Neurohormonal Activation Research Articles

Biological Pathways in Adolescent Aortic Stiffness.

BackgroundAortic stiffening begins in youth and antedates future hypertension. In adults, excess weight, systemic inflammation, dyslipidemia, insulin resistance, neurohormonal activation, and altered adipokines are implicated in the pathogenesis of increased aortic stiffness. In adolescents, we assessed the relations of comprehensive measures of aortic stiffness with body mass index (BMI) and related but distinct circulating biomarkers.Methods and ResultsA convenience sample of 246 adolescents (mean age, 16±2 years; 45% female, 24% Black, and 43% Hispanic) attending primary care or preventive cardiology clinics at 2 tertiary hospitals was grouped as normal weight (N=98) or excess weight (N=148, defined as BMI ≥age‐ and sex‐referenced 85th percentile). After an overnight fast, participants underwent anthropometry, noninvasive arterial tonometry, and assays for serum lipids, CRP (C‐reactive protein), glucose, insulin, renin, aldosterone, and leptin. We used multivariable linear regression to relate arterial stiffness markers (including carotid‐femoral pulse wave velocity) to BMI z score and a biomarker panel. Carotid‐femoral pulse wave velocity was higher in excess weight compared with normal weight group (5.0±0.7 versus 4.6±0.6 m/s; P<0.01). After multivariable adjustment, carotid‐femoral pulse wave velocity was associated with BMI z score (0.09 [95% CI, 0.01–0.18]; P=0.04) and with low‐density lipoprotein cholesterol (0.26 [95% CI, 0.03–0.50]; P=0.03).ConclusionsHigher BMI and low‐density lipoprotein cholesterol were associated with greater aortic stiffness in adolescents. Maintaining optimal BMI and lipid levels may mitigate aortic stiffness.

Optimal diuretic strategies in heart failure.

Heart failure (HF) is one of the major causes of morbidity and mortality in the world. According to a 2019 American Heart Association report, about 6.2 million American adults had HF between 2013 and 2016, being responsible for almost 1 million admissions. As the population ages, the prevalence of HF is anticipated to increase, with 8 million Americans projected to have HF by 2030, posing a significant public health and financial burden. Acute decompensated HF (ADHF) is a syndrome characterized by volume overload and inadequate cardiac output associated with symptoms including some combination of exertional shortness of breath, orthopnea, paroxysmal nocturnal dyspnea (PND), fatigue, tissue congestion (e.g., peripheral edema) and decreased mentation. The pathology is characterized by hemodynamic abnormalities that result in autonomic imbalance with an increase in sympathetic activity, withdrawal of vagal activity and neurohormonal activation (NA) resulting in increased plasma volume in the setting of decreased sodium excretion, increased water retention and in turn an elevation of filling pressures. These neurohormonal changes are adaptive mechanisms which in the short term are associated with increased contractility of the left ventricular (LV) and improvement in cardiac output. But chronically, the failing heart is unable to overcome the excessive pressure and volume leading to worsening HF. The primary symptomatic management of ADHF includes intravenous (IV) diuresis to help with decongestion and return to euvolemic status. Even though diuretics have not been shown to provide any mortality benefit, they have been clinically proven to be of significant benefit in the acute decompensated phase, as well as in chronic management of HF. Loop diuretics remain the mainstay of therapy for symptomatic management of HF with use of thiazide diuretics for synergistic effect in the setting of diuretic resistance. Poor diuretic efficacy has been linked with higher mortality and increased rehospitalizations.

Impact of surgical aortic valve replacement on global and regional longitudinal strain across four flow gradient patterns of severe aortic stenosis.

