Risk Of Developing Heart Failure Research Articles

The role of acetylation in obesity-induced cardiac metabolic alterations.

Obesity is a growing public health problem, with its prevalence rate having tripled in the last five decades. It has been shown that obesity is associated with alterations in cardiac energy metabolism, which in turn plays a significant role in heart failure development. During obesity, the heart becomes highly dependent on fatty acid oxidation as its primary source of energy (ATP), while the contribution from glucose oxidation significantly decreases. This metabolic inflexibility is associated with reduced cardiac efficiency and contractile dysfunction. Although it is well recognized that alterations in cardiac energy metabolism during obesity are associated with the risk of heart failure development, the molecular mechanisms controlling these metabolic changes are not fully understood. Recently, posttranslational protein modifications of metabolic enzymes have been shown to play a crucial role in cardiac energy metabolic changes seen in obesity. Understanding these novel mechanisms is important in developing new therapeutic options to treat or prevent cardiac metabolic alteration and dysfunction in obese individuals. This review discusses posttranslational acetylation changes during obesity and their roles in mediating cardiac energy metabolic perturbations during obesity as well as its therapeutic potentials.

Global IL4Rα blockade exacerbates heart failure after an ischemic event in mice and humans.

Ischemic heart failure continues to be a highly prevalent disease among westernized countries and there is great interest in understanding the mechanisms preventing or exacerbating disease progression. The literature suggests an important role for the activation of interleukin-13 or interleukin-4 signaling in improving ischemic heart failure outcomes after myocardial infarction in mice. Dupilumab, a neutralizing antibody that inhibits the shared IL13/IL4 receptor subunit IL4Rα, is widely used for conditions such as ectopic dermatitis in humans. If global depletion of IL4Rα influences ischemic heart failure, either in mice or in humans taking dupilumab, is unknown. Here, we investigated the pathophysiological effects of global IL4Rα genetic deletion in adult mice after surgically induced myocardial infarction (MI). We also determined heart failure risk in patients with ischemic heart disease and concomitant usage of dupilumab using the collaborative patient data network TriNetX. Global deletion of IL4Rα results in exacerbated cardiac dysfunction associated with reduced capillary size after myocardial infarction in mice. In agreement with our findings in mice, dupilumab treatment significantly increased the risk of heart failure development in patients with preexisting diagnosis of ischemic heart disease. Our results indicate that systemic IL4Rα signaling is protective against heart failure development in adult mice and human patients specifically following an ischemic event. Thus, the compelling evidence presented hereby advocates for the development of a randomized clinical trial specifically investigating heart failure development after myocardial ischemia in patients taking dupilumab for another underlying condition.NEW & NOTEWORTHY A body of literature suggests a protective role for IL4Rα signaling postmyocardial infarction in mice. Here, our observational study demonstrates that humans taking the IL4Rα neutralizing antibody, dupilumab, have increased incidence of heart failure following an ischemic event. Similarly, global IL4Rα deletion in mice exacerbates heart failure postinfarct. To our knowledge, this is the first study reporting an adverse association in humans of dupilumab use with heart failure following a cardiac ischemic event.

Risk factors for raised left ventricular filling pressure by cardiovascular magnetic resonance: prognostic insights from UK Biobank

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute for Health and Care Research British Cardiovascular Society. Background Cardiovascular magnetic resonance imaging (CMR) can estimate left ventricular filling pressure (LVFP). The relationship between LVFP, determined by CMR measurements, and established risk factors for cardiovascular disease is unknown. This study quantifies these associations and investigates the prognostic value of CMR-derived LVFP compared to known risk factors for cardiovascular disease. Methods Using data from the UK Biobank prospective observational cohort study, CMR-derived LVFP was calculated using a model incorporating left atrial volume and left ventricular mass. Logistic regression was used to explore the relationships between raised LVFP (≥15mmHg) and typical cardiovascular risk factors. The non-linear relationship between LVFP and age was analysed using ordinary least squares regression and a restricted cubic spline of age with nine knots. Cox proportional hazards regression was used to analyse the relationships between typical cardiovascular risk factors and CMR-derived LVFP, and outcomes of incident heart failure and major adverse cardiovascular events. Results In this prospective population-based cohort study, 39,163 UK Biobank participants had CMR with adequate image quality. In a multivariable logistic regression model, male sex (OR 4.55, 95% CI 3.85–5.42, p<0.001), age (OR 1.89, 95% CI 1.72 - 2.09, per decade increment, p<0.001), BMI (OR 1.57, 95% CI 1.48–1.67, per SD increment, p<0.001), and hypertension (OR 1.46, 95% CI 1.26–1.68, p<0.001) were associated with increased odds of raised LVFP (Figure 1a). A non-linear regression model of the relationship between age and LVFP, adjusted for all covariables studied, showed little correlation between CMR-derived LVFP and age until 70 years, after which LVFP increased rapidly with age (Figure 2). In multivariable Cox regression models, elevated CMR-derived LVFP was associated with increased hazard of incident heart failure (HR 3.31, 95% CI 1.99–5.49, p<0.001) but not MACE (HR 1.33, 95% CI 0.86–2.07, p = 0.20) (Figure 1b). Conclusions Raised LVFP, as determined using CMR, is independently associated with male sex, age, BMI and hypertension. CMR-derived LVFP is independently associated with incident heart failure. These findings may have implications for clinical risk stratification, targeted population screening strategies and public health measures to reduce the risk of heart failure development.

