scholarly journals The effect of different anaesthetics on echocardiographic evaluation of diastolic dysfunction in a heart failure with preserved ejection fraction model

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ilona Cuijpers ◽  
Paolo Carai ◽  
Pedro Mendes-Ferreira ◽  
Steven J. Simmonds ◽  
Paul Mulder ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Preserved Ejection Fraction ◽  
Echocardiographic Evaluation ◽  
Human Pathology ◽  
Pulsed Wave Doppler ◽  
Lowering Drug ◽  
Effective Diagnosis ◽  
Isovolumic Relaxation

Abstract Heart failure with preserved ejection fraction (HFpEF) is currently untreated. Therapeutics development demands effective diagnosis of diastolic dysfunction in animal models mimicking human pathology, which requires appropriate anaesthetics. Here, we investigated which anaesthetic, ketamine/xylazine or isoflurane, could be used to reveal diastolic dysfunction in HFpEF-diseased obese ZSF1 rats by echocardiography. First, diastolic dysfunction was confirmed by pressure-volume loops in obese compared to lean control ZSF1 rats. In echocardiography, ketamine/xylazine, unlike isoflurane, was able to demonstrate impaired relaxation in obese ZSF1 rats, as reflected by impaired early (E) and late (A) filling peak velocities, decreased E/A ratio, and a prolonged deceleration and isovolumic relaxation time. Interestingly, ketamine/xylazine induced a wider separation of both tissue and pulsed wave Doppler-derived echocardiographic waves required for diastolic dysfunction diagnosis, potentially by reducing the heart rate (HR), while isoflurane resulted in merged waves. To assess whether HR-lowering alone explained the differences between the anaesthetics, echocardiography measurements under isoflurane with and without the HR-lowering drug ivabradine were compared. However, diastolic dysfunction could not be diagnosed in ivabradine-treated obese ZSF1 rats. In summary, ketamine/xylazine compared to isoflurane is the anaesthetic of choice to detect diastolic dysfunction by echocardiography in rodent HFpEF, which was only partly mediated by HR-lowering.

Global constructive work and left atrial reservoir function is reduced in patients with heart failure with preserved ejection fraction compared with patients with preclinical diastolic dysfunction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L.G Tunyan ◽  
A.L Chilingaryan ◽  
K.G Adamyan ◽  
P.H Zelveyan ◽  
L.R Tumasyan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Left Atrial ◽  
Speckle Tracking ◽  
Volume Index ◽  
Funding Source ◽  
Preserved Ejection Fraction ◽  
Constructive Work ◽  
Isovolumic Relaxation

Abstract   Heart failure with preserved ejection fraction (HFpEF) remains an unresolved issue with morbidity and mortality comparable with that of reduced EF HF. Diastolic dysfunction (DD) is the hallmark of HFpEF but it is unclear why some patients do not develop symptoms and remain in preclinical DD (PDD) stage with the same degree of DD as patients with HFpEF. We assumed that patients with HFpEF might have more deteriorated global myocardial work (GW) and left atrial reservoir longitudinal strain (LALS) parameters compared with PDD patients. Methods 210 patients (150 female, mean age 71±5 years) of which 118 with PDD and 92 with HFpEF were enrolled in this study. PDD was diagnosed if patients had normal NT-proBNP values, and at least 3 of the following echocardiographic criteria at rest or after diastolic stress echocardiography: end-systolic left atrial volume index (LAVi) >34 ml/m2, LV E/e' >13, average LV e' >8.5, and systolic pulmonary artery pressure >30 mmHg. GW index (GWI) was obtained from pressure-strain loops composed from speckle tracking analysis indexed to brachial systolic blood pressure, global constructive work (GCW) was measured as the sum of positive work due to myocardial shortening during systole and negative work due to lengthening during isovolumic relaxation, global wasted work (GWW) was calculated as energy loss by myocardial lengthening in systole and shortening in isovolumic relaxation, and GW efficiency (GWE) as the percentage ratio of constructive work to the sum of constructive work and wasted work. LALS was measured by speckle tracking echocardiography as average value of two basal segments in apical 4 chamber view along LAVi and 4D LV mass index (LVMi) offline by experienced echocardiographer who was unaware of the study aims. Results Patients with PDD and HFpEF have comparable values of LAVi, LVMi, GWI, GWW, and GWE (LAVi 38.4±3.9 ml/m2 vs 39.1±4.1 ml/m2, p=NS; LVMi 82.8±11.4 g/m2 vs 83.5±10.2 g/m2, p=NS; PDD GWI 2389±154 mmHg% vs 2368±139 mmHg%, p=NS; GWW 62±5 mmHg% vs 65±4 mmHg%, p=NS; GWE PDD 89±9% vs 87±11%, p=NS). LALS and GCW were significantly reduced in patients with HFpEF compared with PDD patients (LALS 21.3±7% vs 29±5%, p<0.01; GCW 1964±112 mmHg% vs 2259±164 mmHg%, p<0.01). Conclusion Patients with HFpEF have reduced LALS and GCW compared with PDD patients. Both parameters are indicative for LA and LV myocardial fibrotic burden respectively which might be one of the probable explanations of PDD transition to HFpEF. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Committee of Science at Ministry of Education of Republic of Armenia

