Intravenous levosimendan vs. dobutamine in acute decompensated heart failure patients on beta-blockers.

AIMS: The aim of this study is to compare the effects of a 24 h intravenous infusion of levosimendan and a 48 h infusion of dobutamine on invasive haemodynamics in patients with acutely decompensated chronic NYHA class III-IV heart failure. All patients were receiving optimal oral therapy including a beta-blocker. METHODS AND RESULTS: This was a multinational, randomized, double-blind, phase IV study in 60 patients; follow-up was 1 month. There was a significant increase in cardiac index and a significant decrease in pulmonary capillary wedge pressure (PCWP) at 24 and 48 h for both dobutamine and levosimendan. The improvement in cardiac index with levosimendan was not significantly different from dobutamine at 24 h (P = 0.07), but became significant at 48 h (0.44 +/- 0.56 vs. 0.66 +/- 0.63 L/min/m(2); P = 0.04). At 24 h, the reduction in the mean change in PCWP from baseline was similar for levosimendan and dobutamine, however, at 48 h the difference was more marked for levosimendan (-3.6 +/- 7.6 vs. -8.3 +/- 6.7 mmHg; P = 0.02). No difference was observed between the groups for change in NYHA class, beta-blocker use, hospitalizations, treatment discontinuations or rescue medication use. Reduction in B-type natriuretic peptide (BNP) was significantly greater with levosimendan at 48 h (P = 0.03). According to physician's assessment, the improvement in fatigue (P = 0.01) and dyspnoea (P = 0.04) was in favour of dobutamine treatment, and hypotension was significantly more frequent with levosimendan (P = 0.007). No increase in atrial fibrillation or ventricular tachycardia was seen in either group. CONCLUSION: A 24 h levosimendan infusion achieved haemodynamic and neurohormonal improvement that was at least comparable at 24 h and superior at 48 h to a 48 h dobutamine infusion.

Everolimus with reduced calcineurin inhibitor in thoracic transplant recipients with renal dysfunction: a multicenter, randomized trial.

BACKGROUND: The proliferation signal inhibitor everolimus offers the potential to reduce calcineurin inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking. METHODS: In a 12-month, open-labeled, multicenter study, maintenance thoracic transplant patients (glomerular filtration rate > or =20 mL/min/1.73m and <90 mL/min/1.73 m) >1 year posttransplant were randomized to continue their current CNI-based immunosuppression or start everolimus with predefined CNI exposure reduction. RESULTS: Two hundred eighty-two patients were randomized (140 everolimus, 142 controls; 190 heart, 92 lung transplants). From baseline to month 12, mean cyclosporine and tacrolimus trough levels in the everolimus cohort decreased by 57% and 56%, respectively. The primary endpoint, mean change in measured glomerular filtration rate from baseline to month 12, was 4.6 mL/min with everolimus and -0.5 mL/min in controls (P<0.0001). Everolimus-treated heart and lung transplant patients in the lowest tertile for time posttransplant exhibited mean increases of 7.8 mL/min and 4.9 mL/min, respectively. Biopsy-proven treated acute rejection occurred in six everolimus and four control heart transplant patients (P=0.54). In total, 138 everolimus patients (98.6%) and 127 control patients (89.4%) experienced one or more adverse event (P=0.002). Serious adverse events occurred in 66 everolimus patients (46.8%) and 44 controls (31.0%) (P=0.02). CONCLUSION: Introduction of everolimus with CNI reduction offers a significant improvement in renal function in maintenance heart and lung transplant recipients. The greatest benefit is observed in patients with a shorter time since transplantation.

Endothelin-1 across the lung circulation in patients with pulmonary arterial hypertension and influence of epoprostenol infusion.

