Publications by authors named "Johan Lassus"

80 Publications

Renal function and the effects of vericiguat in patients with worsening heart failure with reduced ejection fraction: insights from the VICTORIA (Vericiguat Global Study in Subjects with HFrEF) trial.

Eur J Heart Fail 2021 May 17. Epub 2021 May 17.

Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada.

Aims: Vericiguat reduced the primary composite outcome of cardiovascular death or heart failure (HF) hospitalization in patients with worsening HF with reduced ejection fraction (HFrEF) and a lower limit of baseline estimated glomerular filtration rate (eGFR) of 15 mL/min/1.73 m . We evaluated the relationship between the efficacy of vericiguat and baseline and subsequent changes in renal function.

Methods And Results: In VICTORIA, core laboratory serum creatinine was measured at baseline (n = 4956) and weeks 16, 32, and 48. Worsening renal function (WRF), defined as an increase ≥0.3 mg/dL in creatinine from baseline to week 16, was assessed via a Cox model with respect to subsequent primary events. Mean age was 69 years, 24% were female, and mean baseline eGFR was 61 mL/min/1.73 m . During 48 weeks of treatment, the trajectories in eGFR and creatinine with vericiguat were similar to placebo (P = 0.50 and 0.18). The beneficial effects of vericiguat on the primary outcome were not influenced by baseline eGFR (interaction P = 0.48). WRF occurred in 15% of patients and was associated with worse outcomes (adjusted hazard ratio 1.28, 95% confidence interval 1.11-1.47; P < 0.001), but the beneficial effects of vericiguat on the primary outcome were similar in patients with or without WRF (interaction P = 0.76).

Conclusion: Renal function trajectories were similar between vericiguat- and placebo-treated patients and the beneficial effects of vericiguat on the primary outcome were consistent across the full range of eGFR and irrespective of WRF.
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http://dx.doi.org/10.1002/ejhf.2221DOI Listing
May 2021

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!

Ann Intensive Care 2021 Mar 15;11(1):46. Epub 2021 Mar 15.

Department of Cardiology, Heart and Lung Center, University of Helsinki, Helsinki University Hospital, HUS, 00029, Helsinki, Finland.

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http://dx.doi.org/10.1186/s13613-021-00839-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960823PMC
March 2021

External validation and comparison of the CardShock and IABP-SHOCK II risk scores in real-world cardiogenic shock patients.

Eur Heart J Acute Cardiovasc Care 2020 Jan 31. Epub 2020 Jan 31.

Intensive Cardiac Care Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, CIBERCV, Spain.

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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http://dx.doi.org/10.1177/2048872619895230DOI Listing
January 2020

Predictive value of plasma proenkephalin and neutrophil gelatinase-associated lipocalin in acute kidney injury and mortality in cardiogenic shock.

Ann Intensive Care 2021 Feb 5;11(1):25. Epub 2021 Feb 5.

Department of Cardiology, Heart and Lung Center, Helsinki University Hospital, University of Helsinki, 00029 HUS, Helsinki, Finland.

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-PENK > 105.7 pmol/L and P-NGAL > 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.
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http://dx.doi.org/10.1186/s13613-021-00814-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865050PMC
February 2021

Mortality risk prediction in elderly patients with cardiogenic shock: results from the CardShock study.

ESC Heart Fail 2021 04 31;8(2):1398-1407. Epub 2021 Jan 31.

Division of Emergency Medicine, Department of Emergency Medicine and Services, Helsinki University Hospital, PO Box 900, Helsinki, 00029 HUS, Finland.

Aims: This study aimed to assess the utility of contemporary clinical risk scores and explore the ability of two biomarkers [growth differentiation factor-15 (GDF-15) and soluble ST2 (sST2)] to improve risk prediction in elderly patients with cardiogenic shock.

Methods And Results: Patients (n = 219) from the multicentre CardShock study were grouped according to age (elderly ≥75 years and younger). Characteristics, management, and outcome between the groups were compared. The ability of the CardShock risk score and the IABP-SHOCK II score to predict in-hospital mortality and the additional value of GDF-15 and sST2 to improve risk prediction in the elderly was evaluated. The elderly constituted 26% of the patients (n = 56), with a higher proportion of women (41% vs. 21%, P < 0.05) and more co-morbidities compared with the younger. The primary aetiology of shock in the elderly was acute coronary syndrome (84%), with high rates of percutaneous coronary intervention (87%). Compared with the younger, the elderly had higher in-hospital mortality (46% vs. 33%; P = 0.08), but 1 year post-discharge survival was excellent in both age groups (90% in the elderly vs. 88% in the younger). In the elderly, the risk prediction models demonstrated an area under the curve of 0.75 for the CardShock risk score and 0.71 for the IABP-SHOCK II score. Incorporating GDF-15 and sST2 improved discrimination for both risk scores with areas under the curve ranging from 0.78 to 0.84.

Conclusions: Elderly patients with cardiogenic shock have higher in-hospital mortality compared with the younger, but post-discharge outcomes are similar. Contemporary risk scores proved useful for early mortality risk prediction also in the elderly, and risk stratification could be further improved with biomarkers such as GDF-15 or sST2.
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http://dx.doi.org/10.1002/ehf2.13224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006692PMC
April 2021

Association of miR-21-5p, miR-122-5p, and miR-320a-3p with 90-Day Mortality in Cardiogenic Shock.

Int J Mol Sci 2020 Oct 26;21(21). Epub 2020 Oct 26.

Unit of Cardiovascular Research, Minerva Foundation Institute for Medical Research, 00029 Helsinki, Finland.

