W. H. Van Gilst

The EuroHeart Failure survey programme-- a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis.

BACKGROUND The European Society of Cardiology (ESC) has published guidelines for the investigation of patients with suspected heart failure and, if the diagnosis is proven, their subsequent management. Hospitalisation provides a key point of care at which time diagnosis and treatment may be refined to improve outcome for a group of patients with a high morbidity and mortality. However, little international data exists to describe the features and management of such patients. Accordingly, the EuroHeart Failure survey was conducted to ascertain if appropriate tests were being performed with which to confirm or refute a diagnosis of heart failure and how this influenced subsequent management. METHODS The survey screened consecutive deaths and discharges during 2000-2001 predominantly from medical wards over a 6-week period in 115 hospitals from 24 countries belonging to the ESC, to identify patients with known or suspected heart failure. RESULTS A total of 46788 deaths and discharges were screened from which 11327 (24%) patients were enrolled with suspected or confirmed heart failure. Forty-seven percent of those enrolled were women. Fifty-one percent of women and 30% of men were aged >75 years. Eighty-three percent of patients had a diagnosis of heart failure made on or prior to the index admission. Heart failure was the principal reason for admission in 40%. The great majority of patients (>90%) had had an ECG, chest X-ray, haemoglobin and electrolytes measured as recommended in ESC guidelines, but only 66% had ever had an echocardiogram. Left ventricular ejection fraction had been measured in 57% of men and 41% of women, usually by echocardiography (84%) and was <40% in 51% of men but only in 28% of women. Forty-five percent of women and 22% of men were reported to have normal left ventricular systolic function by qualitative echocardiographic assessment. A substantial proportion of patients had alternative explanations for heart failure other than left ventricular systolic or diastolic dysfunction, including valve disease. Within 12 weeks of discharge, 24% of patients had been readmitted. A total of 1408 of 10434 (13.5%) patients died between admission and 12 weeks follow-up. CONCLUSIONS Known or suspected heart failure comprises a large proportion of admissions to medical wards and such patients are at high risk of early readmission and death. Many of the basic investigations recommended by the ESC were usually carried out, although it is not clear whether this was by design or part of a general routine for all patients being admitted regardless of diagnosis. The investigation most specific for patients with suspected heart failure (echocardiography) was performed less frequently, suggesting that the diagnosis of heart failure is still relatively neglected. Most men but a minority of women who underwent investigation of cardiac function had evidence of moderate or severe left ventricular dysfunction, the main target of current advances in the treatment of heart failure. Considerable diagnostic uncertainty remains for many patients with suspected heart failure, even after echocardiography, which must be resolved in order to target existing and new therapies and services effectively.

The EuroHeart Failure Survey programme - a survey on the quality of care among patients with heart failure in Europe Part 2 : treatment

Background National surveys suggest that treatment of heart failure in daily practice differs from guidelines and is characterized by underuse of recommended medications. Accordingly, the Euro Heart Failure Survey was conducted to ascertain how patients hospitalized for heart failure are managed in Europe and if national variations occur in the treatment of this condition. Methods The survey screened discharge summaries of 11 304 patients over a 6-week period in 115 hospitals from 24 countries belonging to the ESC to study their medical treatment. Results Diuretics (mainly loop diuretics) were prescribed in 86.9% followed by ACE inhibitors (61.8%), beta-blockers (36.9%), cardiac glycosides (35.7%), nitrates (32.1%), calcium channel blockers (21.2%) and spironolactone (20.5%). 44.6% of the population used four or more different drugs. Only 17.2% were under the combination of diuretic, ACE inhibitors and beta-blockers. Important local variations were found in the rate of prescription of ACE inhibitors and particularly beta-blockers. Daily dosage of ACE inhibitors and particularly of beta-blockers was on average below the recommended target dose. Modelling-analysis of the prescription of treatments indicated that the aetiology of heart failure, age, co-morbid factors and type of hospital ward influenced the rate of prescription. Age 70 years, in patients with respiratory disease and increased in cardiology wards, in ischaemic heart failure and in male subjects. Prescription of cardiac glycosides was significantly increased in patients with supraventricular tachycardia/atrial fibrillation. Finally, the rate of prescription of antithrombotic agents was increased in the presence of supraventricular arrhythmia, ischaemic heart disease, male subjects but was decreased in patients over 70. Conclusion Our results suggest that the prescription of recommended medications including ACE inhibitors and beta-blockers remains limited and that the daily dosage remains low, particularly for beta-blockers. The survey also identifies several important factors including age, gender, type of hospital ward, co morbid factors which influence the prescription of heart failure medication at discharge.

Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity

Abstract. Hillege HL, Janssen WMT, Bak AAA, Diercks GFH, Grobbee DE, Crijns HJGM, van Gilst WH, de Zeeuw D, de Jong PE for the PREVEND Study group (University of Groningen and University Hospital Groningen, Groningen; University Medical centre, Utrecht, the Netherlands). Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity. J Intern Med 2001; 249: 519–526.

The fibrosis marker galectin-3 and outcome in the general population

Abstract.  de Boer RA, van Veldhuisen DJ, Gansevoort RT, Muller Kobold AC, van Gilst WH, Hillege HL, Bakker SJL, van der Harst P (University of Groningen). The fibrosis marker galectin‐3 and outcome in the general population. J Intern Med 2012; 272: 55–64.

Gene expression of proteins influencing the calcium homeostasis in patients with persistent and paroxysmal atrial fibrillation

OBJECTIVE Persistent atrial fibrillation (AF) results in an impairment of atrial function. In order to elucidate the mechanism behind this phenomenon, we investigated the gene expression of proteins influencing calcium handling. METHODS Right atrial appendages were obtained from eight patients with paroxysmal AF, ten with persistent AF (> 8 months) and 18 matched controls in sinus rhythm. All controls underwent coronary artery bypass grafting, whereas most AF patients underwent Coxs MAZE surgery (n = 12). All patients had a normal left ventricular function. Total RNA was isolated and reversely transcribed into cDNA. In a semi-quantitative polymerase chain reaction the cDNA of interest and of glyceraldehyde-3-phosphate dehydrogenase were coamplified and separated by ethidium bromide-stained gel electrophoresis. Slot blot analysis was performed to study protein expression. RESULTS L-type calcium channel alpha 1 and sarcoplasmic reticulum Ca(2+)-ATPase mRNA (-57%, p = 0.01 and -28%, p = 0.04, respectively) and protein contents (-43%, p = 0.02 and -28%, p = 0.04, respectively) were reduced in patients with persistent AF compared to the controls. mRNA contents of phospholamban, ryanodine receptor type 2 and sodium/calcium exchanger were comparable. No changes were observed in patients with paroxysmal AF. CONCLUSIONS Alterations in gene expression of proteins involved in the calcium homeostasis occur only in patients with long-term persistent AF. In the absence of underlying heart disease, the changes are rather secondary than primary to AF.

Prevention of one-year vein-graft occlusion after aortocoronary-bypass surgery : a comparison of low-dose aspirin, low-dose aspirin plus dipyridamole, and oral anticoagulants

Aspirin, alone or in combination with dipyridamole, is known to prevent occlusion of aortocoronary vein grafts. The benefit of dipyridamole in addition to aspirin remains controversial, and the efficacy and safety of oral anticoagulants for prevention of vein-graft occlusion have not been established. We assessed one-year angiographic vein-graft patency after aortocoronary-bypass surgery in 948 patients assigned to receive aspirin, aspirin plus dipyridamole, or oral anticoagulants in a prospective, randomised trial. The design was double-blind and placebo-controlled for the aspirin groups, but open for oral anticoagulant treatment. Dipyridamole (5 mg/kg per 24 h intravenously for 28 h, followed by 200 mg twice daily) and oral anticoagulants (desired prothrombin time range 2.8-4.8 international normalised ratio) were started before surgery, and aspirin (50 mg per day) was started after surgery. Clinical outcome was assessed by the incidence of myocardial infarction, thrombosis, major bleeding, or death. Occlusion rate of distal anastomoses was 11% in the aspirin plus dipyridamole group versus 15% in the aspirin group (relative risk 0.76, 95% CI 0.54-1.05) and 13% in the oral anticoagulants group. Clinical events occurred in 20.3% of patients receiving aspirin plus dipyridamole compared with 13.9% of the aspirin group (relative risk 1.46, 95% CI 1.02-2.08) and 16.9% of the oral anticoagulants group. Our data provide no convincing evidence that addition of dipyridamole to 50 mg aspirin per day improves aortocoronary vein-graft patency. Moreover, there is evidence that the combination increases the overall clinical-event rate. Compared with aspirin, oral anticoagulants provided no benefit.

