28 results on '"Harjola, Veli-Pekka"'
Search Results
2. Acute heart failure: diagnostic and prognostic assessment
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Chioncel, Ovidiu, additional, Filippatos, Gerasimos, additional, Mebazaa, Alexandre, additional, Harjola, Veli-Pekka, additional, and Masip, Josep, additional
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- 2023
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3. Quantifying Hemodynamic Cardiac Stress and Cardiomyocyte Injury in Normotensive and Hypertensive Acute Heart Failure
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Nikola Kozhuharov, Eleni Michou, Desiree Wussler, Maria Belkin, Corinna Heinisch, Johan Lassus, Krista Siirilä-Waris, Harjola Veli-Pekka, Nisha Arenja, Thenral Socrates, Albina Nowak, Samyut Shrestha, Julie Valerie Willi, Ivo Strebel, Danielle M. Gualandro, Katharina Rentsch, Micha T. Maeder, Thomas Münzel, Mucio Tavares de Oliveira Junior, Arnold von Eckardstein, Tobias Breidthardt, and Christian Mueller
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acute heart failure ,pathophysiology ,natriuretic peptides ,cardiac troponin ,Biology (General) ,QH301-705.5 - Abstract
Background: The characterization of the different pathophysiological mechanisms involved in normotensive versus hypertensive acute heart failure (AHF) might help to develop individualized treatments. Methods: The extent of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring the B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT) concentrations in 1152 patients presenting with centrally adjudicated AHF to the emergency department (ED) (derivation cohort). AHF was classified as normotensive with a systolic blood pressure (SBP) of 90–140 mmHg and hypertensive with SBP > 140 mmHg at presentation to the ED. Findings were externally validated in an independent AHF cohort (n = 324). Results: In the derivation cohort, with a median age of 79 years, 43% being women, 667 (58%) patients had normotensive and 485 (42%) patients hypertensive AHF. Hemodynamic cardiac stress, as quantified by the BNP and NT-proBNP, was significantly higher in normotensive as compared to hypertensive AHF [1105 (611–1956) versus 827 (448–1419) pg/mL, and 5890 (2959–12,162) versus 4068 (1986–8118) pg/mL, both p < 0.001, respectively]. Similarly, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF [41 (24–71) versus 33 (19–59) ng/L, p < 0.001]. A total of 313 (28%) patients died during 360 days of follow-up. All-cause mortality was higher in patients with normotensive AHF vs. patients with hypertensive AHF (hazard ratio 1.66, 95%CI 1.31–2.10; p < 0.001). Normotensive patients with a high BNP, NT-proBNP, or hs-cTnT had the highest mortality. The findings were confirmed in the validation cohort. Conclusion: Biomarker profiling revealed a higher extent of hemodynamic stress and cardiomyocyte injury in patients with normotensive versus hypertensive AHF.
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- 2024
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4. Low body temperature and mortality in older patients with frailty in the emergency department
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Alakare, Janne, Kemp, Kirsi, Strandberg, Timo, Castrén, Maaret, Tolonen, Jukka, and Harjola, Veli-Pekka
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- 2022
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5. Soluble triggering receptor expressed on myeloid cells-1 is a marker of organ injuries in cardiogenic shock: results from the CardShock Study
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Kimmoun, Antoine, Duarte, Kevin, Harjola, Veli-Pekka, Tarvasmäki, Tuukka, Levy, Bruno, Mebazaa, Alexandre, and Gibot, Sebastien
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- 2022
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6. Characteristics and costs of electric scooter injuries in Helsinki: a retrospective cohort study
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Vasara, Henri, Toppari, Linda, Harjola, Veli-Pekka, Virtanen, Kaisa, Castrén, Maaret, and Kobylin, Arja
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- 2022
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7. The emergency department arrival mode and its relations to ED management and 30-day mortality in acute heart failure: an ancillary analysis from the EURODEM study
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Harjola, Pia, Tarvasmäki, Tuukka, Barletta, Cinzia, Body, Richard, Capsec, Jean, Christ, Michael, Garcia-Castrillo, Luis, Golea, Adela, Karamercan, Mehmet A., Martin, Paul-Louis, Miró, Òscar, Tolonen, Jukka, van Meer, Oene, Palomäki, Ari, Verschuren, Franck, Harjola, Veli-Pekka, and Laribi, Said
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- 2022
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8. miR‐619‐5p and cardiogenic shock in patients with ST‐segment elevation myocardial infarction.
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Escate, Rafael, Padró, Teresa, Suades, Rosa, Sans‐Roselló, Jordi, Devaux, Yvan, Lakkisto, Päivi, Harjola, Veli‐Pekka, Sionis, Alessandro, and Badimon, Lina
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ST elevation myocardial infarction ,CARDIOGENIC shock ,DISEASE risk factors - Abstract
Background: Cardiogenic shock (CS) is a severe myocardial dysfunction secondary to various cardiac conditions including ST‐segment elevation acute myocardial infarction (STEMI) and associated with a high risk of death. Little is known on epigenetic determinants in CS. Here, we investigated plasma miRNAs in relation to CS stratification in STEMI‐patients. Methods: STEMI‐patients (n = 49), with (CS, n = 25) and without CS (non‐CS, n = 24) fulfilling inclusion criteria were included from HSCSP‐cohort (Derivation‐cohort). CS‐miRNAs were analysed by Affymetrix‐microarray and RT‐PCR. Results were validated in a second cohort of CS‐patients (CardShock: n = 35) with similar inclusion/exclusion criteria as the derivation cohort. In silico analysis were performed to identify potential miRNA target genes. Results: Of the 5‐miRNA signature obtained from microarray analysis, miR‐619‐5p showed higher levels in CS than in Non‐CS patients (p =.003) and discriminating power for CS by ROC (AUC:.752, p =.003). miR‐619‐5p directly associated with risk scores [GRACE, p =.001; CardShock, p <.001]. Furthermore, miR‐619‐5p showed discrimination power for death in CS. Thus, miRNA levels were significantly higher in patients with mortality outcome both in the Derivation HSCSP‐cohort (p =.02; AUC:.78 ±.095) and the Validation CardShock‐cohort (p =.017; AUC:.737 ±.086) By in silico analysis, miR‐619‐5p target genes and TNF‐alpha were involved in the regulation of inflammation. miR‐619‐5p and TNF‐alpha levels discriminated mortality outcome in CS‐patients during 30‐day follow‐up (Validation‐Cohort: ROC:.812, p =.002; HR: 9.99, p =.003). Conclusions: Up‐regulation of miR‐619‐5p is found in the plasma of STEMI‐patients with CS and mortality outcome. These findings highlight the specificity of epigenetic regulation of inflammation on the disease severity of MI. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Diagnosis and treatment of right ventricular failure secondary to acutely increased right ventricular afterload (acute cor pulmonale). A Clinical Consensus Statement of the Association for Acute CardioVascular Care (ACVC) of the ESC
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Arrigo, Mattia, primary, Price, Susanna, additional, Harjola, Veli-Pekka, additional, Huber, Lars C, additional, Schaubroeck, Hannah A I, additional, Vieillard-Baron, Antoine, additional, Masip, Josep, additional, and Mebazaa, Alexandre, additional
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- 2023
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10. Diagnosis and treatment of right ventricular failure secondary to acutely increased right ventricular afterload (acute cor pulmonale): a clinical consensus statement of the Association for Acute CardioVascular Care of the European Society of Cardiology.
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Arrigo, Mattia, Price, Susanna, Harjola, Veli-Pekka, Huber, Lars C, Schaubroeck, Hannah A I, Vieillard-Baron, Antoine, Mebazaa, Alexandre, and Masip, Josep
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- 2024
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11. Reply to: High levels of plasma biomarkers at 24 h were found to be strong predictors of 90-day mortality: beware of some potential confounders!
