GENECHOC study: genetic markers of arrhythmic risk in heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Anys ◽  
S Rigade ◽  
S Rigade ◽  
E Baron ◽  
E Baron ◽  
...  
Keyword(s):  
Heart Failure ◽  
Genetic Markers ◽  
Left Ventricular ◽  
European Ancestry ◽  
Left Ventricular Ejection ◽  
P Value ◽  
Funding Source ◽  
Ventricular Ejection Fraction ◽  
Cardioverter Defibrillator ◽  
Genome Wide

Abstract Background Ventricular arrhythmic events are responsible for 50% of death in heart failure but no reliable predictive marker is known to discriminate patients at risk of fatal arrhythmia. Interestingly, familial predisposition has been reported suggesting a role of genetic factors. Purpose Identify genetic markers increasing the arrhythmic risk in heart failure population. Method We prospectively included heart failure patients with left ventricular ejection fraction (LVEF) under 35% and a cardioverter defibrillator in primary prevention in 22 French centres between 2009 and 2017. Patients were followed for 72 months and divided into two groups: cases with an arrhythmic event during follow-up and controls. A Genome Wide Association Study (GWAS) was done. Single Nucleotide Polymorphisms (SNPs) genotyping was performed on Affymetrix Axiom Precision Medicine Research Array plates. To complement the directly genotyped SNPs we performed large-scale imputation based on the Haplotype Reference Consortium European ancestry panel leading to a dataset of 7,5 million of SNPs. Results 332 cases and 567 controls were included (86% men, mean age at implantation 52±11 years). 78% of patients had ischaemic cardiopathy, 20% had dilated cardiomyopathy. Mean LVEF was 27±5%. No statistical difference was found between cases and controls on clinical parameters, biological results, electrocardiographic measures. No locus shows genome-wide significant association (p<5.10–8) on the GWAS analysis. However, 16 signals with a p-value between 5.10–8 and 5.10–5 were investigated. eQTL and chromatin conformation point to 35 genes with cardiac expression previously associated with heart failure, cardiomyopathies, cardiogenesis, arrhythmias and inflammation. Variants identified point to regulatory regions of the genome and may then propose a molecular mechanism predisposing patients to arrhythmias. Conclusion No locus raises genome-wide significance, but several signals with a nominal p-value point to relevant genes and pathways. Replication of the GWAS is ongoing on a cohort of 156 new patients with a less severe cardiopathy implanted with a cardioverter defibrillator in secondary prevention. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Nantes University Hospital

Right ventricular speckle tracking in patients with heart failure – a comparison of right ventricular measures

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I.J Lundorff ◽  
M Sengeloev ◽  
S Pedersen ◽  
D Modin ◽  
N.E Bruun ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Right Ventricular ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Private Company ◽  
Ventricular Ejection Fraction ◽  
Risk Of Mortality ◽  
Patients With Heart Failure

Abstract Background RV dysfunction is associated with increased mortality and morbidity in patients with heart failure. Due to the complex shape and position of the RV, assessing RV function from echocardiographic images remains a challenge. Purpose We have previously found that global longitudinal strain from 2DSTE is superior to left ventricular ejection fraction (LVEF) in identifying HFrEF patients with high risk of mortality. In this study we wanted to examine RV 2DSTE in patients with HFrEF and compare its prognostic value to conventional RV measures. Methods and results Echocardiographic examinations were retrieved from 701 patients with HFrEF. RV estimates were analysed offline, and end point was all-cause mortality. During follow-up (median 39 months) 118 patients (16.8%) died. RV GLS and RV FWS remained associated with mortality after multivariable adjustment, independent of TAPSE (RV GLS: HR 1.07, 95% CI 1.02–1.13, p=0.010, per 1% decrease) (RV FWS: HR 1.05, 95% CI 1.01–1.09, p=0.010, per 1% decrease). This seemed to be caused by significant associations in men as TAPSE remained as the only independent prognosticator in women. All RV estimates provided prognostic information incremental to established risk factors and significantly increased C-statistics (TAPSE: 0.74 to 0.75; RVFAC: 0.74 to 0.75; RVFWS: 0.74 to 0.77; RVGLS: 0.74 to 0.77). Conclusions RV strain from 2DSTE was associated with mortality in patients with HFrEF, independent of TAPSE and established risk factors. Our results indicate that RV strain is particularly valuable in male patients, whereas in women TAPSE remains a stronger prognosticator. RV GLS and the risk of mortality Funding Acknowledgement Type of funding source: Private company. Main funding source(s): PGJ reports receiving lecture fee from Novo Nordisk.

