scholarly journals Transcriptomic Research in Heart Failure with Preserved Ejection Fraction: Current State and Future Perspectives

2020 ◽  
Vol 6 ◽  
Author(s):  
Sebastian Rosch ◽  
Karl-Philipp Rommel ◽  
Markus Scholz ◽  
Holger Thiele ◽  
Philipp Lurz

Heart failure with preserved ejection fraction (HFpEF) is increasing in incidence and has a higher prevalence compared with heart failure with reduced ejection fraction. So far, no effective treatment of HFpEF is available, due to its complex underlying pathophysiology and clinical heterogeneity. This article aims to provide an overview and a future perspective of transcriptomic biomarker research in HFpEF. Detailed characterisation of the HFpEF phenotype and its underlying molecular pathomechanisms may open new perspectives regarding early diagnosis, improved prognostication, new therapeutic targets and tailored therapies accounting for patient heterogeneity, which may improve quality of life. A combination of cross-sectional and longitudinal study designs with sufficiently large sample sizes are required to support this concept.

BJGP Open ◽  
2021 ◽  
pp. BJGPO.2021.0094
Author(s):  
Faye Forsyth ◽  
James Brimicombe ◽  
Joseph Cheriyan ◽  
Duncan Edwards ◽  
Richard Hobbs ◽  
...  

BackgroundMany patients with heart failure with preserved ejection fraction (HFpEF) are undiagnosed, and UK general practice registers do not typically record HF sub-type. Improvements in management of HFpEF is dependent on improved identification and characterisation of patients in primary care.AimsTo describe a cohort of patients recruited from primary care with suspected HFpEF and compare patients in whom HFpEF was confirmed and refuted.Design and SettingBaseline data from a longitudinal cohort study of patients with suspected HFpEF recruited from primary care in two areas of England.MethodsA screening algorithm and review were used to find patients on HF registers without a record of reduced ejection fraction. Baseline evaluation included cardiac, mental and physical function, clinical characteristics and patient reported outcomes. Confirmation of HFpEF was clinically adjudicated by a cardiologist.ResultsNinety-three (61%) of 152 patients were confirmed HFpEF. The mean age of patients with HFpEF was 79.3, 46% were female, 80% had hypertension, and 37% took 10 or more medications. Patients with HFpEF were more likely to be obese, pre-frail/frail, report more dyspnoea and fatigue, were more functionally impaired, and less active than patients in whom HFpEF was refuted. Few had attended cardiac rehabilitation.ConclusionsPatients with confirmed HFpEF had frequent multimorbidity, functional impairment, frailty and polypharmacy. Although comorbid conditions were similar between people with and without HFpEF, the former had more obesity, symptoms and worse physical function. These findings highlight the potential to optimise well-being through comorbidity management, medication rationalisation, rehabilitation, and supported self-management.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Shahryar M Chowdhury ◽  
Kimberly E McHugh ◽  
Stephanie S Gaydos ◽  
carolyn taylor ◽  
Eric M Graham ◽  
...  

Introduction: The cardiac mechanics that contribute to the development of heterogenous heart failure phenotypes in Fontan patients have not been investigated. The objective of this study was to investigate the differences in contractility, afterload, and ventriculo-arterial (VA) coupling between patients with heart failure and preserved ejection fraction (HFpEF) versus heart failure with reduced ejection fraction (HFrEF). Methods: Core-lab echocardiograms were obtained from the publically-available Pediatric Heart Network Fontan Cross-sectional Study database. Ejection fraction was considered abnormal if < 50%. Diastolic function was defined as abnormal if the diastolic pressure:volume quotient (lateral E:e’/end-diastolic volume) was > 10 th percentile. Patients were divided into three groups: 1 = normal EF and normal diastolic function, 2 = decreased EF with normal diastolic function, 3 = normal EF with abnormal diastolic function. End-systolic elastance (Ees), a measure of contractility, and arterial elastance (Ea), a measure of afterload, were calculated. VA coupling was defined as Ea/Ees. Results: 238 patients (61% left, 39% right ventricular dominant) were included. Differences between groups are reported in the Table. Conclusion: Both Fontan patients with HFpEF and HFrEF display increased afterload compared to their non-heart failure counterparts. However, HFpEF patients displayed a hypercontractile state to maintain a VA coupling ratio comparable to the non-heart failure group. These measures of cardiac mechanics may be useful in identifying the mechanisms that drive Fontan patients toward HFpEF versus HFrEF phenotypes.


2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Kazunori Omote ◽  
Frederik H. Verbrugge ◽  
Barry A. Borlaug

Approximately half of all patients with heart failure (HF) have a preserved ejection fraction, and the prevalence is growing rapidly given the aging population in many countries and the rising prevalence of obesity, diabetes, and hypertension. Functional capacity and quality of life are severely impaired in heart failure with preserved ejection fraction (HFpEF), and morbidity and mortality are high. In striking contrast to HF with reduced ejection fraction, there are few effective treatments currently identified for HFpEF, and these are limited to decongestion by diuretics, promotion of a healthy active lifestyle, and management of comorbidities. Improved phenotyping of subgroups within the overall HFpEF population might enhance individualization of treatment. This review focuses on the current understanding of the pathophysiologic mechanisms underlying HFpEF and treatment strategies for this complex syndrome. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Gianluigi Savarese ◽  
Camilla Hage ◽  
Ulf Dahlström ◽  
Pasquale Perrone-Filardi ◽  
Lars H Lund

