scholarly journals Comprehensive Physiological Modeling Provides Novel Insights Into Heart Failure With Preserved Ejection Fraction Physiology

2021 ◽  
Author(s):  
David M. Kaye ◽  
Emil Wolsk ◽  
Shane Nanayakkara ◽  
Justin Mariani ◽  
Christian Hassager ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Blood Volume ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Linear Interaction ◽  
Ventricular Ejection Fraction ◽  
Left Ventricular Stiffness ◽  
Pulmonary Capillary

Background Although a rapid rise in left atrial pressure during exertion is considered pathognomonic of heart failure with preserved ejection fraction (HFpEF), the fundamental circulatory determinants of this response are not clear, impacting upon the development of more effective therapies. We aimed to comprehensively describe the circulatory mechanics of patients with HFpEF at rest and during exercise in comparison with controls. Methods and Results We performed simultaneous right‐heart catheterization and echocardiography at rest and during exercise in 22 healthy control volunteers and 60 patients with confirmed HFpEF. Using detailed individual patient‐level hemodynamic and left ventricular ejection fraction data we performed computer simulations to evaluate the circulatory parameters including the estimated stressed blood volumethat contribute to the resting and exercise pulmonary capillary pressure. At rest and during exercise, left ventricular stiffness (V 30 , the end‐diastolic pressure–volume relationship at a filling pressure of 30 mm Hg), left ventricular elastance, and arterial elastance were all significantly greater in HFpEF than in controls. Stressed blood volume was significantly greater in HFpEF (26.9±5.4 versus 20.2±4.7 mL/kg, P <0.001), becoming even more pronounced during exercise (40.9±3.7 versus 27.5±7.0 mL per 70 kg, P <0.001). During exercise, the magnitude of the change in stressed blood volume ( r =0.67, P <0.001) and left ventricular stiffness ( r =−0.44, P <0.001) were key determinants of the rise in pulmonary capillary wedge pressure. Further detailed modeling studies showed that the hemodynamic response to exercise results from a complex non‐linear interaction between circulatory parameters. Conclusions The circulatory determinants of HFpEF physiology are complex. We identified stressed blood volume at rest and during exercise is a novel, key factor, therebyrepresenting an important potential therapeutic target.

Abstract 17311: Ventricular Arrhythmias and Fibrosis in Patients With Heart Failure and Preserved Ejection Fraction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Natasha Cuk ◽  
Jae H Cho ◽  
Donghee Han ◽  
Joseph E Ebinger ◽  
Eugenio Cingolani
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiac Mri ◽  
Ventricular Arrhythmias ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction ◽  
Patients With Heart Failure ◽  
Ventricular Fibrosis

Introduction: Sudden death due to ventricular arrhythmias (VA) is one of the main causes of mortality in patients with heart failure and preserved ejection fraction (HFpEF). Ventricular fibrosis in HFpEF has been suspected as a substrate of VA, but the degree of fibrosis has not been well characterized. Hypothesis: HFpEF patients with increased degree of fibrosis will manifest more VA. Methods: Cedars-Sinai medical records were probed using Deep 6 artificial intelligence data extraction software to identify patients with HFpEF who underwent cardiac magnetic resonance imaging (MRI). MRI of identified patients were reviewed to measure extra-cellular volume (ECV) and degree of fibrosis. Ambulatory ECG monitoring (Ziopatch) of those patients were also reviewed to study the prevalence of arrhythmias. Results: A total of 12 HFpEF patients who underwent cardiac MRI were identified. Patients were elderly (mean age 70.3 ± 7.1), predominantly female (83%), and overweight (mean BMI 32 ± 9). Comorbidities included hypertension (83%), dyslipidemia (75%), and coronary artery disease (67%). Mean left ventricular ejection fraction by echocardiogram was 63 ± 8.7%. QTc as measured on ECG was not significantly prolonged (432 ± 15 ms). ECV was normal in those patients for whom it was available (24.2 ± 3.1, n = 9) with 3/12 patients (25%) demonstrating ventricular fibrosis by MRI (average burden of 9.6 ± 5.9%). Ziopatch was obtained in 8/12 patients (including all 3 patients with fibrosis) and non-sustained ventricular tachycardia (NSVT) was identified in 5/8 (62.5%). One patient with NSVT and without fibrosis on MRI also had a sustained VA recorded. In those patients who had Ziopatch monitoring, there was no association between presence of fibrosis and NSVT (X2 = 0.035, p = 0.85). Conclusions: Ventricular fibrosis was present in 25% of HFpEF patients in this study and NSVT was observed in 62.5% of those patients with HFpEF who had Ziopatch monitoring. The presence of fibrosis by Cardiac MRI was not associated with NSVT in this study; however, the size of the cohort precludes broadly generalizable conclusions about this association. Further investigation is required to better understand the relationship between ventricular fibrosis by MRI and VA in patients with HFpEF.

