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1.
Article in English | MEDLINE | ID: mdl-38986509

ABSTRACT

BACKGROUND AND HYPOTHESIS: Heart failure is characterized as cardiac dysfunction resulting in elevated cardiac filling pressures with symptoms and signs of congestion. Distinguishing heart failure from other causes of similar presentations in patients with kidney failure is challenging but necessary, and is needed in randomized controlled trials (RCTs) to accurately estimate treatment effects. The objective of this study was to review heart failure events, their diagnostic criteria and adjudication in RCTs of patients with kidney failure treated with dialysis. We hypothesized that heart failure events, diagnostic criteria and adjudication were infrequently reported in RCTs in dialysis. METHODS: We conducted a meta-epidemiologic systematic review of RCTs from high impact medical, nephrology and cardiology journals from 2000 to 2020. RCTs were eligible if they enrolled adults receiving maintenance dialysis for kidney failure and evaluated any intervention. Results. Of 561 RCTs in patients receiving dialysis, 36 (6.4%) reported heart failure events as primary (10, 27.8%) or secondary (31, 86.1%) outcomes. 10 of the 36 (27.8%) RCTs provided heart failure event diagnostic criteria and 5 of these 10 (50%) adjudicated heart failure events. These 10 RCTs included event diagnostic criteria for heart failure or heart failure hospitalizations, and their criteria included dyspnea (5/10), edema (2/10), rales/crackles (4/10), chest x-ray pulmonary edema or vascular redistribution (4/10), treatment in an acute setting (6/10) and ultrafiltration or dialysis (4/10). No study explicitly distinguished heart failure from volume overload secondary to non-adherence or underdialysis. CONCLUSION: Overall, we found that heart failure events are infrequently reported in RCTs in dialysis and are heterogeneously defined. Further research is required to develop standardized diagnostic criteria that are practical and meaningful to patients and clinicians.

2.
Article in English | MEDLINE | ID: mdl-38986512

ABSTRACT

BACKGROUND: Patients undergoing aortic valve replacement (AVR) have high readmission rates. Several risk factors have been proposed as potential modifiable targets, including anemia. We examined the association between anemia at discharge and subsequent outcomes in these patients. METHODS: Using Danish nationwide registries, we identified all patients who underwent AVR between 2015-2021, were alive at discharge (index date), and had an available hemoglobin (Hb) measurement taken between procedure and discharge. Patients were categorized as having i) moderate/severe anemia (Hb<6.2 mmol/L) or ii) no/mild anemia (Hb≥6.2 mmol). The one-year rates of all-cause mortality, all-cause hospital admission, heart failure (HF) admission, and atrial fibrillation (AF) admission were compared using multivariable Cox regression models. RESULTS: 8,614 patients were identified; 2,847 (33.1%) had moderate/severe anemia (60.2% male, median age 74) and 5,767 (66.9%) had no/mild anemia (68.0% male, median age 76). For these two groups, respectively, the cumulative one-year incidences of the outcomes were: i) all-cause mortality: 5.1% vs. 4.3%; ii) all-cause admission: 53.8% vs. 47.5%; iii) AF admission: 14.0% vs. 11.6%); iv) HF admission: 6.8% vs. 6.2%. In adjusted analysis, moderate/severe anemia, compared with no/mild anemia, was associated with higher rates of all-cause mortality (hazard ratio (HR) 1.27 [95%CI 1.02-1.58]), all-cause admission (HR 1.22 [95%CI 1.14-1.30]), and AF admission (HR 1.23 [95%CI 1.08-1.40]), but not HF admission (HR 1.09 [95%CI 0.91-1.31]). CONCLUSION: In patients undergoing AVR, moderate/severe anemia at discharge, compared with no/mild anemia, was associated with increased all-cause mortality, all-cause hospital admission, and AF admission, but not HF admission, at one-year post-discharge.

