Early Stages Of Heart Failure Research Articles

Proteomic profiling for detection of early-stage heart failure in the community.

AimsBiomarkers may provide insights into molecular mechanisms underlying heart remodelling and dysfunction. Using a targeted proteomic approach, we aimed to identify circulating biomarkers associated with early stages of heart failure.Methods and resultsA total of 575 community‐based participants (mean age, 57 years; 51.7% women) underwent echocardiography and proteomic profiling (CVD II panel, Olink Proteomics). We applied partial least squares‐discriminant analysis (PLS‐DA) and a machine learning algorithm [eXtreme Gradient Boosting (XGBoost)] to identify key proteins associated with echocardiographic abnormalities. We used Gaussian mixture modelling for unbiased clustering to construct phenogroups based on influential proteins in PLS‐DA and XGBoost. Of 87 proteins, 13 were important in PLS‐DA and XGBoost modelling for detection of left ventricular remodelling, left ventricular diastolic dysfunction, and/or left atrial reservoir dysfunction: placental growth factor, kidney injury molecule‐1, prostasin, angiotensin‐converting enzyme‐2, galectin‐9, cathepsin L1, matrix metalloproteinase‐7, tumour necrosis factor receptor superfamily members 10A, 10B, and 11A, interleukins 6 and 16, and α1‐microglobulin/bikunin precursor. Based on these proteins, the clustering algorithm divided the cohort into two distinct phenogroups, with each cluster grouping individuals with a similar protein profile. Participants belonging to the second cluster (n = 118) were characterized by an unfavourable cardiovascular risk profile and adverse cardiac structure and function. The adjusted risk of presenting echocardiographic abnormalities was higher in this phenogroup than in the other (P < 0.0001).ConclusionsWe identified proteins related to renal function, extracellular matrix remodelling, angiogenesis, and inflammation to be associated with echocardiographic signs of early‐stage heart failure. Proteomic phenomapping discriminated individuals at high risk for cardiac remodelling and dysfunction.

Raman imaging-based phenotyping of murine primary endothelial cells to identify disease-associated biochemical alterations

Raman spectroscopy is successfully becoming an analytical tool used to characterize alterations in the biochemical composition of cells. In this work, we identify the features of Raman spectra of murine primary endothelial cells (EC) isolated from lungs, heart, liver, brain, kidney and aorta of normal mice, as well as from heart, lung and liver in a murine model of heart failure (HF) in Tgαq*44 mice. Primary cells were measured in suspension immediately after their isolation. Raman images showed that isolated primary EC were elliptical or circular, and did not show organ-specific spectral features for any of the studied organ, i.e. lungs, heart, liver, brain, kidney and aorta. Principal Component Analysis pairwise analysis of primary endothelial cells from FVB mice and Tgαq*44 mice revealed an increased protein content in EC isolated from the heart and increased lipid content in EC isolated from the lung in Tgαq*44 mice. No significant differences were found in the EC isolated from the liver using the same chemometric procedure. To our knowledge, this is the first report in which Raman spectroscopy has been used to characterize the biochemical phenotype of primary murine EC with developing HF. This pilot study shows that Raman-based analysis of freshly isolated primary EC did not revealed organ-specific features, however disease-associated changes were found in the coronary and pulmonary EC in the early stage of heart failure in Tgαq*44 mice.

Oral health-related quality of life in patients with heart failure and left ventricular assist devices\u2014results of a cross-sectional study

ObjectivesThe aim of this cross-sectional study was to compare oral health-related quality of life (OHRQoL) of patients with left ventricular assist device (LVAD) and heart failure (HF).Material and methodsSeventy-four patients with LVAD were recruited from University Department for Cardiac Surgery, Leipzig Heart Center, Germany. A group of 72 patients with HF was composed by matching (age, gender, smoking). The German short form of oral health impact profile (OHIP G14) was applied. Health-related quality of life (HRQoL) was measured by short form 36 survey (SF-36). Dental conditions (decayed-, missing- and filled-teeth [DMF-T]), remaining teeth and periodontal findings were assessed. Statistics: t-test, Mann-Whitney U test, Kruskal-Wallis test, chi-square or Fisher test, linear regression.ResultsAge, gender, smoking, underlying disease, co-morbidities and oral findings were comparable between groups (p > 0.05). OHIP G14 sum score was 3.53 ± 6.82 (LVAD) and 2.92 ± 5.35 (HF; p = 0.70), respectively. The scales SF-36 physical functioning (p = 0.05) and SF-36 social functioning (p < 0.01) were worse in LVAD. In the LVAD group, the DMF-T and remaining teeth negatively correlated with OHIP G14 sum score (p < 0.01). In HF patients, positive correlations were found between OHIP G14 and D-T (p < 0.01) and remaining teeth (p = 0.04). Moreover, DMF-T (p = 0.03) and remaining molars/premolars (p = 0.02) were negatively correlated with SF-36 scales in HF.ConclusionsOral health and OHRQoL was comparable between LVAD and HF; thereby, OHRQoL reflected the clinical oral status.Clinical relevanceDental care, with beginning in early stage of HF, should be fostered to preserve teeth and support quality of life before and after LVAD implantation.

