex was an independent predictor of a high advisory impact on general well-being as assessed with a purpose-designed question (odds ratio 2.24; P = .04). Device-related concerns decreased over time (d = -0.17; P = .002), but no changes were seen for other PROs. CONCLUSION: The Riata advisory is associated with a persistent small reduction in device acceptance and a small increase in device-related concerns with minimal improvement over time. Female sex is a predictor of a high negative advisory impact on general well-being. A need for counseling may arise in vulnerable subsets of patients.