Single-chamber Versus Dual-chamber Implantable Cardioverter Defibrillators: Do We Need Physiologic Pacing in The Course?

Background: Many patients with ICD receive different antiarrhythmic drugs (e.g. sotalol, amiodarone, β-blockers) because of ventricular or atrial tachycardias. These drugs can cause AV-block or chronotropic incompetence resulting in a higher percentage of ventricular pacing. Methods: We analyzed in a retrospective study the impact of DDD(R) versus VVI(R) mode on subjective (NYHA classification) and objective parameters [brain natriuretic peptide (BNP), 6 minute walk test, echocardiography] in 12 of 120 patients (age 60.2 ± 11.2 years; 10 males, 2 females) who needed an upgrading of a single to a dual chamber ICD. The ICD had to be upgraded because of chronotropic incompetence in all patients with signs of progressing heart failure. Data were collected in VVI(R)-pacing and after 6 and 12 months in DDD(R)-pacing with a long AV-interval and AV hysteresis to reduce ventricular pacing. Results: The 6 minute walk test (392.4 ± 91.4 vs. 324.6 ± 93.3 m, P < 0.001), NYHA-classification (1.4 ± 0.3 vs. 2.6 ± 0.8, P < 0.0001), BNP (234.1 ± 73.5 vs. 410.4 ± 297.0 pg/ml, P < 0.001), left ventricular ejection fraction (49.8 ± 9.6 vs. 36.5 ± 10.9 %, P < 0.0001) and A-wave (73.6 ± 13.7 vs. 41.0 ± 14.0 cm/sec, P < 0.0001) improved with DDD(R)-pacing after 12 months. The ventricular pacing decreased (84.2 ± 18.1 vs. 1.1 ± 1.7 %, P < 0.0001) after 12 months by DDD(R)-pacing with long AV-interval (220.0 ± 10.4 ms) and AV hysteresis. Conclusion: Our data show a superiority of DDD(R) mode versus VVI(R) mode regarding subjective and objective parameters as NYHA-classification, BNP, 6 minute walk test, left ventricular ejection fraction and left ventricular endsystolic volume after 12 months. The improvements seem to depend on the reduction of ventricular pacing with advanced atrial contraction. But only a small number of patients needed the upgradation

Quantum annealing initialization of the quantum approximate optimization algorithm

The quantum approximate optimization algorithm (QAOA) is a prospective near-term quantum algorithm due to its modest circuit depth and promising benchmarks. However, an external parameter optimization required in QAOA could become a performance bottleneck. This motivates studies of the optimization landscape and search for heuristic ways of parameter initialization. In this work we visualize the optimization landscape of the QAOA applied to the MaxCut problem on random graphs, demonstrating that random initialization of the QAOA is prone to converging to local minima with sub-optimal performance. We introduce the initialization of QAOA parameters based on the Trotterized quantum annealing (TQA) protocol, parameterized by the Trotter time step. We find that the TQA initialization allows to circumvent the issue of false minima for a broad range of time steps, yielding the same performance as the best result out of an exponentially scaling number of random initializations. Moreover, we demonstrate that the optimal value of the time step coincides with the point of proliferation of Trotter errors in quantum annealing. Our results suggest practical ways of initializing QAOA protocols on near-term quantum devices and reveals new connections between QAOA and quantum annealing.Comment: 10 pages, 9 figures; typos corrected, references adde

The prediction of ICD therapy in multicenter automatic defibrillator implantation trial (MADIT) II like patients: a retrospective analysis

Objectives MADIT II like patients have not been compared to patients without an electrophysiological study, patients in whom ventricular tachycardia or fibrillation were induced in an electrophysiological study (EPS) and patients without an inducibility in EPS in one study. Background The multicenter automatic defibrillator implantation trial (MADIT) II showed a benefit of ICD implantation in patients with ischemic heart disease.Methods We performed a retrospective analysis in 93 patients with an ischemic heart disease and an ejection fraction ≤30% who had an ICD implanted with a follow-up at least an 18 months. Patients were divided into 3 groups according to the primary indication for ICD implantation: without EPS (group I), patients in whom ventricular tachycardia or fibrillation were inducible in EPS (group II) or patients without an inducibility in EPS (group III). Results During the mean follow-up of 32.9 ± 16.1 months 289 appropriate ICD therapies and 10 deaths occurred. The incidence of appropriate ICD therapies did not differ significantly between the groups (group I 40%, group II 54% and group III 48% of patients). We found in group II a higher risk of appropriate ICD therapies with occurrence of a specific constellation of EPS values. These patients showed a 15-fold risk (P = 0.005) of an appropriate ICD therapy. Furthermore a brain natriuretic peptide value of 265 pg/ml also predicted an appropriate ICD therapy with a 3.5-fold risk (P = 0.017).Conclusion In the present retrospective study the results of MADIT II were affirmed in the case of incidence of ventricular arrhythmias in patients with an EF < 30% and coronary heart disease. The prediction of an appropriate ICD therapy with EPS was only achieved in patients with inducibility in the EPS