Left ventricular remodeling in normotensive Wistar rats exposed to intermittent hypoxia of different duration

Intermittent hypoxia has been studied for many years as a promising non-pharmacological method of cardiovascular disease prevention. Hypoxic effects are accompanied by structural and functional changes in the myocardium. There is a direct link between the duration of hypoxic exposures and the severity of left ventricular myocardial remodeling. A range of histochemical markers of myocardial remodeling (cardiotrophin-1, titin, collagen type 1, annexin V) characterizing parenchymal-stromal relationships in the myocardium has shown high informativeness and prognostic value. The aim of the study was to examine cardiotrophin-1, titin, collagen type 1, annexin V and the morphofunctional state of the left ventricle of the heart in experimental rats exposed to intermittent 15-day (IH15) and 60-day hypoxia (IH60). Materials and methods. Intermittent hypoxia was modeled using 30 normotensive male Wistar rats, 7–8 months old, which were randomly assigned to 3 experimental groups of 10 animals each: 1) INT – a control group – intact animals (196.3 ± 6.8 g); 2) IH15 – 15-day hypoxia (205.6 ± 4.1 g); 3) IH60 – 60-day hypoxia (201.1 ± 5.5 g). The study compared the effects of intermittent hypoxia of varying duration: 15-day and 60-day hypoxia. Experimental modeling of intermittent hypoxia of 2 terms revealed a number of differences between the effects dependent on this factor duration through functional (blood pressure measurement, echocardiography) and immunofluorescent studies. Results. Blood pressure in rats of both groups was in the normotensive range, but an increase in systolic by 10 % and diastolic by 19 % was found in IH60 group compared to IH15 group (p < 0.05). In IH15 group, there was a significant decrease in end-diastolic dimension by 20 %, end-systolic dimension by 22 %, an increase in the thickness of left ventricular posterior wall by 44 % and interventricular septum by 33 % as well as left ventricular mass by 12 %, indicating concentric remodeling of the left ventricle, the development of which was confirmed by a 76 % increase in relative wall thickness compared to that in the control group (p < 0.05). Along with these changes, a decrease in end-diastolic volume by 47 %, end-systolic volume by 48 %, stroke volume by 49 % and cardiac output by 50 % with preserved ejection fraction was revealed (p < 0.05). While the parameters of IH60 rats were characterized by an increase in the thickness of interventricular septum by 33 % and left ventricular posterior wall by 17 %, as well as left ventricle mass by 23 %, relative left ventricular wall thickness was 15 % higher than the control value (p < 0.05). At the same time, diastolic volume was 9 % decreased and systolic volume was 24 % increased (p < 0.05). Also, cardiac output was increased by 58 % compared to that in 15-day hypoxic rats with an 8 % decrease in ejection fraction (p < 0.05). The concentrations of markers in IH60 group exceeded those in IH15, namely: cardiotrophin-1 by 39 %, titin by 70 %, collagen type 1 by 60 % and annexin V by 130 % (p < 0.05). Conclusions. 15-day hypoxia forms concentric left ventricular hypertrophy according to echocardiography findings; the study of marker profile of myocardial remodeling has revealed the development of moderate hypertrophy with increased resilient-elastic properties and decreased intensity of cardiomyocyte death. Remodeling caused by 60-day hypoxia is characterized by the eccentric pattern of changes with severe hypertrophy, significant fibrosis associated with apoptosis of cardiomyocytes. Such morphofunctional state of the myocardium may indicate the initial stages of maladaptation, increasing the risk of heart failure development.

Heart failure as a complication of myocardial infarction: rational therapy. Case report

Heart failure (HF) is still a frequent complication of myocardial infarction. Timely identification of subjects at risk for HF development and early initiation of guideline-directed HF therapy in these patients, can decrease the HF burden. This article aims at summarizing clinical data on established pharmacological therapies in treating post-MI patients with left ventricular systolic dysfunction and signs and symptoms of HF.

