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Both acute and advanced heart failure are an increasing threat in term of survival, quality of life and socio-economical burdens. Paradoxically, the use of successful treatments for chronic heart failure can prolong life but—per definition—causes the rise in age of patients experiencing acute decompensations, since nothing at the moment helps avoiding an acute or final stage in the elderly population. To complicate the picture, acute heart failure syndromes are a collection of symptoms, signs and markers, with different aetiologies and different courses, also due to overlapping morbidities and to the plethora of chronic medications. The palette of cardio-and vasoactive drugs used in the hospitalization phase to stabilize the patient’s hemodynamic is scarce and even scarcer is the evidence for the agents commonly used in the practice (e.g. catecholamines). The pipeline in this field is poor and the clinical development chronically unsuccessful. Recent set backs in expected clinical trials for new agents in acute heart failure (AHF) (omecamtiv, serelaxine, ularitide) left a field desolately empty, where only few drugs have been approved for clinical use, for example, levosimendan and nesiritide. In this consensus opinion paper, experts from 26 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, The Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, Turkey, U.K. and Ukraine) analyse the situation in details also by help of artificial intelligence applied to bibliographic searches, try to distil some lesson-learned to avoid that future projects would make the same mistakes as in the past and recommend how to lead a successful development project in this field in dire need of new agents., SCOPUS: re.j, info:eu-repo/semantics/published

Über die Zeit hinweg betrachtet, zerfallen unsere IT-Lösungen in Einzelteile. Das hat zur Folge, dass Systeme aus immer mehr einzelnen Bestandteilen bestehen, die es zu integrieren und zu betreiben gilt.

Background: \ud The angiotensin receptor–neprilysin inhibitor sacubitril–valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor–neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear.\ud \ud Methods: \ud We randomly assigned 4822 patients with New York Heart Association (NYHA) class II to IV heart failure, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril–valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. Primary outcome components, secondary outcomes (including NYHA class change, worsening renal function, and change in Kansas City Cardiomyopathy Questionnaire [KCCQ] clinical summary score [scale, 0 to 100, with higher scores indicating fewer symptoms and physical limitations]), and safety were also assessed.\ud \ud Results: \ud There were 894 primary events in 526 patients in the sacubitril–valsartan group and 1009 primary events in 557 patients in the valsartan group (rate ratio, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P=0.06). The incidence of death from cardiovascular causes was 8.5% in the sacubitril–valsartan group and 8.9% in the valsartan group (hazard ratio, 0.95; 95% CI, 0.79 to 1.16); there were 690 and 797 total hospitalizations for heart failure, respectively (rate ratio, 0.85; 95% CI, 0.72 to 1.00). NYHA class improved in 15.0% of the patients in the sacubitril–valsartan group and in 12.6% of those in the valsartan group (odds ratio, 1.45; 95% CI, 1.13 to 1.86); renal function worsened in 1.4% and 2.7%, respectively (hazard ratio, 0.50; 95% CI, 0.33 to 0.77). The mean change in the KCCQ clinical summary score at 8 months was 1.0 point (95% CI, 0.0 to 2.1) higher in the sacubitril–valsartan group. Patients in the sacubitril–valsartan group had a higher incidence of hypotension and angioedema and a lower incidence of hyperkalemia. Among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit with sacubitril–valsartan in patients with lower ejection fraction and in women.\ud \ud Conclusions: \ud Sacubitril–valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failure and an ejection fraction of 45% or higher. (Funded by Novartis; PARAGON-HF ClinicalTrials.gov number, NCT01920711.)

This study sought to evaluate the incidence, the predictors, and the associations with outcomes of changes in ejection fraction (EF) in heart failure (HF) patients.EF determines therapy in HF, but information is scarce about incidence, determinants, and prognostic implications of EF change over time.Patients with ≥2 EF measurements were made in the Swedish Heart Failure Registry were categorized as heart failure with preserved ejection fraction (HFpEF) (EF ≥50%), heart failure with midrange ejection fraction (HFmrEF) (EF 40% to 49%), or heart failure with reduced ejection fraction (HFrEF) (EF 40%). Changes among categories were recorded, and associations among EF changes, predictors, and all-cause mortality and/or HF hospitalizations were analyzed using logistic and Cox regressions.Of 4,942 patients at baseline, 18% had HFpEF, 19% had HFmrEF, and 63% had HFrEF. During follow-up, 21% and 18% of HFpEF patients transitioned to HFmrEF and HFrEF, respectively; 37% and 25% of HFmrEF patients transitioned to HFrEF and HFpEF, respectively; and 16% and 10% of HFrEF patients transitioned to HFmrEF and HFpEF, respectively. Predictors of increased EF included female sex, cases of less severe HF, and comorbidities. Predictors of decreased EF included diabetes, ischemic heart disease, and cases of more severe HF. Use of renin-angiotensin-system inhibitors was associated with lower likelihood of EF increase, but not with EF decrease, i.e., stable EF. Increased EF was associated with a lower risk (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.55 to 0.69) and decreased EF with a higher risk (HR: 1.15; 95% CI: 1.01 to 1.30) of mortality and/or HF hospitalizations. Prognostic implications were most evident for transitions to and from HFrEF.Increases in EF occurred in one-fourth of HFrEF and HFmrEF patients, and decreases occurred in more than one-third of patients with HFpEF and HFmrEF. EF change was associated with a wide range of important clinical and organizational factors as well as with outcomes, particularly transitions to and from HFrEF.

