AimsThe calcium sensitizer levosimendan may counteract stunning after reperfusion of ischaemic myocardium, but no randomized placebo-controlled trials exist regarding its use in PCI-treated ST-segment elevation infarction (STEMI). We evaluated the efficacy and safety of levosimendan in patients with a primary PCI-treated STEMI complicated by symptomatic heart failure (HF). Methods and resultsA total of 61 patients developing clinical signs of HF within 48 h after a primary PCI-treated STEMI (including cardiogenic shock) were randomized double-blind to a 25 h infusion of levosimendan or placebo. The primary endpoint was change in wall motion score index (WMSI) from baseline to day 5 measured by echocardiography. There was a significantly larger improvement in WMSI from baseline to day 5 in the levosimendan group compared with placebo (from 1.94 + 0.20 to 1.66 + 0.31 vs. 1.99 + 0.22 to 1.83 + 0.26, respectively, P ¼ 0.031). There were significantly more episodes of hypotension during study drug infusion in the levosimendan group (67% vs. 36%, P ¼ 0.029), but no significant difference in blood pressure at the end of infusion or in use of vasopressors. No significant between-group differences in changes in NT-proBNP levels, clinical composite score, frequency of atrial fibrillation or ventricular arrhythmia, infarct size at 6 weeks, or new clinical events up to 6 months were found. One and four patients died in the levosimendan and placebo group, respectively. ConclusionsLevosimendan treatment improved contractility in post-ischaemic myocardium in patients with PCI-treated STEMI complicated by HF. The treatment was well tolerated, without any increase in arrhythmias. ------------------------------ KeywordsLevosimendan † Acute heart failure † ST-elevation myocardial infarction † Wall motion score index † Myocardial stunning

Only patients with JDM and no controls had subclinical left ventricular diastolic dysfunction; the patients with elevated E/E' also had high prevalence of pathological ECG and hypertension. High disease activity 1-year post diagnosis predicted high E/E' at follow-up. The findings suggest that subclinical heart disease is related to the systemic nature of JDM.

Acute heart failure and/or cardiogenic shock are frequently triggered by ischemic coronary events. Yet, there is a paucity of randomized data on the management of patients with heart failure complicating acute coronary syndrome, as acute coronary syndrome and cardiogenic shock have frequently been defined as exclusion criteria in trials and registries. As a consequence, guideline recommendations are mostly driven by observational studies, even though these patients have a particularly poor prognosis compared to heart failure patients without signs of coronary artery disease. In acute heart failure, and especially in cardiogenic shock related to ischemic conditions, vasopressors and inotropes are used. However, both pathophysiological considerations and available clinical data suggest that these treatments may have disadvantageous effects. The inodilator levosimendan offers potential benefits due to a range of distinct effects including positive inotropy, restoration of ventriculo-arterial coupling, increases in tissue perfusion, and anti-stunning and anti-inflammatory effects. In clinical trials levosimendan improves symptoms, cardiac function, hemodynamics, and end-organ function. Adverse effects are generally less common than with other inotropic and vasoactive therapies, with the notable exception of hypotension. The decision to use levosimendan, in terms of timing and dosing, is influenced by the presence of pulmonary congestion, and blood pressure measurements. Levosimendan should be preferred over adrenergic inotropes as a first line therapy for all ACS-AHF patients who are under beta-blockade and/or when urinary output is insufficient after diuretics. Levosimendan can be used alone or in combination with other inotropic or vasopressor agents, but requires monitoring due to the risk of hypotension.