Significance of the echocardiographic evaluation of left atrial myocardial strain for early diagnosis of heart failure with preserved ejection fraction

Kardiologiia ◽  
2021 ◽  
Vol 61 (8) ◽  
pp. 68-75
Author(s):  
E. K. Serezhina ◽  
A. G. Obrezan
Keyword(s):  
Heart Failure ◽  
Early Diagnosis ◽  
Ejection Fraction ◽  
Left Atrial ◽  
Myocardial Dysfunction ◽  
Systolic Dysfunction ◽  
Myocardial Strain ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Echocardiographic Evaluation

This systematic review is based on 19 studies from Elsevier, PubMed, Embase, and Scopus databases, which were found by the following keywords: LA strain (left atrial strain), STE (speckle tracking echocardiography), HF (heart failure), and HFpEF (heart failure with preserved ejection fraction). The review focuses on results and conclusions of studies on using the 2D echocardiographic evaluation of left atrial (LA) myocardial strain for early diagnosis of HFpEF in routine clinical practice. Analysis of the studies included into this review showed a significant decline of all LA functions in patients with HFpEF. Also, multiple studies have reported associations between decreased indexes of LA strain and old age, atrial fibrillation, left ventricular hypertrophy, left and right ventricular systolic dysfunction, and LV diastolic dysfunction. Thus, the review indicates significant possibilities of using indexes of LA strain in evaluation of early stages of both systolic and diastolic myocardial dysfunction. Notably, LA functional systolic and diastolic indexes are not sufficiently studied despite their growing significance for diagnosis and prognosis of patients with HFpEF. For this reason, in addition to existing models for risk stratification in this disease, including clinical characteristics and/or echocardiographic data, future studies should focus on these parameters. 

scholarly journals Opportunistic screening models for high-risk men and women to detect diastolic dysfunction and heart failure with preserved ejection fraction in the community

2018 ◽  
Vol 26 (6) ◽  
pp. 613-623 ◽  
Author(s):  
Aisha Gohar ◽  
Rogier F Kievit ◽  
Gideon B Valstar ◽  
Arno W Hoes ◽  
Evelien E Van Riet ◽  
...  
Keyword(s):  
Heart Failure ◽  
High Risk ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Men And Women ◽  
Ventricular Diastolic Dysfunction

Background The prevalence of undetected left ventricular diastolic dysfunction is high, especially in the elderly with comorbidities. Left ventricular diastolic dysfunction is a prognostic indicator of heart failure, in particularly of heart failure with preserved ejection fraction and of future cardiovascular and all-cause mortality. Therefore we aimed to develop sex-specific diagnostic models to enable the early identification of men and women at high-risk of left ventricular diastolic dysfunction with or without symptoms of heart failure who require more aggressive preventative strategies. Design Individual patient data from four primary care heart failure-screening studies were analysed (1371 participants, excluding patients classified as heart failure and left ventricular ejection fraction <50%). Methods Eleven candidate predictors were entered into logistic regression models to be associated with the presence of left ventricular diastolic dysfunction/heart failure with preserved ejection fraction in men and women separately. Internal-external cross-validation was performed to develop and validate the models. Results Increased age and β-blocker therapy remained as predictors in both the models for men and women. The model for men additionally consisted of increased body mass index, moderate to severe shortness of breath, increased pulse pressure and history of ischaemic heart disease. The models performed moderately and similarly well in men (c-statistics range 0.60–0.75) and women (c-statistics range 0.51–0.76) and the performance improved significantly following the addition of N-terminal pro b-type natriuretic peptide (c-statistics range 0.61–0.80 in women and 0.68–0.80 in men). Conclusions We provide an easy-to-use screening tool for use in the community, which can improve the early detection of left ventricular diastolic dysfunction/heart failure with preserved ejection fraction in high-risk men and women and optimise tailoring of preventive interventions.

