A real-world assessment of the burden associated with hospitalizations in US patients with heart failure and left ventricular ejection fraction (LVEF) greater than 40%

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Lahoz ◽  
R Studer ◽  
G Farries ◽  
C Proudfoot ◽  
S Suminska ◽  
...  
Keyword(s):  
Heart Failure ◽  
Renal Disease ◽  
The United States ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Private Company ◽  
Ventricular Ejection Fraction ◽  
Hospitalization Rates ◽  
The Us

Abstract Background and purpose Heart failure (HF) is one of the leading causes of hospitalization among older adults and is associated with a large burden of disease for the individual, the patient's family, healthcare systems, and society. This study assessed the burden of hospitalizations in patients with HF with LVEF >40% in the United States (US). Methods This retrospective, non-interventional study identified adult patients with incident or prevalent HF in Optum® de-identified Electronic Health Record (EHR) dataset (2007–2018) between 01/01/2013 and 31/12/2017. Optum's longitudinal EHR repository is derived from dozens of healthcare provider organizations in the US, that include more than 700 Hospitals and 7000 Clinics; treating >95 million patients receiving care in the US. Patients were followed for up to 1 year or until last active date whichever occurred first. Comorbidities, all-cause hospitalizations (AcH) and primary cause HF hospitalizations (HFH) were analysed. Results 120,606 patients with HF and LVEF >40% (54% female) with a mean (SD) age of 71 (13) yrs were included, representing 80,324.74 patient-yrs follow-up (days). Common comorbidities were hypertension (91.8%), ischemic heart disease (IHD, 71.4%), atrial fibrillation (AF, 54.8%), renal disease (54.1%), type 2 diabetes (T2D, 50.7%), obesity (44.6%) and anemia (39%). Comorbidities including IHD (72.9% vs. 68.4%), AF (56.4% vs. 51.6%) and T2D (51.1% vs. 49.9%) were more often recorded in patients with LVEF >40-≤60% than >60% cohort while hypertension (91.6% vs. 92.2%), renal disease (53.8% vs. 54.6%), obesity (43.9% vs. 46.1%) and anemia (38.1% vs. 40.9%) had significantly higher frequency in the LVEF >60% cohort. The annualized AcH rate for patients with LVEF>40% was 1.44 and annualized HFH rate was 0.24 with a median length of stay of 3 and 4 days, respectively. Annualized hospitalization rates were significantly higher for women than men (both AcH and HFH). AcH rates were significantly higher and HFH rates were significantly lower for patients with LVEF>60% compared with LVEF >40-≤60. Conclusions This study demonstrates that patients with HF and LVEF >40% experience significant burden from comorbidities and hospitalizations from any-cause and for HF. The hospitalization rates are higher in women (both AcH and HFH) or patients with LVEF >60% (AcH only). Further focus on reduction of hospitalizations and interdisciplinary management of patients with HF should be warranted. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novartis Pharma AG

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 Sacubitril/valsartan improves ventilation stability in patients with chronic heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Sciarrone ◽  
C Borrelli ◽  
A Giannoni ◽  
F Gentile ◽  
A Aimo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Apnea Hypopnea Index ◽  
Funding Source ◽  
Systolic Pulmonary Artery Pressure ◽  
Private Company ◽  
Ventricular Ejection Fraction ◽  
The Impact

Abstract Background Sacubitril/valsartan (SV) ameliorates symptoms and prognosis in patients with heart failure and reduced ejection fraction (HFrEF), but the reasons for such effects are unclear. The impact of SV on ventilation has never been investigated. In HFrEF, apneas are highly prevalent both at daytime and nighttime and are associated with increased mortality. Purpose We hypothesize that treatment with SV could favourably stabilize ventilation by reducing the severity of central apneas in patients with HFrEF. Methods 51 patients with HFrEF (mean age 67±9 years, mean left ventricular ejection fraction, LVEF 27±7%) and apneas defined by an apnea-hypopnea index, AHI≥5 (median 16, interquartile range 8–28) events/hour, eligible to treatment with SV and previously on optimal medical therapy for HFrEF, were enrolled. An extensive evaluation including cardiac ultrasound and a 24-hour cardiorespiratory monitoring was performed. Results After six months of treatment with SV, left ventricle systolic and diastolic function, mitral regurgitation (MR), left atrial volume (LAVI) and systolic pulmonary artery pressure (sPAP) were improved. Severity of apneas was reduced by 50%, 65% and 36% throughout the 24-hour, at daytime and nighttime, respectively. Conclusion Besides its known efficacy on cardiac remodeling, SV positively decreases the apneic burden in patients with HFrEF. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics unrestricted grant

