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Background: The possibility to use built-in smartphone-cameras for photoplethysmographic (PPG) recording of pulse waves lead to the release of numerous health apps, claiming to measure blood pressure (BP) based on PPG signals. Even though these apps are highly popular, not a single one is clinically validated. Aim of the current study was to test systolic BP (sBP) estimation by a promising new algorithm in a large clinical setting.Methods: The study was designed based on the European Society of Hypertension International Protocol Revision 2010. Each individual received 7 sequential BP measurements, starting with the reference device - an automated oscillometric cuff device - followed by the PPG recording at the patients' index finger.Results: A total 1,036 subjects were recruited of which 965 could be included for final analysis leading to 2,895 pairs of comparison. Mean (±SD) error between test and reference device was -0.41 (±16.52) mmHg. Only 38.1% of all 2,895 BP comparisons reached a delta within ±5 mmHg, while 29.3% reached a delta larger than 15 mmHg. Bland-Altman plot showed an overestimation of smartphone sBP in comparison to reference sBP in low range and an underestimation in high sBP range.Conclusions: According to the European Society of Hypertension International Protocol Revision 2010 specifications the algorithm failed validation criteria for sBP measurement and was not commercialized. These findings emphasize that health apps should be rigorously validated according to common guidelines before market release as under- and/or overestimation of BP is potentially exposing persons at health risks in short and long term.Trial Registration: ClinicalTrials.gov, number NCT02552030. [ABSTRACT FROM AUTHOR]

Background: The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS.Aims: We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups.Methods: We enrolled 7213 patients at 459 sites in 31 countries. Prespecified subgroups for primary safety and efficacy analyses included age, sex, race, global region, stroke or transient ischemic attack prior to qualifying event, time to randomization, hypertension, and diabetes mellitus.Results: Mean age was 66.9 ± 9.8 years; 24% were under 60 years. Older patients had more hypertension, coronary disease, and cancer. Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infarction. Women comprised 38% of participants and were older than men. Patients from East Asia were oldest whereas those from Latin America were youngest. Patients in the Americas more frequently were on aspirin prior to the qualifying stroke. Acute cortical infarction was more common in the United States, Canada, and Western Europe, whereas prior radiographic infarctions were most common in East Asia. Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke, with earliest enrollments in Asia and Eastern Europe.Conclusions: NAVIGATE-ESUS is the largest randomized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS. The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is an arrhythmia that occurs as a result of numerous pathophysiological processes in the atria. High rate, neurohumoral activation, aging and chronic stretch activate a variety of signaling pathways leading to electrical and structural remodeling. In particular, endomysial fibrosis within the epicardial layer, which also occurs as a result of AF itself, can disrupt electrical connections between muscle bundles. This leads to electrical dissociation not only within the epicardial layer, but also between the epicardial layer and the endocardial bundle network. Although the normal, healthy atrium has a complex 3-dimensional shape, differences in activation time between the epicardial layer and the underlying trabecular network in the atrial free walls are small, and the atrial walls essentially function as a 2-dimensional surface for propagating fibrillation waves. However, progressive structural remodeling leads to increased dissociation of epicardial and endocardial activation patterns. Epi-endocardial dissociation allows fibrillation waves to propagate between epicardium and endocardium, and become visible as ‘breakthrough waves’ that add to the overall complexity of fibrillatory conduction and thus to AF stability. This process greatly increases the effective surface area available to fibrillation waves and causes the atrial walls to behave as a 3-dimensional substrate. Computer models support that this behavior can increase AF stability. Under these conditions, ectopic activity originating from e.g. the pulmonary veins is likely to trigger longer episodes of AF. Experiments using simultaneous endo-epicardial mapping of AF suggest that disseminated, irregular and non-repetitive ectopic focal discharges might also occur during AF. The increasingly 3-dimensional character of AF as a result of structural remodeling lowers the responsiveness to antiarrhythmic compounds and ablation therapy, thus advocating early rhythm control strategies. [ABSTRACT FROM AUTHOR]

