Response by Pfeffer et al to Letter Regarding Article, “Heart Failure With Preserved Ejection Fraction in Perspective”

Pfeffer, Marc A.; Shah, Amil M.; Borlaug, Barry A.

doi:10.1161/circresaha.119.315591

Cited by 3 publications

(1 citation statement)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CMD, linked with traditional cardiovascular risk factors 5 and stressors, through microvascular rarefication and decreased cardiomyocyte energy availability, also has the potential to disrupt mechanistic functioning of cardiomyocytes, including transverse tubules, contributing to increased ventricular remodeling and stiffness. 6 This may be associated with dysfunctional LV mechanics prior to the onset of overt myocardial dysfunction, fibrosis, and symptoms of heart failure and a circulating biomarker for transverse tubule disruption would be useful for identifying patients with CMD at risk of developing HFpEF.…”

Section: Introductionmentioning

confidence: 99%

Association of coronary microvascular dysfunction and cardiac bridge integrator 1, a cardiomyocyte dysfunction biomarker

Pacheco

Wei

Shufelt

et al. 2021

Clinical Cardiology

View full text Add to dashboard Cite

Background: Coronary microvascular dysfunction (CMD) is associated with heart failure with preserved ejection fraction (HFpEF); however, pathophysiology is not well described. Hypothesis:We hypothesized that CMD in women with suspected ischemia with no obstructive coronary artery disease (INOCA) is associated with cardiomyocyte dysfunction reflected by plasma levels of a cardiomyocyte calcium handling protein, cardiac bridge integrator 1 (cBIN1). Methods: Women with suspected INOCA undergoing coronary function testing were included. Coronary flow reserve, vasodilation to nitroglycerin, change in coronary blood flow (ΔCBF), and vasodilation to acetylcholine (ΔAch) were evaluated. cBIN1 score (CS) levels in these women (n = 39) were compared to women with HFpEF (n = 20), heart failure with reduced ejection fraction (HFrEF) (n = 36), and reference controls (RC) (n = 50). Higher CS indicates cardiomyocyte tubule dysfunction.Results: INOCA, HFpEF, and HFrEF women were older than RC (p < .05). Higher CS was associated with vasoconstriction to acetylcholine (r = À0.43, p = .011) with a trend towards lower ΔCBF (r = 0.30, p = .086). Higher CS was specific for ΔAch and ΔCBF but had limited sensitivity. INOCA women had higher CS than RC, but lower CS than HFpEF/HFrEF groups (p < .001).Conclusions: CS, a plasma biomarker indicating poor cardiomyocyte health, was higher in women with suspected INOCA as compared to RC, but lower than in

show abstract

Section: Introductionmentioning

confidence: 99%

Association of coronary microvascular dysfunction and cardiac bridge integrator 1, a cardiomyocyte dysfunction biomarker

Pacheco

Wei

Shufelt

et al. 2021

Clinical Cardiology

View full text Add to dashboard Cite

show abstract

Improving the Characterization of Stage A and B Heart Failure by Adding Global Longitudinal Strain

Haji

Huynh

Wong

et al. 2022

JACC: Cardiovascular Imaging

View full text Add to dashboard Cite

Modulating Sirtuin Biology and Nicotinamide Adenine Diphosphate Metabolism in Cardiovascular Disease—From Bench to Bedside

et al. 2021

View full text Add to dashboard Cite

Sirtuins (SIRT1–7) comprise a family of highly conserved deacetylases with distribution in different subcellular compartments. Sirtuins deacetylate target proteins depending on one common substrate, nicotinamide adenine diphosphate (NAD+), thus linking their activities to the status of cellular energy metabolism. Sirtuins had been linked to extending life span and confer beneficial effects in a wide array of immune-metabolic and cardiovascular diseases. SIRT1, SIRT3, and SIRT6 have been shown to provide protective effects in various cardiovascular disease models, by decreasing inflammation, improving metabolic profiles or scavenging oxidative stress. Sirtuins may be activated collectively by increasing their co-substrate NAD+. By supplementing NAD+ precursors, NAD+ boosters confer pan-sirtuin activation with protective cardiometabolic effects in the experimental setting: they improve endothelial dysfunction, protect from experimental heart failure, hypertension and decrease progression of liver steatosis. Different precursor molecules were applied ranging from nicotinamide (NAM), nicotinamide mononucleotide (NMN) to nicotinamide riboside (NR). Notably, not all experimental results showed protective effects. Moreover, the results are not as striking in clinical studies as in the controlled experimental setting. Species differences, (lack of) genetic heterogeneity, different metabolic pathways, dosing, administration routes and disease contexts may account for these challenges in clinical translation. At the clinical scale, caloric restriction can reduce the risks of cardiovascular disease and raise NAD+ concentration and sirtuin expression. In addition, antidiabetic drugs such as metformin or SGLT2 inhibitors may confer cardiovascular protection, indirectly via sirtuin activation. Overall, additional mechanistic insight and clinical studies are needed to better understand the beneficial effects of sirtuin activation and NAD+ boosters from bench to bedside.

show abstract

Response by Pfeffer et al to Letter Regarding Article, “Heart Failure With Preserved Ejection Fraction in Perspective”

Cited by 3 publications

References 3 publications

Association of coronary microvascular dysfunction and cardiac bridge integrator 1, a cardiomyocyte dysfunction biomarker

Association of coronary microvascular dysfunction and cardiac bridge integrator 1, a cardiomyocyte dysfunction biomarker

Improving the Characterization of Stage A and B Heart Failure by Adding Global Longitudinal Strain

Modulating Sirtuin Biology and Nicotinamide Adenine Diphosphate Metabolism in Cardiovascular Disease—From Bench to Bedside

Contact Info

Product

Resources

About