DREAM-ICD-II Study.

BACKGROUND: Regulatory authorities of most industrialized countries recommend 6 months of private driving restriction after implantation of a secondary prevention implantable cardioverter-defibrillator (ICD). These driving restrictions result in significant inconvenience and social implications. This study aimed to assess the incidence rate of appropriate device therapies in contemporary recipients of a secondary prevention ICD. METHODS: This retrospective study at 3 Canadian tertiary care centers enrolled consecutive patients with new secondary prevention ICD implants between 2016 and 2020. RESULTS: For a median of 760 days (324, 1190 days), 721 patients were followed up. The risk of recurrent ventricular arrhythmia was highest during the first 3 months after device insertion (34.4%) and decreased over time (10.6% between 3 and 6 months, 11.7% between 6 and 12 months). The corresponding incidence rate per 100 patient-days was 0.48 (95% CI, 0.35-0.64) at 90 days, 0.28 (95% CI, 0.17-0.45) at 180 days, and 0.21 (95% CI, 0.13-0.33) between 181 and 365 days after ICD insertion (P<0.001). The cumulative incidence of arrhythmic syncope resulting in sudden cardiac incapacitation was 1.8% within the first 90 days and subsequently dropped to 0.4% between 91 and 180 days (P<0.001) after ICD insertion. CONCLUSIONS: The incidence rate of appropriate therapies resulting in sudden cardiac incapacitation in contemporary recipients of a secondary prevention ICD is much lower than previously reported and declines significantly after the first 3 months. Lowering driving restrictions to 3 months after the index cardiac event seems safe, and revision of existing guidelines should be considered in countries still adhering to a 6-month period. Existing restrictions for private driving after implantation of a secondary prevention ICD should be reconsidered.

Leucocyte-derived micro-RNAs as candidate biomarkers in Brugada syndrome.

AIMS: Risk stratification for sudden cardiac death in patients with Brugada syndrome remains a major challenge. Contemporary risk prediction models have only modest predictive value. The aim of this study was to assess the role of micro-RNAs from peripheral blood as candidate biomarkers in Brugada syndrome. METHODS AND RESULTS: In this prospective study, Brugada patients and unaffected control individuals were enrolled for analysis of leucocyte-derived microRNAs (miRNAs) levels. Expression levels of 798 different circulating miRNAs were analysed on the NanoString® nCounter platform. All results were cross-validated by using a quantitative polymerase chain reaction. Micro-RNA expression levels of Brugada patients were compared with clinical data. A total of 21 definite Brugada patients (38% with a history of ventricular arrhythmia or cardiac arrest) and 30 unaffected control individuals were included in the study. Micro-RNA analysis showed a distinct expression profile in Brugada patients with 42 differentially expressed markers (38 up-regulated, 4 down-regulated miRNAs). The symptom status of Brugada patients was associated with a distinct miRNA signature. Micro-RNAs 145-5p and 585-3p were significantly up-regulated in symptomatic Brugada patients (P = 0.04). Incorporating miRNAs 145-5p and 585-3p into a multivariable model demonstrated significantly increased symptom prediction (area under the curve = 0.96; 95% confidence interval: 0.88-1.00). CONCLUSION: Brugada patients display a distinct miRNA expression profile compared with unaffected control individuals. There is also evidence that certain miRNAs (miR-145-5p and miR-585-3p) are associated with the symptom status of Brugada patients. The results suggest the principal utility of leucocyte-derived miRNAs as prognostic biomarkers for Brugada syndrome.

Acute transvenous pacemaker lead thrombosis early after implantation: A rare clinical scenario.

Symptomatic thrombus formation due to a permanent pacemaker (PM) lead is a rare complication. It could be associated with serious outcome and should be suspected in patients who present with unexplained right heart failure, dyspnea, or syncope following dual-chamber PM implantation. A timely decision to perform an echocardiographic examination, followed by medical, thrombolytic, or surgical treatment can be necessary. We describe the case of an 84-year-old man who presented with syncope and hypotension a few days after PM implantation. A transesophageal echocardiography revealed a mobile mass in the right atrium attached to the pacemaker lead. Intravenous heparin allowed a complete resolution of the thrombus.

