Left Ventricle Diastolic Function Research Articles

P6295Methotrexate reduces cardiac remodeling and improves left ventricle function in rats with Takotsubo cardiomyopathy

Abstract Introduction Takotsubo cardiomyopathy (TC) is characterized by cardiac disfunction and left ventricle (LV) remodeling caused, mainly, by physical or emotional stress. Previously, we have shown in atherosclerotic rabbits that methotrexate (MTX), an anti-inflammatory chemotherapeutic agent, is capable of reducing the inflammatory process and atherosclerotic lesions. Purpose To investigate the effect of MTX treatment in rats with TC. Methods TC was induced in Wistar rats with 2 injections of isoproterenol (85mg/kg) with a 24h interval. Animals were allocated in 3 experimental groups: CT: animals induced and treated with saline; TK: animal induced with isoproterenol and treated with saline; TK-MTX: animals induced with isoproterenol and treated with MTX (1mg/kg). Animals were treated every week for 4 weeks. After the treatment, echocardiography, morphometry and molecular analysis (Western blot) of the LV were performed. Results TK and TK-MTX groups did not show cardiac dilation or LV intraventricular septum and posterior wall thickening. However, compared to TK, the treatment with MTX improved both LV systolic and diastolic function. In addition, the treatment diminished myocytes diameter and subendocardial and interstitial fibrosis of the LV. Protein expression of pro-apoptotic factors (caspase 3 and BAX), pro-inflammatory cytokine TNF-α, metalloproteinase 2, transforming growth factor beta, collagen I and III and hypoxia-inducible factor 2 alfa were all decreased. Vascular endothelial growth factor (VEGF) and adenosine A1 receptor showed increased protein expression in TK-MTX group when compared to CT and TK. There was correlation of myocardial fibrosis (r2=-0.57), myocytes diameter (r2=-0.78) and VEGF expression (r2=0.58) with LV systolic disfunction. Also, myocardial fibrosis (r2=0.57) and VEGF expression (r2=-0.68) correlated with diastolic disfunction in the LV. Animals treated with MTX did not present any toxicity. Conclusion Treatment with MTX diminished apoptosis, the expression of TNF-α and metalloproteinases, cardiac hypertrophy and myocardial fibrosis. Besides that, the treatment increased angiogenesis and strongly improved cardiac function of the LV. MTX, possibly through an increase in the production of intracellular adenosine, could be considered as a feasible treatment for TC. Acknowledgement/Funding FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo)

P778Valsartan reduces level of soluble ST2 and left ventricle remodeling in patients with dual chamber pacemaker

Abstract Introduction Permanent right ventricle pacing leads to left ventricle remodeling, its systolic dysfunction and symptomatic heart failure in the long run. Valsartan is well known for its preventive anti-remodeling function in the post infarction heart remodeling. Objectives To assess the effect of valsartan on left ventricle remodeling in patients with second and third degree atrioventricular block with first-time implantation of dual chamber pacemaker. Methods This was a randomized, double-blind, placebo controlled single center study. One hundred eligible patients were assigned in a 1:1:1 fashion to receive placebo, valsartan 80mg or 160mg once daily, respectively. Echocardiographic assessment of left ventricle geometry, its systolic and diastolic function was performed at baseline and at twelve months. One patient from placebo group suffered stroke. We present the baseline date for 100 enrolled patients and follow-up data for 88 patients who have completed the study. Data in valsartan arms are pooled in one group. Concentration of soluble ST2 was measured in duplicates with Aspect Reader (Critical Diagnostics). Results Results are presented in table. Data are presented as mean and standard deviation. Table 1 Placebo (n=28) Valsartan (n=60) ANOVA Baseline 12 mths Baseline 12 mths sST2, ng/mL 36.0±16.0 39.4±15.3 35.1±15.2 19.9±6.5 0.01 LVEF, % 60±8 55±9 60±8 58±8 0.01 LVEDD, mm 48±5 50±4 48±6 49±5 NS LVESD, mm 29±4 32±5 29±5 31±4 NS LVEDV, mL 79±12 84±13 80±12 81±13 NS LVESV, mL 32±5 38±7 31±5 34±6 0.01 E/A 0.94±0.12 0.92±0.13 0.94±0.15 0.95±0.15 NS DecT, ms 211±38 226±43 223±45 218±37 0.01 IVRT, ms 98±14 108±17 101±17 99±18 0.01 Conclusion Valsartan has protective effect of left ventricle remodeling and function. It may be useful in prevention of pacing induced heart failure. Decrease in soluble ST2 concentration may help explain the alternative mechanism for protective role of valsartan. (NCT01805804)

P4502Noninvasively assessed mitochondrial function estimated by skin fluorescence is abnormal in coronary artery disease

