1406Inhaled iloprost, exercise hemodynamics, and ventricular performance in heart failure with preserved ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J.-F Cheng ◽  
C.-K Wu ◽  
C.-Y Huang ◽  
Z.-W Chen ◽  
S.-Y Chen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Output ◽  
Ejection Fraction ◽  
Study Drug ◽  
Left Ventricular ◽  
Stroke Work ◽  
Preserved Ejection Fraction ◽  
Ventricular Performance ◽  
Inhaled Iloprost ◽  
Exercise Hemodynamics

Abstract Background A dramatic increase in pulmonary capillary wedge pressure (PCWP) during exercise is observed in patients with heart failure with preserved ejection fraction (HFpEF). The prostacyclin pathway is involved in pulmonary hypertension and iloprost is a prostacyclin analogue. The acute onset vasodilator effect of inhaled iloprost makes it a good candidate to decrease exercise-induced PCWP. This study determined whether iloprost inhalation could improve exercise hemodynamics and cardiac reserve in HFpEF. Methods Thirty-four HFpEF subjects were enrolled in this double-blind, randomized, placebo-controlled, parallel-group trial. Subjects received invasive cardiac catheterization and underwent expired gas analysis at rest and during exercise, before and 15 minutes after treatment with either inhaled iloprost or placebo. Results At baseline, enrolled subjects showed an increase in PCWP during exercise (PCWP = 16 (14–23) mmHg to 27 (21–36) mmHg; p<0.0001). After drug inhalation treatment, the primary endpoint was achieved whereby exercise PCWP was significantly reduced by iloprost compared to placebo (adjusted mean: 20 (16–29) mmHg vs. 23 (17–32) mmHg; p=0.002). Iloprost showed a trend for better cardiac output reserve with exercise (0.2 (−1.3 to 1.2) L/min vs. −0.7 (−1.9 to 0.1) L/min; p=0.099) and normalized the increase in cardiac output relative to oxygen consumption. Iloprost improved the pulmonary artery pressure flow relationships in HFpEF and showed a trend for increased left ventricular stroke work with exercise compared to placebo, indicating an improvement in ventricular performance with stress. Table shows exercise baseline-corrected values (exercise values after receiving study drug minus exercise values prior to study drug) Placebo (n=17) Iloprost (n=17) p Value PA systolic, mmHg 0 (−4 to 6) −11 (−23 to −5) <0.0001 PCWP, mmHg −2 (−3 to 2) −7 (−12 to −5) <0.0001 PVR, mmHg/l/min 0 (−0.5 to 0.3) −0.1 (−0.5 to 0.4) 0.9 SVR, DSC 102 (16 to 188) 5 (−162 to 108) 0.057 LVSW, g/beat −3 (−30 to 6) 7 (−13 to 20) 0.079 CO, l/min −0.7 (−1.9 to 0.1) 0.2 (−1.3 to 1.2) 0.099 Stroke volume, ml −8 (−24 to 1) 0 (−19 to 10) 0.3 Values are median (interquartile range). Conclusions Iloprost inhalation improved hemodynamic deficit during exercise in patients with HFpEF. Prospective trials testing long-term iloprost therapy in this population are warranted.

Effect of ivabradine in heart failure: a meta-analysis of heart failure patients with reduced versus preserved ejection fraction

2021 ◽  
pp. 1-16
Author(s):  
Noémi Tóth ◽  
Alexandra Soós ◽  
Alex Váradi ◽  
Péter Hegyi ◽  
Benedek Tinusz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Clinical Trials ◽  
Ejection Fraction ◽  
Meta Analysis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cochrane Library ◽  
Preserved Ejection Fraction ◽  
Ventricular Performance

In clinical trials of heart failure reduced ejection fraction (HFrEF), ivabradine seemed to be an effective heart rate lowering agent associated with lower risk of cardiovascular death. In contrast, ivabradine failed to improve cardiovascular outcomes in heart failure preserved ejection fraction (HFpEF) despite the significant effect on heart rate. This meta-analysis is the first to compare the effects of ivabradine on heart rate and mortality parameters in HFpEF versus HFrEF. We screened three databases: PubMed, Embase, and Cochrane Library. The outcomes of these studies were mortality, reduction in heart rate, and left ventricular function improvement. We compared the efficacy of ivabradine treatment in HFpEF versus HFrEF. Heart rate analysis of pooled data showed decrease in both HFrEF (–17.646 beats/min) and HFpEF (–11.434 beats/min), and a tendency to have stronger bradycardic effect in HFrEF (p = 0.094) in randomized clinical trials. Left ventricular ejection fraction analysis revealed significant improvement in HFrEF (5.936, 95% CI: [4.199–7.672], p < 0.001) when compared with placebo (p < 0.001). We found that ivabradine significantly improves left ventricular performance in HFrEF, at the same time it exerts a tendency to have improved bradycardic effect in HFrEF. These disparate effects of ivabradine and the higher prevalence of non-cardiac comorbidities in HFpEF may explain the observed beneficial effects in HFrEF and the unchanged outcomes in HFpEF patients after ivabradine treatment.

