A comparison of the effects of selective and non-selective mineralocorticoid antagonism on glucose homeostasis of heart failure patients with glucose intolerance or type II diabetes: A randomized controlled double-blind trial.

Mineralocorticoid receptor antagonists (MRAs) decrease morbidity and mortality in patients with heart failure (HF). However, spironolactone, a non-selective MRA, has been shown to exert a harmful effect on glucose homeostasis. The objective of this multicenter, randomized, controlled, double-blind trial was to compare the effects of spironolactone to those of the selective MRA eplerenone on glucose homeostasis among 62 HF patients with glucose intolerance or type II diabetes. Trial registration number:NCT01586442.

Toward Thiophene-Annulated Graphene Nanoribbons.

Narrow thiophene-edged graphene nanoribbons (GNRs) were prepared from polychlorinated thiophene-containing poly(p-phenylene)s using the photochemical, metal-free cyclodehydrochlorination (CDHC) reaction. 1 H NMR and Raman spectroscopy confirmed the structures of the GNRs. The regioselectivity of the CDHC reaction allows the preparation of both laterally symmetrical and unsymmetrical GNRs and, consequently, the modulation of their optical and electronic properties.

Breaking Bonds and Forming Nanographene Diradicals with Pressure.

New anthanthrone-based polycyclic scaffolds possessing peripheral crowded quinodimethanes have been prepared. While the compounds adopt a closed-shell butterfly-shaped structure in the ground state, a curved-to-planar fluxional inversion is accessible with a low energy barrier through a biradicaloid transition state. Inversion is primarily driven by the release of strain associated with steric hindrance at the peri position of the anthanthrone core; a low-lying diradical state is accessible through planarization of the core, which is attained in solution at moderate temperatures. The most significant aspect of this transformation is that planarization is also achieved by application of mild pressure in the solid state, wherein the diradical remains kinetically trapped. Complementary information from quantum chemistry, 1 H NMR, and Raman spectroscopies, together with magnetic experiments, is consistent with the formation of a nanographene-like structure that possesses radical centers localized at the exo-anthanthrone carbons bearing phenyl substituents.

Cruciform alkynylated anthanthrene derivatives: a structure-properties relationship case study.

An efficient and versatile synthetic strategy toward cruciform anthanthrene compounds using Sonogashira couplings steps was developed. Acetylenic linkers were used to effectively extend the π-conjugation of polycyclic anthanthrone and anthanthrene compounds and tune their optoelectronic properties. Structure-property relationships supported by DFT calculations indicated more effective π-conjugation along the 6,12 axis than along the 4,10 axis. These molecules displayed strong J-aggregation both in solution and in the solid state and proved to be highly photostable with reversible redox processes, which are properties of interest in materials sciences.

Sex-specific interaction effects of age, occupational status, and workplace stress on psychiatric symptoms and allostatic load among healthy Montreal workers.

Socio-demographics and workplace stress may affect men and women differently. The aim of this cross-sectional study was to assess sex-specific interactions among age, occupational status, and workplace Demand-Control-Support (D-C-S) factors in relation to psychiatric symptoms and allostatic load levels representing multi-systemic "wear and tear". It was hypothesized that beyond main effects, D-C-S factors would be moderated by occupational status and age in sex-specific directions predictive of subjective psychiatric symptoms and objective physiological dysregulations. Participants included healthy male (n = 81) and female (n = 118) Montreal workers aged 20 to 64 years (Men: M = 39.4 years, SD = 11.3; Women: M = 42.8 years, SD = 11.38). The Job Content Questionnaire was administered to assess workplace D-C-S factors that included psychological demands, decisional latitude, and social support. Occupational status was coded using the Nam--Powers--Boyd system derived from the Canadian census. Psychiatric symptoms were assessed using the Beck Anxiety Scale and the Beck Depression Inventory II. Sex-specific allostatic load indices were calculated based on fifteen biomarkers. Regression analyses revealed that higher social support was associated with less depressive symptoms in middle aged (p = 0.033) and older men (p = 0.027). Higher occupational status was associated with higher allostatic load levels for men (p = 0.035), while the reverse occurred for women (p = 0.048). Women with lower occupational status but with higher decision latitude had lower allostatic load levels, as did middle-aged (p = 0.031) and older women (p = 0.003) with higher psychological demands. In summary, age and occupational status moderated workplace stress in sex-specific ways that have occupational health implications.