Abstract 13104: The Concomitant Inflammation Affect the Ratio of N-terminal Pro B-type Natriuretic Peptide to B-type Natriuretic Peptide in Patients With Heart Failure and Preserved Ejection Fraction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Tsutomu Kawai ◽  
Takahisa Yamada ◽  
Tetsuya Watanabe ◽  
Shunsuke Tamaki ◽  
Shungo Hikoso ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Natriuretic Peptide ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction ◽  
Inflammatory Status ◽  
Patients With Heart Failure ◽  
Multicenter Prospective Observational Study

Backgrounds: Although B-type natriuretic peptide (BNP) and N-terminal pro B-type natriuretic peptide (NT-proBNP ) are interrelated parameters in assessment heart failure severity and prognosis, the ratio of NT-proBNP to BNP (NT-proBNP/BNP) are affected by various clinical factors, such as renal function. However, little is known about the influence of inflammation on NT-proBNP/BNP in patients with heart failure and preserved ejection fraction (HFpEF). Methods and Results: Patients data were extracted from PURSUIT-HFpEF registry, which is a multicenter prospective observational study including patients hospitalized for acute heart failure with left ventricular ejection fraction of >50%. Of 871 patients, data of BNP and NT-proBNP was available in 654 patients. The median baseline concentration of BNP was 474 pg/ml (299-720), NT-proBNP was 3310 pg/ml (1740-6840), and NT-proBNP/BNP was 7.6 (5.0-11.8). In multivariable linear regression analyses, older age [odds ratio (OR); 1.05, 95% confidence interval (CI); 1.02-1.09, p=0.001], higher creatinine [OR; 2.63, 95% CI; 1.66-4.16, p<0.001], and higher C-reactive protein (CRP) [OR; 1.17, 95% CI; 1.06-1.28, p<0.001] were significantly associated with a higher NT-proBNP/BNP (>median value of 7.6). However, other factors expected to affect NT-proBNP/BNP, such as atrial fibrillation and body mass index, were not associated with a higher NT-proBNP/BNP in this study. Patients in the highest CRP quartile had significantly higher NT-proBNP/BNP than those with other quartiles. Conclusion: In HFpEF patients, concomitant inflammation was associated with high NT-proBNP/BNP, which indicated that we need a careful interpretation on these two natriuretic peptides of patients with HFpEF and inflammatory status, such as infection.

1407Drug effect of luseogliflozin and voglibose on heart failure with preserved ejection fraction in diabetic patients: a multicenter randomized-controlled trial

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Ejiri ◽  
T Miyoshi ◽  
H Kihara ◽  
Y Hata ◽  
T Nagano ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction

Abstract Background Recent randomized, placebo-controlled trial in patients with type 2 diabetes demonstrated that the sodium-glucose cotransporter 2 inhibitors reduced mortality, cardiovascular events and hospitalization for heart failure. However, those trials were not specialized design to investigate the effect of sodium-glucose cotransporter 2 inhibitors in patients with heart failure, in particular with heart failure with preserved ejection fraction. Purpose The aim of this study was to evaluate the drug efficacy of luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, compared with voglibose, an alpha-glucosidase inhibitor, using brain natriuretic peptide (BNP) in type 2 diabetes patients with heart failure with preserved ejection fraction. Methods This study was a prospective, multicenter, open-label, randomized-controlled trial, comparing luseogliflozin 2.5 mg once daily or voglibose 0.2 mg three times daily in patients with type 2 diabetes suffering from heart failure with preserved ejection fraction (left ventricular ejection fraction >45% and BNP ≥35 pg/ml2) in a 1:1 randomization fashion. Randomization was undertaken using a computer-generated random sequence web response system. The primary outcome was the difference from baseline in BNP after 12 weeks of treatment between two drugs. The key secondary outcomes were the change from baseline in left ventricular ejection fraction and E/e' in echocardiographic parameters, body weight, glycohemoglobin level after 12 weeks of treatment. The safety outcomes included the incidence of major adverse cardiovascular events, hypoglycemic adverse events, and urinary tract infection. Results Between December 2015 and September 2018, 173 patients from 16 hospitals and clinics have been included in this study. Of those, 83 patients were assigned to receive luseogliflozin and 82 to receive voglibose. There was no significant difference in the reduction in the BNP concentration after 12 weeks from baseline between the two groups; the ratio of the average values at week 12 to the baseline value was 0.91 in the luseoglifllzin group as compared with 0.98 in the voglibose group (percent change, −9.0% vs. −1.9%, ratio of change with luseogliflozin vs. voglibose, 0.93; 95% confidence interval, 0.78 to 1.10; p=0.26). The key secondary outcomes including left ventricular ejection fraction, E/e', body weight, glycohemoglobin level and the safety outcomes did not differ significantly between the two groups. Conclusions In type 2 diabetes patients with heart failure with preserved ejection fraction, the administration of luseogliflozin did not lead to a significant reduction in the BNP concentration than that of voglibose. Left ventricular ejection fraction, E/e', body weight and glycohemoglobin level after 12 weeks of treatment, comparing with at baseline did not differ significantly between the two groups. (UMIN Clinical Trial Registry number, UMINehz748.005618395) Acknowledgement/Funding Novartis