Cardiogenic shock (CS) is a life-threatening emergency. New biomarkers are needed in order to detect patients at greater risk of adverse outcome. Our aim was to assess the characteristics of miR-21-5p, miR-122-5p, and miR-320a-3p in CS and evaluate the value of their expression levels in risk prediction. Circulating levels of miR-21-5p, miR-122-5p, and miR-320a-3p were measured from serial plasma samples of 179 patients during the first 5-10 days after detection of CS, derived from the CardShock study. Acute coronary syndrome was the most common cause (80%) of CS. Baseline (0 h) levels of miR-21-5p, miR-122-5p, and miR-320a-3p were all significantly elevated in nonsurvivors compared to survivors ( < 0.05 for all). Above median levels at 0h of each miRNA were each significantly associated with higher lactate and alanine aminotransferase levels and decreased glomerular filtration rates. After adjusting the multivariate regression analysis with established CS risk factors, miR-21-5p and miR-320a-3p levels above median at 0 h were independently associated with 90-day all-cause mortality (adjusted hazard ratio 1.8 (95% confidence interval 1.1-3.0), = 0.018; adjusted hazard ratio 1.9 (95% confidence interval 1.2-3.2), = 0.009, respectively). In conclusion, circulating plasma levels of miR-21-5p, miR-122-5p, and miR-320a-3p at baseline were all elevated in nonsurvivors of CS and associated with markers of hypoperfusion. Above median levels of miR-21-5p and miR-320a-3p at baseline appear to independently predict 90-day all-cause mortality. This indicates the potential of miRNAs as biomarkers for risk assessment in cardiogenic shock.
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http://dx.doi.org/10.3390/ijms21217925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662780PMC
October 2020

Kinetics of procalcitonin, C-reactive protein and interleukin-6 in cardiogenic shock - Insights from the CardShock study.

Int J Cardiol 2021 01 22;322:191-196. Epub 2020 Aug 22.

Emergency Medicine, University of Helsinki and Department of Emergency Medicine and Services, Helsinki University Hospital, Helsinki, Finland.

Background: Inflammatory responses play an important role in the pathophysiology of cardiogenic shock (CS). The aim of this study was to investigate the kinetics of procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) in CS and to assess their relation to clinical presentation, other biochemical variables, and prognosis.

Methods: Levels of PCT, CRP and IL-6 were analyzed in serial plasma samples (0-120h) from 183 patients in the CardShock study. The study population was dichotomized by PCT ≥ and < 0.5 μg/L, and IL-6 and CRP above/below median.

Results: PCT peaked already at 24 h [median PCT 0.71 μg/L (IQR 0.24-3.4)], whereas CRP peaked later between 48 and 72 h [median CRP 137 mg/L (59-247)]. PCT levels were significantly higher among non-survivors compared with survivors from 12 h on, as were CRP levels from 24 h on (p < 0.001). PCT ≥ 0.5 μg/L (60% of patients) was associated with clinical signs of systemic hypoperfusion, cardiac and renal dysfunction, acidosis, and higher levels of blood lactate, IL-6, growth-differentiation factor 15 (GDF-15), and CRP. Similarly, IL-6 > median was associated with clinical signs and biochemical findings of systemic hypoperfusion. PCT ≥ 0.5 μg/L and IL-6 > median were associated with increased 90-day mortality (50% vs. 30% and 57% vs. 22%, respectively; p < 0.01 for both), while CRP showed no prognostic significance. The association of inflammatory markers with clinical infections was modest.

Conclusions: Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis.
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http://dx.doi.org/10.1016/j.ijcard.2020.08.069DOI Listing
January 2021

Kidney and liver dysfunction in cardiogenic shock.

Authors:
Johan Lassus

Curr Opin Crit Care 2020 08;26(4):417-423

Heart and Lung Center, Cardiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Purpose Of Review: Organ dysfunction is a key feature of cardiogenic shock. Active revascularization and contemporary management in intensive care has improved prognosis in cardiogenic shock, but mortality is still unacceptably high. This review will discuss the prevalence, manifestation, management and clinical impact of kidney and liver dysfunction in cardiogenic shock.

Recent Findings: Patients with cardiogenic shock more frequently have several comorbidities that make them at risk of developing multiorgan failure, including renal and liver dysfunction. Kidney and liver injury and dysfunction will markedly increase mortality of patients with cardiogenic shock. Management requires active monitoring of organ function and knowledge of criteria for detection and classification of organ injury. The SOFA score for prediction of mortality in the critically ill incorporates organ injury and can be used also in cardiogenic shock, but risk prediction models specific for cardiogenic shock exist. Biomarkers reflecting different pathways activated in cardiogenic shock correlate with severity of organ dysfunction and may improve risk prediction in cardiogenic shock. Preliminary data suggest that they can even be future treatment targets.

Summary: Monitoring renal and hepatic function and identifying injury and dysfunction of these organs is essential for the management and mortality risk assessment of patients in cardiogenic shock.
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http://dx.doi.org/10.1097/MCC.0000000000000746DOI Listing
August 2020

Acute coronary syndromes and acute heart failure: a diagnostic dilemma and high-risk combination. A statement from the Acute Heart Failure Committee of the Heart Failure Association of the European Society of Cardiology.

Eur J Heart Fail 2020 08 29;22(8):1298-1314. Epub 2020 Apr 29.

Department of Internal Medicine, Belgrade University School of Medicine and Heart Failure Center, Belgrade University Medical Center, Belgrade, Serbia.