scholarly journals Wearable Cardioverter-Defibrillator Used as a Telemonitoring System in a Real-Life Heart Failure Unit Setting

2021 ◽  
Vol 10 (22) ◽  
pp. 5435
Author(s):  
Christian Blockhaus ◽  
Stephan List ◽  
Hans-Peter Waibler ◽  
Jan-Erik Gülker ◽  
Heinrich Klues ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Real Life ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Specific Patient ◽  
Ventricular Ejection Fraction ◽  
Cardioverter Defibrillator ◽  
Wearable Cardioverter Defibrillator ◽  
Heart Failure Unit

Background: In patients with reduced left ventricular ejection fraction (LVEF) who are at risk of sudden cardiac death, a wearable cardioverter-defibrillator (WCD) is recommended as a bridge to the recovery of LVEF or as a bridge to the implantation of a device. In addition to its function to detect and treat malignant arrhythmia, WCD can be used via an online platform as a telemonitoring system to supervise patients’ physical activity, compliance, and heart rate. Methods: We retrospectively analyzed 173 patients with regard to compliance and heart rate after discharge. Results: Mean WCD wearing time was 59.75 ± 35.6 days; the daily wearing time was 21.19 ± 4.65 h. We found significant differences concerning the patients’ compliance. Men showed less compliance than women, and younger patients showed less compliance than patients who were older. Furthermore, we analyzed the heart rate from discharge until the end of WCD prescription and found a significant decrease from discharge to 4, 8, or 12 weeks. Conclusion: WCD can be used as a telemonitoring system to help the involved heart failure unit or physicians attend to and adjust the medical therapy. Furthermore, specific patient groups should be educated more intensively with respect to compliance.

854Predictors of ventricular tachyarrhythmia in patients with implantable cardioverter-defibrillator and non-ischaemic systolic heart failure

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
E Jedrzejczyk-Patej ◽  
M Mazurek ◽  
M Lazar ◽  
P Pruszkowska-Skrzep ◽  
T Podolecki ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Ventricular Arrhythmia ◽  
Implantable Cardioverter Defibrillator ◽  
Atrial Flutter ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Urban Region ◽  
Ventricular Ejection Fraction ◽  
Cardioverter Defibrillator

Abstract Funding Acknowledgements none OnBehalf none Background The benefit of an implantable cardioverter-defibrillator (ICD) in patients with ischaemic heart failure (HF) has been well proven but the benefit of ICD in subjects with non-ischaemic systolic HF is less well-established. Consequently, there is very limited evidence which patients with non-ischaemic HF would benefit most from receiving an ICD. Aim To determine the incidence and predictors of ventricular arrhythmia in patients with ICD and non-ischaemic systolic HF. Methods Study population consisted of 420 consecutive patients with ICD and non-ischaemic systolic HF monitored remotely (on a daily basis) between 2010 and 2017 in tertiary care university hospital, in a densely inhabited, urban region of Poland. Sixty-six percentage of patients had cardiac resynchronization therapy with defibrillator (CRT-D). Results During the median follow-up of 1645 days (range: 507-3515) sustained ventricular arrhythmia occurred in 100 patients (23.8%). Of those, ventricular fibrillation (VF), ventricular tachycardia (VT) or VT/VF (combined) occurred in 10 (10.0%), 77 (77.0%) and 13 (13.0%) patients, respectively. Patients with versus without ventricular arrhythmia did differ with respect to baseline variables such as: left ventricular end diastolic diameter (LVEDD) - median of 67 mm [49-82] vs 62 mm [46-78]; post-inflammatory HF (17 vs 9.7%, P = 0.045); atrial fibrillation/atrial flutter - AF/AFL (57 vs. 38.1%, P = 0.0009); supraventricular arrhythmia (SVT) - any supraventricular arrythmia >100/min other than AF/AFL (27 vs. 15.9%, P = 0.01); and left ventricular ejection fraction - EF (25 vs. 28%, P = 0.01). No differences were observed for age, sex, NYHA class, mitral regurgitation, common comorbidities (including diabetes and chronic renal disease) or concomitant medications. On  multivariable regression analysis, LVEDD (HR 1.05, 95% CI 1.004-1.09, P = 0.03), AF/AFL (HR 1.81, 95% CI 1.21-2.72, P = 0.004) and SVT (HR 1.91, 95% CI 1.21-3.01, P = 0.006) were identified as independent predictors of sustained ventricular arrhythmia in patients with ICD and non-ischaemic HF. All-cause mortality in patients with VT/VF was significantly higher than in subjects without sustained ventricular arrhythmias (33% vs. 20%, P = 0.03). Conclusions Ventricular arrhythmia occurred in 23.8% of patients with systolic non-ischaemic HF during 4.5 years of observation and was associated with significantly worse prognosis compared with subjects free of VT/VF. Left ventricular dimension, atrial fibrillation/atrial flutter and supraventricular tachycardia were identified as independent predictors for ventricular arrhythmia.