Findings of remote monitoring of implantable cardioverter defibrillators during the COVID-19 pandemic.

BACKGROUND: Monitoring of cardiac implantable electronic devices was highly impacted by the COVID-19 pandemic considering the high volume of in-person visits for regular follow-up. Recent recommendations highlight the important role of remote monitoring to prevent exposure to the virus. This study compared remote monitoring of implantable cardioverter defibrillators (ICDs) in patients whose in-person annual visit was substituted for a remote monitoring session with patients who were already scheduled for a remote monitoring session. METHODS: This was a cross-sectional observational study of 329 consecutive patients between 20 March and 24 April 2020. Group 1 included 131 patients whose in-person annual visit was substituted for a remote monitoring session. Group 2 included 198 patients who underwent a remote monitoring session as scheduled in their usual device follow-up. The time interval since the last in-person visit was 13.3 ± 3.2 months in group 1 and 5.9 ± 1.7 months in group 2 (P < .01). RESULTS: In group 1, 15 patients (11.5%) experienced a clinical event compared to 15 patients (7.6%) in group 2 (P = .25). Nineteen patients (14.5%) required a physician intervention in group 1 compared to 19 patients (9.6%) in group 2 (P = .22). Two patients (1.5%) in group 1 and four patients (2.0%) in group 2 required an early in-person follow-up visit during the pandemic (P > .99). CONCLUSION: Remote monitoring of ICDs is useful to identify clinical events and allows physicians to treat patients appropriately during the COVID-19 pandemic regardless of the time interval since their last in-person visit. It reduces significantly in-person visit for regular follow-up.

Validation of a novel single lead ambulatory ECG monitor - Cardiostat™ - Compared to a standard ECG Holter monitoring.

BACKGROUND: Cardiostat™ is a single lead ambulatory ECG monitor. Recording is made through 2 electrodes positioned in a lead 1-like configuration. We first validated its accuracy for atrial fibrillation detection compared to a 12-lead ECG. In the second phase of the study, arrhythmia detection accuracy was compared between Cardiostat™ ambulatory ECG and a standard 24 h Holter ECG monitoring. METHOD/RESULTS: Phase one of the study included patients undergoing cardioversion for atrial fibrillation (AF) or atrial flutter. Cardiostat™ tracings were compared with standard 12-lead ECG. In the second phase, patients undergoing 24 h ambulatory Holter ECG monitoring for control or suspicion of atrial fibrillation (AF) were included. Simultaneous Holter monitoring and Cardiostat™ ECG recordings were performed. Tracings were analysed and compared. Two hundred twelve monitoring were compared. AF was diagnosed in 73 patients. Agreement between Cardiostat™ ECG and standard Holter monitoring was 99% for AF detection with kappa = 0.99. Kappa correlation for atrial flutter detection was only moderate at 0.51. AF burden was similar in both recordings. Noise hindered analysis in a greater proportion with Cardiostat™ compared to Holter ambulatory ECG (8.5 vs 3.8%). CONCLUSION: Cardiostat™ ambulatory ECG device showed excellent correlation with the standard Holter ECG monitoring for AF detection. Holter monitoring was however superior to discriminate premature atrial and ventricular beats and to qualify the morphology of PVCs since it has more vectors for analysis. Added value of Cardiostat™ includes longer monitoring duration, less cumbersome installation and water resistance.

Detection and reaction thresholds for reverse alarms in noise with and without passive hearing protection.

