Browsing by Subject "Cardiogenic shock"

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  • Cerlinskaite, Kamile; Javanainen, Tuija; Cinotti, Raphael; Mebazaa, Alexandre (2018)
    Acute heart failure (AHF) is a life-threatening medical condition, where urgent diagnostic and treatment methods are of key importance. However, there are few evidence-based treatment methods. Interestingly, despite relatively similar ways of management of AHF throughout the globe, mid-term outcome in East Asia, including South Korea is more favorable than in Europe. Yet, most of the treatment methods are symptomatic. The cornerstone of AHF management is identifying precipitating factors and specific phenotype. Multidisciplinary approach is important in AHF, which can be caused or aggravated by both cardiac and non-cardiac causes. The main pathophysiological mechanism in AHF is congestion, both systemic and inside the organs (lung, kidney, or liver). Cardiac output is often preserved in AHF except in a few cases of advanced heart failure. This paper provides guidance on AHF management in a time-based approach. Treatment strategies, criteria for triage, admission to hospital and discharge are described.
  • Tolppanen, Heli; Rivas-Lasarte, Mercedes; Lassus, Johan; Sans-Rosello, Jordi; Hartmann, Oliver; Lindholm, Matias; Arrigo, Mattia; Tarvasmäki, Tuukka; Kober, Lars; Thiele, Holger; Pulkki, Kari; Spinar, Jindrich; Parissis, John; Banaszewski, Marek; Silva-Cardoso, Jose; Carubelli, Valentina; Sionis, Alessandro; Harjola, Veli-Pekka; Mebazaa, Alexandre (2017)
    Background: The clinical CardShock risk score, including baseline lactate levels, was recently shown to facilitate risk stratification in patients with cardiogenic shock (CS). As based on baseline parameters, however, it may not reflect the change in mortality risk in response to initial therapies. Adrenomedullin is a prognostic biomarker in several cardiovascular diseases and was recently shown to associate with hemodynamic instability in patients with septic shock. The aim of our study was to evaluate the prognostic value and association with hemodynamic parameters of bioactive adrenomedullin (bio-ADM) in patients with CS. Methods: CardShock was a prospective, observational, European multinational cohort study of CS. In this sub-analysis, serial plasma bio-ADM and arterial blood lactate measurements were collected from 178 patients during the first 10 days after detection of CS. Results: Both bio-ADM and lactate were higher in 90-day non-survivors compared to survivors at all time points (P <0.05 for all). Lactate showed good prognostic value during the initial 24 h (AUC 0.78 at admission and 0.76 at 24 h). Subsequently, lactate returned normal ( 55.7 pg/mL) at 48 h compared to those with low bio-ADM levels (49.1 vs. 22.6%, P = 0.001). High levels of bio-ADM were associated with impaired cardiac index, mean arterial pressure, central venous pressure, and systolic pulmonary artery pressure during the study period. Furthermore, high levels of bio-ADM at 48 to 96 h were related to persistently impaired cardiac and end-organ function. Conclusions: Bio-ADM is a valuable prognosticator and marker of impaired hemodynamics in CS patients. High levels of bio-ADM may show shock refractoriness and developing end-organ dysfunction and thus help to guide therapeutic approach in patients with CS.