BACKGROUND: The endothelin-1 (ET-1) system plays a pathophysiologic role in patients with pulmonary arterial hypertension (PAH). Results from previous studies assessing the transpulmonary gradient of ET-1 have been inconsistent. The influence of an intravenous epoprostenol infusion on the transpulmonary ET-1 gradient is unknown. METHODS: In a prospective investigation, serum concentrations of ET-1 were measured in 39 consecutive patients (31 women; mean age, 20-77 years) with pulmonary hypertension (33 with PAH) and compared with 20 controls. The effect of intravenous epoprostenol administration on the transpulmonary gradient of ET-1 was analyzed in 13 patients with pulmonary hypertension. Blood samples were taken simultaneously from the pulmonary artery and radial artery. RESULTS: The serum levels of ET-1 were significantly higher in the arterial (3.9 +/- 1.28 vs 2.53 +/- 0.24 pg/ml, p < 0.001) and mixed venous blood samples (3.9 +/- 1.21 vs 2.52 +/- 0.29 pg/ml, p < 0.001) in patients with pulmonary hypertension than in controls. The arterial/venous ratio of ET-1 in patients (1.0 +/- 0.1) and in the control group (1.0 +/- 0.05) was similar (p = 0.79). During intravenous epoprostenol infusion, there were no changes in the mean transpulmonary ET-1 gradient (0.98 +/- 0.07 vs 0.96 +/- 0.09, p = 0.52), despite significant hemodynamic changes. CONCLUSION: The ET-1 radial artery/pulmonary artery ratio of unity indicates a balanced release and clearance of ET-1 across the lung circulation in controls and in patients with different forms of pulmonary hypertension. ET-1 levels across the pulmonary circulation did not change during epoprostenol infusion.

Right ventricular cardiomyopathy: timing of heart transplantation in Uhl's anomaly and arrythmogenic right ventricular cardiomyopathy.

Transplant indications for right ventricular (RV) cardiomyopathy have not been defined. We report on two boys, aged 18 and 17 years, one with arrhythmogenic right ventricular cardiomyopathy (ARVC) and one with Uhl's anomaly. Both had implantable cardioverter defibrillator (ICD) for the prevention of sudden death (SD), but were not considered urgent heart transplant candidates due to the absence of heart failure symptoms. A ventricular tachycardia-induced cardiac collapse occurred at school in the Uhl patient and in hospital in the ARVC patient. In both patients, ICD shocks intermittently restored sinus rhythm but with inadequate circulation. Only the ARVC patient received early chest compressions and was saved to heart transplantation. Due to RV failure, both patients had evidence of Fontan-type physiology, in whom pulmonary blood flow is passive and propelled by the transpulmonary pressure gradient and intrathoracic pressure alterations produced by breathing. In these cases, at resuscitation, systemic circulation is not established until after pulmonary blood flow is restored by breathing or chest compressions. An ICD alone is therefore not sufficient for the prevention of SD. When invasive data show evidence of Fontan-type circulation, the patient may be considered for heart transplantation.

Pulmonary hemodynamics as predictors of mortality in patients awaiting lung transplantation.

Lung transplantation (LTx) is a therapeutic option for patients with end-stage lung disease. However, the mortality rate of patients on the waiting list is high. The purpose of this study was to examine the prognostic value of cardio-pulmonary hemodynamics for death in patients awaiting LTx. Retrospectively, 177 patients with advanced lung disease accepted for LTx at Sahlgrenska University Hospital from January 1990 through December 2003 were studied. Patient demographics, pulmonary function tests, gas exchange and hemodynamic variables were included in the analysis. Death while awaiting LTx was the primary endpoint for all analyses. Mean age was 49 +/- 9 years. Main diagnoses were alpha 1 antitrypsin deficiency (n = 56), chronic obstructive pulmonary disease (n = 61), cystic fibrosis (n = 14) and interstitial lung disease (n = 46). Thirty patients died (17%). LTx was performed in 143 cases. By univariate analyses, forced vital capacity (FVC) % of predicted, pulmonary vascular resistance (PVR) and diagnosis were associated with risk for death. In multivariate analysis PVR (HR, 1.22; 95% CI, 1.06-1.41; P = 0.006) and FVC% of predicted (HR, 0.97; 95% CI, 0.94-0.99; P = 0.01) were independently associated with death. Patients with increased PVR and a lower FVC % of predicted awaiting LTx should be considered for a higher organ allocation priority. Assessment of pulmonary hemodynamics needs to be considered during evaluation for LTx.

