PRessure-based Evaluation of Disease Improvement in the Course of TAVI (PREDIC-TAVI)

Investigation of the Relationship Between Changes in Modern Wave-Based Hemodynamic Metrics and Procedural Success or Clinical Improvement in Patients With Severe Aortic Stenosis Following Transcatheter Aortic Valve Replacement (TAVR)

The goal of this prospective observational study is to learn if advanced heart pressure wave analysis (using methods called WIA and REPA) can help predict the success of the procedure and long-term recovery in adults (aged 60-90) with severe Aortic Stenosis who are undergoing Transcatheter Aortic Valve Replacement (TAVR/TAVI).

The main questions it aims to answer are:

Do changes in heart pressure wave patterns immediately after the new valve is implanted relate to improvements in a patient's quality of life and heart health over the following year?

Can these advanced wave measurements better predict major heart complications (MACE) at 30 days, 180 days and 1 year compared to standard clinical tests?

Participants will:

Undergo a standard TAVR (TAVI) procedure as part of their regular medical care to replace a narrowed heart valve.

Have their aortic pressure waves recorded through a catheter during the routine procedure (this happens during the surgery and does not require any additional incisions or invasive steps).

Complete quality-of-life surveys (EQ-5D-5L) and clinical assessments before the procedure.

Be followed up via telephone calls or electronic health records at 30 days, 180 days and 12 months after the procedure to check on their recovery and overall health status.

Study Overview

• Status: Not yet recruiting
• Conditions: Aortic Stenosis
• Intervention / Treatment: Procedure: Transcatheter aortic valve replacement (TAVR / TAVI)

Detailed Description

Background and Rationale:

Severe Aortic Stenosis (AS) is characterized by the progressive calcification and narrowing of the aortic valve leaflets, leading to a significant mechanical obstruction in the Left Ventricular Outflow Tract (LVOT). While Transcatheter Aortic Valve Replacement (TAVR) has become the gold standard for high-risk and increasingly intermediate-to-low-risk patients, the clinical response remains heterogeneous. Current procedural success is primarily evaluated using steady-flow metrics such as Mean Pressure Gradient (MG) and Aortic Valve Area (AVA). However, the total workload on the Left Ventricle (LV) is not merely a function of valvular resistance but also involves pulsatile components including arterial compliance, wave reflections, and valvulo-arterial impedance. In many TAVR candidates, concomitant systemic arterial stiffness and reduced vascular compliance complicate the hemodynamic profile, making traditional gradients insufficient to fully characterize the true obstructive load and ventricular performance, e.g. in certain disease endotypes subgroups "paradoxical" low-flow, low-gradient (LFLG) phenotypes.

The PREDIC-TAVI study utilizes state-of-the-art wave mechanics to provide a granular assessment of the cardiovascular system's response to TAVR:

1. Wave Intensity Analysis (WIA): By analyzing simultaneous changes in pressure and flow (or flow-surrogates), WIA identifies the energy flux of forward-traveling waves (Forward Compression Waves [FCW] generated by LV ejection and Forward Expansion Waves [FEW] during relaxation) and backward-traveling waves (Backward Compression Waves [BCW] reflected from the systemic tree and the stenotic valve).
2. Reservoir-Excess Pressure Analysis (REPA): This method decomposes the measured aortic pressure waveform into a reservoir pressure (Pr), reflecting the global arterial storage and compliance dynamics, and an excess pressure (Pxs), representing the dynamic, wave-related component of the pulse. Parameters such as P-infinity (Pinf) serve as proxies for microcirculatory closing pressures.

Study Design and Procedural Methodology: This is a prospective, single-center, observational cohort study. Consecutive patients (aged 60-90 years) with a multidisciplinary "Heart Team" diagnosis of severe AS and a clinical indication for TAVR will be enrolled. The study employs a high-fidelity "pressure-only" approach for hemodynamic analysis. During the routine TAVR procedure, proximal aortic pressure waveforms will be recorded via fluid-filled catheters at a minimum sampling rate of 100 Hz. Recordings will be captured at two specific time points:

• Baseline (Pre-Implantation): Immediately prior to valve deployment under stable hemodynamic conditions.
• Post-Implantation: Following valve deployment and stabilization. Data acquisition occurs within the standard clinical workflow, requiring no additional invasive maneuvers. Waveforms are analyzed offline using standardized signal-processing algorithms (Savitzky-Golay filtering, beat segmentation, and diastolic exponential fitting) to derive delta-WIA and delta-REPA metrics.