To evaluate the impact of surgical aortic valve replacement (SAVR) on global (GLS) and regional longitudinal strain (RLS) across four flow-gradient patterns of severe aortic stenosis (AS) 3 months after surgery.A total of 103 patients with severe AS (aortic valve area < 1.0 cm2) were examined by speckle tracking echocardiography the day before SAVR and at 3-months follow-up. Patients were stratified into four flow-gradient patterns by stroke volume index (>35 mL/m2 vs. ≤35 mL/m2) and mean transaortic gradients (>40 mmhg vs. ≤40 mmhg): normal-flow, high gradient (NF/HG); low-flow, high gradient (LF/HG); normal-flow, low gradient (NF/LG); low-flow, low gradient (LF/LG). Strain analysis comprised GLS and RLS at a basal (BLS), mid-ventricular (MLS) and apical level (ALS).Patients with high gradients improved GLS (NF/HG: 16.1 ± 3.5 % vs. 17.3 ± 3.4 %, p = 0.03 and LF/HG: 15.4 ± 3.6 % vs. 16.9 ± 3.1 %, p = 0.03), BLS (NF/HG: 12.7 ± 3.1 % vs. 14.2 ± 3.1 %, p = 0.003 and LF/HG: 11.4 ± 3.2 % vs. 13.8 ± 2.7 %, p = 0.005) and MLS (NF/HG: 15.4 ± 3.3 % vs. 16.5 ± 3.3 %, p = 0.04 and LF/HG: 14.5 ± 3.1 % vs. 16.2 ± 2.7 %, p = 0.01) whereas patients with low gradients showed no improvements three months after SAVR. ALS did not change significantly in any group. Patients with high gradients demonstrated a reduction in left ventricular (LV) mass index (p < 0.001) and N-terminal pro-Brain Natriuretic Peptide levels (p < 0.001) following SAVR in contrast to patients with low gradients.Patients with high gradient severe AS improve GLS and RLS three months after SAVR with concomitant reduction of LV mass and neurohormonal activation whereas patients with low gradients do not improve longitudinal strain, LV mass or neurohormonal activation.

Association of Global Longitudinal Strain With Clinical Status and Mortality in Patients With Chronic Heart Failure

Global longitudinal strain (GLS) is an emerging echocardiographic biomarker of cardiac function in heart failure (HF). Evidence from large-scale studies comprehensively investigating GLS for its association with clinical phenotypes and mortality in asymptomatic and symptomatic chronic HF is limited. To assess the factors associated with GLS and its prognostic value in patients with chronic HF. The observational, prospective MyoVasc cohort study enrolled 3289 individuals with asymptomatic to symptomatic HF between January 17, 2013, and April 27, 2018. The median follow-up was 3.2 years (interquartile range, 2.0-4.0 years). Participants with stages A to D HF according to American Heart Association (AHA) criteria were examined at a dedicated study center. Echocardiography was performed with GLS measurement by independent reviewers. Data were analyzed from September 2, 2019, to January 15, 2020. All-cause and cardiac mortality were recorded by structured follow-up and validated via death certificates. In the study sample, data on GLS were available on 2440 individuals, of whom 2186 (mean [SD] age, 65.0 [10.5] years; 1418 [64.9%] men) were classified as having AHA HF stages A to D. Mean (SD) GLS worsened across AHA stages from stage A (n = 434; -19.44 [3.15%]) to stage B (n = 629; -18.01 [3.46%]) to stages C/D (n = 1123; -15.52 [4.64%]). Age (β = -0.27; 95% CI, -0.47 to -0.067; per decade, P = .009), female sex (β = -1.2; 95% CI, -1.6 to -0.77; per decade, P < .001), obesity (β = 0.64; 95% CI, 0.25-1.0; P = .001), atrial fibrillation (β = 1.2; 95% CI, 0.69-1.6; P < .001), myocardial infarction (β = 1.5; 95% CI, 1.00-2.1; P < .001), and estimated glomerular filtration rate (β = -0.53; 95% CI, -0.73 to -0.32; per SD, P < .001) were independently associated with GLS in multivariable regression analysis. Global longitudinal strain was associated with the severity of HF as reflected by N-terminal prohormone B-type natriuretic protein (NT-proBNP) levels after additionally adjusting for cardiac structure and function (P < .001). During follow-up, GLS was associated with all-cause mortality (hazard ratio [HR] per SD, 1.55; 95% CI, 1.19-2.01; P < .001) and cardiac death (HR per SD, 2.32; 95% CI, 1.57-3.42; P < .001) independent of image quality, observer variability, clinical profile, HF medications, NYHA class, and cardiac structure and function. After further adjustment for the NT-proBNP level, GLS remained associated with cardiac death (HR per SD, 1.60; 95% CI, 1.07-2.41; P = .02) but not all-cause mortality (HR per SD, 1.26; 95% CI, 0.95-1.66; P = .11). In patients with chronic HF, GLS was associated with clinical and cardiac status, reflected neurohormonal activation, and was associated with cardiac mortality independent of clinical and cardiac status. These findings suggest that GLS may serve as a useful tool to improve risk stratification in patients with HF.