scholarly journals Baseline and Dynamic Risk Predictors of Appropriate Implantable Cardioverter Defibrillator Therapy

2020 ◽  
Vol 9 (20) ◽  
Author(s):  
Katherine C. Wu ◽  
Shannon Wongvibulsin ◽  
Susumu Tao ◽  
Hiroshi Ashikaga ◽  
Michael Stillabower ◽  
...  
Keyword(s):  
Heart Failure ◽  
Random Forest ◽  
Left Ventricular Ejection Fraction ◽  
Left Atrial ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Time Varying ◽  
Ventricular Ejection Fraction ◽  
Cardioverter Defibrillator

Background Current approaches fail to separate patients at high versus low risk for ventricular arrhythmias owing to overreliance on a snapshot left ventricular ejection fraction measure. We used statistical machine learning to identify important cardiac imaging and time‐varying risk predictors. Methods and Results Three hundred eighty‐two cardiomyopathy patients (left ventricular ejection fraction ≤35%) underwent cardiac magnetic resonance before primary prevention implantable cardioverter defibrillator insertion. The primary end point was appropriate implantable cardioverter defibrillator discharge or sudden death. Patient characteristics; serum biomarkers of inflammation, neurohormonal status, and injury; and cardiac magnetic resonance‐measured left ventricle and left atrial indices and myocardial scar burden were assessed at baseline. Time‐varying covariates comprised interval heart failure hospitalizations and left ventricular ejection fractions. A random forest statistical method for survival, longitudinal, and multivariable outcomes incorporating baseline and time‐varying variables was compared with (1) Seattle Heart Failure model scores and (2) random forest survival and Cox regression models incorporating baseline characteristics with and without imaging variables. Age averaged 57±13 years with 28% women, 66% white, 51% ischemic, and follow‐up time of 5.9±2.3 years. The primary end point (n=75) occurred at 3.3±2.4 years. Random forest statistical method for survival, longitudinal, and multivariable outcomes with baseline and time‐varying predictors had the highest area under the receiver operating curve, median 0.88 (95% CI, 0.75‐0.96). Top predictors comprised heart failure hospitalization, left ventricle scar, left ventricle and left atrial volumes, left atrial function, and interleukin‐6 level; heart failure accounted for 67% of the variation explained by the prediction, imaging 27%, and interleukin‐6 2%. Serial left ventricular ejection fraction was not a significant predictor. Conclusions Hospitalization for heart failure and baseline cardiac metrics substantially improve ventricular arrhythmic risk prediction.

Residual inflammation is a major determinant of myocardial recovery and cardiovascular outcome in takotsubo patients

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Lachmet-Thebaud ◽  
B Marchandot ◽  
K Matsushita ◽  
C Sato ◽  
C Dagrenat ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Death ◽  
Left Ventricular ◽  
Cardiovascular Outcome ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Ventricular Ejection Fraction ◽  
Cox Regression Analysis ◽  
The Impact

