Kidney Injury in Patients with Heart Failure-related Cardiogenic Shock: Results from an International, Multicenter Cohort Study

J. Sundermeyer (Hamburg)¹, C. Kellner (Hamburg)¹, B. Beer (Hamburg)¹, L. C. Besch (Hamburg)¹, A. Dettling (Hamburg)², L. F. Bertoldi (Milan)³, S. Blankenberg (Hamburg)¹, J. Dauw (Ghent)⁴, D. Eckner (Nürnberg)⁵, I. Eitel (Lübeck)⁶, T. Graf (Lübeck)⁶, P. Horn (Mönchengladbach)⁷, J. Jozwiak-Nozdrzykowska (Leipzig)⁸, P. Kirchhof (Hamburg)⁹, S. Kluge (Hamburg)¹⁰, A. Linke (Dresden)¹¹, U. Landmesser (Berlin)¹², P. Lüdike (Osnabrück)¹³, E. Lüsebrink (Bonn)¹⁴, N. Majunke (Leipzig)⁸, N. Mangner (Dresden)¹⁵, S. Möbius-Winkler (Jena)¹⁶, P. Nordbeck (Würzburg)¹⁷, M. Orban (München)¹⁸, F. Pappalardo (Alessandria)¹⁹, M. Pauschinger (Nürnberg)⁵, M. Pazdernik (Prague)²⁰, A. Proudfoot (London)²¹, M. Kelham (London)²², T. Rassaf (Essen)²³, H. Reichenspurner (Hamburg)²⁴, C. Scherer (München)¹⁸, C. Schulze (Jena)¹⁶, R. H. G. Schwinger (Weiden i. d. Oberpfalz)²⁵, C. Skurk (Berlin)²⁶, M. Sramko (Prague)²⁰, G. Tavazzi (Bravia)²⁷, H. Thiele (Leipzig)⁸, L. Villanova (Milan)²⁸, N. Morici (Milano)²⁹, E. B. Winzer (Dresden)¹⁵, D. Westermann (Freiburg im Breisgau)³⁰, B. Schrage (Hamburg)^1
1Universitäres Herz- und Gefäßzentrum Hamburg Klinik für Kardiologie Hamburg, Deutschland; ²Universitätsklinikum Hamburg-Eppendorf Klinik für Kardiologie Hamburg, Deutschland; ³Cardio Center, Humanitas Clinical and Research Center – IRCCS, Rozzano, Milan, Italy Milan, Italien; ⁴Department of Cardiology, AZ Sint-Lucas Ghent, Belgien; ⁵Universitätsklinik der Paracelsus Medizinischen Privatuniversität Klinik für Innere Medizin 8, Schwerpunkt Kardiologie Nürnberg, Deutschland; ⁶Universitätsklinikum Schleswig-Holstein Medizinische Klinik II / Kardiologie, Angiologie, Intensivmedizin Lübeck, Deutschland; ⁷Städtische Kliniken Mönchengladbach GmbH Kardiologie & Angiologie Mönchengladbach, Deutschland; ⁸Herzzentrum Leipzig - Universität Leipzig Klinik für Innere Medizin/Kardiologie Leipzig, Deutschland; ⁹Universitäres Herz- und Gefäßzentrum Hamburg Klinik für Kardiologie Lübeck, Deutschland; ¹⁰University Medical Center Hamburg-Eppendorf, Department of Intensive Care Medicine, Hamburg, Germany Hamburg, Deutschland; ¹¹Herzzentrum Dresden GmbH an der TU Dresden Klinik für Innere Medizin und Kardiologie Dresden, Deutschland; ¹²Deutsches Herzzentrum der Charite (DHZC) Klinik für Kardiologie, Angiologie und Intensivmedizin Berlin, Deutschland; ¹³Marienhospital Osnabrück Klinik für Innere Medizin / Kardiologie und Intensivmedizin Osnabrück, Deutschland; ¹⁴Universitätsklinikum Bonn Medizinische Klinik und Poliklinik II Bonn, Deutschland; ¹⁵Herzzentrum Dresden GmbH an der TU Dresden Klinik für Innere Medizin, Kardiologie und Intensivmedizin Dresden, Deutschland; ¹⁶Universitätsklinikum Jena Klinik für Innere Medizin I - Kardiologie Jena, Deutschland; ¹⁷Universitätsklinikum Würzburg Medizinische Klinik und Poliklinik I Würzburg, Deutschland; ¹⁸LMU Klinikum der Universität München Medizinische Klinik und Poliklinik I München, Deutschland; ¹⁹Dept Cardiothoracic and Vascular Anesthesia and Intensive Care, AO SS Antonio e Biagio e Cesare Arrigo Alessandria, Italien; ²⁰Department of Cardiology, IKEM Prague, Tschechische Republik; ²¹Department of Perioperative Medicine, St. Bartholomew’s Hospital London, Großbritannien; ²²Department of Perioperative Medicine, St. Bartholomew's Hospital London, Großbritannien; ²³Universitätsklinikum Essen Klinik für Kardiologie und Angiologie Essen, Deutschland; ²⁴Universitäres Herz- und Gefäßzentrum Hamburg Klinik und Poliklinik für Herz- und Gefäßchirurgie Hamburg, Deutschland; ²⁵Kliniken Nordoberpfalz AG Medizinische Klinik II, Kardiologie Weiden i. d. Oberpfalz, Deutschland; ²⁶Charité - Universitätsmedizin Berlin CC 11: Med. Klinik für Kardiologie Berlin, Deutschland; ²⁷Department of Clinical-Surgical, Diagnostic and Paediatric Sciences, University of Pavia Italy; Anesthesia and Intensive Care, Fondazione Policlinico San Matteo Hospital IRCCS Bravia, Italien; ²⁸Unità di Cure Intensive Cardiologiche and De Gasperis Cardio-Center, ASST Grande Ospedale Metropolitano Niguarda Milan, Italien; ²⁹IRCCS Fondazione Don Gnocchi, ONLUS, Santa Maria Nascente Milano, Italien; ³⁰Universitäts-Herzzentrum Freiburg - Bad Krozingen Innere Medizin III, Kardiologie und Angiologie Freiburg im Breisgau, Deutschland