Soluble Angiotensin-Converting Enzyme 2, Cardiac Biomarkers, Structure, and Function, and Cardiovascular Events (from the Atherosclerosis Risk in Communities Study)

Membrane-bound angiotensin-converting enzyme 2 is important in regulation of the renin-angiotensin-aldosterone system, but the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) is unclear. We evaluated the association of sACE2 with cardiac biomarkers, structure, and function and cardiovascular events in the Atherosclerosis Risk in Communities Study. sACE2 was measured in a subset of 497 participants (mean age 78±5.4 years, 53% men, 27% black); Cox regression analyses assessed prospective associations of sACE2 with time to first CVD event at median 6.1-year follow-up. sACE2 was higher in men, blacks, and participants with prevalent CVD, diabetes, or hypertension. Higher sACE2 levels were associated with significantly higher biomarkers of cardiac injury (high-sensitivity cardiac troponin I and T, N-terminal pro-B-type natriuretic peptide), greater left ventricular mass index, and impaired diastolic function in linear regression analyses, and with increased risk for heart failure hospitalization (adjusted hazard ratio per natural log unit increase [HR] 1.32, 95% confidence interval [CI] 1.10 to 1.58), CVD events (HR 1.34, 95% CI 1.13 to 1.60), and all-cause death (HR 1.26, 95% CI 1.01 to 1.57). In an elderly biracial cohort, sACE2 was positively associated with biomarkers reflecting myocardial injury and neurohormonal activation, left ventricular mass index, impaired diastolic function, CVD, events and all-cause death.

Exploring the mechanisms of action of gliflozines in heart failure and possible implications in pulmonary hypertension

Although results from two major trials trials have shown a clear benefit of gliflozines in the management of heart failure (HF) irrespective of diabetes status, the mechanism of cardiac benefits remains incompletely understood. Gliflozines have an osmotic diuretic effect that differs from that of other diuretic classes, resulting in greater electrolyte-free water clearance, and clinical studies have shown that intravascular volume depletion is rare and occurs at similar frequency in the gliflozines and placebo groups. As a consequence of the negligible effects on the blood volume and body's fluid balance compared to diuretics, gliflozines may limit the reflex neurohumoral stimulation and activation of renin-angiotensin-aldosterone system (RAAS). Since neurohormonal and RAAS activation in patients with HF reduced or ejection fraction (HFrEF and HFpEF) also leads to systemic and pulmonary arterial stiffening, pulmonary hypertension (PH) and PH-related right ventricular failure, gliflozines may lead to a mitigation of systemic and pulmonary arterial stiffening, which in turn can reduce the degree of PH associated with HFrEF or HFpEF, can improve the ventricular arterial coupling and can reduce the overload of the left and right ventricle, improving their function. The current review discusses the latest findings regarding the effects of SGLT2 inhibitors on heart failure with focus also on pulmonary hypertension, discussing the molecular mechanisms involved.

Depression and Rehospitalization in Patients With Heart Failure After Discharge From Hospital to Home: An Integrative Review

Patients with heart failure are known to be particularly vulnerable to depression resulting in adverse health outcomes. However, there has been no literature review on current evidence regarding the relationship between depression and rehospitalization. This review aims to explore the relationship between depression and rehospitalization in patients with heart failure. A systematic review employing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines included articles published between 2001 and 2019 taken from Scopus, PubMed, CINAHL, and PsycINFO databases. We identified 12 relevant studies with participants ranging from 115 to 160,169 patients. Heart failure patients with depression were more likely to be rehospitalized than those without. To explain this, few reasons have been proposed. First, depression could disrupt the regulation of autonomic nervous system, neurohormonal activation, and body’s natural rhythm. Second, depressed patients tend to have poor adherence to medication. Healthcare providers should not only focus on drug and dietary management but also on implementing effective interventions to manage depression, in order to reduce the risk of rehospitalization. Moreover, palliative care should start at the stage of heart failure diagnosis to improve quality of life, better outcomes, and lower cost of care for the patients.