Acute coronary syndrome is a precipitant of acute heart failure in a substantial proportion of cases, and the presence of both conditions is associated with a higher risk of short-term mortality compared to acute coronary syndrome alone. The diagnosis of acute coronary syndrome in the setting of acute heart failure can be challenging. Patients may present with atypical or absent chest pain, electrocardiograms can be confounded by pre-existing abnormalities, and cardiac biomarkers are frequently elevated in patients with chronic or acute heart failure, independently of acute coronary syndrome. It is important to distinguish transient or limited myocardial injury from primary myocardial infarction due to vascular events in patients presenting with acute heart failure. This paper outlines various clinical scenarios to help differentiate between these conditions and aims to provide clinicians with tools to aid in the recognition of acute coronary syndrome as a cause of acute heart failure. Interpretation of electrocardiogram and biomarker findings, and imaging techniques that may be helpful in the diagnostic work-up are described. Guidelines recommend an immediate invasive strategy for patients with acute heart failure and acute coronary syndrome, regardless of electrocardiographic or biomarker findings. Pharmacological management of patients with acute coronary syndrome and acute heart failure should follow guidelines for each of these syndromes, with priority given to time-sensitive therapies for both. Studies conducted specifically in patients with the combination of acute coronary syndrome and acute heart failure are needed to better define the management of these patients.
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http://dx.doi.org/10.1002/ejhf.1831DOI Listing
August 2020

Prognostic impact of angiographic findings, procedural success, and timing of percutaneous coronary intervention in cardiogenic shock.

ESC Heart Fail 2020 04 12;7(2):768-773. Epub 2020 Mar 12.

Heart and Lung Center, Helsinki University Hospital, Helsinki University, Helsinki, Finland.

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, CI 1.29-5.18) and TIMI flow <3 post-PCI (HR 2.41, CI 1.4-4.15) were associated with 90-day mortality. Procedural PCI complications were recorded in 51 (35%) patients, arrhythmic complications being the most common (n = 32, 63%). The incidence of complications was similar between survivors and non-survivors (31% vs. 42%, P = 0.21).

Conclusions: Multivessel disease is associated with worse survival in ACS-related CS. In patients undergoing PCI, arrhythmic complications were common, but not associated with excess mortality. Successful revascularization of the IRA had positive effect on outcome despite delay from symptom onset.
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http://dx.doi.org/10.1002/ehf2.12637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160464PMC
April 2020

The association of long-term outcome and biological sex in patients with acute heart failure from different geographic regions.

Eur Heart J 2020 04;41(13):1357-1364

Inserm UMR-S 942 MASCOT, Hôpital Lariboisière - Bâtiment Viggo Petersen 41, boulevard de la Chapelle, 75475 Paris Cedex 10, France.

Aims: Recent data from national registries suggest that acute heart failure (AHF) outcomes might vary in men and women, however, it is not known whether this observation is universal. The aim of this study was to evaluate the association of biological sex and 1-year all-cause mortality in patients with AHF in various regions of the world.

Methods And Results: We analysed several AHF cohorts including GREAT registry (22 523 patients, mostly from Europe and Asia) and OPTIMIZE-HF (26 376 patients from the USA). Clinical characteristics and medication use at discharge were collected. Hazard ratios (HRs) for 1-year mortality according to biological sex were calculated using a Cox proportional hazards regression model with adjustment for baseline characteristics (e.g. age, comorbidities, clinical and laboratory parameters at admission, left ventricular ejection fraction). In the GREAT registry, women had a lower risk of death in the year following AHF [HR 0.86 (0.79-0.94), P < 0.001 after adjustment]. This was mostly driven by northeast Asia [n = 9135, HR 0.76 (0.67-0.87), P < 0.001], while no significant differences were seen in other countries. In the OPTIMIZE-HF registry, women also had a lower risk of 1-year death [HR 0.93 (0.89-0.97), P < 0.001]. In the GREAT registry, women were less often prescribed with a combination of angiotensin-converting enzyme inhibitors and beta-blockers at discharge (50% vs. 57%, P = 0.001).

Conclusion: Globally women with AHF have a lower 1-year mortality and less evidenced-based treatment than men. Differences among countries need further investigation. Our findings merit consideration when designing future global clinical trials in AHF.
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http://dx.doi.org/10.1093/eurheartj/ehaa071DOI Listing
April 2020

External validation and comparison of the CardShock and IABP-SHOCK II risk scores in real-world cardiogenic shock patients.

Eur Heart J Acute Cardiovasc Care 2020 Jan 31:2048872619895230. Epub 2020 Jan 31.

Intensive Cardiac Care Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, CIBERCV, Spain.

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%, <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, =0.65). Their discrimination performance was only modest when applied to non-acute coronary syndrome patients (0.648 vs 0.619, respectively, =0.31). Calibration was acceptable for both scores (Hosmer-Lemeshow =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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http://dx.doi.org/10.1177/2048872619895230DOI Listing
January 2020

CT-IGFBP-4 as a novel prognostic biomarker in acute heart failure.

ESC Heart Fail 2020 04 22;7(2):434-444. Epub 2020 Jan 22.

HyTest Ltd, Intelligate 1, Joukahaisenkatu 6, Turku, 20520, Finland.

Aims: Insulin-like growth factor binding protein-4 (IGFBP-4) fragments have been shown to predict the risk of major adverse cardiovascular events, including segment-elevation myocardial infarction, in patients with acute coronary syndrome. We evaluated the prognostic value of the carboxy-terminal fragment of IGFBP-4 (CT-IGFBP-4) for all-cause mortality in emergency room patients with acute heart failure (AHF).