Abstract 12291: Natriuretic Peptide Levels and Predicting Risk of Developing New Diabetes Mellitus or Metabolic Syndrome: A Population Based Study

Introduction: The prevalence of metabolic syndrome (MS), and diabetes mellitus (DM) is increasing, and the use of biomarkers to identify subjects at risk of developing MS or DM may be useful for disease prevention. Natriuretic peptides (NPs) are well known for their role as biomarkers in heart failure (HF), but are increasingly being recognized for their favorable metabolic actions and potential role as risk modifiers for the development of DM and MS. To date, however, this risk relationship has not been well defined in the general population. Hypothesis: Adults in the general population with lower NP levels are at higher risk for developing DM or MS. Methods: A retrospective review of the Olmsted County Heart Function Study cohort, a population-based random sample of 2042 Olmsted County, MN residents aged ≥ 45 years. A subgroup of community-dwelling subjects without MS or DM at Visit 1 was identified and subjects returned for followup after 4 years (Visit 2). We compared the characteristics of subjects that developed MS or DM after 4 years to those that did not. Results: Of the 911 subjects who did not have MS or DM at visit 1, 93 (10.2%) developed either MS or DM at visit 2. Subjects who developed MS or DM at visit 2 were more likely to have higher baseline BMI (p <0.001), lower HDL (p<0.001), higher triglycerides (p < 0.001), higher insulin (p< 0.001), higher aldosterone (p < 0.001) levels, lower NT-proANP (p<0.001) and lower NT-proBNP levels (p < 0.01) compared to those that did not develop MS or DM. Those that developed MS or DM were also at higher risk for development of HF when controlling for age and sex (HR 2.73 CI 1.25-5.96). On univariate analysis, higher baseline levels of NT-proANP and NT pro-BNP had a significant negative association with developing new MS or DM (ORs per 1 SD increase: 0.64, CI 0.51-0.79 p < 0.0001 and 0.76, CI 0.62-0.95 p=0.016, respectively). Conclusions: Among adults aged ≥ 45 years in the community, low levels of NT- ANP and NT-proBNP are associated with increased risk of development of DM and MS. Further studies are warranted to determine if potentiating the natriuretic peptide system would delay the development of DM or MS.

Aortic valve calcium in relation to subclinical cardiac dysfunction and risk of heart failure in the general population

Abstract Background Emerging evidence suggests that aortic valve calcium (AVC) is associated with adverse cardiovascular outcomes, while the association of (early) AVC with subclinical cardiac dysfunction and with risk of heart failure (HF) remains unclear. Purpose To determine the association of CT-assessed AVC with echocardiographic measurements of cardiac dysfunction, and with HF in the general population. Methods We included 2,348 participants (mean age 68.5 years, 52% women) of the Rotterdam Study, who had AVC measured between 2003 and 2006, and without a history of HF at baseline. Linear regression models were used to explore cross-sectional associations of AVC with echocardiographic measures at baseline. All participants were followed for HF event until December 2016. Cox proportional hazard models were used to assess the association of AVC with incident HF. Models were adjusted for potential confounders. Results The presence of AVC was associated with 3.14 g/m2 (95% CI, 1.50 to 4.79) higher mean left ventricular mass indexed by body surface area. One-unit larger log (AVC+1) was associated with 0.01 mm (95% CI 0.01 to 0.02) larger mean left atrial size. During a median follow-up of 9.8 years, 182 incident HF cases were identified. Presence of AVC was associated with 37% greater risk for HF (HR, 1.37; 95% CI, 1.01 to 1.87). One-unit larger log (AVC+1) was associated with 11% larger risk of HF (HR, 1.11; 95% CI, 1.04 to 1.18). Compared with the AVC =0, AVC ≥100 had 1.70 folded risk of HF (HR, 1.70; 95% CI, 1.17 to 2.49). Conclusions The levels of AVC were associated with markers of left ventricular structure and with risk of HF, independent of traditional cardiovascular risk factors. Larger CT-assessed AVC is an indicative of increased risk for development of HF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Netherlands Organization for the Health Research and Development (ZonMw)Dutch Heart Foundation (03-004-2021-T050)

No cardiac sequelae after COVID-19: results of the one year follow-up with echocardiography and biomarkers

