Clinical profiles, pharmacotherapies and prognosis in acute heart failure : Focus on vasoactive medications

Acute heart failure (AHF), one of the most common reasons for hospitalizations, is associated with high mortality. Its management is challenging and should be tailored according to different clinical manifestations that range from less severe hypertensive AHF to the most severe form, cardiogenic shock (CS), with its extremely poor prognosis. Acute coronary syndrome (ACS) precipitates over one-third of AHF (ACS-AHF) cases. The aim of this thesis is to analyze current real-life AHF management, with emphasis on vasoactive therapies, in relation to different AHF clinical presentations and specifically CS. In addition, the study targets for characterization two poorly described clinical pictures: 1) ACS-AHF and 2) CS complicated by acute kidney injury (AKI), a common organ injury in the critically ill. Data from two independent prospectively collected patient cohorts in this thesis comprise the FINN-AKVA (Finnish Acute Heart Failure) study, which is a national multicenter study including 620 patients hospitalized for AHF, and the European multicenter CardShock study including 219 patients with CS. Furosemide was the most common therapy for AHF regardless of clinical presentation, often administered even during the initial CS phase. Other intravenous medications and non-invasive ventilation varied according to the AHF clinical picture of AHF. Systolic blood pressure (SBP) was one of the main predictors of AHF-therapy utilization. Considering previous and current European guideline recommendations, use of nitrates was rather low, especially in hypertensive AHF. Compared with AHF patients without concomitant ACS (nACS-AHF), ACS-AHF manifested as a more severe clinical presentation and more frequently as de novo AHF. Guideline-recommended AHF therapies and invasive coronary procedures were more frequent in ACS-AHF. However, angiography (35%) and revascularization (percutaneous coronary intervention 16% and coronary artery bypass graft surgery 10%) rates were low. ACS-AHF was associated with higher 30-day mortality than was AHF without concomitant ACS (13% vs 8%). Use of vasopressors and inotropes was rather frequent in patients without shock, especially in pulmonary edema, and in ACS-AHF as well. They were used almost invariably in CS, noradrenaline being the most common vasopressor and dobutamine the inotrope of choice. Adrenaline was associated not only with excessive cardiac but also with 90-day mortality. In turn, noradrenaline combined with either dobutamine or levosimendan was associated with a more positive prognosis; these two combinations appeared to be alternatives with equivalent outcomes. Patients with CS frequently developed AKI during their first 48 hours of shock, but incidence varied by definition. The AKI definition based on urine output (UO) seemed rather liberal compared with one based on creatinine or on cystatin C (CysC). In addition, creatinine- and CysC-defined AKIs were independently related to higher 90-day mortality, whereas the UO-based AKI definition was not. A stricter cutoff of <0.3 mL/kg/h for average UO during a 6-hour period was more accurate in mortality prediction. AKI was correlated with findings of arterial hypotension, low cardiac output, and venous congestion. This study raises questions as to how well the AHF guidelines and recommended therapies are implemented in clinical practice. In addition, the study describes the clinical importance of ACS in AHF and of AKI in CS.Äkillinen eli akuutti sydämen vajaatoiminta (ASV) on yksi yleisimmistä sairaalahoitoon johtavista sairauksista ja siihen liittyy huomattavan korkea kuolleisuus. ASV:n hoito on haastavaa johtuen erilaisista taudinkuvista, jotka ulottuvat korkean verenpaineen aiheuttamasta ASV:sta erittäin huonoennusteiseen sydänperäiseen sokkiin. ASV:n taustalla on usein sepelvaltimotautikohtaus. Väitöskirjassa selvitetään hoitojen, ja erityisesti verenkiertoon vaikuttavien (vasoaktiivisten) lääkkeiden, toteutumista suhteessa ASV:n eri taudinkuviin ja erityisesti sydänperäisen sokkiin. Lisäksi siinä kuvataan kaksi aiemmin huonosti tunnettua taudinkuvaa: 1) sepelvaltimotautikohtauksen aiheuttama ASV, ja 2) sydänperäinen sokki, jota komplisoi akuutti munuaisvaurio, joka on yleinen kriittisesti sairailla. Furosemidi oli useimmin käytetty hoito riippumatta taudinkuvasta, ja sitä käytettiin usein myös sydänperäisen sokin varhaisvaiheessa. Muiden ASV:n hoitojen käyttö vaihteli taudinkuvan mukaan. Systolinen verenpaine oli yksi tärkeimmistä hoidon toteutumista ennustavista tekijöistä. Nitraattien käyttö vaikutti alimitoitetulta eurooppalaisiin hoitosuosituksiin nähden erityisesti korkean verenpaineen aiheuttamassa ASV:ssa. Sen sijaan vasopressorien ja inotrooppien käyttö oli melko yleistä muilla kuin sokkipotilailla, ja etenkin akuutissa keuhkopöhössä sekä sepelvaltimotautikohtauksen aiheuttamassa ASV:ssa. Adrenaliinin käytön turvallisuus vaikutti kyseenalaiselta, sillä sen käyttöön liittyi korostunut sydänlihasvaurio ja 90 päivän ylikuolleisuus. Sepelvaltimotautikohtauksen aiheuttamaan ASV:aan liittyi vakavampi taudinkuva ja lisääntynyt 30 päivän kuolleisuus (13% vs 8%) verrattuna muiden tekijöiden aiheuttamaan tautiin. Siitä huolimatta sepelvaltimoiden varjoainekuvausten (35%) ja verenkierron palauttamiseen tähtäävien toimenpiteiden (pallolaajennus 16% ja ohitusleikkaus 10%) toteutuminen oli suhteellisen vähäistä. Sydänperäisessa sokissa kehittyi usein akuutti munuaisvaurio 48 tunnin sisällä sokin alusta, mutta ilmaantuvuus vaihteli akuutin munuaisvaurion määritelmien (kreatiniini, virtsantulo ja kystatiini C) välillä. Akuutti munuaisvaurio liittyi riittämättömään verenvirtaukseen ja laskimotungokseen viittaaviin löydöksiin, ja se ennusti voimakkaasti lisääntynyttä 90 päivän kuolleisuutta. Tiukennetun virtsantuloon perustuvan raja-arvon - <0,3 ml/kg/h 6 tunnin ajan - osoitettiin ennustavan kuolleisuutta nykyistä määritelmää paremmin. Tutkimuksen tulokset auttavat kiinnittämään huomiota ASV:n suositusten mukaisten hoitojen toteutumisen mahdollisiin epäkohtiin. Tutkimus lisää myös ymmärrystä kahden aiemmin vaillinaisesti kuvatun taudinkuvan piirteistä ja ennusteellisesta merkityksestä

