Objective: We aimed to analyze the association among flow patterns, gene expression, and histologic alterations of the proximal aorta in patients with aortic valve disease.Methods: A total of 131... Show moreObjective: We aimed to analyze the association among flow patterns, gene expression, and histologic alterations of the proximal aorta in patients with aortic valve disease.Methods: A total of 131 patients referred for aortic valve replacement were grouped by valve dysfunction (aortic stenosis vs aortic regurgitation) and valve morphology (bicuspid vs tricuspid). On the basis of magnetic resonance imaging, aortic tissue from outer and inner curvature was collected for gene expression and histologic analysis. To identify differences in aortic remodeling, age- and sex-adjusted data for inflammation (CCL2, VCAM1, inflammation and atherosclerosis) and medial degeneration (COL147, ELN, fibrosis, elastin fragmentation, and cystic medial necrosis) were compared.Results: First, we compared all patients with aortic regurgitation (n = 64) and patients with aortic stenosis (n = 67). In patients with aortic regurgitation, COL147 expression and all histologic markers were significantly increased. With respect to aortic diameter, all subsequent analyses were refined by considering only individuals with aortic diameter 40 mm or greater. Second, patients with bicuspid aortic valve were compared, resulting in a similar aortic diameter. Although patients with aortic regurgitation were younger, no differences were found in gene expression or histologic level. Third, valve morphology was compared in patients with aortic regurgitation. Although aortic diameter was similar, patients with regurgitant bicuspid aortic valve were younger than patients with regurgitant tricuspid aortic valve. Inflammatory markers were similar, whereas markers for medial degeneration were increased in patients with regurgitant tricuspid aortic valve.Conclusions: Our results indicate that the proximal aorta in patients with aortic regurgitation showed an increased inflammation and medial degeneration compared with patients with aortic stenosis. Refining both groups by valve morphology, in patients with bicuspid aortic valve, no difference except age was detected between aortic regurgitation and aortic stenosis. In patients with aortic regurgitation, tricuspid aortic valve revealed increased markers for medial degeneration but no differences regarding inflammatory markers. Show less
Background and Purpose-Our study aim was to estimate risk of incident stroke based on levels of hs-cTn (high-sensitivity cardiac troponin), a specific biomarker indicating myocardial injury, in the... Show moreBackground and Purpose-Our study aim was to estimate risk of incident stroke based on levels of hs-cTn (high-sensitivity cardiac troponin), a specific biomarker indicating myocardial injury, in the general population, patients with atrial fibrillation, and patients with previous stroke.Methods-Embase, PubMed, and Web of Science were searched until March 14, 2019 to identify relevant articles. Randomized controlled trials and cohort studies assessing the risk of incident stroke based on hs-cTn were eligible. Pooled adjusted hazard ratios including 95% CI were calculated using a random-effects model due to study heterogeneity per population, coding of hs-cTn (categorical/continuous data), per hs-cTn subunit (T or I), for low risk of bias, and for all-cause and ischemic stroke separately.Results-We included 17 articles with 96 702 participants. In studies conducted in the general population (n=12; 77 780 participants), the pooled adjusted hazard ratio for incident stroke was 1.25 (CI, 1.10-1.40) for high versus low hs-cTn (as defined by included studies) during an average follow-up of 1 to 20 years (median 10). When categorical data were used, this was increased to 1.58 (CI, 1.26-1.90). The results were robust when accounting for stroke classification (all-cause stroke/ischemic stroke), hs-cTn subunit, risk of bias, and coding of hs-cTn. In patients with atrial fibrillation (4 studies; 18 725 participants), the pooled adjusted hazard ratio for incident stroke was 1.95 (CI, 1.29-2.62) for high versus low hs-cTn. Due to lack of data (one study, 197 participants), no meta-analysis could be performed in patients with previous stroke.Conclusions-This meta-analysis suggests that hs-cTn can be regarded as a risk marker for incident stroke, with different effect size in different subgroups. More research about the association between hs-cTn and incident stroke in high-risk populations is needed, especially in patients with history of ischemic stroke. Show less
Alogna, A.; Schwarzl, M.; Manninger, M.; Hamdani, N.; Zirngast, B.; Kloth, B.; ... ; Post, H. 2018
