Publications by authors named "Heli Tolppanen"

27 Publications

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Drug Treatment of Heart Failure with Reduced Ejection Fraction: Defining the Role of Vericiguat.

Drugs 2021 Sep 3. Epub 2021 Sep 3.

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

Vericiguat, a novel stimulator of soluble guanylate cyclase (sGC), has shown promising results in patients with heart failure and reduced ejection fraction (HFrEF) in the recent VICTORIA trial. The nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway is disturbed in heart failure, leading to increased formation of reactive oxygen species and reduced NO bioavailability, and resultant myocardial dysfunction, adverse left ventricular remodeling, and cardiorenal syndrome. Restoration of sufficient NO-sGC-cGMP signaling has been proposed as an important treatment target in heart failure, beyond neurohormonal blockage and afterload reduction. Vericiguat has a dual mode of action on this axis, it both sensitizes sGC to low levels of NO, and can directly stimulate sGC in the absence of any endogenous NO. VICTORIA was a Phase 3 trial that compared vericiguat, at a target dose of 10 mg, with placebo in 5050 patients with HFrEF (ejection fraction < 45%) on top of guideline-indicated therapy. The composite endpoint was the first occurrence of cardiovascular death or hospitalization for heart failure. The median follow up was 10.8 months. The included patients had to have had a heart failure-related hospitalization or need of IV diuretic therapy in the past 6 months, making it a particularly high risk and vulnerable patient population. The composite endpoint occurred less frequently with vericiguat than with placebo (35.5% vs 38.5%, p = 0.02). Adverse events were common in both groups, syncope was more common with vericiguat than with placebo (4% vs 3.5%, p = 0.03). Compared to the other recent large trials in HFrEF, PARADIGM-HF and DAPA-HF, patients in VICTORIA were older, more symptomatic (up to 40% NYHA IIIIV class), had higher N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP) levels, and were more vulnerable since 84% had been hospitalized for heart failure in the previous 6 months. While drugs involving the neurohormonal pathways are effective in slowing down the progression of disease in more stable HFrEF, vericiguat may be a drug of choice particularly in the highest risk patients with recent or recurrent hospitalizations despite full background medication. The drug has also shown safety in patients with reduced renal function. This article discusses the place in therapy of vericiguat in patients with HFrEF, which is a heterogenous group in terms of etiology, clinical profiles, and comorbidities.
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http://dx.doi.org/10.1007/s40265-021-01586-yDOI Listing
September 2021

Hydroxychloroquine reduces interleukin-6 levels after myocardial infarction: The randomized, double-blind, placebo-controlled OXI pilot trial.

Int J Cardiol 2021 Aug 4;337:21-27. Epub 2021 May 4.

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

Objectives: To determine the anti-inflammatory effect and safety of hydroxychloroquine after acute myocardial infarction.

Method: In this multicenter, double-blind, placebo-controlled OXI trial, 125 myocardial infarction patients were randomized at a median of 43 h after hospitalization to receive hydroxychloroquine 300 mg (n = 64) or placebo (n = 61) once daily for 6 months and, followed for an average of 32 months. Laboratory values were measured at baseline, 1, 6, and 12 months.

Results: The levels of interleukin-6 (IL-6) were comparable at baseline between study groups (p = 0.18). At six months, the IL-6 levels were lower in the hydroxychloroquine group (p = 0.042, between groups), and in the on-treatment analysis, the difference at this time point was even more pronounced (p = 0.019, respectively). The high-sensitivity C-reactive protein levels did not differ significantly between study groups at any time points. Eleven patients in the hydroxychloroquine group and four in the placebo group had adverse events leading to interruption or withdrawal of study medication, none of which was serious (p = 0.10, between groups).

Conclusions: In patients with myocardial infarction, hydroxychloroquine reduced IL-6 levels significantly more than did placebo without causing any clinically significant adverse events. A larger randomized clinical trial is warranted to prove the potential ability of hydroxychloroquine to reduce cardiovascular endpoints after myocardial infarction.
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http://dx.doi.org/10.1016/j.ijcard.2021.04.062DOI Listing
August 2021

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

The heart failure specialists of tomorrow: a network for young cardiovascular scientists and clinicians.

ESC Heart Fail 2020 06 30;7(3):873-877. Epub 2020 Apr 30.

Centre for Heart Diseases, University Hospital, Wroclaw, and Department of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland.

