Sensors for Rate Responsive Pacing

Advances in pacemaker technology in the 1980s have generated a wide variety of complex multiprogrammable pacemakers and pacing modes. The aim of the present review is to address the different rate responsive pacing modalities presently available in respect to physiological situations and pathological conditions. Rate adaptive pacing has been shown to improve exercise capacity in patients with chronotropic incompetence. A number of activity and metabolic sensors have been proposed and used for rate control. However, all sensors used to optimize pacing rate metabolic demands show typical limitations. To overcome these weaknesses the use of two sensors has been proposed. Indeed an unspecific but fast reacting sensor is combined with a more specific but slower metabolic one. Clinical studies have demonstrated that this methodology is suitable to reproduce normal sinus behavior during different types and loads of exercise. Sensor combinations require adequate sensor blending and cross checking possibly controlled by automatic algorithms for sensors optimization and simplicity of programming. Assessment and possibly deactivation of some automatic functions should be also possible to maximize benefits from the dual sensor system in particular conditions. This is of special relevance in patient whose myocardial contractility is limited such as in subjects with implantable defibrillators and biventricular pacemakers. The concept of closed loop pacing, implementing a negative feedback relating pacing rate and the control signal, will provide new opportunities to optimize dual-sensors system and deserves further investigation. The integration of rate adaptive pacing into defibrillators is the natural consequence of technical evolution

Transcatheter aortic valve implantation in 2015

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Design and Evaluation of Heterobivalent PAR1–PAR2 Ligands as Antagonists of Calcium Mobilization

A novel class of bivalent ligands targeting putative protease-activated receptor (PAR) heteromers has been prepared based upon reported antagonists for the subtypes PAR1 and PAR2. Modified versions of the PAR1 antagonist RWJ-58259 containing alkyne adapters were connected via cycloaddition reactions to azide-capped polyethylene glycol (PEG) spacers attached to imidazopyridazine-based PAR2 antagonists. Initial studies of the PAR1–PAR2 antagonists indicated that they inhibited G alpha q-mediated calcium mobilization in endothelial and cancer cells driven by both PAR1 and PAR2 agonists. Compounds of this novel class hold promise for the prevention of restenosis, cancer cell metastasis, and other proliferative disorders

Metabolic, inflammatory and haemostatic effects of a low-dose continuous combined HRT in women with type 2 diabetes: potentially safer with respect to vascular risk?

BACKGROUND Conventional hormone replacement therapy (HRT) containing conjugated equine oestrogen (CEE) and medroxyprogesterone acetate (MPA) increases triglyceride, C- reactive protein (CRP) and coagulation Factor VII concentrations, potentially explaining their increased coronary heart disease (CHD) and stroke risk. OBJECTIVE To assess the metabolic effects of a continuous combined HRT containing 1 mg oestradiol and 0.5 mg norethisterone or matching placebo. DESIGN Double-blind, randomized placebo-controlled trial. PATIENTS Fifty women with type 2 diabetes. MEASUREMENTS Classical and novel risk factors for vascular disease. RESULTS Triglyceride concentration was not altered (P = 0.31, change in active arm relative to placebo) and low-density lipoprotein (LDL) cholesterol concentration declined 13% (P = 0.018). IL-6 concentration (mean difference -1.42 pg/ml, 95% CI: -2.55 to - 0.29 IU/dl, P = 0.015), Factor VII (-32 IU/dl, -43 to -21 IU/l, P lt 0.001) and tissue plasminogen activator antigen (by 13%, P = 0.005) concentrations fell, but CRP was not significantly altered (P = 0.62). Fasting glucose (P = 0.026) also declined significantly, but there are no significant effects on HBA1c, Factor IX or APC resistance. CONCLUSIONS HRT containing 1 mg oestradiol and 0.5 mg norethisterone may avoid the adverse metabolic effects potentially implicated in the elevated CHD and stroke risk induced by conventional higher dose HRT. This type of preparation may therefore be more suitable than conventional HRT for women at elevated CHD risk such as those with type 2 diabetes. Large randomized controlled trials of such low dose preparations, powered for cardiovascular end points, are now needed