Abstract Mitochondrial NADH undergoes oxygenation to NAD+ and NADH molecules, activated by ultraviolet light, start to emit fluorescence at a wavelength 460nm. This phenomenon can be measured to non-invasively assess mitochondrial function in the forearm epidermis at rest, during transient ischaemia, and afterward reperfusion assuming that it reflects abnormal microvascular circulation. We hypothesized that flow-dependent skin fluorescence (FDSF) is abnormal in patients with coronary atherosclerosis. Methods Prototype device manufactured by Angionica (Poland) was used to quantify FDSF recorded in forearm before, during and after 100 s of brachial artery occlusion in 63 individuals (26 with coronary artery disease (CAD) and 37 healthy volunteers. The absolute value of baseline FDSF (BASE), maximum FDSF (MAX), minimal FDSF (MIN), percentage ischemic response (IR) and hyperemic response (HR) were measured. Age, lipid profile, fasting glucose, HbA1c, C-reactive protein (CRP), systolic and diastolic blood pressure, pulse wave velocity (PWV), augmentation index, time domain heart rate variability parameters (SDNN, rMSSD) and estimated apnea/hypopnea index -eAHI (Holter ECG based), BMI, intima-media thickness (IMT), left ventricle systolic and diastolic function were determined in all study participants to search for potential correlations with FDSF. Results Measurements were feasible in all study subjects and examination duration was 9±1min. Hyperemic response (HR) was significantly lower in patients with CAD vs controls: 10,4 vs. 14,36 vs 14,73 – p=0,025. Other parameters: BASE, MAX, MIN, and IR were not significantly different between groups (p>0,05). In the entire group, HR was correlated with age (r=−0,23 p=0,037), and with total or LDL cholesterol (r=0,37 p=0,001 and r=0,36 p=0,001). Interestingly, HR was also positively correlated with SDNN (r=0,26 p=0,044) and rMSSD (r=0,29 p=0,026). Mode of FDSF examination Conclusion Abnormal mitochondrial function probably secondary to microcirculatory disorder is detectable by noninvasive skin fluorescence test as decreased hyperemic response in patients with coronary disease. Age and cholesterol concentration as well as autonomic balance Holter indices are correlated with hyperemic response. Acknowledgement/Funding POIR.01.01.01.0540/15-00

Ratio of Early Mitral Inflow Velocity to the Global Diastolic Strain Rate and Global Left Ventricular Longitudinal Systolic Strain Predict Overall Mortality and Major Adverse Cardiovascular Events in Hemodialysis Patients.

Background The ratio of early mitral inflow velocity to the global diastolic strain rate (E/E'sr) and global longitudinal systolic strain (GLS) of the left ventricle (LV) are emerging indices of diastolic and systolic functions, respectively, for the LV. Their prognostic significance in the prediction of mortality and cardiovascular (CV) outcomes remains underexplored in hemodialysis (HD) patients. Methods This prospective study included 190 maintenance HD patients. The E/E'sr ratio and GLS were assessed using two-dimensional speckle tracking echocardiography. The clinical outcomes included overall mortality, CV mortality, and major adverse cardiovascular events (MACE). The associations between the E/E'sr ratio, GLS, and clinical outcomes were evaluated using multivariate Cox regression analysis. The incremental values of the E/E'sr ratio and GLS in outcome prediction were assessed by χ2 changes in Cox models. Results Over a median follow-up period of 3.7 years, there were 35 overall deaths, 16 CV deaths, and 45 MACE. Impaired diastolic function with a higher E/E'sr ratio was associated with overall mortality (HR, 1.484; 95% CI, 1.201−1.834; p < 0.001), CV mortality (HR, 1.584; 95% CI, 1.058–2.371; p = 0.025), and MACE (HR, 1.205; 95% CI, 1.040−1.397; p = 0.013) in multivariate adjusted Cox analysis. Worsening GLS was associated with overall mortality (HR, 1.276; 95% CI, 1.101−1.480; p = 0.001), CV mortality (HR, 1.513; 95% CI, 1.088−2.104; p = 0.014), and MACE (HR, 1.214; 95% CI, 1.103−1.337; p < 0.001). The E/E'sr ratio and GLS had better outcome prediction than the E to early diastolic mitral annular velocity (E/E') ratio and left ventricular ejection fraction (LVEF). Moreover, adding the E/E'sr ratio and GLS to Cox models containing relevant clinical and conventional echocardiographic parameters improved the prediction of overall mortality (p < 0.001), CV mortality (p < 0.001), and MACE (p < 0.001). Conclusion The E/E'sr ratio and GLS, as emerging indices of LV diastolic and systolic functions, significantly predict mortality and CV outcomes and outperform conventional echocardiographic parameters in outcome prediction in HD patients.