U ovom radu je opisan postupak projektiranja analogne aktivne audio skretnice korak po korak služeći se programom FilterShop. Prvi korak bio je pronalaženje idealne prijenosne karakteristike pojedinih sekcija te cijelog sustava. Kako bi ubrzali i olakšali optimizaciju pojedinih sekcija sustav je prvotno modeliran pomoću generičkih prijenosnih funkcija. Takav postupak omogućuje pronalaženje parametara idealne prijenosne karakteristike bez korištenja relativno složenih krugova. Nakon pronalaženja optimiziranih prijenosnih funkcija pojedinih sekcija krenulo se u realizaciju audio skretnice. Prijenosne funkcije 2. reda su realizirane pomoću Kerwin-Huelsman-Newcomb (KHN) univerzalne filtarske sekcije, a u proračunu je korišten algoritam napisan u MATLABU. Za prijenosne karakteristike 1. reda upotrebljeni su aktivni visokopropusni ili niskopropusni filtri 1. reda u neinvertirajučem spoju. Ukupni odziv realizirane audio skretnice se podudara sa optimiziranim odzivom. This final thesis describes the process of designing analog audio active crossover by using the FilterShop. First step is finding the ideal transfer function of separate sections and of complete system. To accelerate optimization, the system is first constructed by generic transfer functions. In this way complicated circuitry is avoided. Second step includes realization of audio crossover. Second-order transfer functions are implemented with Kerwin-Huelsman-Newcomb (KHN) general-purpose (GP) section. To make the design of general-purpose section easier MATLAB function, which calculates values of elements, was written. First-order functions are implemented with acitive highpass or lowpass noninverting filters. Complete system response matches with optimized response from the first part.

Cilj prvog dijela rada je napraviti trosmjernu aktivnu digitalnu skretnicu s točkama skretanja od 200 Hz i 2 kHz, optimiziranim IIR odzivom u programskom alatu FilterShop. Tri su zvučnika koja se nalaze u zvučničkoj kutiji – niskotonski, srednjetonski i visokotonski te na svaki od njih treba doći audio signal odgovarajuće frekvencije. Potrebno je također kompenzirati propade u točkama skretanja, što se radi koristeći razne mogućnosti i opcije programskog alata FilterShop. Također, dizajnirana su tri pasivna ljestvičasta RLC filtra koji dokazano imaju manju osjetljivost na tolerancije elemenata u pojasu propuštanja. Oni su pretvoreni u digitalne valne filtre koji imaju manju osjetljivost na kvantizaciju koeficijenata, a dizajn je provjeren u programu MATLAB. Uspoređena je osjetljivost klasičnog IIR digitalnog filtra s ljestvičastim digitalnim valnim filtrom i dobiveni rezultati su u skladu s Fettweis-Orchardovim teoremom – digitalni valni filtar pokazao je puno manju osjetljivost promjena njegove amplitudno-frekvencijske karakteristike na efekte kvantizacije koeficijenata u pojasu propuštanja. The objective of the first part of the thesis is to get a three-way active digital crossover with crossover points of 200 Hz and 2 kHz, optimized IIR response in design tool FilterShop. There are three speakers in the box – woofer, midrange and tweeter, and therefore on each of them an audio signal of the corresponding frequency has to arrive. It is also necessary to compensate for the dips in crossover points, which is done using a variety of features and options of the software tool FilterShop. Also, three passive RLC ladder filters are designed, that are proved to have lower sensitivity to component tolerances in the passband of the filter. They have been transformed into digital wave filters having lower sensitivity to coefficient quantization and the design has been tested and verified in the program MATLAB. Sensitivity of the digital wave filter has been compared to the sensitivity of the classical IIR digital filter and the obtained results are along the Fettweis-Orchard theorem – digital wave filter is less sensitive to changes of its amplitude-frequency characteristic due to coefficient quantization effect in the passband.

Detta examensarbete utfördes på Syntronics kontor i Linköping. De hade en idé om att göra en porttelefon med hjälp av ett kretskort som de själva utvecklat, Midrange-plattformen. Detta kretskort är till för att vara flexibelt och kunna användas till olika syften. De förutsättningar jag utgick ifrån var att fortsätta på ett annat projekt som hade undersökt möjligheterna till att koppla in en videokamera till Midrange-plattformen. Jag skulle således fortsätta med samma hårdvara som de valt ut och använt. Min uppgift var att utveckla en Android tablet-app samt ta fram ett protokoll för överföring av bilder/video från Midrange-plattformen till Androidappen. Resultatet blev en Androidapp och ett egendefinierat protokoll för överföring av bilder. Men då problem uppstod med användningen av den kamera som jag fick gjordes istället en simulerad version av Midrange-plattformen med inkopplad kamera.