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Jäntti, Toni, Harjola, Veli-Pekka, Haapio, Mikko, and Lassus, Johan
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- 2021
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12. Systematic geriatric assessment for older patients with frailty in the emergency department: a randomised controlled trial
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Alakare, Janne, Kemp, Kirsi, Strandberg, Timo, Castrén, Maaret, Jakovljević, Dimitrije, Tolonen, Jukka, and Harjola, Veli-Pekka
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- 2021
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13. Speed and Nighttime Usage Restrictions and the Incidence of Shared Electric Scooter Injuries
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Pakarinen, Oskari, primary, Kobylin, Arja, additional, Harjola, Veli-Pekka, additional, Castrén, Maaret, additional, and Vasara, Henri, additional
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- 2023
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14. Effect of Inhaled Xenon on Cardiac Function in Comatose Survivors of Out-of-Hospital Cardiac Arrest—A Substudy of the Xenon in Combination With Hypothermia After Cardiac Arrest Trial
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Saraste, Antti, Ballo, Haitham, Arola, Olli, Laitio, Ruut, Airaksinen, Juhani, Hynninen, Marja, Bäcklund, Minna, Ylikoski, Emmi, Wennervirta, Johanna, Pietilä, Mikko, Roine, Risto O., Harjola, Veli-Pekka, Niiranen, Jussi, Korpi, Kirsi, Varpula, Marjut, Scheinin, Harry, Maze, Mervyn, Vahlberg, Tero, and Laitio, Timo
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- 2021
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15. Acute heart failure and valvular heart disease: A scientific statement of the Heart Failure Association, the Association for Acute CardioVascular Care and the European Association of Percutaneous Cardiovascular Interventions of the European Society of Cardiology
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Chioncel, Ovidiu, primary, Adamo, Marianna, additional, Nikolaou, Maria, additional, Parissis, John, additional, Mebazaa, Alexandre, additional, Yilmaz, Mehmet Birhan, additional, Hassager, Christian, additional, Moura, Brenda, additional, Bauersachs, Johann, additional, Harjola, Veli‐Pekka, additional, Antohi, Elena‐Laura, additional, Ben‐Gal, Tuvia, additional, Collins, Sean P., additional, Iliescu, Vlad Anton, additional, Abdelhamid, Magdy, additional, Čelutkienė, Jelena, additional, Adamopoulos, Stamatis, additional, Lund, Lars H., additional, Cicoira, Mariantonietta, additional, Masip, Josep, additional, Skouri, Hadi, additional, Gustafsson, Finn, additional, Rakisheva, Amina, additional, Ahrens, Ingo, additional, Mortara, Andrea, additional, Janowska, Ewa A., additional, Almaghraby, Abdallah, additional, Damman, Kevin, additional, Miro, Oscar, additional, Huber, Kurt, additional, Ristic, Arsen, additional, Hill, Loreena, additional, Mullens, Wilfried, additional, Chieffo, Alaide, additional, Bartunek, Jozef, additional, Paolisso, Pasquale, additional, Bayes‐Genis, Antoni, additional, Anker, Stefan D., additional, Price, Susanna, additional, Filippatos, Gerasimos, additional, Ruschitzka, Frank, additional, Seferovic, Petar, additional, Vidal‐Perez, Rafael, additional, Vahanian, Alec, additional, Metra, Marco, additional, McDonagh, Theresa A., additional, Barbato, Emanuele, additional, Coats, Andrew J.S., additional, and Rosano, Giuseppe M.C., additional
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- 2023
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16. PROGNOSTIC VALUE OF CIRCULATING SECRETONEURIN CONCENTRATIONS IN PATIENTS WITH CARDIOGENIC SHOCK: THE CARDSHOCK STUDY
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Omland, Torbjorn, primary, Azibani, Feriel, additional, Kimmmoun, Antoine, additional, Harjola, Veli-Pekka, additional, Lassus, Johan P.E., additional, and Mebazaa, Alexandre, additional
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- 2023
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17. Cost-Effectiveness of Empagliflozin in Combination with Standard Care versus Standard Care Only in the Treatment of Heart Failure Patients in Finland
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Hallinen, Taru, primary, Kivelä, Santtu, additional, Soini, Erkki, additional, Harjola, Veli-Pekka, additional, and Pesonen, Mari, additional
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- 2023
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18. Acute heart failure and valvular heart disease: A scientific statement of the Heart Failure Association, the Association for Acute CardioVascular Care and the European Association of Percutaneous Cardiovascular Interventions of the European Society of Cardiology
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Chioncel, Ovidiu, Adamo, Marianna, Nikolaou, Maria, Parissis, John, Mebazaa, Alexandre, Yilmaz, Mehmet Birhan, Hassager, Christian, Moura, Brenda, Bauersachs, Johann, Harjola, Veli-Pekka, Antohi, Elena-Laura, Ben-Gal, Tuvia, Collins, Sean P, Iliescu, Vlad Anton, Abdelhamid, Magdy, Čelutkienė, Jelena, Adamopoulos, Stamatis, Lund, Lars H, Cicoira, Mariantonietta, Masip, Josep, Skouri, Hadi, Gustafsson, Finn, Rakisheva, Amina, Ahrens, Ingo, Mortara, Andrea, Janowska, Ewa A, Almaghraby, Abdallah, Damman, Kevin, Miro, Oscar, Huber, Kurt, Ristic, Arsen, Hill, Loreena, Mullens, Wilfried, Chieffo, Alaide, Bartunek, Jozef, Paolisso, Pasquale, Bayes-Genis, Antoni, Anker, Stefan D, Price, Susanna, Filippatos, Gerasimos, Ruschitzka, Frank, Seferovic, Petar, Vidal-Perez, Rafael, Vahanian, Alec, Metra, Marco, Mcdonagh, Theresa A, Barbato, Emanuele, Coats, Andrew J S, and Rosano, Giuseppe M C
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Acute heart failure ,Management ,Valvular heart disease - Abstract
Acute heart failure (AHF) represents a broad spectrum of disease states, resulting from the interaction between an acute precipitant and a patient's underlying cardiac substrate and comorbidities. Valvular heart disease (VHD) is frequently associated with AHF. AHF may result from several precipitants that add an acute haemodynamic stress superimposed on a chronic valvular lesion or may occur as a consequence of a new significant valvular lesion. Regardless of the mechanism, clinical presentation may vary from acute decompensated heart failure to cardiogenic shock. Assessing the severity of VHD as well as the correlation between VHD severity and symptoms may be difficult in patients with AHF because of the rapid variation in loading conditions, concomitant destabilization of the associated comorbidities and the presence of combined valvular lesions. Evidence-based interventions targeting VHD in settings of AHF have yet to be identified, as patients with severe VHD are often excluded from randomized trials in AHF, so results from these trials do not generalize to those with VHD. Furthermore, there are not rigorously conducted randomized controlled trials in the setting of VHD and AHF, most of the data coming from observational studies. Thus, distinct to chronic settings, current guidelines are very elusive when patients with severe VHD present with AHF, and a clear-cut strategy could not be yet defined. Given the paucity of evidence in this subset of AHF patients, the aim of this scientific statement is to describe the epidemiology, pathophysiology, and overall treatment approach for patients with VHD who present with AHF.