Methods And Results: CT-IGFBP-4, N-terminal pro brain natriuretic peptide (NT-proBNP), and C-reactive protein (CRP) were measured at admission from the lithium-heparin plasma of 156 patients with AHF. All-cause mortality was recorded for 1 year. Receiver operator characteristic (ROC) curves, Kaplan-Meier, and Cox proportional hazard ratio analyses were performed to evaluate the prognostic value of the various clinical variables, CT-IGFBP-4, NT-proBNP, CRP, and their combinations. During 1 year of follow-up, 52 (33.3%) patients died. CT-IGFBP-4 only weakly correlated with NT-proBNP (Pearson correlation coefficient r = 0.16, P = 0.044) and did not correlate with CRP (r = 0.08, P = 0.35), emphasizing the different nature of these biomarkers. The receiver operator characteristic area under the curve (ROC AUC) of CT-IGFBP-4 for the prediction of all-cause mortality (0.727) was significantly higher than that of NT-proBNP (0.680, P = 0.045) and CRP (0.669, P = 0.016). The combination of CT-IGFBP-4, NT-proBNP, and CRP predicted mortality significantly better (ROC AUC = 0.788) than any of the biomarkers alone (P < 0.01 for all). The addition of CT-IGFBP-4 to a clinical prediction model that included age, gender, systolic blood pressure, creatinine, and sodium levels, as well as the history of previous heart failure, coronary artery disease, and hypertension significantly improved the mortality risk prediction (ROC AUC 0.774 vs. 0.699, P = 0.025). Cox hazard analysis indicated that elevated CT-IGFBP-4 was independently associated with 1 year mortality (hazard ratio 3.26, P = 0.0008) after adjustment for age, gender, history of previous heart failure, coronary artery disease, hypertension, chronic kidney failure, history of diabetes, heart rate, haemoglobin, plasma sodium, NT-proBNP, CRP, cystatin C, and elevated cardiac troponin I or T. Patients with increased levels of either two or three of the biomarkers CT-IGFBP-4, NT-proBNP, and CRP had significantly higher mortality risk (adjusted hazard ratio 10.04, P < 0.0001) than patients with increased levels of one or none of the biomarkers.

Conclusions: CT-IGFBP-4 was independently associated with all-cause mortality in patients with AHF. Compared with single biomarkers, the combination of CT-IGFBP-4, NT-proBNP, and CRP improved the prediction of all-cause mortality in patients with AHF.
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http://dx.doi.org/10.1002/ehf2.12590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160480PMC
April 2020

Evaluation of kidney function throughout the heart failure trajectory - a position statement from the Heart Failure Association of the European Society of Cardiology.

Eur J Heart Fail 2020 04 7;22(4):584-603. Epub 2020 Jan 7.

IRCCS, San Raffaele Pisana, Rome, Italy.

Appropriate interpretation of changes in markers of kidney function is essential during the treatment of acute and chronic heart failure. Historically, kidney function was primarily assessed by serum creatinine and the calculation of estimated glomerular filtration rate. An increase in serum creatinine, also termed worsening renal function, commonly occurs in patients with heart failure, especially during acute heart failure episodes. Even though worsening renal function is associated with worse outcome on a population level, the interpretation of such changes within the appropriate clinical context helps to correctly assess risk and determine further treatment strategies. Additionally, it is becoming increasingly recognized that assessment of kidney function is more than just glomerular filtration rate alone. As such, a better evaluation of sodium and water handling by the renal tubules allows to determine the efficiency of loop diuretics (loop diuretic response and efficiency). Also, though neurohumoral blockers may induce modest deteriorations in glomerular filtration rate, their use is associated with improved long-term outcome. Therefore, a better understanding of the role of cardio-renal interactions in heart failure in symptom development, disease progression and prognosis is essential. Indeed, perhaps even misinterpretation of kidney function is a leading cause of not attaining decongestion in acute heart failure and insufficient dosing of guideline-directed medical therapy in general. This position paper of the Heart Failure Association Working Group on Cardio-Renal Dysfunction aims at improving insights into the interpretation of renal function assessment in the different heart failure states, with the goal of improving heart failure care.
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http://dx.doi.org/10.1002/ejhf.1697DOI Listing
April 2020

Circulating dipeptidyl peptidase 3 is a myocardial depressant factor: dipeptidyl peptidase 3 inhibition rapidly and sustainably improves haemodynamics.

Eur J Heart Fail 2020 02 31;22(2):290-299. Epub 2019 Aug 31.

Inserm UMR-S 942, Cardiovascular Markers in Stress Conditions (MASCOT), University of Paris, Paris, France.

Aims: Acute heart failure is a high mortality disease and its pathophysiology is not completely understood. Dipeptidyl peptidase 3 (DPP3) is a cytosolic enzyme involved in angiotensin II and enkephalins cleavage. The aim of this study was to investigate the association of circulating DPP3 (cDPP3) levels and mortality in cardiogenic shock patients and to determine the effects of high cDPP3 on organ function in a heart failure (HF) model in mice.

Methods And Results: cDPP3 was measured in 174 patients in cardiogenic shock and high cDPP3 levels were associated with an increased short-term mortality risk (standardized hazard ratio: 1.4 (1.1-1.8)) and severe organ dysfunction. Additionally, a rapid decrease in cDPP3 in cardiogenic shock patients within 24 h of admission was associated with a favourable outcome. This study showed that injection of DPP3 induced myocardial depression (-10 ± 2% of shortening fraction) and impaired kidney haemodynamics (+0.30 ± 0.02 of renal resistive index) in healthy mice. cDPP3 inhibition by Procizumab, a specific antibody directed against cDPP3, promptly normalized cardiac function and kidney haemodynamics in an acute heart failure mouse model, with a marked reduction in oxidative stress and inflammatory signalling.