The "Heart failure specialists of Tomorrow" (HoT) group gathers young researchers, physicians, basic scientists, nurses and many other professions under the auspices of the Heart Failure Association of the European Society of Cardiology. After its foundation in 2014, it has quickly grown to a large group of currently 925 members. Membership in this growing community offers many advantages during, before, and after the 'Heart Failure and World Congress on Acute Heart Failure'. These include: eligibility to receive travel grants, participation in moderated poster sessions and young researcher and clinical case sessions, the HoT walk, the career café, access to the networking opportunities, and interaction with a large and cohesive international community that constantly seeks multinational collaborations.
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http://dx.doi.org/10.1002/ehf2.12674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261537PMC
June 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

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

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

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

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

Acute kidney injury in cardiogenic shock: definitions, incidence, haemodynamic alterations, and mortality.

Eur J Heart Fail 2018 03 27;20(3):572-581. Epub 2017 Sep 27.

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

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http://dx.doi.org/10.1002/ejhf.958DOI Listing
March 2018

Combined Measurement of Soluble ST2 and Amino-Terminal Pro-B-Type Natriuretic Peptide Provides Early Assessment of Severity in Cardiogenic Shock Complicating Acute Coronary Syndrome.

Crit Care Med 2017 Jul;45(7):e666-e673

1INSERM UMR-S942, Paris, France.2Heart Center, Päijät-Häme Central Hospital, Lahti, Finland.3Division of Cardiology, Heart and Lung Center, Helsinki University and Helsinki University Hospital, Helsinki, Finland.4Intensive Cardiac Care Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute IIB-SantPau, Universidad Autónoma de Barcelona, Barcelona, Spain.5Department of Anesthesia and Critical Care, University Hospital Saint Louis Lariboisière, APHP, Paris, France.6Department of Clinical Chemistry, University of Eastern Finland and Eastern Finland Laboratory Centre, Kuopio, Finland.7Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland.8Division of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland.9Clinical research platform (URCEST-CREST), University Hospitals Paris Est, APHP, Saint Antoine Hospital, Paris, France.10Heart Failure Clinic and Secondary Cardiology Department, Attikon University Hospital, Athens, Greece.11Department of Internal Medicine and Cardiology, University Hospital Brno, Brno, Czech Republic.12International Clinical Research Centre, ICRC, Brno, Czech Republic.13Division of Cardiology, Massachusetts General Hospital, Boston, MA.14Department of Emergency Care, Helsinki University and Helsinki University Hospital, Helsinki, Finland.15University Paris Diderot, Sorbonne Paris Cité, Paris, France.

Objectives: Mortality in cardiogenic shock complicating acute coronary syndrome is high, and objective risk stratification is needed for rational use of advanced therapies such as mechanical circulatory support. Traditionally, clinical variables have been used to judge risk in cardiogenic shock. The aim of this study was to assess the added value of serial measurement of soluble ST2 and amino-terminal pro-B-type natriuretic peptide to clinical parameters for risk stratification in cardiogenic shock.

Design: CardShock (www.clinicaltrials.gov NCT01374867) is a prospective European multinational study of cardiogenic shock. The main study introduced CardShock risk score, which is calculated from seven clinical variables at baseline, and was associated with short-term mortality.

Setting: Nine tertiary care university hospitals.

Patients: Patients with cardiogenic shock caused by acute coronary syndrome (n=145).

Interventions: In this substudy, plasma samples from the study patients were analyzed at eight time points during the ICU or cardiac care unit stay. Additional prognostic value of the biomarkers was assessed with incremental discrimination improvement.

Measurements And Main Results: The combination of soluble ST2 and amino-terminal pro-B-type natriuretic peptide showed excellent discrimination for 30-day mortality (area under the curve, 0.77 at 12 hr up to 0.93 at 5-10 d after cardiogenic shock onset). At 12 hours, patients with both biomarkers elevated (soluble ST2, ≥ 500 ng/mL and amino-terminal pro-B-type natriuretic peptide, ≥ 4,500 ng/L) had higher 30-day mortality (79%) compared to those with one or neither biomarkers elevated (31% or 10%, respectively; p < 0.001). Combined measurement of soluble ST2 and amino-terminal pro-B-type natriuretic peptide at 12 hours added value to CardShock risk score, correctly reclassifying 11% of patients.

