A man in his seventies with fatigue and renal failure. / En mann i 70-årene med utmattelse og nyresvikt.

A man in his seventies underwent routine heart examinations as part of workup for kidney transplantation. Unexpected findings led to more extensive investigations and revealed two rare systemic diseases as causes of his heart failure.

Neutrophil extracellular trap components and myocardial recovery in post-ischemic acute heart failure.

OBJECTIVE: The role of neutrophil extracellular traps (NETs) in acute heart failure is unknown. We recently showed that interleukin 8, a putative NETs stimulator, was associated with myocardial recovery in acute heart failure complicating ST-elevation myocardial infarction (STEMI). In this exploratory post-hoc study, we aimed to investigate the role of NETs components in relation to myocardial function and interleukin 8 in STEMI patients with symptomatic acute heart failure. METHODS: In 61 STEMI patients developing acute heart failure within 48 hours of successful revascularization, wall motion score index (WMSI), global longitudinal strain (GLS) and left ventricular ejection fraction (LVEF) were assessed by echocardiography at baseline and on day 5. Blood drawn at baseline and days 1, 2 and 5 was used to quantify double-stranded DNA (dsDNA), myeloperoxidase-DNA complexes (MPO-DNA) and citrullinated histone 3 (CitH3). The area under the curve (AUC) of each NETs marker and interleukin 8 was approximated for the first 5 days. RESULTS: dsDNAAUC and MPO-DNAAUC correlated significantly with change in WMSI from baseline to day 5 (rs = 0.28 for both, p≤0.05), whereas NETs AUCs did not correlate with changes in GLS and LVEF. dsDNAAUC was significantly correlated with interleukin 8AUC (r = 0.40, p = 0.003). However, mixed model regression could not identify a significant effect of the NETs components on myocardial function parameters. CONCLUSIONS: In this cohort with acute heart failure complicating STEMI, NETs components were partly correlated with myocardial function and interleukin 8 levels, yet no causal relationship between NETs components and myocardial recovery could be established. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT00324766.

Short-Term Therapies for Treatment of Acute and Advanced Heart Failure-Why so Few Drugs Available in Clinical Use, Why Even Fewer in the Pipeline?

Both acute and advanced heart failure are an increasing threat in term of survival, quality of life and socio-economical burdens. Paradoxically, the use of successful treatments for chronic heart failure can prolong life but-per definition-causes the rise in age of patients experiencing acute decompensations, since nothing at the moment helps avoiding an acute or final stage in the elderly population. To complicate the picture, acute heart failure syndromes are a collection of symptoms, signs and markers, with different aetiologies and different courses, also due to overlapping morbidities and to the plethora of chronic medications. The palette of cardio- and vasoactive drugs used in the hospitalization phase to stabilize the patient's hemodynamic is scarce and even scarcer is the evidence for the agents commonly used in the practice (e.g. catecholamines). The pipeline in this field is poor and the clinical development chronically unsuccessful. Recent set backs in expected clinical trials for new agents in acute heart failure (AHF) (omecamtiv, serelaxine, ularitide) left a field desolately empty, where only few drugs have been approved for clinical use, for example, levosimendan and nesiritide. In this consensus opinion paper, experts from 26 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, The Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, Turkey, U.K. and Ukraine) analyse the situation in details also by help of artificial intelligence applied to bibliographic searches, try to distil some lesson-learned to avoid that future projects would make the same mistakes as in the past and recommend how to lead a successful development project in this field in dire need of new agents.

Trifecta has lower gradient and less prosthesis-patient mismatch than Mosaic Ultra in the aortic position: A prospective randomized study.