scholarly journals The Volume Regulation Graph versus the Ejection Fraction as Metrics of Left Ventricular Performance in Heart Failure with and without a Preserved Ejection Fraction: A Mathematical Model Study

2015 ◽  
Vol 9s1 ◽  
pp. CMC.S18748 ◽  
Author(s):  
Theo J.C. Faes ◽  
Peter L.M. Kerkhof
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Pressure ◽  
Systolic Dysfunction ◽  
Ventricular Volume ◽  
Systemic Circulation ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Ventricular Performance ◽  
End Diastolic Volume

In left ventricular heart failure, often a distinction is made between patients with a reduced and a preserved ejection fraction (EF). As EF is a composite metric of both the end-diastolic volume (EDV) and the end-systolic ventricular volume (ESV), the lucidity of the EF is sometimes questioned. As an alternative, the ESV–EDV graph is advocated. This study identifies the dependence of the EF and the EDV–ESV graph on the major determinants of ventricular performance. Numerical simulations were made using a model of the systemic circulation, consisting of an atrium–ventricle valves combination; a simple constant pressure as venous filling system; and a three-element Windkessel extended with a venous system. ESV–EDV graphs and EFs were calculated using this model while varying one by one the filling pressure, diastolic and systolic ventricular elastances, and diastolic pressure in the aorta. In conclusion, the ESV–EDV graph separates between diastolic and systolic dysfunction while the EF encompasses these two pathologies. Therefore, the ESV–EDV graph can provide an advantage over EF in heart failure studies.

scholarly journals Disturbed ventricular-arterial coupling and increased left atrial stiffness in a patient with heart failure with preserved ejection fraction and hyperaldosteronism: a case report

2019 ◽  
Vol 3 (4) ◽  
pp. 1-6 ◽  
Author(s):  
Svenja Meyhöfer ◽  
Sebastian M Schmid ◽  
Mathias Hohl ◽  
Jan-Christian Reil
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Clinical Symptoms ◽  
Obese Woman ◽  
Left Ventricular ◽  
Stroke Work ◽  
Preserved Ejection Fraction ◽  
Aldosterone Antagonist ◽  
Left Atrial Stiffness

Abstract Background Aldosterone is involved in almost all parts of the cardiovascular system. Hyperaldosteronism causes arterial hypertension and might predispose to stroke, atrial fibrillation, and heart failure. Case summary A 60-year-old obese woman with long-standing hypertension, hypokalaemia, and shortness of breath was admitted to our hospital. Hypertension was caused by primary hyperaldosteronism due to an adenoma of the adrenal gland. Detailed transthoracic echocardiography revealed diastolic dysfunction, disturbed ventricular–arterial interaction, and atrial compliance resulting in heart failure with preserved ejection fraction (HFPEF). Three months of aldosterone antagonist treatment improved ventricular–arterial coupling, while left ventricular diastolic and atrial dysfunction remained unchanged. Discussion Presumably, hyperaldosteronism is the reason for HFPEF in this case. Standard criteria to diagnose HFPEF include clinical symptoms of heart failure and an ejection fraction (EF) &gt;50% as well as echocardiographically or invasively assessed elevated filling pressures. Single beat pressure-volume analysis gives insights on the pathophysiology of increased filling pressures, showing in our case diastolic dysfunction as well as disturbed ventricular–arterial interaction. Three months of aldosterone antagonist treatment reduced blood pressure with concomitant improvement of ventricular–arterial interaction, thereby reducing stroke work while stroke volume remained nearly unchanged. Diastolic dysfunction and increased atrial stiffness were unaltered.