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- 2023
19. Performance of Early Capillary Refill Time Measurement on Outcomes in Cardiogenic Shock: An Observational, Prospective Multicentric Study
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Merdji, Hamid, primary, Curtiaud, Anais, additional, Aheto, Antoine, additional, Studer, Antoine, additional, Harjola, Veli-Pekka, additional, Monnier, Alexandra, additional, Duarte, Kevin, additional, Girerd, Nicolas, additional, Kibler, Marion, additional, Ait-Oufella, Hafid, additional, Helms, Julie, additional, Mebazaa, Alexandre, additional, Levy, Bruno, additional, Kimmoun, Antoine, additional, and Meziani, Ferhat, additional
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- 2022
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20. Soluble urokinase-type plasminogen activator receptor improves early risk stratification in cardiogenic shock
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Hongisto, Mari, Lassus, Johan, Tarvasmäki, Tuukka, Sans-Roselló, Jordi, Tolppanen, Heli, Kataja, Anu, Jäntti, Toni, Sabell, Tuija, Banaszewski, Marek, Silva-Cardoso, Jose, Parissis, John, Jurkko, Raija, Spinar, Jindrich, Castrén, Maaret, Mebazaa, Alexandre, Masip, Josep, Harjola, Veli-Pekka, Universitat Autònoma de Barcelona, HUS Emergency Medicine and Services, Department of Diagnostics and Therapeutics, University of Helsinki, HUS Heart and Lung Center, Department of Medicine, Kardiologian yksikkö, and Clinicum
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Supar ,MYOCARDIAL-INFARCTION ,PREDICTION ,MORTALITY ,Biomarker ,General Medicine ,3126 Surgery, anesthesiology, intensive care, radiology ,Cardiology and Cardiovascular Medicine ,Critical Care and Intensive Care Medicine ,Cardiogenic shock ,Risk stratification ,suPAR - Abstract
Aims Soluble urokinase–type plasminogen activator receptor (suPAR) is a biomarker reflecting the level of immune activation. It has been shown to have prognostic value in acute coronary syndrome and heart failure as well as in critical illness. Considering the complex pathophysiology of cardiogenic shock (CS), we hypothesized suPAR might have prognostic properties in CS as well. The aim of this study was to assess the kinetics and prognostic utility of suPAR in CS. Methods and results SuPAR levels were determined in serial plasma samples (0–96 h) from 161 CS patients in the prospective, observational, multicentre CardShock study. Kinetics of suPAR, its association with 90-day mortality, and additional value in risk-stratification were investigated. The median suPAR-level at baseline was 4.4 [interquartile range (IQR) 3.2–6.6)] ng/mL. SuPAR levels above median were associated with underlying comorbidities, biomarkers reflecting renal and cardiac dysfunction, and higher 90-day mortality (49% vs. 31%; P = 0.02). Serial measurements showed that survivors had significantly lower suPAR levels at all time points compared with nonsurvivors. For risk stratification, suPAR at 12 h (suPAR12h) with a cut-off of 4.4 ng/mL was strongly associated with mortality independently of established risk factors in CS: OR 5.6 (95% CI 2.0–15.5); P = 0.001) for death by 90 days. Adding suPAR12h > 4.4 ng/mL to the CardShock risk score improved discrimination identifying high-risk patients originally categorized in the intermediate-risk category. Conclusion SuPAR associates with mortality and improves risk stratification independently of other previously known risk factors in CS patients.
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- 2022
21. Characteristics and costs of electric scooter injuries in Helsinki: a retrospective cohort study
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Vasara, Henri, primary, Toppari, Linda, additional, Harjola, Veli-Pekka, additional, Virtanen, Kaisa, additional, Castrén, Maaret, additional, and Kobylin, Arja, additional
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- 2022
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22. Soluble triggering receptor expressed on myeloid cells-1 is a marker of organ injuries in cardiogenic shock: results from the CardShock Study
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GREAT-Network, CardShock Investigators, Kimmoun, Antoine, Duarte, Kevin, Harjola, Veli-Pekka, Tarvasmäki, Tuukka, Lassus, Johan, Jurkko, Raija, Tolppanen, Heli, Nieminen, Markku S., Järvinen, Kristiina, Nieminen, Tuomo, Pulkki, Kari, Soininen, Leena, Sund, Reijo, Tierala, Ilkka, Tolonen, Jukka, Varpula, Marjut, BOZEC, Erwan, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsinki University Hospital [Finland] (HUS), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), The CardShock study was supported by grants from Aarne Koskelo Foundation, the Finnish Cardiac Foundation, and the Finnish State funding for university-level health research., CardShock Investigators and the GREAT network: Katerina Koniari, Astrinos Voumvourakis, Apostolos Karavidas, John Parissis, Jordi Sans-Rosello, Montserrat Vila, Albert Duran-Cambra, Alessandro Sionis, Jiri Parenica, Roman Stipal, Ondrej Ludka, Marie Palsuva, Eva Ganovska, Petr Kubena, Jindrich Spinar, Matias G Lindholm, Christian Hassager, Lars Køber, Tom Bäcklund, Johan Lassus, Raija Jurkko, Heli Tolppanen, Markku S Nieminen, Kristiina Järvinen, Tuomo Nieminen, Kari Pulkki, Leena Soininen, Reijo Sund, Ilkka Tierala, Jukka Tolonen, Marjut Varpula, Tuomas Korva, Mervi Pietilä, Anne Pitkälä, Rossella Marino, Salvatore Di Somma, Marco Metra, Michela Bulgari, Valentina Lazzarini, Valentina Carubelli, Alexandra Sousa, Jose Silva-Cardoso, Carla Sousa, Mariana Paiva, Inês Rangel, Rui Almeida, Teresa Pinho, Maria Júlia Maciel, Marek Banaszewski, Janina Stepinska, Anna Skrobisz, Piotr Góral, Uwe Zeymer, Holger Thiele, HUS Emergency Medicine and Services, Department of Diagnostics and Therapeutics, Helsinki University Hospital Area, University of Helsinki, HUS Heart and Lung Center, Clinicum, Kardiologian yksikkö, HUS Internal Medicine and Rehabilitation, Department of Medicine, Päijät-Häme Welfare Consortium, Department of Clinical Chemistry and Hematology, HUSLAB, and Department of Social Research (2010-2017)
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Inotrope ,medicine.medical_specialty ,Myeloid ,Shock, Cardiogenic ,Renal function ,Hemodynamics ,Inflammation ,PHARMACOLOGICAL INHIBITION ,030204 cardiovascular system & hematology ,03 medical and health sciences ,LIMITS ,0302 clinical medicine ,INFLAMMATION ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Internal medicine ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,Myocardial infarction ,Outcome ,Cardiogenic Shock ,business.industry ,Cardiogenic shock ,General Medicine ,medicine.disease ,Triggering Receptor Expressed on Myeloid Cells-1 ,[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Blood pressure ,medicine.anatomical_structure ,3121 General medicine, internal medicine and other clinical medicine ,Cardiology ,STREM ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers - Abstract
Aims Optimal outcome after cardiogenic shock (CS) depends on a coordinated healing response in which both debris removal and extracellular matrix tissue repair play a crucial role. Excessive inflammation can perpetuate a vicious circle, positioning leucocytes as central protagonists and potential therapeutic targets. High levels of circulating Triggering Receptor Expressed on Myeloid cells-1 (TREM-1), were associated with death in acute myocardial infarction confirming excessive inflammation as determinant of bad outcome. The present study aims to describe the association of soluble TREM-1 with 90-day mortality and with various organ injuries in patients with CS. Methods and results This is a post-hoc study of CardShock, a prospective, multicenter study assessing the clinical presentation and management in patients with CS. At the time of this study, 87 patients had available plasma samples at either baseline, and/or 48 h and/or 96-120 h for soluble TREM-1 (sTREM-1) measurements. Plasma concentration of sTREM-1 was higher in 90-day non-survivors than survivors at baseline [median: 1392 IQR: (724-2128) vs. 621 (525-1233) pg/mL, p = 0.008), 48 h (p = 0.019) and 96-120 h (p = 0.029). The highest tertile of sTREM-1 at baseline (threshold: 1347 pg/mL) was associated with 90-day mortality with an unadjusted HR 3.08 CI 95% (1.48-6.42). sTREM-1 at baseline was not associated to hemodynamic parameters (heart rate, blood pressure, use of vasopressors or inotropes) but rather with organ injury markers: renal (estimated glomerular filtration rate, p = 0.0002), endothelial (bio-adrenomedullin, p = 0.018), myocardial (Suppression of Tumourigenicity 2, p = 0.002) or hepatic (bilirubin, p = 0.008). Conclusion In CS patients TREM-1 pathway is highly activated and gives an early prediction of vital organ injuries and outcome. [GRAPHICS] .
