Aims
Few investigations have been conducted to identify genetic determinants of common, polygenetic forms of heart failure (HF), and only a limited number of these genetic associations have been ...validated by multiple groups.
Methods and results
We performed a case–control study to further investigate the potential impact of 14 previously reported candidate genes on the risk of HF and specific HF sub‐types. We also performed an exploratory genome‐wide study. We included 799 patients with HF and 1529 controls. After adjusting for age, sex, and genetic ancestry, we found that the C allele of rs2234962 in BAG3 was associated with a decreased risk of idiopathic dilated cardiomyopathy (odds ratio 0.42, 95% confidence interval 0.25–0.68, P = 0.0005), consistent with a previous report. No association for the other primary variants or exploratory genome‐wide study was found.
Conclusions
Our findings provide independent replication for the association between a common coding variant (rs2234962) in BAG3 and the risk of idiopathic dilated cardiomyopathy.
•Among a heterogenous population of patients with inconclusive noninvasive stress testing, unsupervised hierarchical clustering approach enabled to determine 3 mutually exclusive and clinically ...distinct phenogroups.•The 3 phenogroups of patients with an inconclusive stress test have distinct outcomes in terms of cardiovascular events and all-cause mortality.•Using the clustering analysis, patients in the phenogroup with the worse prognosis (history of CABG and reduced LVEF) could benefit the most from treatment intensification and new therapy.•While the presence of inducible ischemia was involved in the clustering method, inducible ischemia by stress cardiovascular magnetic resonance was associated with the occurrence of CV events in each phenogroup.
Inconclusive non-invasive stress testing is associated with impaired outcome. This population is very heterogeneous, and its characteristics are not well depicted by conventional methods.
To identify patient subgroups by phenotypic unsupervised clustering, integrating clinical and cardiovascular magnetic resonance data to unveil pathophysiological differences between subgroups of patients with inconclusive stress tests.
Between 2008 and 2020, consecutive patients with a first inconclusive non-invasive stress test referred for stress cardiovascular magnetic resonance were followed for the occurrence of major adverse cardiovascular events (defined as cardiovascular death or myocardial infarction). A cluster analysis was performed on clinical and cardiovascular magnetic resonance variables.
Of 1402 patients (67% male; mean age 70±11years) who completed the follow-up (median 6.5years, interquartile range 5.6–7.5years), 197 experienced major adverse cardiovascular events (14.1%). Three distinct phenogroups were identified based upon unsupervised hierarchical clustering of principal components: phenogroup 1=history of percutaneous coronary intervention with viable myocardial infarction and preserved left ventricular ejection fraction; phenogroup 2=atrial fibrillation with preserved left ventricular ejection fraction; and phenogroup 3=coronary artery bypass graft with non-viable myocardial scar and reduced left ventricular ejection fraction. Using survival analysis, the occurrence of major adverse cardiovascular events (P=0.007), cardiovascular mortality (P=0.002) and all-cause mortality (P<0.001) differed among the three phenogroups. Phenogroup 3 presented the worse prognosis. In each phenogroup, ischaemia was associated with major adverse cardiovascular events (phenogroup 1: hazard ratio 2.79, 95% confidence interval 1.61–4.84; phenogroup 2: hazard ratio 2.59, 95% confidence interval 1.69–3.97; phenogroup 3: hazard ratio 3.16, 95% confidence interval 1.82–5.49; all P<0.001).
Cluster analysis of clinical and cardiovascular magnetic resonance variables identified three phenogroups of patients with inconclusive stress testing, with distinct prognostic profiles.
Summary
Hydropower currently accounts for 63% of Canada's total electricity generation and is bound to increase with the energy demands of a growing population. With damming and flow regulation known ...as major threats to aquatic biodiversity and river and floodplain habitats, an improved understanding of the specific impacts of river regulation is needed for the proper management of these systems.
Although interactions among river flow and thermal regimes have been described in the literature, their concurrent influence on fish guild responses has yet to be analysed for temperate rivers. Such an analysis may be used to identify the ecological traits linked with the flow and thermal variables reflecting river regulation.
Extensive field surveys were conducted across 25 unregulated and regulated rivers to estimate fish species density and biomass. Fish guild models were developed to characterise morphologic, trophic, reproductive, habitat preferences and behavioural traits, as well as phylogenetic associations. To characterise ecologically relevant components of the flow and thermal regimes of rivers, we calculated indices based on the magnitude, frequency, duration, timing and rate of change in each driver. Model relationships between fish biomass and density estimates were then run using redundancy analyses (RDA) on each type of guild and dominant patterns of flow and thermal variability.
Variables representing the magnitude of summer temperatures and intra‐annual flow variability were consistently selected as independent drivers of fish guild responses (>86% of RDA models), clearly showing the importance of integrating thermal regimes in current river hydro‐ecological studies.