How do nurses record pedagogical activities? Nurses' documentation in patient records in a cardiac rehabilitation unit for patients who have undergone coronary artery bypass surgery.

AIMS: To describe the use of pedagogically related keywords and the content of notes connected to these keywords, as they appear in nursing records in a coronary artery bypass graft (CABG) surgery rehabilitation unit. BACKGROUND: Nursing documentation is an important component of clinical practice and is regulated by law in Sweden. Studies have been carried out in order to evaluate the educational and rehabilitative needs of patients following CABG surgery but, as yet, no study has contained an in-depth evaluation of how nurses document pedagogical activities in the records of these patients. METHODS: The records of 265 patients admitted to a rehabilitation unit following CABG surgery were analysed. The records were structured in accordance with the VIPS model. Using this model, pedagogically related keywords: communication, cognition/development and information/education were selected. The analysis of the data consisted of three parts: the frequency with which pedagogically related keywords are used, the content and the structure of the notes. RESULTS: Apart from the term 'communication', pedagogically related keywords were seldom used. Communication appeared in all records describing limitations, although no explicit reference was made to pedagogical activities. The notes related to cognition/development were grouped into the following themes: nurses' actions, assessment of knowledge and provision of information, advice and instructions as well as patients' wishes and experiences. The themes related to information were the provision of information and advice in addition to relevant nursing actions. The structure of the documentation was simple. CONCLUSIONS: The documentation of pedagogical activities in nursing records was infrequent and inadequate. RELEVANCE TO CLINICAL PRACTICE: The patients' need for knowledge and the nurses' teaching must be documented in the patient records so as to clearly reflect the frequency and quality of pedagogical activities.

Assessment of pulmonary vascular resistance by Doppler echocardiography in patients with pulmonary arterial hypertension.

BACKGROUND: Assessment of pulmonary artery pressures, cardiac output (CO) and pulmonary vascular resistance (PVR) is crucial in the management of patients with pulmonary arterial hypertension (PAH). The aim of the present study was to investigate whether Doppler echocardiography can be used to determine PVR in patients with PAH. METHODS: Forty-two patients were included and Doppler echocardiography was performed simultaneously (n = 22) and non-simultaneously (n = 60) with right heart catheterization. The tricuspid regurgitation velocity was used to estimate pulmonary arterial peak systolic and diastolic (PADP) pressures (Bernoulli equation). At the time of pulmonary valve opening, right ventricular pressure equals PADP. The tricuspid regurgitation velocity at the time of pulmonary valve opening was measured by superimposing the time from the QRS to the onset of pulmonary flow on the tricuspid regurgitation velocity envelope. Pulmonary capillary wedge pressure, right atrial pressure and CO were assessed using standard Doppler echocardiography methods. Right heart catheterization was performed using Swan-Ganz catheters and thermodilution for CO determination. RESULTS: The differences (mean +/- SD) between catheter and simultaneous/non-simultaneous Doppler echocardiography were 0.3 +/- 0.8 (p = 0.10)/-0.3 +/- 1.1 (p = 0.06) liter/min for CO, 2.9 +/- 5.1 (p = 0.02)/-1.2 +/- 7.4 (p = 0.2) mm Hg for the transpulmonary gradient (TPG) and 0.3 +/- 2.1 (p = 0.65)/0.8 +/- 2.4 (p = 0.02) Wood unit for PVR. The correlation coefficients between catheter and simultaneous/non-simultaneous Doppler echocardiography were 0.86/0.75 for CO, 0.92/0.90 for TPG and 0.93/0.92 for PVR. CONCLUSIONS: A comprehensive hemodynamic assessment that includes CO, TPG and PVR can be provided by Doppler echocardiography in patients with severe pulmonary hypertension.