Background: In cardiogenic shock (CS), severe hypoperfusion ultimately triggers multi-organ damage and death. As renal function is sensitive to changes in perfusion and congestion, it might reflect CS severity. Furthermore, kidney injury can contribute to organ damage in cardiogenic shock. We therefore performed a systematic assessment of kidney injury and its relation to outcomes in patients with cardiogenic shock due to heart failure.

 

Purpose: The aim of this study was to quantify the prevalence of kidney injury at baseline and its association with outcomes in patients with heart failure (HF) related CS.

 

Methods: In this international observational study, patients with HF-CS (e.g. caused by severe de-novo or acute-on-chronic HF; but not by acute myocardial infarction) from 16 tertiary-care centers in five countries were enrolled. To investigate differences in clinical presentation, complications and creatine- as well as glomerular filtration rate (GFR)-based renal function, multivariable mixed effects logistic regression models were fitted. Cox regression models were fitted to evaluate the association between parameters of renal function and 30-day mortality. In all models, adjustments were made for age, sex, lactate, pH, prior resuscitation, mechanical ventilation and ischemic cardiomyopathy.

 

Results: A total of 1030 CS patients were analyzed: mean age was 64 (interquartile range [IQR] 52-75) years, 740 (71.8%) were male. The median lactate level upon admission was 5.0 (IQR 2.7-8.6) mmol/l, baseline pH was 7.3 (IQR 7.2-7.4), median LVEF 20 (IQR 15-30) %, and 395 (38.6%) patients had a prior cardiac arrest. Patients with HF-CS presented with a baseline creatinine of 1.7 (IQR 1.2-2.5) mg/dl with a corresponding CKD-EPI-GFR of 38.6 (IQR 23.4-59.1) ml/min/1.73m².

Patient characteristics such as age (OR 2.25, 95% CI 1.48-3.4, p<0.001), lactate levels exceeding 5 mmol/l (OR 1.88, 95% CI 1.19-2.97, p=0.007), increased severity of CS (SCAI shock stage E, OR 3.57, 95% CI 1.63-7.81, p=0.002), and a preexisting diagnosis of HF (OR 2.17, 95% CI 1.38-3.42, p<0.001) were more common in patients with severely reduced renal function (≤38.6 ml/min/1.73m²) at baseline. Importantly, these patients had a higher mortality rate compared to those with better renal function during the index event (21% absolute mortality difference, 61.3% for baseline GFR ≤38.6 ml/min/1.73m² vs. 40.3% for baseline GFR >38.6 ml/min/1.73m², adjusted hazard ratio 1.34, 95% CI 1.04-1.73, p=0.022, Figure 1). Furthermore, patients with HF-CS and severely reduced renal function were more likely to receive renal replacement therapy (OR 3.35, 95% CI 2.28-4.93, p<0.001), and were more likely to experience complications, such as sepsis (OR 1.74, 95% CI 1.28-2.71, p=0.014), and bleeding events (OR 1.48, 95% CI 1.02-2.15, p=0.039).

 

Conclusion: In patients with HF-CS, impaired renal function at the index event is associated with higher 30-day mortality and an increased incidence of complications, even after adjustment for conventional markers of hypoperfusion. These hypothesis-generating data suggest that acute kidney damage could be a useful marker for prognosis in HF-CS. They also create a prospect to consider interventions improving kidney function in HF-CS.

Figure 1: Kaplan-Meier curves, baseline GFR ≤38.6 ml/min/1.73m² vs. >38.6 ml/min/1.73m² in heart failure-related cardiogenic shock.

HR: hazard ratio; CI: confidence interval; GFR: Glomerular Filtration Rate.