Background: Patients with long QT syndrome (LQTS) are at increased risk not only for ventricular arrhythmias but also for atrial pathology including atrial fibrillation (AF). Some patients with “lone” AF carry Na+-channel mutations. Objective: The purpose of this study was to determine the mechanisms underlying atrial pathology in LQTS. Methods: In mice with a heterozygous knock-in long QT syndrome type 3 (LQT3) mutant of the cardiac Na+ channel (ΔKPQ-SCN5A) and wild-type (WT) littermates, atrial size, function, and electrophysiologic parameters were measured in intact Langendorff-perfused hearts, and histologic analysis was performed. Results: Atrial action potential duration, effective refractory period, cycle length, and PQ interval were prolonged in ΔKPQ-SCN5A hearts (all P <.05). Flecainide (1 μM) reversed atrial action potential duration prolongation and induced postrepolarization refractoriness (P <.05). Arrhythmias were infrequent during regular rapid atrial rate in both WT and ΔKPQ-SCN5A but were inducible in 15 (38%) of 40 ΔKPQ-SCN5A and 8 (29%) of 28 WT mice upon extrastimulation. Pacing protocols generating rapid alterations in rate provoked atrial extrasystoles and arrhythmias in 6 (66%) of 9 ΔKPQ-SCN5A but in 0 (0%) of 6 WT mice (P <.05). Atrial diameter was increased by nearly 10% in ΔKPQ-SCN5A mice >5 months old without increase in fibrotic tissue. Conclusion: Murine hearts bearing an LQT3 mutation show abnormalities in atrial electrophysiology and subtle changes in atrial dimension, including an atrial arrhythmogenic phenotype on provocation. These results support clinical data suggesting that LQTS mutations can cause atrial pathology and arrhythmogenesis and indicate that murine sodium channel LQTS models may be useful for exploring underlying mechanisms. [ABSTRACT FROM AUTHOR]

Abstract: The progressive nature of atrial fibrillation (AF) has been demonstrated in numerous experimental as well as clinical investigations. Electrical remodeling (shortening of atrial refractoriness) develops within the first days of AF and contributes to the increase in stability of the arrhythmia. However, “domestication of AF” must also depend on other mechanisms since the stability of AF continues to increase after electrical remodeling has been completed. Chronic atrial stretch induces activation of numerous signaling pathways leading to cellular hypertrophy, fibroblast proliferation and tissue fibrosis. The resulting electro-anatomical substrate is characterized by increased non-uniform anisotropy and local conduction heterogeneities facilitating reentry in the dilated atria. Atrial fibrosis may lead to disruption of the electrical side-to-side junctions between muscle bundles. This can result in electrical dissociation between neighboring muscle bundles, i.e. they become activated out-of-phase. Recent mapping studies in goats with persistent AF showed that electrical dissociation can not only occur between neighboring muscle bundles but also in the third dimension, i.e. between the epicardial layer and the endocardial bundle network. Such endo-epicardial dissociation will significantly increase the number of wavefronts which can simultaneously be present in the atrial wall. This article reviews data suggesting a role of endo-epicardial dissociation in dilated and fibrillating atria, for the self-perpetuating nature of AF as well as its possible implications for therapeutic interventions. [Copyright &y& Elsevier]

The silent pandemic of bacterial antimicrobial resistance is a leading cause of death worldwide, prolonging hospital stays and raising health-care costs. Poor incentives to develop novel pharmacological compounds and the misuse of antibiotics contribute to the bacterial antimicrobial resistance crisis. Therapeutic drug monitoring (TDM) based on blood analysis can help alleviate the emergence of bacterial antimicrobial resistance and effectively decreases the risk of toxic drug concentrations in patients' blood. Antibiotic tissue penetration can vary in patients who are critically or chronically ill and can potentially lead to treatment failure. Antibiotics such as β-lactams and glycopeptides are detectable in non-invasively collectable biofluids, such as sweat and exhaled breath. The emergence of wearable sensors enables easy access to these non-invasive biofluids, and thus a laboratory-independent analysis of various disease-associated biomarkers and drugs. In this Personal View, we introduce a three-level model for TDM of antibiotics to describe concentrations at the site of infection (SOI) by use of wearable sensors. Our model links blood-based drug measurement with the analysis of drug concentrations in non-invasively collectable biofluids stemming from the SOI to characterise drug concentrations at the SOI. Finally, we outline the necessary clinical and technical steps for the development of wearable sensing platforms for SOI applications. [ABSTRACT FROM AUTHOR]

