Clinical Manifestations Of Heart Failure Research Articles

The functional role of circRNA CHRC through miR-431-5p/KLF15 signaling axis in the progression of heart failure

Pathological myocardial hypertrophy is a common early clinical manifestation of heart failure, with noncoding RNAs exerting regulatory influence. However, the molecular function of circular RNAs (circRNAs) in the progression from cardiac hypertrophy to heart failure remains unclear. To uncover functional circRNAs and identify the core circRNA signaling pathway in heart failure, we construct a global triple network (microRNA, circRNA, and mRNA) based on the competitive endogenous RNA (ceRNA) theory. We observe that cardiac hypertrophy related circRNA (circRNA CHRC), within the ceRNA network, is down-regulated in both transverse aortic constriction (TAC) mice and Ang-II--treated primary mouse cardiomyocytes. Silencing circRNA CHRC increases cross-sectional cell area, atrial natriuretic peptide, and β-myosin heavy chain levels in primary mouse cardiomyocytes. Further screening reveals that circRNA CHRC targets the miR-431-5p/KLF15 axis implicated in heart failure progression in vivo and in vitro. Immunoprecipitation with anti-Ago2-RNA confirms the interaction between circRNA CHRC and miR-431-5p, while miR-431-5p mimics reverse Klf15 activation caused by circRNA CHRC overexpression. In summary, circRNA CHRC attenuates cardiac hypertrophy via sponging miR-431-5p to maintain the normal level of Klf15 expression.

Dynamics of Right Ventricle Pressure During Stress Echocardiography in Patients with Heart Failure with Preserved Ejection Fraction

Shortness of breath during physical exertion is a non-specific symptom that can hide such potentially dangerous diseases as structural or functional bronchopulmonary, coronary heart disease, structural cardiac disease, but the frequent cause is left ventricle diastolic dysfunction due to its significant hypertrophy. Pathogenetic mechanisms leading to this symptom require detailed study for the possibility of a comprehensive approach in the treatment of such patients with the aim of maximally improving their prognosis and quality of life. Objective — evaluate changes in right ventricle systolic pressure during stress echocardiography in patients with LV myocardial hypertrophy and clinical manifestations of heart failure, search for other mechanisms leading to clinical symptoms. Materials and methods. The study included 49 patients with shortness of breath during physical exertion, who underwent further diagnostic examination after exclusion of coronary stenotic lesions by invasive coronary and ventricular angiography. Patients were excluded from bronchopulmonary pathology using spirometry and chest radiography, structural heart pathology using echocardiography, microvascular angina using echocardiography with intravenous dipyridamole infusion, and the change in systolic pressure in the right ventricle was investigated using echocardiography during a physical exercise test. Results and discussion. There were no cases of infiltrative lung changes, signs of emphysema, or other manifestations of significant pathology according to X-ray data. Spirometry also showed the absence of significant functional abnormalities. Echocardiography revealed significant hypertrophy of LV myocar­dium (thickness of IVS — on average (14.1 ± 0.5) mm, posterior wall thickness — on average (13.5 ± 0.3) mm) with the presence of LV diastolic dysfunction and echocardiographic signs of increased end-diastolic pressure in the LV, which was confirmed invasively during coronary and ventricular angiography. In 9 (18.4 %) cases, heart wall thickening was due to hypertrophic cardiomyopathy according to cardiac MRI, these patients had LV outflow tract obstruction and mild pulmonary hypertension at rest. Conducting strain imaging showed the presence of signs of myocardial ischemia (segmental contractility disorder) with varying degrees of severity (from 1 to 5 segments), which spread to the IVS, the apex of the heart and, less often, to the anterior wall of the LV. All patients experienced an increase in pulmonary artery systolic pressure during exercise, on average, from (37.4 ± 2.1) to (47.1 ± 1.6) mm Hg. Conclusions. The pathogenic mechanism underlying shortness of breath in patients with LV myocardial hypertrophy involves transient pulmonary hypertension occurring during exercise due to left ventricular diastolic dysfunction. Another contributing factor is the development of myocardial ischemia during physical exertion, which, in the absence of coronary stenosis and microvascular angina, is attributed to inadequate supply of coronary blood flow volume velocity relative to the significant left ventricular hypertrophy.

Current Insights and Future Directions in the Treatment of Heart Failure with Preserved Ejection Fraction.

Heart failure is a clinical syndrome associated with poor quality of life, substantial healthcare resource utilization, and premature mortality, in large part related to high rates of hospitalizations. The clinical manifestations of heart failure are similar regardless of the ejection fraction. Unlike heart failure with reduced ejection fraction, there are few therapeutic options for treating heart failure with preserved ejection fraction. Molecular therapies that have shown reduced mortality and morbidity in heart failure with reduced ejection have not been proven to be effective for patients with heart failure and preserved ejection fraction. The study of pathophysiological processes involved in the production of heart failure with preserved ejection fraction is the basis for identifying new therapeutic means. In this narrative review, we intend to synthesize the existing therapeutic means, but also those under research (metabolic and microRNA therapy) for the treatment of heart failure with preserved ejection fraction.

