Characterization of Cardiac Sympathetic Nervous System and Inflammatory Activation in HFpEF Patients

Kaye, D.; Nanayakkara, Shane; Wang, Bing; Shihata, Waled A.; Marques, Francine Z.; Esler, Murray; Lambert, Gavin W.; Mariani, Justin A.

doi:10.1016/j.jacbts.2021.11.007

Cited by 29 publications

(18 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the most likely explanation for our results is the recent finding that proinflammatory signaling is predominantly active during the initial phase of pressure overload remodeling, that is, development of concentric hypertrophy, and not required to maintain a more advanced HFpEF substrate. 30,31 These findings are in line with a recent report by Kaye et al 32 that did not detect excess cardiac inflammatory cytokine release in HFpEF patients. Combined with the current results this would refine the cardiac proinflammatory HFpEF paradigm as being temporally restricted to active concentric remodeling as shown in Figure 4.…”

Section: Discussionsupporting

confidence: 89%

Left Ventricular Gene Expression in Heart Failure With Preserved Ejection Fraction—Profibrotic and Proinflammatory Pathways and Genes

高野

Bradshaw

Abrahante

et al. 2023

Circ: Heart Failure

View full text Add to dashboard Cite

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent and has few treatments. The molecular mechanisms and resultant signaling pathways that underlie the development of HFpEF are poorly defined. It has been proposed that activation of proinflammatory pathways plays a role in the development of cardiac fibrosis. The signature of gene expression (transcriptome) of previously validated left ventricular biopsies obtained from patients with HFpEF and matched referent controls allows for an unbiased assessment of proinflammatory and profibrotic signaling pathways and genes. METHODS: Epicardial left ventricular biopsies from stringently selected HFpEF patients (HFpEF, n=16) and referent control patients (CTR, n=14) were obtained during aortocoronary bypass surgery. The subepicardial myocardium was flash-frozen to build a repository that was parallel-processed for RNA sequencing to allow for an unsupervised in-depth comparison of the left ventricular transcriptome. RESULTS: The average patient age was 67±10 years. When compared with controls, patients with HFpEF were hypertensive with a higher body mass index (kg/m 2 : 30±5 versus 37±6; P <0.01) and elevated NT-proBNP levels (pg/mL: 155 [89–328] versus 1554 [888–2178]; P <0.001). The transcriptome analysis revealed differential expression of 477 genes many of which were involved in profibrotic pathways including extracellular matrix production and posttranslational modification but no proinflammatory signature. CONCLUSIONS: The transcriptome analysis of left ventricular myocardial samples from patients with HFpEF confirms an overabundant extracellular matrix gene expression, the basis of myocardial fibrosis, without a signature of activated proinflammatory pathways or genes.

show abstract

Section: Discussionsupporting

confidence: 89%

Left Ventricular Gene Expression in Heart Failure With Preserved Ejection Fraction—Profibrotic and Proinflammatory Pathways and Genes

高野

Bradshaw

Abrahante

et al. 2023

Circ: Heart Failure

View full text Add to dashboard Cite

show abstract

“…Rarely cardiac output is increased in HF due to vasodilation and decreased peripheral resistance (high high-output HF) [ 12 ]. The studies on patients with low- and high-output HF, support the idea that preservation or maintenance of the arterial blood pressure is the main trigger for the development of neurohormonal overactivity (activation of the sympathetic nervous system (SNS) and the renin-angiotensin aldosterone system (RAAS)) [ 13 , 14 ]) signaling to the kidney to retain sodium and water which seen in all forms of HF [ 15 ]. However prolonged neurohormonal overactivity results in endothelial dysfunction, myocardial fibrosis, skeletal myopathy, and inflammation [ 16 ].…”

Section: Pathophysiologymentioning

confidence: 99%

The Neurohormonal Overactivity Syndrome in Heart Failure

Xanthopoulos

Skoularigis²,

Triposkiadis³

2023

Life

View full text Add to dashboard Cite

Heart failure (HF) is categorized arbitrarily based on the left ventricular ejection fraction (LVEF) in HF with reduced (HFrEF; LVEF < 40%), mildly reduced (HFmrEF; LVEF 40–49%), or preserved ejection fraction (HFpEF; LVEF ≥ 50%). In this opinion paper, based on (patho)physiological considerations, we contend that the neurohormonal overactivity syndrome (NOHS), which is present in all symptomatic HF patients irrespective of their LVEF, not only contributes to the development of signs and symptoms but it is also a major determinant of patients’ outcomes. In this regard, NHOS is the only currently available treatment target in HF and should be combatted in most patients with the combined use of diuretics and neurohormonal inhibitors (β-blockers, angiotensin receptor-neprilysin inhibitor/angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, mineralocorticoid antagonists, and sodium-glucose co-transporter 2 inhibitors). Unfortunately, despite the advances in therapeutics, HF mortality remains high. Probably machine learning approaches could better assess the multiple and higher-dimension interactions leading to the HF syndrome and define clusters of HF treatment efficacy.

show abstract

“…Measurement of the coronary sinus and arterial blood catecholamine concentrations can be a possible solution to estimate transcardiac NE despite its possible surgical risks. Kaye et al found that arterial and transcardiac NE are significantly higher in heart failure with preserved ejection fraction patients than controls ( 43 ). However, the risks of interventional surgery make it difficult to implement for general patients.…”

Section: Cardiac Sympathetic Activity Assessmentmentioning

confidence: 99%

The Mechanism of Cardiac Sympathetic Activity Assessment Methods: Current Knowledge

Zheng

2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

This review has summarized the methods currently available for cardiac sympathetic assessment in clinical or under research, with emphasis on the principles behind these methodologies. Heart rate variability (HRV) and other methods based on heart rate pattern analysis can reflect the dominance of sympathetic nerve to sinoatrial node function and indirectly show the average activity level of cardiac sympathetic nerve in a period of time. Sympathetic neurotransmitters play a key role of signal transduction after sympathetic nerve discharges. Plasma or local sympathetic neurotransmitter detection can mediately display sympathetic nerve activity. Given cardiac sympathetic nerve innervation, i.e., the distribution of stellate ganglion and its nerve fibers, stellate ganglion activity can be recorded either directly or subcutaneously, or through the surface of the skin using a neurophysiological approach. Stellate ganglion nerve activity (SGNA), subcutaneous nerve activity (SCNA), and skin sympathetic nerve activity (SKNA) can reflect immediate stellate ganglion discharge activity, i.e., cardiac sympathetic nerve activity. These cardiac sympathetic activity assessment methods are all based on the anatomy and physiology of the heart, especially the sympathetic innervation and the sympathetic regulation of the heart. Technological advances, discipline overlapping, and more understanding of the sympathetic innervation and sympathetic regulation of the heart will promote the development of cardiac sympathetic activity assessment methods.

show abstract

Characterization of Cardiac Sympathetic Nervous System and Inflammatory Activation in HFpEF Patients

Cited by 29 publications

References 69 publications

Left Ventricular Gene Expression in Heart Failure With Preserved Ejection Fraction—Profibrotic and Proinflammatory Pathways and Genes

Left Ventricular Gene Expression in Heart Failure With Preserved Ejection Fraction—Profibrotic and Proinflammatory Pathways and Genes

The Neurohormonal Overactivity Syndrome in Heart Failure

The Mechanism of Cardiac Sympathetic Activity Assessment Methods: Current Knowledge

Contact Info

Product

Resources

About