Theo Meister

The blood-gonadal barrier protects the germline from parental exposures. A phenomenon known as intergenerational inheritance suggests that, exceptionally, this barrier can be surpassed with consequences for the subsequent generation. Specific diet regimes and early traumatic experiences have been among the chronic stressors shown to be able to lead to intergenerational inheritance in mammals. Less is known about how acute stress can affect the germline. Cardiac damage leads to several alterations in peripheral organs and, overall, affects blood flow, metabolism, and the immune response. Whether cardiac damage can also affect the reproductive system is not known and might offer new insights into the potential inheritance of cardiovascular disease. Here, we used zebrafish and mouse models to explore the intergenerational role of cardiac damage and repair. In the first week after a cardiac cryolesion, male zebrafish gonads and gametes activated responses associated with inflammation. In sperm, chromatin accessibility was found altered in response to cardiac cryolesion. Offspring of cryoinjured zebrafish males revealed changes in cardiac function and cardiac gene expression. Induction of systemic sterile inflammation in the paternal generation mimicked cardiac injury effects in the following generation, while anti-inflammatory treatments in the injured paternal generation partially recovered F1 cardiac features. Similar features were found in mouse testis after a neonatal injury, and in the hearts of their offspring, suggesting a conserved role of sterile inflammation as a vector for intergenerational transmission of cardiac injury. Teaser: A cardiac injury triggers inflammation. This affects the parental germline and leads to phenotypic alterations in offspring. Graphical

Introduction: Grading of aortic stenosis (AS) is paramount to determine the ideal timing for aortic valve replacement. However, echocardiographic assessment of AS is challenging and subject to inaccuracy. Increased turbulent kinetic energy (TKE) in the aorta, created by a restricted opening stenotic aortic valve, could serve as a new marker for assessing AS severity. However, in this contest, TKE evaluated with ultrasound colour Doppler have not yet been clinically validated. Methods and results: Porcine aortic valves were tested ex-vivo in a left heart mock loop under various flowrates (1, 2.5, and 4 L/min) and three stiffness grades (SGa, SGb, SGc as native, stiffer, and stiffest stiffness grade, respectively). Reference TKE values were obtained using backlight particle tracking velocimetry. In parallel, TKE was estimated from ultrasound colour Doppler measurements by computing the local spatial fluctuations of blood flow velocities. Transvalvular pressure gradients were evaluated both with continuous wave Doppler and pressure sensors (PGaolv). At 4 L/min, pressure gradients with continuous wave Doppler for SGc reached severe AS levels (41 mmHg ± 14). Both TKE measurement methods, adjusted for flow rates, increased significantly across all stiffness grades and distinguished between severe (SGc) and non-severe (SGa and SGb) AS. Conclusion: In this ex-vivo AS model, both TKE measurement methods successfully differentiated severe from non-severe AS. These findings underscore the potential importance of ultrasound colour Doppler echocardiography in estimating energy loss through turbulence, paving the way for the development of a new diagnostic tool for grading AS severity.

Background and Aims: Non-adherence to antihypertensive therapy is a major contributor to poor blood pressure (BP) control, increased cardiovascular risk, and higher healthcare costs. Behavioral economics suggests that financial incentives and mobile-based interventions may support behavior change, yet evidence for such strategies in central Europe is limited. Objective: The BEHAVE-HTN study evaluates whether a multi-faceted medication adherence mobile application (mApp) with behavioral economic principles—including reminders, gamification, and financial incentives—improves medication adherence in patients with hypertension compared to standard of care. Methods: This multi-center, randomized, open-label trial will include 180 outpatients with hypertension taking four or more pills daily. Participants will be randomized into three groups (n = 60 per group): (A) mApp with contingent financial incentives, (B) mApp without incentives, and (C) standard of care. All participants will receive a Medication Event Monitoring System (MEMS) dispenser to objectively track adherence. The primary endpoint is the difference in mean MEMS adherence between group A and the control group at 90 days. A co-primary endpoint compares MEMS adherence in the final vs. initial month of the intervention. Secondary outcomes include changes in BP, app-reported adherence, and patient-reported feedback on the mApp. Results: Currently, participant inclusion has been nearly completed. We are undergoing data clearing and are planning data analysis. These steps are planned for autumn 2025. Conclusion: This study will provide evidence on whether a multi-faceted medication adherence mobile App — with or without financial incentives—can improve medication adherence in hypertensive patients. The findings may support the implementation of mobile health strategies in routine hypertension care. Trial Registration: SNCTP000004345; ClinicalTrials.gov Identifier: NCT04708756

BACKGROUND Non-adherence to antihypertensive therapy is a major contributor to poor blood pressure control, increased cardiovascular risk, and higher healthcare costs. Behavioral economics suggests that financial incentives and mobile-based interventions may support behavior change, yet evidence for such strategies in Central Europe is limited. OBJECTIVE The COLLABREE study evaluates whether a multi-faceted mobile application with behavioral economic principles—including reminders, gamification, and financial incentives—improves medication adherence in patients with hypertension compared to standard of care. METHODS This multi-center, randomized, open-label trial will include 180 outpatients with hypertension taking four or more pills daily. Participants will be randomized into three groups (n = 60 per group): (A) Collabree app with contingent financial incentives, (B) Collabree app without incentives, and (C) standard of care. All participants will receive a Medication Event Monitoring System (MEMS) to objectively track adherence. The primary endpoint is the difference in mean adherence between Group A and the control group at 90 days. A co-primary endpoint compares adherence in the final vs. initial month of the intervention. Secondary outcomes include changes in blood pressure, self-reported adherence, and patient-reported feedback on the app. RESULTS Currently, participant inclusion has been nearly completed. We are undergoing data clearing and are planning data analysis. These steps are planned for autumn 2025. CONCLUSIONS This study will provide evidence on whether a multi-faceted digital intervention—with or without financial incentives—can improve medication adherence in hypertensive patients. The findings may support the implementation of mobile health strategies in routine hypertension care. CLINICALTRIAL SNCTP000004345; ClinicalTrials.gov Identifier: NCT04708756

Cardiovascular diseases represent a leading cause of maternal morbidity and mortality in industrialized countries. High blood pressure during pregnancy is a major driver of short- and long-term cardiovascular health in both mother and child. Screening and adequate treatment of elevated blood pressure before pregnancy significantly reduce mortality risk to mother and child. A 30-year-old woman with middle aortic coarctation (MAC) previously treated with aortic stenting was referred to our cardio-obstetrics with plans to become pregnant. The clinical examination revealed severe hypertension with a significant blood pressure gradient between the upper and lower limbs. The patient underwent computed tomography angiography showing re-stenosis of the aorta. After the analysis of the benefit risk of all treatment options, percutaneous transluminal aortic in-stent re-stenting was performed. Following the intervention, blood pressure profile significantly improved but remained slightly elevated further necessitating the introduction of an antihypertensive therapy. This clinical case condenses several challenges encountered in the management of hypertension in women who plan to become pregnant. Firstly, it emphasizes the fact that secondary causes of chronic hypertension, including MAC, do not have to be overlooked in childbearing age patient. Secondly, it illustrates the need for a multidisciplinary analysis of all available treatment options in view of a future pregnancy. Finally, it discusses the particular follow-up and potential complications in pregnant women with MAC and aortic stent.