Trygve Husebye

Randomized Comparison of Stentless Versus Stented Valves for Aortic Stenosis Effects on Left Ventricular Mass

Background— 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 ≤25 mm in diameter were randomly allocated to a stentless (n=93) or a stented supra-annular (n=97) valve. There were no significant differences in mean LVMI between the stentless versus stented groups at baseline (176±62 and 182±63 g/m2, respectively) or at 6 months (142±49 and 131±45 g/m2, respectively), although within-group changes from baseline to 6 months were highly significant. Changes in LVMI measured by cardiovascular MR (n=38) were consistent with the echo findings. There was a greater reduction in peak aortic velocity (P<0.001) and a greater increase in indexed effective orifice area (P<0.001) 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.

Panic disorder in chest pain patients referred for cardiological outpatient investigation

Objectives. The aims of the study were to: (i) determine the prevalence of panic disorder (PD) in patients referred to cardiological outpatient clinics for evaluation of chest pain; (ii) compare psychiatric comorbidity, psychological distress, pain characteristics and suicidal ideation in PD and non‐PD patients; (iii) compare the prevalence of coronary risk factors and medical comorbidity in PD and non‐PD patients; and (iv) describe current PD treatment and need for PD treatment as expressed by PD patients.

Levosimendan in acute heart failure following primary percutaneous coronary intervention-treated acute ST-elevation myocardial infarction. Results from the LEAF trial: a randomized, placebo-controlled study.

The 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).

The effect of aortic valve replacement on plasma B-type natriuretic peptide in patients with severe aortic stenosis--one year follow-up.

B‐type natriuretic peptide (BNP) is synthesized in cardiac tissue in response to increased wall stress and myocardial hypertrophy.

Osteoprotegerin levels predict mortality in patients with symptomatic aortic stenosis

Abstract.  Ueland T, Aukrust P, Dahl CP, Husebye T, Solberg OG, Tønnessen T, Aakhus S, Gullestad L (Oslo University Hospital Rikshospitalet; University of Oslo; Oslo University Hospital Rikshospitalet; Oslo University Hospital Ullevål; Oslo University Hospital Rikshospitalet; and Oslo University Hospital Ullevål, Oslo, Norway). Osteoprotegerin levels predict mortality in patients with symptomatic aortic stenosis. J Intern Med 2011; 270: 452–460.

A Long-Term Follow-Up Study of Chest Pain Patients: Effect of Panic Disorder on Mortality, Morbidity, and Quality of Life

Aims: The aim was to assess the association between panic disorder (PD) and the long-term outcome of chest pain patients with or without coronary artery disease (CAD). Methods: Patients (n = 199) consecutively referred to a cardiology outpatient clinic because of chest pain were reassessed after 9 years. At the initial examination 16% suffered from CAD and 38% from PD. Data were collected on mortality, cardiac events, cardiac risk factors, chest pain, anxiety and depression (SCL-90-R), and health-related quality of life (SF-36). Results: The death rate in the study population was not significantly different from that in the general population and no significant associations were found between PD at baseline and mortality and cardiac morbidity at follow-up. PD was associated with significantly higher follow-up scores of chest pain intensity (p = 0.025), depression (p = 0.005), anxiety (p = 0.039), and poorer health-related quality of life: physical functioning (p = 0.004), role physical (p = 0.001), body pain (p = 0.007), and general health (p < 0.001). Conclusions: PD has a negative long-term effect on psychological and physical well-being of chest pain patients which emphasizes the necessity of identifying PD patients and offering them adequate treatment.

Alterations in circulating activin A, GDF‐15, TGF‐β3 and MMP‐2, ‐3, and ‐9 during one year of left ventricular reverse remodelling in patients operated for severe aortic stenosis

Patients with aortic stenosis (AS) develop left ventricular remodelling with cardiomyocyte hypertrophy and increased fibrosis. Following aortic valve replacement (AVR) reverse remodelling usually takes place.

The role of levosimendan in acute heart failure complicating acute coronary syndrome: A review and expert consensus opinion

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.

Association of interleukin 8 and myocardial recovery in patients with ST-elevation myocardial infarction complicated by acute heart failure.

Background No 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. Methods A 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. Results Only 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. Conclusion High 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 Registration ClinicalTrials.gov NCT00324766

Prosthetic heart valve thrombosis during dicloxacillin therapy

A 76-year-old woman receiving warfarin after aortic valve replacement experienced prosthetic valve thrombosis during dicloxacillin therapy. Successful thrombolysis was achieved with tissue plasminogen activator. The international normalized ratio (INR) on admission was reduced to 1.4 and an increased warfarin dosage was required for three weeks following discontinuation of dicloxacillin treatment in order to maintain therapeutic INRs. Careful monitoring of INRs and titration of the warfarin dosage is recommended when dicloxacillin is prescribed to patients receiving warfarin.