RATIONALE Severe increase in right ventricular pressure can compromise left ventricular (LV) function because of impaired interventricular interaction and aggravate the symptoms. OBJECTIVES To... Show moreRATIONALE Severe increase in right ventricular pressure can compromise left ventricular (LV) function because of impaired interventricular interaction and aggravate the symptoms. OBJECTIVES To elucidate how nonsevere idiopathic pulmonary arterial hypertension (IPAH) influences LV function because of impaired interventricular interaction. METHODS Invasive pressure-volume (PV) loop analysis obtained by conductance catheterization was performed at rest and during atrial pacing in patients with mild IPAH (n = 10) compared with patients with isolated LV diastolic dysfunction (DD) (n = 10) and control subjects without heart failure symptoms (n = 9). MEASUREMENTS AND MAIN RESULTS Patients with nonsevere IPAH (pulmonary artery pressure mean 29 ± 5 mm Hg) and patients with DD showed preserved systolic (ejection fraction 63 ± 12% and 62 ± 9%) and impaired LV diastolic function at rest (LV stiffness 0.027 ± 0.012 ml(-1) and 0.029 ± 0.014 ml(-1)). During pacing at 120 per minute patients with IPAH and DD decreased their stroke volume (-25% and -30%; P < 0.05) and failed to increase cardiac output significantly. Opposite to patients with DD and control subjects, temporary preload reduction during inferior vena cava occlusion initially induced an expansion of LV end-diastolic volume in IPAH (+7%; P < 0.05), whereas end-diastolic pressure continuously dropped. This resulted in an initial downward shift to the right of the PV loop indicating better LV filling, which was associated with a temporary improvement of cardiac output (+11%; P < 0.05) in the patients with IPAH, but not in patients with DD and control subjects. CONCLUSIONS Mild idiopathic pulmonary arterial pressure impairs LV diastolic compliance even in the absence of the intrinsic LV disease and contributes to the reduced cardiac performance at stress. Show less
Kasner, M.; Westermann, D.; Steendijk, P.; Drose, S.; Poller, W.; Schultheiss, H.P.; Tschope, C. 2012
Background-The pathophysiology of heart failure with normal ejection fraction (HFNEF) is still under discussion. Here we report the influence of cardiac inflammation on extracellular matrix (ECM)... Show moreBackground-The pathophysiology of heart failure with normal ejection fraction (HFNEF) is still under discussion. Here we report the influence of cardiac inflammation on extracellular matrix (ECM) remodeling in patients with HFNEF. Methods and Results-We investigated left ventricular systolic and diastolic function in 20 patients with HFNEF and 8 control patients by conductance catheter methods and echocardiography. Endomyocardial biopsy samples were also obtained, and ECM proteins as well as cardiac inflammatory cells were investigated. Primary human cardiac fibroblasts were outgrown from the endomyocardial biopsy samples to investigate the gene expression of ECM proteins after stimulation with transforming growth factor-beta. Diastolic dysfunction was present in the HFNEF patients compared with the control patients. In endomyocardial biopsy samples from HFNEF patients, we found an accumulation of cardiac collagen, which was accompanied by a decrease in the major collagenase system (matrix metalloproteinase-1) in the heart. Moreover, a subset of inflammatory cells, which expressed the profibrotic growth factor transforming growth factor-beta, could be documented in the HFNEF patients. Stimulation of primary human cardiac fibroblasts from HFNEF patients with transforming growth factor-beta resulted in transdifferentiation of fibroblasts to myofibroblasts, which produced more collagen and decreased the amount of matrix metalloproteinase-1, the major collagenase in the human heart. A positive correlation between cardiac collagen, as well as the amount of inflammatory cells, and diastolic dysfunction was evident and suggests a direct influence of inflammation on fibrosis triggering diastolic dysfunction. Conclusions-Cardiac inflammation contributes to diastolic dysfunction in HFNEF by triggering the accumulation of ECM. (Circ Heart Fail. 2011;4:44-52.) Show less
Kasner, M.; Gaub, R.; Sinning, D.; Westermann, D.; Steendijk, P.; Hoffmann, W.; ... ; Tschope, C. 2010
Strain rate imaging provides direct information on intrinsic myocardial function and may improve the diagnostic of diastolic dysfunction in heart failure with normal ejection fraction (HFNEF). We... Show moreStrain rate imaging provides direct information on intrinsic myocardial function and may improve the diagnostic of diastolic dysfunction in heart failure with normal ejection fraction (HFNEF). We therefore correlated global strain with pressure-volume (PV) loop analysis and compared it with flow and tissue Doppler measurements. Longitudinal two-dimensional strain rate and flow and tissue Doppler (TDI) indices were measured simultaneously and correlated with diastolic indices of PV relationship obtained by a conductance catheter in 21 patients with HFNEF and 12 controls. HFNEF patients showed a reduced global strain rate during isovolumetric relaxation (SRIVR) [0.27 (0.12-0.39) vs. 0.44 (0.29-0.56) s(-1), P = 0.028]. Global strain rate during early (SRE) and late (SRL) diastole did not defer from controls. Their ratios with early transmitral flow, E/SRIVR and E/SRE, were both elevated in HFNEF [3.68 (2.57-7.52) vs. 1.73 (1.47-2.37) m, P = 0.007 and 1.13 (0.76-1.36) vs. 0.83 (0.57-1.04) m, P = 0.030]. SRE and SRIVR correlated with left ventricular (LV) relaxation tau (r = 0.40 and 0.47, P < 0.05); E/SRIVR and E/SRE with LV end-diastolic pressure (r = 0.49 and 0.57, P < 0.01) and LV stiffness constant beta (r = 0.42 and 0.43, P < 0.01). Neither of the strain rate indices were significantly more accurate than TDI (area under the curve: SRE 0.55, SRIVR 0.70, E'/A' 0.72, E/SRE 0.75, E/SRIVR 0.80, and E/E' 0.83). Strain rate imaging is accurate in detecting increased LV stiffness in HFNEF, but it is not superior to already established TDI analysis including E/E' in patients with only mild degree of disease. Show less