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- 2022
23. Soluble urokinase-type plasminogen activator receptor improves early risk stratification in cardiogenic shock .
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Hongisto, Mari, Lassus, Johan, Tarvasmäki, Tuukka, Sans-Roselló, Jordi, Tolppanen, Heli, Kataja, Anu, Jäntti, Toni, Sabell, Tuija, Banaszewski, Marek, Silva-Cardoso, Jose, Parissis, John, Jurkko, Raija, Spinar, Jindrich, Castrén, Maaret, Mebazaa, Alexandre, Masip, Josep, Harjola, Veli-Pekka, for the CardShock Study Investigators and the GREAT Network, Virogates, and Diagnostics, Roche
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- 2022
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24. Outcome of patients with different clinical presentations of high-risk pulmonary embolism.
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Ebner, Matthias, Sentler, Carmen, Harjola, Veli-Pekka, Bueno, Héctor, Lerchbaumer, Markus H., Hasenfuß, Gerd, Eckardt, Kai-Uwe, Konstantinides, Stavros V., and Lankeit, Mareike
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- 2021
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25. External validation and comparison of the CardShock and IABP-SHOCK II risk scores in real-world cardiogenic shock patients
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Rivas-Lasarte, Mercedes, Sans-Roselló, Jordi, Collado-Lledó, Elena, González-Fernández, Víctor, Noriega, Francisco J, Hernández-Pérez, Francisco J, Fernández-Martínez, Juan, Ariza, Albert, Lidón, Rosa-Maria, Viana-Tejedor, Ana, Segovia-Cubero, Javier, Harjola, Veli-Pekka, Lassus, Johan, Thiele, Holger, and Sionis, Alessandro
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Background: Mortality from cardiogenic shock remains high and early recognition and risk stratification are mandatory for optimal patient allocation and to guide treatment strategy. The CardShock and the Intra-Aortic Balloon Counterpulsation in Acute Myocardial Infarction Complicated by Cardiogenic Shock (IABP-SHOCK II) risk scores have shown good results in predicting short-term mortality in cardiogenic shock. However, to date, they have not been compared in a large cohort of ischaemic and non-ischaemic real-world cardiogenic shock patients.Methods: The Red-Shock is a multicentre cohort of non-selected cardiogenic shock patients. We calculated the CardShock and IABP-SHOCK II risk scores in each patient and assessed discrimination and calibration.Results: We included 696 patients. The main cause of cardiogenic shock was acute coronary syndrome, occurring in 62% of the patients. Compared with acute coronary syndrome patients, non-acute coronary syndrome patients were younger and had a lower proportion of risk factors but higher rates of renal insufficiency; intra-aortic balloon pump was also less frequently used (31% vs 56%). In contrast, non-acute coronary syndrome patients were more often treated with mechanical circulatory support devices (11% vs 3%, p<0.001 for both). Both risk scores were good predictors of in-hospital mortality in acute coronary syndrome patients and had similar areas under the receiver-operating characteristic curve (area under the curve: 0.742 for the CardShock vs 0.752 for IABP-SHOCK II, p=0.65). Their discrimination performance was only modest when applied to non-acute coronary syndrome patients (0.648 vs 0.619, respectively, p=0.31). Calibration was acceptable for both scores (Hosmer-Lemeshow p=0.22 for the CardShock and 0.68 for IABP-SHOCK II).Conclusions: In our cohort, both the CardShock and the IABP-SHOCK II risk scores were good predictors of in-hospital mortality in acute coronary syndrome-related cardiogenic shock.
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- 2024
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26. Cardiogenic shock; focus on ventilatory strategies, the elderly, and biomarker-based risk stratification
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Hongisto, Mari, University of Helsinki, Faculty of Medicine, Department of Cardiology, Doctoral Program in Clinical Research, Department of Emergency Medicine and ServicesHelsinki University Hospital, Helsingin yliopisto, lääketieteellinen tiedekunta, Kliininen tohtoriohjelma, Helsingfors universitet, medicinska fakulteten, Doktorandprogrammet i klinisk forskning, Hartikainen, Juha, Hongisto, Mari, Harjola, Veli-Pekka, and Lassus, Johan
- Subjects
lääketieteellinen - Abstract
Cardiogenic shock (CS) is the most severe form of acute heart failure (HF) characterized by hypotension and systemic hypoperfusion caused by cardiac dysfunction. Prolonged hypotension provokes neurohumoral compensatory mechanisms and systemic inflammatory responses, leading to organ injury followed by multiorgan failure and poor prognosis. CS may be caused by various etiological factors, acute coronary syndromes (ACS) being the most common cause. In addition to prompt recognition of CS, the cause of shock should be treated urgently, as by means of immediate revascularization in the case of ACS-related CS. Although aggressive therapy options, such as mechanical circulatory devices and ventilatory support, may be used, this approach is demanding on the patient, carries risk for complications, and requires additional healthcare resources. Despite advanced therapy options, prognosis in CS is still very poor with a short-term mortality rate up to 40%. Appropriate risk assessment in the early stage of shock is crucial to identify patients most likely to benefit from intensive and costly treatment. The aim of this thesis was to assess the treatment of respiratory failure in CS, focusing on the use of different ventilatory strategies and their impact on outcome; to evaluate the contemporary clinical picture, prognosis, and risk assessment of elderly (≥ 75 years) CS patients; and to investigate prognostic properties of two novel biomarkers in the early phase of CS. The study population consisted of the multinational, observational, prospective CardShock study, which included 219 patients with both ACS and non-ACS etiologies. Study I evaluated the use of different ventilatory strategies in CS. Although most patients (63%) were treated with invasive mechanical ventilation (IMV), a fair number were successfully treated with non-invasive ventilation (NIV) (12%). The intensity of respiratory support required was dependent on the severity of shock; those treated with IMV suffered from more severe shock and had higher 90-day mortality compared with those treated with NIV (49% vs. 27%). However, after balancing the IMV and NIV groups with shock severity and clinical characteristics, the choice of ventilatory strategy itself did not influence the outcome. Study II assessed the key features of elderly (≥ 75 years) CS patients. The elderly constituted a quarter of the population. Despite similar etiology and treatment of shock, they had a higher in-hospital mortality rate compared with younger patients (46% vs. 33%). However, those elderly patients who survived to hospital discharge had a prognosis comparable to that of the younger. The two contemporary risk prediction scores, the CardShock risk score and the IABP-SHOCK II risk score, proved to be useful in the early risk stratification in the elderly patients as well. Furthermore, by incorporating the novel biomarkers into the scores, the risk prediction ability of the scores improved markedly. Study III evaluated concentrations