OBJECTIVE: To measure masked detection and reaction thresholds for two reverse alarms (tonal and broadband) and compare results to available standards and psychoacoustic criteria for setting alarm levels. DESIGN: Alarm detection and reaction thresholds were adaptively measured in 80-dBA background noises without hearing protection (Experiment 1), and with a passive earmuff-style hearing protection device (HPD) (Experiment 2). STUDY SAMPLE: Twenty-four young adults with normal hearing in each experimental group. RESULTS: Reverse alarms remained audible at levels well-below background noises [thresholds: -11 to -25 dB signal-to-noise ratio (SNR)], with and without the selected HPD. Detection was more influenced by alarm and noise type, while reaction was more susceptible to HPD use. HPD use resulted in lower detection thresholds by up to 2.5 dB compared to unprotected listening but increased reaction thresholds by 5-10 dB depending on the alarm. CONCLUSIONS: Since noise type appears to have a more limited effect on reaction thresholds, adjusting alarms based on a global dBA method appears preferable to methods based on masked detection thresholds. However, while the >0 dB SNR recommended in ISO 9533 seems adequate for unprotected listening, an additional 5-10 dB may be warranted to elicit the same reaction when the selected HPD is used.

Remote Magnetic Navigation for Catheter Ablation in Patients With Congenital Heart Disease: A Review.

In patients with congenital heart disease, challenges to catheter-based arrhythmia interventions are unique and numerous given the complexity of the underlying defects, anatomic and surgical intervention variants including baffles, conduits, patches, and/or shunts. Remote magnetic navigation offers significant advantages in these cases that may present with limited vascular access or difficult access to the target cardiac chambers implicated by the previous surgical interventions. We reviewed the data available on the safety, feasibility, and effectiveness of magnetic navigation for the treatment of arrhythmia in congenital heart disease and discussed the specific challenges related to various congenital defects and repair with the potential advantages offered by magnetic navigation in these circumstances.

Safety of Cefazolin Test Dose in Patients With Penicillin Allergy Just Prior to Cardiac Device Implantation: A Single-Centre Experience.

Background: Cephalosporins are the cornerstone of cardiac device infection prophylaxis. Owing to fears of cross-reactivity, penicillin-allergic patients are exposed to potentially more-toxic drugs, with decreased efficacy. We evaluated the safety of a cefazolin test dose (CTD) in self-reported penicillin-allergic patients. Methods: In this single-centre study, we evaluated consecutive patients with chart documentation of penicillin allergy undergoing cardiac device implantation, over a 2-year period. A CTD was performed if no cephalosporin allergy or severe anaphylactic reaction to penicillin had been documented. Patients were given 2 doses of 100 mg IV cefazolin, and if no allergic reaction occurred after 5 minutes, the full dose (1800 mg) was administered in the electrophysiology laboratory just before the implantation procedure. Results: A total of 2200 patients were included. The frequency of reported penicillin allergy was 9.3% (n = 204). In 80% of cases, the type of allergic reaction was not reported in medical notes or was unknown by the patient. A CTD was performed in 67.6% of patients with a penicillin allergy (n = 138). A total of 5 adverse events occurred (3.6% of patients [95% confidence interval, 1.1%-6.1%]) - 4 skin rashes and 1 tongue edema. These 5 patients became asymptomatic after antihistaminic and corticosteroid IV treatment. Even if the test dose was negative, 79% of patients also were administered vancomycin before the procedure, as it requires a 1-hour infusion prior to the CTD in the implantation procedure room. Conclusion: A CTD in most penicillin-allergic patients appears to be safe and allows its use per recommended guidelines.