Conclusion: Our study demonstrated cDPP3 is a newly discovered myocardial depressant factor, the levels of which at admission are associated with mortality in severe HF patients. Furthermore, inhibition of cDPP3 by Procizumab improved haemodynamics in a mouse model of HF. Our results suggest that DPP3 could be a new biomarker and biotarget for severe HF.
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http://dx.doi.org/10.1002/ejhf.1601DOI Listing
February 2020

Levels of Growth Differentiation Factor 15 and Early Mortality Risk Stratification in Cardiogenic Shock.

J Card Fail 2019 Nov 13;25(11):894-901. Epub 2019 Jul 13.

Cardiology, Helsinki University and Heart and Lung Center, Helsinki University Hospital, Helsinki, Finland. Electronic address:

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 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%, P < .001). Serial sampling showed that non-survivors had significantly higher GDF-15 levels at all time points (P < .001 for all). Furthermore, non-survivors displayed increasing and survivors declining GDF-15 levels during the first days in CS. Higher levels of GDF-15 were independently associated with mortality. A GDF-15 cutoff >7000 ng/L was identified as a strong predictor of death (OR 5.0; 95% CI 1.9-3.8, P = .002). Adding GDF-15 >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.
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http://dx.doi.org/10.1016/j.cardfail.2019.07.003DOI Listing
November 2019

Protein-based cardiogenic shock patient classifier.

Eur Heart J 2019 08;40(32):2684-2694

Heart Institute, Hospital Universitari Germans Trias i Pujol, c/ Canyet SN, 08916 Badalona, Spain.

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 immunosorbent 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.
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http://dx.doi.org/10.1093/eurheartj/ehz294DOI Listing
August 2019

Hypoalbuminemia is a frequent marker of increased mortality in cardiogenic shock.

PLoS One 2019 16;14(5):e0217006. Epub 2019 May 16.

Cardiology, University of Helsinki and Department of Cardiology, Heart and Lung Center, Helsinki University Hospital, Helsinki, Finland.

Introduction: The prevalence of hypoalbuminemia, early changes of plasma albumin (P-Alb) levels, and their effects on mortality in cardiogenic shock are unknown.

Materials And Methods: P-Alb was measured from serial blood samples in 178 patients from a prospective multinational study on cardiogenic shock. The association of hypoalbuminemia with clinical characteristics and course of hospital stay including treatment and procedures was assessed. The primary outcome was all-cause 90-day mortality.

Results: Hypoalbuminemia (P-Alb < 34g/L) was very frequent (75%) at baseline in patients with cardiogenic shock. Patients with hypoalbuminemia had higher mortality than patients with normal albumin levels (48% vs. 23%, p = 0.004). Odds ratio for death at 90 days was 2.4 [95% CI 1.5-4.1] per 10 g/L decrease in baseline P-Alb. The association with increased mortality remained independent in regression models adjusted for clinical risk scores developed for cardiogenic shock (CardShock score adjusted odds ratio 2.0 [95% CI 1.1-3.8], IABP-SHOCK II score adjusted odds ratio 2.5 [95%CI 1.2-5.0]) and variables associated with hypoalbuminemia at baseline (adjusted odds ratio 2.9 [95%CI 1.2-7.1]). In serial measurements, albumin levels decreased at a similar rate between 0h and 72h in both survivors and nonsurvivors (ΔP-Alb -4.6 g/L vs. 5.4 g/L, p = 0.5). While the decrease was higher for patients with normal P-Alb at baseline (p<0.001 compared to patients with hypoalbuminemia at baseline), the rate of albumin decrease was not associated with outcome.

Conclusions: Hypoalbuminemia was a frequent finding early in cardiogenic shock, and P-Alb levels decreased during hospital stay. Low P-Alb at baseline was associated with mortality independently of other previously described risk factors. Thus, plasma albumin measurement should be part of the initial evaluation in patients with cardiogenic shock.

Trial Registration: NCT01374867 at ClinicalTrials.gov.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217006PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522037PMC
February 2020

Serum Lactate and A Relative Change in Lactate as Predictors of Mortality in Patients With Cardiogenic Shock - Results from the Cardshock Study.

Shock 2020 01;53(1):43-49

Department of Cardiology, University Hospital Copenhagen, Rigshospitalet, Denmark.

Introduction: Cardiogenic shock complicating acute myocardial infarction has a very high mortality. Our present study focuses on serial measurement of lactate during admission due to cardiogenic shock and the prognostic effect of lactate and a relative change in lactate in patients after admission and the institution of intensive care treatment.

Methods And Results: This is a secondary analysis of the CardShock study. Data on lactate at baseline were available on 217 of 219 patients.In the study population, the median baseline lactate was 2.8 mmol/L (min-max range, 0.5-23.1 mmol/L).At admission, lactate was predictive of 30-day mortality with an adjusted Hazard ratio (HR) of 1.20 mmol/L (95% confidence interval, CI 1.14-1.27). Within the first 24 h of admission, baseline lactate remained predictive of 30-day mortality. Lactate at 6 h had a HR of 1.14 (95% CI 1.06-1.24) and corresponding values at 12 and 24 h had a HR of 1.10 (1.04-1.17), and of HR 1.19 (95% CI 1.07-1.32), respectively. A 50% reduction in lactate within 6 h resulted in a HR of 0.82 (95% CI 0.72-0.94). Corresponding hazard ratios at 12 and 24 h, were 0.87 (95% CI 0.76-0.98) and 0.74 (95% CI 0.60-0.91), respectively.

