Claes-Håkan Bergh

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.

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 ≥20 mL/min/1.73m2 and <90 mL/min/1.73 m2) >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.

Myocardial Turnover of Endogenous Opioids and Calcitonin-Gene-Related Peptide in the Human Heart and the Effects of Spinal Cord Stimulation on Pacing-Induced Angina Pectoris

Earlier studies have shown that spinal cord stimulation (SCS) has antianginal and anti-ischemic effects in severe coronary artery disease. In the present study, 14 patients were subjected to right-sided atrial catheterization and atrial pacing. The patients were paced to angina during a control session and during spinal cord stimulation. Myocardial extraction of β-endorphin (BE) during control pacing (8 ± 22%) changed to release at the maximum pacing rate during treatment (–21 ± 47%, a negative value representing release). Furthermore, the results indicate local myocardial turnover of leuenkephalin, BE and calcitonin-gene-related peptide. In addition, it is implied that SCS may induce myocardial release of BE which could explain the beneficial effects in myocardial ischemia.

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

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 β‐blocker.

The effects of moxonidine, a novel imidazoline, on plasma norepinephrine in patients with congestive heart failure

OBJECTIVE To evaluate the dose response relationship of moxonidine on plasma concentration of norepinephrine during acute and chronic administration in patients with congestive heart failure (CHF). BACKGROUND Sympathetic activation is increased in heart failure. Moxonidine is an imidazoline ligand acting on the central nervous system (CNS) receptors to decrease sympathetic activation. METHODS Ninety-seven patients with heart failure and New York Heart Association class II-III symptoms and ejection fraction <40% were randomized to placebo or one of three target doses of moxonidine, 0.1, 0.2 or 0.3 mg administered twice daily. An initial dose of moxonidine 0.1 mg twice a day (b.i.d.) was followed by weekly increments of 0.1 mg b.i.d. until target dose. The second and third study days occurred after four weeks (at target dose) and after 12 weeks, respectively. At each study day, repeated blood samples were drawn. RESULTS There was a significant dose-related decrease of systolic blood pressure across all three study days. Heart rate decreased significantly on study day 3 in a dose-related manner. The acute 2 h decrease in plasma norepinephrine in response to all three doses of moxonidine was significantly different compared with placebo after four and 12 weeks. There was a significant linear relation between dose and plasma norepinephrine after four and 12 weeks in both 2 h peak and the time averaged effect (>8 h). The number of adverse events was similar in the moxonidine and placebo groups. CONCLUSIONS The increased sympathetic activation in CHF can be reduced by moxonidine through CNS inhibition.

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

To study the achievability of device weaning in patients receiving left ventricular assist devices (LVADs) as a bridge to transplantation.

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.

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.

Fatal Dilated Cardiomyopathy Associated with a Mitochondrial DNA Deletion

A 27-year-old man was admitted to hospital because of severe cardiac failure. Investigation revealed dilated cardiomyopathy with a left ventricular ejection fraction of 15–20%. During adolescence the patient had been investigated for growth retardation and he also had progressive external ophthalmoplegia. There had been no symptoms of cardiac disease until 2 weeks before admittance. An endomyocardial biopsy showed cardiomyocytes deficient in cytochrome c oxidase (COX) in a mosaic pattern. A skeletal muscle biopsy showed mitochondrial myopathy with COX-deficient ragged-red fibers. Molecular genetic analysis revealed a heteroplasmic, 3.8-kb, mitochondrial DNA (mtDNA) deletion in heart and muscle. PCR-based quantification of the proportion of mtDNA with deletion showed 47% mutated mtDNA in the myocardial biopsy and 68% in muscle. In spite of treatment, the condition deteriorated and the patient died 5 days after admittance. This case demonstrates that mtDNA deletions may occasionally be the cause of severe dilated cardiomyopathy, and that morphological and molecular genetic diagnosis may be obtained by endomyocardial biopsy.

Weaning from mechanical support in a patient with acute heart failure and multiple sclerosis

We describe a 19-year-old woman developing acute left ventricular heart failure during her first exacerbation of multiple sclerosis. Histopathologic examination of myocardial tissue showed extensive myocytolysis. A left ventricular assist device was implanted. Three months later the cardiac function was restored and the left ventricular assist device was explanted. After 1 year the patient still remains well and her cardiac function is normal.