Transition states and greedy exploration of the QAOA optimization landscape

The QAOA is a variational quantum algorithm, where a quantum computer implements a variational ansatz consisting of p layers of alternating unitary operators and a classical computer is used to optimize the variational parameters. For a random initialization the optimization typically leads to local minima with poor performance, motivating the search for initialization strategies of QAOA variational parameters. Although numerous heuristic intializations were shown to have a good numerical performance, an analytical understanding remains evasive. Inspired by the study of energy landscapes, in this work we focus on so-called transition states (TS) that are saddle points with a unique negative curvature direction that connects to local minima. Starting from a local minimum of QAOA with p layers, we analytically construct 2p + 1 TS for QAOA with p + 1 layers. These TS connect to new local minima, all of which are guaranteed to lower the energy compared to the minimum found for p layers. We introduce a Greedy procedure to effectively maneuver the exponentially increasing number of TS and corresponding local minima. The performance of our procedure matches the best available initialization strategy, and in addition provides a guarantee for the minimal energy to decrease with an increasing number of layers p. Generalization of analytic TS and the Greedy approach to other ans\"atze may provide a universal framework for initialization of variational quantum algorithms.Comment: 5 pages, 4 figures, comments are welcom

Avoiding barren plateaus using classical shadows

Variational quantum algorithms are promising algorithms for achieving quantum advantage on nearterm devices. The quantum hardware is used to implement a variational wave function and measure observables, whereas the classical computer is used to store and update the variational parameters. The optimization landscape of expressive variational ansätze is however dominated by large regions in parameter space, known as barren plateaus, with vanishing gradients, which prevents efficient optimization. In this work we propose a general algorithm to avoid barren plateaus in the initialization and throughout the optimization. To this end we define a notion of weak barren plateaus (WBPs) based on the entropies of local reduced density matrices. The presence of WBPs can be efficiently quantified using recently introduced shadow tomography of the quantum state with a classical computer. We demonstrate that avoidance of WBPs suffices to ensure sizable gradients in the initialization. In addition, we demonstrate that decreasing the gradient step size, guided by the entropies allows WBPs to be avoided during the optimization process. This paves the way for efficient barren plateau-free optimization on near-term devices

Novel approaches to whole sporozoite vaccination against malaria

AbstractThe parasitic disease malaria threatens more than 3 billion people worldwide, resulting in more than 200 million clinical cases and almost 600,000 deaths annually. Vaccines remain crucial for prevention and ultimately eradication of infectious diseases and, for malaria, whole sporozoite based immunization has been shown to be the most effective in experimental settings. In addition to immunization with radiation-attenuated sporozoites, chemoprophylaxis and sporozoites (CPS) is a highly efficient strategy to induce sterile protection in humans. Genetically attenuated parasites (GAP) have demonstrated significant protection in rodent studies, and are now being advanced into clinical testing. This review describes the existing pre-clinical and clinical data on CPS and GAP, discusses recent developments and examines how to transform these immunization approaches into vaccine candidates for clinical development

Exhaled breath condensate acidification in acute lung injury

AbstractLung injury in ventilated lungs may occur due to local or systemic disease and is usually caused by or accompanied by inflammatory processes. Recently, acidification of exhaled breath condensate pH (EBC-pH) has been suggested as marker of inflammation in airway disease. We investigated pH, ammonia, lactate, pCO2, HCO3−, IL-6 and IL-8 in EBC of 35 ventilated patients (AECC-classification: ARDS: 15, ALI: 12, no lung injury: 8).EBC-pH was decreased in ventilated patients compared to volunteers (5.85±0.32 vs. 7.46±0.48; P<0.0001). NH4+, lactate, HCO3−, pCO2, IL-6 and IL-8 were analyzed in EBC and correlated with EBC-pH. We observed correlations of EBC-pH with markers of local (EBC IL-6: r=−0.71, P<0.0001, EBC IL-8: r=−0.68, P<0.0001) but not of systemic inflammation (serum IL-6, serum IL-8) and with indices of severity of lung injury (Murray's Lung Injury Severity Score; r=−0.73, P<0.0001, paO2/FiO2; r=0.54, P<0.001). Among factors potentially contributing to pH of EBC, EBC-lactate and EBC-NH4+ were found to correlate with EBC-pH.Inflammation-induced disturbances of regulatory mechanisms, such as glutaminase systems may result in EBC acidification. EBC-pH is suggested to represent a marker of acute lung injury caused by or accompanied by pulmonary inflammation

Effects of Music Listening on Cortisol Levels and Propofol Consumption during Spinal Anesthesia

Background: This study explores effects of instrumental music on the hormonal system (as indicated by serum cortisol and adrenocorticotropic hormone), the immune system (as indicated by immunoglobulin A) and sedative drug requirements during surgery (elective total hip joint replacement under spinal anesthesia with light sedation). This is the first study investigating this issue with a double-blind design using instrumental music. Methodology/Principal Findings: Patients (n = 40) were randomly assigned either to a music group (listening to instrumental music), or to a control group (listening to a non-musical placebo stimulus). Both groups listened to the auditory stimulus about 2 h before, and during the entire intra-operative period (during the intra-operative light sedation, subjects were able to respond lethargically to verbal commands). Results indicate that, during surgery, patients of the music group had a lower propofol consumption, and lower cortisol levels, compared to the control group. Conclusion/Significance: Our data show that listening to music during surgery under regional anesthesia has effects on cortisol levels (reflecting stress-reducing effects) and reduces sedative requirements to reach light sedation