Abstract Objective To evaluate the need for cardiac monitoring of unselected patients recovered from COVID-19 and to estimate the risk of heart failure development after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods During March 2020 and January 2021, 106 patients recovered from SARS-CoV-2 (alfa and beta variants) were enrolled in the prospective observational cohort study, CoSuBr (Covid Survivals in Brno). The diagnosis was established by reverse transcription polymerase chain reaction on swab test of the upper respiratory tract. Demographic parameters, patient history, clinical evaluation, cardiac biomarkers, ECG and echocardiography were recorded within three visits (V1 at least six weeks after infection, V2 three months later and V3 one year after V1). Results The study group (n=106) included 58% women, mean age was 46 years (range 18–77 years). Mean time interval between the onset of the infection and the follow-up visit was 107 days. One quarter (24.5%) of the patients required hospitalisation during the acute phase of the disease, the rest recovered at home. 74% suffered from mild form, 3.8% moderate, 18.3% severe and 2.9% of critical form of the disease. At the time of enrolment 63.5% of the patients were referring the ongoing symptoms, while more than half of the whole group (50.9%) mentioned at least one symptom of possible cardiac origin (breathing problems, palpitations, exercise intolerance, fatigue). During one year follow up after COVID-19 infection there was no decrease of left ventricle ejection fraction (V1: 62.1±5.26% to V3: 60.8±6.24%, p=0,150), no changes of troponin (4.8±3.41 to 4.7±3.31ng/L; p=0.417) and NT-proBNP (74.3±75.15 to 95.3±137.28pg/mL; p=0,315). There was a mild decrease of right ventricle end diastolic diameter (28.9±5.59 to 26.8±3.83mm, p<0.001), while no right ventricle dysfunction was detected. There was a very mild progress in a left ventricle diastolic diameter (47.9±6.34 to 49.3±4.21mm; p<0.001) between V1 a V3, a mild enlargement of left atrium (37.1±5.85 to 38.2±5.65mm; p=0,021) and non-significant trend to impairment of left ventricle diastolic dysfunction. There was a mild change of pulmonary artery systolic pressure (24.7±7.92 to 27.5±6.97mmHg; p=0,038). Conclusion Despite many information regarding cardiac impairment of SARS-CoV-2 our study does not suggest increased risk of development of heart failure during the one year follow-up. Based on our results the routine echocardiography and biomarkers collection is currently not recommended after COVID-19 recovery. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): MH CZ - DRO; MEYS - RI CZECRIN

Pharmacological selectivity of SGLT2 inhibitors and cardiovascular outcomes in patients with type 2 diabetes: a meta-analysis

Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus. However, SGLT2 inhibitors show great variance in pharmacological selectivity to SGLT2 over SGLT1. Reduced functional capacity of SGLT1 is associated with lower risk of heart failure development and mortality in humans. Yet, the clinical relevance of additional pharmacological SGLT1 inhibition is unclear. Purpose To assess whether additional pharmacological SGLT1 blockade adds further benefits to SGLT2 inhibition. Methods In this preregistered meta-analysis, we included randomized placebo-controlled cardiovascular outcome trials (CVOTs) of SGLT2 inhibitors assessing MACE (composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke) in patients with type 2 diabetes. Hazard ratios (HRs) and 95% confidence intervals (CIs) of prespecified clinical endpoints were pooled using a random-effects model. Interactions were assessed according to low versus high pharmacological SGLT2 selectivity of the given medication. Mixed-effects meta-regression analysis was performed to quantify correlation between pharmacological SGLT2:SGLT1 selectivity ratio and clinical outcomes. Results A total of 6 independent CVOTs comprising 57553 type 2 diabetic patients (mean age 64.6±7.9 years; 36769 [63.9%] men) were included. Overall, SGLT2 inhibitors significantly reduced risk of adverse cardiovascular and renal outcomes, but had no significant impact on the risk of fatal and nonfatal stroke compared with placebo (HR, 0.92; 95% CI, 0.77–1.10; p=0.36; I2=63%). Agents with clinically relevant SGLT1 inhibitory effect (sotagliflozin, canagliflozin) significantly reduced the risk of stroke (HR, 0.78; 95% CI, 0.64–0.94) compared with placebo, whereas those with high SGLT2 selectivity did not (HR, 1.06; 95% CI, 0.92–1.22), yielding a significant interaction (p=0.018). The difference was also significant in patients with estimated glomerular filtration rate (eGFR) lower than 60 mL/min/1.73 m2 (p=0.047). Meta-regression indicated that lower SGLT2:SGLT1 pharmacological selectivity ratio was associated with lower risk of stroke (pseudo-R2=78%; p=0.011), which was evident even after adjusting for baseline eGFR values (p=0.047). Pharmacological selectivity of SGLT2 inhibitors had no significant impact on any other assessed clinical outcomes, including hospitalization for heart failure and all-cause death. Conclusion These hypothesis-generating results indicate that targeting SGLT1 in addition to SGLT2 inhibition might constitute a new avenue for stroke risk reduction in patients with type 2 diabetes. Further confirmatory studies are needed. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This project was supported by grants from the National Research, Development and Innovation Office (NKFIH) of Hungary (K134939 to T.R.), and by the New National Excellence Program of the Ministry of Human Capacities of Hungary (ÚNKP-21-3-II-SE-45 to A.A.S.).