Zhenwu Decoction:connotation interpretation based on severe cases and modern pathophysiological mechanisms and application in treatment of heart failure in critical care unit

Zhenwu Decoction is recorded in Treatise on Febrile Diseases by an outstanding physician ZHANG Zhong-jing in the Han dynasty. With effect of warming yang, transforming Qi, and promoting urination, Zhenwu Decoction is mainly used to treat edema due to yang deficiency. The studies of the severe and critical cases and the pathophysiological mechanisms have demonstrated that the record of Zhenwu Decoction in Treatise on Febrile Diseases describes the clinical symptoms and therapeutic regimen of acute heart failure. The syndrome treated by this formula may be related to the misdiagnosis and wrong treatment. Due to the difficult distinguishing between cardiogenic dyspnea and pulmonary dyspnea, high doses of Ephedrae Herba may be misused for inducing sweating, which may finally lead to the acute aggravation of heart failure, electrolyte disorder, and pulmonary infection. The syndrome treated by Zhenwu Decoction can illustrate the lack of experience of ancient physicians in treating acute heart failure. The description of "trembling and shivering" may be the clinical manifestation of heart failure, which is an upgraded version of "trembling and shaking" treated by Linggui Zhugan Decoction.(1)In terms of diseases, Zhenwu Decoction is suitable for the treatment of acute or chronic heart failure, cardiorenal syndrome, and diuretic resistance. The decoction is especially suitable for treating whole heart failure, acute heart failure, heart failure with reduced ejection fraction, and heart failure with the syndrome of sold and dampness. In addition, it can be used to treat both type Ⅱ and type Ⅳ cardiorenal syndrome.(2)In terms of symptoms, Zhenwu Decoction can be used for treating chest tightness, palpitations, lower limb edema, difficult urination or increased urine output, fear of cold, pale fat tongue with teeth marks, white and slippery tongue fur, and deep or slow pulse.(3)In terms of the pharmacological mechanism, Zhenwu Decoction treats heart failure following the principle of promoting urination, expanding blood vessels, and invigorating heart in modern medicine. Aconiti Lateralis Radix Praparata is the sovereign herb in the formula, with the recommended dosage of 30-60 g. However, arrhythmia may be caused by high doses of Aconiti Lateralis Radix Praparata, which should be used with concern. In addition to Zhenwu Decoction, Shenqi Pills, Renshen Decoction, Wuling Powder, and Fangji Huangqi Decoction with the effect of invigorating spleen, replenishing Qi, warming Yang, and promoting urination can be used in the recovery stage. The therapy of reinforcing Yang was the last choice for critical cases due to the lack of medical conditions, unclear clinical diagnosis in history, which should be treated objectively now.

24-year-old obese woman with dilated cardiomyopathy: a case report of obese cardiomyopathy

Background: Dilated cardiomyopathy is a disease characterized by enlargement of the heart ventricles with impaired left ventricular or biventricular systolic function. Obesity is a risk factor for changes in the structure and function of the heart, known as obese cardiomyopathy. The purpose of writing this case report is to holistically discuss obesity as a risk factor for dilated cardiomyopathy based on a literature review. Case presentation: A 24-year-old woman complained of shortness of breath 2 months ago, appeared during activities and while she slept at night, and improved when sitting and resting. Other complaints are palpitations, swollen feet, nausea, and vomiting. Childhood history of obesity. Blood pressure 160/95 mmHg, respiratory rate 22 times/minute, and body mass index 33.8 kg/m2 (obesity II). The jugular venous pressure is increased. Auscultation revealed a systolic murmur at ICS 4 grade 3/6 and pulmonary crackles, with pitting edema in the legs. Electrocardiography revealed sinus tachycardia. Laboratory tests showed high triglycerides and total cholesterol, and other laboratories were within normal limits. Echocardiographic examination showed decreased left ventricular systolic function, severe left ventricular dilatation, and an ejection fraction of 27.9%. No significant lesions were found during the angiographic examination. A magnetic resonance imaging examination revealed non-ischemic cardiomyopathy, moderate left ventricular dysfunction, and severe right ventricular dysfunction. Patients were given heart failure therapy according to guidelines. On routine control, the patient's condition was stable. Conclusion: Obesity is believed to be a risk factor for dilated cardiomyopathy through an increased hemodynamic load, neurohormonal dysregulation, inflammation, and lipotoxicity. Modalities such as the electrocardiogram, echocardiography, and magnetic resonance imaging can support the results of examinations for diagnosing dilated cardiomyopathy due to obesity. The management of obese cardiomyopathy involves changing lifestyles and administering drugs according to the clinical manifestations of heart failure.

Cardiometabolic Care: Assessing Patients with Diabetes Mellitus with No Overt Cardiovascular Disease in the Light of Heart Failure Development Risk.

The mechanisms leading to the development of heart failure (HF) in diabetes mellitus (DM) patients are multifactorial. Assessing the risk of HF development in patients with DM is valuable not only for the identification of a high-risk subgroup, but also equally important for defining low-risk subpopulations. Nowadays, DM and HF have been recognized as sharing similar metabolic pathways. Moreover, the clinical manifestation of HF can be independent of LVEF classification. Consequently, approaching HF should be through structural, hemodynamic and functional evaluation. Thus, both imaging parameters and biomarkers are important tools for the recognition of diabetic patients at risk of HF manifestation and HF phenotypes, and arrhythmogenic risk, and eventually for prognosis, aiming to improve patients' outcomes utilizing drugs and non-pharmaceutical cardioprotective tools such as diet modification.