Longitudinal Follow-up and Clinical Endpoints: The study aims to correlate acute intra-procedural hemodynamic changes with multidimensional clinical outcomes at three distinct follow-up intervals:

1. 1-Month Follow-up (30 ± 5 days):
2. 6-Month Follow-up (180 ± 14 days):
3. 12-Month Follow-up (1 Year ± 3 weeks):

Primary Outcome Measures:

• Clinical Improvement: Assessed via the change in health-related quality of life using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) index scores and Visual Analog Scale (VAS).
• Major Adverse Cardiovascular Events (MACE): A composite of all-cause mortality, stroke (major/minor), myocardial infarction, and unplanned hospitalizations due to heart failure or valve dysfunction, classified according to Valve Academic Research Consortium 3 (VARC-3) criteria. All cause mortality and any ED admissions are separately assessed.

Statistical Analysis Plan: The relationship between hemodynamic deltas and clinical outcomes will be analyzed using Pearson/Spearman correlations and linear regression. To account for the longitudinal follow-up and baseline clinical covariates (e.g., age, gender, comorbidities, and baseline LVEF), Generalized Linear Mixed Models (GLMM) will be utilized. Receiver Operating Characteristic (ROC) curves and Area Under the Curve (AUC) values will be calculated to determine the predictive power of wave-based metrics for 1-year MACE. OR/HR will be calculated for endpoints.

Sample Size Rationale: Based on current literature, TAVR is expected to significantly increase FCW energy and Pxs. To detect a moderate correlation (r=0.35) between these changes and the EQ-5D-5L index with 80% power and 5% alpha, a minimum of 62 patients is required. To ensure robust 1-year MACE prediction (assuming a 28% event rate in the TAVR population per SWEDEHEART registry data) and to account for technical or follow-up attrition, a target enrollment of at least 100 consecutive patients is established.

Scientific Contribution: The PREDIC-TAVI-IMAEH study seeks to define a new "physiological success" signature for TAVR. By moving beyond static gradients, this research aims to improve the diagnostic and prognostic algorithms for severe AS, providing clinicians with sensitive markers to optimize valve deployment and better anticipate the recovery trajectory of complex cardiovascular patients.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Serkan Aslan, Ass. Prof MD; Phone Number: +90(212) 692 20 00; Email: drserkanaslan@gmail.com
• Study Contact Backup: Name: Ahmet Tas, MD PhD; Phone Number: +90(212) 692 20 00; Email: ahmettas.cor@gmail.com

Study Locations

• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye)
    • Istanbul Mehmet Akif Ersoy Educational and Training Hospital
    • Principal Investigator: Serkan Aslan, Ass Prof MD
    • Principal Investigator: Ahmet Tas, MD PhD
    • Principal Investigator: Mehmet Erturk, Prof MD
    • Sub-Investigator: Gonca Donmez, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Consecutive patients with inclusion criteria who are clinical candidates for TAVI based on multidisciplinary heart team evaluation.

Description

Inclusion Criteria:

• Age 60-90 years.

Confirmed diagnosis of severe Aortic Stenosis (AS) and a confirmed guideline-based indication for Transcatheter Aortic Valve Implantation (TAVI) by a multidisciplinary Heart Team, in accordance with the latest ESC/EACTS guidelines.

(In the presence of Vmax ≥ 4.0 m/s, Mean Gradient ≥ 40 mmHg, or AVA ≤ 1.0 cm²; applicable primarily to all symptomatic patients, adopting a proactive approach regarding age limits and risk profiles. Guidelines recommend TAVI as the first-line therapy [Class I] for all patients aged 70 and older with anatomical suitability and a tricuspid valve structure, regardless of surgical risk. For patients under 70, TAVI is recommended when surgical risk is high or surgery is deemed unsuitable. In asymptomatic individuals, a decline in left ventricular ejection fraction [LVEF] below 55% [not attributable to other causes] constitutes a Class I indication for intervention. Early intervention [Class IIa] is considered for patients with preserved EF but high-risk markers such as very severe stenosis [Vmax > 5.0 m/s], rapid progression [increase > 0.3 m/s/year], significant NT-proBNP elevation [> 3 times the upper limit of normal], or severe pulmonary hypertension. In cases of low-flow, low-gradient [LFLG] AS, the indication for TAVI arises if true-severe stenosis is confirmed via dobutamine stress echocardiography or CT calcium scoring [Male ≥ 2000, Female ≥ 1200]. All treatment decisions are finalized by a multidisciplinary Heart Team assessing anatomy, frailty, and patient preferences.)

Written informed consent.

Exclusion Criteria:

• Active infection, uncontrolled systemic disease, active malignancy, or life expectancy < 1 month.

Pregnant or lactating patients.

Pressure tracings with significant artifacts hindering analysis or uncontrolled arrhythmia (e.g., atrial fibrillation with rapid ventricular response).