Correlation between non-invasive myocardial work indices and main parameters of systolic and diastolic function: results from the EACVI NORRE study.

The present study sought to evaluate the correlation between indices of non-invasive myocardial work (MW) and left ventricle (LV) size, traditional and advanced parameters of LV systolic and diastolic function by 2D echocardiography (2DE). A total of 226 (85 men, mean age: 45 ± 13 years) healthy subjects were enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. Global work index (GWI), global constructive work (GCW), global work waste (GWW), and global work efficiency (GWE) were estimated from LV pressure-strain loops using custom software. Peak LV pressure was estimated non-invasively from brachial artery cuff pressure. LV size, parameters of systolic and diastolic function and ventricular-arterial coupling were measured by echocardiography. As advanced indices of myocardial performance, global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were obtained. On multivariable analysis, GWI was significantly correlated with GLS (standardized beta-coefficient = -0.23, P < 0.001), ejection fraction (EF) (standardized beta-coefficient = 0.15, P = 0.02), systolic blood pressure (SBP) (standardized beta-coefficient = 0.56, P < 0.001) and GRS (standardized beta-coefficient = 0.19, P = 0.004), while GCW was correlated with GLS (standardized beta-coefficient = -0.55, P < 0.001), SBP (standardized beta-coefficient = 0.71, P < 0.001), GRS (standardized beta-coefficient = 0.11, P = 0.02), and GCS (standardized beta-coefficient = -0.10, P = 0.01). GWE was directly correlated with EF and inversely correlated with Tei index (standardized beta-coefficient = 0.18, P = 0.009 and standardized beta-coefficient = -0.20, P = 0.004, respectively), the opposite occurred for GWW (standardized beta-coefficient =--0.14, P = 0.03 and standardized beta-coefficient = 0.17, P = 0.01, respectively). The non-invasive MW indices show a good correlation with traditional 2DE parameters of myocardial systolic function and myocardial strain.

The Outcome of Diabetic Patients with Cardiomyopathy in Critical Care Unit: Hospital and Short-Term Outcome in a Period of Six Months to One Year.

BACKGROUND:Diabetes mellitus (DM) is a major risk factor for heart failure (HF) and coronary artery disease (CAD). DM may cause structural changes involving the left ventricle (LV) systolic and diastolic function.AIM:To compare patients who have diabetes and ischemic cardiomyopathy (ICM) to those with diabetic cardiomyopathy (DMCMP) regarding LV systolic function, diastolic function, in hospital long term and short-term mortality.METHODS:Ninety diabetic patients with heart failure and left ventricular ejection fraction (LVEF) ≤ 35%, admitted to Critical Care Medicine department Cairo University were divided into two groups based on coronary angiography results; group I (ICM) n = 48 patients and group II (DMCMP) n = 42 patients.RESULTS:Group I patients had higher mean age (63 ± 7 years), (p = 0.004), Hypertension (p < 0.001) and dyslipidemia (p = 0.008) were significantly more present in group I compared to group II. No significant differences were found regarding LVEF, global longitudinal strain (GLS), E/A and E/É ratio in both groups. A significant difference in the wall motion score index (WMSI) in group I; (1.4 ± 0.4) versus group II; (1.1 ± 0.2), (p = 0.005) was found. In the study, 6 patients had a cardiogenic shock with no documented in-hospital mortality. At 6 months, statistically, significantly higher mortality rates were found in group I, (p = 0.006), while at one year there was no significant difference in the mortality between the two groups, (p = 0.077). In comparison of the survived and non-survived patients at 6 months and one year in group I (ICM) there was a significant difference in LVEF (40 ± 6% vs 23 ± 6%, p < 0.001), GLS (- 8.1 ± 2.4 vs - 4.6 ± 2.6, p = 0.007), E/A (1.25 ± 0.91 vs 1.8 ± 0.5, p = 0.038), E/É (11.68 ± 7.5 vs 21.3 ± 3.6, p = 0.001) respectively. In group ll (DMCMP) there was no documented mortality at 6 months follow up, however, at one year there was statistically significant difference in the mortality between survived and non-survived patients; the LVEF (35 ± 8% vs 25 ± 2%, p = 0.014), GLS (-7.9 ± 2.9% vs -5 ± 0.1%, p = 0.032), E/A (1.45 ± 0.8 vs 3.3 ± 0, p = 0.006) respectively. The E/É ratio in group ll was not significantly different between the groups (15.73 ± 5.3 vs 15 ± 1, p = 0.873).CONCLUSION:The combination of cardiomyopathy and diabetes affects LV systolic and diastolic function; however; ischemic cardiomyopathy and diabetic cardiomyopathy had a similar systolic and diastolic function. Ischemic cardiomyopathy is associated with worse prognosis compared to diabetic cardiomyopathy.