Exercise-Induced Excessive Blood Pressure Elevation Is Associated with Cardiac Dysfunction in Male Patients with Essential Hypertension.

Cardiopulmonary exercise testing (CPET) has been used to explore the blood pressure response and potential cardiovascular system structure and dysfunction in male patients with essential hypertension during exercise, to provide a scientific basis for safe and effective exercise rehabilitation and improvement of prognosis. A total of 100 male patients with essential hypertension (aged 18-60) who were admitted to the outpatient department of the Center for Diagnosis and Treatment of Cardiovascular Diseases of Jilin University from September 2018 to January 2021 were enrolled in this study. The patients had normal cardiac structure in resting state without clinical manifestations of heart failure or systematic regularization of treatment at the time of admission. Symptom-restricted CPET was performed and blood pressure was measured during and after exercise. According to Framingham criteria, male systolic blood pressure (SBP) ≥210 mmHg during exercise was defined as exercise hypertension (EH), and the subjects were divided into EH group (n = 47) and non-EH group (n = 53). Based on whether the oxygen pulse (VO2/HR) plateau appeared immediately after anaerobic threshold (AT), the EH group was further divided into the VO2/HR plateau immediately after AT (EH-ATP) group (n = 19) and EH-non-ATP group (n = 28). The basic clinical data and related parameters, key CPET indicators, were compared between groups. Body mass index (BMI) visceral fat, resting SBP, and SBP variability in EH group were significantly higher than those in non-EH group. Moreover, VO2/HR at AT and the ratio of VO2/HR plateau appearing immediately after AT in EH group were significantly higher than those in the non-EH group. The resting SBP, 15-minute SBP variability, and the presence of VO2/HR plateau were independent risk factors for EH. In addition, work rate (WR) at AT but also WR, oxygen consumption per minute (VO2), VO2/kg, and VO2/HR at peak were significantly lower in the EH-ATP group compared to the EH-non-ATP group. Peak diastolic blood pressure (DBP) increment and decreased △VO2/△WR for AT to peak were independent risk factors for VO2/HR plateau appearing immediately after AT in EH patients. EH patients have impaired autonomic nervous function and are prone to exercise-induced cardiac dysfunction. EH patients with exercise-induced cardiac dysfunction have reduced peak cardiac output and exercise tolerance and impaired vascular diastolic function. CPET examination should be performed on EH patients and EH patients with exercise-induced cardiac dysfunction to develop precise drug therapy and effective individual exercise prescription, to avoid arteriosclerosis and exercise-induced cardiac damage. The retrospective study protocol was approved by medical ethics committee of the First Hospital of Jilin University (AF-IRB-032-06 No. 2021-015). The study was registered with the Chinese Clinical Trials Register, registration number: ChiCTR2100053140.

LEFT VENTRICULAR REMODELING IN HEART FAILURE (PART I): CURRENT UNDERSTANDING OF PATHOMECHANISMS AND RELATED MYOCARDIAL DYSFUNCTION

Aim: to provide a literature review of the current data on various pathomechanisms of left ventricular (LV) remodeling in heart failure (HF) patients and their role in the development and progression of myocardial dysfunction. This paper is a first part of the review, devoted to the current state of pathophysiology of LV remodeling in HF.
 Material and methods. The thematic scientific papers, published during the last decade, constituted the study material. The research methodology involved bibliosemantic method and structural and logical analysis.
 Results and discussion. LV remodeling is the result of complex changes at the molecular, cellular and tissue levels, affecting the myocardial mass, geometry and performance, and ultimately leading to HF development and progression. LV systolic dysfunction occurs through the numerous mechanisms, including the defects in sarcomere function, abnormal excitation-contraction coupling and calcium homeostasis, ion channel dysfunction, mitochondrial and metabolic abnormalities, depressed cardiomyocytes survival signaling, redox pathobiology, inflammation and inadequate vasculogenesis. The term «LV diastolic dysfunction» covers the alterations in diastolic distensibility, filling or relaxation of the LV, regardless of whether LV (global) systolic function is normal or abnormal, and regardless of whether the patient has clinical manifestations of HF. The up-to-date pathophysiological paradigm of the development and progression of HF with LV diastolic dysfunction and preserved LV (global) systolic function considers systemic inflammation as a key pathomechanism of structural and functional changes of the myocardium, promoted by various cardiovascular and extracardiac conditions. In its turn, the systemic inflammation promotes endothelial dysfunction, contributing to multiple end-organ damage.
 Conclusion. The deepening one`s knowledge of various pathomechanisms of LV remodeling and related myocardial dysfunction in HF patients is an important prerequisite for identifying new perspectives on further fundamental research аnd more rational designing of future clinical trials.