Contexte: Les céphalosporines sont la pierre angulaire de la prophylaxie des infections des dispositifs cardiaques. En raison du risque appréhendé de réactivité croisée, les patients allergiques à la pénicilline se trouvent exposés à des médicaments potentiellement plus toxiques, qui s'avèrent aussi moins efficaces. Nous avons évalué l'innocuité d'une dose d'essai de céfazoline chez des patients qui s'étaient dits allergiques à la pénicilline. Méthodologie: Dans cette étude monocentrique, nous avons suivi pendant deux ans des patients consécutifs dont le dossier médical faisait état d'une allergie à la pénicilline et chez qui un dispositif cardiaque devait être implanté. Une dose d'essai de céfazoline a été administrée aux patients sans antécédents documentés d'allergie aux céphalosporines ou de réaction anaphylactique sévère à la pénicilline. Deux doses de 100 mg de céfazoline ont été administrées par voie intraveineuse. En l'absence de réaction allergique après cinq minutes, les patients recevaient la dose complète (1 800 mg) au laboratoire d'électrophysiologie juste avant l'implantation du dispositif cardiaque. Résultats: Au total, 2 200 patients ont été inscrits à l'étude. Le taux de signalement de l'allergie à la pénicilline était de 9,3 % (n = 204). Dans 80 % des cas, le type de réaction allergique n'a pas été précisé dans les notes médicales ou était inconnu du patient. Une dose d'essai de céfazoline a été administrée à 67,6 % des patients allergiques à la pénicilline (n = 138). Au total, cinq événements indésirables se sont produits (3,6 % des patients [intervalle de confiance à 95 % : 1,1-6,1 %]) ­ quatre éruptions cutanées et un œdème de la langue. Les cinq patients touchés par ces événements sont devenus asymptomatiques après avoir reçu un antihistaminique et un corticostéroïde par voie intraveineuse. Même en l'absence de réaction allergique à la dose d'essai, 79 % des patients ont reçu de la vancomycine avant l'intervention, cet agent devant être administré par perfusion durant une heure avant la dose d'essai de céfazoline dans la salle d'intervention. Conclusion: Chez la plupart des patients allergiques à la pénicilline, une dose d'essai de céfazoline semble sans danger et permet d'avoir recours à ce médicament conformément aux lignes directrices.

Extraembryonic proteases regulate Nodal signalling during gastrulation.

During gastrulation, a cascade of inductive tissue interactions converts pre-existing polarity in the mammalian embryo into antero-posterior pattern. This process is triggered by Nodal, a protein related to transforming growth factor-beta (TFG-beta) that is expressed in the epiblast and visceral endoderm, and its co-receptor Cripto, which is induced downstream of Nodal. Here we show that the proprotein convertases Spc1 and Spc4 (also known as Furin and Pace4, respectively) are expressed in adjacent extraembryonic ectoderm. They stimulate Nodal maturation after its secretion and are required in vivo for Nodal signalling. Embryo explants deprived of extraembryonic ectoderm phenocopy Spc1(-/-); Spc4(-/-) double mutants in that endogenous Nodal fails to induce Cripto. But recombinant mature Nodal, unlike uncleaved precursor, can efficiently rescue Cripto expression. Cripto is also expressed in explants treated with bone morphogenetic protein 4 (BMP4). This indicates that Nodal may induce Cripto through both a signalling pathway in the embryo and induction of Bmp4 in the extraembryonic ectoderm. A lack of Spc1 and Spc4 affects both pathways because these proteases also stimulate induction of Bmp4.

Twiddler Syndrome without Lead Dislodgment Discovered by Remote Monitoring.

Twiddler syndrome is an uncommon yet dangerous phenomenon usually resulting in lead displacement with loss of capture of cardiac implantable electronic devices. In this case report, we present an interesting case of Twiddler syndrome without lead dislodgment which was detected by an alert triggered by an increase in impedance on remote monitoring.

Characterization of the insoluble proteome of Lactococcus lactis by SDS-PAGE LC-MS/MS leads to the identification of new markers of adaptation of the bacteria to the mouse digestive tract.

We characterized the insoluble proteome of Lactococcus lactis using 1D electrophoresis-LC-MS/MS and identified 313 proteins with at least two different peptides. The identified proteins include 89 proteins having a predicted signal peptide and 25 predicted to be membrane-located. In addition, 67 proteins had alkaline isoelectric point values. Using spectra and peptide counts, we compared protein abundances in two different conditions: growth in rich medium, and after transit in the mouse digestive tract. We identified the large mechanosensitive channel and a putative cation transporter as membrane markers of bacterial adaptation to the digestive tract.

Ventricular Arrhythmia in Septal and Apical Hypertrophic Cardiomyopathy: The French-Canadian Experience.