Global work index by non-invasive pressure-strain loops: a novel parameter to assess left ventricular performance in the early stages of heart failure with preserved or mid-range ejection fraction after acute myocardial infarction.

To determine the relationship between myocardial work (MW) indices derived from non-invasive pressure-strain loops (PSL) and established parameters of left ventricular (LV) performance in patients with acute myocardial infarction (AMI) and heart failure (HF) with preserved or mid-range ejection fraction (HFpEF/HFmrEF). Speckle-tracking echocardiography (STE) was used to determine MW indices and global longitudinal strain (GLS) in the first 24-48 hours after admission in patients with AMI, HF symptoms, NT-proBNP >300 pg/mL and left ventricular ejection fraction (LVEF) >40%. MW was calculated by using PSL, which combine strain and non-invasive blood pressure measurement. Global MW index (GWI) was defined as the work inside the area of the PSL. Forty-nine patients (mean age 68±13 years) fulfilled the inclusion criteria. Both GWI (1057±338 mmHg%) and GLS (-10.4±3.3%) were reduced in the majority of the patients. However, a proportion of patients with abnormal GLS showed normal GWI. There was a strong inverse relationship between GWI and GLS (r=-0.81). GWI demonstrated a strong relationship with LVEF (r=0.69) and a moderate correlation to NT-proBNP (n=-0.29). NT-proBNP showed a tendency to higher values in patients with more reduced GWI (820 [590-2550] vs 707 [460-1335], p=0.17). Out of the diastolic dysfunction parameters, GWI showed moderate correlations to LA volume index (r-0.29), E/A (r=-0.23) and E/e' (r=-0.39), which were also significantly more impaired in patients with more reduced GWI. Non-invasive PSL might bring further information to LVEF and GLS in patients AMI at the early stages of HFpEF/HFmrEF, since LV performance depends on both contractile properties and variations in load in the ischemic segments.

Activation of the M3AChR and Notch1/HSF1 Signaling Pathway by Choline Alleviates Angiotensin II-Induced Cardiomyocyte Apoptosis.

Angiotensin II- (Ang II-) induced cardiac hypertrophy and apoptosis are major characteristics of early-stage heart failure. Choline exerts cardioprotective effects; however, its effects on Ang II-induced cardiomyocyte apoptosis are unclear. In this study, the role and underlying mechanism of choline in regulating Ang II-induced cardiomyocyte apoptosis were investigated using a model of cardiomyocyte apoptosis, which was induced by exposing neonatal rat cardiomyocytes to Ang II (10−6 M, 48 h). Choline promoted heat shock transcription factor 1 (HSF1) nuclear translocation and the intracellular domain of Notch1 (NICD) expression. Consequently, choline attenuated Ang II-induced increases in mitochondrial reactive oxygen species (mtROS) and promotion of proapoptotic protein release from mitochondria, including cytochrome c, Omi/high-temperature requirement protein A2, and second mitochondrial activator of caspases/direct inhibitor of apoptosis-binding protein with low P. The reversion of these events attenuated Ang II-induced increases in cardiomyocyte size and numbers of terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling-positive cells, presumably via type 3 muscarinic acetylcholine receptor (M3AChR). Indeed, downregulation of M3AChR or Notch1 blocked choline-mediated upregulation of NICD and nuclear HSF1 expression, as well as inhibited mitochondrial apoptosis pathway and cardiomyocyte apoptosis, indicating that M3AChR and Notch1/HSF1 activation confer the protective effects of choline. In vivo studies were performed in parallel, in which rats were infused with Ang II for 4 weeks to induce cardiac apoptosis. The results showed that choline alleviated cardiac remodeling and apoptosis of Ang II-infused rats in a manner related to activation of the Notch1/HSF1 pathway, consistent with the in vitro findings. Taken together, our results reveal that choline impedes oxidative damage and cardiomyocyte apoptosis by activating M3AChR and Notch1/HSF1 antioxidant signaling, and suggest a novel role for the Notch1/HSF1 signaling pathway in the modulation of cardiomyocyte apoptosis.

