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Hypertensive heart disease (HHD) can no longer be considered as the beneficial adaptive result of the hypertrophy of cardiomyocytes in response to pressure overload leading to the development of left ventricular hypertrophy. The current evidence indicates that in patients with HHD, pathological lesions in the myocardium lead to maladaptive structural remodeling and subsequent alterations in cardiac function, electrical activity, and perfusion, all contributing to poor outcomes. Diffuse myocardial interstitial fibrosis is probably the most critically involved lesion in these disorders. Therefore, in this review, we will focus on the histological characteristics, the mechanisms, and the clinical consequences of myocardial interstitial fibrosis in patients with HHD. In addition, we will consider the most useful tools for the noninvasive diagnosis of myocardial interstitial fibrosis in patients with HHD, as well as the most effective available therapeutic strategies to prevent its development or facilitate its regression in this patient population. Finally, we will issue a call to action for the need for more fundamental and clinical research on myocardial interstitial fibrosis in HHD. [ABSTRACT FROM AUTHOR]

• Physical exercise training favors large and positive changes in exerkines concentration in adults living with type 2 diabetes mellitus. • Changes in exerkines are related to improvements in clinical metabolic parameters (e.g., glycated hemoglobin, waist circumference, body mass). • We identified an optimal dosage for exercise prescription in this clinical population. This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise prescription. A systematic search for relevant studies was performed in 3 databases. Randomized controlled trials investigating the effects of exercise training on at least one of the following exerkines were included: adiponectin, apelin, brain-derived neurotrophic factor, fetuin-A, fibroblast growth factor-21, follistatin, ghrelin, interleukin (IL)-6, IL-8, IL-10, IL-15, IL-18, leptin, myostatin, omentin, resistin, retinol-binding protein 4, tumor necrosis factor-α, and visfatin. Forty randomized controlled trials were selected for data extraction (n = 2160). Exercise training induces changes in adiponectin, fetuin-A, fibroblast growth factor-21, IL-6, IL-10, leptin, resistin, and tumor necrosis factor-α levels but has no significant effects on apelin, IL-18, and ghrelin compared to controls. Physical exercise training favored large and positive changes in pooled exerkines (i.e., an overall effect size calculated from several exerkines) (Hedge's g = 1.02, 95% confidence interval (95%CI): 0.76−1.28), which in turn were related to changes in glycated hemoglobin (mean difference (MD) = −0.81%, 95%CI: −0.95% to −0.67%), fasting glucose (MD = −23.43 mg/dL, 95%CI: −30.07 mg/dL to −16.80 mg/dL), waist circumference (MD = −3.04 cm, 95%CI: −4.02 cm to −2.07 cm), and body mass (MD = −1.93 kg, 95%CI: −2.00 kg to −1.86 kg). Slightly stronger effects were observed with aerobic, resistance, or high-intensity interval protocols at moderate- to vigorous-intensity and with programs longer than 24 weeks that comprise at least 3 sessions per week and more than 60 min per session. Exercise training represents an anti-inflammatory therapy and metabolism-improving strategy with minimal side effects for patients with type 2 diabetes mellitus. [Display omitted] [ABSTRACT FROM AUTHOR]

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Copyright of Nefrologia is the property of Revista Nefrologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Supplemental Digital Content is available in the text. [ABSTRACT FROM AUTHOR]