CORRELATION OF BLOOD PRESSURE CHANGES WITH THE FUNCTIONAL CAPACITY IN HEART FAILURE PATIENTS WITH PRESERVED AND MID-RANGE EJECTION FRACTION

Objective: 6-minute walk test (6-MWT) reflects the daily activity of heart failure (HF) patients who develop progressive limitation of functional capacity (FC). Our aim was to assess different blood pressure (BP) parameters and their changes after 6-MWT in patients with HF with mid-range ejection fraction (EF) (HFmEF) and HF with preserved EF (HFpEF) and correlate them with the FC assessed by 6-minute walk distance (6-MWD). Design and method: Patients presented with clinical manifestations of HF were admitted to Cardiology Department and medically stabilized. 40 HFmEF patients and 50 HFpEF patients underwent 6-MWT according to the American Thoracic Society guidelines 2002. Different BP parameters before and after 6-MWT were recorded including systolic blood pressure, diastolic blood pressure (DBP), mean BP, pulse pressure (PP), and proportionate pulse pressure (PPP) defined as the ratio of PP and SBP. Limited FC was defined as 6-MWD < 300 M. Abnormal BP response to exercise (ABPRE) was defined as a decrease, no increase or an increase of the SBP after exercise by < 20 MMHG. Results: The mean 6-MWD was 325.3 ± 56.84 meters (M), 316.1 ± 61.33 M, 332.66 ± 52.44 M in all patients, HFmEF patients, and HFpEF patients respectively. 6-MWD and limited FC showed no significant difference between the 2 groups. Limited FC affected 42.5 % and 33 % of HFmEF and HFpEF patients respectively. ABPRE affected 28 (31.1 %) of patients and was significantly higher in HFmEF than HFpEF patients. Independent predictors of limited FC were lower EF, PP and PPP and higher DBP in HFmEF patients and lower EF in HFpEF patients. Cut-off points for prediction of limited included PP < 32.5 MMHG and PPP < 30.22 % in HFmEF patients, PP < 37.5 MMHG and PPP < 32.67 % in HFpEF patients, and EF < 42.5 % in all patients (figure 1). Conclusions: The 6-MWT is well tolerated by HF patients and easy to perform in clinical practice. Simple bed-side measurement of BP parameters correlated with the FC and predicted limited FC in HFmEF and HFpEF patients.

Short-term anthracyclines-induced cardiotoxicity in breast cancer patients.

e18703 Background: Anthracycline-containing regimens are effective treatment of early breast cancer; however, they can induce irreversible myocardial damage, leading to significant morbidity and mortality. The main aim of this study was to describe and evaluate early anthracycline cardiotoxicity. Methods: This was a prospective study including breast cancer patients who where candidates for adjuvant anthracycline-based chemotherapy. Patients were assessed at baseline with history, physical exam, standard 12-lead electrocardiography (ECG) and 2D echocardiography, and then shortly after completion of anthracycline-based chemotherapy. We reported the ECG parameters, LVEF calculated using Simpson's biplane method and global longitudinal strain (GLS). Cardiotoxicity was defined as a decline ≥ 5% in LVEF accompanied or not by clinical manifestations of heart failure, or a decline ≥ 10% in GLS. Statistical analysis was performed using SPSS version 26. For comparisons, we used two-tailed Student's t-test. Associations between risk factors and cardiotoxicity were assessed using linear and logistic regression; a p value < 0.05 was considered significant. Results: 171 patients with stage I (10.3%), stage II (81%) or stage III (8.7%) invasive ductal breast carcinoma, with a mean age of 48,1 ± 10 years. Obesity was found in 59 patients and 92 were overweight. Among comorbidities, hypertension was present in 11.7%, diabetes mellitus in 5.2%, and dyslipidemia in 4.6%. The most common concomitant medications were β-blockers in 6.4%, followed by angiotensin II receptor blockers in 5.2%, Statins in 4.6%, biguanides in 5.2%. Cardiac function was assessed 12 ± 7 days before and 19 ± 8 days post chemotherapy. 94 patients received Doxorubicin with a cumulative dose of 240 mg/m2, and 77 received Epirubicin with a cumulative dose of 300 mg/m2. Subclinical Cardiotoxicity was observed in 9 patients (5.2%), defined as a decline ≥ 5% in LVEF and in one patient (0.5%) defined by GLS decline ≥ 10%. This patient had the lowest post-therapy LVEF (40.2%) of the cohort. LVEF and GLS although reduced significantly after treatment, remained within the normal range. (LVEF: 62.8 ± 3% vs. 58 ± 6%, p = 0.03), (GLS: -19.0 ± 2.4% vs. -17.1 ± 1.0%, p = 0.01). Patients receiving Doxorubicin had lower LVEF compared to Epirubicin after therapy (57.1 ± 2% vs. 61.4 ± 2%, p = 0.03). Additionally, we found significant ECG changes in Heart Rate (72.6 ± 11,6 vs. 85.2 ± 14.4 bpm, p = 0.013) and QTc (410.1 ± 24.9 vs. 427.7 ± 26.5 ms, p = 0.032). Cardiotoxicity was not associated with any cardiovascular risk factors. Doxorubicin use was the only risk factor, confirmed on multivariate analysis (p = 0,02). Conclusions: Anthracycline-based chemotherapy has detrimental subclinical effect on electrical activity and left ventricle systolic function in the short term after adjuvant chemotherapy. We did not observe any significant effect of risk factors, it is therefore important to monitor all patients.