Adenosine Kinase Inhibition Augments Conducted Vasodilation and Prevents Left Ventricle Diastolic Dysfunction in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is often manifested as impaired cardiovascular reserve. We sought to determine if conducted vasodilation, which coordinates microvascular resistance longitudinally to match tissue metabolic demand, becomes compromised in HFpEF. We hypothesized that the metabolic vasodilator adenosine facilitates and that inhibition of ADK (adenosine kinase) augments conducted vasodilation for a more efficient myocardial perfusion and improved left ventricle (LV) diastolic function in HFpEF. We assessed conducted vasodilation in obese ZSF1 rats that develop LV diastolic dysfunction and is used to model human HFpEF. Additionally, conducted vasodilation was measured in arterioles isolated from the right atrial appendages of patients with HFpEF. We found a markedly reduced conducted vasodilation both in obese ZSF1 rats and in patients with HFpEF. Impaired conducted vasodilation was accompanied by increased vascular ADK expression. Isolated rat and human arterioles incubated with adenosine (10 nmol/L) or ADK inhibitor ABT-702 (0.1 µmol/L) both displayed augmented conducted vasodilation. Treatment of obese ZSF1 rats with ABT-702 (1.5 mg/kg, IP for 8 weeks) prevented LV diastolic dysfunction, and in a crossover design augmented conducted vasodilation and improved LV diastolic function. ABT-702 treated obese ZSF1 rats exhibited reduced expression of myocardial carbonic anhydrase 9 and collagen, surrogate markers of myocardial hypoxia. Upregulation of vascular ADK mitigates adenosine-facilitated conducted vasodilation in obese ZSF1 rats and in patients with HFpEF. We propose that pharmacological inhibition of ADK could be beneficial for therapeutic augmentation of conducted vasodilation, thereby improving tissue perfusion and LV diastolic function in HFpEF.

Arterial Stiffness, Galectin-3, Tgf-Beta1 And Diastolic Dysfunction In Patients With Atrial Fibrillation

Background and Aims: Carotid-femoral pulse wave velocity (cfPWV) characterizes arterial stiffness is associated with increased risk of cardiovascular complications. The objective of this study was to compare cfPWV in patients with atrial fibrillation(AFib) and healthy individuals and to identify the relationship between arterial stiffness, diastolic function of left ventricle(DFLV) and serum levels of galectin-3(Gal-3), transforming growth factor beta1(TGF-beta1) - substances with profibrogenic effects.

Impact of Severe Pulmonary Arterial Hypertension on the Left Heart and Prognostic Implications

Severe pulmonary arterial hypertension (sPAH) results in a dilated and dysfunctional right ventricle (RV) together with a small left ventricle (LV) with preserved systolic function. RV size and function parameters have an established association with poor prognosis in sPAH. We sought to determine the impact of RV geometry and function on LV mechanics and its relationship with mortality. We studied 114 patients (54±13years) with sPAH, normal LV ejection fraction (LVEF), and complete two-dimensional transthoracic echocardiograms (TTE) and compared them with 70 normal controls of similar age and gender distribution. TTE measurements of atrial sizes, ventricular volumes and function, tricuspid and mitral regurgitation (TR, MR), and LV diastolic function were performed. Speckle-tracking strain was measured in all four chambers, including LV global longitudinal strain (GLS). Cox proportional hazards regression with forward selection was performed to determine the associations between measured indices and mortality over a 20-month follow-up period. Kaplan-Meier curves were generated for variables most associated with death. Compared with controls, sPAH patients had greater TR severity and right-chamber size with worse function. Of note, LVEF was normal in both groups. Left atrial peak strain and LV GLS were reduced in sPAH, with greater reductions in nonsurvivors. In multivariate analysis, right atrial volume index (hazard ratio [HR]=1.02 [CI, 1.01-1.04], P<.01), RV free-wall strain (HR=1.08; CI [1.01-1.15]; P=.03), and LV GLS (HR=1.11 [CI, 1.01-1.22]; P=.04) were independently associated with mortality. Although PAH is predominantly a right heart disease, in our cohort of sPAH with normal LVEF, LV GLS was independently associated with death in addition to RV and right atrial abnormalities. These findings indicate that the role of left heart dysfunction in sPAH may be underappreciated in clinical practice.

INTEREST IN EVALUATION OF THE LEFT ATRIUM FUNCTION IN HYPERTENSION

Objective:Hypertension is a common pathology in the world and in our climates. It affects the left atrium and the diastolic function of left ventricle. The LA has an impact on the filling and performance of the LV. The purpose of our study is to evaluate the impact of hypertension on the function of

EXPRESS: Left ventricular early diastolic strain rate detected by two-dimensional speckle tracking echocardiography and disease severity in pre-capillary pulmonary hypertension.

