Service Dominant Logic and Business Process Blueprinting: Enhancing the View on Performance by Integrating the Customer Perspective

Today process-oriented approaches to solve business challenges are state of the art. However most business process management methods focus on increased performance only from the firm’s perspective and neglect the increasing importance of value co-creation between the firm and the customer. Modern business process management methods not only need to concentrate on the internal performance of processes, but need to include the customer’s perspective. In this article we introduce the method of “Business Process Blueprinting” that combines both points of view. By enhancing business process modeling with the marketing concept of service blueprinting, we offer a method to visualize and analyze the firm’s and customer’s perspective within one integrated approach and reduce the gap between information management and marketing. This opens up the path towards an enhanced understanding of process performance in terms of a stronger inclusion of revenue into costing and analyzing and influencing subsequent usage processes

Renal and hepatic function of patients with severe tricuspid regurgitation undergoing inferior caval valve implantation

Due to progressive abdominal-venous congestion severe tricuspid regurgitation (TR) is a common cause of cardiorenal and cardiohepatic syndrome. We initiated the TRICAVAL study to compare interventional valve implantation into the inferior vena cava (CAVI) versus optimal medical therapy (OMT) in severe TR. In the present subanalysis, we aimed to evaluate the effects of CAVI on clinical signs of congestion, renal and hepatic function. TRICAVAL was an investigator-initiated, randomized trial. Twenty-eight patients with severe TR were randomized to OMT or CAVI using an Edwards Sapien XT valve. Probands who completed the 3-month follow-up (CAVI [n = 8], OMT [n = 10]) were evaluated by medical history, clinical examination, and laboratory testing at baseline, 3 and 12 months. After 3 months, the CAVI group exhibited a significant reduction of body weight (from 80.7 [69.0-87.7] kg to 75.5 [63.8-84.6] kg, p < 0.05) and abdominal circumference (from 101.5 +/- 13.8 cm to 96.3 +/- 15.4 cm, p <= 0.01) and a trend to lower doses of diuretics compared to OMT. Renal and hepatic function parameters did not change significantly. Within a short-term follow-up, CAVI led to an improvement of clinical signs of venous congestion and a non-significant reduction of diuretic doses compared to OMT

Impact of inferior caval valve implantation on severity of tricuspid regurgitation and right heart function

Aims: Severe tricuspid regurgitation (TR) is a common finding in heart failure patients and associated with increased mortality. New interventional therapeutic options are needed as many heart failure patients are unfit for surgery. The TRICAVAL study compared valve implantation into the inferior vena cava (CAVI) with optimal medical therapy (OMT) in patients with severe TR. Here, we report details on the impact of CAVI on TR severity as well as right heart function and morphology. Methods and results: We randomized 28 patients with severe TR to CAVI (n = 14) with transfemoral implantation of an Edwards Sapien XT valve into the inferior vena cava or OMT (n = 14). Inclusion and exclusion criteria were based on anatomical and clinical parameters. Echocardiographic measurements were performed at baseline, at the first postoperative day and one, three, and twelve months after randomization. As proof of concept of an effective sealing of the inferior vena cava, we detected a significant decrease in systolic hepatic vein reflux volume (11.0 [6.2-21.9] mL vs 3.5 [0.6-8.5] mL,P = .016) and hepatic vein diameter (11.5 [10.0-14.8] mm vs 10.0 [9.3-11.8] mm,P = .034) at thirty-day follow-up. However, CAVI had no significant impact on TR, cardiac function, and morphology. Conclusions: Caval valve implantation significantly reduced systolic reflux into the hepatic veins but was not associated with an improvement in cardiac function, morphology, or TR severity

Associations of 2D speckle tracking echocardiography-based right heart deformation parameters and invasively assessed hemodynamic measurements in patients with pulmonary hypertension

Background: We aimed to evaluate associations of right atrial (RA) and right ventricular (RV) strain parameters assessed by 2D speckle tracking echocardiography (2D STE) with invasively measured hemodynamic parameters in patients with and without pulmonary hypertension (PH). Methods: In this study, we analyzed 78 all-comer patients undergoing invasive hemodynamic assessment by left and right heart catheterization. Standard transthoracic echocardiographic assessment was performed under the same hemodynamic conditions. RA and RV longitudinal strain parameters were analyzed using 2D STE. PH was defined as invasively obtained mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest and was further divided into pre-capillary PH (pulmonary capillary wedge pressure [PCWP] ≤ 15 mmHg), post-capillary PH (PCWP > 15 mmHg) and combined PH (PCWP > 15 mmHg and difference between diastolic PAP and PCWP of ≥7 mmHg). Correlation analyses between variables were calculated with Pearson's or Spearman's correlation coefficient as applicable. Results: Out of 78 patients, 45 presented with PH. Within the PH group, 39 had post-capillary, five had combined pre- and post-capillary PH, and one had pre-capillary PH. Patients with PH had a significantly increased RA area (PH 22.0 ± 9.2 cm2, non-PH 17.3 ± 10.7 cm2; p = 0.003) and end-systolic RV area (PH 14.7 ± 6.1, non-PH 11.9 ± 4.8 cm2; p = 0.022). RV mid strain was significantly reduced in PH (PH -17.4 ± 7.8, non-PH: - 21.6 ± 5.5; p = 0.019). Average peak systolic RA strain (RAS) and average peak systolic RV strain (RVS) showed a significant association with mPAP (r = - 0.470, p = 0.001 and r = 0.490, p = 0.001, respectively) and with PCWP (r = - 0.296, p = 0.048 and r = 0.365, p = 0.015, respectively) in patients with PH. Furthermore, RV apical, mid and basal strain as well as RV free wall strain showed moderate associations with mPAP. In patients without PH, there were no associations detectable between RA or RV strain parameters and mPAP and PCWP. Conclusion: In an all-comer cohort, RA and RV strain parameters showed significant associations with invasively assessed mPAP and PCWP in patients with predominantly post-capillary PH. These associations may be useful in clinical practice to assess the impact of post-capillary PH on myocardial right heart function

