PRessure-based Evaluation of Disease Improvement in the Course of TAVI

Official title

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)

Overview

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.

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.

Interventions

• Procedure Transcatheter aortic valve replacement (TAVR / TAVI)
  TAVI is performed as per standard procedural guidelines

Primary outcome measures

• EQ-5D-5L [Time frame: baseline at admission, at 1 month, 6 months and 12 months follow up]
• MACE [Time frame: at 1 month, 6 months and 12 months follow up]
• WIA [Time frame: immediately before and after implantation of prosthetic valve (intraprocedural)]
• REPA [Time frame: Immediately before and after implantation of prosthetic valve (intraprocedural)]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Turkey (Türkiye) · 1 center

• Istanbul Mehmet Akif Ersoy Educational and Training Hospital — Istanbul

Publications

• Tas A, Alan Y, Ozcan A, Parker KH, van de Hoef T, Sezer M, Piek JJ. Ventricular-Coronary Interaction Delay is Associated With Discordance Between Fractional Flow Reserve and Coronary Flow Reserve in Intermediate Coronary Stenoses. Am J Cardiol. 2025 Aug 1;248:80-88. doi: 10.1016/j.amjcard.2025.04.003. Epub 2025 Apr 11. PMID 40222466
• Michail M, Hughes AD, Comella A, Cameron JN, Gooley RP, McCormick LM, Mathur A, Parker KH, Brown AJ, Cameron JD. Acute Effects of Transcatheter Aortic Valve Replacement on Central Aortic Hemodynamics in Patients With Severe Aortic Stenosis. Hypertension. 2020 Jun;75(6):1557-1564. doi: 10.1161/HYPERTENSIONAHA.119.14385. Epub 2020 Apr 20. PMID 32306768
• Rolandi MC, Wiegerinck EM, Casadonte L, Yong ZY, Koch KT, Vis M, Piek JJ, Baan J Jr, Spaan JA, Siebes M. 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 Apr;9(4):e002356. doi: 10.1161/CIRCINTERVENTIONS.114.002356. PMID 27001805
• Abbas AE, Mando R, Kadri A, Khalili H, Hanzel G, Shannon F, Al-Azizi K, Waggoner T, Kassas S, Pilgrim T, Okuno T, Camacho A, Selberg A, Elmariah S, Bavry A, Ternacle J, Christensen J, Gheewala N, Pibarot P, Mack M. Comparison of Transvalvular Aortic Mean Gradients Obtained by Intraprocedural Echocardiography and Invasive Measurement in Balloon and Self-Expanding Transcatheter Valves. J Am Heart As PMID 34585593
• Naidu S, Chen T, Fiorilli P, Li RH, Desai N, Szeto WY, Giri J, Kobayashi T, Atluri P, Herrmann HC. Measuring TAVR Prosthesis Gradient Immediately Post-Procedure May Underestimate its Significance. JACC Cardiovasc Interv. 2022 Jan 10;15(1):120-121. doi: 10.1016/j.jcin.2021.09.012. No abstract available. PMID 34991821
• Yordanov TR, Al-Farra H, Ravelli ACJ, Houterman S, de Mol BA, Winkelman TA, Timmers L, Vis M, Tonino P, Delewi R, Abu-Hanna A, Henriques JPS; NHR THI Registration Committee. Incidence and trends of patient MACE outcomes after Transcatheter Aortic Valve Implantation (TAVI): analysis by age and sex. Neth Heart J. 2026 Jan;34(1):36-44. doi: 10.1007/s12471-025-02006-6. Epub 2025 Dec 17. PMID 41405821
• Baron SJ, Magnuson EA, Lu M, Wang K, Chinnakondepalli K, Mack M, Thourani VH, Kodali S, Makkar R, Herrmann HC, Kapadia S, Babaliaros V, Williams MR, Kereiakes D, Zajarias A, Alu MC, Webb JG, Smith CR, Leon MB, Cohen DJ; PARTNER 3 Investigators. Health Status After Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients With Aortic Stenosis. J Am Coll Cardiol. 2019 Dec 10;74(23) PMID 31577923
• Osnabrugge RL, Arnold SV, Reynolds MR, Magnuson EA, Wang K, Gaudiani VA, Stoler RC, Burdon TA, Kleiman N, Reardon MJ, Adams DH, Popma JJ, Cohen DJ; CoreValve U.S. Trial Investigators. Health status after transcatheter aortic valve replacement in patients at extreme surgical risk: results from the CoreValve U.S. trial. JACC Cardiovasc Interv. 2015 Feb;8(2):315-323. doi: 10.1016/j.jcin.2014.08.016. PMID 25700755

Identifiers

NCT: NCT07509554 · PREDIC-TAVI-IMAEH

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