The plasma levels of long noncoding RNA LIPCAR are elevated in heart failure (HF) patients with reduced ejection fraction and associated with left ventricular remodeling and poor outcomes. We studied whether the presence of chronic kidney disease (CKD), as defined by an estimated glomerular filtration rate value <60mL/(min·1.73m2) modified the associations of plasma LIPCAR with left ventricular remodeling and outcomes in HF patients. Two hundred and thirty-four patients (mean age 74 [9.14] years, 50% male) were enrolled and followed for 4.73 (0.24-7.25) years. Plasma LIPCAR was detected by real-time quantitative polymerase chain reaction. LIPCAR was increased ( P=0.005) in patients compared with 17 age- and sex-matched controls, directly correlated with age ( P=0.001) and with the maximal early transmitral flow velocity to the mean peak early diastolic velocity of the mitral annulus displacement ratio ( P=0.001) and inversely correlated with estimated glomerular filtration rate ( P<0.001). LIPCAR was associated with hospitalization for HF, cardiovascular death, and a composite of hospitalization for HF or cardiovascular death ( P≤0.010), these associations being dependent of estimated glomerular filtration rate. The interactions between estimated glomerular filtration rate and LIPCAR with respect to these outcomes were statistically significant or of borderline significance ( P≤0.060). LIPCAR was increased in CKD patients compared with non-CKD patients ( P=0.021). LIPCAR was independently associated with hospitalization for HF ( P≤0.039) only in non-CKD patients, but its addition to traditional risk factors did not improve risk prediction in these patients. In conclusion, plasma LIPCAR prognosticates outcomes in elderly HF patients without CKD. Thus, there is an effect modification of CKD on the association of circulating LIPCAR with outcomes in HF patients. [ABSTRACT FROM AUTHOR]

Myocardial fibrosis is a main contributor to the development of heart failure (HF). CT-1 (cardiotrophin-1) and Gal-3 (galectin-3) are increased in HF and associated with myocardial fibrosis. The aim of this study is to analyze whether CT-1 regulates Gal-3. Proteomic analysis revealed that Gal-3 was upregulated by CT-1 in human cardiac fibroblasts in parallel with other profibrotic and proinflammatory markers. CT-1 upregulation of Gal-3 was mediated by ERK (extracellular signal-regulated kinase) 1/2 and Stat-3 (signal transducer and activator of transcription 3) pathways. Male Wistar rats and B6CBAF1 mice treated with CT-1 (20 µg/kg per day) presented higher cardiac Gal-3 levels and myocardial fibrosis. In CT-1-treated rats, direct correlations were found between cardiac CT-1 and Gal-3 levels, as well as between Gal-3 and perivascular fibrosis. Gal-3 genetic disruption in human cardiac fibroblasts and pharmacological Gal-3 inhibition in mice prevented the profibrotic and proinflammatory effects of CT-1. Dahl salt-sensitive hypertensive rats with diastolic dysfunction showed increased cardiac CT-1 and Gal-3 expression together with cardiac fibrosis and inflammation. CT-1 and Gal-3 directly correlated with myocardial fibrosis. In HF patients, myocardial and plasma CT-1 and Gal-3 were increased and directly correlated. In addition, HF patients with high CT-1 and Gal-3 plasma levels presented an increased risk of cardiovascular death. Our data suggest that CT-1 upregulates Gal-3 which, in turn, mediates the proinflammatory and profibrotic myocardial effects of CT-1. The elevation of both molecules in HF patients identifies a subgroup of patients with a higher risk of cardiovascular mortality. The CT-1/Gal-3 axis emerges as a candidate therapeutic target and a potential prognostic biomarker in HF. [ABSTRACT FROM AUTHOR]

Pressure overload causes cardiac fibroblast activation and transdifferentiation, leading to increased interstitial fibrosis formation and subsequently myocardial stiffness, diastolic and systolic dysfunction, and eventually heart failure. A better understanding of the molecular mechanisms underlying pressure overload-induced cardiac remodeling and fibrosis will have implications for heart failure treatment strategies. The microRNA (miRNA)-221/222 family, consisting of miR-221-3p and miR-222-3p, is differentially regulated in mouse and human cardiac pathology and inversely associated with kidney and liver fibrosis. We investigated the role of this miRNA family during pressure overload-induced cardiac remodeling. In myocardial biopsies of patients with severe fibrosis and dilated cardiomyopathy or aortic stenosis, we found significantly lower miRNA-221/222 levels as compared to matched patients with nonsevere fibrosis. In addition, miRNA-221/222 levels in aortic stenosis patients correlated negatively with the extent of myocardial fibrosis and with left ventricular stiffness. Inhibition of both miRNAs during AngII (angiotensin II)-mediated pressure overload in mice led to increased fibrosis and aggravated left ventricular dilation and dysfunction. In rat cardiac fibroblasts, inhibition of miRNA-221/222 derepressed TGF-β (transforming growth factor-β)-mediated profibrotic SMAD2 (mothers against decapentaplegic homolog 2) signaling and downstream gene expression, whereas overexpression of both miRNAs blunted TGF-β-induced profibrotic signaling. We found that the miRNA-221/222 family may target several genes involved in TGF-β signaling, including JNK1 (c-Jun N-terminal kinase 1), TGF-β receptor 1 and TGF-β receptor 2, and ETS-1 (ETS proto-oncogene 1). Our findings show that heart failure-associated downregulation of the miRNA-221/222 family enables profibrotic signaling in the pressure-overloaded heart. [ABSTRACT FROM AUTHOR]