Abstract P201: Social Determinants Of Health Modulate Risk Of Heart Failure Development In A Federally Qualified Health Center Population

Introduction: Social determinants of health (SDoH) are known predictors of heart failure, though their incorporation into existing risk models is limited, and these models are not widely implemented. In particular, there are limited studies of heart failure risk within federally qualified health centers (FQHCs) tailored to quantify the effects of several SDoH including sexual and gender minority status, socioeconomic factors, and neighborhood characteristics. Hypothesis: We assessed the hypothesis that risk factors among several SDoH domains would modulate heart failure risk when controlled for traditional biologic risk factors and significantly improve the performance of a predictive model among patients at Howard Brown Health, a FQHC. Methods: We retrospectively identified all patients at Howard Brown Health from January 1, 2012 through December 31, 2019 using electronic health records. The association between risk factors and heart failure diagnosis, defined as having one heart failure-associated ICD code, was assessed by multivariate logistic regression. Missing data were imputed with the R mice package. Neighborhood-level data were obtained from the 2019 American Community Survey. Machine learning was used to predict heart failure with several algorithms including gradient boosting machine via the R caret package. Results: Among 99,047 patients, 130 (0.13%) had heart failure. On multivariate logistic regression, these patients were significantly more likely than peers to be older (OR 0.0002, p<0.001), smoke (OR = 0.0035, p<0.001), have diabetes (OR 0.3, p<0.001), have dyslipidemia (OR 0.3, p<0.001), have hypertension (OR 0.001, p<0.001) or have coronary heart disease (OR 0.8, p<0.001. Non-Hispanic whites were at lower risk than non-Hispanic blacks (OR 0.0008, p<0.01) and at higher risk than Hispanic patients (OR -0.0006, p<0.05). Patients with lower household incomes, government insurance or no insurance, or those who lived in neighborhoods with lower median household incomes were also all more likely to have heart failure (all p<0.05). The machine learning predictive models incorporating SDoH and without SDoH respectively had sensitivities of 87% and 82%, specificities of 85% and 80%, positive predictive values of 99.98% and 99.98%, and negative predictive values of 0.9% and 0.8%. Conclusions: Biologic comorbidities portend the highest heart failure risk. Race and economic factors, including neighborhood level variables, predict the highest heart failure risk among measured SDoH in this FQHC population. A machine learning model is able to predict heart failure with biologic comorbidities, and SDoH improve model performance. In conclusion, future research incorporating SDoH—in particular race and economic characteristics—into risk assessments or predictive modeling may aid early detection and prevention of heart failure and reduce health disparities.

Association of retinal atherosclerosis assessed using Keith-Wagener-Barker system with incident heart failure and other atherosclerotic cardiovascular disease: Analysis of 319,501 individuals from the general population

Background and aimsIt is not known whether the presence of retinal atherosclerosis (RA) is associated with incident heart failure (HF) in the general population. We aimed to investigate the relationship between RA and the risk of HF development using a nationwide population-based database. MethodsWe studied 319,501 adults without a history of cardiovascular disease (CVD) and with available data on retinoscopy at health check-up registered in the JMDC Claims Database between January 2005 and April 2020. We performed Cox regression analyses to assess the relationship of RA, defined as Keith-Wagener-Barker system grade ≥1, with incident HF and other CVD, including myocardial infarction (MI), angina pectoris (AP), and stroke. ResultsThe median age (interquartile range) was 47 (41–54) years, and 159,710 participants (50.0%) were men. RA was observed in 26,168 participants (8.2%). During a median (interquartile range) follow-up of 2.9 (1.6–4.6) years, 6,821 (2.1%) HF, 692 (0.2%) MI, 7,016 (2.2%) AP and 3,584 (1.1%) stroke events occurred. After adjustment for potential confounders, multivariable Cox regression analyses showed that RA was associated with a greater incidence of HF (hazard ratio 1.13, 95% confidence interval [CI] 1.05–1.21) and other CVDs. Hazard ratios of RA for MI, AP, and stroke were 1.17 (95% CI, 0.95–1.44), 1.13 (95% CI, 1.05–1.21), and 1.25 (95% CI, 1.14–1.37), respectively. This association was present in all subgroups. ConclusionsThe assessment of RA may be useful to identify people at high-risk for the development of HF and other atherosclerotic CVD events in a general population.

