Diastolic Heart Failure Patients Research Articles

Abstract 15602: Impact of COVID-19 on Cardiovascular Outcomes in Patients Hospitalized With Chronic Heart Failure: A Nationwide Propensity-Matched Analysis

Introduction: Coronavirus 19 (COVID-19) has rapidly emerged as a major contributor to hospitalizations and readmissions, with growing evidence emphasizing its correlation with adverse outcomes in heart failure (HF). This study aims to investigate the impact of COVID-19 on cardiovascular outcomes in patients hospitalized with HF. Goals: To assess the impact COVID-19 on mortality, readmissions, and other cardiovascular outcomes in HF patients. Methods: Patients >18 years hospitalized with a diagnosis of chronic HF and COVID-19 were identified in the 2020 National Readmissions Database. Nearest propensity matching (PSM) was conducted using a 1:1 ratio for demographic, social, and clinical variables. PSM was repeated for systolic and diastolic heart failure subgroups. Outcomes with <10 cases were excluded per HCUP rules. Results: Amongst the 1,922,680 CHF patients identified, 461 had COVID-19. Baseline characteristics are shown in Table 1. After matching, COVID-19 showed no significant impact on mortality, 30- and 90- day readmissions, acute myocardial infarction, or acute kidney injury (AKI). Interestingly, the subgroup analysis revealed that COVID-19 significantly reduced AKI in diastolic HF (Table 2). Conclusions: Patients with COVID-19 hospitalized with HF are not at a higher risk for mortality, readmissions, or other cardiovascular outcomes. Interestingly, a significant reduction in AKI was observed in diastolic HF patients with COVID-19, warranting further investigation.

POOR ACHIEVEMENT OF THE TARGET BLOOD PRESSURE LEVELS ASSOCIATED WITH DIASTOLIC HEART FAILURE IN PATIENTS WITH RESISTANT HYPERTENSION

Objective: Aim of this study was to assess the impact of not achievement of the target blood pressure levels on the presence of the diastolic heart failure in patient with resistant hypertension (RH). Design and method: The study included patients with arterial hypertension who received 3 and more AH drugs and had BP > 140/90 mm Hg and were admitted to the department of secondary hypertension. In all patients we performed the following examinations: anthropometry, office blood pressure, electrocardiography (ECG), echocardiography, ABPM, sleep apnea determination, blood biochemical analysis, determination of levels of TTH, T3, T4, blood renin, blood aldosterone levels, blood cortisol level and metanephrine in the urine. Results: The study included 1146 patients with RH who received 3 or more antihypertensive drugs with the level of office blood pressure at admission > = 140/90 mm Hg. The mean age was 57,9 ± 0,37 years. The average body weight is 87,7 ± 0,61 kg, body mass index - 31,0 ± 0,19 kg/m2. Baseline office SBP/DBP - 174,6 ± 0,64/100,5 ± 0,38 mmHg. Half of the patients (51.4%) received 3 antihypertensive drugs, four drugs - 37.1%, five drugs - 9.1%, and six drugs - 2.4% respectively. Our data showed that after correction of the therapy only 31% of patients who received 3 or more antihypertensive drugs had true resistant hypertension. Fixed combinations were taken by 71.9% of patients. Patients who did not achieve target BP had significantly higher cortisol level (155.0 ± 44.0 vs 35.9 ± 20.8 ng/l) and the highest left ventricular mass index (147.5 ± 3.46 vs 135.3 ± 1.74 g/m2), obesity (42.9 vs 37.5 %), kidney function abnormalities (2.7 vs 0.8 %), and also we noted the higher prevalence of the diastolic heart failure in comparison with patients who achieved target BP (16.9 vs 8.5 %). Conclusions: Not achievement of the target blood pressure levels was associated with the presence of the diastolic heart failure in patients with resistant hypertension

0550 Positive Airway Pressure for Obstructive Sleep Apnea in Diastolic Heart Failure Patients Reduces Healthcare Resource Utilization