Telemedical Monitoring Based on Implantable Devices-the Evolution Beyond the CardioMEMS™ Technology.

Purpose of the ReviewWe aimed to provide an overview of telemedical monitoring and its impact on outcomes among heart failure (HF) patients.Recent FindingsMost HF readmissions may be prevented if clinical parameters are strictly controlled via telemedical monitoring. Predictive algorithms for patients with cardiovascular implantable electronic devices (e.g., Triage-HF Plus by Medtronic or HeartLogic by Boston Scientific) were developed to identify patients at significantly increased risk of HF events. However, randomized control trial-based data are heterogeneous regarding the advantages of telemedical monitoring in HF patients. The likelihood of adverse clinical outcomes increases when pulmonary artery pressure (PAP) rises, usually days to weeks before clinical manifestations of HF. A wireless monitoring system (CardioMEMS™) detecting changes in PAP was proposed for HF patients. CardioMEMS™ transmits data to the healthcare provider and allows to institute timely intensification of HF therapies. CardioMEMS™-guided pharmacotherapy reduced a risk of HF-related hospitalization (hazard ratio [HR]: 0.72; 95% confidence interval (CI) 0.60–0–0.85; p < 0.01).SummaryRelevant developments and innovations of telemedical care may improve clinical outcomes among HF patients. The use of CardioMEMS™ was found to be safe and cost-effective by reducing the rates of HF hospitalizations.

Impaired Left Ventricular Ejection Fraction Induces “Very Early Pre-Diagnostic” Hemopoietic Modifications in Myeloid Leukemia Patients

Background: There is strong association between clonal hematopoiesis of undetermined prognosis (CHIP) and coronary artery disease (CAD) development. Indeed, ischemic heart disease is a leading cause of congestive heart failure (CHF) in western society. CH induces not only enhanced risk for myeloid malignancies, but also significant cardiovascular morbidity in elderly patients (pt). Pt with impaired ejection fraction (EF) and clinical manifestation of heart failure frequently initiates systemic pro-inflammatory state [SPS] characterized by interleukin-6 (IL6) and tumor necrosis factor alpha (TNF-α) upregulation. Previous studies suggest that such an inflammatory state is capable of sustaining and/or accelerating hemopoietic clonal selection/dominance. How these CHF induced inflammatory changes affect “peripheral blood cell count composition' in pt with suspected CHIP is unknown. However, modifications in peripheral blood count data ”months before hemopoietic malignancy diagnosis“ may inform association between clonal dynamics and hemopoietic output under CHF stress. The primary objective of our study was to investigate effect of heart failure in ”pre- AML diagnosis“ peripheral blood count data to detect ”early“ hemopoietic modifications induced by CHF. Methods: After IRB approval, AML pt diagnosed with and without CHF were selected for analysis. Given possible differential inflammatory effect between pt exhibiting CHF with and with low EF, we analyzed peripheral blood cell count in pt with ”echocardiographically confirmed“ EF <> 50% and those pt with and without clinically documented CHF [cdCHF]. Descriptive statistics was performed for categorical and continues variable with Chi-square and t-test. SAS software was used for analysis. Results: 27/152 (17.7%) and 125/152 (82.2%) pt developed or not EF <50%. Median age was 71.1 years (y) v 61.2 y, in pt with and without EF<50%, p=<0.0001. Aging was negatively correlated with EF, [R= -0.25, p=0.001]. Median age was 73 y v 61 y, for pt with and without cdCHF, p=0.001. 100% and 82% of pt were male among those with and without EF <50%. In pt who had or did not have EF <55% Favorable (fav), Intermediate (Int) and unfavorable (unfav) ELN-2017 subgroups were 3.23% vs 13.6%; 42% vs 46%; and 55% vs 40%, p=0.07. To address our main hypothesis that CHF induces ”early pre-diagnostic AML' hemopoietic modifications, CBC data at 6 and 12 months (m) before AML onset in pt with and without EF<50% v those with and without cdCHF was extracted. At 12 m prior AML diagnosis, EF<> 50% detected differential expression for WBC [p=0.07], Hemoglobin [p=0.002], platelets [p=0.05] and absolute lymphocyte count (ALC) [p=0.006] [Fig 1, panel A, C, I, K]. Similarly, EF <>50% at 6 m prior AML diagnosis detected differential expression for platelets [p=0.01], ALC [p=0.04] [Fig 1, panel D, J, L]. In contrast, cdCHF detected only differential hemoglobin at 12 m [p=0.01]. Conclusions: CHF induces quantitative count defects 6 and 12 m before AML diagnosis. Changes are characterized by WBC, hemoglobin, platelets and ALC decline that are directly correlated with objective left ventricular EF impairment, but not with only clinical CHF. Our study adds body of evidence to support the role of CHF with low EF as “hemopoietic cell extrinsic stressor'. CHF associated with low EF seems to be prerequisite for hemopoietic stress in hosts with already initiated clonal hematopoiesis. Our findings have important experimental implications, especially for studies that seek to understand how cell extrinsic stressors facilitate clonal progression. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Study protocol: Traditional Chinese Medicine (TCM) syndrome differentiation for heart failure patients and its implication for long-term therapeutic outcomes of the Qiliqiangxin capsules

