Clinical profile and contemporary management of patients with heart failure with preserved ejection fraction: results from the CHECK-HF registry.

BACKGROUND: Clinical management of heart failure with preserved ejection fraction (HFpEF) centres on treating comorbidities and is likely to vary between countries. Thus, to provide insight into the current management of HFpEF, studies from multiple countries are required. We evaluated the clinical profiles and current management of patients with HFpEF in the Netherlands. METHODS: We included 2153 patients with HFpEF (defined as a left ventricular ejection fraction ≥ 50%) from the CHECK-HF registry, which included patients from 2013 to 2016. RESULTS: Median age was 77 (IQR 15) years, 55% were women and the most frequent comorbidities were hypertension (51%), renal insufficiency (45%) and atrial fibrillation (AF, 38%). Patients between 65 and 80 years and those over 80 years had on average more comorbidities (up to 64% and 74%, respectively, with two or more comorbidities) than patients younger than 65 years (38% with two or more comorbidities, p-value < 0.001). Although no specific drugs are available for HFpEF, treating comorbidities is advised. Beta-blockers were most frequently prescribed (78%), followed by loop diuretics (74%), renin-angiotensin system (RAS) inhibitors (67%) and mineralocorticoid receptor antagonists (MRAs, 39%). Strongest predictors for loop-diuretic use were older age, higher New York Heart Association class and AF. CONCLUSION: The medical HFpEF profile is determined by the underlying comorbidities, sex and age. Comorbidities are highly prevalent in HFpEF patients, especially in elderly HFpEF patients. Despite the lack of evidence, many HFpEF patients receive regular beta-blockers, RAS inhibitors and MRAs, often for the treatment of comorbidities.

A comparison of the efficacy and tolerability of titrate-to-goal regimens of simvastatin and fluvastatin: a randomized, double-blind study in adult patients at moderate to high risk for cardiovascular disease.

BACKGROUND: Use of cholesterol-lowering regimens has been shown to reduce the risk of coronary heart disease (CHD), both in primary and secondary prevention. However, there have been few studies of the relative benefits and risks of the various cholesterol-lowering agents in patient groups with specific risk factors for CHD. OBJECTIVE: The primary goal of this study was to compare the proportions of adult patients with primary hypercholesterolemia and a moderate to high risk for CHD achieving National Cholesterol Education Program low-density lipoprotein cholesterol (LDL-C) goals with titrate-to-goal regimens of simvastatin and fluvastatin. METHODS: This was a multicenter, prospective, randomized, double-blind, parallel-group study enrolling adult patients with type IIa or IIb primary hypercholesterolemia, LDL-C levels <6.0 mmol/L (<232.0 mg/dL), and triglyceride levels <4.5 mmol/L (<398.6 mg/dL), and either CHD or other atherosclerotic disease (the CHD, or high-risk, group), or multiple risk factors for CHD (the MRF, or moderate-risk, group). After a 6-week washout period, patients were randomized to 18 weeks of treatment at an initial dosage of simvastatin 10 mg once daily or fluvastatin 20 mg once daily. At 6- and 12-week titration visits, the dosage in patients who had not acheived the LDL-C goal could be increased to simvastatin 20 mg once daily and then 40 mg once daily, or to fluvastatin 40 mg once daily and then 40 mg twice daily. Lipid profiles were obtained at each titration visit and at the end of treatment. In addition to the comparison between treatments, secondary comparisons were made between the CHD and MRF subgroups within each treatment group. Statistical significance was assessed using analysis of variance. RESULTS: A total of 478 patients were enrolled, 237 in the simvastatin group and 241 in the fluvastatin group. There were no significant between-group differences in patients' characteristics at baseline. At the end of the study, 60.8% (135/222) of patients in the simvastatin group had reached target LDL-C goals, compared with 35.1% (76/216) in the fluvastatin group (P < 0.001). In the simvastatin CHD and MRF subgroups, 49% and 73%, respectively, reached the LDL-C target, compared with 19% and 50% in the corresponding fluvastatin subgroups (P < 0.001). The proportion of patients requiring titration was higher in the fluvastatin group than in the simvastatin group (87.1% and 64.1%, respectively; P = 0.001). The incidence of adverse events was similar between groups. CONCLUSION: In this study, more patients with primary hypercholesterolemia and CHD or multiple risk factors for CHD reached LDL-C goals with simvastatin treatment and required less titration than those who received fluvastatin treatment.

Symptomatic pectus excavatum in seniors (SPES): a cardiovascular problem? : A prospective cardiological study of 42 senior patients with a symptomatic pectus excavatum.

OBJECTIVES: There is no consensus among physicians as to whether or not pectus excavatum can produce symptoms sometimes even severe enough to justify a surgical procedure. The aim of this study was to assess the prevalence and severity of complaints and symptoms of senior patients with a pectus excavatum and to evaluate the results of surgical correction of the chest deformation. DESIGN: This is a prospective clinical study, case series. PARTICIPANTS: The participants are 42 senior patients with a pectus excavatum and somatic complaints. METHODS: Cardiological screening included medical history taking, physical examination, electrocardiography, transthoracic echocardiography and treadmill cardiography. Complaints, symptoms and test results were arranged in a clinical score. Indication for a therapeutic surgical correction by a modified Ravitch operation was a high clinical score in combination with radiological evidence of cardiac compression on CT or MRI. RESULTS: The clinical picture of the 42 senior patients with a pectus excavatum showed complaints of fatigue and low exercise tolerance, shortness of breath, palpitations, inspiratory obstruction and sometimes chest discomfort or pain. The serious and sometimes invalidating complaints of 19 patients (45%) had started only in their fourth or fifth decade of life and were labelled in 12 patients (63%) as 'Unexplained cardiovascular complaints'. To date, 11 patients have undergone surgical procedures. Symptoms were reduced substantially or had disappeared completely. All patients indicated that their health-related quality of life was significantly improved. CONCLUSION: Recognising the clinical picture of SPES is relevant because surgical reconstruction of the chest can provide substantial relief of symptoms.