Advanced chronic heart failure: A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology.

Therapy has improved the survival of heart failure (HF) patients. However, many patients progress to advanced chronic HF (ACHF). We propose a practical clinical definition and describe the characteristics of this condition. Patients that are generally recognised as ACHF often exhibit the following characteristics: 1) severe symptoms (NYHA class III to IV); 2) episodes with clinical signs of fluid retention and/or peripheral hypoperfusion; 3) objective evidence of severe cardiac dysfunction, shown by at least one of the following: left ventricular ejection fraction<30%, pseudonormal or restrictive mitral inflow pattern at Doppler-echocardiography; high left and/or right ventricular filling pressures; elevated B-type natriuretic peptides; 4) severe impairment of functional capacity demonstrated by either inability to exercise, a 6-minute walk test distance<300 m or a peak oxygen uptake<12-14 ml/kg/min; 5) history of >1 HF hospitalisation in the past 6 months; 6) presence of all the previous features despite optimal therapy. This definition identifies a group of patients with compromised quality of life, poor prognosis, and a high risk of clinical events. These patients deserve effective therapeutic options and should be potential targets for future clinical research initiatives.

The feasibility of left ventricular mechanical support as a bridge to cardiac recovery.

OBJECTIVE: To study the achievability of device weaning in patients receiving left ventricular assist devices (LVADs) as a bridge to transplantation. METHODS: Eighteen consecutive patients receiving a LVAD between September 1997 and June 2002 were included in the study. During a four-month follow-up, patients were repeatedly evaluated with right heart catheterization and echocardiography and, if functional improvement was observed, studied with the device turned off. Cardiac recovery was defined as off-pump LVEF>or=40% together with a significant improvement in invasive haemodynamic measurements (CI>or=2.5 and PCWP

Influence of central inhibition of sympathetic nervous activity on myocardial metabolism in chronic heart failure: acute effects of the imidazoline I1-receptor agonist moxonidine.

Although beta-adrenergic blockade is beneficial in heart failure, inhibition of central sympathetic outflow using moxonidine has been associated with increased mortality. In the present study, we studied the acute effects of the imidazoline-receptor agonist moxonidine on haemodynamics, NA (noradrenaline) kinetics and myocardial metabolism. Fifteen patients with CHF (chronic heart failure) were randomized to a single dose of 0.6 mg of sustained-release moxonidine or matching placebo. Haemodynamics, NA kinetics and myocardial metabolism were studied over a 2.5 h time period. There was a significant reduction in pulmonary and systemic arterial pressures, together with a decrease in cardiac index in the moxonidine group. Furthermore, there was a simultaneous reduction in systemic and cardiac net spillover of NA in the moxonidine group. Analysis of myocardial consumption of substrates in the moxonidine group showed a significant increase in non-esterified fatty acid consumption and a possible trend towards an increase in myocardial oxygen consumption compared with the placebo group (P=0.16). We conclude that a single dose of moxonidine (0.6 mg) in patients already treated with a beta-blocker reduced cardiac and overall sympathetic activity. The finding of increased lipid consumption without decreased myocardial oxygen consumption indicates a lack of positive effects on myocardial metabolism under these conditions. We suggest this might be a reason for the failure of moxonidine to prevent deaths in long-term studies in CHF.

Daclizumab to prevent rejection after cardiac transplantation.