  • Tolppanen, Heli; Rivas-Lasarte, Mercedes; Lassus, Johan; Sans-Roselló, Jordi; Hartmann, Oliver; Lindholm, Matias; Arrigo, Mattia; Tarvasmäki, Tuukka; Köber, Lars; Thiele, Holger; Pulkki, Kari; Spinar, Jindrich; Parissis, John; Banaszewski, Marek; Silva-Cardoso, Jose; Carubelli, Valentina; Sionis, Alessandro; Harjola, Veli-Pekka; Mebazaa, Alexandre (Springer Paris, 2017)
    Abstract Background The clinical CardShock risk score, including baseline lactate levels, was recently shown to facilitate risk stratification in patients with cardiogenic shock (CS). As based on baseline parameters, however, it may not reflect the change in mortality risk in response to initial therapies. Adrenomedullin is a prognostic biomarker in several cardiovascular diseases and was recently shown to associate with hemodynamic instability in patients with septic shock. The aim of our study was to evaluate the prognostic value and association with hemodynamic parameters of bioactive adrenomedullin (bio-ADM) in patients with CS. Methods CardShock was a prospective, observational, European multinational cohort study of CS. In this sub-analysis, serial plasma bio-ADM and arterial blood lactate measurements were collected from 178 patients during the first 10 days after detection of CS. Results Both bio-ADM and lactate were higher in 90-day non-survivors compared to survivors at all time points (P < 0.05 for all). Lactate showed good prognostic value during the initial 24 h (AUC 0.78 at admission and 0.76 at 24 h). Subsequently, lactate returned normal (≤2 mmol/L) in most patients regardless of later outcome with lower prognostic value. By contrast, bio-ADM showed increasing prognostic value from 48 h and beyond (AUC 0.71 at 48 h and 0.80 at 5–10 days). Serial measurements of either bio-ADM or lactate were independent of and provided added value to CardShock risk score (P < 0.001 for both). Ninety-day mortality was more than double higher in patients with high levels of bio-ADM (>55.7 pg/mL) at 48 h compared to those with low bio-ADM levels (49.1 vs. 22.6%, P = 0.001). High levels of bio-ADM were associated with impaired cardiac index, mean arterial pressure, central venous pressure, and systolic pulmonary artery pressure during the study period. Furthermore, high levels of bio-ADM at 48 to 96 h were related to persistently impaired cardiac and end-organ function. Conclusions Bio-ADM is a valuable prognosticator and marker of impaired hemodynamics in CS patients. High levels of bio-ADM may show shock refractoriness and developing end-organ dysfunction and thus help to guide therapeutic approach in patients with CS. Study identifier of CardShock study NCT01374867 at clinicaltrials.gov
  • Kataja, Anu; Tarvasmäki, Tuukka; Lassus, Johan; Kober, Lars; Sionis, Alessandro; Spinar, Jindrich; Parissis, John; Carubelli, Valentina; Cardoso, Jose; Banaszewski, Marek; Marino, Rossella; Nieminen, Markku S.; Mebazaa, Alexandre; Harjola, Veli-Pekka (2018)
    Background: Altered mental status is among the signs of hypoperfusion in cardiogenic shock, the most severe form of acute heart failure. The aim of this study was to investigate the prevalence of altered mental status, to identify factors associating with it, and to assess the prognostic significance of altered mental status in cardiogenic shock. Methods: Mental status was assessed at presentation of shock in 215 adult cardiogenic shock patients in a multinational, prospective, observational study. Clinical picture, biochemical variables, and short-term mortality were compared between patients presenting with altered and normal mental status. Results: Altered mental status was detected in 147 (68%) patients, whereas 68 (32%) patients had normal mental status. Patients with altered mental status were older (68 vs. 64 years, p=0.04) and more likely to have an acute coronary syndrome than those with normal mental status (85% vs. 74%, p=0.04). Altered mental status was associated with lower systolic blood pressure (76 vs. 80 mmHg, p=0.03) and lower arterial pH (7.27 vs. 7.35, p Conclusions: Altered mental status is a common clinical sign of systemic hypoperfusion in cardiogenic shock and is associated with poor outcome. It is also associated with several biochemical findings that reflect inadequate tissue perfusion, of which low arterial pH is independently associated with altered mental status.