Abstract Introduction Although diastolic heart failure (HFpEF) patients frequently have comorbid obstructive sleep apnea (OSA), which has been associated with poor prognosis, the impact of positive airway pressure (PAP) therapy remains unclear. This retrospective study sought to investigate the association between 1 year adherence to PAP therapy and healthcare resource utilization (HCRU) in patients with newly diagnosed OSA and comorbid HFpEF. Methods A national sample of administrative claims data linked to objective PAP therapy usage was used for this analysis. Eligible patients either had two healthcare encounters or one hospitalization with a diastolic heart failure ICD-10 diagnosis code the year prior to being diagnosed with OSA and initiated on PAP therapy. HCRU was measured as a composite outcome of hospitalizations and emergency room (ER) visits. Propensity score matching was used to create well-balanced groups with differing PAP adherence levels to assess the association with 1 year HCRU outcomes. Risk-adjusted models were used to generate the number needed to treat (NNT) that referred to the number of patients that need to become adherent to PAP from non-adherent to avoid 1 visit. Results 4,237 patients with OSA and comorbid HFpEF were included. With propensity score matching, 963 PAP adherent and 963 non-adherent patients remained. After 1 year of PAP therapy, adherent patients had fewer visits than non-adherent patients (1.16 visits per subject vs. 1.75, p < 0.001), driven by a 57% reduction in hospitalizations and a 36% reduction in ER visits for adherent patients. Total HCRU costs were lower in adherent patients than in non-adherent patients ($12,732 vs. $15,610, p< 0.01). Converting 1 patient from non-adherent to adherent would avoid 1.25 visits (either ER visit or hospitalization), with an NNT of 0.8. Conclusion HFpEF patients with OSA that are adherent to PAP therapy for 1 year have fewer hospitalizations and ER visits than patients that are not adherent. More importantly, HCRU costs were lower in adherent patients, highlighting the clinical and economic benefits of treating OSA with PAP therapy in HFpEF patients. Support (if any) Funding Source: ResMed

Worse In-Hospital Outcomes Among Patients With Heart Failure (HF) and Concomitant Influenza Infection.

A sizable proportion of heart failure (HF) admissions is precipitated by respiratory infections. Influenza has been linked to higher rates of HF hospitalizations and in-hospital morbidity and mortality. We aimto describe the in-hospital outcomes of systolic HF vs. diastolic HF admissions with concomitant influenza infection in US hospitalizations from 2016 to 2017. Materials and Methods:We queried the National Inpatient Sample (NIS) from 2016 to 2017 for discharge diagnosis for SHF and DHF and influenza per ICD-10 CM codes. Using binominal logistic regression analysis and adjusting for demographic and comorbid conditions, we compared the outcomes of SHF vs. DHF admissions with concomitant influenza as an independent risk factor for inpatient mortality, acute respiratory failure, ICU admission,assisted ventilation, as well as length of stay, and total hospital costs. A total of 7,490,596 HF weighted admissions were analyzed, among which 0.9% had concomitant influenza infection. SHF and DHF admissions with influenza had higher mortality, ICU admission, ventilation assistance, and acute respiratory failure when compared to those without influenza. Among influenza admissions, those with SHF had higher mortality (6.6% vs. 5%, adjusted odds ratio - aOR 1.31, p<0.001) compared to DHF. While intensive care unit (ICU) admission(7.8% vs. 5.2%, aOR 1.30, p<0.001) and ventilation assistance rates (22.1% vs. 18.9%, aOR 1.15, p<0.001) were greater among SHF patients with influenza, acute respiratory failure was more common amongst diastolic HF with influenza (46.6% vs. 51.2%, aOR 0.86, p<0.001).Finally, SHF patients with concomitant influenza had higher inpatient costs ($82,788) when compared to diastolic HF patients ($66,373) and a longer in-hospital stay (7.29 days compared to 6.98 days in the diastolic HF group)p <0.001. Concomitant influenza infection in hospitalized patients with HF is associated with higher mortality, ICU admission, and the need for assisted ventilation, especially in those with SHF. A greater emphasis on vaccination against influenza may improve in-patient outcomes among HF patients.

Pediatric Diastolic Heart Failure: Clinical Features Description of 421 Cases.