Conclusions: The combination of results for soluble ST2 and amino-terminal pro-B-type natriuretic peptide provides early risk assessment beyond clinical variables in patients with acute coronary syndrome-related cardiogenic shock and may help therapeutic decision making in these patients.
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http://dx.doi.org/10.1097/CCM.0000000000002336DOI Listing
July 2017

Mid-regional pro-atrial natriuretic peptide to predict clinical course in heart failure patients undergoing cardiac resynchronization therapy.

Europace 2017 Nov;19(11):1848-1854

INSERM UMR-S 942, Paris, France.

Aims: Cardiac resynchronization therapy (CRT) induces reverse cardiac remodelling in heart failure (HF), but many patients receiving CRT remain non-responders. This study assessed the role of amino-terminal-pro-B-type natriuretic peptide (NT-proBNP), mid-regional-pro-atrial natriuretic peptide (MR-proANP), and mid-regional-pro-adrenomedullin (MR-proADM) at the time of device implantation to predict favourable clinical course (CRT response and/or risk of MACE) in HF patients receiving CRT.

Methods And Results: A total of 137 HF patients were prospectively included. Blood was drawn from the coronary sinus (CS) at CRT implantation, and from a peripheral vein (PV) simultaneously and after 6 months. Clinical CRT response at 6 months and major adverse cardiovascular events (MACE) at 2 years were assessed. Baseline PV-levels of MR-proANP (202 vs. 318 pmol/L, P = 0.009) and MR-proADM (843 vs. 1112 pmol/L, P = 0.02) were lower in CRT responders compared with non-responders. At 6 months, CRT responders showed a decrease in MR-proANP levels, compared with an increase in non-responders (-32 vs. +7 pmol/L, P = 0.02). During the same period, NT-proBNP decreased by a similar way in responders and non-responders, while MR-proADM was unchanged in both groups. High baseline MR-proANP, either in PV (OR 0.41, 95% CI 0.24-0.71, P = 0.002) or CS (OR 0.32, 95% CI 0.15-0.70, P = 0.005) was associated with reduced likelihood of CRT response. Furthermore, PV and CS levels of NT-proBNP, MR-proANP, and MR-proADM were all associated with increased risk of 2-year MACE (all P < 0.01).

Conclusion: Mid-regional-pro-atrial natriuretic peptide may assist prediction of clinical course in HF patients undergoing CRT implantation. Low circulating MR-proANP at the time of device implantation is associated with CRT response and more favourable outcome.
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http://dx.doi.org/10.1093/europace/euw305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834135PMC
November 2017

Soluble CD146 Is a Novel Marker of Systemic Congestion in Heart Failure Patients: An Experimental Mechanistic and Transcardiac Clinical Study.

Clin Chem 2017 Jan 25;63(1):386-393. Epub 2016 Oct 25.

INSERM UMR-S 942, Paris, France;

Background: Soluble CD146 (sCD146), is an endothelial marker with similar diagnostic power as natriuretic peptides in decompensated heart failure (HF). While natriuretic peptides are released by the failing heart, sCD146 may be released by veins in response to stretch induced by systemic congestion in HF. This study investigated the source, effects of vascular stress on release and prognostic properties of sCD146 in HF.

Methods: In a peripheral venous stress study, plasma concentrations of sCD146 and N-terminal probrain natriuretic-peptide (NT-proBNP) were measured in 44 HF patients at baseline and after 90 min of unilateral forearm venous congestion. In addition, sCD146 and NT-proBNP were measured in peripheral vein (PV) and coronary sinus (CS) blood samples of 137 HF patients and the transcardiac gradient was calculated. Those patients were followed for major adverse cardiovascular events (MACE) during 2 years.

Results: The induction of venous stress was associated with a pronounced increase in circulating concentrations of sCD146 in the congested arm (+60 μg/L) compared to the control arm (+16 μg/L, P = 0.025), while no difference in NT-proBNP concentrations was seen. In contrast to positive transcardiac gradient for NT-proBNP, median sCD146 concentrations were lower in CS than in PV (396 vs 434, P < 0.001), indicating a predominantly extracardiac source of sCD146. Finally, increased PV concentrations of sCD146 were associated with higher risk of MACE at 2 years.

Conclusions: Soluble CD146 is released from the peripheral vasculature in response to venous stretch and may reflect systemic congestion in chronic HF patients.
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http://dx.doi.org/10.1373/clinchem.2016.260471DOI Listing
January 2017

Adrenomedullin: a marker of impaired hemodynamics, organ dysfunction, and poor prognosis in cardiogenic shock.