Conclusion: The main findings of the present study are that baseline lactate is a powerful predictor of 30-day mortality, lactate at 6, 12, and 24 h after admission are predictors of 30-day mortality, and a relative change in lactate is a significant predictor of survival within the first 24 h after instituting intensive care treatment adding information beyond the information from baseline values.
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http://dx.doi.org/10.1097/SHK.0000000000001353DOI Listing
January 2020

Current Use and Impact on 30-Day Mortality of Pulmonary Artery Catheter in Cardiogenic Shock Patients: Results From the CardShock Study.

J Intensive Care Med 2020 Dec 7;35(12):1426-1433. Epub 2019 Feb 7.

Critical Care Department, Hospital Sant Joan Despi Moisès Broggi, Consorci Sanitari Integral, University of Barcelona, Barcelona, Spain.

Background: Cardiogenic shock (CS) is the most life-threatening manifestation of acute heart failure. Its complexity and high in-hospital mortality may justify the need for invasive monitoring with a pulmonary artery catheter (PAC).

Methods: Patients with CS included in the CardShock Study, an observational, prospective, multicenter, European registry, were analyzed, aiming to describe the real-world use of PAC, evaluate its impact on 30-day mortality, and the ability of different hemodynamic parameters to predict outcomes.

Results: Pulmonary artery catheter was used in 82 (37.4%) of the 219 patients. Cardiogenic shock patients who managed with a PAC received more frequently treatment with inotropes and vasopressors, mechanical ventilation, renal replacement therapy, and mechanical assist devices ( < .01). Overall 30-day mortality was 36.5%. Pulmonary artery catheter use did not affect mortality even after propensity score matching analysis (hazard ratio = 1.17 [0.59-2.32], = .66). Cardiac index, cardiac power index (CPI), and stroke volume index (SVI) showed the highest areas under the curve for 30-day mortality (ranging from 0.752-0.803) and allowed for a significant net reclassification improvement of 0.467 (0.083-1.180), 0.700 (0.185-1.282), 0.683 (0.168-1.141), respectively, when added to the CardShock risk score.

Conclusions: In our contemporary cohort of CS, over one-third of patients were managed with a PAC. Pulmonary artery catheter use was associated with a more aggressive treatment strategy. Nevertheless, PAC use was not associated with 30-day mortality. Cardiac index, CPI, and SVI were the strongest 30-day mortality predictors on top of the previously validated CardShock risk score.
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http://dx.doi.org/10.1177/0885066619828959DOI Listing
December 2020

Circulating levels of microRNA 423-5p are associated with 90 day mortality in cardiogenic shock.

ESC Heart Fail 2019 02 24;6(1):98-102. Epub 2018 Nov 24.

Division of Emergency Medicine, University of Helsinki and Department of Emergency Medicine and Services, Helsinki University Hospital, Helsinki, Finland.

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 , 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.
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http://dx.doi.org/10.1002/ehf2.12377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352887PMC
February 2019

Rationale and design of the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial.

Eur J Heart Fail 2018 11 21;20(11):1591-1600. Epub 2018 Sep 21.

Ziekenhuis Oost-Limburg, Genk, Belgium.

Aims: Decisive evidence on the optimal diuretic agent, dosing schedule, and administration route is lacking in acute heart failure (AHF) with congestion. The Acetazolamide in Decompensated heart failure with Volume OveRload (ADVOR) trial is designed to test the hypothesis that the carbonic anhydrase inhibitor acetazolamide, a potent inhibitor of proximal tubular sodium reabsorption, improves decongestion when combined with loop diuretic therapy in AHF, potentially leading to better clinical outcomes.

Methods: The ADVOR trial is set up as a multicentre, randomized, double-blind, placebo-controlled study, aiming to recruit 519 patients with AHF and clinically evident volume overload. All study participants receive high-dose intravenous loop diuretics as background therapy and are randomized towards intravenous acetazolamide at a dose of 500 mg once daily vs. placebo, stratified according to including study centre and ejection fraction (< 40% vs. ≥ 40%). The primary endpoint is successful decongestion with no more than trace oedema assessed on the third morning after hospital admission, with good diuretic efficacy defined as a urine output > 3.5 L during the first 30-48 h of decongestive treatment. Secondary endpoints include all-cause mortality or heart failure readmission after 3 months, length of hospital stay for the index admission, and longitudinal changes in the EuroQol-5 dimensions questionnaire.

Conclusion: ADVOR will investigate if acetazolamide combined with loop diuretic therapy improves decongestion in AHF with volume overload.
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http://dx.doi.org/10.1002/ejhf.1307DOI Listing
November 2018

Correction to: Epinephrine and short-term survival in cardiogenic shock: an individual data meta-analysis of 2583 patients.

Intensive Care Med 2018 11;44(11):2022-2023

Department of Anesthesiology and Critical Care, APHP - Saint Louis Lariboisière University Hospitals, University Paris Diderot and INSERM UMR-S 942, Paris, France.

Because of a technical error, the code corresponding to the outcome for the Basir et al. cohort was mis-implemented in the original version of our article. Characteristics of the cohort are in fact the followings.
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http://dx.doi.org/10.1007/s00134-018-5372-9DOI Listing
November 2018

Prognostic impact of baseline and residual SYNTAX scores in cardiogenic shock.