Abstract 13772: Percent Predicted Peak Oxygen Pulse Predicts Vascular Responses to Exercise in HFpEF

Introduction: Cardiopulmonary exercise testing (CPET) can help identify early stages of heart failure with preserved ejection fraction (HFpEF). We sought to determine if percent predicted peak oxygen pulse (%PredO 2 P, as defined by peak oxygen uptake/heart rate), a noninvasive measure combining stroke volume and peripheral oxygen extraction, could serve as a marker of the hemodynamic response to exercise in HFpEF patients. Methods: 154 consecutive patients who underwent maximal CPET (RER&gt;1.05) and were diagnosed with HFpEF (defined as LVEF&gt;50% and PCWP/CO &gt;2 mmHg*min/L or supine resting PCWP &gt;15 mmHg) were included. Exclusion criteria included patients who were taking AV nodal agents, were paced, or had atrial fibrillation. Peak O 2 P and percent predicted were calculated using the Wasserman equation for peak VO2 in conjunction with peak predicted heart rate (220-age). Results: Tertiles of %PredO 2 P were determined with first tertile at 42.1-76.2%, second tertile at 76.2-94.4%, and third tertile at 94.4-139.2%. Baseline parameters differed across %PredO 2 P tertiles ( Table 1 ) with BMI increasing (trend p=0.014). Peak cardiac output (1 st : 10.0±3.0 L/min, 2 nd : 11.1±2.4, 3 rd : 11.5±3.5; p=0.038) and peak stroke volume (1 st : 70.6±20.1 mL, 2 nd : 83.0±16.6, 3 rd : 92.7±20.1; p&lt;0.001) were higher across tertiles, whereas peak HR (1 st : 143±23 bpm, 2 nd : 135±25, 3 rd : 123±26; p&lt;0.001) and peak SVR (1 st : 959±304 dynes*s/cm 5 , 2 nd : 831±187, 3 rd : 810±321; p=0.009) were lower. Exercise PAP/CO slope (1 st : 4.5±2.1 mmHg*min/L, 2 nd : 3.6±1.6, 3 rd : 3.3±1.7; p=0.003) and PCWP/CO slope (1 st : 3.4±1.8 mmHg*min/L, 2 nd : 2.9±1.4, 3 rd : 2.8±2.0; p=0.015) were lower across tertiles of %PredO 2 P. Conclusions: %PredO 2 P is a noninvasive variable that associates with vascular responses to exercise in HFpEF patients. Higher %PredO 2 P was associated with improved vascular responses to exercise with lower SVR, PAP/CO and PCWP/CO slopes.

Abstract 13566: Clinical Utility of Noninvasive Assessment of Flow-pressure Relationship in Scleroderma

Introduction: Cardiac involvement in Systemic sclerosis (SSc), especially left ventricular diastolic dysfunction (DD), is high prevalence and associated with high mortality. Thus, the early detection of left ventricular DD might be important to manage SSc. Recent study has shown that exercise stress test may evaluate an early stage of heart failure in patients with normal resting echocardiogram. Hypothesis: We hypothesized that SSc patients with normal resting hemodynamics may present early phase of left ventricular DD by exercise echocardiogram, leading to the model of predicting long-term outcomes. Methods: Between January 2014 and December 2018, we prospectively enrolled 140 SSc patients who underwent 6-minute walk (6MW) stress echocardiographic studies with normal range of estimated mean pulmonary arterial pressure (mPAP) (&lt;25mmHg) and mean pulmonary artery wedge pressure (mPAWP) (&lt;15mmHg) at rest. We used ΔmPAP/Δcardiac output (CO) to assess pulmonary vascular reserve and ΔmPAWP/ΔCO to assess left ventricular (LV) reserve between resting and post-6MW point. Results: During a median period of 3.6 years, 25 patients (18%) reached the composite outcome. Both ΔmPAP/ΔCO and ΔmPAWP/ΔCO in patients with events were significantly higher than in ones without events (8.9±3.8mmHg/l/min vs. 3.0±1.7mmHg/l/min; p=0.002, and 2.2±0.9mmHg/l/min vs. 0.9±0.5mmHg/l/min; p&lt;0.001, respectively). In addition, ΔmPAWP/ΔCO is strongly associated with events (p=0.04) in patients with normal ΔmPAP/ΔCO (≤median value), although ΔmPAWP/ΔCO had weak impact in patients with abnormal ΔmPAP/ΔCO (&gt;median value) (p=0.23). Conclusions: Exercise echocardiography revealed impaired LV functional reserve in SSc patients with normal resting hemodynamics. Furthermore, in the group of normal pulmonary vascular function, the patients with impaired LV functional reserve had significantly shorter event-free survival than the ones with non-impaired LV function. Thus, the evaluation of early left ventricular DD with 6MW may detect high-risk group in SSc patients.

Evaluation of the Efficacy of Crataegus oxyacantha in Dogs with Early-Stage Heart Failure.