Background and AimHeart failure in children differs substantially from the adult population. Clinical characteristics of pediatric diastolic heart failure has rarely been reported. In this study, we aimed to summary the causes, clinical features, lab tests, and treatment effect of pediatric diastolic heart failure.MethodsThis study was a single center, retrospective study conducted in Children’s Hospital of Chongqing Medical University. Children who were diagnosed with diastolic heart failure (DHF) without systolic heart failure (SHF) between 2006 and 2014 were included. Meanwhile, SHF (without DHF) cases were also collected from 2013 to 2014.ResultsA total of 421 DHF and 42 SHF cases were included. The average age of pediatric DHF was 1.89 ± 3.29 years old, significant younger than that of SHF (4.65 ± 4.90). The top three cardiovascular causes of DHF were complex congenital heart malformations (53.4%), simple congenital heart defect (15.7%), and cardiomyopathy (7.4%). Alternatively, number of cardiomyopathy cases (57.1%) ranked first in SHF group. Simple congenital heart diseases (CHDs) rarely caused SHF. The most common symptom and sign were tachypnea and hepatomegaly in pediatric HF. Symptoms like cyanosis, feeding difficulty, be fidgety, pale, fatigue, and edema were valuable in differential diagnosis of DHF and SHF in children. B-type natriuretic peptide (BNP) increase was found in 36.9% of DHF children, and 60% in SHF patients. Sensitivity of BNP greater than 100 pg/ml in diagnosis of DHF was 0.37, and specificity of it was 0.86. Diastolic function indicators, such as E/A (early wave/late wave) ratio, IVRT (isovolumic relaxation time) were significant recovered after treatment in DHF patients. Less therapeutic benefits were achieved in children with cardiomyopathy induced DHF, in compared with non-cardiomyopathy patients.ConclusionPediatric DHF and SHF were largely different in primary causes, clinical symptoms and signs and short-term prognosis. There was a limit diagnostic value of BNP with 100 pg/ml as cut-off value in pediatric DHF. Larger, multicenter studies of pediatric DHF are required in the future.

The relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and diastolic heart failure in patients with COVID-19.

Diastolic dysfunction has been reported in patients with COVID-19. Due to the role of N-terminal pro-brain natriuretic peptide (NT-proBNP) in the diagnosis of heart failure, this study investigated the relationship between serum NT-proBNP levels and diastolic heart failure in patients with COVID-19. This descriptive-analytical study was performed at Ayatollah Rouhani Hospital in Babol. Fifty-two patients with confirmed COVID-19 diagnosis, who were admitted to the ICU, were included in this study. The primary outcome was about the relationship and predictive role of NT-proBNP and diastolic heart failure in patients with severe SARS-CoV-2 infection. Patients with pro BNP > 125 pg/ml underwent echocardiography, and the relationship between echocardiographic indices and NT-proBNP was assessed as the secondary outcome. Our study showed that plasma NT-proBNP levels in patients with increased diastolic dysfunction were associated with disease severity. It was also found that the cut-off point of NT-proBNP = 799 pg/ml could be a predictor of diastolic dysfunction grades two and three. In this study, patients with a serum NT-proBNP level > 799 had 37 times higher chance of having diastolic dysfunction than those with a serum NT-proBNP < 799. Patients with NT-proBNP > 556 had RV_EA > 2 in echocardiography, indicating increased right-sided filling pressures. Despite the confounding factors in the interpretation of the NT-proBNP level in COVID-19, its level can be used to estimate the presence of high-grade diastolic heart failure on the left side and the right side of the heart and the presence of high filling pressures. Lower levels of NT-proBNP are associated with right-sided diastolic failure.

NR3C2 genotype is associated with response to spironolactone in diastolic heart failure patients from the Aldo-DHF trial.

This study aimed to determine if variants in NR3C2, which codes the target protein of spironolactone, or CYP11B2, which is involved in aldosterone synthesis, were associated with spironolactone response, focused on the primary end point of diastolic function (E/e'), in Aldosterone Receptor Blockade in Diastolic Heart Failure (Aldo-DHF) participants. Post-hoc genetic analysis. Data and samples were derived from the multi-center, randomized, double-blind, placebo-controlled Aldo-DHF trial. Aldo-DHF participants treated with spironolactone (n=184) or placebo (n=178) were included. Participants were genotyped for NR3C2 rs5522, NR3C2 rs2070951 and CYP11B2 rs1799998 via pyrosequencing. In the placebo and spironolactone arms, separate multivariable linear regression analyses were performed for change in E/e' with each single nucleotide polymorphism (SNP), adjusted for age, sex, and baseline E/e'. To discern potential mechanisms of a genotype effect, associated SNPs were further examined for their association with change in blood pressure, circulating procollagen type III N-terminal peptide (PIIINP), and left atrial area. Carriers of the rs5522 G allele in the placebo arm had a greater increase in E/e' over the 12-month course of the trial compared to noncarriers (β=1.10; 95% confidence interval [CI]: 0.05-2.16; p=0.04). No corresponding E/e' worsening by rs5522 genotype was observed in the spironolactone arm. None of the other genotypes were associated with change in E/e'. Compared to noncarriers, rs5522 G carriers also had a greater increase in left atrial area with placebo (β=0.83; 95% CI: 0.17-1.48; p=0.01) and a greater reduction in diastolic blood pressure with spironolactone (β=-3.56; 95% CI: -6.73 to -0.39; p=0.03). Serum PIIINP levels were similar across rs5522 genotypes. Our results suggest that spironolactone attenuates progression of diastolic dysfunction associated with the NR3C2 rs5522 G allele. Validation of our findings is needed.