  • Jäntti, Toni; Segersvärd, Heli; Tolppanen, Heli; Tarvasmäki, Tuukka; Lassus, Johan; Devaux, Yvan; Vausort, Melanie; Pulkki, Kari; Sionis, Alessandro; Bayes-Genis, Antoni; Tikkanen, Ilkka; Lakkisto, Päivi; Harjola, Veli-Pekka (2019)
    Aims The role of microRNAs has not been studied in cardiogenic shock. We examined the potential role of miR-423-5p level to predict mortality and associations of miR-423-5p with prognostic markers in cardiogenic shock. Methods and results We conducted a prospective multinational observational study enrolling consecutive cardiogenic shock patients. Blood samples were available for 179 patients at baseline to determine levels of miR-423-5p and other biomarkers. Patients were treated according to local practice. Main outcome was 90 day all-cause mortality. Median miR-423-5p level was significantly higher in 90 day non-survivors [median 0.008 arbitrary units (AU) (interquartile range 0.003-0.017) vs. 0.004 AU (0.002-0.009), P = 0.003]. miR-423-5p level above median was associated with higher lactate (median 3.7 vs. 2.4 mmol/L, P = 0.001) and alanine aminotransferase levels (median 68 vs. 35 IU/L, P <0.001) as well as lower cardiac index (1.8 vs. 2.4, P = 0.04) and estimated glomerular filtration rate (56 vs. 70 mL/min/1.73 m(2), P = 0.002). In Cox regression analysis, miR-423-5p level above median was associated with 90 day all-cause mortality independently of established risk factors of cardiogenic shock [adjusted hazard ratio 1.9 (95% confidence interval 1.2-3.2), P = 0.01]. Conclusions In cardiogenic shock patients, above median level of miR-423-5p at baseline is associated with markers of hypoperfusion and seems to independently predict 90 day all-cause mortality.
  • Tarvasmäki, Tuukka; Lassus, Johan; Varpula, Marjut; Sionis, Alessandro; Sund, Reijo; Kober, Lars; Spinar, Jindrich; Parissis, John; Banaszewski, Marek; Cardoso, Jose Silva; Carubelli, Valentina; Di Somma, Salvatore; Mebazaa, Alexandre; Harjola, Veli-Pekka; CardShock Study Investigators (2016)
    Background: Vasopressors and inotropes remain a cornerstone in stabilization of the severely impaired hemodynamics and cardiac output in cardiogenic shock (CS). The aim of this study was to analyze current real-life use of these medications, and their impact on outcome and on changes in cardiac and renal biomarkers over time in CS. Methods: The multinational CardShock study prospectively enrolled 219 patients with CS. The use of vasopressors and inotropes was analyzed in relation to the primary outcome, i.e., 90-day mortality, with propensity score methods in 216 patients with follow-up data available. Changes in cardiac and renal biomarkers over time until 96 hours from baseline were analyzed with linear mixed modeling. Results: Patients were 67 (SD 12) years old, 26 % were women, and 28 % had been resuscitated from cardiac arrest prior to inclusion. On average, systolic blood pressure was 78 (14) and mean arterial pressure 57 (11) mmHg at detection of shock. 90-day mortality was 41 %. Vasopressors and/or inotropes were administered to 94 % of patients and initiated principally within the first 24 hours. Noradrenaline and adrenaline were given to 75 % and 21 % of patients, and 30 % received several vasopressors. In multivariable logistic regression, only adrenaline (21 %) was independently associated with increased 90-day mortality (OR 5.2, 95 % CI 1.88, 14.7, p = 0.002). The result was independent of prior cardiac arrest (39 % of patients treated with adrenaline), and the association remained in propensity-score-adjusted analysis among vasopressor-treated patients (OR 3.0, 95 % CI 1.3, 7.2, p = 0.013); this was further confirmed by propensity-score-matched analysis. Adrenaline was also associated, independent of prior cardiac arrest, with marked worsening of cardiac and renal biomarkers during the first days. Dobutamine and levosimendan were the most commonly used inotropes (49 % and 24 %). There were no differences in mortality, whether noradrenaline was combined with dobutamine or levosimendan. Conclusion: Among vasopressors and inotropes, adrenaline was independently associated with 90-day mortality in CS. Moreover, adrenaline use was associated with marked worsening in cardiac and renal biomarkers. The combined use of noradrenaline with either dobutamine or levosimendan appeared prognostically similar.