Вплив низькомолекулярної (до 5 кДа) фракції з сердець новонароджених поросят на біохімічні показники сироватки крові щурів після інфаркту міокарда

Досліджено вплив низькомолекулярної (до 5 кДа) фракції з сердець новонароджених поросят, отриманої методом ультрафільтрації, на процес регенерації серцевого м’яза після моделювання катехоламінового інфаркту міокарда щурів у порівнянні з препаратом “Актовегін”. Хроматографічні і біохімічні дослідження показали, що склад низькомолекулярних речовин фракції і препарату “Актовегін” відрізняється кількісно і якісно. В дослідженнях in vivo також виявлені істотні відмінності в ефективності дії “Актовегіну” і низькомолекулярної фракції на процеси відновлення міокарда після експериментального інфаркту. Зокрема, встановлено, що введення фракції до 5 кДа експериментальним тваринам значно прискорювало зниження і нормалізацію активності ензимів-маркерів інфаркту міокарда порівняно з контролем (фізіологічний розчин) і препаратом “Актовегін”.Исследовано влияние низкомолекулярной (до 5 кДа) фракции из сердец новорожденных поросят, выделенной методом ультрафильтрации, на процесс регенерации сердечной мышцы после моделирования катехоламинового инфаркта миокарда крыс в сравнении с препаратом “Актовегин”. Хроматографические и биохимические исследования показали, что состав низкомолекулярных компонентов фракции и препарата “Актовегин” отличается количественно и качественно. В исследованиях in vivo выявлены также значительные отличия в эффективности действия препарата “Актовегин” и низкомолекулярной фракции на процессы восстановления миокарда после экспериментального инфаркта. В частности, установлено, что введение фракции до 5 кДа экспериментальным животным значительно ускоряло снижение и нормализацию активности энзимов-маркеров инфаркта миокарда в сравнении с контролем (физиологический раствор) и препаратом “Актовегин”.The influence of a low-molecular fraction (below 5 kD) isolated from newborn piglet hearts by the method of ultrafiltration on the cardiac muscle regeneration in rats with the model of catecholamine myocardial infarction in comparison with the reference drug Actovegin is investigated. Chromatographic and biochemical studies show that the compositions of low-molecular substances from the fraction and reference preparation Actovegin differ quantitatively and qualitatively. In in vivo studies, the significant differences in the effectivenesses of the action of drug Actovegin and the low-molecular fraction on the regenerative processes in myocardium after experimental infarction are revealed. In particular, it is established that the administration of the fraction below 5 kD to experimental animals causes a decrease and a normalization in the activity of marker enzymes of myocardial infarction in comparison with the control (saline) and preparation Actovegin

Impact of a Right Ventricular Impedance Sensor on the Cardiovascular Responses to Exercise in Pacemaker Dependent Patients

Background. The evaluation of the heart rate (HR) response to exercise is important for the assessment of the rate response algorithm of sensor-controlled pacemakers. This study examined the effects of a right ventricular impedance sensor driven pacemaker on the cardiovascular responses to incremental exercise in pacemaker dependent patients. Methods. Twelve patients (70.5 ± 9.5 years; 5 Females: 7 Males) implanted with an Inos2+ closed loop stimulation (CLS) pacemaker were compared to 12 healthy age and sex matched controls (70.6 ± 4.8 years). All subjects performed the chronotropic assessment exercise protocol (CAEP). Variables of interest included HR, cardiac output (Q), oxygen uptake (Vo2) and blood pressure (BP). Data were analyzed at rest, throughout exercise and during recovery. Furthermore, patient chronotropic responses were compared to a reference chronotropic response slope for aerobic exercise. Results. There were no differences between groups for HR or Q. response throughout exercise. At peak exercise, V.o2 (mL.kg-1.min-1) was higher for the controls (p < 0.05). The patient chronotropic response slope was comparable to the CAEP reference slope from rest to both the anaerobic threshold (AT) and peak exercise. During recovery, no differences were observed between the groups for any parameters or for the HR decay slopes. Conclusions. Up to the anaerobic threshold, the right ventricular impedance sensor driven pacemaker delivered a pacing rate that contributed to an overall cardiovascular response similar to that observed in healthy age matched subjects