Correlation of Suppression of Tumourigenicity 2 with hsCRP, NT-proBNP and Left Ventricular Ejection Fraction in Patients with Myocardial Infarction

Introduction: Soluble Suppression of Tumourigenicity 2 (sST2) represents a clinically relevant biomarker and has predictive evidence in acute Myocardial Infarction (MI) and predicts cardiovascular death and risk of heart failure development in these patients. The data about the correlation of sST2, N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP)in the Indian population is lacking. Aim: To find a correlation of ST2 level at the time of admission with NT-proBNP, hsCRP and Left Ventricular Ejection Fraction (LVEF) in patients with MI, and the association of ST2 levels with mortality. Materials and Methods: This longitudinal observational study was conducted at Poona Hospital and Research Centre, Pune, Maharashtra, India, between June 2018 and August 2019, among 75 myocardial infarction patients above 18 years of age. ST2, NT-proBNP and hsCRP levels were checked within 6 hour of hospitalisation. The primary outcome measures were to study the correlation of ST2 levels at the time of admission with hsCRP, NT-proBNP and LVEF. The secondary outcome measures were to study the association of ST2 levels with in-hospital and onemonth mortality. The medians of continuous variables of two groups and three groups were-tested using the Mann-Whitney U test and Kruskal-Wallis H test respectively. The correlation analysis was performed using Spearman’s method. Results: The mean age of the study population was 57.8±7.2 years. The mortality rate was 60% (12/75). ST2 levels showed a statistically significant positive correlation with NT-proBNP (r =0.703, p-value=0.001) and hsCRP (r=0.873, p-value=0.001), whereas, ST2 levels showed a negative correlation with LVEF (r=- 0.711, p-value=0.001) in MI patients. The median ST2 levels were significantly higher in-hospital (215.3 ng/dL vs 94 ng/dL) and one month (219.5 ng/dL vs 92.0 ng/dL) mortality as compared to survived MI patients. Conclusion: ST2 levels showed a statistically significant positive correlation with NT-proBNP and hsCRP and were associated with in-hospital and one month mortality in MI patients.

Therapeutic potential of targeting oxidative stress in diabetic cardiomyopathy

Even in the absence of coronary artery disease and hypertension, diabetes mellitus (DM) may increase the risk for heart failure development. This risk evolves from functional and structural alterations induced by diabetes in the heart, a cardiac entity termed diabetic cardiomyopathy (DbCM). Oxidative stress, defined as the imbalance of reactive oxygen species (ROS) has been increasingly proposed to contribute to the development of DbCM. There are several sources of ROS production including the mitochondria, NAD(P)H oxidase, xanthine oxidase, and uncoupled nitric oxide synthase. Overproduction of ROS in DbCM is thought to be counterbalanced by elevated antioxidant defense enzymes such as catalase and superoxide dismutase. Excess ROS in the cardiomyocyte results in further ROS production, mitochondrial DNA damage, lipid peroxidation, post-translational modifications of proteins and ultimately cell death and cardiac dysfunction. Furthermore, ROS modulates transcription factors responsible for expression of antioxidant enzymes. Lastly, evidence exists that several pharmacological agents may convey cardiovascular benefit by antioxidant mechanisms. As such, increasing our understanding of the pathways that lead to increased ROS production and impaired antioxidant defense may enable the development of therapeutic strategies against the progression of DbCM. Herein, we review the current knowledge about causes and consequences of ROS in DbCM, as well as the therapeutic potential and strategies of targeting oxidative stress in the diabetic heart.

Опыт применения расчета объемной фракции интерстициального коллагена у больных артериальной гипертонией

The aim of the research is to optimize the assessment of collagen volumetric fraction in patients with stage 1 and 2 hypertensions. Material and methods. In total 39 patients with arterial hypertension took part in the study. Group 1 included patients (n = 13) with stage 1 hypertension, the second group included patients with stage 2 hypertension (n = 26). To verify structural changes in the left ventricle, all subjects underwent comprehensive examination, including history taking, anthropometric data taking, ECG study with the calculation of general QRS (mm) as a total indicator of R wave amplitude in 12 electrocardiographic leads, and echocardiography according to standard technique. Statistical analysis, based on the data obtained, was carried out using SPSS soft ware package. Furthermore, there was comparison of collagen volumetric fraction calculation (СVFC) according to the method of J. Shirani et al. (1992), and by our own formula based on nonlinear regression equation. Results. When calculating СVFC in accordance with the formula of J. Shirani et al. (1992), СVFC values (%) in the 1st group of subjects were 8.48 [5.5; 9.7]; in the 2nd group they were 11.16 [0.5; 1.7], (U = 51.0, p = 0.45). When studying groups СVFC in accordance with the alternative formula, more statistically signifi cant diff erences were observed: СVFC values in the 1st group were 23.5 [21.4; 30.4], in the 2nd group - 29.5 [25.5; 35.7] (U = 105.0, p = 0.049). Conclusion. The developed method for calculating collagen volumetric fraction is more pathogenetically suffi cient. Th is makes it possible to determine this indicator more accurately for identifying a group of patients suffering from stage 1 and 2 hypertension, with a high risk of heart failure development for its wide use in clinical practice to monitor them more frequent and to correct their therapy.