  • Chioncel, Ovidiu; Parissis, John; Mebazaa, Alexandre; Thiele, Holger; Desch, Steffen; Bauersachs, Johann; Harjola, Veli-Pekka; Antohi, Elena-Laura; Arrigo, Mattia; Gal, Tuvia B.; Celutkiene, Jelena; Collins, Sean P.; DeBacker, Daniel; Iliescu, Vlad A.; Jankowska, Ewa; Jaarsma, Tiny; Keramida, Kalliopi; Lainscak, Mitja; Lund, Lars H.; Lyon, Alexander R.; Masip, Josep; Metra, Marco; Miro, Oscar; Mortara, Andrea; Mueller, Christian; Mullens, Wilfried; Nikolaou, Maria; Piepoli, Massimo; Price, Susana; Rosano, Giuseppe; Vieillard-Baron, Antoine; Weinstein, Jean M.; Anker, Stefan D.; Filippatos, Gerasimos; Ruschitzka, Frank; Coats, Andrew J. S.; Seferovic, Petar (2020)
    Cardiogenic shock (CS) is a complex multifactorial clinical syndrome with extremely high mortality, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ failure and death. There is a large spectrum of CS presentations resulting from the interaction between an acute cardiac insult and a patient's underlying cardiac and overall medical condition. Phenotyping patients with CS may have clinical impact on management because classification would support initiation of appropriate therapies. CS management should consider appropriate organization of the health care services, and therapies must be given to the appropriately selected patients, in a timely manner, whilst avoiding iatrogenic harm. Although several consensus-driven algorithms have been proposed, CS management remains challenging and substantial investments in research and development have not yielded proof of efficacy and safety for most of the therapies tested, and outcome in this condition remains poor. Future studies should consider the identification of the new pathophysiological targets, and high-quality translational research should facilitate incorporation of more targeted interventions in clinical research protocols, aimed to improve individual patient outcomes. Designing outcome clinical trials in CS remains particularly challenging in this critical and very costly scenario in cardiology, but information from these trials is imperiously needed to better inform the guidelines and clinical practice. The goal of this review is to summarize the current knowledge concerning the definition, epidemiology, underlying causes, pathophysiology and management of CS based on important lessons from clinical trials and registries, with a focus on improving in-hospital management.
  • Leopold, Valentine; Gayat, Etienne; Pirracchio, Romain; Spinar, Jindrich; Parenica, Jiri; Tarvasmäki, Tuukka; Lassus, Johan; Harjola, Veli-Pekka; Champion, Sebastien; Zannad, Faiez; Valente, Serafina; Urban, Philip; Chua, Horng-Ruey; Bellomo, Rinaldo; Popovic, Batric; Ouweneel, Dagmar M.; Henriques, Jose P. S.; Simonis, Gregor; Levy, Bruno; Kimmoun, Antoine; Gaudard, Philippe; Basir, Mir Babar; Markota, Andrej; Adler, Christoph; Reuter, Hannes; Mebazaa, Alexandre; Chouihed, Tahar (2018)
    Catecholamines have been the mainstay of pharmacological treatment of cardiogenic shock (CS). Recently, use of epinephrine has been associated with detrimental outcomes. In the present study we aimed to evaluate the association between epinephrine use and short-term mortality in all-cause CS patients. We performed a meta-analysis of individual data with prespecified inclusion criteria: (1) patients in non-surgical CS treated with inotropes and/or vasopressors and (2) at least 15% of patients treated with epinephrine administrated alone or in association with other inotropes/vasopressors. The primary outcome was short-term mortality. Fourteen published cohorts and two unpublished data sets were included. We studied 2583 patients. Across all cohorts of patients, the incidence of epinephrine use was 37% (17-76%) and short-term mortality rate was 49% (21-69%). A positive correlation was found between percentages of epinephrine use and short-term mortality in the CS cohort. The risk of death was higher in epinephrine-treated CS patients (OR [CI] = 3.3 [2.8-3.9]) compared to patients treated with other drug regimens. Adjusted mortality risk remained striking in epinephrine-treated patients (n = 1227) (adjusted OR = 4.7 [3.4-6.4]). After propensity score matching, two sets of 338 matched patients were identified and epinephrine use remained associated with a strong detrimental impact on short-term mortality (OR = 4.2 [3.0-6.0]). In this very large cohort, epinephrine use for hemodynamic management of CS patients is associated with a threefold increase of risk of death.