Ann Intensive Care 2017 Dec 4;7(1). Epub 2017 Jan 4.

INSERM UMR-S942, Paris, France.

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.
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http://dx.doi.org/10.1186/s13613-016-0229-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5209311PMC
December 2017

Use of noninvasive and invasive mechanical ventilation in cardiogenic shock: A prospective multicenter study.

Int J Cardiol 2017 Mar 27;230:191-197. Epub 2016 Dec 27.

Emergency Medicine, University of Helsinki, Department of Emergency Care, Helsinki University Hospital, Helsinki, Finland.

Background: Despite scarce data, invasive mechanical ventilation (MV) is widely recommended over non-invasive 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 24h 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 67years, 74% were men. The MV and NIV groups did not differ in age, medical history, etiology of CS, PaO/FiO 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 PaO were independent predictors of mortality, whereas 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.
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http://dx.doi.org/10.1016/j.ijcard.2016.12.175DOI Listing
March 2017

Effect of precipitating factors of acute heart failure on readmission and long-term mortality.

ESC Heart Fail 2016 Jun 21;3(2):115-121. Epub 2016 Jan 21.

INSERM UMR-S 942ParisFrance; PRES Sorbonne Paris CitéUniversité Paris DiderotParisFrance; Department of Anesthesiology and Critical Care Medicine, APHPSaint Louis Lariboisière University HospitalsParisFrance.

Aims: Acute heart failure (AHF) is one of the leading causes of unscheduled hospitalization and is associated with frequent readmissions and substantial mortality. Precipitating factors of AHF influence short-term mortality, but their effect on outcome after hospital discharge is unknown. The present study assessed the effect of precipitating factors on readmission and long-term survival in the overall population and in patients aged 75 years or younger.

Methods And Results: Patients admitted with AHF ( = 755) included in the multicentre cohort 'Biomarcoeurs' were included in the study. Precipitating factors of AHF were classified in four main groups: acute coronary syndrome, atrial fibrillation, acute pulmonary disease and other causes. Hospital readmission during 90 days after discharge and survival at 1 year were analysed. Precipitating factors influenced readmissions and survival. Acute pulmonary disease was associated with fewer readmissions (HR 0.61, 95% confidence interval (CI) 0.37-0.99,  = 0.049), especially in patients aged 75 years or younger (HR 0.20, 95% CI 0.06-0.63,  = 0.006), whereas atrial fibrillation (HR 2.23, 95% CI 1.29-3.85,  = 0.004) and acute coronary syndrome (HR 2.23, 95% CI 1.02-4.86,  = 0.044) were associated with more readmissions. Patients with acute pulmonary disease at admission showed higher mortality (HR 1.59, 95% CI 1.04-2.43,  = 0.034), especially in subjects aged 75 years or younger (HR 2.52, 95% CI 1.17-5.41,  = 0.018).

Conclusions: Precipitating factors of AHF substantially influenced outcome after hospitalization. In particular, patients with AHF precipitated by acute pulmonary disease showed fewer readmissions and higher 1 year mortality, especially in patients aged 75 years or younger.
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http://dx.doi.org/10.1002/ehf2.12083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066631PMC
June 2016

Ventricular conduction abnormalities as predictors of long-term survival in acute de novo and decompensated chronic heart failure.

ESC Heart Fail 2016 Mar 30;3(1):35-43. Epub 2015 Oct 30.

Heart and Lung Center, Cardiology Helsinki University Hospital Finland.

Aims: Data on the prognostic role of left and right bundle branch blocks (LBBB and RBBB), and nonspecific intraventricular conduction delay (IVCD; QRS ≥ 110 ms, no BBB) in acute heart failure (AHF) are controversial. Our aim was to investigate electrocardiographic predictors of long-term survival in patients with AHF and acutely decompensated chronic heart failure (ADCHF).

Methods And Results: We analysed the admission electrocardiogram of 982 patients from a multicenter European cohort of AHF with 3.9 years' mean follow-up. Half (51.5%,  = 506) of the patients had AHF. LBBB, and IVCD were more common in ADCHF than in AHF: 17.2% vs. 8.7% ( < 0.001) and 20.6% vs. 13.2% ( = 0.001), respectively, and RBBB was almost equally common (6.9% and 8.1%;  = 0.5), respectively. Mortality during the follow-up was higher in patients with RBBB (85.4%) and IVCD (73.7%) compared with patients with normal ventricular conduction (57.0%);  < 0.001 for both. The impact of RBBB on prognosis was prominent in AHF (adjusted HR 1.93, 1.03-3.60;  = 0.04), and IVCD independently predicted death in ADCHF (adjusted HR 1.79, 1.28-2.52;  = 0.001). Both findings were pronounced in patients with reduced ejection fraction. LBBB showed no association with increased mortality in either of the subgroups. The main results were confirmed in a validation cohort of 1511 AHF patients with 5.9 years' mean follow-up.