We investigated and compared the correlations between two-dimensional speckle tracking echocardiography detected left ventricular peak early diastolic strain rates (global: left ventricular global peak early diastolic strain rate; septum: left ventricular peak early diastolic strain rate of septum; free wall: left ventricular peak early diastolic strain rate of free wall) and disease severity in pre-capillary pulmonary hypertension. Seventy-four pre-capillary pulmonary hypertension patients (23 males and 51 females, 35 ± 13 years) and thirty healthy controls were consecutively recruited for two-dimensional speckle tracking echocardiography analyses in our study. Medical records of pre-capillary pulmonary hypertension patients were reviewed to capture clinical data; risk assessments were performed based on the 2015 ESC Guidelines. Compared with healthy controls, left ventricular global peak early diastolic strain rate was lower in pre-capillary pulmonary hypertension patients (1.11 ± 0.60 s−1 versus 1.47 ± 0.45 s−1, P = 0.001), especially that of the septum (1.13 ± 0.58 s−1 versus 1.68 ± 0.46 s−1, P<0.001). Linear correlation analyses showed significant but weak correlations between left ventricle diastolic parameters and peak oxygen consumption, N-terminal pro-brain natriuretic peptide, and conventional echocardiographic right ventricle parameters: E/E′, tricuspid annular plane systolic excursion, S′, and fractional area change. No or weak correlations were observed between left ventricle diastolic parameters and hemodynamics. Multivariate logistic regression analyses showed left ventricular global peak early diastolic strain rate (OR: 0.304; 95%CI: 0.101–0.911) and left ventricular peak early diastolic strain rate of septum (OR: 0.252; 95%CI: 0.075–0.848) independently predict intermediate–high risk of pulmonary hypertension patients, even adjusted by age, gender, and body mass index. Receive operating characteristic curves showed that all the three models had the capacity to predict intermediate–high risk of pulmonary hypertension patients, and the model including left ventricular peak early diastolic strain rate of septum showed the strongest predictive capacity (area under the curve = 0.76, 95%CI: 0.59–0.93). Two-dimensional speckle tracking echocardiography detected left ventricle diastolic function parameters are significantly correlated with clinical data and can independently predict intermediate–high risk in pre-capillary pulmonary hypertension patients; the dysfunction of interventricular septum may make major contribution.

Relationship among long-term aircraft noise exposure, blood pressure profile, and arterial stiffness.

To assess the impact of long-term exposure to aircraft noise on blood pressure (BP), prevalence of arterial hypertension, and indices of asymptomatic organ damage. Using acoustic maps, we selected and further compared people living (average 35 years) in areas exposed to high, more than 60 dB (n = 101), and low aircraft noise, less than 55 dB (n = 100). Medical history taking, office BP measurement, ambulatory BP monitoring, and echocardiographic and arterial stiffness measurements were performed. Exposure to aircraft noise did not increase the prevalence of arterial hypertension (50%, both groups) but was associated with higher office (88.3 ± 11.4 vs. 79.8 ± 8.6 mmHg, P < 0.001) and night-time DBP (66.6 ± 9.5 vs. 63.6 ± 7.3 mmHg, P < 0.01). Participants exposed to a high aircraft noise level had a higher carotid-femoral pulse wave velocity (PWV) (10.3 ± 1.8 vs. 9.4 ± 1.4 m/s, P < 0.01) and lower early mitral annulus velocity (e') (8.4 ± 2.9 vs. 9.2 ± 3.4 cm/s, P = 0.047). These differences were independent of age, sex, BMI, education, time spent at home, smoking status, alcohol consumption, and antihypertensive treatment. Higher office and night-time DBP, PWV, and e' values were explicitly observed in exposed normotensive participants. PWV in aircraft noise-exposed normotensive participants was equal to that of two decades older unexposed normotensive participants and was significantly associated with noise annoyance. Long-term aircraft noise exposure is related to higher office and night-time DBP, more advanced arterial stiffness, and unfavourable left ventricle diastolic function changes. Accelerated arterial stiffening was observed in those exposed to aircraft noise, even normotensive participants, to a degree depending on noise annoyance.

