scholarly journals Impaired preload reserve is an important haemodynamic characteristics that discriminates between physiological ageing and overt heart failure with preserved ejection fraction

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
A Shono ◽  
K Matsumoto ◽  
N Yamada ◽  
K Kusunose ◽  
M Suzuki ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background  Ageing process per se is a major risk factor for heart failure (HF). In fact, the incidence of HF with preserved ejection fraction (HFpEF) dramatically increases with age. Although ageing plays a central role in the development of HFpEF, not all the elderly patients develop clinical HFpEF. Multiple abnormalities in the cardiovascular system have been proposed to contribute to the development of HFpEF. However, the pathophysiology that discriminates between physiological ageing and overt HFpEF is incompletely understood. Purpose  The purpose of this study was to assess the effects of ageing on the cardiac structures and haemodynamics. Moreover, we evaluated the determinant factor that discriminates between physiological ageing and overt HFpEF by non-invasive preload increasing manoeuvre using leg-positive pressure (LPP) stress echocardiography. Methods  A total of 91 subjects were prospectively recruited in this study: 22 patients with HFpEF and 69 healthy controls. Normal controls were further stratified into 3 age groups: young (n = 19, 20-40 years of age), middle-aged (N = 25, 40-65 years) and elderly (n = 25, >65 years). All subjects underwent LPP stress with a continuous external pressure of 90 mmHg around both lower limbs using dedicated airbags (Fig.).  Results  The left ventricular mass index (LVMI; young, 68 ± 19 g/m²; middle-age, 70 ± 18 g/m²; elderly, 84 ± 21 g/m²) and also the relative wall thickness (RWT; young, 0.34 ± 0.09; middle-age, 0.41 ± 0.06; elderly 0.55 ± 0.10) increased with ageing, which was accelerated in HFpEF (LVMI: 111 ± 32 g/m², RWT; 0.63 ± 0.19, ANOVA P < 0.001, respectively). Although baseline LV ejection fraction and cardiac output were quite comparable between groups, E/e’ ratio significantly increased with with ageing (ANOVA P < 0.001, Fig.). During LPP stress, E/e’ ratio significantly increased in the middle-aged and elderly groups (from 8.8 ± 2.7 to 9.7 ± 3.3, and from 11.4 ± 2.4 to 13.0 ± 2.2, P < 0.05, respectively), which was further deteriorated in HFpEF (from 16.8 ± 5.8 to 18.0 ± 7.6, P < 0.05). On the other hand, stroke volume index (SVi) significantly increased in each healthy group during LPP stress (young; from 45 ± 10 to 50 ± 11 mL/m², middle-age; from 39 ± 7 to 44 ± 6 mL/m² and elderly; from 37 ± 7 to 43 ± 8 mL/m², all P < 0.001), while SVi failed to increase in the HFpEF group (from 45 ± 13 to 45 ± 14 mL/m², P = 0.60). In a multivariate logistic regression analysis, LVMI (hazard ratio; HR 1.055, P < 0.05), baseline E/e’ (HR 1.444; P < 0.05), and ΔSVi (HR 0.755; P < 0.05) during LPP stress were the independent parameters that characterised overt HFpEF. Conclusions  Striking parallels between structure-function alterations were observed in the physiological cardiovascular ageing process, which was further accelerated in patients with HFpEF. Not only structural remodeling and impaired diastolic function, but also impaired systolic reserve during preload stress is important haemodynamic feature that characterise the pathophysiology of HFpEF. Abstract Figure.

2019 ◽  
Vol 28 (01) ◽  
pp. 044-049
Author(s):  
Sidhi Purwowiyoto ◽  
Budhi Purwowiyoto ◽  
Amiliana Soesanto ◽  
Anwar Santoso