Balneotherapy in Stimulating Resistance to Infections – the Little-used Health Resort’s Potential During the COVID-19 Pandemic

To function properly, the human immune system must be adequately stimulated. Immune activity is stimulated as a result of the use of vaccines as well as the exposure of the body to infections. This type of stimulation only increases the specific humoral immunity, characterized by relatively short duration, and targeted at a well-defined antigen. In the case of the COVID-19 virus, immune memory cells persist for up to one year. In parallel with specific stimulation, it is necessary to develop non-specific immunity. It is the body’s first line of defense against infection, affects many microorganisms, and supports specific immunity. We can develop and strengthen this immunity using non-pharmacological methods, including balneotherapy, physical activity, and an appropriate diet. There is now much scientific evidence showing the effectiveness of balneotherapy in improving innate immunity. In in vitro and in vivo studies with high scientific credibility, the following effects of balneotherapy on the immune system were demonstrated: stimulation of the proliferation of T lymphocytes (especially CD4), normalization of the ratio between lymphocytes with different cytotoxic and anti-inflammatory effects, increased number of granulocytes and stimulation of the phagocytic activity of granulocytes and macrophages, lowering the concentration of proinflammatory cytokines and stimulating the secretion of anti-inflammatory cytokines, CRP, prostaglandins (PGE2), as well as antioxidant and neurohormonal activity. Among treatments with balneoimmunostimulatory effects, one should mention sulfide baths, peloid compresses, brine baths, radon treatments, and hot baths. These treatments are mainly used as part of health resort treatment. In Poland, health resort treatment represents excellent health potential. Unfortunately, it is very modestly used in activities aimed at improving the immunity of Polish society. This treatment would be best combined in patients after vaccination and in a certain period before vaccination, which would significantly increase the effectiveness of prophylactic vaccinations.

PROGNOSTIC IMPORTANCE OF HYPONATREMIA IN ACUTE STELEVATION MYOCARDIAL INFARCTION

Background: Hyponatremia has been shown to be a predictor of cardiovascular mortality among patients with heart failure. In fact, the neurohormonal activation that accompanies acute myocardial infarction is similar to that which accompanies heart failure. Aims And Objectives : To nd out the prognostic importance of hyponatremia in acute ST elevation myocardial infarction. Material And Methods: 100 consecutive patients presenting with acute ST-elevation myocardial infarction admitted to N.R.I Medical college and General hospital from March 2019 to March 2020 were studied. Qualifying patients underwent detailed history and clinical examination. Plasma sodium concentrations were obtained on admission and at 24, 48 and 72 hours thereafter. The primary end point was all cause mortality within 30 days following myocardial infarction. Results: In our study, substantial proportion of patients who presented with acute ST elevation myocardial infarction were hyponatremic on admission or developed hyponatremia shortly after admission. The odd's ratio for 30-day mortality was found to be high in the hyponatremic groups compared to normal group. We also found a signicant linear relationship between severity of hyponatremia and mortality. Multivariate analysis was performed which identied hyponatremia on admission or early development of hyponatremia as a signicant independent predictor of 30 day mortality. Conclusion: In our study we concluded that hyponatremia on admission or early development of hyponatremia in patients with acute ST elevation myocardial infarction is an independent predictor of 30-day mortality. Plasma sodium levels may serve as a simple marker to identify patients at risk.

Metabolic syndrome and heart failure: mechanism and management.

Heart failure (HF) and metabolic syndrome (MetS) are syndromes that affect a large proportion of the world population. MetS is known to be one of the risk factors of HF, and it can also act as comorbidity in HF. This review aims to further discuss the mechanism of MetS in causing HF, the management of MetS in order to prevent HF, and the management of MetS in HF patients. Visceral adiposity is the primary trigger of MetS which is followed by chronic inflammation, insulin resistance, and neurohormonal activation. All the mechanisms causing MetS play also an important role in the progression of HF. The MetS approach can be achieved by managing its components according to the current guidelines and careful management of MetS should be done in patients with HF. MetS is closely related to the progression of HF so that comprehensive management which involves a multidisciplinary team is necessary for managing patients with metabolic syndrome and heart failure.

Covid-19-Induced Dysautonomia: A Menace of Sympathetic Storm.