3.
ESC Heart Fail ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992950

ABSTRACT

AIMS: A high extracellular water (ECW) to intracellular water (ICW) ratio of skeletal muscle as assessed by bioelectrical impedance analysis is reportedly associated with loss of muscle strength. However, the validity of this index for heart failure (HF), which is likely associated with changes in the water distribution, is unclear. METHODS AND RESULTS: This study involved 190 patients with HF. The total ECW and ICW of both upper and lower extremities were measured, and a high ECW/ICW ratio was defined as an ECW/ICW ratio higher than the median (≥0.636 for men, ≥0.652 for women). Low muscle strength was defined as reduced handgrip strength according to the criteria established by the Asian Working Group for Sarcopenia. Patients with a high ECW/ICW ratio had a lower handgrip strength (21.1 ± 8.1 kg vs. 27.6 ± 9.3 kg, P ≤ 0.05) and 6 min walk distance (329 ± 116 m vs. 440 ± 114 m) than those with a low ECW/ICW ratio. An increasing ECW and/or decreasing ICW was associated with a higher ECW/ICW ratio and a lower handgrip strength (P < 0.05). In the multivariate logistic regression analysis, a high ECW/ICW ratio and low skeletal muscle mass were independently associated with low muscle strength (P < 0.05). CONCLUSIONS: A high ECW/ICW ratio in limb muscles, that is, the water imbalance of increasing ECW and/or decreasing ICW, is useful in assessing muscle quality in patients with HF.

4.
Article in English | MEDLINE | ID: mdl-38995611

ABSTRACT

Coronary artery disease (CAD), acute coronary syndrome (ACS), and heart failure (HF) are major global health issues with high morbidity and mortality rates. Biomarkers like cardiac troponins (cTn) and natriuretic peptides (NPs) are crucial tools in cardiology, but numerous new biomarkers have emerged, proving increasingly valuable in CAD/ACS. These biomarkers are classified based on their mechanisms, such as fibrosis, metabolism, inflammation, and congestion. The integration of established and emerging biomarkers into clinical practice is an ongoing process, and recognizing their strengths and limitations is crucial for their accurate interpretation, incorporation into clinical settings, and improved management of CVD patients. We explored established biomarkers like cTn, NPs, and CRP, alongside newer biomarkers such as Apo-A1, IL-17E, IgA, Gal-3, sST2, GDF-15, MPO, H-FABP, Lp-PLA2, and ncRNAs; provided evidence of their utility in CAD/ACS diagnosis and prognosis; and empowered clinicians to confidently integrate these biomarkers into clinical practice based on solid evidence.

5.
Article in English | MEDLINE | ID: mdl-39010823

ABSTRACT

Pulmonary hypertension is a group of diseases characterized by elevated pulmonary artery pressure and pulmonary vascular resistance with significant morbidity and mortality. The most prevalent type is pulmonary hypertension secondary to left heart disease (PH-LHD). The available experimental models of PH-LHD use partial pulmonary clamping by technically nontrivial open chest surgery with lengthy recovery. We present a simple model in which reduction of the cross-sectional area of the ascending aorta is achieved not by external clamping, but by partial intravascular obstruction without opening the chest. In anesthetized rats, a blind polyethylene tubing was advanced from the right carotid artery to just above the aortic valve. The procedure is quick and easy to learn. Three weeks after the procedure, left heart pressure overload was confirmed by measuring left ventricular end diastolic pressure by puncture (1.3±0.2 vs. 0.4±0.3 mmHg in controls, mean±sd, P<0.0001). The presence of pulmonary hypertension was documented by measuring pulmonary artery pressure by catheterization (22.3±2.3 vs. 16.9±2.7 mmHg, P=0.0282) and by detecting right ventricular hypertrophy and increased muscularization of peripheral pulmonary vessels. Contributions of precapillary vascular segment and of vasoconstriction to the increased pulmonary vascular resistance were demonstrated, respectively, by arterial occlusion technique and by normalization of resistance by a vasodilator, sodium nitroprusside, in isolated lungs. These changes were comparable, but not additive, to those induced by an established pulmonary hypertension model, chronic hypoxic exposure. Intravascular partial aortic obstruction offers an easy model of pulmonary hypertension induced by left heart disease that has a vasoconstrictor and precapillary component.