Caregiver burden of patients with heart failure with a left-ventricular ejection fraction (LVEF) less than or equal to 60%: a cross-sectional survey in the EU

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Lahoz ◽  
S Corda ◽  
C Proudfoot ◽  
A.F Fonseca ◽  
S Cotton ◽  
...  
Keyword(s):  
Heart Failure ◽  
Caregiver Burden ◽  
Nyha Class ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Cross Sectional Survey ◽  
Private Company ◽  
Cross Sectional ◽  
Patients With Heart Failure

Abstract Background and purpose The majority of patients with heart failure (HF) have difficulties in independently carrying out activities of daily living and hence, require support from caregivers (CGs). This study assessed the quality of life (QoL) of CGs of HF patients with sub-normal LVEF (≤60%). Methods A cross-sectional survey of HF patients and their CGs was conducted in France, Germany, Italy, Spain and the UK. Cardiologists and primary care physicians completed patient record forms (PRF) between June and November 2019. Caregivers of the same patients were invited to complete a caregiver self-completion survey, which included the Family Caregiver QoL Scale (FAMQOL) and EQ-5D. Patient demographics were derived from PRFs. Results 361 CGs (73.1% female, mean age: 58.8 yrs) and HF patients (39.9% female, mean age: 71.2 yrs) were included. 58.2% of the CGs were spouses, 23.4% a child of the patient. On average, CGs devoted 20 hrs/week in the care of HF patients; this CG time increased from 12 to 26 hrs/week with NYHA class I to III/IV of the HF patient. Further, anxiety/stress was experienced overall by 29/31% of CGs which increased from 27/17% for NYHA I to 40/41% for NYHA III/IV of the HF patient (Table 1). Conclusions Caregivers of patients with HF and LVEF ≤60% spend a significant amount of time to provide daily support to HF patients. Patients with progressive disease were older, more polymorbid and had a higher disease duration. These factors likely contributed towards increased caregiver burden of HF patients with increased NYHA class. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novartis Pharma AG

scholarly journals Novel antisense therapy targeting microRNA-132 in patients with heart failure

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
J Taubel ◽  
W Hauke ◽  
S Rump ◽  
J Viereck ◽  
S Batkai ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Fibrosis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Private Company ◽  
Ventricular Ejection Fraction ◽  
Pharmacodynamic Effects ◽  
Amino Terminal ◽  
Patients With Heart Failure

Abstract Background Cardiac microRNA-132-3p (miR-132) levels are increased in patients with heart failure (HF) and mechanistically drive cardiac remodelling processes. CDR132L, a specific antisense oligonucleotide, is a first-in-class miR-132 inhibitor that attenuates and even reverses HF in preclinical models. Purpose The aim of the current clinical Phase 1b study was to assess safety, pharmacokinetics, target engagement, and exploratory pharmacodynamic effects of CDR132L in patients on standard-of-care therapy for chronic ischaemic HF in a randomized, placebo-controlled, double-blind, dose-escalation study. Methods Patients had left ventricular ejection fraction between ≥30% and <50% or amino terminal fragment of pro-brain natriuretic peptide (NT-proBNP) >125 ng/L at screening. Twenty-eight patients were randomized to receive CDR132L (0.32, 1, 3, and 10 mg/kg body weight) or placebo (0.9% saline) in two intravenous infusions, 4 weeks apart in four cohorts of seven (five verum and two placebo) patients each. Results CDR132L was safe and well tolerated, without apparent dose-limiting toxicity. A pharmacokinetic/pharmacodynamic dose modelling approach suggested an effective dose level at ≥1 mg/kg CDR132L. CDR132L treatment resulted in a dose-dependent, sustained miR-132 reduction in plasma. Patients given CDR132L ≥1 mg/kg displayed median 23.3% NT-proBNP reduction, vs. 0.9% median increase in the control group. CDR132L treatment induced significant QRS narrowing and positive trends for cardiac fibrosis biomarkers. Conclusions This study is the first clinical trial of an antisense drug in HF patients. CDR132L was safe and well tolerated, confirmed linear plasma pharmacokinetics with no signs of accumulation, and suggests cardiac functional improvements. The indicative efficacy of this drug is very encouraging justifying additional clinical studies to confirm the beneficial CDR132L pharmacodynamic effects for the treatment of HF. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Cardior Pharmaceuticals GmbH