Exercise improves morbidity, fatality rate, and quality of life in heart failure with low ejection fraction, but fewer data available in heart failure with preserved ejection fraction (HFPEF).The purpose of this study is to test the hypothesis that exercise training might improve the longitudinal intrinsic left ventricular (LV) function in HFPEF patients.This quasi-experimental study had recruited 30 patients with HFPEF. Exercise training program had been performed for a month with a total of 20 times exercise sessions and evaluated every 2 weeks. Echocardiography was performed before sessions, second week and fourth week of exercise training. Six-minute walk tests (6MWTs) and quality-of-life variables using Minnesota living with HF scoring and the 5-item World Health Organization Well-Being Index scoring were measured before and after exercise as well.Left ventricular filling pressure, represented by the ratio of early diastolic mitral flow velocity/early diastolic annular velocity and left atrial volume index, improved during exercise. The longitudinal intrinsic LV function, represented by four-chamber longitudinal strain, augmented during exercise (p < 0.001). Aerobic capacity, measured by 6MWT, increased significantly (p = 0.001). Quality of life improved significantly during exercise (p < 0.001).Exercise training was suggested to improve the longitudinal intrinsic LV function and quality of life in HFPEF. Clinical Trial Registration: ACTRN12614001042639.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Soeren Jan Backhaus ◽  
Torben Lange ◽  
Elisabeth George ◽  
Kristian Hellenkamp ◽  
Roman Gertz ◽  
...  

Introduction: Invasive right heart catherization (RHC) using exercise-stress is the reference-standard for the diagnosis of heart failure with preserved ejection fraction (HFpEF) but carries the risk of the procedure. Real-time cardiovascular magnetic resonance (RT-CMR) imaging allows bicycle exercise CMR with unprecedented temporal and spatial resolution and may represent a novel non-invasive alternative. Methods: The HFpEF stress trial (NCT03260621) prospectively included 75 patients with echocardiographic signs of diastolic dysfunction and dyspnoea on exertion (E/E’>8, NYHA≥II) who underwent echocardiography, RHC and RT-CMR at rest and exercise-stress. HFpEF was defined according to pulmonary capillary wedge pressure (PCWP ≥15mmHg at rest or ≥25mmHg during exercise stress). RT-CMR functional assessments included time-volume-curves for total and early (1/3) diastolic left ventricular (LV) filling or left atrial (LA) emptying and LV/LA long axis strain (LAS). Results: HFpEF patients (n=34, mean PCWP rest 13mmHg, stress 27mmHg) had higher E/e’ (12.5 vs 9.15), NT-proBNP (255 vs 75ng/l) and LA volume index (43.8 vs 36.2ml/m 2 ) compared to non-HFpEF patients (n=34, rest 8mmHg, stress 18mmHg, p≤0.001 for all). There were no differences in RT-CMR LV total and early diastolic filling at rest and during exercise-stress (p≥0.164). In contrast, RT-CMR revealed impaired stress LA total (p=0.033) and early (p<0.001) diastolic emptying in HFpEF. LA LAS was the only impaired parameter at rest (p<0.001) and emerged as the best predictor for the presence of HFpEF during exercise-stress testing (AUC rest 0.82 vs stress 0.93, p=0.029). Conclusions: RT-CMR allows highly accurate identification of HFpEF during physiological exercise and may establish itself as a novel non-invasive diagnostic alternative for routine clinical use.


2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Jenna C Edwards ◽  
Madeleine Dionne ◽  
T. D Olver ◽  
Jan R Ivey ◽  
Pamela K Thorne ◽  
...  

Introduction: Heart failure with preserved ejection fraction (HFpEF) is clinically characterized by an increased incidence in females and many comorbidities including type 2 diabetes (T2D) and obesity. Animal models accurately representing clinical HFpEF are lacking; thus, the purpose of this study was to examine left ventricular (LV) mechanics in a novel Ossabaw swine model of chronic pressure-overload (aortic-banding; AB) and T2D (Western diet; WD) using two dimensional speckle tracking echocardiography (2D-STE). We hypothesized that global LV strain would be decreased primarily in the longitudinal direction in WD-AB animals. Methods: Female Ossabaws were randomly divided into 2 groups: CON (n=5) and WD-AB (n=5). LV function and strain were measured at 1 year of age after 6 mo. of AB and 9 mo. of WD via pressure-volume relations and 2D-STE. Significance was set at P < 0.05 using t-test vs. CON. Results: In the WD-AB group, ejection fraction (EF%) and end diastolic volume were normal (>50%), and observed in parallel with increased LV weight, lung weight, and LV diastolic wall thickness (i.e. concentric hypertrophy). WD-AB group had increased HOMA-IR and body surface area, two common features in T2D. In WD-AB animals, although global longitudinal systolic strain rate and end systolic displacement were increased, stroke volume index was decreased. Early diastolic rotation rate was decreased, while global longitudinal late diastolic strain rate was increased in the WD-AB group. These changes, considered in parallel with an increased end diastolic pressure-volume relationship in WD-AB animals, are consistent with diastolic dysfunction. In contrast, longitudinal, radial, and circumferential early diastolic strain rates increased in the WD-AB group. Conclusion: Contrary to our hypothesis, LV longitudinal strain was increased during both systole and diastole, and observed in parallel with decreased early diastolic untwisting in WD-AB animals. Our results suggest alterations to LV mechanics do not preserve normal systolic and diastolic cardiac function, despite normal resting EF%, in this novel translational model of pressure-overload HF with potential relevance to human HFpEF including associated clinical comorbidities (sex, obesity, and T2D).