6.
J Am Heart Assoc ; 13(14): e035264, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38958130

ABSTRACT

BACKGROUND: 123Iodine-meta-iodobenzylguanidine scintigraphy is useful for assessing cardiac autonomic dysfunction and predict outcomes in heart failure (HF). The relationship of cardiac sympathetic function with myocardial remodeling and diffuse fibrosis remains largely unknown. We aimed to evaluate the cardiac sympathetic function of patients with HF and its relation with myocardial remodeling and exercise capacity. METHODS AND RESULTS: Prospectively enrolled patients with HF (New York Heart Association class II-III) were stratified into HF with preserved left ventricular ejection fraction [LVEF] ≥45%) and reduced LVEF. Ventricular morphology/function and myocardial extracellular volume (ECV) fraction were quantified by cardiovascular magnetic resonance, global longitudinal strain by echocardiography, cardiac sympathetic function by heart-to-mediastinum ratio from 123iodine-meta-iodobenzylguanidine scintigraphy. All participants underwent cardiopulmonary exercise testing. The cohort included 33 patients with HF with preserved LVEF (LVEF, 60±10%; NT-proBNP [N-terminal pro-B-type natriuretic peptide], 248 [interquartile range, 79-574] pg/dL), 28 with HF with reduced LVEF (LVEF, 30±9%; NT-proBNP, 743 [interquartile range, 250-2054] pg/dL) and 20 controls (LVEF, 65±5%; NT-proBNP, 40 [interquartile range, 19-50] pg/dL). Delayed (4 hours) 123iodine-meta-iodobenzylguanidine heart-to-mediastinum ratio was lower in HF with preserved LVEF (1.59±0.25) and HF with reduced LVEF (1.45±0.16) versus controls (1.92±0.24; P<0.001), and correlated negatively with diffuse fibrosis assessed by ECV (R=-0.34, P<0.01). ECV in segments without LGE was increased in HF with preserved ejection fraction (0.32±0.05%) and HF with reduced left ventricular ejection fraction (0.31±0.04%) versus controls (0.28±0.04, P<0.05) and was associated with the age- and sex-adjusted maximum oxygen consumption (peak oxygen consumption); (R=-0.41, P<0.01). Preliminary analysis indicates that cardiac sympathetic function might potentially act as a mediator in the association between ECV and NT-proBNP levels. CONCLUSIONS: Abnormally low cardiac sympathetic function in patients with HF with reduced and preserved LVEF is associated with extracellular volume expansion and decreased cardiopulmonary functional capacity.


Subject(s)
Biomarkers , Heart Failure , Stroke Volume , Sympathetic Nervous System , Ventricular Remodeling , Humans , Male , Female , Heart Failure/physiopathology , Middle Aged , Ventricular Remodeling/physiology , Sympathetic Nervous System/physiopathology , Aged , Biomarkers/blood , Stroke Volume/physiology , Prospective Studies , Ventricular Function, Left/physiology , Peptide Fragments/blood , Natriuretic Peptide, Brain/blood , Exercise Tolerance/physiology , Fibrosis , 3-Iodobenzylguanidine , Exercise Test , Myocardium/pathology , Myocardium/metabolism , Heart/innervation , Heart/physiopathology , Echocardiography , Radiopharmaceuticals , Radionuclide Imaging
7.
Patient Educ Couns ; 127: 108367, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38981405

ABSTRACT

OBJECTIVE: The purpose of the study was to describe demographic and health literacy correlates of learning style in older adults with heart failure (HF). METHODS: Cross sectional data on learning styles (VARK Questionnaire, 16 items) and health literacy (S-TOFHLA, 36 items) were collected. Preferred learning style was determined and correlated to health literacy and demographic measures. RESULTS: 116 participants with heart failure (M age = 75.1 (SD 12.5) years, M health literacy of 19 (SD 11.5). Most identified as male (59 %); with inadequate health literacy (67 %). Thirty percent reported a multimodal learning style preference with a kinesthetic (r = .33, p = .03) and not a visual preference (r = -.49, p < .001). Among unimodal learning styles, the most frequent was kinesthetic (26.7 %). Those with lower literacy levels were older (r = -.44, p = <.001), had less education (r = .48, p < .001) and reported a kinesthetic learning preference (r = .37, p = .001). CONCLUSION: Older individuals identifying as male, with low health literacy, preferred a kinesthetic approach to HF education. Future research should consider the linkage between education tailored to learning style, health literacy and outcomes. PRACTICE IMPLICATIONS: Assessment of learning style should be completed prior to an educational encounter.