Conclusions: Conduction abnormalities predict long-term survival differently in AHF and ADCHF. RBBB predicts mortality in AHF, and IVCD in ADCHF. LBBB has no additive predictive value in AHF requiring hospitalization.
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http://dx.doi.org/10.1002/ehf2.12068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061091PMC
March 2016

Physiological changes in pregnancy.

Cardiovasc J Afr 2016 Mar-Apr;27(2):89-94

INSERM UMRS 942, Paris, France; University Paris Diderot, Sorbonne Paris Cité, Paris; Department of Anesthesia and Critical Care, Hôpital Lariboisière, APHP, France.

Physiological changes occur in pregnancy to nurture the developing foetus and prepare the mother for labour and delivery. Some of these changes influence normal biochemical values while others may mimic symptoms of medical disease. It is important to differentiate between normal physiological changes and disease pathology. This review highlights the important changes that take place during normal pregnancy.
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http://dx.doi.org/10.5830/CVJA-2016-021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928162PMC
March 2017

Management of acute heart failure in elderly patients.

Arch Cardiovasc Dis 2016 Jun-Jul;109(6-7):422-30. Epub 2016 May 12.

INSERM UMR-S 942, Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France; Department of Anaesthesiology and Critical Care Medicine, AP-HP, Saint Louis Lariboisière University Hospitals, Paris, France.

Acute heart failure (AHF) is the most common cause of unplanned hospital admissions, and is associated with high mortality rates. Over the next few decades, the combination of improved cardiovascular disease survival and progressive ageing of the population will further increase the prevalence of AHF in developed countries. New recommendations on the management of AHF have been published recently, but as elderly patients are under-represented in clinical trials, and scientific evidence is often lacking, the diagnosis and management of AHF in this population is challenging. The clinical presentation of AHF, especially in patients aged>85years, differs substantially from that in younger patients, with unspecific symptoms, such as fatigue and confusion, often overriding dyspnoea. Older patients also have a different risk profile compared with younger patients: often heart failure with preserved ejection fraction, and infection as the most frequent precipitating factor of AHF. Moreover, co-morbidities, disability and frailty are common, and increase morbidity, recovery time, readmission rates and mortality; their presence should be detected during a geriatric assessment. Diagnostics and treatment for AHF should be tailored according to cardiopulmonary and geriatric status, giving special attention to the patient's preferences for care. Whereas many elderly AHF patients may be managed similarly to younger patients, different strategies should be applied in the presence of relevant co-morbidities, disability and frailty. The option of palliative care should be considered at an early stage, to avoid unnecessary and harmful diagnostics and treatments.
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http://dx.doi.org/10.1016/j.acvd.2016.02.002DOI Listing
January 2017

Clinical picture and risk prediction of short-term mortality in cardiogenic shock.

Eur J Heart Fail 2015 May 28;17(5):501-9. Epub 2015 Mar 28.

Emergency Medicine, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.

Aims: The aim of this study was to investigate the clinical picture and outcome of cardiogenic shock and to develop a risk prediction score for short-term mortality.

Methods And Results: The CardShock study was a multicentre, prospective, observational study conducted between 2010 and 2012. Patients with either acute coronary syndrome (ACS) or non-ACS aetiologies were enrolled within 6 h from detection of cardiogenic shock defined as severe hypotension with clinical signs of hypoperfusion and/or serum lactate >2 mmol/L despite fluid resuscitation (n = 219, mean age 67, 74% men). Data on clinical presentation, management, and biochemical variables were compared between different aetiologies of shock. Systolic blood pressure was on average 78 mmHg (standard deviation 14 mmHg) and mean arterial pressure 57 (11) mmHg. The most common cause (81%) was ACS (68% ST-elevation myocardial infarction and 8% mechanical complications); 94% underwent coronary angiography, of which 89% PCI. Main non-ACS aetiologies were severe chronic heart failure and valvular causes. In-hospital mortality was 37% (n = 80). ACS aetiology, age, previous myocardial infarction, prior coronary artery bypass, confusion, low LVEF, and blood lactate levels were independently associated with increased mortality. The CardShock risk Score including these variables and estimated glomerular filtration rate predicted in-hospital mortality well (area under the curve 0.85).

