-
1.
Flavanols from Nature: A Phytochemistry and Biological Activity Review.
Luo, Y, Jian, Y, Liu, Y, Jiang, S, Muhammad, D, Wang, W
Molecules (Basel, Switzerland). 2022;(3)
Abstract
Flavanols, a common class of secondary plant metabolites, exhibit several beneficial health properties by acting as antioxidant, anticarcinogen, cardioprotective, anti-microbial, anti-viral, and neuroprotective agents. Furthermore, some flavanols are considered functional ingredients in dairy products. Based on their structural features and health-promoting functions, flavanols have gained the attention of pharmacologists and botanists worldwide. This review collects and summarizes 121 flavanols comprising four categories: flavan-3-ols, flavan-4-ols, isoflavan-4-ols, and flavan-3,4-ols. The research of the various structural features and pharmacological activities of flavanols and their derivatives aims to lay the groundwork for subsequent research and expect to provide mentality and inspiration for the research. The current study provides a starting point for further research and development.
-
2.
Effect of Inotropes on Patient-Reported Health Status in End-Stage Heart Failure: A Review of Published Clinical Trials.
Clarke, JD, Riello, R, Allen, LA, Psotka, MA, Teerlink, JR, Lindenfeld, J, Desai, NR, Ahmad, T
Circulation. Heart failure. 2021;(2):e007759
Abstract
BACKGROUND A growing population of patients with end-stage heart failure (HF) with reduced ejection fraction has limited treatment options to improve their quality and quantity of life. Although positive inotropes have failed to show survival benefit, these agents may enhance patient-reported health status, that is, symptoms, functional status, and health-related quality of life. We sought to review the available clinical trial data on positive inotrope use in patients with end-stage HF and to summarize evidence supporting the use of these agents to improve health status of patients with end-stage HF. METHODS A literature review of randomized controlled trials examining the use of positive inotropy in HF with reduced ejection fraction was conducted. We searched MEDLINE, SCOPUS, and Web of Science between January 1980 to December 2018 for randomized controlled trials that used as their main outcome measures the effects of inotrope therapy on (1) morbidity/mortality, (2) symptoms, (3) functional status, or (4) health-related quality of life. Inotropes of interest included adrenergic agents, phosphodiesterase inhibitors, calcium sensitizers, myosin activators, and SERCA2a (sarcoplasmic reticulum Ca2+-ATPase) modulators. RESULTS Twenty-two out of 26 inotrope randomized controlled trials measured the effect of inotropes on at least one patient-reported health status domain. Among the 22 studies with patient-related health status outcomes, 11 (50%) gauged symptom response, 15 (68%) reported functional capacity changes, and 12 (54%) reported health-related quality of life measures. Fourteen (64%) of these trials noted positive outcomes in at least one health status domain measured; 11 (79%) of these positive studies used agents that worked through phosphodiesterase inhibition. CONCLUSIONS There has been a lack of standardization surrounding measurement of patient-centered outcomes in studies of inotropes for end-stage HF with reduced ejection fraction. The degree to which positive inotropes can improve patient-reported health status and the adverse risk they pose remains unknown.
-
3.
Cardiovascular Protection With Sodium-Glucose Cotransporter-2 Inhibitors and Mineralocorticoid Receptor Antagonists in Chronic Kidney Disease: A Milestone Achieved.
Sarafidis, P, Papadopoulos, CE, Kamperidis, V, Giannakoulas, G, Doumas, M
Hypertension (Dallas, Tex. : 1979). 2021;(5):1442-1455
Abstract
Chronic kidney disease (CKD) and cardiovascular disease are intimately linked. They share major risk factors, including age, hypertension, and diabetes, and common pathogenetic mechanisms. Furthermore, reduced renal function and kidney injury documented with albuminuria are independent risk factors for cardiovascular events and mortality. In major renal outcome trials and subsequent meta-analyses in patients with CKD, ACE (angiotensin-converting enzyme) inhibitors and ARBs (angiotensin II receptor blockers) were shown to effectively retard CKD progression but not to significantly reduce cardiovascular events or mortality. Thus, a high residual risk for cardiovascular disease progression under standard-of-care treatment is still present for patients with CKD. In contrast to the above, several outcome trials with SGLT-2 (sodium-glucose cotransporter-2) inhibitors and MRAs (mineralocorticoid receptor antagonists) clearly suggest that these agents, apart from nephroprotection, offer important cardioprotection in this population. This article discusses existing evidence on the effects of SGLT-2 inhibitors and MRAs on cardiovascular outcomes in patients with CKD that open new roads in cardiovascular protection of this heavily burdened population.
-
4.