Adjuvant radiotherapy-induced cardiac changes among patients with early breast cancer: a three-year follow-up study

Background: In this study, we evaluate the evolution of cardiac changes during a three-year follow-up after adjuvant breast radiotherapy (RT).Methods: Sixty patients with left-sided and 20 patients with right-sided early stage breast cancer without chemotherapy were included in this prospective study. Echocardiography and cardiac biomarkers were evaluated before, immediately after and 3 years after RT. Radiation doses to cardiac structures were calculated.Results: In echocardiography, left ventricle (LV) systolic measurements had impaired at 3 years compared to baseline: the mean global longitudinal strain (GLS) worsened from –18 ± 3 to –17 ± 3 (p = .015), LV ejection fraction from 62 ± 5% to 60 ± 4% (p = .003) and the stroke volume from 73 ± 16 mL to 69 ± 15 mL (p = .015). LV diastolic function was also negatively affected: the isovolumetric relaxation time was prolonged (p = .006) and the first peak of diastole decreased (p = .022). Likewise, left atrial (LA) measurements impaired. These changes in echocardiography were more prominent in left-sided than in right-sided patients. The concurrent aromatase inhibitor (AI) use was associated with GLS impairment. In all patients, the N-terminal pro-brain natriuretic peptide (proBNP) values were median (interquartile range) 74 (41–125) ng/L at baseline, 75 (41–125) ng/L at the end of RT and 96 (56–162) ng/L at 3 years (p < .001 from baseline to 3 years). However, proBNP did not increase in right-sided patients.Conclusion: During the 3-year follow-up after RT, negative subclinical changes in cardiac biomarkers and in LV systolic and diastolic function were observed. The measured changes were more pronounced in left-sided patients. In addition, AI use was associated with impaired cardiac systolic function.

Асоціація поліморфізму гена ендотеліальної NO-синтази (NOS3–786T&gt;C) з тяжкістю діастолічної дисфункції лівого шлуночка і легеневої гіпертензії в пацієнтів із серцевою недостатністю та збереженою фракцією викиду лівого шлуночка

The aim – to determine polymorphisms of the nitric oxide synthase gene -786T&gt;C rs 2070744 and the association of the corresponding genotypes with the severity of left ventricle (LV) diastolic dysfunction (DD), pulmonary hypertension (PH) and elastic properties of the arteries in patients with arterial hypertension (AH) and heart failure (HF) with preserved ejection fraction (EF).Materials and methods. We included 69 patients (pts) with AH and HF with preserved EF (31 female (41.9 %) and 33 male (58.1 %)), aged 67.4±10.2 years; II–III class NYHA, hemodynamically stable. According to Shah’s criteria, the «aging» phenotype was identified in 11 (15.9 %) pts, «obesity» – 14 (20.3 %) pts, «coronary artery disease» – 16 (23.2 %) pts, «pulmonary hypertension» – 17 (24.6 %) pts (with a significant predominance of patients with CC genotype), «arterial hypertension» – 17 (24.6 %) pts.Results and discussion. «Wild» homozygous TT genotype was found in 34 pts (49.3 %, TT group), heterozygous TC genotype – in 21 pts (30.4 %, TC group) and «mutant» homozygous CC genotype – in 14 pts (20.3 %, CC group). The groups did not differ in gender (male 19 or 55.9 %, 12 or 60 % and 11 or 61.1 %, p&lt;0.05) and average age (67.1±8.9, 65.4±10.6 and 64.9±10.3 years p&gt;0.05), and in prevalence of comorbidities. The worst result of 6-minute walk test was in the CC group compared with TT and TC (371.8±77.7, 385.7±85.4 and 314.3±69.1, p&lt;0.05), as well as higher NT-proBNP level (668.1±317.8, 636.9±433.2 and 806.9±369.7, p&lt;0.05), greater LVMI (187.4±37.1, 182.2±25.7 and 195.2±28.5, p&lt;0.05). There was markedly more pronounced DD LV in the CC group compared with TT and TC, according to average e’ (p&lt;0.05) and E/e’ (p&lt;0.05). SPAP was the highest in the CC group (p&lt;0.05), as well as PCWP and TPG (p&lt;0.05). Patients of the CC group had worse elastic properties of arteries according to AIx75 (p&lt;0.001) and PWVc-f (p&lt;0.05), with a decrease in SAC (by 38.2 and 29 % compared to TT and TC (p&lt;0.05) and an increase in Ea, respectively, by 21 and 9 % (p&lt;0.05). According to the cuff test in patients of the CC group, compared with those in the TT and TC groups, worsening of endotelium-dependent vasodilation, respectively by 19.8 and 17.3 % (p&lt;0.05) was revealed.Conclusions. Compared to other polymorphisms, the CC genotype of the NOS3 rs 2070744 gene is associated with greater severity of DD LV, LH and impaired LV diastolic function and elastic properties of systemic arteries, according to pulse wave analysis in patients with AH and HF with preserved EF.