2019 ◽  
Vol 10 ◽  
pp. 204201881986159 ◽  
Author(s):  
Gaurav S. Gulsin ◽  
Prathap Kanagala ◽  
Daniel C. S. Chan ◽  
Adrian S. H. Cheng ◽  
Lavanya Athithan ◽  
...  

Background: Attempts to characterize cardiac structure in heart failure with preserved ejection fraction (HFpEF) in people with type 2 diabetes (T2D) have yielded inconsistent findings. We aimed to determine whether patients with HFpEF and T2D have a distinct pattern of cardiac remodelling compared with those without diabetes and whether remodelling was related to circulating markers of inflammation and fibrosis and clinical outcomes. Methods: We recruited 140 patients with HFpEF (75 with T2D and 65 without). Participants underwent comprehensive cardiovascular phenotyping, including echocardiography, cardiac magnetic resonance imaging and plasma biomarker profiling. Results: Patients with T2D were younger (age 70 ± 9 versus 75 ± 9y, p = 0.002), with evidence of more left ventricular (LV) concentric remodelling (LV mass/volume ratio 0.72 ± 0.15 versus 0.62 ± 0.16, p = 0.024) and smaller indexed left atrial (LA) volumes (maximal LA volume index 48 ± 20 versus 59 ± 29 ml/m2, p = 0.004) than those without diabetes. Plasma biomarkers of inflammation and extracellular matrix remodelling were elevated in those with T2D. Overall, there were 45 hospitalizations for HF and 22 deaths over a median follow-up period of 47 months [interquartile range (IQR) 38–54]. There was no difference in the primary composite endpoint of hospitalization for HF and mortality between groups. On multivariable Cox regression analysis, age, prior HF hospitalization, history of pulmonary disease and LV mass/volume were independent predictors of the primary endpoint. Conclusions: Patients with HFpEF and T2D have increased concentric LV remodelling, smaller LA volumes and evidence of increased systemic inflammation compared with those without diabetes. This suggests the underlying pathophysiology for the development of HFpEF is different in patients with and without T2D. ClinicalTrials.gov identifier: NCT03050593.


2016 ◽  
Vol 310 (1) ◽  
pp. H4-H13 ◽  
Author(s):  
Mahmoud Abdellatif ◽  
Sara Leite ◽  
Mohamed Alaa ◽  
José Oliveira-Pinto ◽  
Marta Tavares-Silva ◽  
...  