Among the plethora of debilitating neurological disorders of COVID-19 syndrome in survivors, the scope of SARS-CoV-2-induced dysautonomia (DNS) is yet to be understood, though the implications are enormous. Herein, we present an inclusive mini-review of SARS-CoV-2-induced DNS and its associated complications. Although, the direct link between Covid-19 and DSN is still speculative, the hypothetical links are thought to be either a direct neuronal injury of the autonomic pathway or a para/post-infectious immune-induced mechanism. SARS-CoV-2 infection-induced stress may activate the sympathetic nervous system (SNS) leading to neuro-hormonal stimulation and activation of pro-inflammatory cytokines with further development of sympathetic storm. Sympathetic over-activation in Covid-19 is correlated with increase in capillary pulmonary leakage, alveolar damage, and development of acute respiratory distress syndrome. Furthermore, SARS-CoV-2 can spread through pulmonary mechanoreceptors and chemoreceptors to medullary respiratory center in a retrograde manner resulting in sudden respiratory failure. Taken together, DSN in Covid-19 is developed due to sympathetic storm and inhibition of Parasympathetic nervous system-mediated anti-inflammatory effect with development of cytokine storm. Therefore, sympathetic and cytokine storms together with activation of Renin-Angiotensin-System are the chief final pathway involved in the development of DSN in Covid-19.

Extracorporeal veno-venous ultrafiltration in patients with acute heart failure.

Hospitalization for congestive heart failure represents a growing burden for health care systems. Heart failure is characterized by extracellular fluid overload and loop diuretics have been for decades the cornerstone of therapy in these patients. However, extensive use of intra-venous diuretics is characterised by several limitations: risk of worsening renal function and electrolyte imbalance, symptomatic hypotension and development of diuretic resistance. Extracorporealveno-venous ultrafiltration (UF) represents an interesting adjunctive therapy to target congestion in patients with heart failure and fluid overload. UF consists of the mechanical removal of iso-tonic plasma water from the blood through a semipermeable membrane using a pressure gradient generated by a pump. Fluid removal through UF presents several advantages such as removal of higher amount of sodium, predictable effect, limited neuro-hormonal activation, and enhanced spontaneous diuresis and diuretic response. After twenty years of "early" studies, since 2000 some pilot studies and randomized clinical trials with modern devices have been carried out with somehow conflicting results, as discussed in this review. In addition, some practical aspects of UF are addressed.

Underlying Causes of High Output Heart Failure

In the U.S., each year, there are more than 500,000 new cases of all types of heart failure. With high output cardiac failure, there is an elevated cardiac output associated with several conditions and diseases, including obesity, chronic anemia, systemic arterio-venous fistula, hypercapnia, mitochondrial dysfunction, and hyperthyroidism. The underlying pathophysiologic mechanisms relate to a reduction in systemic vascular resistance from arterio-venous shunting or peripheral vasodilation. Often there is a decrease in systemic arterial blood pressure and neurohormonal activation leading to heart failure symptoms of dyspnea and fatigue. In a persistent high output state, patients may experience tachycardia, valvular abnormalities, and ventricular dilatation and/or hypertrophy. In this article, there is a review of high output heart failure, including the prevalence, pathophysiology, and common clinical causes of this disease.

Sinergy between drugs and devices in the fight against sudden cardiac death and heart failure

The impact of sudden cardiac death (SCD) in heart failure (HF) patients is important and prevention of SCD is a reasonable and clinically justified endpoint if associated with a reduction in all-cause mortality. According to literature, in HF with reduced ejection fraction, only three classes of agents were found effective in reducing SCD and all-cause mortality: beta-blockers, mineralcorticoid receptor antagonists and, more recently, angiotensin-receptor neprilysin-inhibitors. In the PARADIGM trial that tested sacubitril/valsartan vs. enalapril, the 20% relative risk reduction in cardiovascular deaths obtained with sacubitril/valsartan was attributable to reductions in the incidence of both SCD and death due to HF worsening and this effect can be added to the known positive effect of implantable cardioverter-defibrillators in appropriately selected patients. In order to maximize the implementation of all the available treatments, patients with HF should be included in virtuous networks with a dialogue between all the physician involved, with commitment by all these physicians for appropriate decision-making on application of pharmacological and device treatments according to available evidence, as well as commitment for drug titration before and after device implant, taking advantage from remote monitoring, and with the safety of back up device therapy when indicated. There are potential synergistic effects of drug therapy, with all the therapies acting on neuro-hormonal and sympathetic activation, but specifically with sacubitril/valsartan, and device therapy, in particular cardiac resynchronization therapy, with added incremental benefits on positive cardiac remodelling, prevention of HF progression, and prevention of ventricular tachyarrhythmias.