Digital phenotyping of student mental health during COVID-19: an observational study of 100 college students.

Objective: This study assessed the feasibility of capturing smartphone based digital phenotyping data in college students during the COVID-19 pandemic with the goal of understanding how digital biomarkers of behavior correlate with mental health. Participants: Participants were 100 students enrolled in 4-year universities. Methods: Each participant attended a virtual visit to complete a series of gold-standard mental health assessments, and then used a mobile app for 28 days to complete mood assessments and allow for passive collection of GPS, accelerometer, phone call, and screen time data. Students completed another virtual visit at the end of the study to collect a second round of mental health assessments. Results: In-app daily mood assessments were strongly correlated with their corresponding gold standard clinical assessment. Sleep variance among students was correlated to depression scores (ρ = .28) and stress scores (ρ = .27). Conclusions: Digital Phenotyping among college students is feasible on both an individual and a sample level. Studies with larger sample sizes are necessary to understand population trends, but there are practical applications of the data today.

Left ventricular versus simultaneous biventricular pacing in patients with heart failure and a QRS complex ≥120 milliseconds.

BACKGROUND: Left ventricular (LV) pacing alone may theoretically avoid deleterious effects of right ventricular pacing. METHODS AND RESULTS: In a multicenter, double-blind, crossover trial, we compared the effects of LV and biventricular (BiV) pacing on exercise tolerance and LV remodeling in patients with an LV ejection fraction ≤35%, QRS ≥120 milliseconds, and symptoms of heart failure. A total of 211 patients were recruited from 11 centers. After a run-in period of 2 to 8 weeks, 121 qualifying patients were randomized to LV followed by BiV pacing or vice versa for consecutive 6-month periods. The greatest improvement in New York Heart Association class and 6-minute walk test occurred during the run-in phase before randomization. Exercise duration at 75% of peak Vo(2) (primary outcome) increased from 9.3±6.4 to 14.0±11.9 and 14.3±12.5 minutes with LV and BiV pacing, respectively, with no difference between groups (P=0.4327). LV ejection fraction improved from 24.4±6.3% to 31.9±10.8% and 30.9±9.8% with LV and BiV pacing, respectively, with no difference between groups (P=0.4530). Reductions in LV end-systolic volume were likewise similar (P=0.6788). The proportion of clinical responders (≥20% increase in exercise duration) to LV and BiV pacing was 48.0% and 55.1% (P=0.1615). Positive remodeling responses (≥15% reduction in LV end-systolic volume) were observed in 46.7% and 55.4% (P=0.0881). Overall, 30.6% of LV nonresponders improved with BiV and 17.1% of BiV nonresponders improved with LV pacing. CONCLUSION: LV pacing is not superior to BiV pacing. However, nonresponders to BiV pacing may respond favorably to LV pacing, suggesting a potential role as tiered therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00901212.

Effect of the Helium Background Gas Pressure on the Structural and Optoelectronic Properties of Pulsed-Laser-Deposited PbS Thin Films.

This work focuses on the dependence of the features of PbS films deposited by pulsed laser deposition (PLD) subsequent to the variation of the background pressure of helium (PHe). The morphology of the PLD-PbS films changes from a densely packed and almost featureless structure to a columnar and porous one as the He pressure increases. The average crystallite size related to the (111) preferred orientation increases up to 20 nm for PHe ≥ 300 mTorr. The (111) lattice parameter continuously decreases with increasing PHe values and stabilizes at PHe ≥ 300 mTorr. A downshift transition of the Raman peak of the main phonon (1LO) occurs from PHe = 300 mTorr. This transition would result from electron-LO-phonon interaction and from a lattice contraction. The optical bandgap of the films increases from 1.4 to 1.85 eV as PHe increases from 50 to 500 mTorr. The electrical resistivity of PLD-PbS is increased with PHe and reached its maximum value of 20 Ω·cm at PHe = 300 mTorr (400 times higher than 50 mTorr), which is probably due to the increasing porosity of the films. PHe = 300 mTorr is pointed out as a transitional pressure for the structural and optoelectronic properties of PLD-PbS films.

Effects of AGTR1 A1166C gene polymorphism in patients with heart failure treated with candesartan.