OBJECTIVE: When aortic valve replacement is needed, a biological valve is usually implanted in patients older than age 60 to 65 years. A large valvular opening area is important to avoid prosthesis-patient mismatch and facilitate reverse left ventricular remodeling. The Trifecta biological valve (St Jude Medical, St Paul, Minn) is, because of its design, believed to reduce transvalvular gradient compared with other biological valves, especially in smaller annuli. Several retrospective studies have compared transvalvular gradients of implanted valves prostheses using the respective manufacturers given size and not the actual annulus size measured by a metric sizer. This makes comparison of the hemodynamic properties of different valve brands and sizes difficult. We therefore performed a prospective randomized study, using the same metric sizer to measure annulus size, and compared hemodynamic profiles of the Trifecta to our standard Mosaic Ultra biological valve (Medtronic, Minneapolis, Minn). METHODS: Ninety elective patients with small to medium annulus diameter undergoing aortic valve replacement were randomized to either Trifecta or Mosaic Ultra. After native valve removal and decalcification, a Hegar-sizer was used to measure true annulus size. Then the largest possible valve of either brand was implanted according to the randomization protocol. Echocardiography was performed 6 months postoperatively. RESULTS: Baseline parameters of the 2 cohorts were comparable. There were lower transvalvular gradients in the Trifecta compared with the Mosaic Ultra group for the given annulus sizes. Severe prosthesis-patient mismatch was present in 28% of patients in the Mosaic group and 3% of patients in the Trifecta group. CONCLUSIONS: Trifecta showed lower transvalvular gradients and less severe prosthesis-patient mismatch compared with Mosaic Ultra for the given annulus sizes. ClinicalTrials.gov Protocol ID: 2011/2596/REK.

Regional diastolic dysfunction in post-infarction heart failure: role of local mechanical load and SERCA expression.

AIMS: Regional heterogeneities in contraction contribute to heart failure with reduced ejection fraction (HFrEF). We aimed to determine whether regional changes in myocardial relaxation similarly contribute to diastolic dysfunction in post-infarction HFrEF, and to elucidate the underlying mechanisms. METHODS AND RESULTS: Using the magnetic resonance imaging phase-contrast technique, we examined local diastolic function in a rat model of post-infarction HFrEF. In comparison with sham-operated animals, post-infarction HFrEF rats exhibited reduced diastolic strain rate adjacent to the scar, but not in remote regions of the myocardium. Removal of Ca2+ within cardiomyocytes governs relaxation, and we indeed found that Ca2+ transients declined more slowly in cells isolated from the adjacent region. Resting Ca2+ levels in adjacent zone myocytes were also markedly elevated at high pacing rates. Impaired Ca2+ removal was attributed to a reduced rate of Ca2+ sequestration into the sarcoplasmic reticulum (SR), due to decreased local expression of the SR Ca2+ ATPase (SERCA). Wall stress was elevated in the adjacent region. Using ex vivo experiments with loaded papillary muscles, we demonstrated that high mechanical stress is directly linked to SERCA down-regulation and slowing of relaxation. Finally, we confirmed that regional diastolic dysfunction is also present in human HFrEF patients. Using echocardiographic speckle-tracking of patients enrolled in the LEAF trial, we found that in comparison with controls, post-infarction HFrEF subjects exhibited reduced diastolic train rate adjacent to the scar, but not in remote regions of the myocardium. CONCLUSION: Our data indicate that relaxation varies across the heart in post-infarction HFrEF. Regional diastolic dysfunction in this condition is linked to elevated wall stress adjacent to the infarction, resulting in down-regulation of SERCA, disrupted diastolic Ca2+ handling, and local slowing of relaxation.

Soluble IL-1 receptor 2 is associated with left ventricular remodelling in patients with ST-elevation myocardial infarction.