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

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)

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<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

scholarly journals The relationship between glycosylation of proBNP at threonine 71, BNP, BNP1–32 and obesity in patients with heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L.K Lewis ◽  
S.D Raudsepp ◽  
T.G Yandle ◽  
C.J Pemberton ◽  
R.N Doughty ◽  
...  
Keyword(s):  
Heart Failure ◽  
New Zealand ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Obese Patients ◽  
Ventricular Ejection Fraction ◽  
National Budget ◽  
National Heart Foundation ◽  
Public Grant

Abstract Background Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Measurement of BNP and NTproBNP are used in HF for diagnosis and prognosis but levels of these peptides are inappropriately low in obesity, a condition which is associated with increased HF. Cleavage of proBNP to produce BNP and NT-proBNP requires proBNP to be unglycosylated at threonine 71 (T71). Gycosylation at T71 is affected by obesity, resulting in lower plasma NT-proBNP concentrations in patients with higher BMI. However the relationships between BMI, proBNP glycosylation and BNP (particularly the bioactive cardio-protective peptide BNP1-32) have not previously been described. Methods Validated in-house assays for BNP, BNP1-32, proBNP, proBNP unglycosylated at T71 (NG-T71) and the commercial Roche assay for NT-proBNP were applied to plasma samples obtained from patients with HF (n=321, PEOPLE study: Prospective Evaluation of Outcome in Patients with Left Ventricular Ejection Fraction). Results Median (IQR) concentrations of BNP, BNP1-32, proBNP, NG-T71 and NTproBNP were 10.7 (5–21), 5 (2–9), 27.8 (9–62), 6.2 (3–22) and 217 (104–425) pmol/L respectively. BMI was inversely related to NG-T71, NT-proBNP, BNP and BNP1-32 (r=−0.19, −0.40, −0.36 and −0.34 respectively, all p<0.01) but not proBNP (r=0.11, ns). ProBNP levels in patients with BMI above or below 30 kg/m2 were similar (29.8 (11.2–56.6) and 22.5 (3.9–65) pmol/L, p=0.51), whereas NG-T71, NT-proBNP, BNP and BNP1-32 levels were increased (p<0.001) in patients with BMI <30 (11.6 (3–25.6), 263 (153–486), 13.8 (6.5–25.5) and 6.3 (2.8–10.4)) compared to BMI >30 (3 (1–16), 127 (63–274), 7.8 (3–14) and 3.6 (1.1–7) respectively. The BMI >30 group had increased ProBNP:NT-proBNP, ProBNP:BNP and ProBNP:BNP1-32 ratios (all p<0.001) and proBNP:NG-T71 (p=0.037), whereas ratios of NG-T71 to BNP, BNP1-32 or NT-proBNP were not related to BMI. Patients with diabetes (n=90) also had lower BNP, BNP1-32 (both p<0.01), NG-T71 and NT-proBNP concentrations (both p<0.05), but not proBNP (p=0.46), and a trend towards a higher proBNP:BNP1-32 ratio (p=0.06). Discussion and conclusion The negative association between BMI and plasma NT-proBNP and BNP is not well understood. We recently reported that obese patients with HF have reduced circulating levels of proBNP unglycosylated at T71. In this expanded sample we show that whilst proBNP remains unaffected by BMI, both immunoreactive BNP and more specifically bioactive BNP1–32 levels, and NT-proBNP, are decreased with obesity in conjunction with increased glycosylation at T71. Increased glycosylation at proBNP-T71 reduces the amount of proBNP cleaved to form NT-proBNP and BNP resulting in decreased production and lowered circulating concentrations of these clinically used marker peptides. Our results provide a robust mechanism to explain the reduction in NT-proBNP and BNP levels observed in obese patients and confirm this is associated with reduced bioactive BNP1–32. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Heart Foundation of New Zealand, nHealth Research Council of New Zealand

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