Fish guild density and biomass were significantly explained (R2Adj = 25–44%) and predicted (R2CV = 35–76%) by flow and thermal variables characterising regimes across unregulated and regulated rivers, whereas total fish density and biomass were not. Fish guild models based on trait–environmental relationships performed better than those based on phylogeny. Our results also showed that the models describing habitat and trophic guilds had the greatest explanatory power (R2Adj = 0.44 and R2Adj = 0.41 respectively).
This study identified differences in guild trait–environment relationships across rivers and the guilds most susceptible to changes in flow and temperature conditions resulting from river regulation. In particular, more constant summer temperatures and lower flow variability favoured habitat and trophic guilds over morphologic, reproductive and behavioural guilds.
Our results showed that maintaining particular aspects of the flow and thermal regime may be important for ensuring the presence of certain guilds in temperate rivers.
This study aimed to assess the impact of pulmonary valve replacement (PVR) on ventricular arrhythmias burden in a population of tetralogy of Fallot (TOF) patients with continuous cardiac monitoring ...by implantable cardioverter-defibrillators (ICDs).
Sudden cardiac death is a major cause of death in TOF, and right ventricular overload is commonly considered to be a potential trigger for ventricular arrhythmias.
Data were analyzed from a nationwide French ongoing study (DAI-T4F) including all TOF patients with an ICD since 2000. Survival data with recurrent events were used to compare the burden of appropriate ICD therapies before and after PVR in patients who underwent PVR over the study period.
A total of 165 patients (mean age 42.2 ± 13.3 years, 70.1% male) were included from 40 centers. Over a median follow-up period of 6.8 (interquartile range: 2.5 to 11.4) years, 26 patients (15.8%) underwent PVR. Among those patients, 18 (69.2%) experienced at least 1 appropriate ICD therapy. When considering all ICD therapies delivered before (n = 62) and after (n = 16) PVR, the burden of appropriate ICD therapies was significantly lower after PVR (HR: 0.21; 95% confidence interval CI: 0.08 to 0.56; p = 0.002). Respective appropriate ICD therapies rates per 100 person-years were 44.0 (95% CI: 35.7 to 52.5) before and 13.2 (95% CI: 7.7 to 20.5) after PVR (p < 0.001). In the overall cohort, PVR before ICD implantation was also independently associated with a lower risk of appropriate ICD therapy in primary prevention patients (HR: 0.29 95% CI: 0.10 to 0.89; p = 0.031).
In this cohort of high-risk TOF patients implanted with an ICD, the burden of appropriate ICD therapies was significantly reduced after PVR. While optimal indications and timing for PVR are debated, these findings suggest the importance of considering ventricular arrhythmias in the overall decision-making process. (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator DAI-T4F; NCT03837574)
Display omitted
Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, and sudden cardiac death represents an important mode of death in these patients. Data evaluating the implantable ...cardioverter defibrillator (ICD) in this patient population remain scarce.
We aimed to describe long-term follow-up of TOF patients implanted with ICD through a nationwide French registry.
Nationwide French Registry including all TOF patients with an ICD initiated in 2010 by the French Institute of Health and Medical Research. The primary time to event endpoint was the time from ICD implantation to first appropriate ICD therapy. Clinical events were centrally adjudicated by a blinded committee.
A total of 165 patients (mean age 42.2±13.3 years, 70.1% males) were included from 40 centers, including 104 (63.0%) in secondary prevention. During a median (IQR) follow-up of 6.8 (2.5–11.4) years, 78 (47.3%) patients received at least one appropriate ICD therapy. The annual incidence of the primary outcome was 10.5% (7.1% and 12.5% in primary and secondary prevention, respectively, P=0.03). Overall, 71 (43.0%) patients presented with at least one ICD complication, including inappropriate shocks in 42 (25.5%) patients and lead dysfunction in 36 (21.8%) patients. Among 61 (37.0%) primary prevention patients, the annual rate of appropriate ICD therapies was 4.1%, 5.3%, 9.5%, and 13.3% in patients with respectively no, one, two, or ≥three guideline-recommended risk factors. QRS fragmentation was the only independent predictor of appropriate ICD therapies (HR 3.47, 95% CI 1.19–10.11), and its integration in a model with current criteria increased the 5-year time-dependent area under the curve from 0.68 to 0.81 (P=0.006) (Fig. 1).
Patients with TOF and an ICD experience high rates of appropriate therapies, including those implanted in primary prevention. The considerable long-term burden of ICD-related complications, however, underlines the need for careful candidate selection. A combination of easy-to-use criteria including QRS fragmentation might improve risk stratification.
PDF