BACKGROUND: The inflammatory response following myocardial infarction (MI) is prerequisite for proper healing of infarcted tissue, but can also have detrimental effects on cardiac function. Interleukin (IL)-1α and IL-1ß are potent inflammatory mediators and their bioactivity is tightly regulated by IL-1 receptor antagonist (IL-1ra) and soluble (s) IL-1 receptors (R). We aimed to examine whether levels of soluble regulators of IL-1 signalling are changed during ST-elevation MI (STEMI) and their associations with parameters of cardiac injury and ventricular remodelling. METHODS: Plasma levels of IL-1Ra, sIL-1R1, sIL-1R2 and sIL-1R accessory protein (sIL-1RAcP) were measured by immunoassays in repeated samples from patients with STEMI (n = 255) and compared to healthy controls (n = 65). RESULTS: IL-1Ra, sIL-1R1 and sIL-1R2 levels were all significantly elevated after STEMI, while levels of sIL-1RAcP were lower compared to controls. sIL-1R2 levels (at different time points) correlated positively with C-reactive protein, myocardial infarct size and change in indexed left ventricular end-diastolic and end-systolic volume (LVEDVi and LVESVi) measured by cardiac MR acutely and after 4 months, and negatively with LV ejection fraction. Patients with >median levels of sIL-1R2 in the acute phase were more likely to have increased change in LVEDVi and LVESVi. Importantly, sIL-1R2 remained significantly associated with change in LVEDVi and LVESVi also after adjustment for clinical covariates. CONCLUSION: Levels of sIL-1R2 are independently associated with parameters of LV adverse remodelling following STEMI.

Acute heart failure following myocardial infarction: complement activation correlates with the severity of heart failure in patients developing cardiogenic shock.

AIMS: Heart failure (HF) is an impending complication to myocardial infarction. We hypothesized that the degree of complement activation reflects severity of HF following acute myocardial infarction. METHODS AND RESULTS: The LEAF trial (LEvosimendan in Acute heart Failure following myocardial infarction) evaluating 61 patients developing HF within 48 h after percutaneous coronary intervention-treated ST-elevation myocardial infarction herein underwent a post hoc analysis. Blood samples were drawn from inclusion to Day 5 and at 42 day follow-up, and biomarkers were measured with enzyme immunoassays. Regional myocardial contractility was measured by echocardiography as wall motion score index (WMSI). The cardiogenic shock group (n = 9) was compared with the non-shock group (n = 52). Controls (n = 44) were age-matched and sex-matched healthy individuals. C4bc, C3bc, C3bBbP, and sC5b-9 were elevated in patients at inclusion compared with controls (P < 0.01). The shock group had higher levels compared with the non-shock group for all activation products except C3bBbP (P < 0.05). At Day 42, all products were higher in the shock group (P < 0.05). In the shock group, sC5b-9 correlated significantly with WMSI at baseline (r = 0.68; P = 0.045) and at Day 42 (r = 0.84; P = 0.036). Peak sC5b-9 level correlated strongly with WMSI at Day 42 (r = 0.98; P = 0.005). Circulating endothelial cell activation markers sICAM-1 and sVCAM-1 were higher in the shock group during the acute phase (P < 0.01), and their peak levels correlated with sC5b-9 peak level in the whole HF population (r = 0.32; P = 0.014 and r = 0.30; P = 0.022, respectively). CONCLUSIONS: Complement activation discriminated cardiogenic shock from non-shock in acute ST-elevation myocardial infarction complicated by HF and correlated with regional contractility and endothelial cell activation, suggesting a pathogenic role of complement in this condition.

Systolic mitral annulus velocity is a sensitive index for changes in left ventricular systolic function during inotropic therapy in patients with acute heart failure.

BACKGROUND: Echocardiography is recommended for assessment of left ventricular systolic function in patients with acute heart failure but few randomised trials have validated techniques like tissue Doppler (TDI) and speckle tracking (STE) in patients with acute heart failure following ST-elevation myocardial infarction. METHODS: This was a substudy from the LEAF (LEvosimendan in Acute heart Failure following myocardial infarction) trial (NCT00324766 ), which randomised 61 patients developing acute heart failure, including cardiogenic shock, within 48 hours after ST-elevation myocardial infarction, double-blind to a 25-hour infusion of levosimendan or placebo. TDI-derived systolic mitral annulus velocity (S'), STE-derived global longitudinal strain (Sl) and strain rate (SRl) were measured at baseline, day 1, day 5 and after 42 days. RESULTS: Datasets rejected for analyses were 2% (TDI) and 17% (STE). S' increased by 23% in the levosimendan group versus 8% in the placebo group from baseline to day 1 ( p= 0.011) and by 30% vs. 3% from baseline to day 5 ( p <0.0005). Significant, but less pronounced, improvements in global Sl ( p = 0.025 and p = 0.032) and in global SRl ( p = 0.046 and p = 0.001) in favour of levosimendan were also present. CONCLUSION: S' by TDI and STE-derived Sl and SRl were sensitive indices for changes in left ventricular systolic function related to treatment with levosimendan. However, S' by TDI was more feasible and sensitive and might be preferred for assessment of changes in left ventricular systolic function in critically ill patients with acute heart failure receiving inotropic therapy.