Zator płucny i guz lewego przedsionka u pacjentki z nowotworem płuca — trudności diagnostyczno-terapeutyczne

A 64 year-old female with a history of hypertension and chronic obstructive pulmonary disease after radical treatment (radiotherapy and chemotherapy) of squamous cell carcinoma of the right lung in 2016, was admitted to the Depart- ment of Cardiology due to pulmonary embolism, confirmed in an angio-CT. Moreover, cancer recurrence on the right lung and a mass spreading through the right upper pulmonary vein to the left atrium (LA) that might be considered to be a thrombus, were demonstrated. The patient, for the week before admission, had suffered from exercise dyspnoea, pain in the lower limbs, and syncope. On admission, the patient presented in a serious general condition. In laboratory tests, elevated D-dimer and NT-proBNP (450 pg/ml) concentrations as well as mild normocytic anaemia were revealed. Echocardiography showed preserved systolic (ejection fraction = 55%) and impaired diastolic left ventricle function, without signs of valvular heart disease. In transoesophageal echocardiography (TEE) in the LA an additional echo of 18 × 12 mm, spreading through the right upper pulmonary vein that might be considered to be a thrombus was revealed. However, due to the location of neo- plastic lesions in the right lung, a cancerous tumour spreading throughout could not be excluded. An abdominal and pelvis CT did not reveal any metastasis. Low molecular weight heparin in a therapeutic dose and acetylsalicylic acid were incorporated into the therapy. A mul- tidisciplinary consultation (oncologist, cardiac surgeon, cardiologist, anaesthesiologist) was conducted and the mass in the LA was initially qualified for surgical resection. Prior to surgery, spirometry and the exclusion of thromboembolic material in the lower limb veins were required. Spirometry demonstrated moderate bronchial obstruction. In ultrasound of the lower limb, deep vein thrombosis was excluded, but a few hypoechal nodules in the shank muscles of the right lower limb were visualised. A suspicion of metastases was confirmed using angio-CT. In the TEE performed after five days of low molecular weight heparin therapy, the previously described mass in the LA reduced its echogenicity and dimensions (to 10 × 8 mm). The patient’s general condition improved slightly. The patient was re-consulted by the cardiac surgeon and, due to presence of distant metastases, was disqualified from surgery. Another oncologist consultation was performed, and further diagnostic and therapeutic aims were established. The therapeutic dose of heparin was maintained.

The PDE9A inhibitor PF04447943 improves coronary arteriole vasodilation and left ventricular diastolic dysfunction in HFpEF

Coronary microvascular dysfunction develops in patients with heart failure with preserved ejection fraction (HFpEF, also known as diastolic heart failure). Phosphodiesterase 9A (PDE9A) was shown to be upregulated in the hypertrophic myocardium in HFpEF patients. The hypothesis tested was that PDE9A inhibition improves coronary arteriole vasodilation and left ventricle (LV) diastolic function in HFpEF. The obese ZSF1 rat, a model of human HFpEF, was employed in which it was found that LV diastolic dysfunction develops by 20 weeks of age. 18‐week old male obese ZSF‐1 rats were treated with PDE9A inhibitor, PF04447943 (3 mg/kg) or vehicle by daily oral gavage for 2 weeks and LV diastolic function was assessed by transthoracic echocardiography (E/A ratio and deceleration time) and vasodilation was examined in isolated and pressurized (70 mmHg) small coronary arteries (150–200 μm in diameter) using videomicroscopy. Results showed that LV relaxation and coronary artery dilations to acetylcholine (ACh) and also to the direct nitric oxide donor, sodium nitroprusside (SNP) were significantly reduced in the 20‐week old vehicle treated obese ZSF‐1 rats, when compared to lean controls. In the PDE9A inhibitor, PF04447943 treated obese ZSF1 rats both LV diastolic function and coronary artery dilations to ACh and SNP were improved significantly. Further results revealed that ex vivo exposure of coronary arteries to PF04447943 (18 nmol/l for 30 minutes) also augmented vasodilation in response to ACh and SNP in the obese ZSF‐1 rats. It was concluded that PDE9A inhibition improves LV diastolic function and increases agonist‐induced coronary arteriole dilation in an animal model of HFpEF.Support or Funding InformationAmerican Heart Association 17GRNT33680171, NIH F31 HL142183‐01 and NIH R01AG054651This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The adenosine kinase inhibitor ABT‐702 improves coronary vasodilator and left ventricle diastolic dysfunction in obese ZSF1 rats