Abstract Background Recent insights have emphasized the importance of myocardial and systemic inflammation in Takotsubo Syndrome (TTS). Objective In a large registry of unselected patients, we sought to evaluate whether residual high inflammatory response (RHIR) could impact cardiovascular outcome after TTS. Methods Patients with TTS were retrospectively included between 2008 and 2018 in three general hospitals. 385 patients with TTS were split into three subgroups, according to tertiles of C-reactive protein (CRP) levels at discharge (CRP<5.2 mg/l, CRP range 5.2 to 19 mg/l, and CRP>19 mg/L). The primary endpoint was the impact of RHIR, defined as CRP>19 mg/L at discharge, on cardiac death or hospitalization for heart failure. Results Follow-up was obtained in 382 patients (99%) after a median of 747 days. RHIR patients were more likely to have a history of cancer or a physical trigger. Left ventricular ejection fraction (LVEF) at admission and at discharge were comparable between groups. By contrast, RHIR was associated with lower LVEF at follow-up (61.7 vs. 60.7 vs. 57.9%; p=0.004) and increased cardiac late mortality (0% vs. 0% vs. 10%; p=0.001). By multivariate Cox regression analysis, RHIR was an independent predictor of cardiac death or hospitalization for heart failure (hazard ratio: 1.97; 95% confidence interval: 1.11 to 3.49; p=0.02). Conclusions RHIR was associated with impaired LVEF recovery and was evidenced as an independent factor of cardiovascular events. All together these findings underline RHIR patients as a high-risk subgroup, to target in future clinical trials with specific therapies to attenuate RHIR. Main results Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): GERCA (Groupe pour l'Enseignement, la prévention et la Recherche Cardiovasculaire en Alsace)

Abstract 14958: Global Longitudinal Strain is a Superior Predictor of All-cause Mortality Compared to Left Ventricular Ejection Fraction in Male Patients with Heart Failure and Without Atrial Fibrillation

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Morten Sengeløv ◽  
Tor Biering-Sørensen ◽  
Peter Godsk Jørgensen ◽  
Niels Eske Bruun ◽  
Thomas Fritz-Hansen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
P Value ◽  
Ventricular Ejection Fraction ◽  
Global Strain ◽  
Echocardiographic Parameters

Object: Myocardial strain deformation analysis (global strain) may be superior to left ventricular ejection fraction (LVEF) in predicting all-cause mortality in patients with heart failure. Methods: In this retrospective study transthoracic echocardiographic examinations were retrieved from Gentofte Hospital heart failure clinic’s database in 1061 patients. The echocardiographic images were subsequently analyzed and conventional echocardiographic parameters and strain data were obtained. Results: During a median follow-up of 40 months 177 (16.7 %) patient died. Mean LVEF was 23.7 % and mean global strain was -8.12.884 (83.3%) were patients alive at follow-up and mean LVEF was 28.2 % while mean global strain was -9.86 %. The risk of dying increased with decreasing tertile of global strain being approximately three times higher for the patients in the lower tertile compared to the highest tertile (1. tertile vs 3. tertile HR: 3.38 95% CI: 2.3 [[Unable to Display Character: &#8211;]] 5.1), p-value: 0.001. Many of the conventional echocardiographic parameters proved to be predictors of mortality. Global strain remained an independent predictor of mortality in cox proportional-hazards models after adjusting for age, gender, BMI, total cholesterol, heart rate, atrial fibrillation, non-independent diabetes mellitus and conventional echocardiographic parameters (p-value: 0.014, 95% CI: 1.04 [[Unable to Display Character: &#8211;]] 1.37) while ejection fraction proved to be insignificant adjusted for aforementioned characteristics (p-value: 0.81, 95% CI: 0.96 [[Unable to Display Character: &#8211;]] 1.05 Atrial fibrillation modified the relationship between GLS and mortality (p for interaction = 0.023). HR 1.08 (CI 0.97 to 1.19, p=0.150) and HR 1.22 (CI 1.15 to 1.29, p<0.001) per 10 % decrease in GLS for patients with and without atrial fibrillation, respectively. Gender also modified the relationship between mean GLS and mortality (p for interaction = 0.047); HR 1.23 (CI 1.16 to 1.30, p<0.001) and HR 1.09 (CI 0.99 to 1.20, p=0.083) per 10 % decrease in GLS for men and women, respectively. Conclusion: In male patients with systolic heart failure and without atrial fibrillation global strain is an independent predictor of all-cause mortality. Furthermore, global strain proved to be a superior prognosticator when compared to left ventricular ejection fraction.

scholarly journals Meta-Analysis of 26 638 Individuals Identifies Two Genetic Loci Associated With Left Ventricular Ejection Fraction

2020 ◽  
Vol 13 (4) ◽  
Author(s):  
Hélène Choquet ◽  
Khanh K. Thai ◽  
Chen Jiang ◽  
Dilrini K. Ranatunga ◽  
Thomas J. Hoffmann ◽  
...  
Keyword(s):  
Heart Failure ◽  
Genetic Epidemiology ◽  
Meta Analysis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Adult Health ◽  
Uk Biobank ◽  
Ventricular Ejection Fraction ◽  
Genome Wide ◽  
A Genome