Telomere length loss due to smoking and metabolic traits

Human age‐dependent telomere attrition and telomere shortening are associated with several age‐associated diseases and poorer overall survival. The aim of this study was to determine longitudinal leucocyte telomere length dynamics and identify factors associated with temporal changes in telomere length.

Comparison of zofenopril and lisinopril to study the role of the sulfhydryl-group in improvement of endothelial dysfunction with ACE-inhibitors in experimental heart failure

We evaluated the role of SH‐groups in improvement of endothelial dysfunction with ACE‐inhibitors in experimental heart failure. To this end, we compared the vasoprotective effect of chronic treatment with zofenopril (plus SH‐group) versus lisinopril (no SH‐group), or N‐acetylcysteine (only SH‐group) in myocardial infarcted (MI) heart failure rats. After 11 weeks of treatment, aortas were obtained and studied as ring preparations for endothelium‐dependent and ‐independent dilatation in continuous presence of indomethacin to avoid interference of vasoactive prostanoids, and the selective presence of the NOS‐inhibitor L‐NMMA to determine NO‐contribution. Total dilatation after receptor‐dependent stimulation with acetylcholine (ACh) was attenuated (−49%, P<0.05) in untreated MI (n=11), compared to control rats with no‐MI (n=8). This was in part due to impaired NO‐contribution in MI (−50%, P<0.05 versus no‐MI). At the same time the capacity for generation of biologically active NO after receptor‐independent stimulation with A23187 remained intact. Chronic treatment with n‐acetylcysteine (n=8) selectively restored NO‐contribution in total dilatation to ACh. In contrast, both ACE‐inhibitors fully normalized total dilatation to ACh, including the part mediated by NO (no significant differences between zofenopril (n=10) and lisinopril (n=8)). Zofenopril, but not lisinopril, additionally potentiated the effect of endogenous NO after A23187‐induced release from the endothelium (+100%) as well as that of exogenous NO provided by nitroglycerin (+22%) and sodium nitrite (+36%) (for all P<0.05 versus no‐MI). We conclude that ACE‐inhibition with a SH‐group has a potential advantage in improvement of endothelial dysfunction through increased activity of NO after release from the endothelium into the vessel wall. Furthermore, this is the first study demonstrating the selective normalizing effect of N‐actylcysteine on NO‐contribution to ACh‐induced dilatation in experimental heart failure.

Gene expression of the natriuretic peptide system in atrial tissue of patients with paroxysmal and persistent atrial fibrillation

Natriuretic Peptide System in AF. Introduction: Circulating cardiac natriuretic peptides play an important role in maintaining volume homeostasis, especially during conditions affecting hemodynamics. During atrial fibrillation (AF), levels of plasma atrial natriuretic peptide (ANP) becomes elevated. The aim of this study was to gather information about gene expression of the natriuretic peptide system on the atrial level in patients with AF.

Vitamin D Biology in Heart Failure: Molecular Mechanisms and Systematic Review

Vitamin D has recently been suggested as an important mediator of blood pressure and cardiovascular disease, including heart failure. In patient with heart failure, low vitamin D levels are associated with adverse outcome and correlate with established clinical correlates and biomarkers. Many precursor states of heart failure, such as hypertension, atherosclerosis, and diabetes are more prevalent in subjects with low vitamin D levels. Recent experimental data have provided clues how vitamin D might exert cardioprotective effects. The steroid hormone vitamin D regulates gene expression of many genes that play a prominent role in the progression of heart failure, such as cytokines and hormones. Specifically, vitamin D is a negative regulator of the hormone renin, the pivotal hormone of the renin-angiotensin system. Mechanistic insights were gained by studying mice deficient for the vitamin D receptor, which develop hypertension and adverse cardiac remodeling mediated via the renin-angiotensin system. Furthermore, vitamin D receptor is expressed in the heart and regulated under pro-hypertrophic stimuli and vitamin D as receptor has been associated with the expression of other hypertrophic genes such as natriuretic peptides. So, epidemiological data and mechanistic studies have provided strong support for a potentially cardioprotective effect of vitamin D. It remains unclear if vitamin D supplementation is beneficial in preventing heart failure or if it could be a therapeutic addendum in the treatment of heart failure. This review summarizes current knowledge on vitamin D and its biology in heart failure.