Impact of SGLT2 Inhibitors on Heart Failure: From Pathophysiology to Clinical Effects.
Palmiero, G, Cesaro, A, Vetrano, E, Pafundi, PC, Galiero, R, Caturano, A, Moscarella, E, Gragnano, F, Salvatore, T, Rinaldi, L, et al
International journal of molecular sciences. 2021;(11)
Abstract
Heart failure (HF) affects up to over 20% of patients with type 2 diabetes (T2DM), even more in the elderly. Although, in T2DM, both hyperglycemia and the proinflammatory status induced by insulin resistance are crucial in cardiac function impairment, SGLT2i cardioprotective mechanisms against HF are several. In particular, these beneficial effects seem attributable to the significant reduction of intracellular sodium levels, well-known to exert a cardioprotective role in the prevention of oxidative stress and consequent cardiomyocyte death. From a molecular perspective, patients' exposure to gliflozins' treatment mimics nutrient and oxygen deprivation, with consequent autophagy stimulation. This allows to maintain the cellular homeostasis through different degradative pathways. Thus, since their introduction in the clinical practice, the hypotheses on SGLT2i mechanisms of action have changed: from simple glycosuric drugs, with consequent glucose lowering, erythropoiesis enhancing and ketogenesis stimulating, to intracellular sodium-lowering molecules. This provides their consequent cardioprotective effect, which justifies its significant reduction in CV events, especially in populations at higher risk. Finally, the updated clinical evidence of SGLT2i benefits on HF was summarized. Thus, this review aimed to analyze the cardioprotective mechanisms of sodium glucose transporter 2 inhibitors (SGLT2i) in patients with HF, as well as their clinical impact on cardiovascular events.
-
5.
Recent advances in pharmacological treatment of heart failure.
Iacoviello, M, Palazzuoli, A, Gronda, E
European journal of clinical investigation. 2021;(11):e13624
-
-
Free full text
-
Abstract
BACKGROUND Over the last years, several trials offered new evidence on heart failure (HF) treatment. DESIGN AND RESULTS For HF with reduced left ventricular ejection fraction, type 2 sodium-glucose cotransporter inhibitors, aside from sacubitril-valsartan, demonstrated extraordinary efficacy in ameliorating patients' prognosis. Some new molecules (eg vericiguat, omecamtiv mecarbil and ferric carboxymaltose) correct iron deficiency and have shown to be capable of furthering reducing the burden of HF hospitalisation. Finally, there is new evidence on the possible therapeutic approaches of HF patients with mid-range or preserved left ventricular ejection fraction. CONCLUSIONS This review aimed to revise the main novelties in the field of HF therapy and focus on how the daily clinical approach to patient treatment is changing.
-
6.
An update on levosimendan in acute cardiac care: applications and recommendations for optimal efficacy and safety.
Heringlake, M, Alvarez, J, Bettex, D, Bouchez, S, Fruhwald, S, Girardis, M, Grossini, E, Guarracino, F, Herpain, A, Toller, W, et al
Expert review of cardiovascular therapy. 2021;(4):325-335
-
-
Free full text
-
Abstract
Introduction: In the 20 years since its introduction to the palette of intravenous hemodynamic therapies, the inodilator levosimendan has established itself as a valuable asset for the management of acute decompensated heart failure. Its pharmacology is notable for delivering inotropy via calcium sensitization without an increase in myocardial oxygen consumption.Areas covered: Experience with levosimendan has led to its applications expanding into perioperative hemodynamic support and various critical care settings, as well as an array of situations associated with acutely decompensated heart failure, such as right ventricular failure, cardiogenic shock with multi-organ dysfunction, and cardio-renal syndrome. Evidence suggests that levosimendan may be preferable to milrinone for patients in cardiogenic shock after cardiac surgery or for weaning from extracorporeal life support and may be superior to dobutamine in terms of short-term survival, especially in patients on beta-blockers. Positive effects on kidney function have been noted, further differentiating levosimendan from catecholamines and phosphodiesterase inhibitors.Expert opinion:Levosimendan can be a valuable resource in the treatment of acute cardiac dysfunction, especially in the presence of beta-blockers or ischemic cardiomyopathy. When attention is given to avoiding or correcting hypovolemia and hypokalemia, an early use of the drug in the treatment algorithm is preferred.
-
7.
Milrinone Use in Persistent Pulmonary Hypertension of the Newborn.