Addition of felodipine to metoprolol vs replacement of metoprolol by felodipine in patients with angina pectoris despite adequate beta-blockade. Results of the Felodipine ER and Metoprolol CR in Angina (FEMINA) Study. Working Group on Cardiovascular Research, The Netherlands (WCN).

AIMS: The study aimed to compare the addition of felodipine to metoprolol, and of the replacement of metoprolol by felodipine, with continuation of metoprolol, in patients with angina pectoris despite optimal beta-blockade. METHODS AND RESULTS: The study was double-blind, parallel, randomized and controlled, and comprised 363 patients from 27 outpatient cardiology clinics in the Netherlands. The patients had angina and positive bicycle exercise tests despite optimal beta-blockade (resting heart rate < 65 beats.min-1). Randomization was to three treatment groups: continuation of metoprolol (control), addition of felodipine to metoprolol, and replacement of metoprolol by felodipine. Exercise tests were repeated after 2 and 5 weeks. The main outcome measure was: exercise result after 5 weeks, compared with baseline, between-group comparison of changes vs control. There were no significant differences in exercise duration and onset of chest pain vs control. The addition of felodipine increased time until 1 mm ST depression (43 s, 95% confidence interval 20-65 s), and decreased both ST depression at highest comparable work load (0.46 mm, 95% confidence interval 0.19-0.72), and maximal ST depression (0.49 mm, 95% confidence interval 0.23-0.74). Exercise results after replacement of metoprolol by felodipine were not different from control, apart from a significant increase in rate pressure product. Significantly more patients experienced adverse events in the felodipine monotherapy group. CONCLUSION: Combination of metoprolol and felodipine is to be preferred to felodipine monotherapy in patients who have signs and symptoms of myocardial ischaemia despite optimal beta-blockade.

Does lowering of cholesterol levels influence functional properties of large arteries?

Hypercholesterolaemia is a risk factor for atherosclerosis and induces endothelial dysfunction. Endothelial dysfunction may increase vascular tone and arterial stiffness and as a consequence may decrease arterial distensibility (DC) and arterial compliance (CC). It is hypothesized that lipid-lowering therapy may enhance DC and CC. Therefore, the present study investigates the effect of lipid-lowering therapy with pravastatin on the haemodynamics, DC and CC of the elastic common carotid artery (CCA), and the muscular femoral (FA) and brachial (BA) arteries in patients with primary hypercholesterolaemia. After an 8-week placebo run-in period with a low-cholesterol diet, 19 patients with total cholesterol concentrations of between 6.5 and 9.0 mmol.l-1 and triglyceride concentrations < 4 mmol.l-1 entered a double-blind placebo controlled crossover study. Patients received pravastatin 40 mg o.d. or placebo, each for 8 weeks. Throughout the study the lipid-lowering diet was continued. With pravastatin, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides were decreased (total cholesterol 26%, LDL-C 35%, triglycerides 16%), while high-density lipoprotein cholesterol (HDL-C) was not changed. Other laboratory values remained within the normal range. Blood pressure, heart rate, cardiac function and systemic vascular resistance were not influenced by pravastatin. Compared to placebo, diameter, distensibility and compliance of all arteries were not statistically significantly changed with pravastatin. These data suggest that, in patients with mild to moderate primary hypercholesterolaemia, short-term lowering of plasma cholesterol does not alter the haemodynamics and vessel wall properties of large arteries.

Discrimination between myocardial and skeletal muscle injury by assessment of the plasma ratio of myoglobin over fatty acid-binding protein.

BACKGROUND: Myoglobin and fatty acid-binding protein (FABP) each are useful as early biochemical markers of muscle injury. We studied whether the ratio of myoglobin over FABP in plasma can be used to distinguish myocardial from skeletal muscle injury. METHODS AND RESULTS: Myoglobin and FABP were assayed immunochemically in tissue samples of human heart and skeletal muscle and in serial plasma samples from 22 patients with acute myocardial infarction (AMI), from 9 patients undergoing aortic surgery (causing injury of skeletal muscles), and from 10 patients undergoing cardiac surgery. In human heart tissue, the myoglobin/FABP ratio was 4.5 and in skeletal muscles varied from 21 to 73. After AMI, the plasma concentrations of both proteins were elevated between approximately 1 and 15 to 20 hours after the onset of symptoms. In this period, the myoglobin/FABP ratio was constant both in subgroups of patients receiving and those not receiving thrombolytics and amounted to 5.3 +/- 1.2 (SD). In serum from aortic surgery patients, both proteins were elevated between 6 and 24 hours after surgery; the myoglobin/FABP ratio was 45 +/- 22 (SD), which is significantly different from plasma values in AMI patients (P < .001). In patients with cardiac surgery, the ratio increased from 11.3 +/- 4.7 to 32.1 +/- 13.6 (SD) during 24 hours after surgery, indicating more rapid release of protein from injured myocardium than from skeletal muscles. CONCLUSIONS: The ratio of the concentrations of myoglobin over FABP in plasma from patients with muscle injury reflects the ratio found in the affected tissue. Since this ratio is different between heart (4.5) and skeletal muscle (20 to 70), its assessment in plasma allows the discrimination between myocardial and skeletal muscle injury in humans.