Conclusion: Although most commonly due to ACS, other causes account for one-fifth of cases with shock. ACS is independently associated with in-hospital mortality. The CardShock risk Score, consisting of seven common variables, easily stratifies risk of short-term mortality. It might facilitate early decision-making in intensive care or guide patient selection in clinical trials.

Trial Registration: NCT01374867.
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http://dx.doi.org/10.1002/ejhf.260DOI Listing
May 2015

Acute heart failure with and without concomitant acute coronary syndromes: patient characteristics, management, and survival.

J Card Fail 2014 Oct 28;20(10):723-730. Epub 2014 Jul 28.

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

Background: Acute coronary syndromes (ACS) may precipitate up to a third of acute heart failure (AHF) cases. We assessed the characteristics, initial management, and survival of AHF patients with (ACS-AHF) and without (nACS-AHF) concomitant ACS.

Methods And Results: Data from 620 AHF patients were analyzed in a prospective multicenter study. The ACS-AHF patients (32%) more often presented with de novo AHF (61% vs. 43%; P < .001). Although no differences existed between the 2 groups in mean blood pressure, heart rate, or routine biochemistry on admission, cardiogenic shock and pulmonary edema were more common manifestations in ACS-AHF (P < .01 for both). Use of intravenous nitrates, furosemide, opioids, inotropes, and vasopressors, as well as noninvasive ventilation and invasive coronary procedures (angiography, percutaneous coronary intervention, coronary artery bypass graft surgery), were more frequent in ACS-AHF (P < .001 for all). Although 30-day mortality was significantly higher for ACS-AHF (13% vs. 8%; P = .03), survival in the 2 groups at 5 years was similar. Overall, ACS was an independent predictor of 30-day mortality (adjusted odds ratio 2.0, 95% confidence interval 1.07-3.79; P = .03).

Conclusions: Whereas medical history and the manifestation and initial treatment of AHF between ACS-AHF and nACS-AHF patients differ, long-term survival is similar. ACS is, however, independently associated with increased short-term mortality.
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http://dx.doi.org/10.1016/j.cardfail.2014.07.008DOI Listing
October 2014

Causes of death and predictors of 5-year mortality in young adults after first-ever ischemic stroke: the Helsinki Young Stroke Registry.

Stroke 2009 Aug 9;40(8):2698-703. Epub 2009 Jul 9.

Department of Neurology, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-00290, Helsinki, Finland.

Background And Purpose: Data on mortality and its prognostic factors after an acute ischemic stroke in young adults are scarce and based on relatively small heterogeneous patient series.

Methods: We analyzed 5-year mortality data of all consecutive patients aged 15 to 49 with first-ever ischemic stroke treated at the Department of Neurology, Helsinki University Central Hospital, from January 1994 to September 2003. We followed up the patients using data from the mortality registry of Statistics Finland. We used life table analyses for calculating mortality risks. Kaplan-Meier method allowed comparisons of survival between clinical subgroups. We used the Cox proportional hazard model for identifying predictors of mortality. Stroke severity was measured using the National Institutes of Health Stroke Scale and the Glasgow Coma Scale.

Results: Among the 731 patients (mean age, 41.5+/-7.4 years; 62.8% males) followed, 78 died. Cumulative mortality risks were 2.7% (95% CI, 1.5% to 3.9%) at 1 month, 4.7% (3.1% to 6.3%) at 1 year, and 10.7% (9.9% to 11.5%) at 5 years with no gender difference. Those > or =45 years of age had lower probabilities of survival. Among the 30-day survivors (n=711), stroke caused 21%, cardioaortic and other vascular causes 36%, malignancies 12%, and infections 9% of the deaths. Malignancy, heart failure, heavy drinking, preceding infection, type 1 diabetes, increasing age, and large artery atherosclerosis causing the index stroke independently predicted 5-year mortality adjusted for age, gender, relevant risk factors, stroke severity, and etiologic subtype.

Conclusions: Despite the overall low mortality after an ischemic stroke in young adults, several recognizable subgroups had substantially increased risk of death in the long term.
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http://dx.doi.org/10.1161/STROKEAHA.109.554998DOI Listing
August 2009
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