  • CardShock Investigators; Hongisto, Mari; Kataja, Anu; Tarvasmäki, Tuukka; Holopainen, Anu; Javanainen, Tuija; Jurkko, Raija; Jäntti, Toni; Kimmoun, Antoine; Levy, Bruno; Mebazaa, Alexandre; Pulkki, Kari; Sionis, Alessandro; Tolppanen, Heli; Wollert, Kai C.; Harjola, Veli-Pekka; Lassus, Johan (2019)
    Background: The aim of this study was to assess the levels, kinetics, and prognostic value of growth differentiation factor 15 (GDF-15) in cardiogenic shock (CS). Methods and Results: Levels of GDF-15 were determined in serial plasma samples (0-120 h) from 177 CS patients in the CardShock study. Kinetics of GDF-15, its association with 90-day mortality, and incremental value for risk stratification were assessed. The median GDF-15(0h) level was 9647 ng/L (IQR 4500-19,270 ng/L) and levels above median were significantly associated with acidosis, hyperlactatemia, renal dysfunction, and higher 90-day mortality (56% vs 28%, P7000 ng/L was identified as a strong predictor of death (OR 5.0; 95% CI 1.9-3.8, P=.002). Adding GDF-15(12h) >7000 ng/L to the CardShock risk score improved discrimination and risk stratification for 90-day mortality. Conclusions: GDF-15 levels are highly elevated in CS and associated with markers of systemic hypoperfusion and end-organ dysfunction. GDF-15 helps to discriminate survivors from non-survivors very early in CS.
  • Jäntti, Toni; Tarvasmäki, Tuukka; Harjola, Veli-Pekka; Pulkki, Kari; Turkia, Heidi; Sabell, Tuija; Tolppanen, Heli; Jurkko, Raija; Hongisto, Mari; Kataja, Anu; Sionis, Alessandro; Silva-Cardoso, Jose; Banaszewski, Marek; DiSomma, Salvatore; Mebazaa, Alexandre; Haapio, Mikko; Lassus, Johan (Springer International Publishing, 2021)
    Abstract Background Acute kidney injury (AKI) is a frequent form of organ injury in cardiogenic shock. However, data on AKI markers such as plasma proenkephalin (P-PENK) and neutrophil gelatinase-associated lipocalin (P-NGAL) in cardiogenic shock populations are lacking. The objective of this study was to assess the ability of P-PENK and P-NGAL to predict acute kidney injury and mortality in cardiogenic shock. Results P-PENK and P-NGAL were measured at different time points between baseline and 48 h in 154 patients from the prospective CardShock study. The outcomes assessed were AKI defined by an increase in creatinine within 48 h and all-cause 90-day mortality. Mean age was 66 years and 26% were women. Baseline levels of P-PENK and P-NGAL (median [interquartile range]) were 99 (71–150) pmol/mL and 138 (84–214) ng/mL. P-PENK > 84.8 pmol/mL and P-NGAL > 104 ng/mL at baseline were identified as optimal cut-offs for AKI prediction and independently associated with AKI (adjusted HRs 2.2 [95% CI 1.1–4.4, p = 0.03] and 2.8 [95% CI 1.2–6.5, p = 0.01], respectively). P-PENK and P-NGAL levels at baseline were also associated with 90-day mortality. For patients with oliguria < 0.5 mL/kg/h for > 6 h before study enrollment, 90-day mortality differed significantly between patients with low and high P-PENK/P-NGAL at baseline (5% vs. 68%, p < 0.001). However, the biomarkers provided best discrimination for mortality when measured at 24 h. Identified cut-offs of P-PENK24h > 105.7 pmol/L and P-NGAL24h > 151 ng/mL