Myxomatous mitral valve disease (MMVD) is the most common cardiopathy in middle-aged dogs. When the dog is asymptomatic and has an enlarged left atrium, treatment is beneficial; however, some allopathic drugs are very costly and may produce side effects. To extend the duration of this asymptomatic phase, complementary therapies such as herbal medicine and homeopathy are available. Although herbal therapy with extract of Crataegus oxyacantha is beneficial, there is a risk of adverse reactions-unlike with homeopathy, where the risk is minimized with the administration of ultra-diluted doses. This study evaluated the efficacy of Crataegus oxyacantha, as mother tincture (MT) and in 6 cH homeopathic formulation, in treating the initial phase of heart failure due to MMVD in a veterinary clinic setting. A total of 30 dogs with MMVD, 7 years or older and weighing up to 10 kg, were randomized into three groups as follows: Crataegus 6 cH, Crataegus MT, and hydroalcoholic solution (placebo). Animals were evaluated through echocardiography parameters, laboratory blood tests, and systolic blood pressure (SBP) measurements at 30, 60, 90, and 120 days after initiation of therapy, for statistical analysis and monitoring of the blinded study. Patients who received Crataegus 6 cH showed a reduction in SBP 60 days after treatment, while those receiving Crataegus MT exhibited a reduction 90 days after the therapy was initiated. There was a significant linear regression when evaluating the effect of treatment with Crataegus 6 cH on SBP measurements over the evaluation intervals (linear equation: SBP = 176.57 mm Hg - 0.21x, where x represents days of treatment). There was an increase in both fractional shortening and isovolumetric relaxation time for those patients receiving the homeopathic formulation. Therapy with Crataegus was beneficial for hypertensive and cardiopathic dogs with MMVD, extending the duration of the asymptomatic phase. The reduction in SBP occurred more swiftly in the 6 cH group than in the MT-treated dogs.

Measurement of Functional Capacity to Discriminate Clinical from Subclinical Heart Failure in Patients ≥65 Years of Age

In order to show that reduced functional capacity in subclinical heart failure portends a higher risk of clinically overt (stage C) heart failure, we obtained the Duke activity status index (DASI) and 6-minute walk distance (6MWD) in 814 patients (age 70 [interquartile range 67 to 74] years, 51% female) with nonischemic subclinical heart failure. Reduced functional capacity was defined as: (1) DASI-derived metabolic equivalents <7, (2) 6MWD <2 standard deviations below the age-based normative mean (excluding those with mobility impairment) and (3) reduced 6MWD with reclassification where DASI was discordant. Based on reduced functional capacity and left ventricular dysfunction (LVD), subjects were classified into; (1) Stage A heart failure (436 with neither LVD nor reduced functional capacity), (2) Stage A with reduced functional capacity (n = 80), (3) Stage B heart failure (182 with LVD but preserved functional capacity) and (4) early stage C heart failure (52 with LVD and reduced functional capacity). Outcome was assessed by Kaplan-Meier survival estimates and Cox proportional hazard ratios. After a median follow-up of 13 months [interquartile range 11 to 19]), 76 (9%) developed heart failure - 6% of Stage A, 10% of Stage A-reduced functional capacity, 9% of Stage B and 37% of early Stage C (p < 0.001). After adjustment (for heart failure risk score, atrial fibrillation, pulmonary disease and therapy), the hazard ratio for development of overt heart failure in early Stage C was 5.92 (95% confidence intervals 2.92 to 11.54, p < 0.001) compared with Stage A and 3.08 (95% confidence intervals 1.47 to 6.47, p = 0.003) compared with Stage B.

An association between echocardiographic left ventricle longitudinal strain and hypertension in general population depending on blood pressure control

Background . Ultrasound assessment of myocardial strain allows non-invasive identification of early stages of heart failure with preserved ventricular ejection fraction. A decline of the left ventricle (LV) global longitudinal strain in hypertension (HT) accompanied by LV hypertrophy (LVH) was reported in clinical samples with manifest HT. Data on the relationship between longitudinal strain and blood pressure (BP) and HT in general population is lacking. Objective . We studied the relationship between LV peak systolic global longitudinal strain ( GLS ) and strain rate ( GSR ) in subjects with high and controlled BP from a general population sample aged over 55 years. Design and methods . The cross-sectional study was based on a population cohort (HAPIEE, Novosibirsk). In a random sample (n = 416, aged 55–84 years old) we performed echocardiography and evaluated GLS and GSR of LV by speckle tracking technique. ANOVA multivariable models were applied. Results. In the studied sample, the prevalence of HT comprised 78,9 %. The mean GLS value was –18,7 ± 3,79 %, and it was lower in men than in women (–18,2 ± 3,85 % vs –19,2 ± 3,66 %, p = 0,005). The mean GSR value was –0,84 ± 0,17s –1 , and did not differ by sex. The absolute value of GLS in HT was lower than in normotensives: –18,5 ± 3,73 % vs –19,9 ± 3,42 %, p = 0,003; this difference was independent of age, sex and LV myocardial mass index (IMM), p = 0,011; but it was attenuated in a multivariable-adjusted model including body mass index (BMI). In HT groups, the GLS was the lowest among those “treated ineffectively” and significantly lower than in normotensives independently of age, sex and myocardium mass index (p = 0,008). The absolute value of GSR in HT was lower than in normotensives: –0,90 ± 0,17 s –1 vs –0,83 ± 0,17s –1 , p < 0,001; and persisted in multivariable models. GSR was the lowest among those “treated ineffectively” and significantly lower than in normotensives in multivariable models independently of age, sex, BMI and myocardial mass index (p = 0,017; 0,002). The average values of LV ejection fraction (Simpson) in all groups were above 50 % without significant inter-group differences (p = 0,904). conclusions. In the studied population sample, GLS and GSR of LV were associated with HT; however, the association between GLS and HT was largely explained by BMI. In hypertensives, the lowest GLS and GSR , as well as higher extent of LVH, were found among those treated ineffectively, which might point at the initial reduction of systolic ventricular function in HT with inadequate BP control.