BackgroundSyndrome differentiation is a commonly used methodology and practice in Traditional Chinese Medicine (TCM) guiding the diagnosis and treatment of diseases including heart failure (HF). However, previous clinical trials seldom consider the impact of syndrome patterns on the outcome evaluation of TCM formulae. Qiliqiangxin (QLQX) capsule is a TCM formula with cardiotonic effect to improve the cardiovascular function for heart failure with proven efficacy from well-designed clinical trials. Though, there is no clinical trial with a large sample size and long assessment period that considers the relationship between TCM syndrome differentiation and the treatment efficacy of QLQX. In the present study, we design a study protocol to evaluate the relationship between TCM syndrome differentiation and the severity of heart failure as well as its progression. Furthermore, we will evaluate the impact of the TCM syndrome patterns on the efficacy of QLQX in the outcome of heart failure.MethodsThis is a clinical study conducted in conjunction with an ongoing clinical trial (QUEST Study) by sharing the parent patient populations but with different aims and independent designed roadmaps to investigate the TCM syndrome pattern distributions and the impacts of syndrome pattern types on the efficacy of QLQX in HF treatment. The clinical trial involves over 100 hospitals in mainland China and Hong Kong SAR with 3080 HF patients. By assessing the morbidity and re-hospitalization, we will verify and apply a modified TCM Questionnaire to collect the clinical manifestations of HF and acquire the tongue images of the patients to facilitate the syndrome differentiation. We will base on the “2014 Consensus from TCM experts on diagnosis and treatment of chronic heart failure” to evaluate the TCM syndromes for the patients. A pilot study with at least 600 patients will be conducted to evaluate the reliability, feasibility and validity of the modified TCM questionnaire for syndrome differentiation of HF and the sample size is calculated based on the confidence level of 95%, population size of 3080 and 5% margin of error. Secondly, we will investigate the characteristic of TCM syndrome distribution of HF patients and its correlation with the functional and biochemical data. Furthermore, we will evaluate the relationship between the TCM syndrome patterns and the efficacy of QLQX in the treatment of heart failure. Lastly, we will investigate the implication of tongue diagnosis in the severity and therapeutic outcome of HF.Expect outcomesTo our knowledge, this is the first large scale clinical trial to evaluate the impacts of TCM syndrome differentiation on the progression and therapeutic outcome of HF patients and explore the diagnostic value of TCM Tongue Diagnosis in HF patients. We expect to obtain direct clinical evidence to verify the importance of TCM syndrome differentiation for the diagnosis and treatment of HF.Trial Registration: The trial was registered at Chinese Clinical Trial Registry, http://www.chictr.org.cn. (Registration No.: ChiCTR1900021929); Date: 2019-03-16.

Ефективність антагоністів альдостерону у хворих на інфаркт міокарда, ускладнений гострою лівошлуночковою недостатністю із збереженою систолічною функцією лівого шлуночка

Актуальність. Гострий інфаркт міокарда (ГІМ) залишається провідною причиною смертності в Україні та світі загалом. Мета. Аналіз впливу еплеренону на перебіг захворювання у хворих на ГІМ, ускладнений розвитком гострої лівошлуночкової недостатності (ГЛШН) із збереженою фракцією викиду лівого шлуночка. Матеріали та методи. Обстежено 137 хворих на ГІМ з елевацією сегмента SТ, ускладнений ГЛШН. Пацієнти розподілені на дві групи: 1-ша група — 65 хворих, які отримували еплеренон, 2-га група — 72 хворих, які не приймали препаратів із групи антагоністів альдостерону. Усі хворі отримували базисну терапію. З них 87 хворим проведена тромболітична терапія. Оцінено клінічні прояви серцевої недостатності (СН), результати ЕхоКС, концентрації N-термінальної мозкової фракції натрійуретичного пропептиду (NT-pro BNP). Результати. Доведений регрес клінічної симптоматики СН, який корелював із позитивною динамікою NT-pro BNP і розмірів камер серця на фоні прийому препарату у складі комплексної терапії ГІМ. Крім того, на фоні тривалого систематичного прийому еплеренону відзначена достовірна позитивна динаміка прогностичних маркерів перебігу післяінфарктного періоду у досліджуваних пацієнтів. Висновки. Застосування еплеренону спричинює гальмування процесів ремоделяції ЛШ у хворих на ГІМ, сприяє контролю об’єму рідини, що зумовлює зменшення та поступовий регрес проявів СН навіть після перенесеної ГЛШН.