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: We sought to identify protein biomarkers of new-onset heart failure (HF) in 3 independent cohorts (HOMAGE cohort [Heart Omics and Ageing], ARIC study [Atherosclerosis Risk in Communities], and FHS [Framingham Heart Study]) and assess if and to what extent they improve HF risk prediction compared to clinical risk factors alone. Methods: A nested case-control design was used with cases (incident HF) and controls (without HF) matched on age and sex within each cohort. Plasma concentrations of 276 proteins were measured at baseline in ARIC (250 cases/250 controls), FHS (191/191), and HOMAGE cohort (562/871). Results: In single protein analysis, after adjusting for matching variables and clinical risk factors (and correcting for multiple testing), 62 proteins were associated with incident HF in ARIC, 16 in FHS, and 116 in HOMAGE cohort. Proteins associated with incident HF in all cohorts were BNP (brain natriuretic peptide), NT-proBNP (N-terminal pro-B-type natriuretic peptide), eukaryotic translation initiation factor 4E-BP1 (4E-binding protein 1), hepatocyte growth factor (HGF), Gal-9 (galectin-9), TGF-alpha (transforming growth factor alpha), THBS2 (thrombospondin-2), and U-PAR (urokinase plasminogen activator surface receptor). The increment in C -index for incident HF based on a multiprotein biomarker approach, in addition to clinical risk factors and NT-proBNP, was 11.1% (7.5%–14.7%) in ARIC, 5.9% (2.6%–9.2%) in FHS, and 7.5% (5.4%–9.5%) in HOMAGE cohort, all P <0.001), each of which was a larger increase than that for NT-proBNP on top of clinical risk factors. Complex network analysis revealed a number of overrepresented pathways related to inflammation (eg, tumor necrosis factor and interleukin) and remodeling (eg, extracellular matrix and apoptosis). Conclusions: A multiprotein biomarker approach improves prediction of incident HF when added to natriuretic peptides and clinical risk factors. [ABSTRACT FROM AUTHOR]