8.
Article in English | MEDLINE | ID: mdl-38981605

ABSTRACT

Glutamine is a critical amino acid that serves as an energy source, building block, and signaling molecule for the heart tissue and the immune system. However, the role of glutamine metabolism in regulating cardiac remodeling following myocardial infarction (MI) is unknown. In this study, we show in adult male mice that glutamine metabolism is altered both in the remote (contractile) area and in infiltrating macrophages in the infarct area after permanent left anterior descending artery occlusion. We found that metabolites related to glutamine metabolism were differentially altered in macrophages at days 1, 3, and 7 after MI using untargeted metabolomics. Glutamine metabolism in live cells was increased after MI relative to no MI controls. Gene expression in the remote area of the heart indicated a loss of glutamine metabolism. Glutamine administration improved LV function at days 1, 3, and 7 after MI, which was associated with improved contractile and metabolic gene expression. Conversely, administration of BPTES, a pharmacological inhibitor of glutaminase-1, worsened LV function after MI. Neither glutamine nor BPTES administration impacted gene expression or bioenergetics of macrophages isolated from the infarct area. Our results indicate that glutamine metabolism plays a critical role in maintaining LV contractile function following MI, and that glutamine administration improves LV function. Glutamine metabolism may also play a role in regulating macrophage function, but macrophages are not responsive to exogenous pharmacological manipulation of glutamine metabolism.

10.
Biomark Med ; 18(9): 441-448, 2024.
Article in English | MEDLINE | ID: mdl-39007838

ABSTRACT

Aim: To evaluate the difference between core temperature and surface temperature (ΔT) as an index for the prognosis of heart failure (HF). Patients & methods: Core temperature and surface temperature were measured in 253 patients with HF. The association of ΔT with prognostic indicators of HF was analyzed. Results: Patients with ΔT ≥2°C were more likely to have lower left ventricular ejection fraction and lower estimated glomerular filtration rate, higher levels of troponin T, brain natriuretic peptide and procalcitonin, and high blood urea nitrogen/creatinine ratio. The risk of death increased by 32% for a 1°C increase in ΔT and was 4.36-times higher in the ΔT ≥2°C group than in the ΔT <2°C group. Conclusion: ΔT may be used to predict the prognosis of patients with HF.


[Box: see text].


Subject(s)
Heart Failure , Humans , Heart Failure/blood , Heart Failure/diagnosis , Heart Failure/mortality , Heart Failure/physiopathology , Male , Female , Aged , Prognosis , Middle Aged , Troponin T/blood , Body Temperature , Natriuretic Peptide, Brain/blood , Stroke Volume , Creatinine/blood , Aged, 80 and over , Blood Urea Nitrogen , Glomerular Filtration Rate , Procalcitonin/blood
11.
Article in English | MEDLINE | ID: mdl-39007928

ABSTRACT

Up to date, digitalis glycosides, also known as "cardiac glycosides", are inhibitors of the Na+/K+-ATPase. They have a long-standing history as drugs used in patients suffering from heart failure and atrial fibrillation despite their well-known narrow therapeutic range and the intensive discussions on their raison d'être for these indications. This article will review the history and key findings in basic and clinical research as well as potentially overseen pros and cons of these drugs.

12.
Inn Med (Heidelb) ; 2024 Jul 15.
Article in German | MEDLINE | ID: mdl-39007960

ABSTRACT

Atrial fibrillation and heart failure are among the most common cardiovascular diseases and have a significant impact on the mortality and morbidity of affected patients. From a pathophysiological perspective, the two diseases are closely related and often perpetuate each other. Therefore, effective management of atrial fibrillation is now a central component of modern heart failure treatment. Based on current data, sinus rhythm should primarily be permanently maintained in patients with systolic heart failure. Catheter ablation has recently proven to be advantageous over purely pharmacological therapy and is therefore the treatment of choice for many patients with heart failure and atrial fibrillation. In patients with diastolic heart failure (heart failure with preserved ejection fraction [HFpEF]), the effect of catheter ablation is less clear. Data from randomized studies are urgently needed in order to further assess efficacy in this population.

