Background In this multi-centre, randomised, placebo-controlled pilot trial, we investigated the clinical and haemodynamic effects of the endothelin-receptor blocker Bosentan in patients with heart failure, preserved ejection fraction and pulmonary hypertension (PH-HFpEF).Materials and Methods Eligible patients received either 12 weeks of Bosentan therapy, or a placebo drug. Patients were thereafter followed for a further period of 12 weeks without the study medication. At three points during the study (study Commencement, Week 12 and Week 24), a six-minute walk test (6MWT), echocardiographic and laboratory assessments were performed, as well as a quality of life survey. Right heart catheterisation (RHC) was undertaken at commencement only. The study was aborted early, after an interim analysis favoured the placebo.Results Six-minute walk distance (6MWD) did not change in the Bosentan group (309.7 +/- 96.3m (Commencement), 317.0 +/- 126.1m (Week 12), 307.0 +/- 84.4m (Week 24); p = 0.86), but almost reached statistical significance in the placebo group from 328.8 +/- 79.6m, to 361.6 +/- 98.2m and 384.0 +/- 74.9m (Week 24); p = 0.075. In the placebo group, estimated systolic pulmonary artery pressure (measured via echocardiography) significantly decreased (from 62.3 +/- 16.7 mmHg [Commencement], 45.3 +/- 13.9 mmHg [Week 12], to 44.6 +/- 14.5 mmHg [Week 24]; p = 0.014) as did right atrial pressure (13.1 +/- 5.3 [Commencement], 10.0 +/- 3.8 [Week 12], to 9.4 +/- 3.2 [Week 24]; p = 0.046).Conclusion Despite this study's limited sample size and premature cessation, it nevertheless suggests that endothelin receptor blockade in patients with PH-HFpEF may have no beneficial effects and could even be detrimental in comparison to a placebo.

Aims: Guidelines have been published for improving management of chronic heart failure (CHF). We examined the association between improved guideline adherence and risk for all-cause death in patients with stable systolic HF.Methods: Data on ambulatory patients (2006-2010) with CHF and reduced ejection fraction (HF-REF) from the Austrian Heart Failure Registry (HIR Austria) were analysed. One-year clinical data and long-term follow-up data until all-cause death or data censoring were available for 1014 patients (age 65 [55-73], male 75%, NYHA class I 14%, NYHA II 56%, NYHA III/IV 30%). A guideline adherence indicator (GAI [0-100%]) was calculated for each patient at baseline and after 12 +/- 3 months that considered indications and contra indications for ACE-I/ARB, beta blockers, and MRA. Patients were considered Delta GAI-positive if GAI improved to or remained at high levels (>= 80%)Delta GAI50+ positivity was ascribed to patients achieving a dose of >= 50% of suggested target dose.Results: Improvements in GAI and GAI50+ were associated with significant improvements in NYHA class and NT-proBNP (1728 [740-3636] to 970 [405-2348]) (p < 0.001). Improvements in GAI50+, but not GAI, were independently predictive of lower mortality risk (HR 0.55 [95% CI 0.34-0.87; p=0.01]) after adjustment for a large variety of baseline parameters and hospitalisation for heart failure during follow-up.Conclusions: Improvement in guideline adherence with particular emphasis on dose escalation is associated with a decrease in long-term mortality in ambulatory HF-REF subjects surviving one year after registration. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Background: Heart failure (HF) developing in hypertensive patients may occur with preserved or reduced left ventricular ejection fraction (PEF [<= 50 %] or REF [< 50 %]). In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), 42,418 high-risk hypertensive patients were randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin, providing an opportunity to compare these treatments with regard to occurrence of hospitalized HFPEF or HFREF. Methods and Results: HF diagnostic criteria were prespecified in the ALLHAT protocol. EF estimated by contrast ventriculography, echocardiography, or radionuclide study was available in 910 of 1367 patients (66.6 %) with hospitalized events meeting ALLHAT criteria. Cox regression models adjusted for baseline characteristics were used to examine treatment differences for HF (overall and by PEF and REF). HF case fatality rates were examined. Of those with EF data, 44.4 % had HFPEF and 55.6 % had HFREF. Chlorthalidone reduced the risk of HFPEF compared with amlodipine, lisinopril, or doxazosin; the hazard ratios were 0.69 (95%-confidence interval [CI], 0.53-0.91; P = 0.009), 0.74 (95%-CI, 0.560.97; P = 0.032), and 0.53 (95%-CI, 0.38-0.73; P < 0.001), respectively. Chlorthalidone reduced the risk of HFREF compared with amlodipine or doxazosin; the hazard ratios were 0.74 (95%-CI, 0.59-0.94; P = 0.013) and 0.61 (95%CI, 0.47-0.79; P < 0.001), respectively. Chlorthalidone was similar to lisinopril with regard to incidence of HFREF (hazard ratio, 1.07; 95%-CI, 0.82-1.40; P = 0.596). After HF onset, death occurred in 29.2 % of participants (chlorthalidone/ amlodipine/lisinopril) with new-onset HFPEF versus 41.9 % in those with HFREF (P < 0.001; median follow-up, 1.74 years); and in the chlorthalidone/doxazosin comparison that was terminated early, 20.0 % of HFPEF and 26.0 % of HFREF patients died (P = 0.185; median follow-up, 1.55 years). Conclusions: In ALLHAT, with adjudicated outcomes, chlorthalidone significantly reduced the occurrence of new-onset hospitalized HFPEF and HFREF compared with amlodipine and doxazosin. Chlorthalidone also reduced the incidence of new-onset HFPEF compared with lisinopril. Among high-risk hypertensive men and women, HFPEF has a better prognosis than HFREF.