had unadjusted hazard ratios of 5.6 (95% CI 3.1–10.7, p < 0.001) and 5.2 (95% CI 2.8–9.8, p < 0.001) for 90-day mortality. The association remained significant despite adjustments with AKI and two risk scores for mortality in cardiogenic shock. Conclusions High levels of P-PENK and P-NGAL at baseline were independently associated with AKI in cardiogenic shock patients. Furthermore, oliguria before study inclusion was associated with worse outcomes only if combined with high baseline levels of P-PENK or P-NGAL. High levels of both P-PENK and P-NGAL at 24 h were found to be strong and independent predictors of 90-day mortality. Trial registration: NCT01374867 at www.clinicaltrials.gov , registered 16 Jun 2011—retrospectively registered
  • CardShock Investigators; Jäntti, Toni; Tarvasmäki, Tuukka; Harjola, Veli-Pekka; Pulkki, Kari; Turkia, Heidi; Sabell, Tuija; Tolppanen, Heli; Jurkko, Raija; Hongisto, Mari; Kataja, Anu; Sionis, Alessandro; Silva-Cardoso, Jose; Banaszewski, Marek; DiSomma, Salvatore; Mebazaa, Alexandre; Haapio, Mikko; Lassus, Johan (2021)
    Background: Acute kidney injury (AKI) is a frequent form of organ injury in cardiogenic shock. However, data on AKI markers such as plasma proenkephalin (P-PENK) and neutrophil gelatinase-associated lipocalin (P-NGAL) in cardiogenic shock populations are lacking. The objective of this study was to assess the ability of P-PENK and P-NGAL to predict acute kidney injury and mortality in cardiogenic shock. Results: P-PENK and P-NGAL were measured at different time points between baseline and 48 h in 154 patients from the prospective CardShock study. The outcomes assessed were AKI defined by an increase in creatinine within 48 h and all-cause 90-day mortality. Mean age was 66 years and 26% were women. Baseline levels of P-PENK and P-NGAL (median [interquartile range]) were 99 (71-150) pmol/mL and 138 (84-214) ng/mL. P-PENK > 84.8 pmol/mL and P-NGAL > 104 ng/mL at baseline were identified as optimal cut-offs for AKI prediction and independently associated with AKI (adjusted HRs 2.2 [95% CI 1.1-4.4, p = 0.03] and 2.8 [95% CI 1.2-6.5, p = 0.01], respectively). P-PENK and P-NGAL levels at baseline were also associated with 90-day mortality. For patients with oliguria <0.5 mL/kg/h for > 6 h before study enrollment, 90-day mortality differed significantly between patients with low and high P-PENK/P-NGAL at baseline (5% vs. 68%, p <0.001). However, the biomarkers provided best discrimination for mortality when measured at 24 h. Identified cut-offs of P-PENK24h > 105.7 pmol/L and P-NGAL(24h) > 151 ng/mL had unadjusted hazard ratios of 5.6 (95% CI 3.1-10.7, p <0.001) and 5.2 (95% CI 2.8-9.8, p <0.001) for 90-day mortality. The association remained significant despite adjustments with AKI and two risk scores for mortality in cardiogenic shock. Conclusions: High levels of P-PENK and P-NGAL at baseline were independently associated with AKI in cardiogenic shock patients. Furthermore, oliguria before study inclusion was associated with worse outcomes only if combined with high baseline levels of P-PENK or P-NGAL. High levels of both P-PENK and P-NGAL at 24 h were found to be strong and independent predictors of 90-day mortality.