on behalf of the ASSERT (Aortic Stentless versus Stented valve assessed by Echocardiography Randomized Trial) InvestigatorsBackground-Aortic valve replacement (AVR) is the established treatment for severe aortic stenosis. In response to the long-term results of aortic homografts, stentless porcine valves were introduced as an alternative low-resistance valve.We conducted a randomized trial comparing a stentless with a stented porcine valve in adults with severe aortic stenosis. Methods and Results-The primary outcome was change in left ventricular mass index (LVMI) measured by transthoracic echocardiography and, in a subset, by cardiovascular MR. Measurements were taken before valve replacement and at 6 and 12 months. Patients undergoing AVR with an aortic annulus Յ25 mm in diameter were randomly allocated to a stentless (nϭ93) or a stented supra-annular (nϭ97) valve. There were no significant differences in mean LVMI between the stentless versus stented groups at baseline (176Ϯ62 and 182Ϯ63 g/m 2 , respectively) or at 6 months (142Ϯ49 and 131Ϯ45 g/m 2 , respectively), although within-group changes from baseline to 6 months were highly significant. Changes in LVMI measured by cardiovascular MR (nϭ38) were consistent with the echo findings. There was a greater reduction in peak aortic velocity (PϽ0.001) and a greater increase in indexed effective orifice area (PϽ0.001) in the stentless group than in the stented group. There were no differences in clinical outcomes between the 2 valve groups. Conclusions-Despite significant differences in indexed effective orifice area and peak flow velocity in favor of the stentless valve, there were similar reductions in left ventricular mass at 6 months with both stented and stentless valves, which persisted at 12 months. (Circulation. 2005;112:2696-2702.)

Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish regulatory authorities for the haemodynamic stabilisation of patients with acutely decompensated chronic heart failure. In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitisation and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced heart failure, right ventricular failure and pulmonary hypertension, cardiac surgery, critical care and emergency medicine. Levosimendan is currently in active clinical evaluation in the US. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and non-cardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, UK and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute heart failure arena in recent times and charts a possible development trajectory for the next 20 years.

PD commonly occurs in this chest pain population. Thus, there is a need to educate physicians caring for these patients about PD identification and treatment.

We report an increase in plasma BNP in patients with AS. Following a further transient increase postoperatively, BNP levels decreased at six and twelve months after AVR. BNP correlated with LVMI preoperatively, and with age both preoperatively and at twelve months.

BackgroundNo data from controlled trials exists regarding the inflammatory response in patients with de novo heart failure (HF) complicating ST-elevation myocardial infarction (STEMI) and a possible role in the recovery of contractile function. We therefore explored the time course and possible associations between levels of inflammatory markers and recovery of impaired left ventricular function as well as levosimendan treatment in STEMI patients in a substudy of the LEvosimendan in Acute heart Failure following myocardial infarction (LEAF) trial.MethodsA total of 61 patients developing HF within 48 hours after a primary PCI-treated STEMI were randomised double-blind to a 25 hours infusion of levosimendan or placebo. Levels of IL-6, CRP, sIL-6R, sgp130, MCP-1, IL-8, MMP-9, sICAM-1, sVCAM-1 and TNF-α were measured at inclusion (median 22 h, interquartile range (IQR) 14, 29 after PCI), on day 1, day 2, day 5 and 6 weeks. Improvement in left ventricular function was evaluated as change in wall motion score index (WMSI) by echocardiography.ResultsOnly circulating levels of IL-8 at inclusion were associated with change in WMSI from baseline to 6 weeks, r = ÷0.41 (p = 0.002). No association, however, was found between IL-8 and WMSI at inclusion or peak troponin T. Furthermore, there was a significant difference in change in WMSI from inclusion to 6 weeks between patients with IL-8 levels below, compared to above median value, ÷0.44 (IQR÷0.57, ÷0.19) vs. ÷0.07 (IQR÷0.27, 0.07), respectively (p<0.0001). Levosimendan did not affect the levels of inflammary markers compared to control.ConclusionHigh levels of IL-8 in STEMI patients complicated with HF were associated with less improvement in left ventricular function during the first 6 weeks after PCI, suggesting a possible role of IL-8 in the reperfusion-related injury of post-ischemic myocardium. Further studies are needed to confirm this hypothesis.Trial RegistrationClinicalTrials.gov NCT00324766