Background: Left ventricular ejection fraction (EF) is an indicator of cardiac function, usually assessed in individuals with heart failure and other cardiac conditions. Although family studies indicate that EF has an important genetic component with heritability estimates up to 0.61, to date only 6 EF-associated loci have been reported. Methods: Here, we conducted a genome-wide association study (GWAS) of EF in 26 638 adults from the Genetic Epidemiology Research on Adult Health and Aging and the UK Biobank cohorts. Results: A meta-analysis combining results from Genetic Epidemiology Research on Adult Health and Aging and UK Biobank identified a novel locus: TMEM40 on chromosome 3p25 (rs11719526; β=0.47 and P =3.10×10 −8 ) that replicated in Biobank Japan and confirmed recent findings implicating the BAG3 locus on chromosome 10q26 in EF variation, with the strongest association observed for rs17617337 (β=−0.83 and P =8.24×10 −17 ). Although the minor allele frequencies of TMEM40 rs11719526 were generally common (between 0.13 and 0.44) in different ethnic groups, BAG3 rs17617337 was rare (minor allele frequencies<0.05) in Asian and African ancestry populations. These associations were slightly attenuated, after considering antecedent cardiac conditions (ie, heart failure/cardiomyopathy, hypertension, myocardial infarction, atrial fibrillation, valvular disease, and revascularization procedures). This suggests that the effects of the lead variants at TMEM40 or BAG3 on EF are largely independent of these conditions. Conclusions: In this large and multiethnic study, we identified 2 loci, TMEM40 and BAG3 , associated with EF at a genome-wide significance level. Identifying and understanding the genetic determinants of EF is important to better understand the pathophysiology of this strong correlate of cardiac outcomes and to help target the development of future therapies.

Partial normalisation of cardiac mechanics with active CRT in patients with chronic failure: a novel application of 3.0T CMR

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Koshy ◽  
J Gierula ◽  
M Paton ◽  
P Swoboda ◽  
A.G Toms ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Output ◽  
Ejection Fraction ◽  
Cardiac Mechanics ◽  
Left Ventricular ◽  
Cardiac Response ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Ventricular Ejection Fraction ◽  
Heart Rates

Abstract Introduction Cardiac resynchronisation therapy (CRT) is a routine treatment for chronic heart failure (CHF) with reduced ejection fraction and conduction delay to improve prognosis. Cardiac mechanics in patients with CHF are believed to be altered from controls based on invasive and echocardiographic based data. Technological advancements in cardiac magnetic resonance (CMR) and devices enable investigation of the cardiac response to CRT over a range of heart rates. Methods Patients with a CRT-D device were enrolled from heart failure clinics at Leeds General Infirmary, UK. After a MRI safety assessment, a baseline device check was conducted by a cardiac physiologist. Left ventricular (LV) volumes and systolic BP were measured at baseline and heart rates of 75, 90, 100, 115, 125, and 140 (randomised order) with CRT active and intrinsic conduction. All scans were conducted using a 3.0 T Siemens Prisma MRI scanner. Analysis of the scans used commercially available software. LV contractility was derived as a ratio of the LV end systolic volume and systolic BP. A post scan device interrogation was conducted to assess for scanning safety. Control participants with a 3.0T MR-conditional dual chamber pacemakers completed a similar protocol. Results Scanning was conducted in 17 CRT patients and 13 controls with a pre and post device and lead interrogation. No patient experienced symptoms related to scanning or device failure. The mean LV ejection fraction at baseline in the CRT cohort was 33.7±12.9%. Left ventricular ejection fraction fell across both cohorts as paced heart rate increased with reduced deterioration in control patients and those with CRT active. Peak LV cardiac output was significantly higher during active CRT (p&lt;0.05). LV contractility was relatively static with CRT disabled (r2=0.13, p=0.38) and improved with CRT active (r2=0.91, p=0.01) and in controls (r2=0.74, p=0.01). Peak LV strain occurred at 100bpm during active CRT and in control patients whereas CRT disabled resulted in earlier deterioration. Conclusion We have demonstrated improvements in cardiac output and contractility consequent to active CRT using 3.0T CMR and subsequently validated via strain analysis. CRT appears to partially normalise cardiac mechanics across the range of heart rates studied. Further work is required to explore this phenomenon on a cellular or metabolic level. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): AK is supported by an unconditional grant provided by Medtronic

Sign in / Sign up

Export Citation Format

Share Document