Exercise intolerance remains a major unmet medical need in patients with heart failure (HF). Skeletal myopathy is currently considered as the major limiting factor for exercise capacity in HF patients. On the other hand, emerging evidence suggest that physical exercise can decrease morbidity and mortality in HF patients. Therefore, mechanistic insights into skeletal myopathy may uncover critical aspects for therapeutic interventions to improve exercise performance in HF. Emerging data reviewed in this article suggest that the assessment of circulating myokines (molecules synthesized and secreted by skeletal muscle in response to contraction that display autocrine, paracrine and endocrine actions) may provide new insights into the pathophysiology, phenotyping and prognostic stratification of HF-related skeletal myopathy. Further studies are required to determine whether myokines may also serve as biomarkers to personalize the modality and dose of physical training prescribed for patients with HF and exercise intolerance. In addition, the production and secretion of myokines in patients with HF may interact with systemic alterations (e.g., inflammation and metabolic disturbances), frequently present in patients with HF. Furthermore, myokines may exert beneficial or detrimental effects on cardiac structure and function, which may influence adverse cardiac remodelling and clinical outcomes in HF patients. Collectively, these data suggest that a deeper knowledge on myokines regulation and actions may lead to the identification of novel physical exercise-based therapeutic approaches for HF patients. Myokine dysregulation in heart failure patients with skeletal myopathy. The imbalance between detrimental and beneficial myokines may have phenotypic consequences which, in turn, may contribute to facilitate the clinical manifestations of heart failure. On the other hand, personalizing the modality and dose of physical exercise aiming to correct the specific imbalance present in each patient may contribute to improve the clinical manifestations of heart failure. (IL-6, −8, −15 interleukin-6, −8, −15; GDF-11, growth differentiation factor-11; FSTL1, follistatin-like protein 1; BDNF, brain-derived neurotrophic factor; FGF-21, fibroblast growth factor-21). [Display omitted] • Myokines are molecules synthesized and secreted by skeletal muscle in response to physical exercise. • Myokines may provide new insights into some aspects of heart failure-related skeletal myopathy. • Myokines may exert beneficial or detrimental effects on cardiac structure and function in heart failure. • Myokines may be useful as potential biomarkers to personalize physical training in heart failure. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate the association between circulating biomarkers of collagen metabolism and elevated left-sided filling pressures (FPs), as assessed from elevated estimated pulmonary capillary wedge pressure (ePCWP), in hypertensive patients with heart failure with normal ejection fraction. Echocardiography was performed and ePCWP was calculated from the formula ePCWP=1.90+1.24(maximum early transmitral flow velocity in diastole:tissue Doppler early mitral annulus velocity). The biomarkers of collagen synthesis (carboxy-terminal propeptide of procollagen type I) and degradation (matrix metalloproteinase [MMP] 1 and tissue inhibitor of MMP-1 [TIMP-1]) were analyzed by ELISA methods. Seventy-eight patients with normal FPs (ePCWP < or =15 mm Hg) and 78 with elevated FPs (ePCWP >15 mm Hg) were included. Compared with controls, the levels of the 3 biomarkers were increased in the 2 groups of patients. The MMP-1:TIMP-1 ratio, an index of MMP-1 activity, was increased in patients with normal FPs and unchanged in patients with elevated FPs. Patients with elevated FPs exhibited higher TIMP-1 levels and a lower MMP-1:TIMP-1 ratio than patients with normal FPs. ePCWP was independently associated with TIMP-1 (r=0.349; P<0.001) and the MMP-1:TIMP-1 ratio (r=-0.240; P<0.01) in all of the patients. Receiver operating characteristic curves showed that a cutoff value of TIMP-1 of 1557 ng/mL provided 64% sensitivity and 67% specificity for predicting elevated FPs with a relative risk of 3.71 (95% CI: 1.91 to 7.22). These findings suggest that, in hypertensive patients with heart failure with normal ejection fraction and elevated FPs, collagen synthesis predominates over degradation because of a relative excess of TIMP-1. This imbalance can facilitate myocardial fibrosis, which, in turn, may contribute to the elevation of FPs in these patients. [ABSTRACT FROM AUTHOR]