Any other condition deemed clinically unsuitable by the investigator.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
TAVI; Patient with severe aortic stenosis who are clinical candidates for TAVI based on multidisciplinary heart team evaluation.	Procedure: Transcatheter aortic valve replacement (TAVR / TAVI); TAVI is performed as per standard procedural guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EQ-5D-5L	The 5-level EQ-5D version (EQ-5D-5L) measures health related quality of life	baseline at admission, at 1 month, 6 months and 12 months follow up
MACE	MACE (defined by VARC-3) will be monitored via electronic health records and telephone-visits.	at 1 month, 6 months and 12 months follow up
WIA	Wave Intensity Analysis (WIA): By analyzing simultaneous changes in pressure and flow (or flow-surrogates), WIA identifies the energy flux of forward and backward-traveling waves with their temporal and amplitude features.	immediately before and after implantation of prosthetic valve (intraprocedural)
REPA	Reservoir-Excess Pressure Analysis (REPA): This method decomposes the measured aortic pressure waveform into a reservoir pressure (Pr), reflecting the global arterial storage and compliance dynamics, and an excess pressure (Pxs), representing the dynamic, wave-related component of the pulse. Parameters such as P-infinity (Pinf) serve as proxies for microcirculatory closing pressures.	Immediately before and after implantation of prosthetic valve (intraprocedural)

Collaborators and Investigators

• Sponsor: Istanbul Mehmet Akif Ersoy Educational and Training Hospital

Publications and helpful links

General Publications

• Tas A, Alan Y, Ozcan A, et al. Ventricular-Coronary Interaction Delay is Associated With Discordance Between Fractional Flow Reserve and Coronary Flow Reserve in Intermediate Coronary Stenoses. Am J Cardiol. 2025;248:80-88. doi:10.1016/j.amjcard.2025.04.003
• Michail M, Hughes AD, Comella A, et al. Acute Effects of Transcatheter Aortic Valve Replacement on Central Aortic Hemodynamics in Patients With Severe Aortic Stenosis. Hypertension. 2020;75(6):1557-1564. doi:10.1161/HYPERTENSIONAHA.119.14385
• Rolandi MC, Wiegerinck EM, Casadonte L, et al. Transcatheter Replacement of Stenotic Aortic Valve Normalizes Cardiac-Coronary Interaction by Restoration of Systolic Coronary Flow Dynamics as Assessed by Wave Intensity Analysis. Circ Cardiovasc Interv. 2016;9(4):e002356. doi:10.1161/CIRCINTERVENTIONS.114.002356
• Abbas AE, Mando R, Kadri A, et al. Comparison of Transvalvular Aortic Mean Gradients Obtained by Intraprocedural Echocardiography and Invasive Measurement in Balloon and Self-Expanding Transcatheter Valves. J Am Heart Assoc. 2021;10(19):e021014. doi:10.1161/JAHA.120.021014
• Naidu S, Chen T, Fiorilli P, et al. Measuring TAVR Prosthesis Gradient Immediately Post-Procedure May Underestimate its Significance. JACC Cardiovasc Interv. 2022;15(1):120-121. doi:10.1016/j.jcin.2021.09.012
• Yordanov TR, Al-Farra H, Ravelli ACJ, et al. Incidence and trends of patient MACE outcomes after Transcatheter Aortic Valve Implantation (TAVI): analysis by age and sex. Neth Heart J. 2026;34(1):36-44. doi:10.1007/s12471-025-02006-6
• Baron SJ., Magnuson EA., Lu M., et al. Health Status After Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients With Aortic Stenosis. J Am Coll Cardiol 2019;74(23):2833-42. Doi: 10.1016/j.jacc.2019.09.007.
• Osnabrugge RL., Arnold S V., Reynolds MR., et al. Health Status After Transcatheter Aortic Valve Replacement in Patients at Extreme Surgical Risk. JACC Cardiovasc Interv 2015;8(2):315-23. Doi: 10.1016/j.jcin.2014.08.016.
• Reynolds MR., Magnuson EA., Wang K., et al. Health-Related Quality of Life After Transcatheter or Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis. J Am Coll Cardiol 2012;60(6):548-58. Doi: 10.1016/j.jacc.2012.03.075.
• Arnold S V., Spertus JA., Vemulapalli S., et al. Quality-of-Life Outcomes After Transcatheter Aortic Valve Replacement in an Unselected Population. JAMA Cardiol 2017;2(4):409. Doi: 10.1001/jamacardio.2016.5302.

Study record dates

Study Major Dates

• Study Start (Estimated): March 30, 2026
• Primary Completion (Estimated): July 30, 2028
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: March 29, 2026
• First Submitted That Met QC Criteria: March 29, 2026
• First Posted (Actual): April 3, 2026

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 29, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: TAVI; TAVR; AORTIC STENOSIS; wave intensity analysis; reservoir excess pressure analysis
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Surgical Procedures, Operative; Cardiovascular Surgical Procedures; Cardiac Surgical Procedures; Thoracic Surgical Procedures; Prosthesis Implantation; Heart Valve Prosthesis Implantation; Transcatheter Aortic Valve Replacement
• Other Study ID Numbers: PREDIC-TAVI-IMAEH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: may be considered based on reasonable request after discussion with IRB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No