scholarly journals Features of heart failure with preserved ejection fraction (HFpEF) in diabetic patients with resistant hypertension

2021 ◽  
Vol 24 (4) ◽  
pp. 304-314
Author(s):  
M. A. Manukyan ◽  
A. Y. Falkovskaya ◽  
V. F. Mordovin ◽  
T. R. Ryabova ◽  
I. V. Zyubanova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Blood Pressure ◽  
Blood Flow ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Resistant Hypertension ◽  
Diabetic Patients ◽  
Preserved Ejection Fraction

BACKGROUND: It is expected that a steady increase in the incidence of diabetes and resistant hypertension (RHTN), along with an increase in life expectancy, will lead to a noticeable increase in the proportion of patients with heart failure with preserved ejection fraction (HFpEF). At the same time, data on the frequency of HFpEF in a selective group of patients with RHTN in combination with diabetes are still lacking, and the pathophysiological and molecular mechanisms of its formation have not been yet studied sufficiently.AIM: To assess the features of the development HFpEF in diabetic and non-diabetic patients with RHTN, as well as to determine the factors associated with HFpEF.MATERIALS AND METHODS: In the study were included 36 patients with RHTN and type 2 diabetes mellitus (DM) (mean age 61.4 ± 6.4 years, 14 men) and 33 patients with RHTN without diabetes, matched by sex, age and level of systolic blood pressure (BP). All patients underwent baseline office and 24-hour BP measurement, echocardiography with assess diastolic function, lab tests (basal glycemia, HbA1c, creatinine, aldosterone, TNF-alpha, hsCRP, brain naturetic peptide, metalloproteinases of types 2, 9 (MMP-2, MMP-9) and tissue inhibitor of MMP type 1 (TIMP-1)). HFpEF was diagnosed according to the 2019 AHA/ESC guidelines.RESULTS: The frequency of HFpEF was significantly higher in patients with RHTN with DM than those without DM (89% and 70%, respectively, p=0.045). This difference was due to a higher frequency of such major functional criterion of HFpEF as E/e’≥15 (p=0.042), as well as a tendency towards a higher frequency of an increase in left atrial volumes (p=0.081) and an increase in BNP (p=0.110). Despite the comparable frequency of diastolic dysfunction in patients with and without diabetes (100% and 97%, respectively), disturbance of the transmitral blood flow in patients with DM were more pronounced than in those without diabetes. Deterioration of transmitral blood flow and pseudo-normalization of diastolic function in diabetic patients with RHTN have relationship not only with signs of carbohydrate metabolism disturbance, but also with level of pulse blood pressure, TNF-alfa, TIMP-1 and TIMP-1 / MMP-2 ratio, which, along with the incidence of atherosclerosis, were higher in patients with DM than in those without diabetes.CONCLUSIONS: Thus, HFpEF occurs in the majority of diabetic patients with RHTN. The frequency of HFpEF in patients with DN is significantly higher than in patients without it, which is associated with more pronounced impairments of diastolic function. The progressive development of diastolic dysfunction in patients with diabetes mellitus is associated not only with metabolic disorders, but also with increased activity of chronic subclinical inflammation, profibrotic state and high severity of vascular changes.

scholarly journals Preload-corrected dynamic Starling mechanism in patients with heart failure with preserved ejection fraction