Прогнозування та діагностика правошлуночкової серцевої недостатності та дисфункції шлуночків серця в період загострення бронхіальної астми у дітей

Актуальність. Бронхіальна астма (БА) вже в дитячому віці може супроводжуватись серцево-судинними ускладненнями у вигляді синдрому гострого легеневого серця, дисфункції шлуночків серця, метаболічної кардіоміопатії, порушень ритму і провідності, що не тільки обтяжує перебіг захворювання, але й додатково знижує якість життя пацієнтів. Ремоделювання серця при БА передує клінічним проявам серцевої недостатності та може самостійно поглиблювати систолічну і діастолічну дисфункцію шлуночків. Мета. Удосконалення прогнозування розвитку серцево-судинних ускладнень у період загострення БА в дітей шляхом визначення факторів ризику розвитку дисфункції шлуночків і розробки додаткових інформативних клініко-ехокардіографічних діагностичних критеріїв правошлуночкової серцевої недостатності. Матеріали та методи. Під нашим спостереженням перебували 85 дітей, хворих на БА, віком від 5 до 17 років, у яких застосовано методи пульсоксиметрії, спірографії, електрокардіографії, допплер-ехокардіографії. Обстеження проводилось у періоді загострення БА при госпіталізації хворого і в періоді поліпшення стану, на 5–6-ту добу перебування у відділенні пульмоалергології комунального закладу «Обласна дитяча клінічна лікарня» Дніпропетровської обласної ради. Критеріями включення в дослідження були алергічна та змішана персистуюча средньотяжка і тяжка астма в період загострення. В дослідження не ввійшли хворі на БА діти в період ремісії, діти з інтермітуючим перебігом астми та легкою персистуючою БА. Для визначення типу й ступеня вентиляційної недостатності використовували метод спірографії з оцінкою показників життєвої ємності легень (ЖЄЛ), об’єму форсованого видиху за 1 секунду (ОФВ1), ОФВ1/ЖЄЛ. Математичне і статистичне опрацювання матеріалів дослідження проводили з використанням методів біостатистики, реалізованих у пакетах програм Microsoft Excel (Office Home Business 2KB4Y-6H9DB-BM47K-749PV-PG3KT), Statistica 6.1 (StatSoft Inc., серійний № AGAR909E415822FA). Результати. Визначено прогностичні клінічні фактори ризику розвитку систоло-діастолічної дисфункції шлуночків серця у випадку можливого нападу БА, до яких було віднесено: наявність у хворої дитини БА тяжкого перебігу; наявність тахікардії у спокої; порушення реполяризації в міокарді шлуночків на електрокардіограмі; наявність у хворого на астму супутнього хронічного тонзиліту; бактеріоносійство у носоглотці; жіночу стать. Розроблено додаткові інформативні діагностичні критерії розвитку правошлуночкової серцевої недостатності в період загострення БА у дітей. Установлено, що застосування еуфіліну поряд із ­b2-агоністами для бронхолітичної терапії дітей у період загострення БА негативно впливає на діастолічну функцію шлуночків серця і сприяє збереженню підвищеного тиску в легеневій артерії. Висновки. Питання покращення можливостей прогнозування розвитку дисфункції шлуночків серця та своєчасної діагностики серцево-судинних ускладнень у період загострення БА у дітей вирішується шляхом визначення клінічних факторів ризику розвитку дисфункції шлуночків і розробки додаткових інформативних клініко-ехокардіографічних діагностичних критеріїв правошлуночкової серцевої недостатності.

Comorbidities and risk factors associated with new onset heart failure in type 2 diabetes

Type 2 diabetes (T2D) is a prevalent comorbidity in both reduced ejection fraction (HFrEF) and preserved heart failure (HFpEF). However, comorbidities and risk factors associated with new onset of heart failure (HF), distinguishing HFrEF and HFpEF in T2D patients have never been investigated. The objective of our study is to assess the occurrence of HF in a T2D population, to identify the clinical factors associated with HFrEF compared to HFpEF. We retrospectively analyzed 966 T2D patients followed in our institution. New onset HF was defined as a clinical manifestation of HF or increased HF therapy. We studied the overall occurrence of HF, HFpEF (EF ≥ 50%) and HFrEF (EF < 50%). Nine hundred sixty-six T2D patients were included (58.7 ± 11.9 years, 368 women). Over a median follow-up of 10 years, 77 (8%) patients had a new onset HF event. HF patients were older ( P < 0.001), more frequently in atrial fibrillation (AF) ( P < 0.001) and had more cardiovascular (CV) events ( P < 0.001). HFpEF patients ( n = 27) compared to HFrEF ( n = 50) are significantly older (71.1 ± 8.5 vs. 66.6 ± 9.5 years, P = 0.04) and have more comorbidities such as AF (56% vs. 32%, P = 0.04), higher blood pressure (150 ± 27 vs. 130 ± 28 mmHg, P = 0.005), higher body mass index (34 ± 6 vs. 30 ± 5.6 kg/m 2 , P = 0.004) and sleep apnea (44% vs. 28%, P < 0.001). Prevalence of history of coronary artery disease is similar between HFpEF and HFrEF (33% vs. 38%, P = 0.7). Interestingly, history of non-ST segment elevation myocardial infarction (NSTEMI) was comparable between HFpEF and HFrEF (19% vs. 22%, P = 0.72). By contrast, none of the HFpEF patients had a history of ST elevation segment myocardial infarction (STEMI) (0% vs. 16%, P = 0.03) ( Fig. 1 ). Patients who develop HF in the T2D population have more CV comorbidities including history of acute coronary syndrome. History of STEMI before HF is strictly associated with the occurrence of HFrEF.