Rheumatoid arthritis significantly increases incidence of heart failure: examination of an underestimated co-morbidity

Abstract Background The association between coronary heart disease and autoimmune inflammatory conditions such as rheumatoid arthritis has been well established and studied. We aim to elucidate another very important, but overlooked co-morbidity: heart failure. Purpose To evaluate the increased incidence of both systolic and diastolic heart failure in patients who have co-morbid rheumatoid arthritis, compared to the general population. We hypothesize that patients with inflammatory diseases such as rheumatoid arthritis will have significantly increased incidence of heart failure which will require earlier screening and prevention in this patient population. Methods This study is based on a systematic review of published literature utilizing MEDLINE, EMBASE and PUBMED that investigated the association between rheumatoid arthritis and congestive heart failure. Our study included 5,220,960 patients. We also performed a meta-regression analysis to evaluate the effect of age on incidence of heart failure. Summary relative risk (RR) and 95% confidence intervals (CI) were estimated using a random-effects model. Results In 5,220,960 patients, the incidence of heart failure was 2-fold higher in patients with rheumatoid arthritis compared to a matched control population (OR 1.835, 95% CI 1.77–1.90, p&amp;lt;0.00001). On meta-regression, when plotting log odds ratio of incidence of heart failure (y-axis) against age (x-axis), incidence increased further with older age (coefficient = 0.344, p=0.0001). Women were also found to have 5-fold higher incidence of heart failure with rheumatoid arthritis. Conclusion For patients with rheumatoid arthritis, there was a markedly higher incidence of heart failure compared to a matched patient population without rheumatoid arthritis. Meta-regression showed a trend towards increased incidence of heart failure with increased age that reached statistical significance. Women were also at a drastically higher risk of heart failure if they had rheumatoid arthritis. Funding Acknowledgement Type of funding source: None

The Relationship of Endothelial Dysfunction with the Development of Diastolic Heart Failure in Patients with Hypertension

Aim . To identify genetic predictors of diastolic dysfunction and signs of endothelial dysfunction in relation to indicators of left ventricular myocardial deformity in patients with hypertension. Material and methods . The study included 74 patients (38 women and 36 men) with hypertension 1-2 stages observed in the cardiology department of the Road clinical hospital at Chita II station. The mean age of patients was 32±9.4 years. Circulating endothelial cells (CEC) were determined by flow cytometry with BT 5000 device and antibodies to CD146+, CD45. Besides, 7AAD ion dye was used to detect living and dead endothelial cells. The number of CD146+, CD45 cells per 500000 blood cells was determined. Changes in CEC, Living/Dead CEC were studied. The data was processed using CXP Cytometer and Kaluza programs. The standard echocardiography, Doppler echocardiography and tissue Doppler echocardiography were used. Frequency distribution of alleles and genotypes: 1 mutation nitric oxide synthase 3 gene NOS3 -786 T&gt;C; ( С -786 Т ) in relation to indicators of left ventricular myocardial deformity was analyzed in hypertensive patients with or without diastolic dysfunction as well as in the control group. Polymerase chain reaction with detection of amplification product in real time (RCR-rt) or electrophoresis in agarose gel on genomic DNA of peripheral blood leukocytes were used for studying gene mutations. Results . Development of diastolic dysfunction in hypertensive patients enhanced with the carrier of the genotype NOS3 -786 CC ( р =0.01 2, x 2 =1 2.53), endothelial dysfunction was manifested by an increase in the number of circulating endotheliocytes and was associated with a decrease in global longitudinal deformation of the left ventricle. Conclusion . Endothelial dysfunction in patients with hypertension is associated with a violation of global longitudinal deformation; and in patients with diastolic dysfunction these abnormalities are more pronounced than in patients without diastolic dysfunction.

Exercise and fluid challenge during right heart catheterisation for evaluation of dyspnoea.