Preserved ejection fraction heart failure (HFpEF) diagnosis remains controversial, and invasive left ventricular (LV) hemodynamic evaluation and/or exercise testing is advocated by many. The stiffer HFpEF myocardium may show impaired stroke volume (SV) variation induced by fluctuating LV filling pressure during ventilation. Our aim was to investigate spectral transfer function (STF) gain from end-diastolic pressure (EDP) to indexed SV (SVi) in experimental HFpEF. Eighteen-week-old Wistar-Kyoto (WKY) and ZSF1 lean (ZSF1 Ln) and obese rats (ZSF1 Ob) randomly underwent LV open-chest (OC, n = 8 each group) or closed-chest hemodynamic evaluation (CC, n = 6 each group) under halogenate anesthesia and positive-pressure ventilation at constant inspiratory pressure. Beat-to-beat fluctuations in hemodynamic parameters during ventilation were assessed by STF. End-diastolic stiffness (βi) and end-systolic elastance (Eesi) for indexed volumes were obtained by inferior vena cava occlusion in OC (multibeat) or single-beat method estimates in CC. ZSF1 Ob showed higher EDP spectrum ( P < 0.001), higher STF gain between end-diastolic volume and EDP, and impaired STF gain between EDP and SVi compared with both hypertensive ZSF1 Ln and normotensive WKY controls ( P < 0.001). Likewise βi was only higher in ZSF1 Ob while Eesi was raised in both ZSF1 groups. On multivariate analysis βi and not Eesi correlated with impaired STF gain from EDP to SVi ( P < 0.001), and receiver-operating characteristics analysis showed an area under curve of 0.89 for higher βi prediction ( P < 0.001). Results support further clinical testing of STF analysis from right heart catheterization-derived EDP surrogates to noninvasively determined SV as screening/diagnostic tool to assess myocardial stiffness in HFpEF.


Author(s):  
Sören J. Backhaus ◽  
Torben Lange ◽  
Elisabeth F. George ◽  
Kristian Hellenkamp ◽  
Roman J. Gertz ◽  
...  

Background: Right heart catheterisation (RHC) using exercise-stress is the reference standard for the diagnosis of heart failure with preserved ejection fraction (HFpEF) but carries the risk of the invasive procedure. We hypothesized that real-time cardiovascular magnetic resonance (RT-CMR) exercise imaging with pathophysiologic data at excellent temporal and spatial resolution may represent a contemporary non-invasive alternative for diagnosing HFpEF. Methods: The HFpEF stress trial (DZHK-17, NCT03260621) prospectively recruited 75 patients with echocardiographic signs of diastolic dysfunction and dyspnea on exertion (E/e'>8, New York Heart Association (NYHA) class ≥II) to undergo echocardiography, RHC and RT-CMR at rest and during exercise-stress. HFpEF was defined according to pulmonary capillary wedge pressure (PCWP ≥15mmHg at rest or ≥25mmHg during exercise stress). RT-CMR functional assessments included time-volume curves for total and early (1/3) diastolic left ventricular (LV) filling, left atrial (LA) emptying and LV/LA long axis strain (LAS). Results: HFpEF patients (n=34, median PCWP rest 13mmHg, stress 27mmHg) had higher E/e' (12.5 vs. 9.15), NT-proBNP (255 vs. 75ng/l) and LA volume index (43.8 vs. 36.2ml/m 2 ) compared to non-cardiac dyspnea patients (n=34, rest 8mmHg, stress 18mmHg, p≤0.001 for all). Seven patients were excluded due to the presence of non HFpEF cardiac disease causing dyspnea on imaging. There were no differences in RT-CMR LV total and early diastolic filling at rest and during exercise-stress (p≥0.164) between HFpEF and non-cardiac dyspnea. RT-CMR revealed significantly impaired LA total and early (p<0.001) diastolic emptying in HFpEF during exercise-stress. RT-CMR exercise-stress LA LAS was independently associated with HFpEF (adjusted odds ratio 0.657, 95% confidence interval [0.516; 0.838], p=0.001) after adjustment for clinical and imaging parameters and emerged as the best predictor for HFpEF (area under the curve rest 0.82 vs. exercise-stress 0.93, p=0.029). Conclusions: RT-CMR allows highly accurate identification of HFpEF during physiological exercise and qualifies as a suitable non-invasive diagnostic alternative. These results will need to be confirmed in multi-centre prospective research studies to establish widespread routine clinical use. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique Identifier: NCT03260621


2019 ◽  
Vol 40 (40) ◽  
pp. 3297-3317 ◽  
Author(s):  
Burkert Pieske ◽  
Carsten Tschöpe ◽  
Rudolf A de Boer ◽  
Alan G Fraser ◽  
Stefan D Anker ◽  
...  