Background: Apical hypertrophic cardiomyopathy (aHCM) is thought to have a more benign clinical course compared to septal HCM (sHCM), but most data have been derived from Asian cohorts. Comparative data on clinical outcome in Caucasian aHCM cohorts are scarce, and the results are conflicting. The aim of this study was to estimate the prevalence and outcome of aHCM in French-Canadians of Caucasian descent. Methods and results: We conducted a retrospective, single-center cohort study. The primary endpoint was a composite of documented sustained ventricular arrhythmia (VA), appropriate ICD therapy, arrhythmogenic syncope, cardiac arrest, or all-cause mortality. A total of 301 HCM patients (65% males) were enrolled including 80/301 (27%) with aHCM and 221/301 (73%) with sHCM. Maximal wall thickness was similar in both groups. Left ventricular apical aneurysm was significantly more common in aHCM (10 vs. 0.5%; p < 0.001). The proportion of patients with myocardial fibrosis ≥ 15% of the left ventricular mass was similar between aHCM and sHCM (21 vs. 24%; p = 0.68). Secondary prevention ICDs were more often implanted in aHCM patients (16 vs. 7%; p = 0.02). The primary endpoint occurred in 26% of aHCM and 10.4% of sHCM patients (p = 0.001) and was driven by an increased incidence of sustained VA (10 vs. 2.3%; p = 0.01). Multivariate analysis identified apical aneurysm and a phenotype of aHCM as independent predictors of the primary endpoint and the occurrence of sustained ventricular tachycardia. Unexplained syncope and a family history of sudden cardiac death were additional predictors for sustained VA. Apical HCM was associated with an increased risk of ventricular arrhythmia even when excluding patients with apical aneurysm. Conclusions: The phenotype of apical HCM is much more common in French-Canadians (27%) of Caucasian descent compared to other Caucasian HCM populations. Apical HCM in French-Canadians is associated with an increased risk for ventricular arrhythmia.

Driving Restrictions and Early Arrhythmias in Patients Receiving a Primary-Prevention Implantable Cardioverter-Defibrillator (DREAM-ICD) Study.

BACKGROUND: Current guidelines recommend 4 weeks of private driving restriction after implantation of a primary-prevention implantable cardioverter-defibrillator (ICD). These driving restrictions result in significant inconvenience and social implications. Advances in medical treatment and ICD programming have lowered the overall rate of device therapies. The objective of this study was to assess the incidence of ICD therapies at 30, 60, and 180 days after implantation. METHODS: Driving Restrictions and Early Arrhythmias in Patients Receiving a Primary-Prevention Implantable Cardioverter-Defibrillator (DREAM-ICD) was a retrospective cohort study conducted at 2 Canadian university centres enrolling patients with new implantation of a primary-prevention ICD. Device programming was standardised according to current guidelines. A total of 803 patients were enrolled. RESULTS: The cumulative rates of appropriate ICD therapies at 30, 60, and 180 days were 0.12%, 0.50%, and 0.75%, respectively. There was no syncope during the first 6 months. The median duration to the first appropriate ICD therapy was 208 (range 23-1109) days after implantation. The rate of inappropriate ICD therapies at 30 days was only 0.2%. Overall, < 13.6% of all appropriate ICD therapies occurred within the first 6 months after implantation. CONCLUSIONS: The rate of appropriate ICD therapies within the first 30 days after device insertion is extremely low in contemporary primary prevention cohorts with guideline-concordant device programming. There was no increased risk for ventricular arrhythmia early after ICD insertion. The results of DREAM-ICD suggest the need for a revision of the existing driving restrictions for primary-prevention ICD recipients.

A Novel Wearable Device for Continuous Ambulatory ECG Recording: Proof of Concept and Assessment of Signal Quality.