of a novel biomarker, growth differentiation factor 15 (GDF-15), in CS. GDF-15 is a stress-responsive cytokine that is expressed under acute and chronic stressful conditions and it has shown prognostic potential in various diseases. In this study GDF-15 levels were already very high at the beginning of CS and associated with markers of hypoperfusion (high lactate, low pH) and various acute organ dysfunctions (heart, renal, liver) indicating severe circulatory failure. High and increasing levels of GDF-15 were associated with a worse outcome, while low and decreasing levels were indicative of better prognosis. Furthermore, GDF-15 improved the early risk stratification of CS beyond the clinical risk score. Study IV investigated the levels of soluble urokinase-type plasminogen activator receptor (suPAR) in the early stage of CS. suPAR is a novel biomarker secreted in response to inflammatory stimuli and thought to reflect the level of immunoactivation. suPAR has prognostic ability in many acute and chronic diseases, including cardiovascular diseases, cancer, and sepsis. In this study, suPAR levels were clearly elevated during the first days of CS. High levels were associated with both acute and chronic organ dysfunctions. suPAR had independent prognostic potential in CS and improved the risk stratification, especially in the patients with intermediate risk. In conclusion, NIV can be used safely in the treatment of respiratory failure in suitable CS patients. The choice of ventilation strategy did not appear to influence outcome. Elderly patients constitute a considerable portion of CS patients with high mortality. Contemporary risk scores are also useful for early risk prediction in this age group. High levels of the novel biomarkers GDF-15 and suPAR are indicative of severe circulatory failure and end-organ injury, suggesting poor prognosis. These biomarkers may be new prognostic tools in the risk assessment of CS. Sydänperäinen sokki on monitahoinen oireyhtymä, jossa sydämen akuutti toimintahäiriö aiheuttaa sen supistumiskyvyn merkittävän heikentymisen johtaen vaikeaan verenkiertovajaukseen, kudosten hapenpuutteeseen ja monielinvaurioon sekä lopulta hoitamattomana kuolemaan. Oireyhtymän patogeneesissä myös elimistön neurohumoraalisilla vasteilla sekä systeemisen tulehdusreaktion kehittymisellä on oma roolinsa. Mikä tahansa sydämen toimintaa heikentävä sairaus voi olla syynä sydänperäiseen sokkiin, useimmiten kyseessä on laaja sydäninfarkti. Hoidon kulmakivenä on sydämen toimintahäiriön aiheuttaneen syyn tunnistaminen ja välitön korjaaminen. Sokkiin liittyvää verenkierto- ja hengitysvajausta hoidetaan tarvittaessa mekaanisia tukilaitteita avuksi käyttäen tehohoito-olosuhteissa, mikä on kuitenkin potilaille raskasta, altistaa komplikaatioille ja vaatii runsaasti terveydenhuollon resursseja. Kehittyneistä hoitotoimenpiteistä huolimatta kuolleisuus sydänperäiseen sokkiin on edelleen korkea noin 40 %. Hoidossa oleellista on sokin tunnistaminen, raskaista hoidoista hyötyvien korkean riskin potilaiden tunnistaminen ja hoitotoimenpiteiden aloittaminen riittävän varhaisessa vaiheessa ennen peruuttamattomien pääte-elinvaurioiden syntymistä. Tämän väitöskirjan tavoitteena oli selvittää sokkiin liittyvän hengitysvajauksen hoitoa keskittyen eri hengitystukimuotojen käyttöön ja niiden mahdolliseen ennustevaikutukseen sekä tutkia iäkkäiden (≥ 75-vuotiaiden) sokkipotilaiden taudin kliinistä kuvaa ja selvittää ajankohtaisten riskipisteytysmallien käyttökelpoisuutta tämän ikäryhmän ennusteen arvioimisessa. Lisäksi tavoitteena oli arvioida kahden uuden biomarkkerin käyttökelpoisuutta sydänperäisen sokin ennustearviossa. Väitöskirjan tutkimusaineisto on peräisin 219 potilasta käsittävästä monikansallisesta, havainnoivasta CardShock –tutkimuksesta. Ensimmäisessä osatyössä tutkittiin sydänperäiseen sokkiin sairastuneiden potilaiden hengitysvajauksen hoitoa ja eri hengitystukimuotojen käyttöä keskittyen non-invasiiviseen (NIV) hengitystukihoitoon. Tutkimuksessa havaittiin, että sydänperäiseen sokkiin sairastuneiden hengitystuen tarve riippui sokin vaikeusasteesta. Suurin osa potilaista (63%) hoidettiin invasiivisella mekaanisella ventilaatiolla (IMV) keinoilmatien kera, mutta merkittävä osa (12%) pärjäsi pelkästään non-invasiivisella ventilaatiolla (NIV). IMV:lla hoidetut potilaat kärsivät vaikeammasta sokin taudinkuvasta ja heillä oli korkeampi 90 päivän kuolleisuus NIV:llä hoidettuihin verrattuna (49% vs. 27%). Hengitystukistrategian valinnalla ei kuitenkaan ollut vaikutusta ennusteeseen. Toisessa osatyössä selvitettiin iäkkäiden (≥ 75-vuotiaiden) sydänperäiseen sokkiin sairastuneiden potilaiden kliinistä taudinkuvaa, hoitoa ja ennustearviota. Neljäsosa potilaista oli yli 75-vuotiaita. Huolimatta sokin samankaltaisesta etiologiasta ja hoidosta iäkkäiden potilaiden sairaalakuolleisuus oli selvästi nuorempia korkeampi (46% vs. 33%). Toisaalta sokista selvinneiden iäkkäiden ennuste ei eronnut nuorempien ennusteesta. Tutkimuksen mukaan sydänperäiseen sokkiin sairastuneille kehitetyt riskipisteytysmallit toimivat hyvin myös iäkkäillä ja niiden ennustearviota voidaan parantaa yhdistämällä ne biomarkkereiden kanssa. Kolmannessa osatyössä tutkittiin biomerkkiaine GDF-15 pitoisuuksia sydänperäisen sokin alkuvaiheessa sekä niiden yhteyttä ennusteeseen. GDF-15-pitoisuuksien tiedetään nousevan elimistön erilaisissa akuuteissa sekä kroonisissa stressitilanteissa ja GDF-15 omaa ennustearvoa useissa eri sairauksissa. Tutkimuksessa havaittiin, että GDF-15–pitoisuudet olivat hyvin korkeita jo sokin ensivaiheessa. Korkeat pitoisuudet olivat yhteydessä kudosten riittämätöntä verenkiertoa kuvastaviin biomarkkereihin (korkea laktaatti ja matala pH) ja elintoimintahäiriöihin (sydän, maksa, munuaiset) sekä huonompaan ennusteeseen. Lisäksi todettiin, että nouseva GDF-15 –taso oli merkki huonosta ennusteesta, kun taas laskevat pitoisuudet kuvastivat parempaa ennustetta. Yhdistettynä kliiniseen riskipisteytysmalliin GDF-15 paransi sokkipotilaiden ennustearviota huomattavasti. Neljännessä osatyössä määritettiin biomerkkiaine suPAR:n pitoisuuksia sydänperäisen sokin alkuvaiheessa. SuPAR on biomerkkiaine, jonka pitoisuus nousee sekä akuuttien että kroonisten tulehduksellisten tilojen yhteydessä kuvastaen elimistön immunoaktivaatiota. Sen on todettu omaavan ennustearvoa useissa eri sairauksissa, kuten syövissä, sepsiksessä sekä sydän- ja verisuonisairauksissa. Tässä tutkimuksessa suPAR-tasot olivat selvästi koholla sydänperäiseen sokkiin sairastuneilla. Korkeat pitoisuudet olivat yhteydessä eri elintoimintahäiriöihin ja suurempaan kuolemanriskiin. Tutkimuksessa todettiin, että suPAR oli itsenäinen sydänperäisen sokin ennustetekijä ja yhdistettynä kliinisen riskipisteytysmallin kanssa se paransi erityisesti keskiriskin potilaiden ennustearviota. Yhteenvetona voidaan todeta, että sydänperäiseen sokkiin liittyvää hengitysvajausta voidaan hoitaa voidaan turvallisesti myös NIV:lla oikein valikoiduilla potilailla, eikä hengitysvajauksen hoitomuodolla ole merkitystä potilaan ennusteen kannalta. Iäkkäät muodostavat merkittävän osan sydänperäiseen sokkiin sairastuneista potilaista ja sokin ennustearvioon luodut kliiniset riskipisteytysmallit toimivat hyvin myös tässä ikäryhmässä. Tutkitut biomerkkiaineet, GDF-15 ja suPAR, kuvastavat sydänperäiseen sokkiin liittyvää vaikeaa verenkiertovajausta sekä siihen liittyviä elintoimintahäiriöitä ja voivat olla avuksi sokkipotilaiden ennustearviossa.
