85 research outputs found
Central haemodynamic abnormalities and outcome in patients with unexplained dyspnoea
No full textAims Little data are available regarding prognostic implications of invasive exercise testing in heart failure with preserved ejection fraction (HFpEF). The present study aimed to investigate whether rest and exercise central haemodynamic abnormalities are associated with adverse clinical outcomes in patients with dyspnea.Methods and results Patients with exertional dyspnoea and ejection fraction >= 50% (n = 764) underwent invasive exercise testing and follow-up for heart failure hospitalization or death. There were 117 patients with events over a median follow-up of 2.7 (interquartile range 0.5-4.6) years. Among patients with normal resting pulmonary artery wedge pressure (PAWP) (= 25 mmHg) was present in 187 (24% of cohort) and was associated with 2.4-fold higher risk of events compared to those with normal exercise PAWP (= 15 mmHg, n = 384 [50%]) displayed even higher risk compared to HFpEF with normal resting PAWP (HR 2.24; 95% CI 1.38-3.65; p = 0.001). Similar findings were observed for rest/exercise right atrial pressure, and rest/exercise pulmonary artery pressures. Higher peak oxygen consumption was associated with decreased risk of events, and this relationship was solely explained by exercise cardiac output. In a multivariable-adjusted Cox model, each 1 standard deviation (SD) increase in exercise PAWP was associated with a 41% greater hazard of events (HR 1.41; 95% CI 1.13-1.76; p = 0.002), while each 1 SD decrease in exercise cardiac output was associated with a 37% increased risk (HR 0.63; 95% CI 0.47-0.83; p = 0.001).Conclusions Haemodynamic abnormalities currently used for diagnosis of HFpEF are associated with increased risk for adverse events. Treatments that reduce central pressures while improving cardiac output reserve may offer greatest benefit to improve outcomes in HFpEF. [GRAPHICS]Barry A. Borlaug is supported by R01 HL128526 and U01 HL160226 from the NHLBI and W81XWH2210245 from the United States Department of Defense. Hidemi Sorimachi is supported by a research fellowship from the Uehara Memorial Foundation, Japan. Kazunori Omote is supported by Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad and the JSPS Overseas Research Fellowships from the Japan Society for the Promotion of Science. Frederik H. Verbrugge is supported by a Fellowship of the Belgian American Educational Foundation (BAEF) and by the Special Research Fund (BOF) of Hasselt University (BOF19PD04). Conflict of interest: BAB receives research support from the National Institutes of Health (NIH) and the United States Department of Defense, as well as research grant funding from AstraZeneca, Axon, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, and Tenax Therapeutics; has served as a consultant for Actelion, Amgen, Aria, Axon Therapies, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, NGM, NXT, and VADovations, and is named inventor (US Patent no. 10,307,179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure. All other authors have nothing to disclose.
The authors thank the staff of the Mayo Clinic Earl Wood Catheterization Laboratory and the patients who agreed to participate in research, allowing for this study to be completed
Association between severity of mitral regurgitation and right ventricular function in patients with moderate to severe mitral regurgitation assessed by invasive hemodynamics measurements
No full textPractical Verification of Lenses: Implementing Formally Verified Lenses using agda2hs
No full textagda2hs is a tool which translates a subset of Agda to readable Haskell. Using agda2hs, programmers can implement libraries in this subset of Agda, formally verify them, and then convert them to Haskell. In this paper we present a new, verified implementation of the lens data type, which is used to access data structures in a readable yet functionally pure way. We show successfully verified lenses for record types and tuples, and also present a lens operating on lists that could not be translated properly. We discuss the obstacles encountered during development, and offer thoughts on possible improvements to agda2hs.CSE3000 Research ProjectComputer Science and Engineerin
Sex and central obesity in heart failure with preserved ejection fraction
No full textAims Obesity is a risk factor for heart failure with preserved ejection fraction (HFpEF), particularly in women, but the mechanisms remain unclear. The present study aimed to investigate the impact of central adiposity in patients with HFpEF and explore potential sex differences. Methods and results A total of 124 women and 105 men with HFpEF underwent invasive haemodynamic exercise testing and rest echocardiography. Central obesity was defined as a waist circumference (WC) >= 88 cm for women and >= 102 cm for men. Exercise-normalized pulmonary capillary wedge pressure (PCWP) responses were evaluated by the ratio of PCWP to workload (PCWP/W) and after normalizing to body weight (PCWL). The prevalence of central obesity (77%) exceeded that of general obesity (62%) defined by body mass index >= 30 kg/m(2). Compared to patients without central adiposity, patients with HFpEF and central obesity displayed greater prevalence of diabetes and dyslipidaemia, higher right and left heart filling pressures and pulmonary artery pressures during exertion, and more severely reduced aerobic capacity. Associations between WC and fasting glucose, low-density lipoprotein (LDL) cholesterol, peak workload, and pulmonary artery pressures were observed in women but not in men with HFpEF. Although increased WC was associated with elevated PCWP in both sexes, the association with PCWP/W was observed in women but not in men. The strength of correlation between PCWP/W and WC was more robust in women with HFpEF as compared to men (Meng's test p = 0.0008), and a significant sex interaction was observed in the relationship between PCWL and WC (p for interaction = 0.02). Conclusions Central obesity is even more common than general obesity in HFpEF, and there appear to be important sexual dimorphisms in its relationships with metabolic abnormalities and haemodynamic perturbations, with greater impact in women.Dr. Borlaug is supported by R01 HL128526 and U01 HL160226, from the National Institutes of Health (NIH). Dr. Verbrugge is supported by the Special Research Fund (BOF) of Hasselt University (BOF19PD04). Conflict of interest: B.A.B. has received research funding from NIH/NHLBI, Axon, AstraZeneca, Corvia, Medtronic, GlaxoSmithKline, Mesoblast, Novartis, Tenax Therapeutics, and received consulting fees/advisory board roles for Actelion, Amgen, Aria, Boehringer Ingelheim, Edwards, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, and VADovations. All other authors have nothing to disclose.
The authors thank the staff of the Mayo Clinic Earl Wood Catheterization Laboratory and the patients who agreed to participate in research, allowing for this study to be completed
Self-Testing and Device-Independent Quantum Random Number Generation with Nonmaximally Entangled States
No full textThe generation of random number sequences, that is, of unpredictable sequences free from any structure, has found numerous applications in the field of information technologies. One of the most sensitive applications is cryptography, whose modern practice makes use of secret keys that must indeed be unpredictable for any potential adversary. This type of application demands highly secure randomness generators.This thesis contributes to the device-independent approach to quantum random number generation (DIRNG, for Device-Independent Random Number Generation). Those methods of randomness generation exploit the fundamental unpredictability of the measurement of quantum systems. In particular, the security of device-independent methods does not appeal to a specific model of the device itself, which is treated as a black box. This approach therefore stands in contrast to more traditional methods whose security rests on a precise theoretical model of the device, which may lead to vulnerabilities caused by hardware malfunctions or tampering by an adversary.Our contributions are the following. We first introduce a family of robust self-testing criteria for a class of quantum systems that involve partially entangled qubit pairs. This powerful form of inference allows us to certify that the contents of a quantum black box conforms to one of those systems, on the sole basis of macroscopically observable statistical properties of the black box.That result leads us to introduce and prove the security of a protocol for randomness generation based on such partially entangled black boxes. The advantage of this method resides in its low shared entanglement cost, which allows to reduce the use of quantum resources (both entanglement and quantum communication) compared to existing DIRNG protocols.We also present a protocol for randomness generation based on an original estimation of the black-box correlations. Contrary to existing DIRNG methods, which summarize the accumulated measurement data into a single quantity---the violation of a unique Bell inequality---, our method exploits a complete, multidimensional description of the black-box correlations that allows it to certify more randomness from the same number of measurements. We illustrate our results on a numerical simulation of the protocol using partially entangled states.La génération de suites de nombres aléatoires, c'est-à-dire de suites imprévisibles et dépourvues de toute structure, trouve de nombreuses applications dans le domaine des technologies de l'information. L'une des plus sensibles est la cryptographie, dont les pratiques modernes font en effet appel à des clés secrètes qui doivent précisément être imprévisibles du point de vue d'adversaires potentiels. Ce type d'application exige des générateurs d'aléa de haute sécurité.Cette thèse s'inscrit dans le cadre de l'approche indépendante des appareils des méthodes quantiques de génération de nombres aléatoires (en anglais, Device-Independent Random Number Generation ou DIRNG). Ces