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.

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.

AIMS: 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). METHODS AND RESULTS: A 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 = 0.031). There were significantly more episodes of hypotension during study drug infusion in the levosimendan group (67% vs. 36%, P = 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. CONCLUSIONS: Levosimendan 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.

Endothelin-1 in the human myocardium and circulating plasma: evaluation before, during and after correction of aortic stenosis with aortic valve replacement.

OBJECTIVES: Due to the pathological effects of endothelin-1 (ET-1) on cardiomyocytes and the extracellular matrix, ET-1 levels may impact on the prognosis of aortic stenosis (AS) patients operated with aortic valve replacement (AVR). We examined ET-1 levels in AS patients throughout the whole AVR process, thus exposing potential therapeutic windows of opportunity. METHODS: Plasma ET-1 levels were measured before and 2 days, 6 and 12 months after AVR in 22 patients with AS. Myocardial ET-1 was measured in biopsies from 7 patients undergoing AVR. Peroperatively, plasma ET-1 was analyzed in the coronary sinus and radial artery before aortic cross-clamp and at 5 and 20 min of reperfusion, in a second group of 30 patients. RESULTS: Circulating ET-1 levels were transiently increased 2.6-fold 2 days following AVR. Myocardial ET-1 protein was 2.1-fold higher in patients with AS compared to controls. Plasma levels of ET-1 correlated to echocardiographic markers of diastolic dysfunction postoperatively. There was no increase in plasma ET-1 during early reperfusion, but veno-arterial differences indicated potential cardiac ET-1 extraction. CONCLUSIONS: Plasma ET-1 increases 2 days following AVR and myocardial ET-1 protein levels are increased in patients with AS before AVR. Peroperatively, no plasma ET-1 augmentation or release from the heart was observed in AS patients.

Cardiac dysfunction in juvenile dermatomyositis: a case-control study.

OBJECTIVE: To compare cardiac function in patients with juvenile dermatomyositis (JDM) with matched controls, and examine associations between pathological electrocardiography (ECG), echocardiographic abnormalities and disease variables in patients with JDM. METHODS: A total of 59 patients with JDM, examined a median 16.8 years (range 2-38 years) after disease onset, were compared with 59 age-matched and sex-matched controls. Echocardiography, including early diastolic transmitral flow/early diastolic tissue velocity (E/E') as a marker for diastolic dysfunction, and 12-channel ECG were performed and analysed blinded to patient information. Disease activity and damage were assessed by clinical examination at follow-up and chart review. RESULTS: E/E' was elevated (>9.5) in 13 (22%) patients versus 0 controls (p<0.001). In all, 10 patients presented with pathological ECG compared to 4 controls (p=0.054). Previous or current hypertension was found in 12 patients versus 0 controls (p<0.001). Among the patients, pathological ECG was found in 6/13 patients with versus 4/44 without elevated E/E' (p=0.002); and systolic blood pressure was correspondingly 132±24 mm Hg versus 112±18 mm Hg in the groups (p=0.012). E/E' correlated with cumulative organ damage assessed at follow-up (r(sp) 0.41, p=0.001) and disease activity at 1 year (r(sp) 0.56, p<0.001), which also predicted pathological E/E' after controlling for age and gender. During disease course, 12% of patients with JDM developed pericarditis. CONCLUSION: 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.

Plasma IL-18 and IL-18BP are altered differently in reverse remodeling following aortic valve replacement.