PHYSICAL SIGNS AND SYMPTOMS PREDICT DIASTOLIC AND SYSTOLIC FUNCTION IN HEART FAILURE PATIENTS

Early stages of heart failure are associated with diastolic dysfunction. However, there are no recommendations for screening echocardiography. Therefore, clinicians need to rely on clinical evaluations. Our aim was to compare symptoms and physical examination signs in heart failure against

Dobutamine stress testing in patients with Fontan circulation augmented by biomechanical modeling.

Understanding (patho)physiological phenomena and mechanisms of failure in patients with Fontan circulation—a surgically established circulation for patients born with a functionally single ventricle—remains challenging due to the complex hemodynamics and high inter-patient variations in anatomy and function. In this work, we present a biomechanical model of the heart and circulation to augment the diagnostic evaluation of Fontan patients with early-stage heart failure. The proposed framework employs a reduced-order model of heart coupled with a simplified circulation including venous return, creating a closed-loop system. We deploy this framework to augment the information from data obtained during combined cardiac catheterization and magnetic resonance exams (XMR), performed at rest and during dobutamine stress in 9 children with Fontan circulation and 2 biventricular controls. We demonstrate that our modeling framework enables patient-specific investigation of myocardial stiffness, contractility at rest, contractile reserve during stress and changes in vascular resistance. Hereby, the model allows to identify key factors underlying the pathophysiological response to stress in these patients. In addition, the rapid personalization of the model to patient data and fast simulation of cardiac cycles make our framework directly applicable in a clinical workflow. We conclude that the proposed modeling framework is a valuable addition to the current clinical diagnostic XMR exam that helps to explain patient-specific stress hemodynamics and can identify potential mechanisms of failure in patients with Fontan circulation.

Serum Metabolic Characteristics and Biomarkers of Early-Stage Heart Failure

Aim: We aimed to identify metabolic characteristics of early-stage heart failure (HF) and related biomarkers. Patients & methods: One hundred and forty-three patients with New York Heart Association class I-IV HF and 34 healthy controls were recruited. Serum metabolic characteristics of class I HF were analyzed and compared with those of class II-IV HF. Potential biomarkers of class I HF with normal N-terminal-pro-B-type natriuretic peptide (NT-proBNP) level were screened and validated in additional 72 subjects (46 class I patients and 26 controls). Results & conclusion: Eleven metabolites were found disturbed in class I HF, and five of which were also disturbed in class II-IV HF. Glutamine and tyrosine showed high value to identify class I HF with normal NT-proBNP level. The diagnostic potential of glutamine was partially confirmed in the validate set, holding a promise to detect early HF with normal NT-proBNP level.

Evaluation of vector mediated gene therapy as a novel approach to mitigate cardiovascular diseases; A short review

Positioning in the top list of mortality and morbidity, cardiovascular disease (CVD) is required new approaches to mitigate the risk and prevalence. Recombinant DNA (rDNA) technology and genome sequencing explore the new horizon to treat CVD through modified therapy. Gene transfer mechanism eventually angiogenic gene therapy provides efficacy in early-stage heart failure. Targeted gene delivery system depicts the novel therapeutic pattern for both genetic disorder and pathophysiological deficit and opens the pathway of early diagnose and treatment. Despite some limitations of a specific vector (viral vector) mediated gene transfer, these new approaches make hope on CVD treatment rather than the surgery and other ways. Furthermore, some vectors are less hazardous than viral vectors to suggest successful non-viral gene modulations to Cardiovascular tissues and perform in the clinical trial. However, plasmid-mediated gene transfer method along with genome editing technology might be the best possible approach for future CVD prognostics and diagnostics.

