Aims: Moderate aortic stenosis (AS) is associated with an increased risk of adverse events. Because outcomes in patients with AS are ultimately driven by the condition of the left ventricle (LV)... Show moreAims: Moderate aortic stenosis (AS) is associated with an increased risk of adverse events. Because outcomes in patients with AS are ultimately driven by the condition of the left ventricle (LV) and not by the valve, assessment of LV remodelling seems important for risk stratification. This study evaluated the association between different LV remodelling patterns and outcomes in patients with moderate AS. Methods and result: Patients with moderate AS (aortic valve area 1.0-1.5 cm(2)) were identified and stratified into four groups according to the LV remodelling pattern: normal geometry (NG), concentric remodelling (CR), concentric hypertrophy (CH), or eccentric hypertrophy (EH). Clinical outcomes were defined as all-cause mortality and a composite endpoint of all-cause mortality and aortic valve replacement (AVR). Of 1931 patients with moderate AS (age 73 +/- 10 years, 52% men), 344 (18%) had NG, 469 (24%) CR, 698 (36%) CH, and 420 (22%) EH. Patients with CH and EH showed higher 3-year mortality rates (28% and 32%, respectively) when compared with patients with NG (19%) (P< 0.001). After multivariable adjustment, CH remained independently associated with mortality (HR 1.258, 95% CI 1.016-1.558; P = 0.035), whereas both CH (HR 1.291, 95% CI 1.088-1.532; P = 0.003) and EH (HR 1.217, 95% CI 1.008-1.470; P= 0.042) were associated with the composite endpoint of death or AVR. Conclusion: In patients with moderate AS, those who develop CH already have an increased risk of all-cause mortality. Assessment of the LV remodelling patterns may identify patients at higher risk of adverse events, warranting closer surveillance, and possibly earlier intervention.[GRAPHICS]. Show less
Phosphorylcholine is a pro-inflammatory epitope exposed on apoptotic cells, and phosphorylcholine monoclonal immunoglobulin (Ig)G antibodies (PC-mAb) have anti-inflammatory properties. In this... Show morePhosphorylcholine is a pro-inflammatory epitope exposed on apoptotic cells, and phosphorylcholine monoclonal immunoglobulin (Ig)G antibodies (PC-mAb) have anti-inflammatory properties. In this study, we hypothesize that PC-mAb treatment reduces adverse cardiac remodelling and infarct size (IS) following unreperfused transmural myocardial infarction (MI). Unreperfused MI was induced by permanent ligation of the left anterior descending (LAD) coronary artery in hypercholesterolaemic APOE*3-Leiden mice. Three weeks following MI, cardiac magnetic resonance (CMR) imaging showed a reduced LV end-diastolic volume (EDV) by 21% and IS by 31% upon PC-mAb treatment as compared to the vehicle control group. In addition, the LV fibrous content was decreased by 27% and LV wall thickness was better preserved by 47% as determined by histological analysis. Two days following MI, CCL2 concentrations, assessed by use of ELISA, were decreased by 81% and circulating monocytes by 64% as assessed by use of FACS analysis. Additionally, local leucocyte infiltration determined by immunohistological analysis showed a 62% decrease after three weeks. In conclusion, the local and systemic inflammatory responses are limited by PC-mAb treatment resulting in restricted adverse cardiac remodelling and IS following unreperfused MI. This indicates that PC-mAb holds promise as a therapeutic agent following MI limiting adverse cardiac remodelling. Show less
Bijl, P. van der; Kostyukevich, M.V.; Khidir, M.; Marsan, N.A.; Delgado, V.; Bax, J.J. 2019
Aims Cardiac resynchronization therapy (CRT) can reduce left ventricular end-systolic volume (LVESV), and a decrease of >= 15% is defined as a response. CRT can also improve LV global... Show moreAims Cardiac resynchronization therapy (CRT) can reduce left ventricular end-systolic volume (LVESV), and a decrease of >= 15% is defined as a response. CRT can also improve LV global longitudinal strain (GLS). Changes in LVESV and LV GLS are individually associated with outcome post-CRT. We investigated LVESV and LV GLS changes and prognostic implications of improvement in LVESV and/or LV GLS, compared with no improvement in either parameter.Methods and results Baseline and 6-month echocardiograms were analysed from CRT recipients with heart failure. LV reverse remodelling was defined as a >= 15% reduction in LVESV at 6 months post-CRT. A >= 5% absolute improvement in LV GLS was defined as a change in LV GLS. A total of 1185 patients were included (mean age 65 +/- 10 years, 73% male), and those with an improvement in LVESV and LV GLS (n = 131, 11.1%) had significantly lower mortality compared with other groups. On multivariable analysis, an improvement in both LVESV and LV GLS [hazard ratio (HR): 0.47; 95% confidence interval (CI): 0.31-0.71; P < 0.001] or an improvement in either LVESV or LV GLS (HR: 0.57; 95% CI: 0.47-0.71; P < 0.001) were independently associated with better prognosis, compared with no improvement in either parameter.Conclusion Either a reduction in LVESV and/or an improvement in LV GLS at 6 months post-CRT are independently associated with improved long-term prognosis, compared with no change in both LVESV and LV GLS. This supports the use of LV GLS as a meaningful parameter in defining CRT response. Show less