BACKGROUND: The benefits of angiotensin II receptor blockers (ARBs) in patients with heart failure who are treated with standard pharmacotherapy, including an angiotensin-converting enzyme (ACE) inhibitor, were demonstrated in 2 large randomized trials. It is currently impossible to determine which patient will benefit from the addition of an ARB. OBJECTIVE: To explore the impact of selected candidate genes on the hemodynamic, neurohormonal, and antiinflammatory effects of candesartan in patients with heart failure who are already being treated with an ACE inhibitor. METHODS: We investigated the impact of 10 candidate genetic polymorphisms on the effects of candesartan in patients with heart failure who are treated with an ACE inhibitor. We evaluated their impact on acute (2 wk) and long-term (24 wk) changes in blood pressure and N-terminal proB-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hsCRP) during treatment with candesartan. RESULTS: Thirty-one patients were included. Homozygotes of the AGTR1 A1166 allele (n = 13) had a greater decrease in systolic (-9.1 +/- 4.7 vs 1.1 +/- 3.3 mm Hg; p = 0.04 by analysis of variance [ANOVA], adjusting for dose) and diastolic blood pressure (-5.1 +/- 1.5 vs 1.9 +/- 1.9 mm Hg; p = 0.005 by ANOVA, adjusting for dose) compared with C1166 allele carriers (n = 18) following 2 weeks of treatment. After 6 months of treatment, C1166 carriers experienced a greater decrease in NT-proBNP (-151.4 [-207; -19.8] ng/L vs 147.3 [-61.3; 882.9] ng/L; p = 0.03) and hsCRP (-0.8 [-2.2; -0.03] mg/L) vs 0.2 [-1.8; 5.3] mg/L; p = 0.09) compared with patients carrying the AA1166 genotype. No other significant association was found. CONCLUSIONS: The results of this proof-of concept study provide the first evidence that the AGTR1 A1166C polymorphism could influence the response to candesartan in patients with heart failure who are receiving ACE inhibitors. Validation of these exploratory findings in larger populations is required before use of the AGTR1 A1166C genotype can be incorporated into clinical practice.

A prospective study of the impact of AGTR1 A1166C on the effects of candesartan in patients with heart failure.

AIM: To evaluate the impact of AGTR1 A1166C (rs5186) on the response to candesartan in patients with heart failure. MATERIALS & METHODS: Prospective, multicentre, open-label study. We studied 299 symptomatic patients with heart failure presenting a left ventricular ejection fraction ≤40%. RESULTS: Reductions in the primary end points of natriuretic peptides were not significantly associated with AGTR1 A1166C. Nevertheless, carrying the 1166C allele was associated with a greater compensatory increase in renin activity (p = 0.037) after 16 weeks of treatment with candesartan and a more modest effect on aldosterone concentrations (p = 0.022). CONCLUSION: AGTR1 1166C carriers may experience a greater long-term compensatory renin-angiotensin-aldosterone system activation following treatment with candesartan. Whether these associations ultimately influence clinical outcomes requires investigation. Clinicaltrials.gov : NCT00400582.

Effects of combined candesartan and ACE inhibitors on BNP, markers of inflammation and oxidative stress, and glucose regulation in patients with symptomatic heart failure.

BACKGROUND: We assessed the effects of candesartan in addition to angiotensin-converting enzyme (ACE) inhibitors on N-terminal pro-type natriuretic peptide (Nt-proBNP), systemic markers of inflammation and oxidative stress as well as on glucose regulation in patients with heart failure (HF). METHODS AND RESULTS: Eighty patients with HF ages 62.5 +/- 8.4 years presenting mostly with New York Heart Association class II symptoms (class II = 57.5%, III = 41.3%), and mean left ventricular ejection fraction 27.1 +/- 7.3% were recruited. The patients were randomized to receive candesartan titrated to 32 mg 1 per day versus placebo in double-blind fashion for 6 months. Nt-proBNP, markers of inflammation and oxidative stress, glucose, insulin, and fasting insulin resistance index were analyzed. Candesartan decreased Nt-proBNP (median value = 12.4% versus -20.4%; [candesartan] P = .05), and high-sensitivity C-reactive protein (hsCRP) (+5.32% versus -20.3% [candesartan]; P = 0.046), without significantly influencing serum interleukin-6, interleukin-18, adhesion molecules, or markers of oxidative stress. Blood glucose decreased in patients treated with candesartan with a significantly greater effect in patients with higher blood glucose levels (P < .01 for interaction). CONCLUSIONS: The addition of candesartan to ACE inhibitor and beta-blocker decreases Nt-proBNP and hsCRP, but does not change the other markers of inflammation or oxidative stress in patients with heart failure. Dual angiotensin-II suppression also decreased blood glucose with a greater impact in patients with higher blood glucose level.