scholarly journals Influence of polypharmacy on patients with heart failure with preserved ejection fraction: a retrospective analysis on adverse outcomes in the TOPCAT trial

2020 ◽  
Vol 71 (702) ◽  
pp. e62-e70
Author(s):  
Yuzhong Wu ◽  
Wengen Zhu ◽  
Xin He ◽  
Ruicong Xue ◽  
Weihao Liang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Retrospective Analysis ◽  
Heart Function ◽  
Left Ventricular ◽  
Adverse Outcomes ◽  
Left Ventricular Ejection ◽  
Controlled Study ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction

BackgroundPolypharmacy is common in heart failure (HF), whereas its effect on adverse outcomes in patients with HF with preserved ejection fraction (HFpEF) is unclear.AimTo evaluate the prevalence, prognostic impacts, and predictors of polypharmacy in HFpEF patients.Design and settingA retrospective analysis performed on patients in the Americas region (including the US, Canada, Argentina, and Brazil) with symptomatic HF and a left ventricular ejection fraction ≥45% in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial, an international, randomised, double-blind, placebo-controlled study conducted during 2006–2013 in six countries.MethodPatients were categorised into four groups: controls (<5 medications), polypharmacy (5–9 medications), hyperpolypharmacy, (10–14 medications), and super hyperpolypharmacy (≥15 medications). The outcomes and predictors in all groups were assessed.ResultsOf 1761 participants, the median age was 72 years; 37.5% were polypharmacy, 35.9% were hyperpolypharmacy, and 19.6% were super hyperpolypharmacy, leaving 7.0% having a low medication burden. In multivariable regression models, three experimental groups with a high medication burden were all associated with a reduction in all-cause death, but increased risks of HF hospitalisation and all-cause hospitalisation. Furthermore, several comorbidities (dyslipidemia, thyroid diseases, diabetes mellitus, and chronic obstructive pulmonary disease), a history of angina pectoris, diastolic blood pressure <80 mmHg, and worse heart function (the New York Heart Association functional classification level III and IV) at baseline were independently associated with a high medication burden among patients with HFpEF.ConclusionA high prevalence of high medication burden at baseline was reported in patients with HFpEF. The high medication burden might increase the risk of hospital readmission, but not the mortality.

Prognostic value of biomarkers in chronic heart failure with preserved left ventricular ejection fraction

2016 ◽  
Vol 88 (9) ◽  
pp. 102-105 ◽  
Author(s):  
T A Nikiforova ◽  
D Yu Shchekochikhin ◽  
F Yu Kopylov ◽  
A L Syrkin
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Prognostic Value ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
The Novel ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction

The paper reviews major biomarkers for determining the prognosis in patients with chronic heart failure and preserved ejection fraction. It also considers cystatin C, one of the novel and probably the most practically important biomarkers.

scholarly journals Study protocol for the PURSUIT-HFpEF study: a Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e038294
Author(s):  
Shinichiro Suna ◽  
Shungo Hikoso ◽  
Takahisa Yamada ◽  
Masaaki Uematsu ◽  
Yoshio Yasumura ◽  
...  
Keyword(s):  
Heart Failure ◽  
Observational Study ◽  
Ejection Fraction ◽  
Acute Decompensated Heart Failure ◽  
Left Ventricular ◽  
University Hospital ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction

IntroductionNeither the pathophysiology nor an effective treatment for heart failure with preserved ejection fraction (HFpEF) has been elucidated to date. The purpose of this ongoing study is to elucidate the pathophysiology and prognostic factors for patients with HFpEF admitted to participating institutes. We also aim to obtain insights into the development of new diagnostic and treatment methods by analysing patient background factors, clinical data and follow-up information.Methods and analysisThis study is a prospective, multicentre, observational study of patients aged ≥20 years admitted due to acute decompensated heart failure with preserved left ventricular ejection fraction (≥50%) and elevated N-terminal-pro brain natriuretic peptide (NT-proBNP) (≥400 pg/mL). The study began in June 2016, with the participation of Osaka University Hospital and 31 affiliated facilities. We will collect data on history in detail, accompanying diseases, quality of life, frailty score, medication history, and laboratory and echocardiographic data. We will follow-up each patient for 5 years, and collect outcome data on mortality, cause of death, and the number and cause of hospitalisation. The target number of registered cases is 1500 cases in 5 years.Ethics and disseminationThe protocol was approved by the Institutional Review Board (IRB) of Osaka University Hospital on 24 February 2016 (ID: 15471), and by the IRBs of the all participating facilities. The findings will be disseminated through peer-reviewed publications and conference presentations.

