PATHFINDER-CHD: prospective registry on adults with congenital heart disease, abnormal ventricular function, and/or heart failure as a foundation for establishing rehabilitative, prehabilitative, preventive, and health-promoting measures: rationale, aims, design and methods.

BACKGROUND: Adults with congenital heart defects (ACHD) globally constitute a notably medically underserved patient population. Despite therapeutic advancements, these individuals often confront substantial physical and psychosocial residua or sequelae, requiring specialized, integrative cardiological care throughout their lifespan. Heart failure (HF) is a critical challenge in this population, markedly impacting morbidity and mortality. AIMS: The primary aim of this study is to establish a comprehensive, prospective registry to enhance understanding and management of HF in ACHD. Named PATHFINDER-CHD, this registry aims to establish foundational data for treatment strategies as well as the development of rehabilitative, prehabilitative, preventive, and health-promoting interventions, ultimately aiming to mitigate the elevated morbidity and mortality rates associated with congenital heart defects (CHD). METHODS: This multicenter survey will be conducted across various German university facilities with expertise in ACHD. Data collection will encompass real-world treatment scenarios and clinical trajectories in ACHD with manifest HF or at risk for its development, including those undergoing medical or interventional cardiac therapies, cardiac surgery, inclusive of pacemaker or ICD implantation, resynchronization therapy, assist devices, and those on solid organ transplantation. DESIGN: The study adopts an observational, exploratory design, prospectively gathering data from participating centers, with a focus on patient management and outcomes. The study is non-confirmatory, aiming to accumulate a broad spectrum of data to inform future hypotheses and studies. PROCESSES: Regular follow-ups will be conducted, systematically collecting data during routine clinical visits or hospital admissions, encompassing alterations in therapy or CHD-related complications, with visit schedules tailored to individual clinical needs. ASSESSMENTS: Baseline assessments and regular follow-ups will entail comprehensive assessments of medical history, ongoing treatments, and outcomes, with a focus on HF symptoms, cardiac function, and overall health status. DISCUSSION OF THE DESIGN: The design of the PATHFINDER-CHD Registry is tailored to capture a wide range of data, prioritizing real-world HF management in ACHD. Its prospective nature facilitates longitudinal data acquisition, pivotal for comprehending for disease progression and treatment impacts. CONCLUSION: The PATHFINDER-CHD Registry is poised to offer valuable insights into HF management in ACHD, bridging current knowledge gaps, enhancing patient care, and shaping future research endeavors in this domain.

Noninvasive determination of carotid-femoral pulse wave velocity depends critically on assessment of travel distance: a comparison with invasive measurement.

OBJECTIVES: European Society of Hypertension guidelines recommend use of carotid- femoral pulse wave velocity (cfPWV) as a favored measure of aortic stiffness. However, there is no consensus on the measurement of distance travelled by the pulse wave along the aorta to the femoral artery. The aim of our study was to compare cfPWV, calculated with commonly used noninvasive methods for travel distance assessment, against aortic PWV measured invasively. METHODS: One hundred and thirty-five patients had aortic PWV measured invasively during cardiac catheterization, from the delay in wave foot and distance travelled as the catheter was withdrawn from the ascending aorta to the aortic bifurcation. On the following day, noninvasive cfPWV was assessed, using the SphygmoCor system, relating the delay between carotid and femoral wavefoot to travel distance, estimated with five different methods on body surface. RESULTS: Mean travel times were in good agreement [(travel time) TTinvasive was 63 ms, TTnoninvasive was 59.3 ms, Spearman's R: 0.8, P < 0.00001]. Mean PWVinvasive was 8.5 m/s. CfPWV, as assessed noninvasively, depended largely on the method used for travel distance estimation: 11.5, 9.9, 8.7, 11.9, and 9.6 m/s, using direct carotid-femoral distance, carotid-femoral minus carotid-suprasternal notch distances, suprasternal notch-femoral minus carotid-suprasternal notch distances, suprasternal notch-femoral plus carotid-suprasternal notch distances, and suprasternal notch-symphysis distance, respectively. There was acceptable correspondence between PWVinvasive and cfPWVnoninvasive (Spearman's R: 0.73-0.77, P < 0.0001). CONCLUSION: For noninvasive assessment of cfPWV, estimation of pulse wave travel distance is critical. Best agreement with invasive measurements was found for the method of subtracting carotid-suprasternal notch distance from suprasternal notch-femoral distance.

Characterization of the T7 promoter system for expressing penicillin acylase in Escherichia coli.

The pac gene encoding penicillin acylase (PAC) was overexpressed under the regulation of the T7 promoter in Escherichia coli. PAC, with its complex formation mechanism, serves as a unique target protein for demonstration of several key strategies for enhancing recombinant protein production. The current T7 system for pac overexpression was fraught with various technical hurdles. Upon the induction with a conventional inducer of isopropyl-beta-D-thiogalactopyranoside (IPTG), the production of PAC was limited by the accumulation of PAC precursors (proPAC) as inclusion bodies and various negative cellular responses such as growth inhibition and cell lysis. The expression performance could be improved by the coexpression of degP encoding a periplasmic protein with protease and chaperone activities. In addition to IPTG, arabinose was shown to be another effective inducer. Interestingly, arabinose not only induced the current T7 promoter system for pac expression but also facilitated the posttranslational processing of proPAC for maturation, resulting in significant enhancement for the production of PAC. Glycerol appeared to have an effect similar to, but not as significant as, arabinose for enhancing the production of PAC. The study highlights the importance of developing suitable genetically engineered strains with culture conditions for enhancing recombinant protein production in E. coli.