Cardiac and renal function in a large cohort of amateur marathon runners

Background Participation of amateur runners in endurance races continues to increase. Previous studies of marathon runners have raised concerns about exercise-induced myocardial and renal dysfunction and damage. In our pooled analysis, we aimed to characterize changes of cardiac and renal function after marathon running in a large cohort of mostly elderly amateur marathon runners. Methods A total of 167 participants of the BERLIN-MARATHON (female n = 89, male n = 78; age = 50.3 ± 11.4 years) were included and cardiac and renal function was analyzed prior to, immediately after and 2 weeks following the race by echocardiography and blood tests (including cardiac troponin T, NT- proBNP and cystatin C). Results Among the runners, 58% exhibited a significant increase in cardiac biomarkers after completion of the marathon. Overall, the changes in echocardiographic parameters for systolic or diastolic left and right ventricular function did not indicate relevant myocardial dysfunction. Notably, 30% of all participants showed >25% decrease in cystatin C-estimated glomerular filtration rate (GFR) from baseline directly after the marathon; in 8%, we observed a decline of more than 50%. All cardiac and renal parameters returned to baseline ranges within 2 weeks after the marathon. Conclusions The increase in cardiac biomarkers after completing a marathon was not accompanied by relevant cardiac dysfunction as assessed by echocardiography. After the race, a high proportion of runners experienced a decrease in cystatin C-estimated GFR, which is suggestive of transient, exercise-related alteration of renal function. However, we did not observe persistent detrimental effects on renal function

Echocardiographic diagnosis, management and monitoring of pulmonary embolism with right heart thrombus in a patient with myotonic dystrophy: a case report

Acute pulmonary embolism (PE) is a common disease which frequently results in life-threatening right ventricular (RV) failure. High-risk PE, presenting with hypotension, shock, RV dysfunction or right heart thrombus is associated with a high mortality, particularly during the first few hours. Accordingly, it is important to commence effective therapy as soon as possible. In the case described in this report, a 49-year-old woman with myotonic dystrophy type 1 presented with acute respiratory failure and hypotension. Transthoracic echocardiography showed signs of right heart failure and a mobile right heart mass highly suspicious of a thrombus. Based on echocardiographic findings, acute thrombolysis was performed resulting in hemodynamic stabilization of the patient and complete resolution of the right heart thrombus. This case underscores the important role of transthoracic echocardiography for the diagnosis, management and monitoring of PE and underlines the efficacy and safety of thrombolysis in the treatment of PE associated with right heart thrombus

A Statin-Loaded Reconstituted High-Density Lipoprotein Nanoparticle Inhibits Atherosclerotic Plaque Inflammation

Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show this effect is mediated through inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show they accumulate in atherosclerotic lesions where they directly affect plaque macrophages. Finally we demonstrate that a three-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a one-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation

Monocytes and macrophages – targets for anti-inflammatory therapies of cardiovascular diseases