This prospective study compared exercise test and intravenous fluid challenge in a single right heart catheter procedure to detect latent diastolic heart failure in patients with echocardiographic heart failure with preserved ejection function. We included 49 patients (73% female) with heart failure with preserved ejection function and pulmonary artery wedge pressure ≤15 mmHg. A subgroup of 26 patients had precapillary pulmonary hypertension. Invasive haemodynamic and gas exchange parameters were measured at rest, 45° upright position, during exercise, after complete haemodynamic and respiratory recovery in lying position, and after rapid infusion of 500 mL isotonic solution. Most haemodynamic parameters increased at both exercise and intravenous fluid challenge, with the higher increase at exercise. Pulmonary vascular resistance decreased by –0.21 wood units at exercise and –0.56 wood units at intravenous fluid challenge (p = 0.3); 20% (10 of 49) of patients had an increase in pulmonary artery wedge pressure above the upper limit of 20 mmHg at exercise, and 20% above the respective limit of 18 mmHg after intravenous fluid challenge. However, only three patients exceeded the upper limit of pulmonary artery wedge pressure in both tests, i.e. seven patients only at exercise and seven other patients only after intravenous fluid challenge. In the subgroup of pulmonary hypertension patients, only two patients exceeded pulmonary artery wedge pressure limits in both tests, further five patients at exercise and four patients after intravenous fluid challenge. A sequential protocol in the same patient showed a significantly higher increase in haemodynamic parameters at exercise compared to intravenous fluid challenge. Both methods can unmask diastolic dysfunction at right heart catheter procedure, but in different patient groups.

Tissue doppler imaging for estimation of left ventricular filling pressure in patients with systolic and diastolic heart failure: a comparative simultaneous doppler catheterization study

Background: Noninvasive assessment of diastolic filling by Doppler echocardiography provides important information about left ventricular (LV) status in selected subsets of patients. This study was designed to assess whether the lateral mitral annular velocity as assessed by tissue Doppler imaging is associated with invasive measures of diastolic LV performance in patients with diastolic and systolic heart failure. Aim of the study was to compare the diagnostic accuracy of lateral mitral annular E/E′ as an estimate of LV filling pressure with invasive LVEDP measurement in subjects with systolic or purely diastolic heart failure.Methods: Total 100 patients were studied, 50 patients with diastolic heart failure and 50 patients with systolic heart failure in patients undergoing diagnostic coronary angiogram. Detailed 2D Echocardiography, Trans mitral Doppler and Tissue Doppler velocities of lateral mitral annulus was obtained. The ratio of peak mitral velocity (E) to lateral mitral annular velocity (E′) by TDI (E/E′) was calculated.Results: The ratio of E/E′ in diastolic group was 13.4±4.9 and in systolic group it was 13.7±5.2. The mean LVEDP in diastolic heart failure patients was 14.3±4.5 and 14.2±4.9 in systolic heart failure patients. The ratio of E/E′ showed a better correlation with LVEDP. E/E′ &lt;8 accurately predicted normal LVEDP, and E/E′ &gt;15 identified increased LVEDP ≥15mmHg.Conclusions: E/E′ is a reliable estimate of LV filling pressures in subjects with systolic and diastolic heart failure. In subjects with diastolic heart failure, E/E′ seems helpful to identify those with truly elevated LV filling pressures. In patients with diastolic heart failure and normal E/E′, a search for other causes of symptoms (pulmonary disease, obesity and so forth) may be warranted.

Serum Magnesium, Calcium and Phosphorus status in Heart Failure patients attending tertiary care center of Nepal

Background: Lack of proper diet and use of different medications in heart failure contributes to electrolyte imbalance. Due to absence of routine measurement, their abnormalities are not recognized. This study is an attempt to portrait a picture of serum levels of electrolytes in heart failure patients&#x0D; Materials and Methods: 102 heart failure patients were enrolled in this study over 6 months period. Serum levels of magnesium, calcium, phosphorus, sodium and albumin were measured. SPSS ver. 20.0 was used to analyze the data. Analysis of Variance was used to find mean differences and Pearson’s correlation was used to establish the correlation.&#x0D; Results: Majority of patient fell under New York Heart Association (NYHA) class II and had isolated systolic heart failure. Mean serum values of sodium and magnesium were below the reference range. Mean values of serum sodium, magnesium and corrected calcium was less in patients receiving diuretics and digitalis. Likewise, serum phosphorus was more with diuretics and digitalis use. Also, serum sodium was less in Acetylcholine Eseterose (ACE) inhibitors use. Isolated diastolic heart failure patients had least serum calcium values. Although, serum sodium and magnesium value in heart failure patients was positively correlated, was not statistically significant.&#x0D; Conclusion: This study showed that low serum sodium and magnesium values are frequently associated in heart failure. Disturbances in other serum electrolytes could also be other cause of complications in heart failure which are not under routine investigation. Identification and correction of these disturbances could have significant impact. However, further studies are required to reinforce this idea.