Myocardial Fibrosis and Left Ventricular Hypertrophy Elevates Cardiovascular Risk in Patients with Diabetes Mellitus

Myocardial fibrosis (MF), detected by late gadolinium enhancement-cardiac magnetic resonance (LGE-CMR), is independently associated with adverse cardiovascular events and thus, holds immense prognostic value in diabetes mellitus (DM). Concurrent LGE and DM further confers elevated risk of heart failure development and progression. Although separate correlations comparing DM with MF or left ventricular hypertrophy (LVH) have been established, their singular and collective impact remains unclear in DM patients without a cardiomyopathy.

Heart failure after myocardial infarction: incidence and predictors.

AimsThe aim of the present paper was to provide an up‐to‐date view on epidemiology and risk factors of heart failure (HF) development after myocardial infarction.Methods and resultsBased on literature review, several clinical risk factors and biochemical, genetic, and imaging biomarkers were identified to predict the risk of HF development after myocardial infarction.ConclusionsHeart failure is still a frequent complication of myocardial infarction. Timely identification of subjects at risk for HF development using a multimodality approach, and early initiation of guideline‐directed HF therapy in these patients, can decrease the HF burden.

Imaging predictors of incident heart failure: a systematic review and meta-analysis.

Preventing the evolution of subclinical cardiac disease into overt heart failure is of paramount importance. Imaging techniques, particularly transthoracic echocardiography (TTE), are well suited to identify abnormalities in cardiac structure and function that precede the development of heart failure. This meta-analysis provides a comprehensive evaluation of 32 studies from 11 individual cohorts, which assessed cardiac indices from TTE (63%), cardiovascular magnetic resonance (CMR; 34%) or cardiac computed tomography (CCT; 16%). Eligible studies focused on measures of left ventricular geometry and function and were highly heterogeneous. Among the variables that could be assessed through a meta-analytic approach, left ventricular systolic dysfunction, defined as left ventricular ejection fraction (LVEF) lower than 50%, and left ventricular dilation were associated with a five-fold [hazard ratio (HR) 4.76, 95% confidence interval (95% CI) 1.85-12.26] and three-fold (HR 3.14, 95% CI 1.37 -7.19) increased risk of heart failure development, respectively. Any degree of diastolic dysfunction conveyed an independent, albeit weaker, association with heart failure (HR 1.48, 95% CI 1.11-1.96), although there was only a trend for left ventricular hypertrophy in predicting incident heart failure (hazard ratio 2.85, 95% CI 0.82-9.85). LVEF less than 50%, left ventricular dilation and diastolic dysfunction are independent predictors of incident heart failure among asymptomatic individuals, while left ventricular hypertrophy seems less predictive. These findings may serve as a framework for implementing imaging-based screening strategies in patients at risk of heart failure and inform future studies testing preventive or therapeutic approaches aiming at thwarting or halting the progression from asymptomatic (preclinical) to overt heart failure.

P516Permanent his bundle pacing: conclusions from the one-year experience of a romanian center

Abstract Background Long term right ventricular pacing has been associated with an increased risk of heart failure development due to pacing induced cardiomyopathy. Therefore, alternatives of more physiological pacing have been evaluated. Amongst them, His bundle pacing (HBP) has emerged in the past two decades as the most physiological method of ventricular pacing due to synchronous activation of both ventricles through the intrinsic conduction system. Although there is an already consistent experience in the United States, China and western Europe regarding His bundle pacing, some countries in central and eastern Europe have little or no experience in this matter. We present the results of our one-year experience after implementing His bundle pacing in a tertiary cardiac pacing center in Romania. Material and methods Between July 2018 and October 2019, HBP using the current available dedicated delivery system was attempted in 50 patients with permanent cardiac pacing indications. Patient characteristics and procedural results were analyzed during implant and at 3 months, 6 months and 1 year follow-ups. Results The mean age of the patients was 70,14 ± 10,58 years and 58 % were male. The main indication for cardiac pacing was atrioventricular block (66%) and 96 % received a dual-chamber pacemaker. No ventricular back-up leads were used. The acute procedural success (selective or nonselective His bundle capture) was achieved in 40 patients (80%). The rest of the patients received either right ventricular or left bundle branch pacing. Selective His bundle pacing was seen in 15 out of 40 patients, with nonselective His bundle pacing in the rest. The acute His pacing threshold was 1.77 ± 1.06 V at 1 ms, the sensed R wave amplitude was 4.2 ± 2.27 mV and total fluoroscopy time was 15.95 ± 10.9 min. The paced QRS duration was very similar to the baseline QRS duration in patients without bundle branch block and significantly narrower in patients with bundle branch block morphology (126,6 ± 23 ms vs. 95,5 ± 21,65 ms, p < 0,001). The presence of a native QRS complex with a bundle branch block morphology was associated with an increased risk of procedural failure, longer fluoroscopy times and higher capture thresholds. Also, pacing threshold (1,91 ± 1,23 vs. 1,62 ± 0,84 V/1ms , p = 0,4) and fluoroscopy times (21,15 ± 10,35 vs. 10,75 ± 8,85 min, p = 0,002) were lower in the second half of the procedures as the learning curve was achieved. There were no significant changes in pacing and sensing thresholds at 3 months, 6 months and 1 year follow-ups. There was only one case of lead dislodgement a week after the procedure that required reintervention. Conclusion His bundle pacing is feasible and easy to implement in an experienced device implantation center, with a high procedural success rate. Improvement of the procedural parameters is achieved while advancing the learning curve. Proper patient selection could influence the outcomes of the procedure.