Size and function of left atrium in patient with heart failure with reduced ejection fraction

Background: Heart failure is a common clinical syndrome and is the final stage of most cardiovascular diseases. Nowadays, the role of left atrium in cardiovascular diseases, especially in HF diseases, is more and more important. At the early stage of heart failure, the size and pump function of left atrium are increased. When the left ventricular function is reduced significantly, left atrial function is alo impaired. Aims of the study: assess size and function of left atrium in patient with heart failure reduced ejection fraction (HFrEF). Establishing the association between two indexs above with some clinical and subclinical characteristics. Subjects and method: 51 HFrEF patients in Hospital of Hue University of Medicine and Pharmacy, who have including criteria. Cross-sectional study. Results: LAVI (ml/m2): 43.19 ± 12.48 ml/m2, percentage of large left atrial patents is 80.4%. LATEF (%): 31.93 ± 7.72%. LAVI has correlation with: LVEDV (r= 0,45); LVESV (r= 0,43); NT-proBNP (r= 0.371). There is a difference LAVI of diastolic dysfunction grades (r= 0.011), There is a difference LAVI of NYHA class (r= 0.016). LATEF has correlation with NTproBNP (r= -0.349). Conclusion: The left atrium’s size is increased and its function is reduced in HFrEF patient. There is a positive correlation between LAVI and LVEDV, LVESV, NTproBNP. The LAVI varies with the diastolic dysfunction grade. And there is a negative correlation between LATEF and NTproBNP. Key words: heart failure reduced ejection fraction; size of left atrium, function of left atrium

Health service use by community-dwelling patients with heart failure in northwest London, 2015–18: a retrospective cohort analysis

BackgroundHeart failure management is complex and requires multidimensional care. Clinical guidelines advocate for the use of integrated care, but few studies have described overall health service use by patients with heart failure. We describe overall care usage by community-dwelling patients with heart failure in northwest London using a dataset linked across multiple health-care settings. MethodsIn this retrospective cohort analysis, we used Whole Systems Integrated Care (WSIC) data, a dataset of individual clinical events from primary care, secondary care, and other (defined as community, mental health, and social care) services in northwest London to analyse a retrospective cohort of patients with heart failure. Patients who remain in the WSIC dataset, were aged at least 18 years on Jan 1, 2015, with known age and gender, and whose diagnosis was not made after their date of death. The primary outcome was health-care usage of each of the three service categories overall as well as individual components of secondary care (eg, outpatient appointments) and other services (eg, nursing contacts). Usage patterns were identified using k-means cluster analysis using all distinct contacts for the whole study period and visualised by a heatmap. Nine health-care use variables were used to identify clusters, and differences between clusters in both clustering and non-clustering variables were analysed using Kruskal-Wallis and Pearson χ2 tests. This study was approved by the Discover Research Advisory Group. FindingsData from 39 301 patients with heart failure across 359 general practices between Jan 1, 2015, and Dec 31, 2018, were analysed. Almost all patients had some health service contact during the study period (21 226 [89·1%] of 23 828 in 2015; 24 876 [90·6%] of 27 443 in 2016; 28 663 [90·8%] of 31 554 in 2017; and 31 584 [91·1%] of 34 651 in 2018). Most commonly used services in 2018 were outpatient appointments (24 283 [70·1%] of 34 651 patients), general practitioner (GP) consultations (20 741 [59·9%] patients), unplanned accident and emergency visits (14 145 [40·8%] patients) and community services (13 762 [39·7%] patients), often for nursing. Use of cardiology-specific services ranged from 1005 (2·9%) patients for community visits to 8231 (23·8%) for outpatient visits. Five clusters of patients were identified, each with significantly different care usage patterns and distinct patient characteristics. Patterns included underuse of GP consultations, relative to the average use by the whole cohort, in patients living in more deprived areas; and increased use of other services in patients older than 75 years and those with three or more comorbidities. InterpretationHealth and social care service use was widespread but varied. Patterns of care usage suggest differences across patient groups. This might be due to variation in patients’ access to care and insufficiently integrated care at earlier stages of heart failure. The limitations of our study are that electronic health records like WSIC are not coded for research and subject to some biases; k-means testing is sensitive to the input variables and selection of k; and our findings require further validation and might not be generalisable to regions beyond the northwest London area. Further research is needed to characterise the patterns we have identified. FundingDr Foster (a Telstra Health company), the National Institute for Health Research (NIHR) Health Services Research, and the Imperial NIHR Biomedical Research Centre and the NIHR Collaboration for Leadership in Applied Health Research and Care for northwest London. The views expressed are those of the authors and not those of the NIHR.

2418Th17 signature, autoimmunity and differentially expressed genes in cardiomyopathy and heart failure