A single-chip full-rate transceiver in 0.13 /spl mu/m standard CMOS consumes less than 1 W. By using a special power-supply concept and a notched high-Q inductor in the VCO, the IC achieves a 0.2 ps rms jitter. A limiting amplifier with a sensitivity of 20 mV at 7 GHz BW enables the CDR to recover data with a BER of <10/sup -12/.

Im letzten Jahrzehnt ist die Zahl der Patienten mit Herzinsuffizienz deutlich angestiegen und stellt heute eines der größten Probleme in den zivilisierten Ländern dar. Während früher die arterielle Hypertonie ursächlich für die Entwicklung einer Herzinsuffizienz war, so ist es heute vorwiegend die koronare Herzkrankheit. Die arterielle Hypertonie ist aber weiterhin neben Diabetes mellitus und Hyperlipidämie ein zusätzlicher Hauptrisikofaktor für die KHK. Neben konservativen Therapieansätzen wie reduzierte Flüssigkeitszufuhr und regelmäßige körperliche Bewegung, insbesondere bei stabiler Herzinsuffizienz, konnten in den letzten Jahrzehnten einzelne Präparategruppen in großen doppelblind randomisierten Studien eine deutliche Mortalitätsreduktion bewirken. ACE-Hemmer und β-Blocker stellen die unverzichtbaren Säulen jeder Basistherapie der Herzinsuffizienz dar. AT1-Rezeptorblocker sind bei ACE-Hemmer und/oder β-Blockerunverträglichkeit indiziert. Dass auch der kombinierte Einsatz aller drei Präparategruppen Vorteile in Bezug auf die Mortalität bringt, konnte in der vor kurzem präsentierten CHARM-Studie gezeigt werden. Der Einsatz von Diuretika ist besonders bei fortgeschrittener Herzinsuffizienz mit Flüssigkeitseinlagerung notwendig und effektiv. Da die unbehandelte Herzinsuffizienz eine hohe Mortalität hat, ist die adäquate und konsequente Behandlung der arteriellen Hypertonie somit ein wichtiger und unabdingbarer Ansatz zur Verhinderung einer Herzinsuffizienz.

Zusammenfassung Im letzten Jahrzehnt ist die Zahl der Patienten mit Herzinsuffizienz deutlich angestiegen und stellt heute eines der größten Probleme in den zivilisierten Ländern dar. Während früher die arterielle Hypertonie ursächlich für die Entwicklung einer Herzinsuffizienz war, so ist es heute vorwiegend die koronare Herzkrankheit. Die arterielle Hypertonie ist aber weiterhin neben Diabetes mellitus und Hyperlipidämie ein zusätzlicher Hauptrisikofaktor für die KHK. Neben konservativen Therapieansätzen wie reduzierte Flüssigkeitszufuhr und regelmäßige körperliche Bewegung, insbesondere bei stabiler Herzinsuffizienz, konnten in den letzten Jahrzehnten einzelne Präparategruppen in großen doppelblind randomisierten Studien eine deutliche Mortalitätsreduktion bewirken. ACE-Hemmer und β-Blocker stellen die unverzichtbaren Säulen jeder Basistherapie der Herzinsuffizienz dar. AT1-Rezeptorblocker sind bei ACE-Hemmer und/oder β-Blockerunverträglichkeit indiziert. Dass auch der kombinierte Einsatz aller drei Präparategruppen Vorteile in Bezug auf die Mortalität bringt, konnte in der vor kurzem präsentierten CHARM-Studie gezeigt werden. Der Einsatz von Diuretika ist besonders bei fortgeschrittener Herzinsuffizienz mit Flüssigkeitseinlagerung notwendig und effektiv. Da die unbehandelte Herzinsuffizienz eine hohe Mortalität hat, ist die adäquate und konsequente Behandlung der arteriellen Hypertonie somit ein wichtiger und unabdingbarer Ansatz zur Verhinderung einer Herzinsuffizienz.

PURPOSE:To present initial experience with emergent stent-graft placement for impending rupture of the descending thoracic aorta.CASE REPORTS:Intramural hematoma (IMH) of the descending thoracic aorta was diagnosed by transesophageal echocardiography and computed tomography in 3 patients with acute onset of severe thoracic pain. Because of signs of impending rupture, e.g., pleural effusion, sustained pain, or transadventitial bleeding, the patients underwent emergency stent-graft placement, which was successful in all cases. No procedure-related complications were observed. Follow-up to 18 months has revealed no evidence of endoleak, and all patients remain free of symptoms.CONCLUSIONS:Emergency stent-graft placement may be a promising alternative to conventional surgery in patients with impending aortic rupture due to IMH.

This paper presents a flexible and efficient approach to deriv ing indirect implications in logic circuits. Indirect implica tions are essential in ATPG, equivalence checking, and netlist optimizati on. Contrary to other methods, our approach is based on a graph model f a circuit’s clause description called the implication grap h. It combines both the flexibility of SAT-based techniques and high e fficiency of structure based methods. As the proposed algorithms oper ate only on the implication graph, they are independent of the chosen logic. Computation of indirect implications is performed by simpl e and efficient graph algorithms. Experimental results for various a pplications relying on indirect implications demonstrate the efficienc y of our approach.