Catheter Cardiovasc Interv 2019 01 12;93(1):1-8. Epub 2018 Sep 12.

Cardiology, University of Helsinki, Heart and Lung Center, Helsinki University Hospital, Helsinki, Finland.

Objectives: The aim was to assess the extent of coronary artery disease and revascularization using baseline SYNTAX Score (bSS) and residual SYNTAX Score (rSS) in patients with cardiogenic shock (CS) secondary to ST-segment elevation myocardial infarction (STEMI). The prognostic impact of SYNTAX Score (SS) was evaluated and assessed for additive value over clinical risk scores.

Background: bSS and rSS have been proven to be useful in risk stratification in stable coronary artery disease as well as in acute coronary syndromes, but they have not been studied in STEMI related CS.

Methods: Patients from a multinational prospective study of CS were analyzed. The study population was divided into tertiles according to bSS. The Cox regression and receiver operating characteristic (ROC) curves were used to assess the predictive power of SS.

Results: Of the 61 studied patients, 85% were male and the mean age was 67 years. Median bSS was 22 (15-32) and rSS 7 (0-13). Ninety-day mortality was 43%. bSS had negative prognostic value in multivariable analysis (HR 1.06, 95% CI 1.01-1.10). However, additive value over clinical risk scores was limited. rSS was not associated with mortality, whereas post-percutaneous coronary intervention (PCI) TIMI flow 3 of infarct-related artery (IRA) predicted better survival.

Conclusions: In STEMI related CS, the added value of bSS and rSS over clinical assessment and risk scores is limited. Our results suggest that while immediate PCI in order to restore blood flow to the IRA is essential, deferring the treatment of residual lesions does not seem to be associated with worse prognosis.
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http://dx.doi.org/10.1002/ccd.27716DOI Listing
January 2019

Epinephrine Versus Norepinephrine for Cardiogenic Shock After Acute Myocardial Infarction.

J Am Coll Cardiol 2018 07;72(2):173-182

Medical-Surgical Intensive Care Unit, Teaching Hospital of Limoges, Limoges, and INSERM CIC 1435, Teaching Hospital of Limoges, Limoges, France.

Background: Vasopressor agents could have certain specific effects in patients with cardiogenic shock (CS) after myocardial infarction, which may influence outcome. Although norepinephrine and epinephrine are currently the most commonly used agents, no randomized trial has compared their effects, and intervention data are lacking.

Objectives: The goal of this paper was to compare in a prospective, double-blind, multicenter, randomized study, the efficacy and safety of epinephrine and norepinephrine in patients with CS after acute myocardial infarction.

Methods: The primary efficacy outcome was cardiac index evolution, and the primary safety outcome was the occurrence of refractory CS. Refractory CS was defined as CS with sustained hypotension, end-organ hypoperfusion and hyperlactatemia, and high inotrope and vasopressor doses.

Results: Fifty-seven patients were randomized into 2 study arms, epinephrine and norepinephrine. For the primary efficacy endpoint, cardiac index evolution was similar between the 2 groups (p = 0.43) from baseline (H0) to H72. For the main safety endpoint, the observed higher incidence of refractory shock in the epinephrine group (10 of 27 [37%] vs. norepinephrine 2 of 30 [7%]; p = 0.008) led to early termination of the study. Heart rate increased significantly with epinephrine from H2 to H24 while remaining unchanged with norepinephrine (p < 0.0001). Several metabolic changes were unfavorable to epinephrine compared with norepinephrine, including an increase in cardiac double product (p = 0.0002) and lactic acidosis from H2 to H24 (p < 0.0001).

Conclusions: In patients with CS secondary to acute myocardial infarction, the use of epinephrine compared with norepinephrine was associated with similar effects on arterial pressure and cardiac index and a higher incidence of refractory shock. (Study Comparing the Efficacy and Tolerability of Epinephrine and Norepinephrine in Cardiogenic Shock [OptimaCC]; NCT01367743).
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http://dx.doi.org/10.1016/j.jacc.2018.04.051DOI Listing
July 2018

Epinephrine and short-term survival in cardiogenic shock: an individual data meta-analysis of 2583 patients.

Intensive Care Med 2018 06 1;44(6):847-856. Epub 2018 Jun 1.

Department of Anesthesiology and Critical Care, APHP - Saint Louis Lariboisière University Hospitals, University Paris Diderot and INSERM UMR-S 942, Paris, France.

Objective: 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.

Design: 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.

Measurements And Results: 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]).

Conclusions: In this very large cohort, epinephrine use for hemodynamic management of CS patients is associated with a threefold increase of risk of death.
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http://dx.doi.org/10.1007/s00134-018-5222-9DOI Listing
June 2018

Predictive value of the baseline electrocardiogram ST-segment pattern in cardiogenic shock: Results from the CardShock Study.

Ann Noninvasive Electrocardiol 2018 09 30;23(5):e12561. Epub 2018 May 30.

Cardiology, Heart and Lung Center, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

Background: The most common aetiology of cardiogenic shock (CS) is acute coronary syndrome (ACS), but even up to 20%-50% of CS is caused by other disorders. ST-segment deviations in the electrocardiogram (ECG) have been investigated in patients with ACS-related CS, but not in those with other CS aetiologies. We set out to explore the prevalence of different ST-segment patterns and their associations with the CS aetiology, clinical findings and 90-day mortality.