OBJECTIVES: Patients with aortic stenosis (AS) develop left ventricular remodeling characterized by changes in extracellular matrix (ECM) and cardiomyocyte-hypertrophy. Aortic valve replacement (AVR) reverses this process (reverse remodeling). We examined plasma levels of interleukin-18 (IL-18) and its binding protein (IL-18BP) before and after AVR for AS since these mediators have been shown experimentally to exert effects on myocardial remodeling. DESIGN: Plasma levels of IL-18 and IL-18BP were analyzed in 22 patients with AS undergoing AVR, preoperatively, two days, six and 12 months postoperatively. Echocardiography and functional testing were performed. RESULTS: IL-18BP was significantly increased by 28% and 15% at two days and six months after AVR, compared to preoperative values. In contrast, IL-18 showed a later peak (increased by 24% at 12 months postoperatively) when IL-18BP was normalized. IL-18 correlated positively with deceleration time (R = 0.44) at this time-point which might indicate an association with diastolic function. CONCLUSIONS: We report for the first time that plasma IL-18 and IL-18BP are differentially regulated after AVR for AS with an early increase in IL-18BP postoperatively followed by a later peak in IL-18 at 12 months. Given the known effects of these mediators on myocardial remodeling and function, they might play a role in the reverse and remodeling process associated with AVR.

Alterations in circulating activin A, GDF-15, TGF-beta3 and MMP-2, -3, and -9 during one year of left ventricular reverse remodelling in patients operated for severe aortic stenosis.

BACKGROUND: 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. AIMS: To examine circulating levels of members of the transforming growth factor (TGF) beta superfamily and matrix metalloproteinases (MMP), known to have important effects on hypertrophy and extracellular matrix, in patients operated for AS. METHODS: Circulating levels of activin A, GDF-15, TGF-beta3, MMP-2, -3, and -9 were measured in twenty-two patients undergoing AVR preoperatively, and 2 days, six months and 12 months postoperatively. Echocardiography and a six minute walking test evaluated reverse remodelling and physical performance. RESULTS: Activin A increased at six (1081.00+/-98.05 pg/ml, p<0.05) and twelve months (1263.09+/-141.43 pg/ml, p<0.05) compared to the preoperative value (855.00+/-76.30 pg/ml) and correlated negatively to physical performance. The preoperative value was also increased compared to controls (639.54+/-63.05 pg/ml, p<0.05). GDF-15, MMP-3 and -9 were all increased at two days postoperatively (p<0.05). MMP-3 correlated with left ventricular end diastolic dimension (p<0.05). MMP-2 did not change during the study period. TGF-beta3 was only slightly reduced at six months postoperatively. CONCLUSION: The observed alteration in circulating levels of members of the TGF-beta superfamily and MMPs might play a role in the reverse remodelling process following AVR for AS.

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.

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

BACKGROUND: B-type natriuretic peptide (BNP) is synthesized in cardiac tissue in response to increased wall stress and myocardial hypertrophy. AIMS: In patients with severe aortic stenosis (AS) we examined the effect of aortic valve replacement (AVR) on plasma BNP and association between BNP and left ventricular mass index (LVMI) preoperatively and in the reverse-remodeling phase twelve months postoperatively. We also examined the correlation between BNP and NYHA-class and between BNP and age. METHODS AND RESULTS: Plasma BNP analyses and echocardiographic measurements were performed preoperatively, before discharge after AVR, and at twelve months in twenty-two patients. BNP was additionally measured at six months. Preoperatively, BNP was 283+/-45 pg/ml (mean+/-SEM). Following an immediate postoperative increase (441+/-38 pg/ml), BNP values decreased towards normal values at six and twelve months (139+/-25 and 130+/-18 pg/ml, respectively). LVMI was 206.5+/-15.8 g/m(2) preoperatively and decreased to 119.7+/-7.2 g/m(2) at twelve months with a correlation between LVMI and BNP preoperatively only (r=0.45, p<0.05). There was no correlation between BNP and NYHA-class, whereas BNP correlated to age both pre- and post-operatively. CONCLUSION: 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.

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 < or =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.