méthodes exploitent la nature fondamentalement imprévisible de la mesure des systèmes quantiques. En particulier, l'appellation "indépendante des appareils" implique que la sécurité de ces méthodes ne fait pas appel à un modèle théorique particulier de l'appareil lui-même, qui est traité comme une boîte noire. Cette approche se distingue donc de méthodes plus traditionnelles dont la sécurité repose sur un modèle théorique précis de l'appareil et peut donc être compromise par un dysfonctionnement matériel ou l'intervention d'un adversaire.Les contributions apportées sont les suivantes. Nous démontrons tout d'abord une famille de critères de "self-testing" robuste pour une classe de systèmes quantiques impliquant des paires de systèmes à deux niveaux (qubits) partiellement intriquées. Cette forme d'inférence particulièrement puissante permet de certifier que le contenu d'une boîte noire quantique est conforme à l'un de ces systèmes, sur base uniquement de propriétés statistiques de la boîte observables macroscopiquement.Ce résultat nous amène à introduire et à prouver la sécurité d'une méthode de génération d'aléa basée sur ces boîtes noires partiellement intriquées. L'intérêt de cette méthode réside dans son faible coût en intrication, qui permet de réduire l'usage de ressources quantiques (intrication ou communication quantique) par rapport aux méthodes de DIRNG existantes.Nous présentons par ailleurs une méthode de génération d'aléa basée sur une estimation statistique originale des corrélations des boîtes noires. Contrairement aux méthodes de DIRNG existantes, qui résument l'ensemble des mesures observées à une seule grandeur (la violation d'une inégalité de Bell unique), notre méthode exploite une description complète (et donc multidimensionnelle) des corrélations des boîtes noires qui lui permet de certifier une plus grande quantité d'aléa pour un même nombre de mesures. Nous illustrons ensuite cette méthode numériquement sur un système de qubits partiellement intriqués.Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe
Pulmonary vascular disease in pulmonary hypertension due to left heart disease: pathophysiologic implications
No full textAIMS: Pulmonary hypertension (PH) and pulmonary vascular disease (PVD) are common and associated with adverse outcomes in left heart disease (LHD). This study sought to characterize the pathophysiology of PVD across the spectrum of PH in LHD. METHODS AND RESULTS: Patients with PH-LHD [mean pulmonary artery (PA) pressure >20 mmHg and PA wedge pressure (PAWP) ≥15 mmHg] and controls free of PH or LHD underwent invasive haemodynamic exercise testing with simultaneous echocardiography, expired air and blood gas analysis, and lung ultrasound in a prospective study. Patients with PH-LHD were divided into isolated post-capillary PH (IpcPH) and PVD [combined post- and pre-capillary PH (CpcPH)] based upon pulmonary vascular resistance (PVR <3.0 or ≥3.0 WU). As compared with controls (n = 69) and IpcPH-LHD (n = 55), participants with CpcPH-LHD (n = 40) displayed poorer left atrial function and more severe right ventricular (RV) dysfunction at rest. With exercise, patients with CpcPH-LHD displayed similar PAWP to IpcPH-LHD, but more severe RV–PA uncoupling, greater ventricular interaction, and more severe impairments in cardiac output, O(2) delivery, and peak O(2) consumption. Despite higher PVR, participants with CpcPH developed more severe lung congestion compared with both IpcPH-LHD and controls, which was associated lower arterial O(2) tension, reduced alveolar ventilation, decreased pulmonary O(2) diffusion, and greater ventilation-perfusion mismatch. CONCLUSIONS: Pulmonary vascular disease in LHD is associated with a distinct pathophysiologic signature marked by greater exercise-induced lung congestion, arterial hypoxaemia, RV–PA uncoupling, ventricular interdependence, and impairment in O(2) delivery, impairing aerobic capacity. Further study is required to identify novel treatments targeting the pulmonary vasculature in PH-LHD
Response to Patoulias et al. letter regarding article “Twelve weeks of treatment with empagliflozin in patients with heart failure and reduced ejection fraction:A double-blinded, randomized, and placebo-controlled trial”
No full textLongitudinal Evolution of Cardiac Dysfunction in Heart Failure and Preserved Ejection Fraction With Normal Natriuretic Peptide Levels
No full textDr Borlaug has received research grants from AstraZeneca, Axon, GlaxoSmith-Kline, Medtronic, Mesoblast, Novo Nordisk, and Tenax Therapeutics, along with consulting fees from Actelion, Amgen, Aria, Axon Therapies, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, NGM, NXT, and VADovations. Dr Borlaug is named inventor on an issued patent (US Patent no. 10 307 179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure. The other authors report no conflicts
The authors thank the staff of the Earl Wood Catheterization Laboratory and the patients who agreed to participate in research, allowing for this study to be complete
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