  • Sabell, Tuija; Banaszewski, Marek; Lassus, Johan; Nieminen, Markku S.; Tolppanen, Heli; Jäntti, Toni; Kataja, Anu; Hongisto, Mari; Køber, Lars; Sionis, Alessandro; Parissis, John; Tarvasmäki, Tuukka; Harjola, Veli-Pekka; Jurkko, Raija (2020)
    Abstract Aims Urgent revascularization is the mainstay of treatment in acute coronary syndrome (ACS) related cardiogenic shock (CS). The aim was to investigate the association of angiographic results with 90-day mortality. Procedural complications of percutaneous coronary intervention (PCI) were also examined. Methods and results This CardShock (NCT01374867) substudy included 158 patients with ACS aetiology and data on coronary angiography and complications during PCI procedure. Survival analysis was conducted with Kaplan?Meier curves and Cox regression analysis. Median age was 67 ± 11 years, and 77% were men. During 90-day follow-up, 66 (42%) patients died. Patients with one-vessel disease (n = 49) had lower mortality than patients with two-vessel (n = 59) or three-vessel (n = 50) disease (25% vs. 48% vs. 52%, P = 0.011). Successful revascularization [Thrombolysis in Myocardial Infarction (TIMI) Flow 3 post-PCI) was achieved more often in survivors than non-survivors (81% vs. 60%, P = 0.019). The median symptom-to-balloon time was 340 (196?660) minutes, with no difference between survivors and non-survivors. In multivariable mortality analysis, multivessel disease (HR 2.59, CI95% 1.29?5.18) and TIMI flow
  • Rueda, Ferran; Borras, Eva; Garcia-Garcia, Cosme; Iborra-Egea, Oriol; Revuelta-Lopez, Elena; Harjola, Veli-Pekka; Cediel, German; Lassus, Johan; Tarvasmäki, Tuukka; Mebazaa, Alexandre; Sabido, Eduard; Bayes-Genis, Antoni (2019)
    Aims Cardiogenic shock (CS) is associated with high short-term mortality and a precise CS risk stratification could guide interventions to improve patient outcome. Here, we developed a circulating protein-based score to predict short-term mortality risk among patients with CS. Methods and results Mass spectrometry analysis of 2654 proteins was used for screening in the Barcelona discovery cohort (n = 48). Targeted quantitative proteomics analyses (n = 51 proteins) were used in the independent CardShock cohort (n = 97) to derive and cross-validate the protein classifier. The combination of four circulating proteins (Cardiogenic Shock 4 proteins-CS4P), discriminated patients with low and high 90-day risk of mortality. CS4P comprises the abundances of liver-type fatty acid-binding protein, beta-2-microglobulin, fructose-bisphosphate aldolase B, and SerpinG1. Within the CardShock cohort used for internal validation, the C-statistic was 0.78 for the CardShock risk score, 0.83 for the CS4P model, and 0.84 (P = 0.033 vs. CardShock risk score) for the combination of CardShock risk score with the CS4P model. The CardShock risk score with the CS4P model showed a marked benefit in patient reclassification, with a net reclassification improvement (NRI) of 0.49 (P = 0.020) compared with CardShock risk score. Similar reclassification metrics were observed in the IABP-SHOCK II risk score combined with CS4P (NRI =0.57; P = 0.032). The CS4P patient classification power was confirmed by enzyme-linked immuno-sorbent assay (ELISA). Conclusion A new protein-based CS patient classifier, the CS4P, was developed for short-term mortality risk stratification. CS4P improved predictive metrics in combination with contemporary risk scores, which may guide clinicians in selecting patients for advanced therapies.