Qasim, A, Jain, SK
NeoReviews. 2020;(3):e165-e178
Abstract
Failure of the normal transition from in utero to ex utero physiology leads to "persistent" pulmonary hypertension of the newborn (PPHN). PPHN is frequently associated with low systemic blood pressure and low cardiac output because of increased right ventricular afterload and myocardial dysfunction. The general management of newborns with PPHN is geared toward maintenance of normothermia, normal serum electrolytes, normal intravascular volume, correction of acidosis, adequate sedation/analgesia, adequate ventilation and oxygenation with optimal lung recruitment, and avoidance of hyperoxia. Inotropic and vasoactive agents are commonly initiated early to increase cardiac output, maintain adequate systemic blood pressure, and enhance oxygen delivery to the tissue. Unfortunately, there is not much evidence on the choice, timing of initiation, dosing, monitoring, and titrating of vasoactive agents in this patient population. In this review, we will discuss the pathophysiology of PPHN and review the use of inotropic, lusitropic, and vasoactive agents in the management of PPHN, with particular attention to milrinone.
-
8.
Mitochondria in acute myocardial infarction and cardioprotection.
Ramachandra, CJA, Hernandez-Resendiz, S, Crespo-Avilan, GE, Lin, YH, Hausenloy, DJ
EBioMedicine. 2020;:102884
Abstract
Acute myocardial infarction (AMI) and the heart failure (HF) that often follows are among the leading causes of death and disability worldwide. As such, new treatments are needed to protect the myocardium against the damaging effects of the acute ischaemia and reperfusion injury (IRI) that occurs in AMI, in order to reduce myocardial infarct (MI) size, preserve cardiac function, and improve patient outcomes. In this regard, cardiac mitochondria play a dual role as arbiters of cell survival and death following AMI. Therefore, preventing mitochondrial dysfunction induced by acute myocardial IRI is an important therapeutic strategy for cardioprotection. In this article, we review the role of mitochondria as key determinants of acute myocardial IRI, and we highlight their roles as therapeutic targets for reducing MI size and preventing HF following AMI. In addition, we discuss the challenges in translating mitoprotective strategies into the clinical setting for improving outcomes in AMI patients.
-
9.
Effects of short-term consumption of strawberry powder on select parameters of vascular health in adolescent males.
Holt, RR, Zuelch, ML, Charoenwoodhipong, P, Al-Dashti, YA, Hackman, RM, Keen, CL
Food & function. 2020;(1):32-44
Abstract
Cardiovascular disease is a leading cause of death in the United States and much of the developed world, costing billions of dollars in lost work time, lower productivity and high health care expenditures. Research on foods and bioactive food components that have cardioprotective benefits may provide new insights as to how modest changes in one's diet may result in a reduced risk of vascular disease. In intervention trials, the consumption of strawberries, either fresh or freeze-dried, has been reported to improve select markers of cardiovascular health, including improved lipid profiles, microvascular function, and platelet reactivity. Consistent with the above, epidemiological studies suggest beneficial effects of strawberries on vascular function. Preliminary studies on the effects of freeze-dried strawberry powder on vascular health are reviewed in the current paper.
-
10.
Allicin pharmacology: Common molecular mechanisms against neuroinflammation and cardiovascular diseases.
Mocayar Marón, FJ, Camargo, AB, Manucha, W
Life sciences. 2020;:117513
Abstract
According to investigations in phytomedicine and ethnopharmacology, the therapeutic properties of garlic (Allium sativum) have been described by ancestral cultures. Notwithstanding, it is of particular concern to elucidate the molecular mechanisms underlying this millenary empirical knowledge. Allicin (S-allyl prop-2-ene-1-sulfinothioate), a thioester of sulfenic acid, is one of the main bioactive compounds present in garlic, and it is responsible for the particular aroma of the spice. The pharmacological attributes of allicin integrate a broad spectrum of properties (e.g., anti-inflammatory, immunomodulatory, antibiotic, antifungal, antiparasitic, antioxidant, nephroprotective, neuroprotective, cardioprotective, and anti-tumoral activities, among others). The primary goal of the present article is to review and clarify the common molecular mechanisms by which allicin and its derivates molecules may perform its therapeutic effects on cardiovascular diseases and neuroinflammatory processes. The intricate interface connecting the cardiovascular and nervous systems suggests that the impairment of one organ could contribute to the dysfunction of the other. Allicin might target the cornerstone of the pathological processes underlying cardiovascular and neuroinflammatory disorders, like inflammation, renin-angiotensin-aldosterone system (RAAS) hyperactivation, oxidative stress, and mitochondrial dysfunction. Indeed, the current evidence suggests that allicin improves mitochondrial function by enhancing the expression of HSP70 and NRF2, decreasing RAAS activation, and promoting mitochondrial fusion processes. Finally, allicin represents an attractive therapeutic alternative targeting the complex interaction between cardiovascular and neuroinflammatory disorders.