BACKGROUND: Daclizumab, a humanized monoclonal antibody against the interleukin-2 receptor, reduced the risk of rejection without increasing the risk of infection among renal-transplant recipients and, in a single-center trial, among cardiac-transplant recipients. We conducted a multicenter, placebo-controlled, double-blind study to confirm these results in cardiac-transplant patients. METHODS: We randomly assigned 434 recipients of a first cardiac transplant treated with standard immunosuppression (cyclosporine, mycophenolate mofetil, and corticosteroids) to receive five doses of daclizumab or placebo. The primary end point was a composite of moderate or severe cellular rejection, hemodynamically significant graft dysfunction, a second transplantation, or death or loss to follow-up within six months. RESULTS: By six months, 104 of 218 patients in the placebo group had reached the primary end point, as compared with 77 of the 216 patients in the daclizumab group (47.7 percent vs. 35.6 percent, P=0.007), a 12.1 percent absolute risk reduction and a 25 percent relative reduction. The rate of rejection was lower in the daclizumab group than in the placebo group (41.3 percent vs. 25.5 percent). Among patients reaching the primary end point, the median time to the end point was almost three times as long in the daclizumab group as in the placebo group during the first 6 months (61 vs. 21 days) and at 1 year (96 vs. 26 days). More patients in the daclizumab group than in the placebo group died of infection (6 vs. 0) when they received concomitant cytolytic therapy. CONCLUSIONS: Daclizumab was efficacious as prophylaxis against acute cellular rejection after cardiac transplantation. Because of the excess risk of death, concurrent or anticipated use of cytolytic therapy with daclizumab should be avoided.

Can brain natriuretic peptide (BNP) be used as a screening tool in general practice?

OBJECTIVE: To investigate plasma brain natriuretic peptide (p-BNP) in consecutive primary care patients for heart failure screening. DESIGN: Open, descriptive. SETTING: Three primary care clinics, university hospital. SUBJECTS: 291 consecutive patients, > or =40 years. MAIN OUTCOME MEASURES: p-BNP and general practitioners estimated probability of CHF. RESULTS: Median p-BNP was 29 ng/L. In 42% p-BNP was >40 ng/L in the first sample. In 41 patients further investigated, median p-BNP was 98 ng/L, with a correlation between p-BNP and physicians' estimation of probability of heart failure (r=0.469, p<0.0001). New York Heart Association class was correlated to p-BNP (r=0.343, p=0.034). No correlation between ejection fraction and p-BNP was seen. CONCLUSION: P-BNP concentrations in unselected primary care patients of 40 years of age or above were elevated in a larger proportion of patients than previously reported. Owing to the low specificity, p-BNP concentration limits have to be defined before the test can be used for screening in primary care.

Predictors and evolution of renal function during 9 years following heart transplantation.

Over a 9-yr period, heart transplantation was performed in 200 patients at Sahlgrenska University Hospital. Of these 200 patients, 151 were followed for 1 to 9 yr with regard to renal function, hemodynamics, cyclosporin A concentrations, and complications. Patients with a preoperative serum creatinine >130 micromol/L received inotropic drugs to test for reversibility of renal dysfunction. The end point was graft failure. The average preoperative GFR of 66 +/- 17 ml/min per 1.73 m(2) declined to 52 +/- 19, 44 +/- 16, and 37 +/- 17 at 1, 5, and 9 yr after heart transplantation, respectively. Altogether, the average GFR declined by 44%. There was no significant correlation between the preoperative GFR and postoperative renal function or survival. Recipient age was a predictor of renal function during the entire follow-up. Severe renal dysfunction (GFR <20 ml/min per 1.73 m(2)) developed in 20% of the patients, which was predicted by the recipient age at transplantation together with the GFR 1 yr after transplantation. A nomogram that shows the risk of developing severe renal dysfunction after heart transplantation is presented. Cyclosporin A concentrations and treatment with statins, calcium channel blockers, or angiotensin-converting enzyme inhibitors did not correlate with the evolution of renal function. Patients with a preoperative depressed renal function who improved on inotropic treatment seemed to have a poorer outcome compared with the other study patients.