Abstract Background Cardiomyopathy may occur due to viral infections or drug induced heart damage. Cardiac myosin released from damaged heart has been shown to be a damage associated molecular pattern which binds to TLR2 or TLR8 and can act as an adjuvant to induce a strong autoimmune response against the heart. The result is autoimmunity against the heart which can lead to apoptosis, fibrosis and heart failure. Purpose Immune biomarkers of the early stages of heart failure are needed to identify individuals who develop progressive heart failure, do not recover their ejection fraction and may be candidates for immunotherapies. Methods Forty-one patients with myocarditis and heart failure &lt;6 months after onset were followed for 12 months and compared to age matched controls. Peripheral blood mononuclear cells were analyzed by FACS analysis and serum analyzed by ELISA for autoantibodies and cytokines. Statistical analysis was determined by Mann Whitney test. Peripheral blood of 10 patients with dilated cardiomyopathy (DCM) vs 19 healthy controls were analyzed for gene expression by RNA sequencing and pathway analysis using Reactome. Results Autoantibodies against human cardiac myosin and the beta-adrenergic receptor were significantly elevated in our cohort and functionally acted on cardiomyocytes to activate protein kinase A. Concomitantly, a Th17+ immunophenotype was significantly elevated in blood as well as in cardiac biopsies. CD4+IL17+ T cells (p=0.0008) and Th17-promoting cytokines TGF beta (p&lt;0.0001), IL-6 (p&lt;0.0001), IL-23 (p=0.0001), GMCSF (p=0.0336) and GMCSF-secreting CD4+ T cells (p=0.0006) were significantly elevated in blood. A Th17 immunophenotype was significantly associated with heart failure primarily in males (p=0.029). Persistent heart failure (NYHA class III and IV) and non-recovery of left ventricular function were associated with significantly higher percentages of IL17A-producing T cells at baseline, 6 and 12 months after onset, and IL-17A (p=0.019) and elevated Th17-promoting cytokines IL-6 (p=0.0001) and TGF-beta (p=0.0076). Decreased T regulatory immunosuppressive cells were significantly (p=0.0006) decreased and correlated with elevated Th17 cytokines in heart failure. Overrepresentation analysis of differentially expressed genes (adj p&lt;0.05) in blood of patients with DCM &gt;1year were identified using Reactome which revealed significant (FDR = 1.52E-13) enrichment of neutrophil degranulation (48 genes). Conclusion Our study illustrates a strong Th17 signature in more severe heart failure early in disease with elevated anti-cardiac myosin autoantibodies in non-recovery of left ventricular function. We observed a strong correlation with Th17-related neutrophil degranulation pathways in later disease, which may be biomarkers of fibrosis progression and disease severity in patients with heart failure. Cardiomyopathy with a Th17 signature might be treated with preventive immunomodulatory therapies such as anti-IL17A. Acknowledgement/Funding National Heart Lung and Blood Institute, Bethesda, MD, USA

P1674High intensity interval exercise program in heart failure patients seems to benefit cardiac power along with aorto-ventricular mechanical pump capacity and cardiorespiratory indices

Abstract Background Cardiac power has been suggested as the most power predictor of mortality in heart failure (HF) patients. In those patients aorta elastic properties and compensation is lost, systolic (and pulse) pressure are therefore reduced and associated with a decrease in ejection duration and pump efficiency. Cardiac rehabilitation programs have showed enhancement in cardiac performance and quality of life in HF patients. Aim Aim of this work was to evaluate the effect of high-intensity interval exercise (i.e., 30 sec at 100% of max workload, followed by 30 sec at rest, on a day-by-day 30 minutes working-out schedule for 12 weeks), on cardiac power, diastolic function indices, right ventricle performance and cardiorespiratory parameters among chronic HF patients. Methods 72 consecutive HF patients (NYHA class II-IV, ejection fraction &lt;50%) who completed the study (exercise training group, n=33, 63±9 years, 88% men, and control group, n=39, 56±11 years, 82% men), underwent cardiopulmonary stress test, non-invasive high-fidelity tonometry of the radial artery, pulse wave velocity measurement using a SphygmoCor device, and echocardiography before and after completion of the training program. Cardiac power output (CPO) (W) was calculated as mean arterial pressure × CO/451, where mean arterial pressure = [(systolic blood pressure − diastolic blood pressure)/3] + diastolic blood pressure. Results Both groups reported similar medical characteristics and physical activity status. General mixed effects models revealed that the intervention group increased 6MWT (by 13%, p&lt;0.05); increased cycle ergometry WRpeak (by 25%, p&lt;0.01), showed higher O2max by 31% (p&lt;0.001) and lower VE/VCO2 (p=0.05), whereas patients in the control group showed nosignificant changes in the aforementioned indices. Also, in the intervention group Emv/Vp was decreased by 14% (p=0.06); E to A ratio by 24% (p=0.004) and E to Emv ratio by 8% (p=0.05); while Stv increased by 25% (p=0.01). Most importantly, the intervention group reduced pulse wave velocity by 9% (p=0.05) and increased augmentation index by 26%; and VTI by 4% (p=0.05); Those parameters were not significantly changed on control group (all p&gt;0.05). Conclusion Hight intensity exercise rehabilitation program revealed beneficial effect on left ventricular diastolic indices and right ventricle performance. As, in those patients compensation of the aorta is also lost and the LV cannot generate the extra force necessary to completely overcome the late systolic augmented pressure, the increase in the augmented pressure (AIa) observed in the intervention group reflects the benefit in aorto-ventricular coupling and cardiac power that boosts systolic pressure and restores a positive influence in pressure, like in early stages of HF. Acknowledgement/Funding None

P2488The 2013 ACC/AHA pooled cohort equations and insulin resistance status for detection of early-stage heart failure in the community