Methods: We analysed the baseline ECG of 196 patients who were included in a multinational prospective study of CS. The patients were divided into 3 groups: (a) ST-segment elevation (STE). (b) ST-segment depression (STDEP). (c) No ST-segment deviation or ST-segment impossible to analyse (NSTD). A subgroup analysis of the ACS patients was conducted.

Results: ST-segment deviations were present in 80% of the patients: 52% had STE and 29% had STDEP. STE was associated with the ACS aetiology, but one-fourth of the STDEP patients had aetiology other than ACS. The overall 90-day mortality was 41%: in STE 47%, STDEP 36% and NSTD 33%. In the multivariate mortality analysis, only STE predicted mortality (HR 1.74, CI 1.07-2.84). In the ACS subgroup, the patients were equally effectively revascularized, and no differences in the survival were noted between the study groups.

Conclusion: ST-segment elevation is associated with the ACS aetiology and high mortality in the unselected CS population. If STE is not present, other aetiologies must be considered. When effectively revascularized, the prognosis is similar regardless of the ST-segment pattern in ACS-related CS.
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http://dx.doi.org/10.1111/anec.12561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931659PMC
September 2018

Prevalence, Temporal Evolution, and Impact on Survival of Ventricular Conduction Blocks in Patients With Acute Coronary Syndrome and Cardiogenic Shock.

Am J Cardiol 2018 07 20;122(2):199-205. Epub 2018 Apr 20.

Heart and Lung Center, Helsinki University Hospital and Helsinki University, Helsinki, Finland.

Changes in QRS duration and pattern are regarded to reflect severe ischemia in acute coronary syndromes (ACS), and ventricular conduction blocks (VCBs) are recognized high-risk markers in both ACS and acute heart failure. Our aim was to evaluate the prevalence, temporal evolution, association with clinical and angiographic parameters, and impact on mortality of VCBs in ACS-related cardiogenic shock (CS). Data of 199 patients with ACS-related CS from a prospective multinational cohort were evaluated with electrocardiogram data from baseline and day 3. VCBs including left or right bundle branch block, right bundle branch block and hemiblock, isolated hemiblocks, and unspecified intraventricular conduction delay were assessed. Fifty percent of patients had a VCB at baseline; these patients were older, had poorer left ventricular function and had more often left main disease compared with those without VCB. One-year mortality was over 2-fold in patients with VCB compared with those without VCB (68% vs 32%, p<0.001). All types of VCBs at baseline were associated with increased mortality, and the predictive value of a VCB was independent of baseline variables and coronary angiography findings. Interestingly, 37% of the VCBs were transient, i.e., disappeared before day 3. However, 1-year mortality was much higher in these patients (69%) compared to patients with persistent (38%) or no VCB (15%, p<0.001). Indeed, a transient VCB was a strong independent predictor of 1-year mortality. In conclusion, our findings propose that any VCB in baseline electrocardiogram, even if transient, identifies very early patients at particularly high mortality risk in ACS-related CS.
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http://dx.doi.org/10.1016/j.amjcard.2018.04.008DOI Listing
July 2018

Management of cardiogenic shock complicating myocardial infarction.

Intensive Care Med 2018 Jun 16;44(6):760-773. Epub 2018 May 16.

Department of Internal Medicine/Cardiology, Heart Center Leipzig - University Hospital, Leipzig, Germany.

Up to 10% of acute coronary syndromes are complicated by cardiogenic shock (CS) with contemporary mortality rates of 40-50%. The extent of ischemic myocardium has a profound impact on the initial, in-hospital, and post-discharge management and prognosis in this patient population. Individualized patient risk assessment plays an important role in determining appropriate revascularization, drug treatment with inotropes and vasopressors, mechanical circulatory support, intensive care support of other organ systems, hospital level of care triage, and allocation of clinical resources. This review will outline the underlying causes and diagnostic criteria, pathophysiology, and treatment of CS complicating acute coronary syndromes with a focus on (a) potential therapeutic issues from the perspective an interventional cardiologist, an emergency physician, and an intensive care physician, (b) the type of revascularization, and (c) new therapeutic advancements in pharmacologic and mechanical percutaneous circulatory support.
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http://dx.doi.org/10.1007/s00134-018-5214-9DOI Listing
June 2018

Comprehensive in-hospital monitoring in acute heart failure: applications for clinical practice and future directions for research. A statement from the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

Eur J Heart Fail 2018 07 30;20(7):1081-1099. Epub 2018 Apr 30.

Imperial College, London, UK.

This paper provides a practical clinical application of guideline recommendations relating to the inpatient monitoring of patients with acute heart failure, through the evaluation of various clinical, biomarker, imaging, invasive and non-invasive approaches. Comprehensive inpatient monitoring is crucial to the optimal management of acute heart failure patients. The European Society of Cardiology heart failure guidelines provide recommendations for the inpatient monitoring of acute heart failure, but the level of evidence underpinning most recommendations is limited. Many tools are available for the in-hospital monitoring of patients with acute heart failure, and each plays a role at various points throughout the patient's treatment course, including the emergency department, intensive care or coronary care unit, and the general ward. Clinical judgment is the preeminent factor guiding application of inpatient monitoring tools, as the various techniques have different patient population targets. When applied appropriately, these techniques enable decision making. However, there is limited evidence demonstrating that implementation of these tools improves patient outcome. Research priorities are identified to address these gaps in evidence. Future research initiatives should aim to identify the optimal in-hospital monitoring strategies that decrease morbidity and prolong survival in patients with acute heart failure.
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http://dx.doi.org/10.1002/ejhf.1204DOI Listing
July 2018
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