Prednisone prevents atrial fibrillation promotion by atrial tachycardia remodeling in dogs.

BACKGROUND: There is evidence suggesting involvement of oxidative stress, inflammation, and calcineurin/nuclear factor of activated T cell pathways in atrial fibrillation. This study evaluated the efficacy of anti-inflammatory and calcineurin-inhibitory drugs on promotion of atrial fibrillation by atrial tachycardia-induced remodeling in dogs. METHODS AND RESULTS: Dogs were subjected to atrial tachypacing at 400 bpm in the absence and presence of treatment with prednisone (15 or 50 mg/day) or ibuprofen (anti-inflammatory) or cyclosporine-A (calcineurin inhibitor). Serial closed-chest electrophysiological studies were performed in each dog at baseline and 2, 4, and 7 days after tachypacing onset. A final open-chest study was performed on day 8. Serum C-reactive protein was measured by ELISA and nitric oxide synthase by Western blotting. The mean duration of induced atrial fibrillation was markedly increased by tachypacing alone, from 26+/-8 to 962+/-317 s (p<0.01), and the atrial effective refractory period was decreased from 117+/-4 to 73+/-7 ms (p<0.001; cycle-length 300 ms). Tachypacing-induced effective refractory period shortening and atrial fibrillation promotion were unaffected by ibuprofen or cyclosporine-A; however, both doses of prednisone suppressed tachypacing-remodeling effects (atrial fibrillation duration to 96+/-60 s and 28+/-11 s at higher and lower doses, respectively; effective refractory period to 101+/-6 ms for higher-dose and 105+/-3 ms for lower-dose group). In addition, prednisone (but not ibuprofen or cyclosporine) significantly decreased C-reactive protein concentrations and attenuated the increase in endothelial nitric oxide synthase expression caused by atrial tachypacing. CONCLUSIONS: Prednisone prevents the electrophysiological and atrial fibrillation-promoting effects of atrial tachycardia-remodeling, possibly by an anti-inflammatory action, whereas the less potent anti-inflammatory ibuprofen and the calcineurin inhibitor cyclosporine-A are without effect.

Effect of simvastatin and antioxidant vitamins on atrial fibrillation promotion by atrial-tachycardia remodeling in dogs.

BACKGROUND: There is evidence for a role of oxidant stress and inflammation in atrial fibrillation (AF). Statins have both antioxidant and antiinflammatory properties. We compared the effects of simvastatin with those of antioxidant vitamins on AF promotion by atrial tachycardia in dogs. METHODS AND RESULTS: We studied dogs subjected to atrial tachypacing (ATP) at 400 bpm in the absence and presence of treatment with simvastatin, vitamin C, and combined vitamins C and E. Serial closed-chest electrophysiological studies were performed in each dog at baseline and 2, 4, and 7 days after tachypacing onset. Atrioventricular block was performed to control ventricular rate. Mean duration of induced AF was increased from 42+/-18 to 1079+/-341 seconds at terminal open-chest study after tachypacing alone (P<0.01), and atrial effective refractory period (ERP) at a cycle length of 300 ms was decreased from 117+/-5 to 76+/-6 ms (P<0.01). Tachypacing-induced ERP shortening and AF promotion were unaffected by vitamin C or vitamins C and E; however, simvastatin suppressed tachypacing-induced remodeling effects significantly, with AF duration and ERP averaging 41+/-15 seconds and 103+/-4 ms, respectively, after tachypacing with simvastatin therapy. Tachypacing downregulated L-type Ca2+-channel alpha-subunit expression (Western blot), an effect that was unaltered by antioxidant vitamins but greatly attenuated by simvastatin. CONCLUSIONS: Simvastatin attenuates AF promotion by atrial tachycardia in dogs, an effect not shared by antioxidant vitamins, and constitutes a potentially interesting new pharmacological approach to preventing the consequences of atrial tachycardia remodeling.

Cardioplegic arrest with L-arginine improves myocardial protection: results of a prospective randomized clinical trial.