Sydämen äkillinen vajaatoiminta

Teema : sydämen vajaatoiminta. Vertaisarvioitu.Sydämen äkillinen vajaatoiminta on yleinen sairaalahoitoon johtava tila, jonka taudinkuva vaihtelee hitaasti ja salakavalasti lisääntyvistä epämääräisistä jaksamattomuus- ja turvotusoireista nopeasti kehittyvään voimakasoireiseen sokkiin, johon kuolleisuus on hyvin suuri. Nykyinen diagnostiikka perustuu kokonaisvaltaiseen arvioon, jossa hyödynnetään natriureettisten peptidien lisäksi sydämen ja keuhkojen kaikukuvausta. Koska laskimoiden ja elinten verentungos eli kongestio on pääasiallinen oireiden, löydösten ja elintoimintahäiriöiden syy, hoitokin perustuu pitkälti tehokkaaseen diureettilääkitykseen, jonka yhteydessä lieviä munuaistoiminnan muutoksia ei tule pelätä. Lisäksi laukaiseva tekijä tai taustasyy tulisi määrittää ja hoitaa mahdollisuuksien mukaan vajaatoiminnan korjaamiseksi. Potilaan ennusteen parantamiseksi systolisen vajaatoiminnan ennusteeseen vaikuttavia lääkkeitä pyritään käyttämään ja optimoimaan mahdollisuuksien mukaan osastohoitojakson aikana.Peer reviewe

The impact of emergency medical services in acute heart failure

Background: Real-life data on the role of emergency medical services (EMS) in acute heart failure (AHF) are scarce. Our aim was to describe prehospital treatment of AHF and to compare patients using EMS with self-presented, non-EMS patients. Methods: Data were collected retrospectively from three university hospitals in Helsinki metropolitan area between July 1, 2012 and July 31, 2013. According to the use of EMS, patients were divided into EMS and non-EMS groups. Results: The study included 873 AHF patients. One hundred were (11.5%) EMS and 773 (88.5%) non-EMS. EMS patients more often had comorbidities. Initial heart rate (HR) and peripheral oxygen saturation (SpO(2)) differed between EMS and non-EMS patients; mean HR 89.2 (SD 22.5) vs. 83.7 (21.5)/min (p = 0.02) and SpO(2) 90.3 (8.6) vs. 92.9 (6.6)% (p= 0.01). However, on presentation to ED EMS patients' vital signs were similar to non-EMS patients'. On presentation to ED 46.0% were normotensive and 68.2% "warm and wet". Thirty-four percentage of EMS patients received prehospital medication. In-hospital mortality was 6.0% and 7.1% (p = 0.84) and length of stay (LOS) 7.7 (7.0) and 8.5 (7.9) days (p= 0.36) in EMS and non-EMS groups. Conclusion: The use of EMS and administration of prehospital medication was low. EMS patients had initially worse HR and SpO(2) than non-EMS patients. However, EMS patients' signs improved and were similar on presentation to ED. There were no differences in in-hospital mortality and LOS. This underscores the need for equal attention to any AHF patient independent of the arrival mode. (c) 2017 Elsevier Ireland Ltd. All rights reserved.Peer reviewe

Effect of baseline characteristics on mortality in the SURVIVE trial on the effect of levosimendan vs dobutamine in acute heart failure: Sub-analysis of the Finnish patients

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The emergency department arrival mode and its relations to ED management and 30-day mortality in acute heart failure : an ancillary analysis from the EURODEM study

