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Abstract Background Diabetes mellitus (DM) has reached epidemic proportions and is an important risk factor for heart failure (HF). Left ventricular diastolic dysfunction (LVDD) is recognized as the earliest manifestation of DM-induced LV dysfunction, but its pathophysiology remains incompletely understood. We sought to evaluate the relationship between proinflammatory cytokine levels (TNF-alpha, IL-6) and tissue Doppler derived indices of LVDD in patients with stable coronary artery disease. Methods We enrolled 41 consecutive patients (mean age 65+/-10 years) submitted for coronary angiography. Echocardiographic assessment was performed in all patients. Pulsed tissue Doppler imaging was performed at the mitral annulus and was characterized by the diastolic early relaxation velocity Em. Conventional transmitral flow was measured with pw-doppler. Early (E) transmitral flow velocity was measured. LVDD was defined as E/Em ratio ≥ 15, E/Em 8-14 was classified as borderline. Plasma levels of TNF-alpha and IL-6 were determined in all patients. A standardized oral glucose tolerance test was performed in subjects without diabetes. Results Patients with E/Em ratio ≥ 15, classified as LVDD and those with E/Em ratio 8-14 (classified as borderline) had significantly higher IL-6 (P = 0,001), TNF-alpha (P < 0,001) and NT-pro- BNP (P = 0,001) plasma levels compared to those with normal diastolic function. TNF-alpha and IL-6 levels remains significantly elevated after adjustment for sex, age, left ventricular ejection function, body mass index, coronary heart disease, smoking, hypertension and diabetes mellitus with linear regression analysis. Furthermore, in subjects LVDD or borderline LV diastolic function, 75% had diabetes or IGT, respectively. When subjects without diabetes were excluded, both IL-6 (P = 0,006) and TNF-alpha (P = 0,002) remained significantly elevated in subjects with E/Em ratio ≥ 15. Conclusion This study reveals that increased plasma levels of IL-6 and TNF-alpha were associated with LVDD. These findings suggest a link between low-grade inflammation and the presence of LVDD. An active proinflammatory process may be of importance in the pathogenesis of diastolic dysfunction.

Background: Left ventricular diastolic dysfunction (LVDD) is considered a precursor of diabetic cardiomyopathy, while insulin resistance (IR) is a precursor of type 2 diabetes mellitus (T2DM) and independently predicts heart failure (HF). We assessed whether IR and abnormalities of the glucose metabolism are related to LVDD. Methods: We included 208 patients with normal ejection fraction, 57 (27%) of whom had T2DM before inclusion. In subjects without T2DM, an oral glucose tolerance test (oGTT) was performed. IR was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The lower limit of the top quartile of the HOMA-IR distribution (3.217) was chosen as threshold for IR. LVDD was verified according to current guidelines. Results: IR was diagnosed in 38 (18%) patients without a history of diabetes. The prevalence of LVDD was 92% in subjects with IR vs. 72% in patients without IR (n = 113), respectively (p = 0.013). In the IR group, the early diastolic mitral inflow velocity (E) in relation to the early diastolic tissue Doppler velocity (averaged from the septal and lateral mitral annulus, E'av) ratio (E/E'av) was significantly higher compared to those without IR (9.8 [8.3-11.5] vs. 8.1 [6.6-11.0], p = 0.011). This finding remains significant when patients with IR and concomitant T2DM based on oGTT results were excluded (E/E'av ratio 9.8 [8.2-11.1)] in IR vs. 7.9 [6.5-10.5] in those without both IR and T2DM, p = 0.014). There were significant differences among patients with and without LVDD regarding the HOMA-IR (1.71 [1.04-3.88] vs. 1.09 [0.43-2.2], p = 0.003). The HOMA-IR was independently associated with LVDD on multivariate logistic regression analysis, a 1-unit increase in HOMA-IR value was associated with an odds ratio for prevalent LVDD of 2.1 (95% CI 1.3-3.1, p = 0.001). Furthermore, the E/E'av ratio increases along the glucose metabolism status from normal glucose metabolism (7.6 [6.2-10.1]) to impaired glucose tolerance (8.8 [7.4-11.0]) and T2DM (10.5 [8.1- 13.2]), respectively (p < 0.001). Conclusions: Insulin resistance is independently associated with LVDD in subjects without overt T2DM. Patients with IR and glucose metabolism disorders might represent a target population to prevent the development of HF. Screening programs for glucose metabolism disturbances should address the assessment of diastolic function and probably IR. [ABSTRACT FROM AUTHOR]

Background: Increased muscle mass index of the left ventricle (LVMi) is an independent predictor for the development of symptoms in patients with asymptomatic aortic stenosis (AS). While the onset of clinical symptoms and left ventricular systolic dysfunction determines a poor prognosis, the standard echocardiographic evaluation of LV dysfunction, only based on measurements of the LV ejection fraction (EF), may be insufficient for an early assessment of imminent heart failure. Contrary, 2-dimensional speckle tracking (2DS) seems to be superior in detecting subtle changes in myocardial function. The aim of the study was to assess these LV function deteriorations with global longitudinal strain (GLS) analysis and the relations to LVMi in patients with AS and normal EF. Methods: 50 patients with moderate to severe AS and 31 controls were enrolled. All patients underwent echocardiography, including 2DS imaging. LVMi measures were performed with magnetic resonance imaging in 38 patients with AS and indexed for body surface area. Results: The total group of patients with AST showed a GLS of -15,2 ± 3,6% while the control group reached -19,5 ± 2,7% (p < 0,001). By splitting the group with AS in normal, moderate and severe increased LVMi, the GLS was -17,0 ± 2,6%, -13,2 ± 3,8% and -12,4 ± 2,9%, respectively (p = 0,001), where LVMi and GLS showed a significant correlation (r = 0,6, p < 0,001). Conclusions: In conclusion, increased LVMi is reflected in abnormalities of GLS and the proportion of GLS impairment depends on the extent of LV hypertrophy. Therefore, simultaneous measurement of LVMi and GLS might be useful to identify patients at high risk for transition into heart failure who would benefit from aortic valve replacement irrespectively of LV EF. [ABSTRACT FROM AUTHOR]

