Clinical Manifestations Of Heart Failure Research Articles

Coronary microvascular dysfunction in heart failure: observations from the MICRO registry

Abstract Background Heart failure (HF) is one of the leading causes of hospitalization in the elderly. Coronary microvascular dysfunction (CMD), among other risk factors, is linked to the pathogenesis and clinical manifestations of HF. Purpose This abstract aims to summarize key findings from a comprehensive analysis of CMD in subgroups of HF, shedding light on its association with hemodynamic parameters. Methods Patients experiencing recurrent angina (CCS II-IV) and no relevant epicardial stenosis were enrolled in a prospective registry (MICRO). Epicardial and microvascular responses (pressure, resistance and flow) were assessed at rest and during adenosine and acetylcholine testing. The impact of an elevated left ventricular end-diastolic pressure (LVEDP) in the absence of clinical signs of HF was also investigated. Results Overall, 188 patients (63% (118) women, mean age 65±11 years) with angina and no epicardial stenosis were enrolled. Patients with HF (n=26) displayed lower hyperemic flow in response to endothelium-independent adenosine (5.2±3.1 vs. 7.3±4.4; P=0.004), lower coronary flow reserve (2.9±1.5 vs. 4.4±1.1; P<0.001) and microvascular resistance reserve (3.3±2.1 vs. 5.2±2.7; P<0.001), and increased microvascular resistance during adenosine-induced hyperemia (25±21 vs. 17±11; P=0.045). An increased LVEDP without clinical signs of HF was not associated with a lower coronary flow reserve (4.3±1.9 vs. 2.6±1.2; P=0.006) or microvascular resistance reserve (4.9±2.1 vs. 2.8±1.7; P=0.004). Microvascular resistance during acetylcholine (endothelium-dependent)-induced hyperemia was lower in HF patients (36.2±23.5 vs. 57.4±37.8; P=0.018). Conclusion(s) Patients with heart failure displayed signs of impaired microvascular endothelium-independent responses while endothelium-dependent reactivity appears to be maintained. An elevated LVEDP without clinical HF was not associated with impaired coronary microvascular function.

Heart failure misdiagnosed as acute cholecystitis: a case report

BackgroundHeart failure is a clinical syndrome characterized by decreased cardiac output, leading to systemic organ hypoxia and resulting in dyspnea, pulmonary edema, organ congestion, and pleural effusion. Owing to the diverse clinical manifestations of heart failure, early diagnosis can be challenging, and misdiagnosis may occur occasionally. The use of echocardiography and blood brain natriuretic peptide can aid in obtaining a more accurate diagnosis.Case presentationThis article presents two case reports of patients who were misdiagnosed with acute cholecystitis. Both patients were young Mongolia males (age 26 and 39 years) who presented to the emergency department with acute upper abdominal pain, abdominal ultrasound revealed gallbladder enlargement, and blood tests suggested mild elevation of bilirubin levels. However, despite the absence of procalcitonin and C-reactive protein elevation, the patients were admitted to the general surgical department with a diagnosis of “acute cholecystitis.” Both patients were given treatment for cholecystitis, but their vital signs did not improve, while later examinations confirmed heart failure. After treatment with diuretics and cardiac glycosides, both patients’ symptoms were relieved.ConclusionWe aim to highlight the clinical manifestations of heart failure and differentiate it from rare conditions such as acute cholecystitis. Physicians should make accurate diagnoses on the basis of physical examinations, laboratory testing and imaging, and surveys while avoiding diagnostic heuristics or mindsets. By sharing these two case reports, we hope to increase awareness to prevent potential complications and improve patient outcomes.

Possibilities of mitochondrial dysfunction diagnosis in chronic heart failure

The article presents preliminary study results of association of direct ultrastructural characteristics of mitochondria (MTC) in cardiomyocytes and indirect signs of mitochondrial dysfunction with clinical course and outcomes of chronic heart failure (CHF). According to electron microscopy of the myocardium a violation of the ultrastructure of MTC of cardiomyocytes is accompanied by a decrease in the rate of oxygen absorption by mitochondria of leukocytes of peripheral blood, separation of oxidation and phosphorylation processes, an increased rate of radiopharmaceuticals leaching from myocardium, indicating mitochondrial membrane damage, low tolerance to physical load and reduced oxygen consumption at peak of load test, which confirms the feasibility of studying associations of indirect signs of mitochondrial dysfunction with ultrastructural changes in the mitochondrial cardiomyocytes and clinical manifestations of heart failure.

TRANSFORM-HF Trial: Choice of loop diuretic in acute heart failure does not matter!

ABSTRACT The major clinical manifestations of heart failure (HF) are due to fluid retention and congestion, and thus, therapy targeting congestion plays a central role in HF management. Furosemide is by far the most commonly prescribed loop diuretic. However, data primarily derived from observational and small randomized trials point toward potential advantages with torsemide use including improvement in functional status, survival, and hospitalization for HF. The TRANSFORM-HF study aimed to answer a pragmatic query faced by physicians managing HF – Does the choice of loop diuretic matter in HF? There was no benefit of torsemide over furosemide in this large study of >2800 patients for mortality, hospitalization, and quality of life. Though, there were a few shortcomings of the study, the results are in sync with current HF guidelines which do not advocate the use of one loop diuretic or other. Hence, the focus in acute HF should be on optimizing the diuretic dose and other guideline-based therapies rather than the type of diuretics. Recent trials of acetazolamide and other diuretics have shown benefits when used in conjunction with loop diuretics. Since the primary care physician is often the first point of medical contact, the manuscript aims to provide insights into their practice. The message is clear that in acute heart failure, there is no benefit of choosing the type of loop diuretic and impetus should be on adding other class diuretics if needed as well as initiating other guideline-directed medical therapies.