Background Acute heart failure patients are often encountered in emergency departments (ED) from 11% to 57% using emergency medical services (EMS). Our aim was to evaluate the association of EMS use with acute heart failure patients' ED management and short-term outcomes. Methods This was a sub-analysis of a European EURODEM study. Data on patients presenting with dyspnoea were collected prospectively from European EDs. Patients with ED diagnosis of acute heart failure were categorized into two groups: those using EMS and those self-presenting (non- EMS). The independent association between EMS use and 30-day mortality was evaluated with logistic regression. Results Of the 500 acute heart failure patients, with information about the arrival mode to the ED, 309 (61.8%) arrived by EMS. These patients were older (median age 80 vs. 75 years, p 30/min in 17.1% patients vs. 7.5%, p = 0.005). The only difference in ED management appeared in the use of ventilatory support: 78.3% of EMS patients vs. 67.5% of non- EMS patients received supplementary oxygen (p = 0.007), and non-invasive ventilation was administered to 12.5% of EMS patients vs. 4.2% non- EMS patients (p = 0.002). EMS patients were more often hospitalized (82.4% vs. 65.9%, p < 0.001), had higher in-hospital mortality (8.7% vs. 3.1%, p = 0.014) and 30-day mortality (14.3% vs. 4.9%, p < 0.001). The use of EMS was an independent predictor of 30-day mortality (OR = 2.54, 95% CI 1.11-5.81, p = 0.027). Conclusion Most acute heart failure patients arrive at ED by EMS. These patients suffer from more severe respiratory distress and receive more often ventilatory support. EMS use is an independent predictor of 30-day mortality.Peer reviewe

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

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

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

Aims The role of microRNAs has not been studied in cardiogenic shock. We examined the potential role of miR-423-5p level to predict mortality and associations of miR-423-5p with prognostic markers in cardiogenic shock. Methods and results We conducted a prospective multinational observational study enrolling consecutive cardiogenic shock patients. Blood samples were available for 179 patients at baseline to determine levels of miR-423-5p and other biomarkers. Patients were treated according to local practice. Main outcome was 90 day all-cause mortality. Median miR-423-5p level was significantly higher in 90 day non-survivors [median 0.008 arbitrary units (AU) (interquartile range 0.003-0.017) vs. 0.004 AU (0.002-0.009), P = 0.003]. miR-423-5p level above median was associated with higher lactate (median 3.7 vs. 2.4 mmol/L, P = 0.001) and alanine aminotransferase levels (median 68 vs. 35 IU/L, P <0.001) as well as lower cardiac index (1.8 vs. 2.4, P = 0.04) and estimated glomerular filtration rate (56 vs. 70 mL/min/1.73 m(2), P = 0.002). In Cox regression analysis, miR-423-5p level above median was associated with 90 day all-cause mortality independently of established risk factors of cardiogenic shock [adjusted hazard ratio 1.9 (95% confidence interval 1.2-3.2), P = 0.01]. Conclusions In cardiogenic shock patients, above median level of miR-423-5p at baseline is associated with markers of hypoperfusion and seems to independently predict 90 day all-cause mortality.Peer reviewe

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

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 (p < 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), p = 0.018; adjusted hazard ratio 1.9 (95% confidence interval 1.2–3.2), p = 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

The association of admission blood glucose level with the clinical picture and prognosis in cardiogenic shock - Results from the CardShock Study

Background: Critically ill patients often present with hyperglycemia, regardless of previous history of diabetes mellitus (DM). Hyperglycemia has been associated with adverse outcome in acute myocardial infarction and acute heart failure. We investigated the association of admission blood glucose level with the clinical picture and short-term mortality in cardiogenic shock (CS). Methods: Consecutively enrolled CS patients were divided into five categories according to plasma glucose level at the time of enrolment: hypoglycemia (glucose = 16.0 mmol/L) hyperglycemia. Clinical presentation, biochemistry, and short-term mortality were compared between the groups. Results: Plasma glucose level of 211 CS patients was recorded. Glucose levels were distributed equally between normoglycemia (26% of patients), mild (27%), moderate (19%) and severe (25%) hyperglycemia, while hypoglycemia (2%) was rare. Severe hyperglycemia was associated with higher blood leukocyte count (17.3 (5.8) E9/L), higher lactate level (4.4 (3.3-8.4) mmol/L) and lower arterial pH (7.23 (0.14)) compared with normoglycemia or mild to moderate hyperglycemia (p <0.001 for all). In-hospital mortality was highest among hypoglycemic (60%) and severely hyperglycemic (56%) patients, compared with 22% in normoglycemic group (p <0.01). Severe hyperglycemia was an independent predictor of in-hospital mortality (OR 3.7, 95% CI 1.19-11.7, p = 0.02), when adjusted for age, gender, LVEF, lactate, and DM. Conclusions: Admission blood glucose level has prognostic significance in CS. Mortality is highest among patients with severe hyperglycemia or hypoglycemia. Severe hyperglycemia is independently associated with high in-hospital mortality in CS. It is also associated with biomarkers of systemic hypoperfusion and stress response. (C) 2016 Elsevier Ireland Ltd. All rights reserved.Peer reviewe