Background: Endotrophin, a collagen type VI-derived peptide, mediates metabolic dysregulation, inflammation, and fibrosis in animal models, but has not been studied in human heart failure (HF). Methods: We examined the association between circulating endotrophin and outcomes in participants suffering from HF with preserved ejection fraction (HFpEF) enrolled in the TOPCAT trial (n=205). Associations were validated in a participant-level meta-analysis (n=810) that included participants with HFpEF from the PHFS study (United States; n=174), PEOPLE cohort (New Zealand; n=168), a randomized trial of vasodilator therapy (United States; n=45), a cohort from Donostia University Hospital and University of Navarra (Spain; n=171), and the TRAINING-HF trial (Spain; n=47). We also assessed associations in HF with reduced ejection fraction in PHFS (n=1,642). Results: Plasma endotrophin levels at baseline were associated with risk of future death (standardized hazard ratio [HR]=1.74; 95% confidence interval [CI]=1.36-2.24; P<0.001) and death or HF-related hospital admission (DHFA; standardized HR=2.11; 95% CI=1.67-2.67; P<0.001) in TOPCAT. Endotrophin improved reclassification and discrimination for these outcomes beyond the MAGGIC risk score and NT-proBNP (N-terminal pro b-type natriuretic peptide). Findings were confirmed in the participant-level meta-analysis. In participants with HF with reduced ejection fraction in PHFS, endotrophin levels were associated with death (standardized HR=1.82; 95% CI=1.66-2.00; P<0.001) and DHFA (standardized HR=1.40; 95% CI=1.31-1.50; P<0.001), but the strength of the latter association was substantially lower than for the MAGGIC risk score (standardized HR=1.93; 95% CI=1.76-2.12) and BNP (standardized HR=1.78; 95% CI=1.66-1.92). Conclusions: Circulating endotrophin levels are independently associated with future poor outcomes in patients with HF, particularly in HFpEF. (Funded by Bristol Myers Squibb; Instituto de Salud Carlos III [Spain] and European Regional Development Fund; European Commission CRUCIAL project; and the U.S. National Institutes of Health National Heart, Lung, and Blood Institute.) [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether torasemide modifies collagen cross-linking in the failing human heart. We analyzed the degree of cross-linking and the expression of the enzyme lysyl oxidase, which regulates cross-linking, in the myocardium of patients with chronic heart failure at baseline and after 8 months of treatment with either torasemide or furosemide in addition to their standard heart failure therapy. Whereas lysyl oxidase protein expression was very scarce in normal hearts, it was highly expressed in failing hearts. Cross-linking was increased (P<0.001) in heart failure patients compared with normal hearts. These 2 parameters decreased (P=0.021 and P=0.034) in torasemide-treated patients and remained unchanged in furosemide-treated patients. In addition, more (P=0.009) patients showed normalization of left ventricular chamber stiffness in the torasemide subgroup than in the furosemide subgroup after treatment. Lysyl oxidase expression correlated with cross-linking (r=0.661; P<0.001), and cross-linking correlated with left ventricular chamber stiffness (r=0.452; P=0.002) in all patients. These findings show for the first time that lysyl oxidase overexpression is associated with enhanced collagen cross-linking in the failing human heart. In addition, we report that the ability of torasemide to correct both lysyl oxidase overexpression and enhanced collagen cross-linking results in normalization of left ventricular chamber stiffness in patients with heart failure. Lysyl oxidase may thus represent a target for reduction of stiff collagen and improvement of left ventricular mechanical properties in heart failure patients. [ABSTRACT FROM AUTHOR]

Inappropriate left ventricular mass is present when the value of left ventricular mass exceeds individual needs to compensate hemodynamic load imposed by increased blood pressure. The goal of this study was to investigate whether plasma concentration of cardiotrophin-1, a cytokine that induces exaggerated hypertrophy in cardiomyocytes with hypertensive phenotype, is related to inappropriate left ventricular mass in patients with essential hypertension. The study was performed in 118 patients with never-treated hypertension and without prevalent cardiac disease. The left ventricular mass prediction from stroke work (systolic blood pressurexDoppler stroke volume), sex, and height (in meters(2.7)) was derived. An observed left ventricular mass/predicted left ventricular mass value >128% defined inappropriate left ventricular mass. Plasma cardiotrophin-1 was measured by an enzyme-linked immunosorbent assay. The studies were repeated in a group of 45 patients after 1 year of antihypertensive treatment. At baseline 67 and 51 patients presented with appropriate and inappropriate left ventricular mass, respectively. Plasma cardiotrophin-1 was higher (P<0.001) in patients with inappropriate mass than in patients with appropriate mass and normotensive controls. A direct correlation was found between cardiotrophin-1 and observed left ventricular mass/predicted left ventricular mass ratio (r=0.330, P<0.001) in all hypertensive patients. After treatment, plasma cardiotrophin-1 decreased and increased in patients in which inappropriate left ventricular mass regressed and persisted, respectively, despite a similar reduction of blood pressure in the 2 subgroups of patients. Albeit descriptive in nature, these results suggest the hypothesis that an excess of cardiotrophin-1 may contribute to inappropriate left ventricular growth in hypertensive patients. [ABSTRACT FROM AUTHOR]