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- 2022
27. Prognostic factors in cardiogenic shock. From bench to bedside - The CardShock Study
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Kataja, Anu, University of Helsinki, Faculty of Medicine, Doctoral Program in Clinical Research, Helsingin yliopisto, lääketieteellinen tiedekunta, Kliininen tohtoriohjelma, Helsingfors universitet, medicinska fakulteten, Doktorandprogrammet i klinisk forskning, Porela, Pekka, Harjola, Veli-Pekka, and Lassus, Johan
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lääketiede - Abstract
Cardiogenic shock (CS) is a state of hypotension and systemic hypoperfusion caused by cardiac dysfunction. CS is the most severe form of acute heart failure and the leading cause of death among patients hospitalized for acute coronary syndrome (ACS), which is the most common etiology of CS. Prolonged hypotension activates neurohormonal compensatory mechanisms and triggers inflammatory responses. CS often leads to multi-organ failure and has a poor prognosis (short-term mortality > 40%). The most important treatment strategy in ACS-related CS is immediate revascularization, usually with percutaneous coronary intervention. CS patients are typically managed in intensive care units and require vasoactive medication, ventilatory support, and sometimes mechanical circulatory support. Patient selection for the most aggressive therapies with possible complications and limited availability requires risk assessment in the initial stage of CS, before organ failure has become irreversible. The aim of this thesis was to evaluate easily available prognostic factors, including mental state evaluation and biomarkers of stress response and inflammation, in the early phase of CS. Data were from the CardShock study, a multinational, prospective, observational cohort of 219 CS patients with both ACS and non-ACS etiologies of CS. Patient recruitment was conducted between 2010 and 2012. Study I investigated baseline blood glucose levels and their relation to clinical picture and prognosis in CS. Hyperglycemia is a common phenomenon among critically ill patients. However, it is unclear whether hyperglycemia is fully adaptive and physiological or harmful during acute illness. In this CS population, blood glucose levels were distributed rather equally between the groups of normoglycemia (4.0-7.9 mmol/L), and mild (8.0-11.9 mmol/L), moderate (12.0-15.9 mmol/L) and severe (> 16 mmol/L) hyperglycemia. Hypoglycemia (< 4.0 mmol/L) was rare. Severe hyperglycemia was associated with acidosis and hyperlactatemia, reflecting profound hypoperfusion. Mortality was highest (60%) among CS patients with severe hyperglycemia or hypoglycemia, whereas patients with normoglycemia had the best prognosis (26% mortality). Moreover, severe hyperglycemia was independently associated with increased mortality. The prognostic value of baseline blood glucose level was less pronounced in patients with known diabetes. Study II evaluated the prevalence and prognostic significance of altered mental status (AMS) at the time of CS detection, and the associations of AMS to biochemistry and hemodynamic parameters. AMS is among the diagnostic criteria for CS as one of the clinical manifestations of end-organ hypoperfusion. Two-thirds of these CS patients presented with AMS at the time of shock detection as a sign of cerebral hypoperfusion. AMS was associated with lower systolic blood pressure and lower left ventricular ejection fraction, acidosis, hyperlactatemia, and hyperglycemia. Of these, acidosis was independently associated with AMS. Moreover, AMS was associated with more than two-fold short-term mortality compared with normal mental status. Study III examined the levels of growth differentiation factor 15 (GDF-15), a stress-responsive protein belonging to the transforming growth factor-β cytokine superfamily, in CS. The expression of GDF-15 is induced in many tissues and cell types in response to acute or chronic stressors. In this CS population, GDF-15 levels were very high already at the time of shock detection. High GDF-15 levels were associated with acidosis, hyperlactatemia, and biomarkers of cardiac, renal, and hepatic dysfunction. Moreover, high GDF-15 levels were independently associated with increased mortality. In addition, the kinetics of GDF-15 were different between survivors and non-survivors during the first days of shock. GDF-15 levels decreased among survivors as a positive response to treatment, whereas GDF-15 levels remained high or even increased among patients who subsequently died. For early risk stratification in CS, a GDF-1512h cut-off of 7000 ng/l was identified and found to provide incremental value to validated clinical risk scores. Study IV analyzed the levels and kinetics of inflammatory markers in CS, including C-reactive protein (CRP), interleukin 6 (IL-6), and procalcitonin (PCT). Inflammatory response with subsequent vasodilation is thought to play an important role in the complex pathophysiology of CS. Inflammatory marker levels were considerably elevated during the first days of shock. PCT peaked at 24 hours, while CRP continued to rise until 48 to 72 hours. High PCT and IL-6 levels were closely associated with acidosis, hyperlactatemia, and clinical findings of systemic hypoperfusion. In addition, high levels of PCT and IL-6 were associated with poor prognosis. During the first days of CS, high inflammatory marker levels seemed to reflect shock severity rather than infectious complications. In conclusion, patients in the early phase of CS present with various clinical and biochemical findings that reflect disturbed homeostasis, including hyperglycemia and AMS. In addition, high levels of GDF-15 and inflammatory markers are detected in CS, indicating organ dysfunction and profound circulatory failure. These should be regarded as warning signs of severe hypoperfusion and poor outcome and should be considered in early risk assessment. Sydänperäinen shokki on äkillisen sydämen vajaatoiminnan vaikein muoto, jossa sydämen pumppaustoiminnan häiriö johtaa voimakkaaseen verenpaineen laskuun ja verenkierron vajaukseen. Sydänperäisen shokin yleisin syy on sepelvaltimotautikohtaukseen liittyvä sydänlihasvaurio, joka aiheuttaa noin 80% tapauksista. Verenpaineen lasku johtaa elimistössä neurohormonaalisten järjestelmien sekä tulehdusvasteen aktivoitumiseen ja usein monielinvaurioon. Sydänperäisen shokin ennuste on huono, sillä jopa puolet potilaista menehtyy sairaalahoidon aikana. Sydänperäinen shokki onkin yleisin kuolinsyy sepelvaltimotautikohtauksen vuoksi sairaalahoitoon joutuneilla potilailla. Tärkein hoitomuoto sepelvaltimotautikohtaukseen liittyvässä shokissa on välitön ahtautuneen sepelvaltimon avaaminen, useimmiten pallolaajennuksella. Potilaat vaativat tyypillisesti tehohoitoa, verenkiertoa tukevaa lääkitystä sekä hengityksen ja toisinaan myös verenkierron tukemista koneellisesti. Edellä mainitut hoitomuodot ovat raskaita, sisältävät huomattavia komplikaatioriskejä ja kuluttavat paljon terveydenhuollon voimavaroja. Näin ollen intensiivisimmät hoidot tulisi rajata potilaille, jotka niistä todennäköisimmin hyötyvät, ja hoito aloittaa välittömästi ennen pysyvien elinvaurioiden kehittymistä. Tämän väitöskirjatyön tavoitteena oli tutkia sydänperäisen shokin alkuvaiheessa todettavia, helposti saatavilla olevia ennustetekijöitä kuten verikokeissa ja potilaan kliinisessä tutkimuksessa havaittavia poikkeavuuksia. Väitöskirjan aineisto on peräisin 219 potilaan CardShock-tutkimuksesta, joka on eurooppalainen etenevä, havainnoiva monikeskustutkimus. Potilasaineisto kerättiin vuosina 2010-2012. Osatyössä I tutkittiin sydänperäiseen shokkiin sairastuneiden potilaiden alkuvaiheen verensokeritasoja ja niiden yhteyttä ennusteeseen. Koholla oleva verensokeritaso eli hyperglykemia on yleinen ilmiö vaikeasti sairailla potilailla. On kuitenkin epäselvää, onko verensokeritason nousu pääosin tarkoituksenmukainen ja fysiologinen ilmiö vai onko se itsessään haitallista äkillisen sairastumisen yhteydessä. Tässä potilasaineistossa verensokeritasot olivat jakautuneet suhteellisen tasaisesti normaalin verensokerin (4.0-7.9 mmol/L) sekä lievän (8.0-11.9 mmol/L), keskivaikean (12.0-15.9 mmol/L) ja vaikean (> 16 mmol/L) hyperglykemian välillä, kun taas matala verensokeri (< 4.0 mmol/L) oli harvinaista. Vaikea hyperglykemia oli yhteydessä veren matalaan pH-arvoon sekä kohonneeseen laktaattipitoisuuteen kuvastaen kudosten hapenpuutetta ja verenkierron vajausta. Kuolleisuus oli suurinta (60%) niillä potilailla, joiden tulovaiheen verensokeri oli joko hyvin korkea tai poikkeuksellisen matala. Vaikea hyperglykemia oli itsenäinen kuolleisuuden riskitekijä. Sen sijaan aiemmin todettu diabetes vähensi verensokerin ennustearvoa sydänperäisessä shokissa. Osatyössä II tarkasteltiin sydänperäisen shokin alkuvaiheessa todetun poikkeavan tajunnantason merkitystä ja ennustevaikutusta. Kahdella kolmasosalla potilaista oli shokin toteamisvaiheessa poikkeava tajunnantaso oireena merkittävästä verenkierron vajauksesta. Poikkeava tajunnantaso oli yhteydessä matalaan verenpaineeseen, voimakkaasti alentuneeseen sydämen pumppaustoimintaan, veren matalaan pH-arvoon sekä kohonneisiin laktaatti- ja verensokeripitoisuuksiin. Näistä tekijöistä poikkeavaan tajunnantasoon oli itsenäisesti yhteydessä vain matala pH. Poikkeavaan tajunnantasoon liittyi yli kaksinkertainen kuolemanriski verrattuna niihin potilaisiin, joiden tajunnantaso säilyi normaalina shokista huolimatta. Osatyössä III määritettiin GDF-15-nimisen proteiinin pitoisuuksia veressä sydänperäisen shokin ensipäivinä ja niiden yhteyttä ennusteeseen. GDF-15:n tarkat vaikutukset elimistössä ovat vielä osittain epäselviä, mutta sen eritys lisääntyy monissa kudoksissa vasteena äkillisiin ja pitkäaikaisiin sairauksiin. Tutkimus osoitti, että GDF-15-tasot ovat hyvin korkeita jo sydänperäisen shokin toteamishetkellä. Korkeaan GDF-15-pitoisuuteen liittyi veren matala pH-arvo, kohonnut laktaattiarvo sekä sydämen, munuaisten ja maksan toimintahäiriöitä kuvastavia muutoksia verikokeissa. Korkea GDF-15-pitoisuus oli yhteydessä lisääntyneeseen kuolleisuuteen, ja erityisen suuri kuolemanriski oli potilailla, joiden GDF-15-pitoisuus nousi hoidosta huolimatta. Sen sijaan GDF-15-tason lasku kuvasti suotuisaa vastetta hoitoon ja hyvää ennustetta. Osatyössä IV tutkittiin tulehdusvastetta kuvastavien biomerkkiaineiden pitoisuuksia veressä sydänperäisen shokin alkuvaiheessa. Elimistön voimakkaan tulehdusreaktion ajatellaan olevan tärkeä tekijä sydänperäisen shokin kehittymisessä. Tutkimuksessa havaittiin, että tulehdusmerkkiaineet olivat selvästi koholla shokin ensipäivinä. Prokalsitoniini (PCT) saavutti huippuarvonsa 24 tunnin kohdalla, kun taas C-reaktiivinen proteiini (CRP) nousi 48-72 tuntiin asti. Korkeat PCT- ja interleukiini 6 (IL-6) -pitoisuudet liittyivät tiiviisti veren matalaan pH-arvoon ja kohonneeseen laktaattiarvoon sekä verenkierron vajausta kuvastaviin kliinisiin löydöksiin. Sen lisäksi korkeat PCT- ja IL-6-pitoisuudet ennustivat kuolleisuutta. Kokonaisuudessaan kohonneet tulehdusmerkkiaineet kuvastivat enemmänkin shokin vaikeusastetta kuin infektioita. Yhteenvetona voidaan todeta, että sydänperäiseen shokkiin sairastuneilla potilailla on monia elimistön tasapainotilan vakavaa häiriintymistä kuvaavia löydöksiä, kuten muutoksia verensokeritasossa tai tajunnassa. Voimakkaasti koholla olevat GDF-15- sekä tulehdusmerkkiainepitoisuudet kuvastavat vaikeaa verenkierron vajausta ja suurta kuolemanriskiä. Näitä löydöksiä voidaan hyödyntää riskiarviossa jo sydänperäisen shokin alkuvaiheessa.