Sacubitril/valsartan treatment relieved the progression of established pulmonary hypertension in rat model and its mechanism

AimsPulmonary hypertension (PH) is a fatal disease identified by progressive elevated pulmonary arterial pressure, which neurohormonal activation is a notable contributor to its development. Sacubitril/valsartan is a complex of sacubitril [via enhancing the natriuretic peptide (NP) system] and valsartan [via blocking the renin-angiotensin-aldosterone system (RAAS)]. Regulation of the two neurohormonal system had been shown to attenuate PH. This study was to explore the role of sacubitril/valsartan in both monocrotaline (MCT)-induced and hypoxia-induced rat models and the underlying mechanism. Main methodsThe rats were treated with MCT or hypoxic environment for 14 days, after that sacubitril/valsartan were given for another 14 days. Hemodynamic measurements and histological assessments were performed. The expression of NPs was measured using RT-PCR and ELISA, while the protein level of natriuretic peptide receptors (NPRs) and AT1 receptor were detected by western blot, the concentrations of cGMP, IL-1β, IL-6, TNF-α and TGF-β1 were tested by ELISA. Key findingsWe found that sacubitril/valsartan significantly improved the hemodynamic and histological data of two PH models. Sacubitril/valsartan suppressed the protein expression of AT1 receptor (P < 0.05). The intervention increased the expression of ANP and CNP (P< 0.05) and therefore upregulated the protein expression of NPRs (P < 0.05), raised the concentration of cGMP (P < 0.05). In addition, the treatment reduced the concentration of IL-1β, IL-6 and TNF-α (P < 0.05) but have no effects on TGF-β1. SignificanceSacubitril/valsartan alleviated PH in MCT-induced and hypoxia-induced rat models by inhibiting the activated RAAS, promoting ANP/NPR-A/cGMP and CNP/NPR-B/cGMP pathway, restoring the NPR-C signaling and the anti-inflammatory effects.

Post-Myocardial Infarction Ventricular Remodeling Biomarkers-The Key Link between Pathophysiology and Clinic.

Studies in recent years have shown increased interest in developing new methods of evaluation, but also in limiting post infarction ventricular remodeling, hoping to improve ventricular function and the further evolution of the patient. This is the point where biomarkers have proven effective in early detection of remodeling phenomena. There are six main processes that promote the remodeling and each of them has specific biomarkers that can be used in predicting the evolution (myocardial necrosis, neurohormonal activation, inflammatory reaction, hypertrophy and fibrosis, apoptosis, mixed processes). Some of the biomarkers such as creatine kinase–myocardial band (CK-MB), troponin, and N-terminal-pro type B natriuretic peptide (NT-proBNP) were so convincing that they immediately found their place in the post infarction patient evaluation protocol. Others that are related to more complex processes such as inflammatory biomarkers, atheroma plaque destabilization biomarkers, and microRNA are still being studied, but the results so far are promising. This article aims to review the markers used so far, but also the existing data on new markers that could be considered, taking into consideration the most important studies that have been conducted so far.

Renin profiling predicts neurohormonal response to sacubitril/valsartan.

AimsClinical trials and observational cohorts show that beneficial effects of sacubitril/valsartan are less strong in an appreciable proportion of patients with heart failure with reduced ejection fraction (HFrEF). Lower blood pressure and impaired renal function predict suboptimal sacubitril/valsartan titration and a less favourable response. Circulating renin encompasses neurohormonal activation, intravascular volume, and renal function. We hypothesized that renin may predict response to sacubitril/valsartan, assessed by changes in N‐terminal fraction of pro‐brain natriuretic peptide (NT‐proBNP).Methods and resultsWe performed a prospective, open‐label, real‐life cohort study. The study population consisted of 80 consecutive HFrEF patients (age 66 ± 10 years, 83% men) planned to initiate sacubitril/valsartan. Clinical and biohumoral assessment, including a full neurohormonal panel, was performed at baseline and at 1, 3, and 6 month follow‐up. Response to sacubitril/valsartan was defined as ≥30% reduction in NT‐proBNP levels from baseline to 6 months. Patients in the lower renin tertile had higher blood pressure and plasma sodium concentration (all P < 0.05). At follow‐up, 38 patients (48%) were classified as responders. Circulating renin was lower in the responder group compared with non‐responders (19.8 mU/L, IQR 3.7–78.0 mU/L vs. 55.0 mU/L, IQR 16.4–483.1 mU/L; P = 0.004). After adjustment for age, renal function, and blood pressure, renin was independently associated to response to sacubitril/valsartan (P = 0.018).ConclusionsIn our preliminary study, we show that circulating renin predicts reduction in NT‐proBNP levels after sacubitril/valsartan initiation in HFrEF patients. Renin assessment might be useful to discriminate potential responders from the subgroup with a weaker expected benefit, thus needing a closer, tailored management strategy.

