Association of discharge transvalvular gradients with long-term mortality after TAVR: Insights from a large international registry

Clin Res Cardiol (2026). DOI 10.1007/s00392-026-02870-1
H. Guthoff (Köln)¹, M. Tessenyi (Köln)², M. Abdel-Wahab (Leipzig)³, W.-K. Kim (Gießen)⁴, G. Witberg ( Petah Tikva )⁵, H. S. Wienemann (Köln)², J. Shamekhi (Bonn)⁶, H. Möllmann (Dortmund)⁷, S. Ludwig (Hamburg)⁸, V. Veulemans (Siegburg)⁹, M. Landt (Bad Segeberg)¹⁰, M. Barbanti ( Enna)¹¹, A. Finkelstein (Tel Aviv)¹², J. Schewel (Hamburg)¹³, N. M. Van Mieghem (Rotterdam)¹⁴, S. Toggweiler (Luzern)¹⁵, T. Rheude (München)¹⁶, L. Nombela-Franco (Madrid)¹⁷, I. J. Amat-Santos (Valladolid)¹⁸, P. Ruile (Bad Krozingen)¹⁹, R. Estévez-Loureiro (Vigo)²⁰, M. Bunc (Ljubljana)²¹, L. Branca (Brescia)²², S. Macherey-Meyer (Köln)²³, O. De Backer (Copenhagen)²⁴, G. Tarantini (Padua)²⁵, D. Mylotte (Galway)²⁶, D. Arzamendi (Barcelona)²⁷, T. Zeus (Düsseldorf)²⁸, C. Tamburino (Catania)²⁹, T. Schmidt (Hamburg)³⁰, A. Rück (Stockholm )³¹, S. Nienaber (Köln)², P. von Stein (Köln)², J. Curio (Köln)², J. Wrobel (Köln)², M. Adam (Köln)², S. Baldus (Köln)²³, T. K. Rudolph (Bad Oeynhausen)³², V. Mauri (Köln)^2
1Universitätsklinikum Köln Klinik III für Kardiologie, Angiologie, Pneumologie und Internistische Intensivmedizin Köln, Deutschland; ²Herzzentrum der Universität zu Köln Klinik III für Innere Medizin Köln, Deutschland; ³Herzzentrum Leipzig - Universität Leipzig Klinik für Innere Medizin/Kardiologie Leipzig, Deutschland; ⁴Universitätsklinikum Gießen und Marburg GmbH Medizinische Klinik I - Kardiologie und Angiologie Gießen, Deutschland; ⁵Division of Cardiology, Rabin Medical Center Petah Tikva , Israel; ⁶Universitätsklinikum Bonn Medizinische Klinik und Poliklinik II Bonn, Deutschland; ⁷Kath. St. Paulus Gesellschaft Klinik für Innere Medizin I Dortmund, Deutschland; ⁸Universitäres Herz- und Gefäßzentrum Klinik für Kardiologie Hamburg, Deutschland; ⁹Helios Klinikum Siegburg Herzzentrum Siegburg, Klinik für Kardiologie, Angiologie Siegburg, Deutschland; ¹⁰Segeberger Kliniken GmbH Herzzentrum Bad Segeberg, Deutschland; ¹¹Università degli Studi di Enna “Kore” Enna, Deutschland; ¹²Tel Aviv Medical Center and Tel Aviv University Tel Aviv, Deutschland; ¹³Asklepios Klinik St. Georg Kardiologie & internistische Intensivmedizin Hamburg, Deutschland; ¹⁴Erasmus University Medical Center Department of Cardiology Rotterdam, Niederlande; ¹⁵Luzerner Kantonsspital Kardiologie, Herzzentrum Luzern, Schweiz; ¹⁶Deutsches Herzzentrum München Klinik für Herz- und Kreislauferkrankungen München, Deutschland; ¹⁷Instituto de Investigación Sanitaria San Carlos Madrid, Spanien; ¹⁸Hospital Clínico Universitario de Valladolid Institute of Heart Sciences Valladolid, Spanien; ¹⁹Universitäts-Herzzentrum Freiburg / Bad Krozingen Klinik für Kardiologie und Angiologie Bad Krozingen, Deutschland; ²⁰Complejo Hospitalario Universitario Alvaro Cunqueiro Vigo, Spanien; ²¹University Medical Center Ljubljana Department of cardiology Ljubljana, Slowenien; ²²Cardiovascular Department, Spedali Civili, Brescia, Italien; ²³Herzzentrum der Universität zu Köln Klinik für Kardiologie, Angiologie, Pneumologie und Internistische Intensivmedizin Köln, Deutschland; ²⁴Rigshospitalet Copenhagen Cardiology Copenhagen, Dänemark; ²⁵Padova University Hospital Division of Cardiology Padua, Italien; ²⁶Bon Secours Hospital Galway, Irland; ²⁷Hospital de la Santa Creu i Sant Pau Barcelona, Spanien; ²⁸Universitätsklinikum Düsseldorf Klinik für Kardiologie, Pneumologie und Angiologie Düsseldorf, Deutschland; ²⁹Ferrarotto Hospital Policlinico Vittorio Emanuele Catania, Italien; ³⁰Asklepios Westklinikum Hamburg Kardiologie Hamburg, Deutschland; ³¹Karolinska University Hospital, Department of Cardiology, Stockholm , Deutschland; ³²Herz- und Diabeteszentrum NRW Allgemeine und Interventionelle Kardiologie/Angiologie Bad Oeynhausen, Deutschland