  • Kataja, Anu; Tarvasmäki, Tuukka; Lassus, Johan; Cardoso, Jose; Mebazaa, Alexandre; Kober, Lars; Sionis, Alessandro; Spinar, Jindrich; Carubelli, Valentina; Banaszewski, Marek; Marino, Rossella; Parissis, John; Nieminen, Markku S.; Harjola, Veli-Pekka (2017)
    Background: Critically ill patients often present with hyperglycemia, regardless of previous history of diabetes mellitus (DM). Hyperglycemia has been associated with adverse outcome in acute myocardial infarction and acute heart failure. We investigated the association of admission blood glucose level with the clinical picture and short-term mortality in cardiogenic shock (CS). Methods: Consecutively enrolled CS patients were divided into five categories according to plasma glucose level at the time of enrolment: hypoglycemia (glucose = 16.0 mmol/L) hyperglycemia. Clinical presentation, biochemistry, and short-term mortality were compared between the groups. Results: Plasma glucose level of 211 CS patients was recorded. Glucose levels were distributed equally between normoglycemia (26% of patients), mild (27%), moderate (19%) and severe (25%) hyperglycemia, while hypoglycemia (2%) was rare. Severe hyperglycemia was associated with higher blood leukocyte count (17.3 (5.8) E9/L), higher lactate level (4.4 (3.3-8.4) mmol/L) and lower arterial pH (7.23 (0.14)) compared with normoglycemia or mild to moderate hyperglycemia (p <0.001 for all). In-hospital mortality was highest among hypoglycemic (60%) and severely hyperglycemic (56%) patients, compared with 22% in normoglycemic group (p <0.01). Severe hyperglycemia was an independent predictor of in-hospital mortality (OR 3.7, 95% CI 1.19-11.7, p = 0.02), when adjusted for age, gender, LVEF, lactate, and DM. Conclusions: Admission blood glucose level has prognostic significance in CS. Mortality is highest among patients with severe hyperglycemia or hypoglycemia. Severe hyperglycemia is independently associated with high in-hospital mortality in CS. It is also associated with biomarkers of systemic hypoperfusion and stress response. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Maack, Christoph; Eschenhagen, Thomas; Hamdani, Nazha; Heinzel, Frank R.; Lyon, Alexander R.; Manstein, Dietmar J.; Metzger, Joseph; Papp, Zoltan; Tocchetti, Carlo G.; Yilmaz, M. Birhan; Anker, Stefan D.; Balligand, Jean-Luc; Bauersachs, Johann; Brutsaert, Dirk; Carrier, Lucie; Chlopicki, Stefan; Cleland, John G.; de Boer, Rudolf A.; Dietl, Alexander; Fischmeister, Rodolphe; Harjola, Veli-Pekka; Heymans, Stephane; Hilfiker-Kleiner, Denise; Holzmeister, Johannes; de Keulenaer, Gilles; Limongelli, Giuseppe; Linke, Wolfgang A.; Lund, Lars H.; Masip, Josep; Metra, Marco; Mueller, Christian; Pieske, Burkert; Ponikowski, Piotr; Ristic, Arsen; Ruschitzka, Frank; Seferovic, Petar M.; Skouri, Hadi; Zimmermann, Wolfram H.; Mebazaa, Alexandre (2019)
    Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation-contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term.
  • Hongisto, Mari; Lassus, Johan; Tarvasmäki, Tuukka; Sionis, Alessandro; Tolppanen, Heli; Lindholm, Matias Greve; Banaszewski, Marek; Parissis, John; Spinar, Jindrich; Silva-Cardoso, Jose; Carubelli, Valentina; Di Somma, Salvatore; Masip, Josep; Harjola, Veli-Pekka (2017)
    Background: Despite scarce data, invasive mechanical ventilation (MV) is widely recommended over noninvasive ventilation (NIV) for ventilatory support in cardiogenic shock (CS). We assessed the real-life use of different ventilation strategies in CS and their influence on outcome focusing on the use of NIV and MV. Methods: 219 CS patients were categorized by the maximum intensity of ventilatory support they needed during the first 24 h into MV (n= 137; 63%), NIV(n= 26; 12%), and supplementary oxygen (n= 56; 26%) groups. We compared the clinical characteristics and 90-day outcome between the MV and the NIV groups. Results: Mean age was 67 years, 74% were men. The MV and NIV groups did not differ in age, medical history, etiology of CS, PaO2/FiO(2) ratio, baseline hemodynamics or LVEF. MV patients predominantly presented with hypoperfusion, with more severe metabolic acidosis, higher lactate levels and greater need for vasoactive drugs, whereas NIV patients tended to be more often congestive. 90-day outcome was significantly worse in the MV group (50% vs. 27%), but after propensity score adjustment, mortality was equal in both groups. Confusion, prior CABG, ACS etiology, higher lactate level, and lower baseline PaO2 were independent predictors of mortality, where as ventilation strategy did not have any influence on outcome. Conclusions: Although MV is generally recommended mode of ventilatory support in CS, a fair number of patients were successfully treated with NIV. Moreover, ventilation strategy was not associated with outcome. Thus, NIV seems a safe option for properly chosen CS patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.