Objectives This study sought to determine the prognostic value of B-type natriuretic peptide (BNP) in patients with heart failure with preserved ejection fraction (HFPEF), in comparison to data in HF ...patients with reduced left ventricular (LV) EF (≤40%). Background Management of patients with HFPEF is difficult. BNP is a useful biomarker in patients with reduced LVEF, but data in HFPEF are scarce. Methods In this study, 615 patients with mild to moderate HF (mean age 70 years, LVEF 33%) were followed for 18 months. BNP concentrations were measured at baseline and were related to the primary outcome, that is, a composite of all-cause mortality and HF hospitalization, and to mortality alone. The population was divided in quintiles, according to LVEF, and patients with reduced LVEF were compared with those with HFPEF. Results There were 257 patients (42%) who had a primary endpoint and 171 (28%) who died. BNP levels were significantly higher in patients with reduced LVEF than in those with HFPEF (p < 0.001). BNP was a strong predictor of outcome, but LVEF was not. Importantly, if similar levels of BNP were compared across the whole spectrum of LVEF, and for different cutoff levels of LVEF, the associated risk of adverse outcome was similar in HFPEF patients as in those with reduced LVEF. Conclusions BNP levels are lower in patients with HFPEF than in patients with HF with reduced LVEF, but for a given BNP level, the prognosis in patients with HFPEF is as poor as in those with reduced LVEF.
Abstract Objectives The present study investigated whether systemic, low-grade inflammation of metabolic risk contributed to diastolic left ventricular (LV) dysfunction and heart failure with ...preseved ejection fraction (HFpEF) through coronary microvascular endothelial activation, which alters paracrine signalling to cardiomyocytes and predisposes them to hypertrophy and high diastolic stiffness. Background Metabolic risk is associated with diastolic LV dysfunction and HFpEF. Methods We explored inflammatory endothelial activation and its effects on oxidative stress, nitric oxide (NO) bioavailability, and cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signalling in myocardial biopsies of HFpEF patients and validated our findings by comparing obese Zucker diabetic fatty/Spontaneously hypertensive heart failure F1 hybrid (ZSF1)-HFpEF rats to ZSF1-Control (Ctrl) rats. Results In myocardium of HFpEF patients and ZSF1-HFpEF rats, we observed the following: 1) E-selectin and intercellular adhesion molecule-1 expression levels were upregulated; 2) NADPH oxidase 2 expression was raised in macrophages and endothelial cells but not in cardiomyocytes; and 3) uncoupling of endothelial nitric oxide synthase, which was associated with reduced myocardial nitrite/nitrate concentration, cGMP content, and PKG activity. Conclusions HFpEF is associated with coronary microvascular endothelial activation and oxidative stress. These lead to a reduction of NO-dependent signalling from endothelial cells to cardiomyocytes, which can contribute to the high cardiomyocyte stiffness and hypertrophy observed in HFpEF.
Abstract Background Diagnosing lymphocytic myocarditis (LM) is challenging because of the large variation in clinical presentation and the limitations inherent in current diagnostic tools. The ...objective of this study was to analyze infiltration of inflammatory cells in quadriceps skeletal muscle of LM patients and investigate the potential diagnostic value of assaying infiltrating inflammatory cells. Methods Quadriceps muscle tissue, obtained at autopsy from control patients (n = 9) and LM patients (n = 21), was analyzed using immunohistochemistry for infiltration of lymphocytes (CD45), macrophages (CD68), neutrophilic granulocytes (myeloperoxidase), and several lymphocyte subtypes (CD3, CD4, CD8, CD20) and using polymerase chain reaction for a panel of myocarditis-associated viruses. Additionally, quadriceps muscle from mice with acute coxsackievirus B3-induced myocarditis and control mice was analyzed for presence of lymphocytes and virus. Results In quadriceps muscle of LM patients the number of infiltrating lymphocytes were significantly increased and LM was diagnosed with specificity of 100% and sensitivity of 71%. Parvovirus B19 was the primary virus found in our patient groups, found in quadriceps tissue of 3 LM patients (although it was also found in 1 control patient). In the mice, enteroviral RNA was present in the quadriceps muscle, although enteroviral capsid proteins and lymphocyte infiltration were found primarily in the adipose tissue within and directly adjacent to the myocyte tissue, rather than in the myocyte tissue itself. Conclusions LM is associated with lymphocyte infiltration and viral presence in quadriceps muscle. This indicates that skeletal muscle biopsy/lymphocyte quantification might be a potential diagnostic tool for LM patients.