Background: Transthoracic echocardiography (TTE) is routinely used to calculate aortic valve area (AVA) by continuity equation (CE). However, accurate measurement of the left ventricular outflow tract (LVOT) can be difficult and flow acceleration in the LVOT may lead to miscalculation of the AVA., Objective: The aim of our study was to compare AVA measurements by standard TTE, cardiac magnetic resonance imaging (MRI) and a hybrid approach combining both techniques., Methods: AVA was calculated in 38 patients (age 73±9 years) with standard TTE, cine-MRI planimetry and a hybrid approach: Hybrid Method 1: TTE-derived LVOT measurement in the CE numerator was replaced by the MRI assessment of the LVOT and AVA was calculated: (LVOT(MRI)/*LVOT-VTI(TTE))/transaortic-VTI(TTE). Method 2: We replaced the SV in the numerator by the MRI-derived SV and calculated AVA = SV(MRI)/ transaortic-VTI(TTE)., Results: Mean AVA derived by TTE was 0.86 cm(2)±0.23 cm(2) and 0.83 cm(2)±0.3 cm(2) by MRI- planimetry, respectively. The mean absolute difference in AVA was 0.03 cm(2) for TTE vs. MRI planimetry. AVA calculated with method 1 and method 2 was 1.23 cm(2)±0.4 cm(2) and 0.92 cm(2)±0.32 cm(2), respectively. The mean absolute difference between TTE and method 1 and method 2 was 0.37 cm(2) and 0.06 cm(2), respectively (p<0.001)., Conclusion: MRI-planimetry of AVA and hybrid method 2 are accurate and showed a good agreement with standard TTE measurements. Therefore, hybrid method 1 is a reasonable alternative if poor acoustic windows or LVOT flow accelerations limit the accuracy of TTE, particularly in patients at high risk for an invasive hemodynamic study.

Background: Growth differentiation factor-15 (GDF-15), a stress-responsive transforming growth factor-ß-related cytokine, is elevated and independently related to an adverse prognosis in systolic heart failure., Objective: This study aimed to investigate plasma levels of GDF-15 in patients with preclinical diastolic dysfunction or heart failure with normal ejection fraction (HFnEF)., Methods: We evaluated 119 patients with normal ejection fraction referred for an elective coronary angiography, 75 (63%) of whom had coronary artery disease. Subjects were classified as having either mild left ventricular diastolic dysfunction (LVDD grade I, n = 61), HFnEF (LVDD grade II or III, n = 38) or normal diastolic function (controls, n = 20). In a subgroup of 20 subjects, changes in cardiac output (CO) were measured by inert gas rebreathing (InnocorTM) in response to an orthostatic hemodynamic test., Results: Growth differentiation factor-15 levels in HFnEF [median 1.08, interquartile range (0.88-1.30) ng/ml] were significantly higher than in controls [0.60 (0.50-0.71) ng/ml, p = 0.003] and in patients with LVDD grade I [0.78 (0.62-1.04) ng/ml, p < 0.001]. In addition, GDF-15 was significantly elevated in patients with LVDD grade I compared to controls (p = 0.003). Furthermore, GDF-15 was correlated with echocardiographic markers of diastolic dysfunction and was correlated with the magnitude of CO response to the change in body position from standing to supine (r = -0.67, p = 0.005)., Conclusion: Growth differentiation factor-15 levels are elevated in subjects with HFnEF and can differentiate normal diastolic function from asymptomatic LVDD. In addition, GDF-15 is associated with a reduced cardiac output response in the orthostatic hemodynamic test.

Objective: The development of diastolic dysfunction (DDF) is multifactorial. Possible mechanisms include metabolic disturbances, myocardial fibrosis, chronic inflammation and endothelial dysfunction. Recognizing early stages of DDF may help to identify patients at risk of developing symptomatic DDF. Therefore, biomarkers reflecting pathophysiological changes within the myocardium were investigated in patients with DDF., Methods: Seventy-seven patients submitted for coronary angiography with stable or suspected coronary artery disease (CAD) were consecutively enrolled. Those without known diabetes mellitus (DM) underwent a standardized oral glucose tolerance test. Echocardiography for the diagnosis of DDF was performed according to the European Society of Cardiology. Matrix metalloproteinase 2 (MMP-2) and soluble P-selectin (sP-selectin) serum concentrations were analyzed using the ELISA technique., Results: A total of 36% of patients had DM and 74% had CAD. The prevalence of DDF was higher in patients with DM (89% versus 74%) and CAD (84% versus 53%) (P<0.05). DDF in patients with DM was more severe with a significantly lower mitral annulus velocity of 6.5 cm/s versus 7.8 cm/s (P<0.01). Patients with DDF showed significantly higher sP-selectin (140.3 mug/L versus 107.6 mug/L, P<0.05) and MMP-2 (270.5 mug/L versus 224.7 mug/L, P<0.05) levels compared with those without DDF. There was a significant correlation between sP-selectin and MMP-2 (P=0.01), independent of the diagnosis of DM or CAD., Conclusion: sP-selectin as a marker for platelet hyperactivity, inflammation and endothelial dysfunction, and MMP-2 as a marker for extracellular matrix turnover were significantly elevated in patients with DDF. This elevation was independent of coexisting DM or CAD. This observation may help to identify and monitor patients with DDF.