Introduction: Changes in N-terminal pro brain natriuretic peptide (NT-proBNP) have been demonstrated to correlate with outcomes in patients with heart failure (HF) and reduced ejection fraction (EF). However the prognostic value of a change in NT-proBNP in patients with heart failure and preserved ejection fraction (HFPEF) is unknown. Hypothesis: To assess the impact of changes in NT-proBNP on all-cause mortality, HF hospitalization and their composite in an unselected population of patients with HFPEF. Methods: 643 outpatients (age 72+12 years; 41% females) with HFPEF (ejection fraction ≥40%) enrolled in the Swedish Heart Failure Registry between 2005 and 2012 and reporting NT-proBNP levels assessment at initial registration and at follow-up were prospectively studied. Patients were divided into 2 groups according the median value of NT-proBNP absolute change that was 0 pg/ml. Median follow-up from first measurement was 2.25 years (IQR: 1.43 to 3.81). Adjusted Cox’s regression models were performed using total mortality, HF hospitalization (with censoring at death) and their composite as outcomes. Results: After adjustments for 19 baseline variables including baseline NT-proBNP, as compared with an increase in NT-proBNP levels at 6 months (NT-proBNP change>0 pg/ml), a reduction in NT-proBNP levels (NT-proBNP change<0 pg/ml) was associated with a 45.2% reduction in risk of all-cause death (HR: 0.548; 95% CI: 0.378 to 0.796; p:0.002), a 50.1% reduction in risk of HF hospitalization (HR: 0.49; 95% CI: 0.362 to 0.689; p<0.001) and a 42.6% reduction in risk of the composite outcome (HR: 0.574; 95% CI: 0.435 to 0.758; p<0.001)(Figure). Conclusions: Reductions in NT-proBNP levels over time are independently associated with an improved prognosis in HFPEF patients. Changes in NT-proBNP could represent a surrogate outcome in phase 2 HFPEF trials.


2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Andreas B. Gevaert ◽  
Katrien Lemmens ◽  
Christiaan J. Vrints ◽  
Emeline M. Van Craenenbroeck

Although the burden of heart failure with preserved ejection fraction (HFpEF) is increasing, there is no therapy available that improves prognosis. Clinical trials using beta blockers and angiotensin converting enzyme inhibitors, cardiac-targeting drugs that reduce mortality in heart failure with reduced ejection fraction (HFrEF), have had disappointing results in HFpEF patients. A new “whole-systems” approach has been proposed for designing future HFpEF therapies, moving focus from the cardiomyocyte to the endothelium. Indeed, dysfunction of endothelial cells throughout the entire cardiovascular system is suggested as a central mechanism in HFpEF pathophysiology. The objective of this review is to provide an overview of current knowledge regarding endothelial dysfunction in HFpEF. We discuss the molecular and cellular mechanisms leading to endothelial dysfunction and the extent, presence, and prognostic importance of clinical endothelial dysfunction in different vascular beds. We also consider implications towards exercise training, a promising therapy targeting system-wide endothelial dysfunction in HFpEF.


2021 ◽  
Vol 9 (11) ◽  
pp. 521-526
Author(s):  
A. Maliki Alaoui ◽  
◽  
Y. Fihri ◽  
A. Ben El Mekki ◽  
H. Bouzelmat ◽  
...  

Heart failure (HF) is a major public issue taking an epidemic dimension globally. Its incidence is continuing to rise because of a growing and aging population. We held a cross-sectional retrospective studyin the cardiology department of Mohamed V military teaching hospital of Rabat in morocco fromSeptember 2019 toSeptember 2021, including 104 patients admitted with HF. The mean age was 68.5 ±10.3year. Hypertension and diabetes mellitus are the most common risk factors. HF with reduced ejection fraction represents about 49%. Forty-four percent had dilated cardiomyopathy. Ischemic heart disease is the first cause of HF.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Alexander T Sandhu ◽  
Jeremy D Goldhaber-Fiebert ◽  
Mintu P Turakhia ◽  
Daniel W Kaiser ◽  
Paul A Heidenreich

Background: For management of heart failure, the value of the CardioMems device remains uncertain. We assessed the cost-effectiveness of the CardioMems device. Methods: We developed a Markov model to determine quality-adjusted life-years (QALYs), cost, and cost-effectiveness of patients with heart failure receiving CardioMems implantation compared to those with routine care. In the main case analysis, we modeled the intervention in the CHAMPION trial cohort, which included patients with NYHA Class III heart failure with a heart failure hospitalization within the past twelve months. We also performed subgroup analyses of patients with preserved ejection fraction or reduced ejection fraction, and a scenario analysis of a second cohort of patients from the CHARM trials with a previous heart failure hospitalization. We obtained event rates and utilities from published trial data; we used costs from literature estimates and Medicare payment data. The main case analysis was calibrated to the hospitalization and survival rates of the CHAMPION trial. Results: In the CHAMPION trial main case analysis, CardioMems reduced lifetime hospitalizations (2.37 versus 3.27), increased months of survival (67 versus 62), increased QALYs (2.66 versus 2.38) and increased costs ($171,132 versus $154,084), yielding a cost of $59,520 per QALY gained or $40,301 per life-year gained. The cost per QALY gained was $71,964 in patients with reduced ejection fraction compared to $34,899 in those with preserved ejection fraction. In less ill patients from the CHARM trials, which included patients with NYHA Class II heart failure, the device cost increased to $110,565 per QALY gained. If the device cost decreased from $17,500 in the main case analysis to $15,000, the intervention would cost less than $50,000 per QALY gained. The duration of effectiveness was initially assumed to be lifelong; if less than 29 months, CardioMems would cost more than $150,000 per QALY gained. Conclusion: The CardioMems device is cost-effective in populations similar to the CHAMPION trial, with a cost of less than $100,000 per QALY gained, if durability of device effectiveness is sustained. Post-marketing surveillance data on the device’s durability will further clarify its value.


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