Left ventricular (LV) filling results from diastolic suction of the left ventricle and passive left atrial (LA) emptying at early diastole and LA contraction at end-diastole. Effects of aging on LA ...and LV geometric characteristics and function and its consequences for LV filling are incompletely understood. Insight into these effects may increase the understanding of diastolic function. Cardiac magnetic resonance imaging was used to study effects of aging on left atrioventricular coupling and LV filling. Forty healthy volunteers underwent cardiac magnetic resonance imaging and were subdivided into 2 age groups of 20 to 40 (younger group) and 40 to 65 years (older group). For the older group, LA volumes were larger (p <0.05) and LV volumes, including stroke volumes, were smaller (p <0.05), whereas ejection fraction remained constant. LA/LV volume ratios were larger (0.27 ± 0.06 vs 0.19 ± 0.03; p <0.001) and correlated with LV mass–volume ratio (r = 0.42, p <0.01). The older group also had lower LA passive emptying (15 ± 3.0 vs 19 ± 4.8 ml/m2 ; p <0.05) and higher LA active emptying volumes (13 ± 3.1 vs 11 ± 3.9 ml/m2 ; p <0.05). For both groups, conduit volume contributed most to LV filling, but was lower in the older group (21 ± 5.1 vs 27 ± 9.0 ml; p <0.05). In conclusion, changes in LA volume and function were age dependent and related to changes in LV mass–volume ratio. Conduit volume contributed most to LV filling and decreased with age, suggesting it to be an indicator of diastolic function.
First among the proposed mechanisms for exercise intolerance in HFpEF is high LV diastolic stiffness (5), which elicits a prompt and large increase in PCWP (7), even at low-level exercise, as ...illustrated in the study by Borlaug et al. At the very low cGMP levels observed in HFpEF myocardium, the cardiomyocytes could well be operating on the ascending limb of the dose-response curve with a concomitant LV systolic shortening deficit and the large increase in LVSW during exercise after nitrite infusion could be consistent with increased myocardial cGMP eliciting a move up the ascending limb.
Over the past decade, myocardial structure, cardiomyocyte function, and intramyocardial signaling were shown to be specifically altered in heart failure with preserved ejection fraction (HFPEF). A ...new paradigm for HFPEF development is therefore proposed, which identifies a systemic proinflammatory state induced by comorbidities as the cause of myocardial structural and functional alterations. The new paradigm presumes the following sequence of events in HFPEF: 1) a high prevalence of comorbidities such as overweight/obesity, diabetes mellitus, chronic obstructive pulmonary disease, and salt-sensitive hypertension induce a systemic proinflammatory state; 2) a systemic proinflammatory state causes coronary microvascular endothelial inflammation; 3) coronary microvascular endothelial inflammation reduces nitric oxide bioavailability, cyclic guanosine monophosphate content, and protein kinase G (PKG) activity in adjacent cardiomyocytes; 4) low PKG activity favors hypertrophy development and increases resting tension because of hypophosphorylation of titin; and 5) both stiff cardiomyocytes and interstitial fibrosis contribute to high diastolic left ventricular (LV) stiffness and heart failure development. The new HFPEF paradigm shifts emphasis from LV afterload excess to coronary microvascular inflammation. This shift is supported by a favorable Laplace relationship in concentric LV hypertrophy and by all cardiac chambers showing similar remodeling and dysfunction. Myocardial remodeling in HFPEF differs from heart failure with reduced ejection fraction, in which remodeling is driven by loss of cardiomyocytes. The new HFPEF paradigm proposes comorbidities, plasma markers of inflammation, or vascular hyperemic responses to be included in diagnostic algorithms and aims at restoring myocardial PKG activity.
Left Ventricular Torsion Rüssel, Iris K., MSc; Götte, Marco J.W., MD, PhD; Bronzwaer, Jean G., MD, PhD ...
JACC. Cardiovascular imaging,
05/2009, Letnik:
2, Številka:
5
Journal Article
Recenzirano
During left ventricular (LV) torsion, the base rotates in an overall clockwise direction and the apex rotates in a counterclockwise direction when viewed from apex to base. LV torsion is followed by ...rapid untwisting, which contributes to ventricular filling. Because LV torsion is directly related to fiber orientation, it might depict subclinical abnormalities in heart function. Recently, ultrasound speckle tracking was introduced for quantification of LV torsion. This fast, widely available technique may contribute to a more rapid introduction of LV torsion as a clinical tool for detection of myocardial dysfunction. However, knowledge of the exact function and structure of the heart is fundamental for understanding the value of LV torsion. LV torsion has been investigated with different measurement methods during the past 2 decades, using cardiac magnetic resonance as the gold standard. The results obtained over the years are helpful for developing a standardized method to quantify LV torsion and have facilitated the interpretation and value of LV torsion before it can be used as a clinical tool.
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