Coronary microvascular dysfunction contributes to the development of heart failure with preserved ejection fraction (HFpEF) for which no effective therapies are currently available. We tested the hypothesis that pharmacological inhibition of adenosine kinase (ADK), the major adenosine metabolizing enzyme, augments coronary artery vasodilation and improves left ventricle (LV) diastolic function in HFpEF. We employed the obese ZSF1 rat model of HFpEF. We assessed agonist‐induced coronary artery dilation and performed echocardiographic assessment of LV diastolic function before and after treatment with selective ADK inhibitor, ABT‐702 (1.5 mg/kg, i.p. for 8‐week). We found that obese ZSF1 rats exhibited impaired acetylcholine (ACh)‐induced coronary artery dilation and LV diastolic dysfunction, as indicated by reduced E/A ratio and increased deceleration time of mitral flow velocity. Treatment with ABT‐702 augmented ACh‐induced coronary vasodilation in obese ZSF1 rats, which was not affected by inhibition of NO synthase, with N(ω)‐nitro‐L‐arginine methyl ester (L‐NAME). ABT‐702 treatment also improved LV diastolic function in obese ZSF‐1 rats, but had no effect on lean controls. Collectively, these data suggest that a pharmacological inhibition of ADK provides beneficial effects on both coronary vasodilator and LV diastolic function in HFpEF.Support or Funding InformationAmerican Heart Association 17GRNT33680171, NIH F31 HL142183‐01 and NIH R01AG054651This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Left ventricular vortex formation time in elite athletes: novel predictor of myocardial performance

BackgroundEfficient transportation of blood through the left ventricle (LV) during diastole depends on vortex formation. Vortex formation time (VFT) can be measured by echocardiography as a dimensionless index. As elite...

Assessment of the functional state of left heart in patients with chronic heart failure with preserved ejection fraction

Aim. To research the myocardial function in patients with chronic heart failure with preserved left ventricular ejection fraction (CHF-PEF) by speckle tracking echocardiography and function of the left atrium. Material and methods . Eighty patients aged from 50 to 68 years with verified CHF-PEF with NYHA (New York Heart Association) class I-IIa and stage A-C of the ABCD classification of the American College of Cardiology, and 30 healthy persons were examined. CHF-PEF was initiated by arterial hypertension and coronary artery disease. In our study we use 6-minute walk test to evaluate the functional class of CHF-PEF, echocardiography and speckle-tracking echocardiography to examine left ventricle systolic, diastolic function and speckle tracking echocardiography to determine the parameters of the myocardial deformation. Results. Patients were divided as followed: 27% had stage A of CHF, 47,9% — stage B, 25,1% — stage C. The average left ventricular ejection fraction (by Simpson’s method) was 63,3±4,43%. Indexed end systolic volume of the left atrium (LP) in CHF-SFV patients 45,2±8,1 ml/m 2 . All patients had the diastolic dysfunction: 60 patients had abnormal relaxation pattern, and 20 patients had pseudonormal pattern. Patients with CHF-PEF had reduced global longitudinal strain (GLS) -16,56±2,61% and GLS rate (GLSR) -0,75±0,11s -1 of the left ventricle and reduced segmental strain and strain rate in basal anteroseptal (-14,72±2,54% and -0,76±0,05s -1 ) and basal anterolateral (-14,27±3,29% and -0,79±0,12s -1 ) segments. Also patients with CHF-PEF has lower reduction of the circular strain and strain rate (-16,63±3,5% and -1,43±0,21s -1 ), (p<0,05) in comparison with the GLS. Changes of the radial strain and strain rate were not revealed. Positive correlation between GLS and left atrium volume (r=0,601, р<0,01) was found. Conclusion . In patients with CHF-PEF we revealed abnormal relaxation pattern and pseudonormal pattern of the diastolic dysfunction. Reduced global and segmental strain and strain rate of the left ventricle were shown, circular strain was slightly reduced, radial strain was unchanged.

Effects of coenzyme Q10 supplementation on diastolic function in patients with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a leading cause of morbidity and mortality without an established treatment. Diastolic dysfunction, the hallmark of HFpEF, is associated with altered myocardial bioenergetics. No previous study has examined the effects of coenzyme Q10 (CoQ10) on left ventricle (LV) diastolic function in patients with HFpEF. We investigated whether CoQ10 could improve LV diastolic function in patients with HFpEF. We performed a randomized controlled trial (RCT) using pretest and posttest control groups of 30 patients with HFpEF. The patients received either CoQ10 100 mg three times a day or no CoQ10 in addition to routine treatment for 30 days. Echocardiographic study was performed at baseline and follow-up. LV diastolic function was evaluated by two dimensional and Doppler echocardiography as follows; average E/e׳, septal and lateral e׳velocity, and left atrium volume index (LAVI). A total of 28 patients completed the study. A statistically significant improvement was observed in the CoQ10 treatment group in terms between groups (∆E/e׳ ‒ 3.6 vs. ‒ 2.4; p = 0.28) and (∆LAVI ‒ 5.4 vs. ‒ 4.4; p = 0.83). Short term CoQ10 supplementation provided no additional benefits in improving LV diastolic function in patients with HFpEF.