2018 ◽  
Vol 124 (1) ◽  
pp. 76-82 ◽  
Author(s):  
Michinari Hieda ◽  
Erin Howden ◽  
Shigeki Shibata ◽  
Takashi Tarumi ◽  
Justin Lawley ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Diastolic Pressure ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Dynamic Modulation ◽  
Power Spectral ◽  
Ventricular Diastolic Dysfunction

The beat-to-beat dynamic Starling mechanism (DSM), the dynamic modulation of stroke volume (SV) because of breath-by-breath changes in left-ventricular end-diastolic pressure (LVEDP), reflects ventricular-arterial coupling. The purpose of this study was to test whether the LVEDP-SV relationship remained impaired in heart failure with preserved ejection fraction (HFpEF) patients after normalization of LVEDP. Right heart catheterization and model-flow analysis of the arterial pressure waveform were performed while preload was manipulated using lower-body negative pressure to alter LVEDP. The DSM was compared at similar levels of LVEDP between HFpEF patients ( n = 10) and age-matched healthy controls ( n = 12) (HFpEF vs. controls: 10.9 ± 3.8 vs. 11.2 ± 1.3 mmHg, P = 1.00). Transfer function analysis between diastolic pulmonary artery pressure (PAD) representing dynamic changes in LVEDP vs. SV index was applied to obtain gain and coherence of the DSM. The DSM gain was significantly lower in HFpEF patients than in the controls, even at a similar level of LVEDP (0.46 ± 0.19 vs. 0.99 ± 0.39 ml·m−2·mmHg−1, P = 0.0018). Moreover, the power spectral density of PAD, the input variability, was greater in the HFpEF group than the controls (0.75 ± 0.38 vs. 0.28 ± 0.26 mmHg2, P = 0.01). Conversely, the power spectral density of SV index, the output variability, was not different between the groups ( P = 0.97). There was no difference in the coherence, which confirms the reliability of the linear transfer function between the two groups (0.71 ± 0.13 vs. 0.77 ± 0.19, P = 0.87). The DSM gain in HFpEF patients is impaired compared with age-matched controls even at a similar level of LVEDP, which may reflect intrinsic LV diastolic dysfunction and incompetence of ventricular-arterial coupling. NEW & NOTEWORTHY The beat-to-beat dynamic Starling mechanism (DSM), the dynamic modulation of stroke volume because of breath-by-breath changes in left-ventricular end-diastolic pressure (LVEDP), reflects ventricular-arterial coupling. Although the DSM gain is impaired in heart failure with preserved ejection fraction (HFpEF) patients, it is not clear whether this is because of higher LVEDP or left-ventricular diastolic dysfunction. The DSM gain in HFpEF patients is severely impaired, even at a similar level of LVEDP, which may reflect intrinsic left-ventricular diastolic dysfunction.

Abstract 14648: Interleukin-18 Blockade Prevents Diastolic Dysfunction in a Mouse Model of Heart Failure With Preserved Ejection Fraction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Jessica A Regan ◽  
Adolofo G Mauro ◽  
Salvatore Carbone ◽  
Carlo Marchetti ◽  
Eleonora Mezzaroma ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Ejection Fraction ◽  
Mouse Model ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Low Dose ◽  
Preserved Ejection Fraction ◽  
Interleukin 18 ◽  
Lv Diastolic Function

Background: Heart failure with preserved ejection fraction (HFpEF) is characterized by elevated left ventricular (LV) filling pressures due to impaired LV diastolic function. Low-dose infusion of angiotensin 2 (AT2) in the mouse induces a HFpEF phenotype without increasing blood pressure. AT2 infusion induces expression of Interleukin-18 (IL-18) in the heart. We therefore tested whether IL-18 mediated AT2-induced LV diastolic dysfunction in this model. Methods: We infused subcutaneously AT2 (0.2 mg/Kg/day) or a matching volume of vehicle via osmotic pumps surgically implanted in the interscapular space in adult wild-type (WT) male mice and IL-18 knock-out mice (IL-18KO). We also treated WT mice with daily intraperitoneal injections of recombinant murine IL-18 binding protein (IL-18bp, a naturally occurring IL-18 blocker) at 3 different doses (0.1, 0.3 and 1.0 mg/kg) or vehicle for 25 days starting on day 3. We performed a Doppler-echocardiography study before implantation and at 28 days to measure LV dimensions, mass, and systolic and diastolic function in all mice. LV catheterization was performed prior to sacrifice to measure LV end-diastolic pressure (LVEDP) using a Millar catheter. Results: AT2 induces a significant increase in isovolumetric relaxation time (IRT) and myocardial performance index (MPI) at Doppler echocardiography and elevation of LVEDP at catheterization, indicative of impaired LV diastolic function, in absence of any measurable effects on systolic blood pressure nor LV dimensions, mass, or systolic function. Mice with genetic deletion of IL-18 (IL-18 KO) or WT mice treated with IL-18bp had no significant increase in IRT, MPI or LVEDP with AT2 infusion. Conclusion: Genetic or pharmacologic IL-18 blockade prevent diastolic dysfunction in a mouse model of HFpEF induced by low dose AT2 infusion, suggesting a critical role of IL-18 in the pathophysiology of HFpEF.