The additional value of patient-reported health status in predicting 1-year mortality after invasive coronary procedures: A report from the Euro Heart Survey on Coronary Revascularisation

Objective: Self-perceived health status may be helpful in identifying patients at high risk for adverse outcomes. The Euro Heart Survey on Coronary Revascularization (EHS-CR) provided an opportunity to explore whether impaired health status was a predictor of 1-year mortality in patients with coronary artery disease (CAD) undergoing angiographic procedures. Methods: Data from the EHS-CR that included 5619 patients from 31 member countries of the European Society of Cardiology were used. Inclusion criteria for the current study were completion of a self-report measure of health status, the EuroQol Questionnaire (EQ-5D) at discharge and information on 1-year follow-up, resulting in a study population of 3786 patients. Results: The 1-year mortality was 3.2% (n = 120). Survivors reported fewer problems on the five dimensions of the EQ-5D as compared with non-survivors. A broad range of potential confounders were adjusted for, which reached a p<0.10 in the unadjusted analyses. In the adjusted analyses, problems with self-care (OR 3.45; 95% CI 2.14 to 5.59) and a low rating (≤ 60) on health status (OR 2.41; 95% CI 1.47 to 3.94) were the most powerful independent predictors of mortality, among the 22 clinical variables included in the analysis. Furthermore, patients who reported no problems on all five dimensions had significantly lower 1-year mortality rates (OR 0.47; 95% CI 0.28 to 0.81). Conclusions: This analysis shows that impaired health status is associated with a 2-3-fold increased risk of all-cause mortality in patients with CAD, independent of other conventional risk factors. These results highlight the importance of including patients' subjective experience of their own health status in the evaluation strategy to optimise risk stratification and management in clinical practice

Clinical results with the 31 mm CoreValve™ in large aortic annuli: The importance of implantation technique

The CoreValve Revalving System (CRS) (Medtronic Inc., Minneapolis, MN, USA) is currently available in four sizes: 23 mm, 26 mm, 29 mm and 31 mm. Aim of our study was to assess the acute clinical results after implantation of a 31 mm CRS

Alginate Scaffolds for Mesenchymal Stem Cell Cardiac Therapy: Influence of Alginate Composition

Despite the success of alginate scaffolds and mesenchymal stem cells (MSCs) therapy in cardiac failure treatment, the impact of the physicochemical environment provided by alginate matrices on cell behavior has never been investigated. The purpose of this work was double: to determine the alginate composition influence on (1) encapsulated rat MSC viability, paracrine activity, and phenotype in vitro and (2) cardiac implantability and in vivo biocompatibility of patch shape scaffolds. Two alginates, differing in composition and thus presenting different mechanical properties when hydrogels, were characterized. In both cases, encapsulated MSC viability was maintained at around 75%, and their secretion characteristics were retained 28 days postencapsulation. In vivo study revealed a high cardiac compatibility of the tested alginates: cardiac parameters were maintained, and rats did not present any sign of infection. Moreover, explanted hydrogels appeared surrounded by a vascularized tissue. However, scaffold implantability was highly dependent on alginate composition. G-type alginate patches, presenting higher elastic and Young moduli than M-type alginate patches, showed a better implantation easiness and were the only ones that maintained their shape and morphology in vivo. As a consequence of alginate chemical composition and resulting hydrogel structuration, G-type alginate hydrogels appear to be more adapted for cardiac implantation