Die Atherosklerose und die erworbene Aortenklappenstenose (AS) werden als chronisch inflammatorische Erkrankungen der arteriellen Gefäßwand bzw. des Klappengewebes angesehen. In der Pathogenese beider Erkrankungen spielen Monozyten und Makrophagen eine bedeutende Rolle und stellen daher potentielle Targets für antiinflammatorische Therapieansätze dar. Ziel einer antiinflammatorischen Therapie in der Atherosklerose ist es, die Atherogenese abzuschwächen und darüberhinaus eine Regression bereits bestehender Plaques herbeizuführen. Dazu gilt es den Gehalt an Makrophagen in atherosklerotischen Plaques zu verringern, die nachteiligen Effekte der inflammatorischen M1 Makrophagen abzuschwächen, sowie eine Verschiebung des M1/M2-Verhältnisses in Richtung des antiinflammatorischen M2 Makrophagen Phänotyps zu bewirken. Diese Ziele konnten im Mausmodell durch eine Korrektur der Hypercholesterinämie mittels Erhöhung von funktionalem Apolipoprotein A-I, sowie durch eine lokale Anwendung eines Statins im atherosklerotischen Plaque erreicht werden. Der Gehalt an Makrophagen im Gewebe wird u.a. durch die Rekrutierung von Monozyten aus dem Blut, sowie die Emigration von Makrophagen aus dem Gewebe beeinflusst. Ein genaues Verständnis dieser Prozesse ist von wesentlicher Bedeutung für die Entwicklung neuartiger Therapiekonzepte für die Atherosklerose und die AS. Es konnte gezeigt werden, dass neuronale Guidance-Moleküle (wie Netrin-1 und Semaphorin 3E) eine Retention von Makrophagen in atherosklerotischen Plaques begünstigen können. Für die AS fehlen noch grundlegende Erkenntnisse zu Monozyten-Makrophagen-Abstammungslinien um geeignete Therapieansätze entwickeln zu können. Es werden daher erstmalig Daten zur Verteilung individueller Monozyten-Subpopulationen (klassische, intermediäre und nicht- klassische Monozyten) bei der AS und nach Behandlung der AS mittels eines Aortenklappenersatzes gezeigt. Es konnte nachgewiesen werden, dass der Gehalt an intermediären Monozyten im Blut von Patienten mit hochgradiger AS erhöht ist und im Verlauf nach Beseitigung der AS mittels eines Aortenklappenersatzes abnimmt. Diese Ergebnisse dienen als Ausgangspunkt für weitere Forschungsprojekte zur Rolle der Monozyten-Subpopulationen in der Pathogenese der AS. Monozyten und Makrophagen stellen vielversprechende Targets für die antiinflammatorische Therapie kardiovaskulärer Erkrankungen dar. Die weitere Vertiefung der Erkenntnisse zur Rolle der Monozyten und Makrophagen in der Pathogenese der Atherosklerose und der AS ist notwendig, um den Weg für neuartige Ansätze zur Modulation dieser Zellen und somit für zukünftige antiinflammatorische Therapiestrategien zu bahnen.This work focuses on monocytes and macrophages as targets for anti- inflammatory therapies of cardiovascular diseases

Alternative splicing in intron 13 of the human eNOS gene: a potential mechanism for regulating eNOS activity

Die endotheliale NO-Synthase (eNOS) gilt als Schlüsselenzym der vaskulären Homöostase. Neben seiner Bedeutung als potenter endogener Vasodilatator ist Stickstoffmonoxid (NO), das Produkt der eNOS, für eine Reihe gefäßprotektiver Eigenschaften verantwortlich. Während für die humane iNOS und nNOS eine Reihe von alternativen Splice-Varianten beschrieben sind, existiert bisher kein Nachweis alternativ gespleißter Isoformen für die eNOS. Im Rahmen der hier vorliegenden Arbeit konnten erstmals alternative Splice-Varianten der humanen eNOS nachgewiesen werden. Die drei neuen Splice-Varianten - eNOS13A, eNOS13B und eNOS13C - entsprechen von Exon 1 bis 13 der humanen eNOS. An das Exon 13 schließt sich jeweils ein neues Exon bestehend aus Intron 13 Sequenzen an, gefolgt von einem Poly-A-Schwanz. Im Falle einer Translation der Splice- Varianten entstehen verkürzte eNOS-Proteine, denen große Teile der Reduktase- Domäne fehlen und die keine eigene eNOS-Aktivität besitzen. Die Koexpression von eNOS mit eNOS13A in COS-7 Zellen führte zu einer Abnahme der eNOS- Aktivität durch die Bildung von Heterodimeren. Die Stabilisierung der full- length eNOS-Proteinmenge nach Proteasominhibition deutet auf einen vorzeitigen Abbau der Heterodimere über das Ubiquitin-Proteasom-System hin. Die drei eNOS Splice-Varianten werden nativ in verschiedenen Endothelzellen und in einer Vielzahl humaner Gewebe exprimiert. Eine besonders hohe Expression an eNOS13A- mRNA konnte in humanem Testis-Gewebe nachgewiesen werden. Die Ergebnisse dieser Arbeit zeigen einen neuartigen potentiellen Mechanismus zur Regulation der eNOS-Aktivität und NO-Produktion über dominant-negative Splice-Varianten der humanen eNOS.NO, the product of endothelial NOS (eNOS), is a major regulator of vascular homeostasis and a critical factor in preventing cardiovascular diseases. Whereas for human iNOS and nNOS a number of different splice variants have been described, no such splice isoforms are known for eNOS so far. This study describes three novel splice variants for human eNOS. These splice variants - termed eNOS13A, eNOS13B and eNOS13C - share the first 13 exons of human eNOS followed by novel overlapping exons containing intron 13 sequences. All three splice variants share the same polyadenylation signal followed by a poly-A tail. When translated, these splice-variants would result in truncated eNOS proteins lacking eNOS activity. Coexpression of full-length and eNOS13A in COS-7 cells diminished eNOS enzyme activity by formation of heterodimers. Coexpression in COS-7 cells with inhibition of the proteasome suggest an enhanced degradation of the heterodimers by the ubiquitin-proteasome-system. All three splice-variants were expressed in different endothelial cells and various human tissues. Expression of eNOS13A was particularly high in human testis. Taken together, these data suggest a new mechanism for the regulation of eNOS activity and NO production by dominant-negative splice variants of human eNOS