P2568Larger vectorcardiographic QRS area is associated with increased risk of heart failure development among left bundle branch block patients: a register-based cohort study

Abstract Background QRS morphology including left bundle branch block (LBBB) and duration remain the most widely used surrogate markers in the 12-lead electrocardiogram (ECG) for assessing ventricular dyssynchrony and predicting future burden of heart failure (HF) and cardiovascular mortality. However, the vectorcardiographic QRS area has recently been proposed and evidence suggest that this marker may more accurately predict HF development. Purpose The aim of this study was to investigate the association between vectorcardiographic QRS area and risk of HF development in LBBB patients. Methods From 2001–2015, the Copenhagen General Practitioners' Laboratory was used to identify patients with a first-time LBBB ECG (QRS>120 ms; LBBB morphology), from which QRS area was derived using the Kors transformation method and grouped into quartiles. Outcome was a composite of HF diagnosis, redeemed prescriptions of loop diuretics, or death from HF. Death from other causes was accounted for as a competing risk. Results We included a total of 2843 LBBB patients who were free of heart failure (median age, 70 years; female, 58%; ischemic heart disease, 9%). QRS area quartiles comprised Q1, 67–158 μVs; Q2, 159–189 μVs; Q3, 190–228 μVs; and Q4, 229–739 μVs. During 6-month, 1-year, and 5-year follow-up, 9%, 12%, and 28% of patients reached the combined HF endpoint, and 1%, 2%, and 8% of patients died from other causes, respectively (Figure 1). After multivariable adjustment, the highest QRS area quartile, Q4, was associated with increased HF risk (adjusted hazard ratio, 1.64; 95% confidence interval, 1.35–2.00) compared with the lowest quartile, Q1. We did not observe any significant increase in HF risk for remaining quartiles (Q2 or Q3 vs. Q1). Figure 1 Conclusions Among primary care patients with newly discovered LBBB, a large vectorcardiographic QRS area (229–739 μVs) is associated with increased risk of developing the incident, combined HF endpoint. This indicates that the QRS area derived using the Kors method may serve as a valuable prognostic marker when assessing risk of HF in patients with LBBB.

SUN-063 Shortened Sleep Duration as a Heart Failure Risk Factor for Patients with Diabetes Mellitus

Heart failure is one of the most common causes of morbidity and mortality. Diabetes mellitus promotes the development of heart failure. Shortened sleep duration causes hormonal and metabolic changes and therefore can be a risk factor of heart failure. The aim of this pilot study was to define the link between the sleep duration and the risk of heart failure development . The study involved 217 patients but only 24 patients (5 male, 19 female) matched inclusion criteria. Self-reported sleep duration was obtained and brain natriuretic peptide (BNP) was measured in plasma using the chemiluminescent microparticle immunoassay (CMIA) ARCHITECT).The statistic relationship of BNP and sleep duration was assessed with test Cruscal-Wallis. The patients were divided into three groups: group «A» including 13 patients (2male), average age 56.9±2.1 with normal sleep duration about 7-9 hours, «B» including 2 (1 male) patients, average age 56.0± 9.0 with long sleep duration 9 hours and more and «C» including 9 patients ( 2 male),average age 62.0±2.1with shortened the sleep duration less 7 hours. Level of BNP obtained 49.7 ± 24.04(SD ±8.01) pg/ml, 17 ± 7.98 (SD ±2.21)pg/ml, 13.5 ± 4.94 (SD ± 3.5)pg/ml for groups A, B, C respectively. The duration of sleep in the group «С» was inversely proportional to the level of BNP in plasma and was significantly different from the group «А»( p = 0.003). Therefore the shortened sleep can be one of the additional risks of heart failure development.