Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure.Methods and results The consortium... Show moreAims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure.Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model.Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction. Show less
Extracellular matrix protein turnover may play an important role in left atrial (LA) remodelling. The aim is to investigate the associations between matrix metalloproteinase (MMPs), tissue... Show moreExtracellular matrix protein turnover may play an important role in left atrial (LA) remodelling. The aim is to investigate the associations between matrix metalloproteinase (MMPs), tissue inhibitor of metalloproteinase (TIMP-1) and LA volume index (LAVI) and if these associations are independent of TIMP-1 levels. Participants from The Hoorn Study, a population-based cohort study (n= 674), underwent echocardiography. Serum MMPs (i.e., MMP-1, MMP-2, MMP-3, MMP-9, and MMP-10) and TIMP-1 levels were measured with ELISA. Multiple linear regression analyses were used. MMP-1 levels were not associated with LAVI. Higher MMP-2 levels were associated with larger LAVI (regression coefficient per SD increase in MMP (95% CI); 0.03 (0.01; 0.05). Higher MMP-3 and MMP-9 levels were associated with smaller LAVI; -0.04 (-0.07; -0.01) and -0.04 (-0.06; -0.02) respectively. Only in women were higher MMP-10 levels associated with larger LAVI; 0.04 (0.00; 0.07,p-interaction 0.04). Additionally, only in women were higher TIMP-1 levels associated with smaller LAVI; -0.05 (-0.09; -0.01,p-interaction 0.03). The associations between MMPs and LAVI were independent of TIMP-1 levels. In conclusion, serum MMPs are associated with LAVI, independent of CVD risk factors and TIMP-1 levels. In addition, these associations differ according to sex and within MMP subgroups. This shows that the role of MMPs in LA remodelling is complex. Show less
Ferro, D.; Brink, H. van den; Amier, R.; Buchem, M. van; Bresser, J. de; Bron, E.; ... ; Heart-Brain Connection Consortium 2020
Background: Patients with heart failure (HF) are at risk for vascular brain injury. Cerebral cortical microinfarcts (CMIs) are a novel MRI marker of vascular brain injury. This study aims to... Show moreBackground: Patients with heart failure (HF) are at risk for vascular brain injury. Cerebral cortical microinfarcts (CMIs) are a novel MRI marker of vascular brain injury. This study aims to determine the occurrence of CMIs in patient with HF and their clinical correlates, including haemodynamic status.Methods: From the Heart-Brain Study, a multicenter prospective cohort study, 154 patients with clinically stable HF without concurrent atrial fibrillation (mean age 69.5 +/- 10.1, 32% female) and 124 reference participants without HF (mean age 65.6 +/- 7.4, 47% females) were evaluated for CMIs on 3 T MRI. CMI presence in HF was tested for associations with vascular risk profile, cardiac function and history, MRI markers of vascular brain injury and cognitive profile.Results: CMI occurrence was higher in patient with HF (17%) than reference participants (7%); after correction for age and sex OR 2.5 [95% CI 1.1-6.0] p=.032; after additional correction for vascular risk factors OR 2.7 [1.0-7.1] p=.052. In patients with HF, CMI presence was associated with office hypertension (OR 2.7 [1.2-6.5] p =.021) and a lower cardiac index (B = -0.29 [-0.55--0.04] p =.023 independent of vascular risk factors), but not with cause or duration of HF. Presence of CMIs was not associated with cognitive performance in patients with HF.Conclusions: CMIs are a common occurrence in patients with HF and related to an adverse vascular risk factor profile and severity of cardiac dysfunction. CMIs thus represent a novel marker of vascular brain injury in these patients. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Brugts, J.J.; Veenis, J.F.; Radhoe, S.P.; Linssen, G.C.M.; Gent, M. van; Borleffs, C.J.W.; ... ; Boer, R.A. de 2019
Background Assessing haemodynamic congestion based on filling pressures instead of clinical congestion can be a way to further improve quality of life (QoL) and clinical outcome by intervening... Show moreBackground Assessing haemodynamic congestion based on filling pressures instead of clinical congestion can be a way to further improve quality of life (QoL) and clinical outcome by intervening before symptoms or weight gain occur in heart failure (HF) patients. The clinical efficacy of remote monitoring of pulmonary artery (PA) pressures (CardioMEMS; Abbott Inc., Atlanta, GA, USA) has been demonstrated in the USA. Currently, the PA sensor is not reimbursed in the European Union as its benefit when applied in addition to standard HF care is unknown in Western European countries, including the Netherlands. Aims To demonstrate the efficacy and cost-effectiveness of haemodynamic PA monitoring in addition to contemporary standard HF care in a high-quality Western European health care system. Methods The current study is a prospective, multi-centre, randomised clinical trial in 340 patients with chronic HF (New York Heart Association functional class III) randomised to HF care including remote monitoring with the CardioMEMS PA sensor or standard HF care alone. Eligible patients have at least one hospitalisation for HF in 12 months before enrolment and will be randomised in a 1:1 ratio. Minimum follow-up will be 1 year. The primary endpoint is the change in QoL as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). Secondary endpoints are the number of HF hospital admissions and changes in health status assessed by EQ-5D-5L questionnaire including health care utilisation and formal cost-effectiveness analysis. Conclusion The MONITOR HF trial will evaluate the efficacy and cost-effectiveness of haemodynamic monitoring by CardioMEMS in addition to standard HF care in patients with chronic HF. Clinical Trial Registration number NTR7672. Show less