P5439Protective effect of angiotensin-neprilysin inhibition compared to angiotensin inhibition on ventricular arrhythmias in spontaneous hypertensive rats

Abstract Background Angiotensin-neprilysin inhibition compared to angiotensin inhibition decreased sudden cardiac death in patients with reduced ejection fraction heart failure. The protective effect from ventricular arrhythmia in diastolic heart failure (DHF) remains unknown. Methods The spontaneous hypertensive rat (SHR) has been well established as a suitable model for studies of DHF. A total of 18 10-week-old male SHR were divided into three groups: sacubitril/valsartan, valsartan and saline (0.9%) (n=6 in each group). Eighteen 10-week-old male Wistar-Kyoto rats (WKY) were served as the control group. After two weeks feeding with sacubitril/valsartan, valsartan and saline in SHR and WKY. Optical mapping was performed to measure the electrical dynamic of cardiac ventricle and the maximal slope of action potential duration restitution was calculated. An S1–S2 pacing protocol was applied at the right ventricle to determine inducibility of ventricular tachycardia and fibrillation (VT/VF). Results SHR revealed increased LV mass than those treated with sacubitril/valsartan, and valsartan. Compared with WKY, SHR had significantly higher max slope (1.32±0.12 vs. 0.28±0.08, p&lt;0.001). SHR was less prone to arrhythmogenicity after treated with valsartan than saline (0.29±0.04 vs. 1.32±0.12, p&lt;0.001). Furthermore, the max slope was even lower in SHR treated with sacubitril/valsartan than those with valsartan (0.10±0.03 vs. 0.29±0.04, p=0.005). The incidence of induced sustained VT/VF (duration &gt;2 second) was significant higher in SHR compared with WKY (18±11.1% vs. 0%, p&lt;0.001) and also higher in SHR treated with valsartan compared with those with sacubitril/valsartan (7±6.5% vs. 5±2.9%, p=0.036). Conclusions Angiotensin-neprilysin inhibition could provide better protection from ventricular arrhythmia than valsartan in SHR, warranting the further investigation of angiotensin-neprilysin inhibition in DHF patients.

Plasma receptor tyrosine kinase RET in pulmonary arterial hypertension diagnosis and differentiation.

BackgroundPulmonary arterial hypertension (PAH) is a serious disease exhibiting unspecific symptoms, as a result of which diagnosis is often delayed and prognosis is poor. The underlying pathophysiology includes vasoconstriction and remodelling of small pulmonary arteries. As receptor tyrosine kinases (RTKs) and their ligands have been shown to promote PAH remodelling, our aim was to evaluate if their plasma levels may be utilised to differentiate between various causes of pulmonary hypertension.Methods28 biomarkers involved in RTK signalling were measured using proximity extension assays in venous plasma from patients with PAH (n=48), chronic thromboembolic pulmonary hypertension (CTEPH) (n=20), pulmonary hypertension due to diastolic (n=33) or systolic (n=36) heart failure and heart failure patients without pulmonary hypertension (n=15), as well as healthy controls (n=20).ResultsPlasma proto-oncogene tyrosine-protein kinase receptor Ret (RET) was decreased (p<0.04) in PAH compared with all disease groups and controls. RET generated a sensitivity of 64.6% and a specificity of 81.6% for detecting PAH from other disease groups. PAH and the other pulmonary hypertension groups showed elevated plasma tyrosine-protein kinase MER (p<0.01), vascular endothelial growth factor (VEGF)-A (p<0.02), VEGF-D (p<0.01), placental growth factor (p<0.01), amphiregulin (p<0.02), hepatocyte growth factor (p<0.01) and transforming growth factor-α (p<0.05) and decreased VEGF receptor-2 (p<0.04) and epidermal growth factor receptor (p<0.01) levels compared with controls.ConclusionPlasma RET differentiates patients with PAH from those with CTEPH, systolic or diastolic heart failure with or without pulmonary hypertension as well as healthy controls. Future studies would be of value to determine the clinical usefulness of RET as a biomarker and its link to PAH pathophysiology.

The effect of perindopril on echocardiographic parameters, NYHA functional class and serum NT-proBNP values in patients with diastolic heart failure.