Abstract Making a firm diagnosis of chronic heart failure with preserved ejection fraction (HFpEF) remains a challenge. We recommend a new stepwise diagnostic process, the ‘HFA–PEFF diagnostic algorithm’. Step 1 (P=Pre-test assessment) is typically performed in the ambulatory setting and includes assessment for HF symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes mellitus, elderly, atrial fibrillation), and diagnostic laboratory tests, electrocardiogram, and echocardiography. In the absence of overt non-cardiac causes of breathlessness, HFpEF can be suspected if there is a normal left ventricular ejection fraction, no significant heart valve disease or cardiac ischaemia, and at least one typical risk factor. Elevated natriuretic peptides support, but normal levels do not exclude a diagnosis of HFpEF. The second step (E: Echocardiography and Natriuretic Peptide Score) requires comprehensive echocardiography and is typically performed by a cardiologist. Measures include mitral annular early diastolic velocity (e′), left ventricular (LV) filling pressure estimated using E/e′, left atrial volume index, LV mass index, LV relative wall thickness, tricuspid regurgitation velocity, LV global longitudinal systolic strain, and serum natriuretic peptide levels. Major (2 points) and Minor (1 point) criteria were defined from these measures. A score ≥5 points implies definite HFpEF; ≤1 point makes HFpEF unlikely. An intermediate score (2–4 points) implies diagnostic uncertainty, in which case Step 3 (F1: Functional testing) is recommended with echocardiographic or invasive haemodynamic exercise stress tests. Step 4 (F2: Final aetiology) is recommended to establish a possible specific cause of HFpEF or alternative explanations. Further research is needed for a better classification of HFpEF.


2020 ◽  
Vol 128 (5) ◽  
pp. 1123-1129 ◽  
Author(s):  
Satyam Sarma ◽  
Erin Howden ◽  
Graeme Carrick-Ranson ◽  
Justin Lawley ◽  
Christopher Hearon ◽  
...  

Women are at increased risk for heart failure with preserved ejection fraction (HFpEF) largely due to higher prevalence of arterial and cardiac stiffening. We were able to identify several subclinical markers of early (stages A and B) HFpEF pathophysiology largely on the basis of exercise blood pressure (BP) response in otherwise healthy middle-aged women. Exercise BP response may be an inexpensive screening tool to identify women at highest risk for developing future HFpEF.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Tal Y Samuel ◽  
Tal Hasin ◽  
Israel Gotsman ◽  
Tanya Weitsman ◽  
Fanny Ben Ivgi ◽  
...  

Background: Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure (HF) in the elderly and is increasing in prevalence. No specific treatment for this condition appears to be effective. Coenzyme Q10 (CoQ10) is an essential cofactor for energy production and reduced levels have been noted in HF. Previous studies have suggested a possible role for CoQ10 in the treatment of HF in particular in the elderly. Aim: To evaluate the effect of CoQ10 supplementation on diastolic function in patients with HFpEF. Methods: A prospective, randomized, double-blind, placebo-controlled trial. Inclusion criteria were age > 50 years, New York Heart Association class II-IV, ejection fraction > 50%, and evidence of impaired diastolic function defined as lateral e' < 0.09 cm/sec, average E/e' > 13 or average E/e' > 8 with additional markers of impaired diastolic function such as delayed relaxation (E/A < 0.5), elevated left atrial volume index (> 40ml / m 2 ) elevated left ventricular mass index ( > 122 gr/ m 2 ♀ or 149 gr/ m 2 ♂) or pulmonary hypertension. Patients with other forms of cardiomyopathies or treated with chronic renal replacement therapy were excluded. Echocardiographic studies and levels of N-terminal pro-B type natriuretic peptide (NT-proBNP) were completed at baseline and following 4 months of CoQ10 (300 mg daily) or placebo supplementation. Results: A total of 39 patients were enrolled, 19 patients in the CoQ10 and 20 patients in the placebo group. Groups were similar in baseline clinical characteristics. Compliance was high and similar between groups (average 208 ± 108 mg/day for the CoQ10 versus 212 ± 95 mg/day for the placebo group). No significant effect was observed on indices of diastolic function or NT-proBNP levels following 4 months of CoQ10 use. Conclusions: Treatment with CoQ10 did not affect indices of diastolic function or NT-proBNP levels in patients with HFpEF. Our study does not support the routine use of CoQ10 in patients with HFpEF.


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