Systematic Brain Natriuretic Peptide Measurement for Cardiac Screening in Patients with Severe Obesity: The OLECOEUR Study.

INTRODUCTION: Heart failure (HF) is difficult to diagnose in obese patients because of cardiovascular and pulmonary comorbidities associated with physical deconditioning, all of which lead to dyspnea. METHODS: The OLECOEUR study is a prospective screening for HF using systematic brain natriuretic peptide (BNP) measurement in ambulatory patients with obesity from a department of Nutrition (Paris, France). Clinical, biological, and echocardiographic data were extracted from electronic medical records. RESULTS: We included 1,506 patients middle-aged (mean age: 47.2 ± 14.6 years old) with severe obesity (mean body mass index: 40.4 ± 6.6 kg/m2). Patients with BNP ≥35 pg/mL had left heart remodeling including thicker interventricular septum (10.4 ± 2.0 vs. 9.6 ± 1.8 mm; p = 0.0008), higher left ventricular mass (89.9 ± 24.3 vs. 77.2 ± 20.0 g/m2; p = 0.0009), and significant changes in both left and right atria consistent with a higher proportion of prior atrial fibrillation. Markers of right heart remodeling on echocardiography were also significantly higher (pulmonary artery systolic pressure: 33.3 ± 17.3 vs. 24.5 ± 6.3 mm Hg; p = 0.0002). CONCLUSION: The OLECOEUR study shows left and right subclinical cardiac remodeling in obese patients screened for HF with systematic dosing of BNP with usual cut-off of 35 pg/mL.

Trends in prevalence of major aetiologies leading to heart failure in young patients: An integrative review.

The prevalence of Heart failure (HF) is increasing with the aging of the population but it is estimated that 10% of HF patients are younger than 50 years-old. HF development in this population is characterized with a fast-growing prevalence, and important disparities according to underlying etiologies or gender. These observations highlight the need to identify specific and preventable factors in these patients, a topic that is under-studied. Here we provide an overview of trends in prevalence of major etiologies leading to HF in young subjects, including genetic factors associated with cardiomyopathies, premature vascular dysfunction and related ischemia, metabolic stress, cardio-toxic responses to different agents, and myocarditis. We also highlight the increasing influence of major risk factors that are driving HF in younger patients, such as obesity, diabetes or arterial hypertension.

Aetiological classification and prognosis in patients with heart failure with preserved ejection fraction.

AIMS: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various causes that may influence prognosis. METHODS AND RESULTS: We extracted the electronic medical records for 2180 consecutive patients hospitalized between 2016 and 2019 for decompensated heart failure. Using a text mining algorithm looking for a left ventricular ejection fraction ≥50% and plasma brain natriuretic peptide level >100 pg/mL, we identified 928 HFpEF patients. We screened for a prevailing cause of HFpEF according to European guidelines and found that 418 (45.0%) patients had secondary HFpEF due to either myocardial (n = 125, 13.5%) or loading condition abnormalities (n = 293, 31.5%), while the remaining 510 (55.0%) patients had idiopathic HFpEF. We assessed the association between the causes of HFpEF and survival collected up to 31 December 2020 using Cox proportional hazards analysis. Even though patients with idiopathic HFpEF were older, frequently female, and had frequent co-morbidities and a higher crude mortality rate compared with secondary HFpEF patients, their prognosis was similar after adjustment for age and sex. Unsupervised clustering analysis revealed three main phenogroups with different distribution of idiopathic vs. secondary HFpEF. The phenogroup with the highest proportion of idiopathic HFpEF (69%) had (i) an excess rate of non-cardiac co-morbidities including chronic obstructive pulmonary disease (31%) or obesity (41%) and (ii) a better prognosis compared with the two other phenogroups enriched with secondary HFpEF. CONCLUSIONS: Aetiological classification provides clinical and prognostic information and may be useful to better decipher the clinical heterogeneity of HFpEF.

Efficacy of epicardial implantation of acellular chitosan hydrogels in ischemic and nonischemic heart failure: impact of the acetylation degree of chitosan.

This work explores the epicardial implantation of acellular chitosan hydrogels in two murine models of cardiomyopathy, focusing on their potential to restore the functional capacity of the heart. Different chitosan hydrogels were generated using polymers of four degrees of acetylation, ranging from 2.5% to 38%, because the degree of acetylation affects their degradation and biological activity. The hydrogels were adjusted to a 3% final polymer concentration. After complete macromolecular characterization of the chitosans and study of the mechanical properties of the resulting hydrogels, they were sutured onto the surface of the myocardium, first in rat after four-weeks of coronary ligation (n=58) then in mice with cardiomyopathy induced by a cardiac-specific invalidation of serum response factor (n=20). The implantation of the hydrogels was associated with a reversion of cardiac function loss with maximal effects for the acetylation degree of 24%. The extent of fibrosis, the cardiomyocyte length-to-width ratio, as well as the genes involved in fibrosis and stress were repressed after implantation. Our study demonstrated the beneficial effects of chitosan hydrogels, particularly with polymers of high degrees of acetylation, on cardiac remodeling in two cardiomyopathy models. Our findings indicate they have great potential as a reliable therapeutic approach to heart failure.

Characterization of a novel intrinsically radiopaque Drug-eluting Bead for image-guided therapy: DC Bead LUMI™.

We have developed a straightforward and efficient method of introducing radiopacity into Polyvinyl alcohol (PVA)-2-Acrylamido-2-methylpropane sulfonic acid (AMPS) hydrogel beads (DC Bead™) that are currently used in the clinic to treat liver malignancies. Coupling of 2,3,5-triiodobenzaldehyde to the PVA backbone of pre-formed beads yields a uniformly distributed level of iodine attached throughout the bead structure (~150mg/mL) which is sufficient to be imaged under standard fluoroscopy and computed tomography (CT) imaging modalities used in treatment procedures (DC Bead LUMI™). Despite the chemical modification increasing the density of the beads to ~1.3g/cm3 and the compressive modulus by two orders of magnitude, they remain easily suspended, handled and administered through standard microcatheters. As the core chemistry of DC Bead LUMI™ is the same as DC Bead™, it interacts with drugs using ion-exchange between sulfonic acid groups on the polymer and the positively charged amine groups of the drugs. Both doxorubicin (Dox) and irinotecan (Iri) elution kinetics for all bead sizes evaluated were within the parameters already investigated within the clinic for DC Bead™. Drug loading did not affect the radiopacity and there was a direct relationship between bead attenuation and Dox concentration. The ability (Dox)-loaded DC Bead LUMI™ to be visualized in vivo was demonstrated by the administration of into hepatic arteries of a VX2 tumor-bearing rabbit under fluoroscopy, followed by subsequent CT imaging.