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- 2022
28. Biomarkers in the assessment of prognosis and organ injury in cardiogenic shock
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Jäntti, Toni, University of Helsinki, Faculty of Medicine, Doctoral Program in Clinical Research, Helsinki University HospitalHeart and Lung CenterDivision of Cardiology, Helsingin yliopisto, lääketieteellinen tiedekunta, Kliininen tohtoriohjelma, Helsingfors universitet, medicinska fakulteten, Doktorandprogrammet i klinisk forskning, Miettinen, Heikki, Lassus, Johan, and Harjola, Veli-Pekka
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lääketiede - Abstract
Cardiogenic shock is the most severe form of acute heart failure. It is a syndrome in which an initial insult results in deterioration of cardiac output, leading to systemic hypoperfusion often with accompanying microcirculatory dysfunction and systemic inflammatory responses resulting in organ injury and high mortality. Despite modern advanced therapies, short-term mortality in cardiogenic shock remains high at approximately 40%. Mortality in cardiogenic shock is often caused by multi-organ failure, but the incidence, sequence and predisposing factors for organ injury and impairment in cardiogenic shock patients remains largely unstudied. Novel invasive therapies, such as mechanical circulatory support devices may be life-saving in certain situations but also carry a high risk of complications, increasing the need for risk assessment tools for selection of suitable patients while avoiding harm and futility. The aim of this thesis was to investigate biomarkers associated with end-organ injury in cardiogenic shock, to assess the incidence of organ injury, and to assess the prognostic importance of the biomarkers in cardiogenic shock patients. The study population was 179 patients enrolled in the multinational, prospective, observational CardShock study with blood samples available. Study I evaluated the prevalence and prognostic importance of several liver biomarkers and their early changes within the first 24 hours of study enrolment. We found that although elevated alanine aminotransferase (ALT) was frequent already at baseline, it was not independently associated with 90-day mortality, whereas an early increase in ALT by 20% or more within the first 24 hours was strongly and independently associated with higher 90-day mortality. Findings in study I suggest that early increases in ALT in patients in cardiogenic shock are related to organ hypoperfusion, which was supported by the association of ALT increase with lower cardiac index and other clinical markers of hypoperfusion. Study II assessed albumin levels in cardiogenic shock patients and their association with 90-day mortality. Hypoalbuminemia was present in 75% of patients in the early phase of cardiogenic shock. Hypoalbuminemia was associated with pre-existing comorbidities, higher levels of C-reactive protein and lower levels of hemoglobin. Plasma albumin levels at baseline were independently associated with 90-day all-cause mortality, with mortality increasing across lower albumin quartiles in a linear fashion. Study III investigated two biomarkers – plasma proenkephalin (P-PENK) and plasma neutrophil gelatinase-associated lipocalin (P-NGAL) – which have previously been shown to be associated with acute kidney injury (AKI). Levels of both P-PENK and P-NGAL differed between patients who did and did not develop AKI defined by an increase in creatinine within 48 hours (AKIcrea48h) as well as between 90-day survivors and nonsurvivors. High baseline levels of both P-PENK and P-NGAL were able to predict the occurrence of AKIcrea48h with reasonable accuracy. High levels of P-PENK and P-NGAL at 24 hours were independently associated with increased 90-day all-cause mortality after adjustments for AKIcrea48h and two risk scores validated for cardiogenic shock patient populations. Study IV examined the associations of a novel biomarker, circulating miR-423-5p, with clinical findings, other biomarkers and outcome. Above median levels of circulating miR-423-5p were associated with markers of hypoperfusion, organ injury and dysfunction. A miR-423-5p level above median also predicted 90-day mortality independently of established risk factors in cardiogenic shock patients. The association of miR-423-5p with high-sensitivity troponin T, an established marker of cardiac injury, depended on the etiology of cardiogenic shock. In conclusion, the studied biomarkers (ALT, albumin, P-PENK, P-NGAL and miR-423-5p) relate to organ injury, provide additional prognostic information compared with clinical risk scores and can be utilized in the risk assessment of patients in cardiogenic shock. Sydänperäinen shokki on sydämen äkillisen vajaatoiminnan vaikea-asteisin ilmenemismuoto. Kyseessä on oireyhtymä, jossa tapahtumaketjun käynnistävä vaurio johtaa sydämen minuuttivirtauksen alenemaan, joka puolestaan yhdessä mikroverenkierron toimintahäiriön ja elimistön tulehdusvasteen kanssa johtaa elimistön verenkiertovajaukseen, elinvaurioihin ja korkeaan kuolleisuuteen. Sydänperäisen shokin hoitomuotojen kehittymisestä huolimatta kuolleisuus on pysynyt edelleen korkeana noin 40%:ssa. Uudet kajoavat hoitokeinot kuten mekaaniset verenkierron tukilaitteet saattavat tietyissä tilanteissa pelastaa ihmishenkiä, mutta niihin toisaalta liittyvät korkeat komplikaatioriskit ovat lisänneet tarvetta työkaluille hoidosta hyötyvien potilaiden tunnistamiseksi haittojen ja hyödyttömien hoitojen välttämiseksi. Tämän väitöskirjan tavoitteena oli arvioida sydänperäiseen shokkiin liittyvien elinvaurioiden biomerkkiaineita ja niiden käyttökelpoisuutta sydänperäisen shokin ennusteen arvioinnissa. Tutkimusaineistona oli 179 monikansalliseen, havainnoivaan ja etenevään CardShock -tutkimukseen osallistunutta potilasta, joilta oli verinäyte saatavilla biomerkkiaineiden analysoimiseksi. Ensimmäisessä osatyössä arvioitiin useiden maksaan liittyvien biomerkkiaineiden poikkeavien löydösten yleisyyttä tässä aineistossa sekä aikaisten 24 tunnin sisällä hoidon alusta tapahtuvien muutosten ennusteellista merkittävyyttä. Tutkimuksessa havaitsimme, että vaikkakin alaniiniaminotransferaasi (ALT) oli usein koholla jo tutkimuksen alkuhetkellä, koholla olevat arvot eivät ennustaneet kuolleisuutta itsenäisesti muista tekijöistä riippumatta toisin kuin ensimmäisten 24 tunnin aikana tapahtuva ALT-arvojen nousu yli 20%, mikä oli itsenäinen ja merkittävä 90-päivän kuolleisuuden riskitekijä. Ensimmäisen osajulkaisun löydösten perusteella aikainen ALT-arvojen nousu näyttää yhdistyvän pääte-elinten verenkiertovajaukseen, mitä tukivat tutkimuksessa todetut ALT-nousun yhdistyminen matalampaan sydänindeksiin ja muihin verenkiertovajauksen kliinisiin ilmentymiin. Toisessa osatyössä tutkittiin albumiinitasoja sydänperäisessä shokissa olevilla potilailla ja niiden yhteyttä 90-päivän kuolleisuuteen. Matalat albumiinitasot olivat yhteydessä useisiin kroonisiin sairauksiin, matalaan hemoglobiiniin ja korkeampiin C-reaktiivisen proteiinin tasoihin. Matalat albumiinitasot olivat hyvin yleisiä tutkimuspotilailla jo sydänperäisen shokin varhaisessa vaiheessa. Plasman albumiinitaso oli itsenäisesti yhteydessä 90-päivän kokonaiskuolleisuuteen, ja kuolleisuus kasvoi suoraviivaisesti suhteessa matalampaan albumiinitasoon. Kolmas osatyö selvitti kahden biomerkkiaineen, plasman proenkefaliinin (P-PENK) ja neutrofiilin gelatinaasiin assosioituvan lipokaliinin (P-NGAL) yhteyttä äkilliseen munuaisvaurioon ja kuolleisuuteen sydänperäisessä shokissa. P-PENK ja P-NGAL-tasot olivat korkeammat sekä 90 päivän kuluessa kuolleilla potilailla, että niillä potilailla, joille kehittyi akuutti munuaisvaurio. Korkeat P-PENK ja P-NGAL lähtötasot ennustivat kreatiniinin nousun perusteella todettua akuuttia munuaisvauriota (AKIkrea48h) kohtuullisella tarkkuudella. Korkeat P-PENK ja P-NGAL tasot 24 tunnin kohdalla liittyivät suurempaan 90-päivän kokonaiskuolleisuuteen itsenäisesti riippumatta vakioinnista AKIkrea48h:n ja kahden sydänperäisen shokin ennusteen arviointiin kehitetyn riskipisteytyksen suhteen. Neljännessä osatyössä tarkasteltiin uuden biomerkkiaineen, verenkierrossa esiintyvän miR-423-5p:n yhteyttä kliinisiin löydöksiin, muihin biomerkkiaineisiin ja päätetapahtumiin. Mediaanitasoja korkeammat miR-423-5p -pitoisuudet yhdistyivät verenkiertovajauksen merkkeihin, sekä elinvaurioihin/toimintahäiriöihin. MiR-423-5p:n yhteys sydänlihasvaurion merkkiaineena käytettyyn herkkään troponiini T:hen riippui sydänperäisen shokin aiheuttajasta. Yhteenvetona voidaan todeta, että tutkitut biomerkkiaineet (ALT, albumiini, P-PENK, P-NGAL sekä miR-423-5p) ovat yhteydessä elinvaurioihin, antavat lisätietoa ennusteesta sydänperäisen shokin ennusteen arviointiin kehitettyjen kliinisten riskipisteytysten lisäksi ja niitä voidaan hyödyntää osana sydänperäisessä shokissa olevien potilaiden riskiarviota.
- Published
- 2021
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