Beyond Pressure Gradients: The Effects of Intervention on Heart Power in Aortic Coarctation

Background In aortic coarctation, current guidelines recommend reducing pressure gradients that exceed given thresholds. From a physiological standpoint this should ideally improve the energy expenditure of the heart and thus prevent long term organ damage. Objectives The aim was to assess the effects of interventional treatment on external and internal heart power (EHP, IHP) in patients with aortic coarctation and to explore the correlation of these parameters to pressure gradients obtained from heart catheterization. Methods In a collective of 52 patients with aortic coarctation 25 patients received stenting and/or balloon angioplasty, and 20 patients underwent MRI before and after an interventional treatment procedure. EHP and IHP were computed based on catheterization and MRI measurements. Along with the power efficiency these were combined in a cardiac energy profile. Results By intervention, the catheter gradient was significantly reduced from 21.8±9.4 to 6.2±6.1mmHg (p<0.001). IHP was significantly reduced after intervention, from 8.03±5.2 to 4.37±2.13W (p < 0.001). EHP was 1.1±0.3 W before and 1.0±0.3W after intervention, p = 0.044. In patients initially presenting with IHP above 5W intervention resulted in a significant reduction in IHP from 10.99±4.74 W to 4.94±2.45W (p<0.001), and a subsequent increase in power efficiency from 14 to 26% (p = 0.005). No significant changes in IHP, EHP or power efficiency were observed in patients initially presenting with IHP < 5W. Conclusion It was demonstrated that interventional treatment of coarctation resulted in a decrease in IHP. Pressure gradients, as the most widespread clinical parameters in coarctation, did not show any correlation to changes in EHP or IHP. This raises the question of whether they should be the main focus in coarctation interventions. Only patients with high IHP of above 5W showed improvement in IHP and power efficiency after the treatment procedure. Trial Registration clinicaltrials.gov NCT02591940


Title of the study
Computer-aided analysis and prediction of the hemodynamic result of treatment strategies for heart disease 2. Ethics Commission -request number (is assigned by the EK) 3. Decisions of other ethics committees in the same case None, but there is a large overlap of the ethics commission of the Charité approved applications EA2/018/09 and EA2/124/07 and especially EA2/110/10 (10.11.2010) 4. The purpose of the study and its objectives; indication of the hypotheses, separated into primary and secondary hypotheses as well as the clinical parameters (primary and secondary endpoints), on the basis of which the hypotheses checked The purpose of the study is the analysis and prediction of the hemodynamic result of interventions in patients with heart disease, particularly stenosis of the aortic isthmus, the pulmonary arteries and the aortic valve. To this end, image-based (MRI) modeling of the function Hypothesis: The image-based modeling can predict hemodynamic parameters. Thus, for a diagnostic heart catheter examination could be replaced, and the hemodynamic effects before the intervention can be simulated and optimized, aiming towards optimized outcome. 5. Explanation of the importance of the study In stenosis of the arteries and the aortic isthmus are often in the course of growth of heart catheterbased interventions, e.g. balloon dilatations or stent placement, necessary. In aortic valve disease it is important to choose the right timing for a valve replacement, as the valve durability is limited (prevention of early intervention) and thus avoide the emergence to heart failure (avoid later complications and reinterventions). For all interventions, it is also important to achieve physiological conditions, because otherwise the risk for re-interventionen increases. With the help of the planned study we will investigate methods with which the hemodynamic effects of an intervention can be simulated (e.g. image-based modeling). MR image data as well as the pressure values of heart catheter investigations are carried out in the framework of routine diagnostics will be used for the image-based modeling.
In patients consenting an MRI exam after an intervention (heart catheter or surgery) will be scheduled without the use of contrast agent. If after intervention (heart catheter or surgery) a clinical indication for an MRI control exists, any of these data is also be supplied to the analysis. 11. Evaluation and consideration of the foreseeable risks and disadvantages of study participation against the expected benefits for the study participants and will in future be ill persons (benefit-risk assessment) Disadvantages are not to be expected.