BACKGROUND: Blood cardioplegic arrest remains the method of choice for myocardial protection. L-arginine has been suggested to improve protection through an increase in nitric oxide production. METHODS: A prospective, randomized, double-blinded clinical trial comparing standard blood cardioplegic solution to L-arginine-enriched solution (7.5 g/500 mL) enrolled 200 patients undergoing coronary artery bypass grafting. Clinical data and biochemical markers of ischemia were recorded. Warm blood cardioplegia (33 degrees C) was administered in 74% of patients and cold blood (20 degrees C) was used in 26% of patients. Both groups averaged three grafts per patient. RESULTS: There were two (2%) deaths in both groups. There were four (4%) myocardial infarctions (MI) in the control group and six (6%) infarctions in the L-arginine group (p = 0.5). For the 190 patients without MI, serum levels of troponin T averaged 0.40+/-0.43, 0.38+/-0.42, and 0.39+/-0.50 microg/L in control patients compared with 0.28+/-0.22, 0.24+/-0.18, and 0.27+/-0.20 microg/L in L-arginine patients, respectively, 12, 24 and 48 hours after coronary artery bypass grafting (p = 0.03). The cardiac index averaged 2.7+/-0.8 L x min(-1) x m(-2) in control patients and 2.9+/-0.7 L x min(-1) x m(-2) in arginine patients immediately after surgery (p = 0.09). Intensive care unit and hospital length of stay averaged 3.5+/-5 days and 7.3+/-6 days in control patients compared with 2.5+/-3 days and 6.1+/-4 days in arginine patients (p = 0.09). CONCLUSIONS: L-arginine-supplemented blood cardioplegic solution is associated with reduced release of biochemical markers of myocardial damage, suggesting improved myocardial protection.

Circulating levels of linoleic acid and HDL-cholesterol are major determinants of 4-hydroxynonenal protein adducts in patients with heart failure.

OBJECTIVE: Measurements of oxidative stress biomarkers in patients with heart failure (HF) have yielded controversial results. This study aimed at testing the hypothesis that circulating levels of the lipid peroxidation product 4-hydroxynonenal bound to thiol proteins (4HNE-P) are strongly associated with those of its potential precursors, namely n-6 polyunsaturated fatty acids (PUFA). METHODS AND RESULTS: Circulating levels of 4HNE-P were evaluated by gas chromatography-mass spectrometry in 71 control subjects and 61 ambulatory symptomatic HF patients along with various other clinically- and biochemically-relevant parameters, including other oxidative stress markers, and total levels of fatty acids from all classes, which reflect both free and bound to cholesterol, phospholipids and triglycerides. All HF patients had severe systolic functional impairment despite receiving optimal evidence-based therapies. Compared to controls, HF patients displayed markedly lower circulating levels of HDL- and LDL-cholesterol, which are major PUFA carriers, as well as of PUFA of the n-6 series, specifically linoleic acid (LA; P=0.001). Circulating 4HNE-P in HF patients was similar to controls, albeit multiple regression analysis revealed that LA was the only factor that was significantly associated with circulating 4HNE-P in the entire population (R (2)=0.086; P=0.02). In HF patients only, 4HNE-P was even more strongly associated with LA (P=0.003) and HDL-cholesterol (p<0.0002). Our results demonstrate that 4HNE-P levels, expressed relative to HDL-cholesterol, increase as HDL-cholesterol plasma levels decrease in the HF group only. CONCLUSION: Results from this study emphasize the importance of considering changes in lipids and lipoproteins in the interpretation of measurements of lipid peroxidation products. Further studies appear warranted to explore the possibility that HDL-cholesterol particles may be a carrier of 4HNE adducts.

Changes in cardiopulmonary reserve and peripheral arterial function concomitantly with subclinical inflammation and oxidative stress in patients with heart failure with preserved ejection fraction.

Background. Changes in cardiopulmonary reserve and biomarkers related to wall stress, inflammation, and oxidative stress concomitantly with the evaluation of peripheral arterial blood flow have not been investigated in patients with heart failure with preserved ejection fraction (HFpEF) compared with healthy subjects (CTL). Methods and Results. Eighteen HFpEF patients and 14 CTL were recruited. Plasma levels of inflammatory and oxidative stress biomarkers were measured at rest. Brain natriuretic peptide (BNP) was measured at rest and peak exercise. Cardiopulmonary reserve was assessed using an exercise protocol with gas exchange analyses. Peripheral arterial blood flow was determined by strain gauge plethysmography. Peak VO2 (12.0 ± 0.4 versus 19.1 ± 1.1 mL/min/kg, P < 0.001) and oxygen uptake efficiency slope (1.55 ± 0.12 versus 2.06 ± 0.14, P < 0.05) were significantly decreased in HFpEF patients compared with CTL. BNP at rest and following stress, C-reactive-protein, interleukin-6, and TBARS were significantly elevated in HFpEF. Both basal and posthyperemic arterial blood flow were not significantly different between the HFpEF patients and CTL. Conclusions. HFpEF exhibits a severe reduction in cardiopulmonary reserve and oxygen uptake efficiency concomitantly with an elevation in a broad spectrum of biomarkers confirming an inflammatory and prooxidative status in patients with HFpEF.