Abstract P394: Angiotensin-(1-7) Attenuates Diastolic Dysfunction And Cardiac Remodeling In Murine Model Of Heart Failure With Preserved Ejection Fraction

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Pariya Edalat ◽  
Karina Gomes ◽  
Noura N Ballasy ◽  
Anshul S Jadli ◽  
Darrell D Belke ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiac Hypertrophy ◽  
Diastolic Dysfunction ◽  
Murine Model ◽  
Cardiac Remodeling ◽  
Control Group ◽  
Chow Diet ◽  
Preserved Ejection Fraction ◽  
Phosphorylation Level

Background: Heart failure with preserved ejection fraction (HFpEF) is a global public health epidemic that accounts for half of the heart failure cases. Various therapeutic approaches have been tested to block the activation of the Renin-Angiotensin System (RAS), including AT1R blockers (ARBs), Angiotensin-Converting Enzyme (ACE) inhibitors (ACEi), and direct renin inhibitors (DRIs) with modest to negligible benefits. The discovery of ACE2, a novel homolog of ACE, has advanced our understanding of the RAS. ACE2 is a monocarboxypeptidase that degrades Ang II into Ang-(1-7), which works via the activation of the Mas receptor. It has been well understood that the actions of Ang-(1-7) attenuate cardiac remodeling, production of ROS, and cardiac fibrosis. Objective: To determine the therapeutic role of Ang-(1-7) in HFpEF and identify the molecular mechanism related to its action. Methods and Results: To generate a murine model of HFpEF, male WT mice (n=24) were subjected to HFD in addition to eNOS inhibition with L-NAME (0.5 g l-1 in drinking water), as previously described. The control group (n=12) received chow diet and normal tap water. The murine model of HFpEF was validated using the non-invasive transthoracic echocardiography and invasive pressure-volume (PV) loop analyses, which exhibited diastolic dysfunction as well as cardiac hypertrophy. To evaluate the effects of Ang-(1-7) on HFpEF, animals were administered with either saline (n=12) or Ang-(1-7) (n=12) (24 μg/kg/day) for four weeks. Ang-(1-7) treatment improved diastolic function by reducing LVEDP (Ctrl: 8.267±1.254; HFD+L-NAME: 17.64±1.925; Ang-(1-7): 9.100±1.578) and Tau value (Ctrl: 7.365±0.5752; HFD+L-NAME: 9.224±0.3569; Ang-(1-7): 7.381±0.3041). Furthermore, Ang-(1-7) reduced cardiac hypertrophy by reducing the phosphorylation level of MAPK ERK 1/2 (Ctrl: 0.9074±0.1088; HFD+L-NAME: 1.212±0.1369; Ang-(1-7): 0.5615±0.1502) and increasing the phosphorylation level of AMPK (Ctrl: 0.1502±0.1502; HFD+L-NAME: 0.6127±0.06414; Ang-(1-7): 0.7852±0.1006). Ang-(1-7) treatment also reduces cardiomyocytes’ size and decreases interstitial fibrosis, as indicated by WGA and PSR staining. Conclusion: Ang-(1-7) treatment attenuated the development of HFD+L-NAME-induced HFpEF, reduced cardiac hypertrophy, and improved metabolic function.

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