A. Predictable therapeutic benefit for the study participants ( individual benefits for the individual patient)
By modeling, participating patients could benefit from gain of knowledge for the future if re-interventions are neccessary and ideally invasive diagnostic heart catheterization. In addition, heart catheter intervention/surgical procedures could be optimized in the future. As Foreseeable medical benefit for the future in the diseased persons ( group use) In future diseased patients diagnostic heart catheter examinations can ideally be replaced by MRI. In addition, the optimized results after heart catheter intervention/OP are expected. C). Risks and burdens to the study participants (all in each list) The MRI study without contrast agent application is in compliance with the safety guidelines, and is without any proven risks.

A. Presentation and any explanation of the inclusion and exclusion criteria
Inclusion criteria were any of the following diseases: pulmonary stenosis, aortic coarctation, aortic aortic valve disease in which MRI image data are available with the intervention Participant information (presented orally and in writing and specify how much time remains between information and Consent (written information as an attachment) Orally by the leader of the study or study physicians as well as written participant information and informed consent (see appendix) In congenital heart disease stenoses of the vessles (e.g., coarctation), and aortic valve disease (bicuspid aortic valve disease) are frequent congenital heart diseases, and often require interventions in children and in the course of growth are necessary. 19. Relationship between study participants and study doctor/doctor (is the study doctor at the same time the doctor?) The study physician is also the treating physician. 20. Declaration on the inclusion of possible from the Sponsor dependent persons n.a.

21.
Measures which allow a determination as to whether a study participants can be participating in several studies at the same time or before the expiry of a specified in the previous study period takes part is the participation in several studies possible?
A simultaneous participation in another study is possible. 28. Procedure to protect the confidentiality of stored data, documents and any samples, presentations of pseudonym coding or anonymization of the data and samples of study participants (initials and date of birth as the encoding scheme are not allowed!) -a description of the separation of medical records, study documentation and assignment of the personal data -the access rights including access to participant identification lists during and after the study by management -Detailed description of the procedure for the transmission, encryption, blocking and deletion (including an indication of any network structure and used server).
On inclusion each participant will be assigned a unique and randomly generated number (ID). For the evaluation of the study associated MRI results and heart catheter findings are only such data used in which the personal characteristics (Name, First Name, Sex, Date of birth, address) by this ID have been replaced.
The study documentation records are separate from the medical records in a locked cabinet. Access to the study documentation including the Participant Identification lists are available to the study leader and instructed employees, which can be study physicians and/or nurses. The study-related data (image data, test results) will be stored on research servers within the DHZB (Intranet). The participant identification lists are stored on a separate computer to which only the study leader and IT staff have access.
29. Declaration on compliance with the Data Protection -assurance that all collected data are stored confidential (respecting data secrecy and medical confidentiality legislation).
-assurance that the identifying Data only the study director or his delegate employees are accessible. -indication of the type of measures to ensure the confidentiality -measures for data protection of transfer of data to third parties no personal reference. -indication of the type of information the extinguishing capabilities -measures to ensure the rights of the participants.
Personal data (First Name, Last Name, Gender, date of birth, address) including disease specific and health care data, in the course of this study are to be collected and the results of the study are associated additional investigations in the event of a study participation are processed as follows: The study physician to whom consent will be fiven first assesses the personal data and records this in the declaration of consent, then a pseudonym will be assigned. All associated study collected and acquired health and disease data as well as the results of the study will be used together with the previously formed pseudonym stored. The key to this data is on a separate computer stored separately on another computer. This is only available to the study leader or instructed employees. After archiving according to the legal retention period, the study data are destroyed or deleted. The publication of the findings of the study will be anonymous at all times. The study leader and commissioned staff have access to in the framework of the study collected data.
Decisions regarding the publication of the data are the responsibility of the director of studies. The publication is always anonymous.
33. Details of the financing of the study : Funding Source (Name and Seat) The project CARDIOPROOF is funded by the European Commission, Brussels.
Name and signature of the applicant: I hereby declare that the information given in this application is correct. I am of the opinion that it is possible that the above study in accordance with the protocol that the national legislation.
I know that I in accordance with §19 Berlin Data Protection Act (BlnDSG) am committed, for automated processing of personal and personobtainable Daten a file and description of methods to create and according to §19a the data protection officer of the Charité has to provide. I am informed that if it is a procedure that allows the data to be processed to a professional secrecy (e.g. medical confidentiality), i according to §5 BlnDSG before using this procedure a prior checking by the Data Protection Officer of the Charité and i must arrange for the procedure only in the case of a positive test result may apply.