Growing evidence has demonstrated that diastolic heart failure occurs in about half of heart failure (HF) patients. We investigated the effects of perindopril on echocardiographic parameters, New York Heart Association (NYHA) functional class and serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels in patients with diastolic heart failure. In total, 108 diastolic heart failure patients aged ≥ 50 years, who had diastolic dysfunction with an ejection fraction ≥ 50%, were enrolled and randomised to one of the two study groups. Perindopril was initiated in the study group and the control group was given standard therapy. Echocardiographic parameters, NT-proBNP levels and NYHA classes were recorded. The patients were followed for 11 (three to 16) months. Eighty-eight patients completed the study. Although diastolic parameters were not changed, A' (septal) velocity (10.8 vs 9.9 cm/s) and Sm (septal) velocity (8.5 vs 7.6 cm/s) were significantly increased in the perindopril compared to the control group. A significant increase in A' (septal) velocity (+0.61 vs -0.28 cm/s, p = 0.04) and a slight increase in Sm (septal) velocity (+0.99 vs 0.36 cm/s, p = 0.054) were noted in the perindopril group. Tissue Doppler septal late diastolic velocities and septal systolic myocardial velocities increased in the perindopril group but NT-proBNP levels, and NYHA class was not changed in this study population.

Circulating Connective Tissue Growth Factor Is Associated with Diastolic Dysfunction in Patients with Diastolic Heart Failure

Background: Connective tissue growth factor (CTGF) and transforming growth factor β1 (TGF-β1) are emerging biomarkers for tissue fibrosis. The aim of this study was to investigate the association between circulating CTGF, TGF-β1 levels and cardiac diastolic dysfunction in patients with diastolic heart failure (DHF). Methods: Admitted subjects were screened for heart failure and those with left ventricular (LV) ejection fraction <45% were excluded. Diastolic dysfunction was defined as functional abnormalities that exist during LV relaxation and filling by echocardiographic criteria. Totally 114 patients with DHF and 72 controls were enrolled. Plasma levels of CTGF, TGF-β1, and B-type natriuretic peptide (BNP) were determined. Results: The plasma CTGF and TGF-β1 levels increased significantly in patients with DHF. Circulating CTGF and TGF-β1 levels were correlated with echocardiographic parameter E/e’ and diastolic dysfunction grading in DHF patients. In multivariate logistic analysis, CTGF was significantly associated with diastolic dysfunction (odds ratio: 1.027, p < 0.001). Plasma CTGF (AUC: 0.770 ± 0.036, p < 0.001) and CTGF/BNP (AUC: 0.839 ± 0.036, p < 0.001) showed good predictive power to the diagnosis of DHF. Conclusions: This finding suggested CTGF could be involved in the pathophysiology of diastolic heart failure and CTGF/BNP might have auxiliary diagnostic value on diastolic heart failure.

Abstract 468: Sirt1 Ameliorates High Fat Diet-induced Diastolic Heart Failure

Approximately half of heart failure patients are diagnosed with diastolic heart failure, which is characterized by impaired relaxation. Cardiac fibrosis is observed in diastolic heart failure patients, which may promote diastolic dysfunction due to increased LV stiffness. Sirt1 is a protein deacetylase that regulates cardiac fibrosis. However, the role of Sirt1 in diastolic heart failure remains unknown. Since obesity is a significant risk factor for diastolic heart failure, we employed a high fat diet (HFD)-induced obese mouse model and cardiac-specific Sirt1 knockout (Sirt1cKO) and overexpression (Sirt1cTG) mice to define the role of Sirt1 in diastolic heart failure. Diastolic dysfunction induced by 1 and 3 months of HFD consumption was exacerbated in Sirt1cKO, evidenced by an increased end-diastolic pressure-volume relationship (EDPVR), an index of diastolic dysfunction obtained by pressure-volume loop analysis (EDPVR: wild-type mice (WT) Normal Diet (ND): 0.069; WT HFD (3 months): 0.11; Sirt1cKO ND: 0.063: Sirt1cKO HFD: 0.18*, p&lt;0.05 vs WT HFD). Consistently, HFD-induced diastolic dysfunction is ameliorated in Sirt1cTG mice (EDPVR: WT ND: 0.062; WT HFD: 0.11; Sirt1cTG ND: 0.061: Sirt1cTG HFD: 0.056*, p&lt;0.05 vs WT HFD). HFD-induced cardiac fibrosis was promoted in Sirt1cKO but ameliorated in Sirt1cTG mice. Moreover, exogenous expression of Sirt1 via adeno-associated virus vector ameliorated HFD-induced diastolic dysfunction and fibrosis (Figure). These results suggest that Sirt1 ameliorates diastolic heart failure, possibly through inhibition of cardiac fibrosis.