13.
Diagnostics (Basel) ; 14(13)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-39001258

ABSTRACT

AIMS: The aims of this study were to compare global longitudinal strain of the left ventricle (LV-GLS) and reservoir strain of the left atrium (R-LAS) values between patients with acute decompensation of chronic heart failure (HF) and a control group. METHODS: Sixteen patients admitted to our ward for acute decompensation of HF were enrolled in this study. Transthoracic echocardiography (TTE) with two-dimensional speckle-tracking analysis (2D ST) was performed in each patient. The patients were divided into two subgroups according to the value of left ventricular ejection fraction (EF) using a cut-off value of ≤40% to distinguish heart failure with reduced ejection fraction (HFrEF) from heart failure with preserved ejection fraction (HFpEF). The control group consisted of 16 individuals without a history of cardiovascular disease, each of whom underwent 2D ST analysis as well. RESULTS: We found that LV-GLS and R-LAS were significantly lower in both the HFrEF and HFpEF subgroups in comparison with the control group (LV-GLS: -13.4 ± 4.7% vs. -19.7 ± 2.5%, p ˂ 0.05; R-LAS: +12.2 ± 6.9% vs. +40.3 ± 7.4%, p ˂ 0.05). Furthermore, there was a significant difference in LV-GLS (-9.6 ± 3.2% vs. -15.2 ± 4.3%, p ˂ 0.05) but not in R-LAS (+13.7 ± 8.6% vs. +11.4 ± 6.2%) between the HFrEF and HFpEF subgroups. CONCLUSIONS: Our study demonstrated a significant difference in LV-GLS and R-LAS in all enrolled HF patients compared to the control group. There was also a significant difference in LV-GLS between the HFrEF and HFpEF subgroups.

14.
Diagnostics (Basel) ; 14(13)2024 Jul 05.
Article in English | MEDLINE | ID: mdl-39001328

ABSTRACT

Identifying patients with left ventricular ejection fraction (EF), either reduced [EF < 40% (rEF)], mid-range [EF 40-50% (mEF)], or preserved [EF > 50% (pEF)], is considered of primary clinical importance. An end-to-end video classification using AutoML in Google Vertex AI was applied to echocardiographic recordings. Datasets balanced by majority undersampling, each corresponding to one out of three possible classifications, were obtained from the Standford EchoNet-Dynamic repository. A train-test split of 75/25 was applied. A binary video classification of rEF vs. not rEF demonstrated good performance (test dataset: ROC AUC score 0.939, accuracy 0.863, sensitivity 0.894, specificity 0.831, positive predicting value 0.842). A second binary classification of not pEF vs. pEF was slightly less performing (test dataset: ROC AUC score 0.917, accuracy 0.829, sensitivity 0.761, specificity 0.891, positive predicting value 0.888). A ternary classification was also explored, and lower performance was observed, mainly for the mEF class. A non-AutoML PyTorch implementation in open access confirmed the feasibility of our approach. With this proof of concept, end-to-end video classification based on transfer learning to categorize EF merits consideration for further evaluation in prospective clinical studies.

15.
Article in English | MEDLINE | ID: mdl-39004591

ABSTRACT

BACKGROUND AND AIMS: Iron deficiency is a major public health concern. We aimed to assess the predictive capability of 4 iron metabolism biomarkers for all-cause and cardiovascular disease-specific mortality in U.S. patients with congestive heart failure (CHF). METHODS AND RESULTS: 1904 CHF patients aged ≥20 years were enrolled from NHANES, 1999-2000 to 2017-2018. All analyses were weighted to provide nationally representative estimates. Among 1905 CHF patients, mean age was 71 years, and 1024 (53.8%), 459 (24.1%), 206 (10.8%), and 216 (11.3%) were Non-Hispanic Black, Non-Hispanic White, Hispanic-Mexican American, and Hispanic-Other Hispanic, respectively. During follow-ups, 1080 deaths occurred. Median follow-up time was 5.08 years. Per-unit increase in natural-logarithmic-transformed iron and transferrin saturation decreased all-cause mortality risk separately by 33.0% (adjusted hazard ratio: 0.670, 95% confidence interval: 0.563 to 0.797, P < 0.001) and 32.6% (0.674, 0.495 to 0.917, 0.013), and per-unit increase in transferrin receptor increased mortality risk by 33.7% (1.337, 1.104 to 1.618, 0.004). Two derivates from 3 significant iron biomarkers were generated - transferrin receptor to natural-logarithmic-transformed iron ratio (TRI) and transferrin receptor to natural-logarithmic-transformed transferrin saturation ratio (TRTS), which were significantly associated with all-cause mortality, with per-unit increase corresponding to 2.692- and 1.655-fold increased all-cause mortality risk (P: 0.003 and 0.023). Only iron and TRTS were associated with the significant risk of cardiovascular disease-specific mortality (P: 0.004 and 0.017). CONCLUSIONS: Our findings identified 3 iron metabolism biomarkers that were individually, significantly, and independently associated with all-cause mortality in patients with CHF, and importantly 2 derivates generated exhibited stronger predictive capability.