Diagnosis of arrhythmic disorders is challenging because of their short-lasting, intermittent character. Conventional technologies of noninvasive ambulatory rhythm monitoring are limited by modest sensitivity. We present a novel form of wearable electrocardiogram (ECG) sensors providing an alternative tool for long-term rhythm monitoring with the potential of increased sensitivity to detect intermittent or subclinical arrhythmia. The objective was to assess the signal quality and R-R coverage of a wearable ECG sensor system compared to a standard 3-lead Holter. In this phase-1 trial, healthy individuals underwent 24-h simultaneous rhythm monitoring using the OMsignal system together with a 3-lead Holter recording. The OMsignal system consists of a garment (bra or shirt) with integrated sensors recording a single-lead ECG and an acquisition module for data storage and processing. Head-to-head signal quality was assessed regarding adequate P-QRS-T distinction and was performed by three electrophysiologists blinded to the recording technology. The accuracy of signal coverage was assessed using Bland-Altman analysis. Fifteen individuals underwent simultaneous 24-h recording. Signal quality and accuracy of the OMgaments was equivalent to Holter-monitoring (84% vs 93% electrophysiologists rating, p = 0.06). Signal coverage of R-R intervals showed a very close overlay between the OMsignal system and Holter signals, mean difference in heart rate of 2 5 bpm. The noise level of OMgarments was comparable to Holter recording. OMgarments provide high signal quality for adequate rhythm analysis, representing a promising novel technology for long-term non-invasive ECG monitoring.

Proteomic investigation of the adaptation of Lactococcus lactis to the mouse digestive tract.

Lactic acid bacteria are used on an industrial scale for the manufacturing of dairy products. It is now intended to develop novel applications of lactic acid bacteria that could be used as living vehicles for the targeting of antigens or therapeutics to the digestive mucosa. The aim of this study was to analyze the adaptations of Lactococcus lactis, a model lactic acid bacteria to the digestive tract and to identify functions required for colonization of the intestine. For this purpose, we combined gnotobiology with proteomics: axenic mice were colonized with a dairy L. lactis strain and the bacterial proteome was examined by 2-DE. As compared to cultures in broth, the proteome profile of bacteria grown in the intestine indicates the activation of metabolic pathways involved in various carbon sources assimilation and suggests the adoption of a mixed acids fermentative metabolism. We identified the product of the ywcC gene as essential for the colonization of the digestive tract and demonstrated that the corresponding gene product (YwcC) possesses a phosphogluconolactonase activity, suggesting an important role of the pentose phosphate pathway for the development of L. lactis in the digestive environment.

Epicardial ablation of ventricular tachycardia in a patient with arrhythmogenic right ventricular dysplasia after failed conventional endocardial ablation: A case for remote navigation with functional image integration.

Arrhythmogenic right ventricular dysplasia (ARVD) is an inheritable heart muscle disease that predominantly affects the right ventricle (RV) and predisposes to ventricular arrhythmias and sudden cardiac death (SCD)1. The natural history is predominantly related to ventricular electric instability which may lead to arrhythmic SCD, mostly in young people and athletes2,3, but may progress with significant RV muscle disease and left-ventricular (LV) involvement and can result in right or biventricular heart failure4. We report on a 54-year-old male with ARVD who underwent an epicardial ventricular tachycardia (VT) ablation using remote magnetic navigation (RMN) after functional imaging from a nuclear perfusion study was fused with a 3D segmentation from computed tomography (CT) imaging.

Utility of a Novel Rapid High-Resolution Mapping System in the Catheter Ablation of Arrhythmias: An Initial Human Experience of Mapping the Atria and the Left Ventricle.

OBJECTIVES: This study sought to assess the clinical efficacy, safety, and clinical utility of a novel electroanatomical mapping system. BACKGROUND: A new mapping system capable of rapidly acquiring detailed maps based on automatic annotation of thousands of points was recently released for clinical use. This is the first description of its utility in humans. METHODS: The first consecutive 20 cases (7 atrial tachycardia, 8 atrial fibrillation, 3 ventricular tachycardia, and 2 ventricular ectopic beat ablations) were analyzed. The system uses a bidirectional deflectable basket catheter with 64 closely spaced mini-electrodes. It automatically accepts and annotates electrograms when a number of predefined criteria are met. RESULTS: Thirty right atrial maps were acquired in 11 (4 to 15) min, consisting of 7,220 (3,467 to 10,947) points, 22 left atrial maps in 11 (6 to 19) min, consisting of 7,818 (4,379 to 12,262) points and 10 left ventricular maps in 37 (14 to 43) min, consisting of 8,709 (2,605 to 15,514) points. The mini-basket catheter could reach all areas of interest without deflectable sheaths. No embolic events, bleeding complications, or endocardial structure damage were observed. Correction of the automatic annotation was performed in 0.02% of points in 4 of 62 maps. The system revealed re-entry circuits of atrial tachyarrhythmias, identified gaps on linear lesions, and identified and correctly annotated the clinical ventricular ectopic beats and channels of slow conduction within ventricular scar. CONCLUSIONS: The novel automatic mapping system was rapid, safe, and efficacious in mapping a variety of cardiac arrhythmias in humans. Further clinical research is needed to optimize its use in the ablation of complex arrhythmias.

