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

Population Structure of Pseudomonas aeruginosa from Five Mediterranean Countries: Evidence for Frequent Recombination and Epidemic Occurrence of CC235

Several studies in recent years have provided evidence that Pseudomonas aeruginosa has a non-clonal population structure punctuated by highly successful epidemic clones or clonal complexes. The role of recombination in the diversification of P. aeruginosa clones has been suggested, but not yet demonstrated using multi-locus sequence typing (MLST). Isolates of P. aeruginosa from five Mediterranean countries (n = 141) were subjected to pulsed-field gel electrophoresis (PFGE), serotyping and PCR targeting the virulence genes exoS and exoU. The occurrence of multi-resistance (≥3 antipseudomonal drugs) was analyzed with disk diffusion according to EUCAST. MLST was performed on a subset of strains (n = 110) most of them had a distinct PFGE variant. MLST data were analyzed with Bionumerics 6.0, using minimal spanning tree (MST) as well as eBURST. Measurement of clonality was assessed by the standardized index of association (IAS). Evidence of recombination was estimated by ClonalFrame as well as SplitsTree4.0. The MST analysis connected 70 sequence types, among which ST235 was by far the most common. ST235 was very frequently associated with the O11 serotype, and frequently displayed multi-resistance and the virulence genotype exoS−/exoU+. ClonalFrame linked several groups previously identified by eBURST and MST, and provided insight to the evolutionary events occurring in the population; the recombination/mutation ratio was found to be 8.4. A Neighbor-Net analysis based on the concatenated sequences revealed a complex network, providing evidence of frequent recombination. The index of association when all the strains were considered indicated a freely recombining population. P. aeruginosa isolates from the Mediterranean countries display an epidemic population structure, particularly dominated by ST235-O11, which has earlier also been coupled to the spread of ß-lactamases in many countries

Sex-specific associations of body composition measures with cardiac function and structure after 8 years of follow-up

We investigated the prospective associations of body composition with cardiac structure and function and explored effect modification by sex and whether inflammation was a mediator in these associations. Total body (BF), trunk (TF) and leg fat (LF), and total lean mass (LM) were measured at baseline by a whole body DXA scan. Inflammatory biomarkers and echocardiographic measures were determined both at baseline and follow-up in the Hoorn Study (n = 321). We performed linear regression analyses with body composition measures as determinant and left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) or left atrial volume index (LAVI) at follow-up as outcome. Additionally, we performed mediation analysis using inflammation at follow-up as mediator. The study population was 67.7 ± 5.2 years and 50% were female. After adjustment, BF, TF and LF, and LM were associated with LVMI with regression coefficients of 2.9 (0.8; 5.1)g/m(2.7), 2.3 (0.6; 4.0)g/m(2.7), 2.0 (0.04; 4.0)g/m(2.7) and − 2.9 (− 5.1; − 0.7)g/m(2.7). Body composition measures were not associated with LVEF or LAVI. These associations were not modified by sex or mediated by inflammation. Body composition could play a role in the pathophysiology of LV hypertrophy. Future research should focus on sex differences in regional adiposity in relation with diastolic dysfunction

A graphical analysis of aspects contributing to the spreading of measurements of left ventricular function

The Simpson's method is the standard technique to determine left ventricular (LV) ejection fraction (EF) on echocardiogra-phy. The large inter-observer variability of measuring LVEF is well documented but not fully understood. A graphical analy-sis was used to elaborate what contributes to the inter-observer difference. Forty-two cardiologists (32 male, 39 +/- 7 years) evaluated the LVEF using the Simpson's method on 15 different echocardiograms (2 and 4 chamber view (2CH/4CH)); the program did not show the result of EF to prevent a bias. End-diastolic (ED) and end-systolic (ES) frames were predefined ensuring measurement at the same time point of the cardiac cycles. After standardization of the LV contour, the differences of the individual contours compared to a reference contour were measured. Also, the spreading of lateral/medial mitral annulus contours and the apex were depicted. A significant spreading of LV-contours was seen with larger contours leading to higher EFs (p < 0.001). Experience did not influence the determination of LVEF. ED-volumes showed more spreading than ES-volumes ((3.6 mm (IQR: 2.6-4.0) vs. 3.4 mm (IQR: 2.8-3.8), p < 0.001). Also, the differences were larger for the 2CH compared to the 4CH (p < 0.001). Variability was significantly larger for lateral than septal wall (p < 0.001) as well as the anterior compared to the inferior wall (p < 0.001). There was a relevant scattering of the apex and medial/ lateral mitral annulus ring. There was a large variability of LV-volumes and LVEF as well as position of mitral valve ring and apex. There were global differences (apical 2CH or 4CH), regional aspects (LV walls) and temporal factors (ED vs. ES). Thus, multiple factors contributed to the large variability

EUK-8, a superoxide dismutase and catalase mimetic, reduces cardiac oxidative stress and ameliorates pressure overload-induced heart failure in the harlequin mouse mutant.

OBJECTIVES: The purpose of this study was to identify apoptosis-inducing factor (AIF) as a cardiac mitochondrial antioxidant and assess the efficacy of EUK-8, a salen-manganese catalytic free radical scavenger, to protect the AIF-deficient myocardium against pressure overload. BACKGROUND: Oxidative stress has been postulated to provoke cell death and pathologic remodeling in heart failure

Plasma Dephosphorylated-Uncarboxylated Matrix Gla-Protein in Systemic Sclerosis Patients: Biomarker Potential for Vascular Calcification and Inflammation

Background: Systemic sclerosis (SSc) patients face an elevated risk of cardiovascular disease (CVD), even when classic cardiovascular risk factors are considered. Plasma dephosphorylated-uncarboxylated Matrix Gla-protein (dp-ucMGP), an inactive form of MGP, is associated with increased CVD risk. Smooth muscle cells, implicated in SSc’s development, are the primary dp-ucMGP producers. This study assessed dp-ucMGP levels and initial CVD events in early-diagnosed SSc patients, investigating its potential as a CVD and all-cause mortality predictor over time. Methods: In a cohort of 87 SSc patients (excluding those with pre-existing CVD or on dialysis), baseline dp-ucMGP levels were measured, along with cardiovascular risk factors. Validation involved assessing dp-ucMGP in a subset of treatment-naive SSc patients. Results: A significantly elevated median dp-ucMGP level of 634 pmol/L (IQR 301) compared with healthy controls (dp-ucMGP p 634 pmol/L) correlated with a higher risk of CVD and/or death (log-rank test: p < 0.01). Conclusions: In summary, dp-ucMGP emerges as a novel biomarker in SSc patients, with elevated levels indicating an increased risk of CVD and/or mortality in this population