Background and Aims: The prognostic relevance of post-procedural transvalvular gradients after transcatheter aortic valve replacement (TAVR) remains controversial. While high residual gradients have been associated with prosthesis dysfunction and premature valve degeneration, low gradients often coincide with conditions such as reduced left ventricular ejection fraction (LVEF) or atrial fibrillation (AF), which themselves are associated with adverse outcomes. Previous studies on this topic yielded conflicting results, and current consensus documents (e.g., VARC-3, ESC/EACTS 2025) primarily address increases in gradients during follow-up rather than the prognostic impact of residual gradients at discharge. This study therefore aimed to elucidate the association between discharge mean transvalvular gradient (dPmean) and long-term mortality in a large multicentre real-world cohort.
Methods: To address this question, we analysed data from 37,413 patients in the international IMPPACT TAVR registry, who underwent TAVR for severe native aortic stenosis across 27 centres in Europe and Israel between 2004 and 2022. Patients were stratified by discharge dPmean quartiles (Q1 <=6, Q2 6-9, Q3 9-12, Q4 >=12 mmHg). Kaplan-Meier estimates and log-rank tests were used. Restricted cubic spline Cox analyses evaluated non-linear associations between discharge dPmean and all-cause mortality through 4 years by valve type (balloon-expandable [BE], self-expanding [SE]).
Results: Baseline age was 81 +/- 6 years, 49% of patients were female, and mean LVEF was 54 +/- 12%. dPmean at discharge was 9.5 +/- 4.6 mmHg, with higher values observed in BE valves (11.1 +/- 4.7 vs. 8.4 +/- 4.1 mmHg, p<0.001). Across discharge dPmean quartiles, 4-year Kaplan-Meier survival increased progressively from 58.6% (Q1) to 65.3% (Q4; log-rank p<0.001), corresponding to a stepwise decline in the hazard of all-cause mortality compared with Q1 (Q2 HR 0.91 [95% CI 0.86-0.97], p=0.004; Q3 HR 0.80 [0.75-0.85], p<0.001; Q4 HR 0.75 [0.71-0.80], p<0.001). In parallel, mean LVEF gradually increased across quartiles from 55.6 +/- 11.7% (Q1) to 57.9 +/- 10.2% (Q4; p<0.001), while AF prevalence gradually decreased from 35.0% to 26.9% (p<0.001). Restricted cubic spline analysis showed a significant non-linear association between discharge gradient and all-cause mortality in the overall cohort and in both valve types (overall p=0.001; BE p=0.007; SE p=0.004). The excess mortality was confined to very low gradients, with hazard ratios crossing 1.0 at 9.5 mmHg (95% CI 8.7-10.3) for BE and 7.3 mmHg (95% CI 6.5-8.4) for SE valves. Beyond these thresholds, risk declined and plateaued, with no significant evidence of harm at higher gradients.
Conclusions: In this large real-world TAVR cohort, low rather than high discharge gradients were associated with increased long-term mortality, independent of valve type. These findings challenge the assumption that low residual gradients reflect procedural success. Instead, low discharge dPmean may be a marker of adverse clinical profiles such as reduced LVEF or AF. Clinical assessment should therefore integrate gradient interpretation with patient characteristics instead of using fixed cut-offs alone. This underscores the need for more direct, flow-independent measures of valve
performance in future research.