Abstract 946: Aberrant Activation of Nitric Oxide Synthase 1 in the Heart Accelerates Diastolic Dysfunction Though Protein S-nitrosylation

Heart failure refers to an inappropriate blood supply to the periphery. Among subtype of heart failure, pathophysiology and effective therapeutic strategy of systolic heart failure is well established. However, molecular mechanism and specific regimens for diastolic heart failure (DHF) still remains unclear. Here we propose nitric oxide synthase (NOS) 1 mediated exacerbation of DHF and therapeutic potential for novel therapeutics. We screened alteration of posttranslational modifications in DHF which were induced either by SAUNA (SAlty drinking water/Unilateral Nephrectomy/Aldosterone) model or transverse aortic constriction (TAC) model and observed that protein S-nitrosylation was dramatically increased. Total RNA sequencing revealed that transcription amount of NOS1 was aberrantly increased in DHF, whereas NOS2 or NOS3 was not changed. Either non-selective NOS inhibitor or specific NOS1 inhibitor effectively blocked diastolic dysfunction. To elucidate the molecular target of S-nitrosylation, we performed biotin switch assay and requested protein sequencing which were newly appeared in the presence of GSNO. Among novel signal, we identified and confirmed that Histone deacetylase (HDAC) 2 was target molecule of NOS1. HDAC2 cysteine 262 and cysteine 274 were responsible residue of NOS1-mediated S-nitrosylation. We generated knock-in mice carrying S-nitrosylation defect HDAC2 mutant, HDAC2 C262A/C274A (2CA). HDAC2 2CA knock-in mice underwent SAUNA surgery or TAC and diastolic function of those mice was measured by early diastole (E) and mitral valve annulus movement (E’). When compared to wild type littermates, the diastolic function assessed by E/E’ ratio in HDAC2 2CA knock-in mice were relatively well conserved both in SAUNA- and TAC-induced DHF model. Survival rate after TAC operation was also dramatically ameliorated in HDAC2 2CA knock-in mice. Taken together, we proposed novel molecular axis, NOS1/S-NO HDAC2, accelerating diastolic dysfunction and which implicated notable molecular target for treatment of DHF patients.

In-Hospital Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement in Relation to Heart Failure Status in the United States: An Analysis of the National Inpatient Sample

Introduction Transcatheter aortic valve replacement (TAVR) is an increasingly common method of valve replacement in patients that are not candidates for open heart surgery. Although comorbid conditions are often present in these patients, there is a dearth of national studies evaluating outcomes in the presence of heart failure. We investigate whether systolic and diastolic heart failure impact hospital utilization and mortality. Methods The 2016 National Inpatient Sample (NIS) was used to find all patients that underwent TAVR in 2016, comparing those with systolic versus diastolic heart failure (Based on ICD-10-CM Codes). Patients with non-chronic forms of heart failure and those who received percutaneous endoscopic aortic valve replacement were excluded. STATA Version 15.1 (College Station, TX) was used for statistical analysis. Multivariate regression was used to calculate weighted nationwide estimates of hospital mortality, length of stay, and total charge. We adjusted for patient (age, sex, ethnicity, and Charlson Comorbidity Index), socioeconomic (median household income, insurance provider), and hospital factors (hospital bed size, region, teaching status, day and month of admission). Results An estimated 40,005 pts who underwent TAVR in 2016 were identified. Of those, 2475 had systolic heart failure and 7830 had diastolic heart failure. After adjusting for confounders, patients with systolic heart failure had longer median length of stay (Table 1) compared to those with diastolic heart failure (+0.483 days, p=0.013). In contrast, no significant differences were found between in hospital mortality (OR 1.32, p=0.565) and total hospital charge (+5324 USD, p=0534). Conclusion Our study is the first to show that there is no significant difference in in-hospital mortality in systolic versus diastolic heart failure patients undergoing TAVR. There was also no difference in total hospital cost between systolic and diastolic heart failure, whereas systolic heart failure was associated with an increased length of stay.

The review of Qili-Qiangxin capsule's effect on the cardiovascular diseases

Qili-Qiangxin capsules have been wildly used for the cardiovascular diseases. Qili-Qiangxin capsules have good effect on the myocardial infarction, dilated cardiomyopathy, congestive heart failure, diastolic heart failure and HFPEF patients. Patients' cardiac function and quality of life can be improved after treatment. In the basic researches, we concluded the mechanisms of Qili-Qiangxin capsules' effect on the heart failure that Qili-Qiangxin capsules could effectively restrain the cardiac remodeling, improve cardiac function.Although the Qili-Qiangxin capsules were wild used in the clinic, its precise molecular mechanisms for cardiovascular diseases remained unknown. Key words: Qi Li Qiang Xin Jiao Nang; Cardiovascular diseases; Heart failure; Molecular mechanisms of pharmacological action (TCD); Chinese patent drugs; Review