Utility of noninvasive arrhythmia mapping in patients with adult congenital heart disease.

Arrhythmia management in patients with adult congenital heart disease (ACHD) is a challenge on many levels, as tachycardic episodes may lead to hemodynamic impairment in otherwise compensated patients even if episodes are only transient. Recently several technical advances, including 3-dimensional (3D) image integration, 3D mapping, and remote magnetic navigation, have been introduced to facilitate curatively intended ablation procedures in patients with ACHD. This review attempts to outline the role of a novel technology of simultaneous, noninvasive mapping in this patient cohort, and gives details of the authors' single-center experience.

Heart failure with anemia: novel findings on the roles of renal disease, interleukins, and specific left ventricular remodeling processes.

BACKGROUND: Anemia is a highly prevalent and strong independent prognostic marker in heart failure (HF), yet this association is not completely understood. Whether anemia is simply a marker of disease severity and concomitant chronic kidney disease or represents the activation of other detrimental pathways remains uncertain. We sought to determine which pathophysiological pathways are exacerbated in patients with HF, reduced ejection fraction (HFrEF) and anemia in comparison with those without anemia. METHODS AND RESULTS: In a prospective study involving 151 patients, selected biomarkers were analyzed, each representing proposed contributive mechanisms in the pathophysiology of anemia in HF. We compared clinical, echocardiographic, and circulating biomarkers profiles among patients with HFrEF and anemia (group 1), HFrEF without anemia (group 2), and chronic kidney disease with preserved EF, without established HF (chronic kidney disease control group 3). We demonstrate here that many processes other than those related to chronic kidney disease are involved in the anemia-HF relationship. These are linked to the pathophysiological mechanisms pertaining to left ventricular systolic dysfunction and remodeling, systemic inflammation and volume overload. We found that levels of interleukin-6 and interleukin-10, specific markers of cardiac remodeling (procollagen type III N-terminal peptide, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase 1, left atrial volume), myocardial stretch (NT-proBNP [N-terminal probrain natriuretic peptide]), and myocyte death (troponin T) are related to anemia in HFrEF. CONCLUSIONS: Anemia is strongly associated not only with markers of more advanced and active heart disease but also with the level of renal dysfunction in HFrEF. Increased myocardial remodeling, inflammation, and volume overload are the hallmarks of patients with anemia and HF. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00834691.

Metabolic adaptation of Lactococcus lactis in the digestive tract: the example of response to lactose.

Lactococcus lactis is a model of food-grade lactic acid bacterium, which can durably colonize the digestive tract of germ-free mice. To study in vivo the bacterial adaptation to a novel nutritional resource brought by alimentation, the lactose-catabolizing strain IL2661 of L. lactis was established in monoxeny in mice. Half of the mice then received a lactose-rich diet. The mouse has no efficient intestinal lactase and is well adapted to a follow-up of the metabolic activity of microbial origin. The analysis of lactose and lactate in the feces suggested that L. lactis was able to use lactose in vivo. We developed a proteomic approach to evaluate in deeper details the metabolic response of the bacterium. We observed that L. lactis switched its metabolism to use the novel carbon source and reduced the level of proteins involved in an alternative mode of ATP production. In parallel, we also found that the amount of proteins involved in transcriptional regulation, transport and catabolism decreased in the presence of lactose. The proteome analysis informed us about the resources used by the bacteria in absence of lactose. In competition experiments, we found that the metabolic adaptation gives a strong ecological advantage to the bacteria able to efficiently utilize lactose.