Abstract 17241: Impaired Left Atrioventricular Coupling Compromises Cardiac Performance in Heart Failure With Preserved Ejection Fraction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Rosita Zakeri ◽  
Hiroyuki Takahama ◽  
Philip A Araoz ◽  
Hon-Chi Lee ◽  
Margaret M Redfield
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Stroke Volume ◽  
Pressure Rise ◽  
Left Ventricular ◽  
Cardiac Performance ◽  
Experimental Hypertension ◽  
Stroke Work ◽  
Preserved Ejection Fraction ◽  
Arterial Elastance

Background: In heart failure with preserved ejection fraction (HFpEF), left ventricular (LV) systolic elastance (Ees) increases in tandem with increases in arterial elastance (Ea), which maintains ejection fraction but limits systolic reserve and precipitates volume sensitivity. The left atrium (LA) lies in series with the LV and contributes to LV stroke volume. We hypothesized that HFpEF is associated with increased LA systolic elastance (E LA ) and deranged atrioventricular (AV) coupling which may additionally compromise cardiac performance. Methods: HFpEF was modeled by experimental hypertension (bilateral renal wrap + DOCA) in elderly dogs (n=9). LA and LV structure, function (echo, MRI) and invasively assessed pressure-volume relationships (PVR, open-chest; pericardiotomy; admittance catheter) were compared to sham-operated young dogs (control; n=13). Results: As compared to controls, HFpEF dogs displayed concentric remodeling, with increased diastolic stiffness, Ea and Ees (p<0.05 for all) and reduced Ea/Ees (p=0.03). LA maximum volume (28±3 vs 23±3mL, p=0.007), LA stroke volume (4±1 vs2±1mL, p=0.006), LA active emptying fraction (18±6 vs 12±2%, p=0.03) and LA ejection rate (51±14 vs 30±16mL/s) were higher in HFpEF versus controls, suggesting increased LA stroke work and inotropy. At matched heart rate and LA pressure, E LA was steeper in HFpEF than control (2.7±0.9 vs 1.5±0.6mmHg/mL, p=0.01) and positively correlated with Ees (r=0.6, p=0.005) and Ea (r=0.66, p=0.002). However AV mismatch occurred as increases in E LA were not proportionate to increases in Ees (Ees/E LA 1.3±0.4 HFpEF vs 0.8±0.4 control, p<0.05). On linear regression, worse AV coupling (i.e. higher Ees/E LA ) was associated with lower LV stroke volume ( Figure ). Conclusion: In experimental HFpEF, despite enhanced LA contractility, AV coupling was deranged. Worse AV coupling may further contribute to reserve dysfunction, LA pressure rise, and susceptibility to pulmonary edema in HFpEF.

scholarly journals Experimental cardiac radiation exposure induces ventricular diastolic dysfunction with preserved ejection fraction

2017 ◽  
Vol 313 (2) ◽  
pp. H392-H407 ◽  
Author(s):  
Hirofumi Saiki ◽  
Gilles Moulay ◽  
Adam J. Guenzel ◽  
Weibin Liu ◽  
Teresa D. Decklever ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Radiation Exposure ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Stroke Work ◽  
Preserved Ejection Fraction ◽  
Ventricular Diastolic Dysfunction

Breast cancer radiotherapy increases the risk of heart failure with preserved ejection fraction (HFpEF). Cardiomyocytes are highly radioresistant, but radiation specifically affects coronary microvascular endothelial cells, with subsequent microvascular inflammation and rarefaction. The effects of radiation on left ventricular (LV) diastolic function are poorly characterized. We hypothesized that cardiac radiation exposure may result in diastolic dysfunction without reduced EF. Global cardiac expression of the sodium-iodide symporter (NIS) was induced by cardiotropic gene (adeno-associated virus serotype 9) delivery to 5-wk-old rats. SPECT/CT (125I) measurement of cardiac iodine uptake allowed calculation of the 131I doses needed to deliver 10- or 20-Gy cardiac radiation at 10 wk of age. Radiated (Rad; 10 or 20 Gy) and control rats were studied at 30 wk of age. Body weight, blood pressure, and heart rate were similar in control and Rad rats. Compared with control rats, Rad rats had impaired exercise capacity, increased LV diastolic stiffness, impaired LV relaxation, and elevated filling pressures but similar LV volume, EF, end-systolic elastance, preload recruitable stroke work, and peak +dP/d t. Pathology revealed reduced microvascular density, mild concentric cardiomyocyte hypertrophy, and increased LV fibrosis in Rad rats compared with control rats. In the Rad myocardium, oxidative stress was increased and in vivo PKG activity was decreased. Experimental cardiac radiation exposure resulted in diastolic dysfunction without reduced EF. These data provide insight into the association between cardiac radiation exposure and HFpEF risk and lend further support for the importance of inflammation-related coronary microvascular compromise in HFpEF. NEW & NOTEWORTHY Cardiac radiation exposure during radiotherapy increases the risk of heart failure with preserved ejection fraction. In a novel rodent model, cardiac radiation exposure resulted in coronary microvascular rarefaction, oxidative stress, impaired PKG signaling, myocardial fibrosis, mild cardiomyocyte hypertrophy, left ventricular diastolic dysfunction, and elevated left ventricular filling pressures despite preserved ejection fraction.

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