16.
Curr Pharm Des ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39005124

ABSTRACT

Loop diuretics are the cornerstone of decongestive therapy in patients presenting with acute heart failure and have been extensively studied in randomized clinical trials. Therefore, in current guidelines, they are the only drug with a class I recommendation to treat signs and symptoms of congestion when present. However, the percentage of patients achieving successful decongestion is suboptimal, and diuretic resistance frequently develops. Patients with a poor response to loop diuretics and those discharged with residual signs of congestion are characterized by a worse prognosis over time. Recently, a renovated interest in different diuretic classes sprouted among heart failure researchers in order to improve decongestion strategies and ameliorate short- and long-term clinical outcomes. Randomized clinical trials investigating associations among diuretic classes and loop diuretics have been performed but yielded variable results. Therefore, despite initial evidence of a possible benefit from some of these compounds, a definite way to approach diuretic resistance via diuretic combination therapy is still missing. The aim of this review is to summarize current clinical evidence on the use of diuretic combination therapy in patients with acute heart failure and to suggest a possible approach to avoid or counteract diuretic resistance.

17.
Circulation ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39005209

ABSTRACT

BACKGROUND: Chronic kidney disease represents one of the strongest risk factors for cardiovascular diseases, and particularly for heart failure. Despite improved pharmaceutical treatments, mortality remains high. Recently, experimental studies demonstrated that mosaic loss of Y chromosome (LOY) associates with cardiac fibrosis in male mice. Since diffuse cardiac fibrosis is the common denominator for progression of all forms of heart failure, we determined the association of LOY on mortality and cardiovascular disease outcomes in patients with chronic kidney disease. METHODS: LOY was quantified in men with stable chronic kidney disease (CARE for HOMe study [XXX], n=279) and dialysis patients (4D study, n=544). The association between LOY and mortality, combined cardiovascular and heart failure-specific end points, and echocardiographic measures was assessed. RESULTS: In CARE for HOMe, the frequency of LOY increased with age. LOY >17% was associated with increased mortality (heart rate, 2.58 [95% CI, 1.33-5.03]) and risk for cardiac decompensation or death (heart rate, 2.30 [95% CI, 1.23-4.27]). Patients with LOY >17% showed a significant decline of ejection fraction and an increase of E/E' within 5 years. Consistently, in the 4D study, LOY >17% was significantly associated with increased mortality (heart rate, 2.76 [95% CI, 1.83-4.16]), higher risk of death due to heart failure and sudden cardiac death (heart rate, 4.11 [95% CI, 2.09-8.08]), but not atherosclerotic events. Patients with LOY >17% showed significantly higher plasma levels of soluble interleukin 1 receptor-like 1, a biomarker for myocardial fibrosis. Mechanistically, intermediate monocytes from patients with LOY >17% showed significantly higher C-C chemokine receptor type 2 expression and higher plasma levels of the C-C chemokine receptor type 2 chemokine (C-C motif) ligand 2, which may have contributed to increased heart failure events. CONCLUSIONS: LOY identifies male patients with chronic kidney disease at high risk for mortality and heart failure events.