Heart failure: the influence of different types on the main arteries kinetics

Abstract Funding Acknowledgements Type of funding sources: None. Nowadays the term "heart-vessels failure" does not exist. Aim To study the kinetics and hemodynamics of arteries in the patients with heart failure with different ejection fraction. Materials and methods In our investigation we included 74 patients with heart failure with preserved ejection fraction more than 55% (44 were men and 30 women). Mediana age – 71,3 years old. In the control group we included 52 practically healthy people without cardiac and vessels pathologies. We divided patients into two groups (I and II) in accordance to the presence of clinical manifestations of heart failure in them. Group I - with clinical symptoms of heart failure (32), group II –without heart failure symptoms (42). We paid attention to the symptoms of heart failure, myocardial infarction, cardiomyopathies, valves defects, operations on heart in anamnesis. We performed 24-hours ECG monitoring, general blood analysis, biochemical blood analysis (lipids, electrolytes, urine, creatinine, bilirubin, potassium, glucose, NT-proBNP), transthoracic echocardiography, ultrasound doppler of brachiocephalic arteries, abdominal aorta branches, lower extremities arteries, renal arteries, chest radiography, ultrasound investigation of B-lines. If prescribed we performed stress echocardiography, transesophageal echocardiography, coronary angiography, renal arteries angiography, pancerebral angiography, magnet tomography of heart. All patients were registered sphygmography of main arteries: a.carotis communis, ulnaris, radialis, a.tibialis posterior. We analyzed the regular contractions in each type of arteries. The main parameters main arteries kinetics using sphygmography we calculated in automatic mode: speed, acceleration, power, work in period of prevalence of inflow over outflow and in period of prevalence of outflow over inflow. Results We analysed the main parameters of arteries kinetics and hemodynamics in each group of patients as well as in control group. We observed the effects: 1)In group II the parameters of arteries kinetics were higher than in group I. It indicates the active propulsive work of arteries in spreading the stroke volume of the heart. 2)In group I the parameters of arteries kinetics were lower than in control group. It indicates that propulsive function of the arteries is reduced in patients with heart failure. Conclusion Arterial vessels are active, full-fledged participant in cardiovascular system. Vessels make an active work in blood movement from the heart to the distal parts and tissues. The clinical manifestations of heart failure are determined not only the heart function but also the function of arteries that is needed to be examined. In patients with preserved ejection fraction we can observe the symptoms of heart failure, the function abilities of arteries are reduced. The term "heart-vessels failure" should be used and applied not only to the heart but also to the arteries function in their coupling with heart. Abstract Figure.

IRON DEFICIENCY IN COMORBIDITY CHRONIC HEART FAILURE AND DIABETES MELLITUS

The clinical significance of iron deficiency in patients with a combination of heart failure and diabetes meLLitus has not been studied. 67 patients with chronic heart failure and diabetes meLLitus were examined. In aLL patients, the clinical manifestations of heart failure, asthenia, anxiety, depression, the concentration of glucose, glycated hemoglobin, iron, ferritin, transferrin, soluble transferrin receptors, hepcidin, erythropoietin, NT-proBNP were studied, echocardiography was performed in one-dimensionaL, two-dimensional and DoppLer modes (wave, constant-wave and tissue) in standard positions according to the generally accepted technique. Iron deficiency was diagnosed in 42 patients. We have established that the deficiency of iron stores in patients with heart failure and diabetes meLLitus contributes to an increase in the cLinicaL manifestations of heart failure, asthenia, anxiety and worsens the indicators of central hemodynamics.It was found that the deficiency of iron store in patients with heart failure and diabetes meLLitus contributes to the disruption of various Links of iron metabolism and an increase in the cLinicaL manifestations of heart failure, asthenia, anxiety and deterioration of central hemodynamic parameters.

PERIPARTUM CARDIOMYOPATHY – A CLINICAL CASE

This article presents a clinical case of peripartum cardiomyopathy in a 21-year-oldpatient with a gestational age of 32 weeks, accompanied by clinical manifestationsof heart failure and Lown-Ganong-Levine (LGL) syndrome. The patient underwentlaboratory and instrumental examinations, including echocardiography and Holtermonitoring. Thyrotoxic cardiomyopathy was ruled out in the process of differentialdiagnosis. The final diagnosis and management of the patient were determinedafter consultation with the State Institution "Institute of Pediatrics, Obstetrics andGynecology, named after Academician O.M. Lukyanova, of the National Academy ofMedical Sciences of Ukraine". Medical treatment significantly improved the patient'scondition and vaginal delivery went without complications. Manifestations of theperipartum cardiomyopathy gradually regressed and completely disappeared 6 monthsafter delivery.This case indicates the importance of timely diagnosis of peripartum cardiomyopathyfor a positive prognosis of patients.

Diastolic dysfunction for nephrologists: diagnosis at the point of care.

Cardiovascular diseases are important causes of morbidity and mortality in the course of chronic kidney disease (CKD). Diastolic dysfunction (DD) may progress with the clinical manifestation of heart failure, known as heart failure with preserved ejection fraction, a condition that precedes systolic dysfunction. The early identification of DD by echocardiography at the point-of-care before the appearance of symptoms and signs of pulmonary congestion and the implementation of appropriate treatment can improve the prognosis of CKD. This review article briefly addresses DD in kidney disease and presents a practical approach to the echocardiographic diagnosis of DD at the point of care.