Cardiotrophin-1 has been shown to be profibrogenic in experimental models. The aim of this study was to analyze whether cardiotrophin-1 is associated with left ventricular end-diastolic stress and myocardial fibrosis in hypertensive patients with heart failure. Endomyocardial biopsies from patients (n=31) and necropsies from 7 control subjects were studied. Myocardial cardiotrophin-1 protein and mRNA and the fraction of myocardial volume occupied by collagen were increased in patients compared with controls (P<0.001). Cardiotrophin-1 overexpression in patients was localized in cardiomyocytes. Cardiotrophin-1 protein was correlated with collagen type I and III mRNAs (r=0.653, P<0.001; r=0.541, P<0.01) and proteins (r=0.588, P<0.001; r=0.556, P<0.005) in all subjects and with left ventricular end-diastolic wall stress (r=0.450; P<0.05) in patients. Plasma cardiotrophin-1 and N-terminal pro-brain natriuretic peptide and serum biomarkers of myocardial fibrosis (carboxy-terminal propeptide of procollagen type I and amino-terminal propeptide of procollagen type III) were increased (P<0.001) in patients compared with controls. Plasma cardiotrophin-1 was correlated with N-terminal pro-brain natriuretic peptide (r=0.386; P<0.005), carboxy-terminal propeptide of procollagen type I (r=0.550; P<0.001), and amino-terminal propeptide of procollagen type III (r=0.267; P<0.05) in all subjects. In vitro, cardiotrophin-1 stimulated the differentiation of human cardiac fibroblast to myofibroblasts (P<0.05) and the expression of procollagen type I (P<0.05) and III (P<0.01) mRNAs. These findings show that an excess of cardiotrophin-1 is associated with increased collagen in the myocardium of hypertensive patients with heart failure. It is proposed that exaggerated cardiomyocyte production of cardiotrophin-1 in response to increased left ventricular end-diastolic stress may contribute to fibrosis through stimulation of fibroblasts in heart failure of hypertensive origin. [ABSTRACT FROM AUTHOR]

Obesity and diabetes mellitus are important metabolic risk factors and frequent comorbidities in heart failure with preserved ejection fraction. They contribute to myocardial diastolic dysfunction (DD) through collagen deposition or titin modification. The relative importance for myocardial DD of collagen deposition and titin modification was investigated in obese, diabetic ZSF1 rats after heart failure with preserved ejection fraction development at 20 weeks.Four groups of rats (Wistar-Kyoto, n=11; lean ZSF1, n=11; obese ZSF1, n=11, and obese ZSF1 with high-fat diet, n=11) were followed up for 20 weeks with repeat metabolic, renal, and echocardiographic evaluations and hemodynamically assessed at euthanization. Myocardial collagen, collagen cross-linking, titin isoforms, and phosphorylation were also determined. Resting tension (Fpassive)-sarcomere length relations were obtained in small muscle strips before and after KCl-KI treatment, which unanchors titin and allows contributions of titin and extracellular matrix to Fpassive to be discerned. At 20 weeks, the lean ZSF1 group was hypertensive, whereas both obese ZSF1 groups were hypertensive and diabetic. Only the obese ZSF1 groups had developed heart failure with preserved ejection fraction, which was evident from increased lung weight, preserved left ventricular ejection fraction, and left ventricular DD. The underlying myocardial DD was obvious from high muscle strip stiffness, which was largely (±80%) attributable to titin hypophosphorylation. The latter occurred specifically at the S3991 site of the elastic N2Bus segment and at the S12884 site of the PEVK segment.Obese ZSF1 rats developed heart failure with preserved ejection fraction during a 20-week time span. Titin hypophosphorylation importantly contributed to the underlying myocardial DD. [ABSTRACT FROM AUTHOR]

Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy (HCM) and a potential substrate for arrhythmias and heart failure. Sarcomere mutations seem to induce profibrotic changes before left ventricular hypertrophy (LVH) develops. To further evaluate these processes, we used cardiac magnetic resonance with T1 measurements on a genotyped HCM population to quantify myocardial extracellular volume (ECV).Sarcomere mutation carriers with LVH (G+/LVH+, n=37) and without LVH (G+/LVH-, n=29), patients with HCM without mutations (sarcomere-negative HCM, n=11), and healthy controls (n=11) underwent contrast cardiac magnetic resonance, measuring T1 times pre- and postgadolinium infusion. Concurrent echocardiography and serum biomarkers of collagen synthesis, hemodynamic stress, and myocardial injury were also available in a subset. Compared with controls, ECV was increased in patients with overt HCM, as well as G+/LVH- mutation carriers (ECV=0.36±0.01, 0.33±0.01, 0.27±0.01 in G+/LVH+, G+/LVH-, controls, respectively; P0.001 for all comparisons). ECV correlated with N-terminal probrain natriuretic peptide levels (r=0.58; P<0.001) and global E’ velocity (r=-0.48; P<0.001). Late gadolinium enhancement was present in >60% of overt patients with HCM but absent from G+/LVH- subjects. Both ECV and late gadolinium enhancement were more extensive in sarcomeric HCM than sarcomere-negative HCM.Myocardial ECV is increased in HCM sarcomere mutation carriers even in the absence of LVH. These data provide additional support that fibrotic remodeling is triggered early in disease pathogenesis. Quantifying ECV may help characterize the development of myocardial fibrosis in HCM and ultimately assist in developing novel disease-modifying therapy, targeting interstitial fibrosis. [ABSTRACT FROM AUTHOR]

We investigated whether the quality of myocardial collagen associates with elevated left-sided filling pressures in 38 hypertensive patients with stage C chronic heart failure. Filling pressures were assessed invasively measuring pulmonary capillary wedge pressure. Left ventricular chamber stiffness constant was calculated from the deceleration time of the early mitral filling wave. The fraction of myocardial volume occupied by total collagen tissue and collagen type I fibers was assessed histomorphologically. The degree of collagen cross-linking (CCL), which determines the formation of insoluble stiff collagen, was assessed by colorimetric and enzymatic procedures. The expression of lysyl oxidase (LOX), which regulates CCL, was assessed by Western blot. Compared with patients with normal pulmonary capillary wedge pressure (≤12 mm Hg; n=16), patients with elevated pulmonary capillary wedge pressure (>12 mm Hg; n=22) exhibited increases of left ventricular chamber stiffness constant, fraction of myocardial volume occupied by total collagen tissue, fraction of myocardial volume occupied by collagen type I fibers, CCL, insoluble stiff collagen, and LOX. Pulmonary capillary wedge pressure was correlated with left ventricular chamber stiffness constant (r=0.639; P<0.001), insoluble stiff collagen (r=0.474; P<0.005), CCL (r=0.625; P<0.001), and LOX (r=0.410; P<0.05) in all of the patients but not with fraction of myocardial volume occupied by total collagen tissue or fraction of myocardial volume occupied by collagen type I fibers. In addition, CCL was correlated with insoluble stiff collagen (r=0.612; P<0.005), LOX (r=0.538; P<0.01), left ventricular chamber stiffness constant (r=0.535; P<0.005), peak filling rate (r=-0.343; P<0.05), ejection fraction (r=-0.430; P<0.01), and amino-terminal propeptide of brain natriuretic peptide (r=0.421; P<0.05) in all of the patients. These associations were independent of confounding factors. These findings indicate that, in hypertensive patients with stage C heart failure, it is only the quality of collagen (ie, degree of cross-linking) that associates with elevated filling pressures. It is suggested that LOX-mediated excessive CCL facilitates the increase in left ventricular stiffness with the resulting elevation of filling pressures in these patients. [ABSTRACT FROM AUTHOR]

This article discusses a study which investigated the association between the quality of myocardial collagen and elevated left-sided filling pressures in hypertensive patients with stage C chronic heart failure. Researchers assessed filling pressures and calculated left ventricular chamber stiffness constant from the deceleration time of the early mitral filling wave. They then assessed the fraction of myocardial volume occupied by total collagen tissue and collagen type I fibers.

The article presents a study that investigates the prevalence of left ventricular diastolic dysfunction in the community. The study was administered through a randomly selected population of men and women wherein their diastolic peak velocities and blood flow in pulmonary veins were assessed using Doppler imaging. The study reveals that 27.3% of the population experienced LV diastolic dysfunction due to the complications in genes and environmental factors.

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)