18.
Circulation ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39005211

ABSTRACT

BACKGROUND: Activation of the immune system contributes to cardiovascular diseases. The role of human-specific long noncoding RNAs in cardioimmunology is poorly understood. METHODS: Single-cell sequencing in peripheral blood mononuclear cells revealed a novel human-specific long noncoding RNA called HEAT4 (heart failure-associated transcript 4). HEAT4 expression was assessed in several in vitro and ex vivo models of immune cell activation, as well as in the blood of patients with heart failure (HF), acute myocardial infarction, or cardiogenic shock. The transcriptional regulation of HEAT4 was verified through cytokine treatment and single-cell sequencing. Loss-of-function and gain-of-function studies and multiple RNA-protein interaction assays uncovered a mechanistic role of HEAT4 in the monocyte anti-inflammatory gene program. HEAT4 expression and function was characterized in a vascular injury model in NOD.CB17-Prkdc scid/Rj mice. RESULTS: HEAT4 expression was increased in the blood of patients with HF, acute myocardial infarction, or cardiogenic shock. HEAT4 levels distinguished patients with HF from people without HF and predicted all-cause mortality in a cohort of patients with HF over 7 years of follow-up. Monocytes, particularly anti-inflammatory CD16+ monocytes, which are increased in patients with HF, are the primary source of HEAT4 expression in the blood. HEAT4 is transcriptionally activated by treatment with anti-inflammatory interleukin-10. HEAT4 activates anti-inflammatory and inhibits proinflammatory gene expression. Increased HEAT4 levels result in a shift toward more CD16+ monocytes. HEAT4 binds to S100A9, causing a monocyte subtype switch, thereby reducing inflammation. As a result, HEAT4 improves endothelial barrier integrity during inflammation and promotes vascular healing after injury in mice. CONCLUSIONS: These results characterize a novel endogenous anti-inflammatory pathway that involves the conversion of monocyte subtypes into anti-inflammatory CD16+ monocytes. The data identify a novel function for the class of long noncoding RNAs by preventing protein secretion and suggest long noncoding RNAs as potential targets for interventions in the field of cardioimmunology.

19.
Hypertension ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39005226

ABSTRACT

BACKGROUND: The 2017 American College of Cardiology/American Heart Association blood pressure guideline recommends initiation of antihypertensive medication for adults with stage 1 hypertension (systolic blood pressure, 130-139 mm Hg, or diastolic blood pressure, 80-89 mm Hg) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10% estimated by the pooled cohort equations (PCEs). In 2023, the American Heart Association published the predicting risk of cardiovascular disease events (PREVENT) equations to estimate ASCVD and total cardiovascular disease risk. METHODS: We analyzed US National Health and Nutrition Examination Survey data from 2013 to 2020 for 1703 adults aged 30 to 79 years without self-reported cardiovascular disease with stage 1 hypertension. We estimated 10-year ASCVD risk by the PCEs and 10-year ASCVD and total cardiovascular disease risk by the base PREVENT equations. Analyses were weighted to represent noninstitutionalized US adults with stage 1 hypertension. RESULTS: Mean 10-year ASCVD risk was 5.4% (95% CI, 5.0%-5.9%) and 2.9% (95% CI, 2.7%-3.1%) using the PCEs and PREVENT equations, respectively. The proportion with 10-year ASCVD risk of 10% to <15% and ≥15% was 8.1% and 7.8% estimated by the PCEs, respectively, and 3.0% and 0.3% estimated by the PREVENT equations, respectively. No participants had a 10-year ASCVD risk ≥10% on the PREVENT equations and <10% on the PCEs, while 12.5% had a 10-year ASCVD risk ≥10% on the PCEs and <10% on the PREVENT equations. The mean 10-year total cardiovascular disease risk estimated by the PREVENT equations was lower than the mean 10-year ASCVD risk on the PCEs. CONCLUSIONS: Among US adults with stage 1 hypertension, the 10-year predicted ASCVD risk estimated by the PREVENT equations was approximately half the risk estimated by the PCEs.

20.
Indian Heart J ; 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39009078

ABSTRACT

Novel therapies for heart failure with reduced ejection fraction (HFrEF) are angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose co-transporter 2 inhibitor (SGLT2i), etc. The purpose of this review is to determine the effects of ARNI and SGLT2i in heart failure (HF), compare the impact of SGLT2i with ARNI, and finally evaluate the current data regarding the combination of these two drugs in HF. Various trials on the respective medications have shown some significant reduction in all-cause mortality and cardiovascular (CV) death. The combination of these drugs has shown more CV benefits than monotherapy. There is emerging data about these two drugs in patients with heart failure with preserved ejection fraction (HFpEF). At present, there are less head-to-head comparison trials of these two drugs. This review provides insights on the current evidence, comparative efficacy, and combination therapy of ARNI and SGLT2i in managing HF, focussing on HFrEF and HFpEF.

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