P2725Transthyretin cardiac amyloidosis in heart failure with preserved ejection fraction: Imaging by Tc-99m bone scan

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Fukuzawa ◽  
S Okino ◽  
H Ishiwaki ◽  
Y Iwata ◽  
T Uchiyama ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Bone Scan ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Myocardial Uptake ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction

Abstract Background Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome with multiple underlying causes. Transthyretin amyloidosis (ATTR) is an underdiagnosed cause of HFpEF. Extraosseous uptake, in particular, myocardial uptake, was observed in a number of ATTR patients examined with the bone scan tracers. Objectives We sought to determine the prevalence of ATTR as detected by the bone scan among the patients admitted due to HFpEF. Methods We screened all consecutive patients ≥60 years old admitted due to HFpEF (left ventricular ejection fraction ≥50%). All eligible patients were offered an echocardiogram and a bone scan (a 99mTc-DPD/MDP/HMDP scintigraphy). Echocardiographic and clinical variables were gathered in all the subjects. The intensity of the myocardial uptake was graded according to a visual scale ranging from 0 to 3 points, in which the absence of uptake was assigned a score of 0 points; uptake less than that of bone (referred to as the adjacent rib), 1 point; uptake similar to that of bone, 2 points; and uptake greater than that of bone, 3 points. The distribution of the uptake in myocardium was defined as focal uptake, diffuse uptake, uptake in a ventricular wall segment, diffuse ventricular uptake, or diffuse biventricular uptake. Results The study included 62 HFpEF patients (52% women, 73±9 years). The bone scintigraphic analysis revealed relatively intense myocardial uptake in 7 of 62 patients (11.2%). 7 patients had intense Tc-99m uptake (score of 2–3) in the cardiac region, showing deposition in both right and left ventricles in every case. Patients with amyloid deposition were older (78±6 vs. 70±12 years, p<0.05), had a lower systolic blood pressure (118±23 vs. 148±28 mmHg, p<0.05), and left ventricular ejection fraction (52±11 vs. 58±6%, p<0.05). Both groups had at least moderate left ventricular hypertrophy and abnormal global longitudinal strain with no significant difference between groups. In 6 all the cases, the final diagnosis of amyloidosis was based on the results of abdominal fat aspiration biopsy. Conclusion ATTR is an underdiagnosed disease that accounts for a significant number (11.2%) of HFpEF cases. These findings create an opportunity for further investigation in the targeted therapy of patients with HFpEF.

scholarly journals Transitioning from Preclinical to Clinical Heart Failure with Preserved Ejection Fraction: A Mechanistic Approach

2020 ◽  
Vol 9 (4) ◽  
pp. 1110 ◽  
Author(s):  
Antoni Bayes-Genis ◽  
Felipe Bisbal ◽  
Julio Núñez ◽  
Enrique Santas ◽  
Josep Lupón ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Ejection Fraction ◽  
Right Ventricular ◽  
Left Atrial ◽  
Interstitial Fibrosis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction

To better understand heart failure with preserved ejection fraction (HFpEF), we need to better characterize the transition from asymptomatic pre-HFpEF to symptomatic HFpEF. The current emphasis on left ventricular diastolic dysfunction must be redirected to microvascular inflammation and endothelial dysfunction that leads to cardiomyocyte remodeling and enhanced interstitial collagen deposition. A pre-HFpEF patient lacks signs or symptoms of heart failure (HF), has preserved left ventricular ejection fraction (LVEF) with incipient structural changes similar to HFpEF, and possesses elevated biomarkers of cardiac dysfunction. The transition from pre-HFpEF to symptomatic HFpEF also involves left atrial failure, pulmonary hypertension and right ventricular dysfunction, and renal failure. This review focuses on the non-left ventricular mechanisms in this transition, involving the atria, right heart cavities, kidneys, and ultimately the currently accepted driver—systemic inflammation. Impaired atrial function may decrease ventricular hemodynamics and significantly increase left atrial and pulmonary pressure, leading to HF symptoms, irrespective of left ventricle (LV) systolic function. Pulmonary hypertension and low right-ventricular function are associated with the incidence of HF. Interstitial fibrosis in the heart, large arteries, and kidneys is key to the pathophysiology of the cardiorenal syndrome continuum. By understanding each of these processes, we may be able to halt disease progression and eventually extend the time a patient remains in the asymptomatic pre-HFpEF stage.

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