Heart failure with anemia: novel findings on the roles of renal disease, interleukins, and specific left ventricular remodeling processes.

BACKGROUND: Anemia is a highly prevalent and strong independent prognostic marker in heart failure (HF), yet this association is not completely understood. Whether anemia is simply a marker of disease severity and concomitant chronic kidney disease or represents the activation of other detrimental pathways remains uncertain. We sought to determine which pathophysiological pathways are exacerbated in patients with HF, reduced ejection fraction (HFrEF) and anemia in comparison with those without anemia. METHODS AND RESULTS: In a prospective study involving 151 patients, selected biomarkers were analyzed, each representing proposed contributive mechanisms in the pathophysiology of anemia in HF. We compared clinical, echocardiographic, and circulating biomarkers profiles among patients with HFrEF and anemia (group 1), HFrEF without anemia (group 2), and chronic kidney disease with preserved EF, without established HF (chronic kidney disease control group 3). We demonstrate here that many processes other than those related to chronic kidney disease are involved in the anemia-HF relationship. These are linked to the pathophysiological mechanisms pertaining to left ventricular systolic dysfunction and remodeling, systemic inflammation and volume overload. We found that levels of interleukin-6 and interleukin-10, specific markers of cardiac remodeling (procollagen type III N-terminal peptide, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase 1, left atrial volume), myocardial stretch (NT-proBNP [N-terminal probrain natriuretic peptide]), and myocyte death (troponin T) are related to anemia in HFrEF. CONCLUSIONS: Anemia is strongly associated not only with markers of more advanced and active heart disease but also with the level of renal dysfunction in HFrEF. Increased myocardial remodeling, inflammation, and volume overload are the hallmarks of patients with anemia and HF. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00834691.

Differences in biomarkers in patients with heart failure with a reduced vs a preserved left ventricular ejection fraction.

BACKGROUND: The differences in concentrations of biomarkers between heart failure (HF) patients with a preserved left ventricular ejection fraction (LVEF), or HF-PEF, and patients with HF with reduced LVEF (HF-REF) have yet to be defined. The objectives of this study were to compare the concentrations and correlation of biomarkers of inflammation, extracellular matrix (ECM) turnover and neurohormonal activation between these populations. METHODS: We performed a cross-sectional study of 29 subjects with symptomatic HF-REF (LVEF = 25.6 ± 5.1%) and 29 subjects with symptomatic HF-PEF (LVEF = 63.3 ± 5.3%). Concentrations of N-terminal proB-type natriuretic peptide (NT-proBNP), high sensitivity C-reactive protein (hsCRP), procollagen type III amino-terminal peptide (PIIINP), matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of MMP (TIMP)-1 were measured. RESULTS: Although NT-proBNP and PIIINP concentrations were higher in patients with HF-REF compared with patients with HF-PEF (both P < 0.05), the only significant difference between the groups remaining after adjusting for possible confounding variables was NT-proBNP (P = 0.02). In patients with HF-REF, NT-proBNP correlated with PIIINP (P < 0.05), TIMP-1 (P < 0.05), and MMP-2 (P = 0.002), while PIIINP correlated with TIMP-1 (P < 0.05) and MMP-2 (P < 0.0001). In patients with a HF-PEF, only high sensitivity C-reactive protein correlated significantly with MMP-2 (P = 0.002). CONCLUSIONS: Patients with HF-REF or HF-PEF presenting similar symptoms and functional limitations exhibit similar concentrations of biomarkers of ECM and inflammation. However, patients with HF-REF exhibit significantly higher NT-proBNP concentrations than patients with HF-PEF. The differences in the correlations observed between the biomarkers between these 2 populations suggest some heterogeneity and differences in the mechanisms related to the release or clearance of biomarkers in HF-REF vs HF-PEF.