Abstract 14054: Soluble ACE2, Cardiac Biomarkers, Structure, Function and Events: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Membrane-bound angiotensin-converting enzyme 2 (ACE2) has been identified to a have prominent role in SARS-COV-2 infection and is an important counter-regulator of renin-angiotensin system. But the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) remains unclear. We sought to identify the association of sACE2 with cardiac biomarkers, structure, function and events in the Atherosclerosis Risk in Communities (ARIC) Study. Methods: sACE2 was measured in a subset of 497 patients from a case-control study of incident heart failure (HF) at visit 5 (2011-2013), mean age 78 (SD 5.4), 53% men and 27% black. We used linear regression to evaluate the associations of sACE2 with cardiac biomarkers (hs-cTnI, hs-cTnT, NT-proBNP) and echocardiographic parameters. We used Cox regression to evaluate associations of sACE2 with risk of HF hospitalization, global CVD events (CHD, ischemic stroke or HF hospitalization) and all-cause death. Results: Over a median follow up of 6.1 (4.6, 6.8) years, 282 global CVD events and 190 all-cause deaths occurred. sACE2 levels were higher in men, blacks, those with prevalent CVD, diabetes and hypertension. Higher sACE2 levels were associated with significantly higher hs-cTnI, hs-cTnT, NT-proBNP levels, greater left ventricular (LV) mass index, impaired diastolic function ( Table ) and increased risk for HF hospitalization (adjusted HR 1.32 per log unit increase, 95% CI 1.10-1.58), global CVD events (HR 1.34, 95% CI 1.13-1.60) and all-cause death (HR 1.26, 95% CI 1.01-1.57). Conclusions: In an elderly biracial cohort, sACE2 was positively associated with biomarkers reflecting myocardial injury and neurohormonal activation, LV mass index, impaired diastolic function, CVD events and all-cause death. Future research is needed to elucidate the significance of sACE2 in development of CVD, not only in patients with SAR—COV2 infection, but the general population

Renal denervation: where do we stand and what is the relevance to the nephrologist?

Catheter-based renal denervation to reduce high blood pressure (BP) has received well-deserved attention after a recent series of sham-controlled trials reported significant antihypertensive efficacy and very favourable tolerability and safety of the intervention. This emerging treatment option is of high relevance to nephrologists. Patients with chronic kidney disease (CKD) are at elevated risk of cardiovascular adverse events and often present with hypertension, which is very difficult to control with medication. Renal denervation promises a new tool to reduce BP and to prevent loss of renal function in this population. The current review considers the role of the kidney and neurohormonal activation in the development of hypertension and the rationale for renal denervation. The current state of the evidence for the effectiveness and tolerability of the procedure is considered from the nephrologists' perspective, with a focus on the potential future role of renal denervation in the management of CKD patients with hypertension.

A Multibiomarker Latent Class Analysis in Moderate to Advanced Heart Failure: Differentiating Factors.

Biomarker science in heart failure (HF) is advancing quickly in our ability to diagnosis and treat patients with this complex syndrome. Researchers are urged to not use single-marker strategies, but instead evaluate biomarkers in patterns to better understand their relationship to one another, as well as disease progression. Latent class mixture modeling allows researchers to determine novel associations between biomarkers. The objectives of this study were to identify and compare latent classes of cardiovascular biomarkers among patients with moderate to advanced HF. This was a cross-sectional study of 96 participants with moderate to advanced HF. Latent class mixture modeling was used to identify unique classes of biomarkers and their associations to sociodemographic and clinical variables. The average age of the sample was 54 years, with most of the sample being men (77%) and having an average ejection fraction of 23%. Two unique classes of biomarkers were identified. Latent class 1 had higher levels of all biomarkers, whereas latent class 2 had lower levels. The higher biomarker class had, on average, more neurohormonal activation and fluid retention; however, the higher levels of biomarker class were not more likely to be diagnosed with advanced HF or have more comorbidities. By identifying classes of biomarkers, providers may be better able to identify patients who are at risk of progressing into advanced HF quicker or those who are more likely to have more severe complications, such as fluid overload or renal disease.