Transluminal balloon angioplasty and stenting of coronary arteries after prior orthotopic heart transplantation: a case report

Introduction. Today, heart failure (HF) is the most common natural outcome of diseases that are not diagnosed and treated in time. Despite the advances in cardiovascular pharmacotherapy, orthotopic heart transplantation is a generally recognized gold standard for the treatment of end-stage heart failure.Brief description. The article describes a 55-year-old male patient admitted to the Cardiology Dispensary (Kabardino-Balkarian Republic) with a clinical picture of non-ST segment elevation acute coronary syndrome (ACS). Earlier in 2017, the patient underwent orthotopic heart transplantation (OHT) for end-stage HF due to dilated cardiomyopathy. Hypertension was registered 2,5 years after surgery, and clinical manifestations of HF were registered for 5 years. In 2024, coronary angiography revealed subtotal stenosis of 95% in the middle segment of the anterior descending artery. Intraoperatively, the consensus assessed the risk and made a decision on surgical endovascular treatment of the stenosis. The postoperative period was uneventful.Discussion. The presented case is an example of timely diagnosis of coronary artery disease in a transplanted heart and successful transluminal balloon angioplasty and stenting of the anterior descending artery.

Modified Ross score and echocardiographic score in children with heart failure: a subgroup analysis

Background Over the past two decades, heart failure in children has increased in terms of symptom recognition and prevalence. The initial clinical manifestations of heart failure in children are non-specific. Therefore, diagnosis requires the support of echocardiography. The symptomatic severity of heart failure in children can be classified through a simple scoring system such as Ross score. The duration of heart disease, duration of therapy, and cardiac remodeling status may have clinical and anatomical effects on the disease. Objective To analyze for a possible correlation between modified Ross score and echocardiographic score by subgroup analysis consisting of duration of heart disease, duration of therapy, and cardiac remodeling. Methods This cross-sectional study included children aged 1 month - 18 years with heart failure who sought treatment at Prof.Dr. I.G.N.G Ngoerah Hospital, Denpasar from June 2019 to February 2020. Cardiac remodeling was defined as >20% increase in left ventricle internal end diastolic dimension (LVIDd) compared to normal values, ??based on body surface area. Spearman’s correlation test was used for statistical analysis. Results A total of 30 subjects were analyzed in this study. The median modified Ross score and echocardiography score were 3 points (range 2-11) and 4 (range 2-6), respectively. The median durations of heart disease and preventive heart failure therapy were 2 years (range 7 days-15 years) and 1 year (range 7 days-15 years), respectively. The mean LVIDd was 4.3 (SD 1.4) cm. Twenty-one out of 30 subjects experienced a ? 20% increase of LVIDd from baseline. The modified Ross score and echocardiographic score had no significant correlation (r=0.18; P=0.33). However, the modified Ross score had significant correlations with duration of heart disease (r=-0.632; P<0.001) as well as duration of therapy (r=-0.584; P=0.001). In addition, no correlation was found between echocardiographic score with heart disease and therapy duration (P>0.05). Echocardiography score and remodelling process was significantly correlated (r=0.64; P<0.001). Conclusion There is no correlation between modified Ross score and echocardiographic score. Duration of heart disease and duration of therapy are significantly negatively correlated with modified Ross scores. The remodelling process is positively correlated with echocardiographic score. Further research on acute symptomatic and validated echocardiographic scores are needed.

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 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 shows 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.

ЭФФЕКТИВНОСТЬ ВНУТРИВЕННОГО ВВЕДЕНИЯ ЖЕЛЕЗА (III) ГИДРОКСИД САХАРОЗНОГО КОМПЛЕКСА У ПАЦИЕНТОВ С ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТЬЮ С СОХРАНЕННОЙ ФРАКЦИЕЙ ВЫБРОСА И ДЕФИЦИТОМ ЖЕЛЕЗА

Abstract. Introduction. Iron deficiency is diagnosed in 59% of patients with chronic heart failure with preserved ejection fraction. The efficacy of iron therapy in these patients has not been studied. Aim. The purpose of the study is to study the effectiveness of intravenous administration of iron (III) hydroxide sucrose complex in patients with chronic heart failure with preserved ejection fraction and iron deficiency. Material and methods. A study was conducted on 55 patients with ischemic heart disease and/or hypertension complicated by chronic heart failure with preserved ejection fraction with iron deficiency (14 men and 41 women), mean age 71.88±6.90 years. Patients of the main group (30 people) in addition to traditional therapy received iron (III) hydroxide-sucrose complex, patients of the control group (25 people) received only traditional therapy. In all patients, functional activity, the severity of clinical manifestations, asthenia, anxiety, depression, quality of life were assessed, echocardioscopy, complete blood count, and iron metabolism were determined. All examinations in the main and control groups were performed before the start of the study, after 2 weeks of therapy, 2 and 6 months after the end of treatment. Statistical analysis of the results at different observation times was performed using Stata/MP version 14.0 and MedCalc Statistical Software version 18.2.1. Results and discussion. The inclusion of iron (III) hydroxide sucrose complex in the complex therapy of iron-deficient patients with chronic heart failure with preserved ejection fraction increases the level of iron, ferritin, hemoglobin and transferrin iron saturation and reduces clinical manifestations of heart failure, severity of asthenia, anxiety, depression and increases physical performance and quality of life. The positive effect of the iron preparation appears by the end of the course of treatment, reaches a maximum after 2 months and lasts for 6 months. Conclusion. To increase the effectiveness of the treatment of patients with chronic heart failure with preserved ejection fraction and iron deficiency, it is recommended to conduct complex therapy, including, in addition to traditional treatment the administration of iron (III) sucrose hydroxide complex.

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.