Abstract: Background and methods: Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. The substrate of AF is composed of a complex interplay between structural and functional changes of the atrial myocardium often preceding the occurrence of persistent AF. However, there are only few animal models reproducing the slow progression of the AF substrate to the spontaneous occurrence of the arrhythmia. Transgenic mice (TG) with cardiomyocyte-directed expression of CREM-IbΔC-X, an isoform of transcription factor CREM, develop atrial dilatation and spontaneous-onset AF. Here we tested the hypothesis that TG mice develop an arrhythmogenic substrate preceding AF using physiological and biochemical techniques. Results: Overexpression of CREM-IbΔC-X in young TG mice (<8weeks) led to atrial dilatation combined with distension of myocardium, elongated myocytes, little fibrosis, down-regulation of connexin 40, loss of excitability with a number of depolarized myocytes, atrial ectopies and inducibility of AF. These abnormalities continuously progressed with age resulting in interatrial conduction block, increased atrial conduction heterogeneity, leaky sarcoplasmic reticulum calcium stores and the spontaneous occurrence of paroxysmal and later persistent AF. This distinct atrial remodelling was associated with a pattern of non-regulated and up-regulated marker genes of myocardial hypertrophy and fibrosis. Conclusions: Expression of CREM-IbΔC-X in TG hearts evokes abnormal growth and development of the atria preceding conduction abnormalities and altered calcium homeostasis and the development of spontaneous and persistent AF. We conclude that transcription factor CREM is an important regulator of atrial growth implicated in the development of an arrhythmogenic substrate in TG mice. [Copyright &y& Elsevier]

Objectives: We aimed to compare the hemodynamic effects of right-atrial-paced (DDD) and right-atrial-sensed (VDD) biventricular paced rhythm on cardiac resynchronization therapy (CRT). Background: Cardiac resynchronization therapy improves hemodynamics in patients with severe heart failure and left ventricular (LV) dyssynchrony. However, the impact of active right atrial pacing on resynchronization therapy is unknown. Methods: Seventeen CRT patients were studied 10 months (range: 1 to 46 months) after implantation. At baseline, the programmed atrioventricular delay was optimized by timing LV contraction properly at the end of atrial contraction. In both modes the acute hemodynamic effects were assessed by multiple Doppler echocardiographic parameters. Results: Compared to DDD pacing, VDD pacing resulted in much better improvement of intraventricular dyssynchrony assessed by the septal-to-posterior wall motion delay (VDD 106 ± 83 ms vs. DDD 145 ± 95 ms; p = 0.001), whereas the interventricular mechanical delay (difference between onset of pulmonary and aortic outflow) did not differ (VDD 20 ± 21 ms vs. DDD 18 ± 17 ms; p = NS). Furthermore, VDD pacing significantly prolonged the rate-corrected LV filling period (VDD 458 ± 123 ms vs. DDD 371 ± 94 ms; p = 0.0001) and improved the myocardial performance index (VDD 0.60 ± 0.18 vs. DDD 0.71 ± 0.23; p &#60; 0.01). Conclusions: Our findings suggest that avoidance of right atrial pacing results in a higher degree of LV resynchronization, in a substantial prolongation of the LV filling period, and in an improved myocardial performance. Thus, the VDD mode seems to be superior to the DDD mode in CRT patients. [Copyright &y& Elsevier]