Abstract Objectives Detection of heart failure (HF) in its subclinical phase would allow timely initiation of preventive measures that counter its pathophysiology. Here, we assessed the usefulness of traditional cardiovascular (CV) risk assessment and insulin resistance status to detect early-stage HF. Methods In 984 participants (mean age, 57.0 years, 52.3% women), we derived echocardiographic indexes of left ventricular (LV) structure and function and calculated the 10-year risk for a first atherosclerotic CV disease (ASCVD) using the 2013 ACC/AHA risk score. We assessed the discriminatory value of this risk score to detect LV maladaptation and the improvements in reclassification by insulin resistance status (HOMA-IR). Results The probability for LV maladaptation rose progressively with the 10-year ASCVD risk increasing. Participants at high 10-year ASCVD risk (&gt;7.5%) had indeed significantly higher odds for LV concentric remodeling (odds ratio, 4.84), LV hypertrophy (OR, 5.93), abnormal LV longitudinal strain (OR, 2.04) and LV diastolic dysfunction (OR, 25.3) as compared to those at low ASCVD risk (&lt;2.5%; P≤0.0003). Adding markers of insulin resistance to the ACC/AHA risk score moderately improved the integrated discrimination and net reclassification of all LV maladaptive phenotypes (P≤0.022) except LV diastolic dysfunction (P≥0.059). LV remodeling and abnormal LS was particularly more likely in insulin-resistant participants with a 10-year ASCVD risk between 5% and 15% than in their insulin-sensitive counterparts. Prediction of early-stage HF profiles 2013 ACC/AHA risk score Addition of insulin resistance status to the 2013 ACC/AHA risk score AUC (95% CI) Integrated Discrimination Improvement Net Reclassification Improvement Absolute IDI (%) P value NRI (95% CI) P value LV concentric remodeling 0.70 (0.66 to 0.74) 0.0083 (11.3%) 0.022 0.23 (0.067 to 0.39) 0.0058 LV hypertrophy 0.70 (0.66 to 0.74) 0.017 (20.7%) 0.0033 0.27 (0.11 to 0.43) 0.0011 Abnormal LV LS 0.56 (0.53 to 0.62) 0.022 (202.0%) &lt;0.0001 0.33 (0.18 to 0.49) &lt;0.0001 LV diastolic dysfunction 0.82 (0.78 to 0.86) 0.0007 (0.45%) 0.84 0.093 (−0.11 to 0.30) 0.38 ≥2 LV abnormalities 0.76 (0.72 to 0.80) 0.0087 (7.3%) 0.071 0.22 (0.042 to 0.40) 0.016 The integrated discrimination improvement (IDI) and net reclassification improvement (NRI) reflect the improvements in classification by adding insulin resistance (by HOMA-IR) to the 2013 ACC/AHA risk score. HOMA-IR, Homeostatic Model for Assessment of Insulin Resistance; LS, longitudinal strain; LV, left ventricular. Risk enhancers of LV maladaptation Conclusions The 2013 ACC/AHA risk score adequately captured the risk for echocardiographic phenotypes of early-stage HF. As risk enhancer, insulin resistance might improve risk stratification of subclinical HF in subjects at intermediate risk. Acknowledgement/Funding The European Union, European Research Council and the Flanders Scientific Research Fund supported this study.

BAOXIN Granules Protected Mouse Model With Elevated Afterload From Cardiac Hypertrophy by Suppressing Both Inflammatory Reaction and Collagen Deposition.

BAOXIN Pill was reported to be effective clinically for chronic heart failure based on the principles of traditional Chinese medicine (TCM), invigorating qi and activating blood. The present study evaluated preclinically the effects of the improved dosage form, BAOXIN Granules, on cardiac hypertrophy. Transverse aortic constriction (TAC) was performed in mice to model cardiac hypertrophy by aortic stenosis for 4 weeks. The sham and TAC group were intragastrically administrated with saline as the controls. Two treatment groups were administrated orally with 10 mg/kg⋅d Enalapril (positive control) or 0.77 g/kg⋅d BAOXIN Granules for 4 weeks respectively. The effects were evaluated by echocardiography, morphology, and biological markers for cardiac function. The specific genes involved in inflammation and fibrosis were also examined for their expressions to investigate the pathways involved in early heart failure. Just as Enalapril, BAOXIN Granules administration markedly attenuated left ventricular hypertrophy and improved heart function as evidenced by echo cardiography, morphology. Accordingly, the biomarkers of the early stage heart failure, ANP, BNP and β-MHC, were decreased in the two treatment groups. We also found that mRNA expressions of some inflammatory factors and fibrosis associated genes were down-regulated in the tissue of heart after treatment. BAOXIN Granules may protect the heart from myocardial hypertrophy caused by increasing left ventricular afterload. It can suppress both inflammatory reaction and collagen deposition during pressure overload. BAOXIN Granules is advised to be tested in clinical trials for heart failure in the future.